bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytoplasmic fragment of CD147 generated by regulated intramembrane proteolysis contributes to HCC by promoting autophagy
Authors: Wu Bo , Cui Jian , Yang Xiang-Min , Liu Zhen-Yu , Song Fei , Li Ling , Jiang Jian-Li , Chen Zhi-Nan 
Published: July 2017

AbstractHepatocellular carcinoma (HCC) is one of the most lethal and prevalent cancers worldwide. CD147 (EMMPRIN or basigin) is a leading gene relating to hepatocarcinogenesis and metastasis, and is detected in transmembrane, exosome or circulating forms in HCC patients. The endosome recycling of CD147 further enhances the function of this oncoprotein from a dynamic perspective. However, previous studies about CD147 mainly focused on one separate form, and little attention has been paid to how the different forms of tumor-derived CD147 changes. Moreover, uncovering the roles of the residual C-terminal portion of CD147 after shedding is inevitable to fully understand CD147 promoting tumor progression. In this study, we discovered that under low-cholesterol condition, CD147 endocytosis is inhibited but its shedding mediated by ADAM10 is enhanced. Further procession of residual CD147 in the lysosome produces nuclear-localized CD147-ICD (intracellular domain of CD147), which contributes to autophagy through NF-κB–TRAIL–caspase8–ATG3 axis. As autophagy endows cancer cells with increased adaptability to chemotherapy, and HAb 18 (a specific antibody targeting CD147) inhibits CD147 shedding and sequential CD147-ICD enhances autophagy, we found the combination of HAb 18 and cisplatin exhibited marked antitumor efficiency.
RETRACTED ARTICLE: mTORC2 regulates hedgehog pathway activity by promoting stability to Gli2 protein and its nuclear translocation
Authors: Maiti Samarpan , Mondal Susmita , Satyavarapu Eswara M , Mandal Chitra 
Published: July 2017

AbstractmTORC2 is aberrantly activated in cancer and therefore is considered to be an important therapeutic target. The hedgehog pathway, which is also often hyperactivated, regulates transcription of several genes associated with angiogenesis, metastasis, cellular proliferation and cancer stem cell (CSC) regeneration. However, the contribution of mTORC2 toward hedgehog pathway activity has not been explored yet. Here we have addressed the molecular cross talk between mTORC2 and hedgehog pathway activities in the context of glioblastoma multiforme, a malignant brain tumor using as a model system. We observed that higher mTORC2 activity enhanced the expression of a few hedgehog pathway molecules (Gli1, Gli2 and Ptch1) and amplified its target genes (Cyclin D1, Cyclin D2, Cyclin E, Snail, Slug and VEGF) both in mRNA and protein levels as corroborated by increased metastasis, angiogenesis, cellular proliferation and stem cell regeneration. Inhibition of mTORC2 formation decreased hedgehog pathway activity and attenuated all these above-mentioned events, suggesting their cross talk with each other. Further investigations revealed that mTORC2 inhibited ubiquitination of Gli2 by inactivating GSK3β, and thus it promotes stability to Gli2 and its nuclear translocation. Moreover, enhanced mTORC2 activity led to the increased clonogenic properties and CD133+ cells, indicating its role in CSC regeneration. mTORC2 inhibitor directed the reduction of hedgehog pathway proteins and also reduced CSCs. Thus, our observations support a role for elevated mTORC2 activity in regulating angiogenesis, metastasis, cellular proliferation and CSC regeneration via hedgehog pathway activity. Taken together, it provides a rationale for including the mTOR2 inhibitor as part of the therapeutic regimen for CSCs.
The EGFR/miR-338-3p/EYA2 axis controls breast tumor growth and lung metastasis
Authors: Liang Yingchun , Xu Xiaojie , Wang Tao , Li Ying , You Wenye , Fu Jing , Liu Yang , Jin Shuai , Ji Quanbo , Zhao Wei , Song Qi , Li Ling , Hong Tian , Huang Junjian , Lyu Zhaohui , Ye Qinong 
Published: July 2017

AbstractDysregulation of the epidermal growth factor receptor (EGFR) promotes cancer cell growth, invasion and metastasis. However, its relevant downstream effectors are still limited. Here, we show that EGFR promotes breast tumor growth and metastasis by downregulating the tumor suppressor micoRNA-338-3p (miR-338-3p) and activating the EYA2 (EYA transcriptional coactivator and phosphatase 2) oncoprotein. EGFR represses miR-338-3p expression largely through HIF1α transcription factor. miR-338-3p inhibits EYA2 expression by binding to the 3′-untranslated region of EYA2. EGFR increases EYA2 expression via HIF1α repression of miR-338-3p. Through the miR-338-3p/EYA2 pathway, EGFR increases breast cancer cell growth, epithelial-to-mesenchymal transition, migration, invasion and lung metastasis in vitro and in a allograft tumor mouse model in vivo. In breast cancer patients, miR-338-3p expression negatively correlates with the expression of EGFR and EYA2, EGFR status positively associates with EYA2 expression, and miR-338-3p and EYA2 predict breast cancer lung metastasis when expressed in primary breast cancers. These data suggest that the miR-338-3p/EYA2 axis contributes to EGFR-mediated tumor growth and lung metastasis and that miR-338-3p activation or EYA2 inhibition or combination therapy targeting EGFR/miR-338-3p/EYA2 axis may be a promising way to treat patients with metastatic cancer.
Structural insights into the mycobacteria transcription initiation complex from analysis of X-ray crystal structures
Authors: Hubin Elizabeth A. , Lilic Mirjana , Darst Seth A. , Campbell Elizabeth A. 
Published: July 2017

AbstractThe mycobacteria RNA polymerase (RNAP) is a target for antimicrobials against tuberculosis, motivating structure/function studies. Here we report a 3.2 Å-resolution crystal structure of a Mycobacterium smegmatis (Msm) open promoter complex (RPo), along with structural analysis of the Msm RPo and a previously reported 2.76 Å-resolution crystal structure of an Msm transcription initiation complex with a promoter DNA fragment. We observe the interaction of the Msm RNAP α-subunit C-terminal domain (αCTD) with DNA, and we provide evidence that the αCTD may play a role in Mtb transcription regulation. Our results reveal the structure of an Actinobacteria-unique insert of the RNAP β′ subunit. Finally, our analysis reveals the disposition of the N-terminal segment of Msm σA, which may comprise an intrinsically disordered protein domain unique to mycobacteria. The clade-specific features of the mycobacteria RNAP provide clues to the profound instability of mycobacteria RPo compared with E. coli.
Baseline value of intrahepatic HBV DNA over cccDNA predicts patient’s response to interferon therapy
Authors: Mu Di , Yuan Fang-Chao , Chen Yu , Jiang Xiao-Yan , Yan Liang , Jiang Ling-Yu , Gong Jian-Ping , Zhang Da-Zhi , Ren Hong , Liao Yong 
Published: July 2017

AbstractMethodology for accurate quantification of intra-hepatic cccDNA has long been a technical challenge, yet it is highly desired in the clinic. Here, we developed a sensitive method for quantification of intrahepatic cccDNA in liver biopsies from patients, which allowed to predict patient’s response to interferon therapy at baseline. Twenty-five patients with HBeAg+ CHB were recruited and liver biopsies were obtained at baseline and 1-year after interferon treatment, respectively. Both intrahepatic cccDNA and HBV DNA were absolutely quantified by a droplet digital PCR amplification system. Patients were categorized as either responder or non-responder group based on their HBeAg status 1-year after interferon therapy. Levels of both intrahepatic HBV DNA and HBV cccDNA were significantly reduced after interferon treatment among the responders, but not the non-responders, in comparison with their levels at baseline. Baseline values of intrahepatic HBV DNA over cccDNA significantly correlated with patient’s response to PEG-IFN therapy (P = 0.000). In addition, HBeAg seroconversion also correlates with a significant reduction in intrahepatic pgRNA production among the responders after interferon therapy (P = 0.030). In conclusion, our results suggest that baseline value of intrahepatic HBV DNA over cccDNA may be a preferable indicator for selecting appropriate patients for IFN-based therapy in the clinic.
Efficient two-step photocarrier generation in bias-controlled InAs/GaAs quantum dot superlattice intermediate-band solar cells
Authors: Kada T. , Asahi S. , Kaizu T. , Harada Y. , Tamaki R. , Okada Y. , Kita T. 
Published: July 2017

AbstractWe studied the effects of the internal electric field on two-step photocarrier generation in InAs/GaAs quantum dot superlattice (QDSL) intermediate-band solar cells (IBSCs). The external quantum efficiency of QDSL-IBSCs was measured as a function of the internal electric field intensity, and compared with theoretical calculations accounting for interband and intersubband photoexcitations. The extra photocurrent caused by the two-step photoexcitation was maximal for a reversely biased electric field, while the current generated by the interband photoexcitation increased monotonically with increasing electric field intensity. The internal electric field in solar cells separated photogenerated electrons and holes in the superlattice (SL) miniband that played the role of an intermediate band, and the electron lifetime was extended to the microsecond scale, which improved the intersubband transition strength, therefore increasing the two-step photocurrent. There was a trade-off relation between the carrier separation enhancing the two-step photoexcitation and the electric-field-induced carrier escape from QDSLs. These results validate that long-lifetime electrons are key to maximising the two-step photocarrier generation in QDSL-IBSCs.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)-elicited effects on bile acid homeostasis: Alterations in biosynthesis, enterohepatic circulation, and microbial metabolism
Authors: Fader Kelly A. , Nault Rance , Zhang Chen , Kumagai Kazuyoshi , Harkema Jack R. , Zacharewski Timothy R. 
Published: July 2017

Abstract2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a persistent environmental contaminant which elicits hepatotoxicity through activation of the aryl hydrocarbon receptor (AhR). Male C57BL/6 mice orally gavaged with TCDD (0.01–30 µg/kg) every 4 days for 28 days exhibited bile duct proliferation and pericholangitis. Mass spectrometry analysis detected a 4.6-fold increase in total hepatic bile acid levels, despite the coordinated repression of genes involved in cholesterol and primary bile acid biosynthesis including Cyp7a1. Specifically, TCDD elicited a >200-fold increase in taurolithocholic acid (TLCA), a potent G protein-coupled bile acid receptor 1 (GPBAR1) agonist associated with bile duct proliferation. Increased levels of microbial bile acid metabolism loci (bsh, baiCD) are consistent with accumulation of TLCA and other secondary bile acids. Fecal bile acids decreased 2.8-fold, suggesting enhanced intestinal reabsorption due to induction of ileal transporters (Slc10a2, Slc51a) and increases in whole gut transit time and intestinal permeability. Moreover, serum bile acids were increased 45.4-fold, consistent with blood-to-hepatocyte transporter repression (Slco1a1, Slc10a1, Slco2b1, Slco1b2, Slco1a4) and hepatocyte-to-blood transporter induction (Abcc4, Abcc3). These results suggest that systemic alterations in enterohepatic circulation, as well as host and microbiota bile acid metabolism, favor bile acid accumulation that contributes to AhR-mediated hepatotoxicity.
Loss of Calreticulin Uncovers a Critical Role for Calcium in Regulating Cellular Lipid Homeostasis
Authors: Wang Wen-An , Liu Wen-Xin , Durnaoglu Serpen , Lee Sun-Kyung , Lian Jihong , Lehner Richard , Ahnn Joohong , Agellon Luis B. , Michalak Marek 
Published: July 2017

AbstractA direct link between Ca2+ and lipid homeostasis has not been definitively demonstrated. In this study, we show that manipulation of ER Ca2+ causes the re-distribution of a portion of the intracellular unesterified cholesterol to a pool that is not available to the SCAP-SREBP complex. The SREBP processing pathway in ER Ca2+ depleted cells remained fully functional and responsive to changes in cellular cholesterol status but differed unexpectedly in basal activity. These findings establish the role of Ca2+ in determining the reference set-point for controlling cellular lipid homeostasis. We propose that ER Ca2+ status is an important determinant of the basal sensitivity of the sterol sensing mechanism inherent to the SREBP processing pathway.
Global deregulation of ginseng products may be a safety hazard to warfarin takers: solid evidence of ginseng-warfarin interaction
Authors: Dong Haiyan , Ma Ji , Li Tao , Xiao Yingying , Zheng Ning , Liu Jian , Gao Yu , Shao Jingwei , Jia Lee 
Published: July 2017

AbstractRecent global deregulation of ginseng as the table food raises our concern about the possible ginseng-warfarin interaction that could be life-threatening to patients who take warfarin for preventing fatal strokes and thromboembolism while using ginseng products for bioenergy recovery. Here we show that quality-control ginsenosides, extracted from ginseng and containing its major active ingredients, produce dose- and time-dependent antagonism in rats against warfarin’s anti-coagulation assessed by INR and rat thrombosis model. The interactions between ginsenosides and warfarin on thrombosis, pharmacokinetics, activities of coagulation factors and liver cytochrome P450 isomers are determined by using thrombosis analyzer, UPLC/MS/MS, ELISA and real-time PCR, respectively. The antagonism correlates well with the related pharmacokinetic interaction showing that the blood plateaus of warfarin reached by one-week warfarin administration are significantly reduced after three-week co-administration of warfarin with ginsenosides while 7-hydroxywarfarin is increased. The one-week warfarin and three-week warfarin-ginsenosides regimen result in restoring the suppressed levels by warfarin of the coagulating factors II, VII and protein Z, and significantly enhance activities of P450 3A4 and 2C9 that metabolize warfarin. The present study, for the first time, provides the solid evidence to demonstrate the warfarin-ginsenoside interaction, and warns the warfarin users and regulation authorities of the dangerous interaction.
Contrasting evolutionary patterns between two haplogroups of Haematobia exigua (Diptera: Muscidae) from the mainland and islands of Southeast Asia
Authors: Low Van Lun , Tan Tiong Kai , Prakash Batah Kunalan , Vinnie-Siow Wei Yin , Tay Sun Tee , Masmeatathip Roungthip , Hadi Upik Kesumawati , Lim Yvonne Ai Lian , Chen Chee Dhang , Norma-Rashid Yusoff , Sofian-Azirun Mohd 
Published: July 2017

AbstractUncovering the hidden diversity and evolutionary history of arthropods of medico-veterinary importance could have significant implications for vector-borne disease control and epidemiological intervention. The buffalo fly Haematobia exigua is an obligate bloodsucking ectoparasite of livestock. As an initial step towards understanding its population structures and biogeographic patterns, we characterized partial cytochrome c oxidase subunit I (COI) and cytochrome b (Cytb) sequences of H. exigua from three distinct geographic regions in Southeast Asia. We detected two distinct mitochondrial haplogroups of H. exigua in our surveyed geographic regions. Haplogroup I is widespread in the Southeast Asian mainland whereas haplogroup II is generally restricted to the type population Java Island. Both haplogroups were detected co-occurring on Borneo Island. Additionally, both haplogroups have undergone contrasting evolutionary histories, with haplogroup I exhibited a high level of mitochondrial diversity indicating a population expansion during the Pleistocene era dating back to 98,000 years ago. However, haplogroup II presented a low level of mitochondrial diversity which argues against the hypothesis of recent demographic expansion.
Antimicrobial Efficacy and Synergy of Metal Ions against Enterococcus faecium, Klebsiella pneumoniae and Acinetobacter baumannii in Planktonic and Biofilm Phenotypes
Authors: Vaidya Misha Y. , McBain Andrew J. , Butler Jonathan A. , Banks Craig E. , Whitehead Kathryn A. 
Published: July 2017

AbstractThe effects of metal ion solutions (silver, copper, platinum, gold and palladium) were determined individually and in combination against Enterococcus faecium, Acinetobacter baumannii and Klebsiella pneumoniae. Platinum, gold and palladium showed the greatest antimicrobial efficacy in zone of inhibition (ZoI) assays. When tested in combinations using ZoI assays, gold/platinum, gold/palladium and platinum/palladium were indicative of synergy. Microbial inhibitory concentration demonstrated platinum and gold against Enterococcus faecium, platinum against Klebsiella pneumoniae and platinum and silver against Acinetobacter baumannii were optimal. Minimal bactericidal concentrations determined the greatest bactericidal activity was again platinum gold and palladium against all three bacteria. Fractional Inhibitory Concentration (FIC) studies demonstrated that the silver/platinum combination against Enterococcus faecium, and silver/copper combination against Acinetobacter baumannii demonstrated antimicrobial synergy. Following crystal violet biofilm assays for single metal ion solutions, antimicrobial efficacies were demonstrated for all the metals against all the bacteria Synergistic assays against biofilms demonstrated gold/palladium, gold/platinumand platinum/palladium resulted in the greatest antimicrobial efficacy. Overall, platinum, palladium and gold metal ion solutions in individual use or combination demonstrated the greatest antimicrobial efficacies against planktonic or biofilm bacteria. This work demonstrates the potential for using a range of metal ions, as biocidal formulations against both planktonic or biofilm bacteria.
Assessment of different techniques for 3D superimposition of serial digital maxillary dental casts on palatal structures
Authors: Vasilakos Georgios , Schilling Roman , Halazonetis Demetrios , Gkantidis Nikolaos 
Published: July 2017

AbstractSerial 3-dimensional dental model superimposition provides a risk-free, detailed evaluation of morphological alterations on a patient’s mouth. Here, we evaluated accuracy and precision of five palatal areas, used for superimposition of maxillary 3D digital dental casts. Sixteen pre- and post-orthodontic treatment dental casts of growing patients (median time lapse: 15.1 months) were superimposed on each palatal area using the iterative closest point algorithm. Area A (medial 2/3 of the third rugae and a small area dorsal to them) was considered the gold standard, due to high anatomical stability. Areas B, C, and D added a distal extension along the midpalatal raphe, an anterior extension to the second rugae, and the remaining palatal surface, respectively. Area E was similar to A, located more posteriorly. Non parametric multivariate models showed minimal or no effect on accuracy and precision by operator, time point, or software settings. However, the choice of superimposition area resulted in statistically significant differences in accuracy and clinically significant differences in detected tooth movement (95% limits of agreement exceeding 1 mm and 3°). Superimposition on area A provided accurate, reproducible, and precise results. Outcomes were comparable for area B, but deteriorated when alternative areas were used.
pH and Urea Estimation in Urine Samples using Single Fluorophore and Ratiometric Fluorescent Biosensors
Authors: Chaudhari Rashmi , Joshi Abhijeet , Srivastava Rohit 
Published: July 2017

AbstractKidney diseases remain often undiagnosed due to inefficient screening methods available at patient’s disposal. Early diagnosis and effective management of kidney problems can best be addressed by the development of biosensors for commonly occurring clinical biomarkers. Here we report the development of single fluorophore and dual fluorophore ratiometric biosensors based on alginate microspheres for pH and urea analysis in urine samples. A facile method of air driven atomization was used for developing these polymeric fluorophore and enzyme based biosensors. Ratiometric biosensors were developed using layer-by-layer coating of polyelectrolyte conjugated to reference fluorophores. Biosensing studies using these biosensors showed that samples in pathophysiological range can be measured having pH range of 4–8 and urea levels between 0–50 mM. Testing of urine samples using these biosensors showed that both pH and urea detection can be accurately performed without interference. Thus, we believe that FITC-Dextran and FITC-Dextran/RuBpy based pH and urea biosensors show a great potential to be translated as a point of care device for pH and urea biosensing in early detection and continuous monitoring of kidney diseases.
Annual variations of monsoon and drought detected by GPS: A case study in Yunnan, China
Authors: Jiang Weiping , Yuan Peng , Chen Hua , Cai Jianqing , Li Zhao , Chao Nengfang , Sneeuw Nico 
Published: July 2017

AbstractThe Global Positioning System (GPS) records monsoonal precipitable water vapor (PWV) and vertical crustal displacement (VCD) due to hydrological loading, and can thus be applied jointly to diagnose meteorological and hydrological droughts. We have analyzed the PWV and VCD observations during 2007.0–2015.0 at 26 continuous GPS stations located in Yunnan province, China. We also obtained equivalent water height (EWH) derived from the Gravity Recovery And Climate Experiment (GRACE) and precipitation at these stations with the same period. Then, we quantified the annual variations of PWV, precipitation, EWH and VCD and provided empirical relationships between them. We found that GPS-derived PWV and VCD (positive means downward movement) are in phase with precipitation and GRACE-derived EWH, respectively. The annual signals of VCD and PWV show linearly correlated amplitudes and a two-month phase lag. Furthermore, the results indicate that PWV and VCD anomalies can also be used to explore drought, such as the heavy drought during winter/spring 2010. Our analysis results verify the capability of GPS to monitor monsoon variations and drought in Yunnan and show that a more comprehensive understanding of the characteristics of regional monsoon and drought can be achieved by integrating GPS-derived PWV and VCD with precipitation and GRACE-derived EWH.
Centrosomal protein 55 activates NF-κB signalling and promotes pancreatic cancer cells aggressiveness
Authors: Peng Tao , Zhou Wei , Guo Feng , Wu He-shui , Wang Chun-you , Wang Li , Yang Zhi-yong 
Published: July 2017

AbstractCentrosomal protein 55 (CEP55) is a microtubule-bundling protein that participants in cell mitosis. It is overexpressed in several solid tumours and promotes the growth and invasion of cancer cells. However, the role of CEP55 in pancreatic cancer (PANC) remains unclear. Herein, upregulated expression of CEP55 (associated with poor prognosis) was detected in PANC using quantitative real-time reverse transcription PCR, western blotting, and immunohistochemistry. Cell migration, colony formation, wound-healing, and Transwell matrix penetration assays, revealed that upregulation of CEP55 promoted PANC cells proliferation, migration, and invasion in vitro, whereas knockdown of CEP55 attenuated it. In an in vivo murine model, CEP55 overexpression accelerated PANC cells tumourigenicity, together with upregulation of the protein levels of invasion-related proteins matrix metalloproteinase (MMP)2, MMP9, and proliferation-related protein Cyclin D1. Downregulation of CEP55 had the reverse effect. Moreover, the nuclear factor κB (NF-κB)/IκBα signalling pathway, which was activated in CEP55-transduced PANC cells and inhibited in CEP55-silenced PANC cells, contributed to CEP55-mediated PANC cell aggressiveness. This study provided new insights into the oncogenic roles of CEP55 and the mechanism by which the NF-κB pathway is hyperactivated in patients with PANC, indicating that CEP55 is a valuable prognostic factor and a potential therapeutic target in PANC.