bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of ribonucleotide synthesis by the Pseudomonas aeruginosa two-component system AlgR in response to oxidative stress
Authors: Crespo Anna , Pedraz Lucas , Van Der Hofstadt Marc , Gomila Gabriel , Torrents Eduard 
Published: December 2017

AbstractRibonucleotide reductases (RNR) catalyze the last step of deoxyribonucleotide synthesis, and are therefore essential to DNA-based life. Three forms of RNR exist: classes I, II, and III. While eukaryotic cells use only class Ia RNR, bacteria can harbor any combination of classes, granting them adaptability. The opportunistic pathogen Pseudomonas aeruginosa surprisingly encodes all three classes, allowing it to thrive in different environments. Here we study an aspect of the complex RNR regulation whose molecular mechanism has never been elucidated, the well-described induction through oxidative stress, and link it to the AlgZR two-component system, the primary regulator of the mucoid phenotype. Through bioinformatics, we identify AlgR binding locations in RNR promoters, which we characterize functionally through EMSA and physically through AFM imaging. Gene reporter assays in different growth models are used to study the AlgZR-mediated control on the RNR network under various environmental conditions and physiological states. Thereby, we show that the two-component system AlgZR, which is crucial for bacterial conversion to the mucoid phenotype associated with chronic disease, controls the RNR network and directs how the DNA synthesis pathway is modulated in mucoid and non-mucoid biofilms, allowing it to respond to oxidative stress.
Controlling bottom-up rapid growth of single crystalline gallium nitride nanowires on silicon
Authors: Wu Ko-Li , Chou Yi , Su Chang-Chou , Yang Chih-Chaing , Lee Wei-I. , Chou Yi-Chia 
Published: December 2017

AbstractWe report single crystalline gallium nitride nanowire growth from Ni and Ni-Au catalysts on silicon using hydride vapor phase epitaxy. The growth takes place rapidly; efficiency in time is higher than the conventional nanowire growth in metal-organic chemical vapor deposition and thin film growth in molecular beam epitaxy. The effects of V/III ratio and carrier gas flow on growth are discussed regarding surface polarity and sticking coefficient of molecules. The nanowires of gallium nitride exhibit excellent crystallinity with smooth and straight morphology and uniform orientation. The growth mechanism follows self-assembly from both catalysts, where Au acts as a protection from etching during growth enabling the growth of ultra-long nanowires. The photoluminescence of such nanowires are adjustable by tuning the growth parameters to achieve blue emission. The practical range of parameters for mass production of such high crystal quality and uniformity of nanowires is suggested.
Runx2 mediated Induction of Novel Targets ST2 and Runx3 Leads to Cooperative Regulation of Hypertrophic Differentiation in ATDC5 Chondrocytes
Authors: Bonyadi Rad Ehsan , Musumeci Giuseppe , Pichler Karin , Heidary Maryam , Szychlinska Marta Anna , Castrogiovanni Paola , Marth Egon , Böhm Christina , Srinivasaiah Sriveena , Krönke Gerhard , Weinberg Annelie , Schäfer Ute 
Published: December 2017

AbstractKnowledge concerning expression and function of Suppression of Tumorigenicity 2 (ST2) in chondrocytes is at present, limited. Analysis of murine growth plates and ATDC5 chondrocytes indicated peak expression of the ST2 transmembrane receptor (ST2L) and soluble (sST2) isoforms during the hypertrophic differentiation concomitant with the expression of the hypertrophic markers Collagen X (Col X), Runx2 and MMP-13. Gain- and loss-of-function experiments in ATDC5 and primary human growth plate chondrocytes (PHCs), confirmed regulation of ST2 by the key transcription factor Runx2, indicating ST2 to be a novel Runx2 target. ST2 knock-out mice (ST2−/−) exhibited noticeable hypertrophic zone (HZ) reduction in murine growth plates, accompanied by lower expression of Col X and Osteocalcin (OSC) compared to wild-type (WT) mice. Likewise, ST2 knockdown resulted in decreased Col X expression and downregulation of OSC and Vascular Endothelial Growth Factor (VEGF) in ATDC5 cells. The ST2 suppression was also associated with upregulation of the proliferative stage markers Sox9 and Collagen II (Col II), indicating ST2 to be a new regulator of ATDC5 chondrocyte differentiation. Runx3 was, furthermore, identified as a novel Runx2 target in chondrocytes. This study suggests that Runx2 mediates ST2 and Runx3 induction to cooperatively regulate hypertrophic differentiation of ATDC5 chondrocytes.
Modeling of autophagy-related gene expression dynamics during long term fasting in European eel (Anguilla anguilla)
Authors: Bolliet Valérie , Labonne Jacques , Olazcuaga Laure , Panserat Stéphane , Seiliez Iban 
Published: December 2017

AbstractAutophagy is an evolutionary conserved cellular self-degradation process considered as a major energy mobilizing system in eukaryotes. It has long been considered as a post-translationally regulated event, and the importance of transcriptional regulation of autophagy-related genes (atg) for somatic maintenance and homeostasis during long period of stress emerged only recently. In this regard, large changes in atg transcription have been documented in several species under diverse types of prolonged catabolic situations. However, the available data primarily concern atg mRNA levels at specific times and fail to capture the dynamic relationship between transcript production over time and integrated phenotypes. Here, we present the development of a statistical model describing the dynamics of expression of several atg and lysosomal genes in European glass eel (Anguilla anguilla) during long-term fasting at two temperatures (9 °C and 12 °C) and make use of this model to infer the effect of transcripts dynamics on an integrated phenotype – here weight loss. Our analysis shows long-term non-random fluctuating atg expression dynamics and reveals for the first time a significant contribution of atg transcripts production over time to weight loss. The proposed approach thus offers a new perspective on the long-term transcriptional control of autophagy and its physiological role.
Evidence of novel miR-34a-based therapeutic approaches for multiple myeloma treatment
Authors: Zarone Mayra Rachele , Misso Gabriella , Grimaldi Anna , Zappavigna Silvia , Russo Margherita , Amler Evzen , Di Martino Maria Teresa , Amodio Nicola , Tagliaferri Pierosandro , Tassone Pierfrancesco , Caraglia Michele 
Published: December 2017

AbstractMiR-34a acts as tumor suppressor microRNA (miRNA) in several cancers, including multiple myeloma (MM), by controlling the expression of target proteins involved in cell cycle, differentiation and apoptosis. Here, we have investigated the combination between miR-34a and γ-secretase inhibitor (γSI), Sirtinol or zoledronic acid (ZOL) in order to enhance the inhibitory action of this miRNA on its canonical targets such as Notch1 and SIRT1, and on Ras/MAPK-dependent pathways. Our data demonstrate that miR-34a synthetic mimics significantly enhance the anti-tumor activity of all the above-mentioned anti-cancer agents in RPMI 8226 MM cells. We found that γSI enhanced miR-34a-dependent anti-tumor effects by activating the extrinsic apoptotic pathway which could overcome the cytoprotective autophagic mechanism. Moreover, the combination between miR-34a and γSI increased the cell surface calreticulin (CRT) expression, that is well known for triggering anti-tumor immunological response. The combination between miR-34a and Sirtinol induced the activation of an intrinsic apoptotic pathway along with increased surface expression of CRT. Regarding ZOL, we found a powerful growth inhibition after enforced miR-34a expression, which was not likely attributable to neither apoptosis nor autophagy modulation. Based on our data, the combination of miR-34a with other anti-cancer agents appears a promising anti-MM strategy deserving further investigation.
Concomitant activation of ETS-like transcription factor-1 and Death Receptor-5 via extracellular signal-regulated kinase in withaferin A-mediated inhibition of hepatocarcinogenesis in mice
Authors: Kuppusamy Panjamurthy , Nagalingam Arumugam , Muniraj Nethaji , Saxena Neeraj K. , Sharma Dipali 
Published: December 2017

AbstractHepatocellular carcinoma (HCC) has the second lowest 5-year survival rate (~16%) of all tumor types partly owing to the lack of effective therapeutic agents. Withaferin A (WA) is a bioactive molecule derived from Withania somnifera and the present study is designed to systemically investigate the anti-HCC efficacy of WA. WA inhibited growth, migration and invasion of HCC cells. Using a phospho-kinase screening array, we discovered that WA increased phosphorylation of ERK and p38 in HCC. Further analyses revealed a key role of ERK leading to increased phosphorylation of p90-ribosomal S6 kinase (RSK) and a concomitant activation of ETS-like transcription factor-1(ELK1) and Death Receptor protein-5 (DR5) in HCC. Importantly, oral administration of WA effectively inhibited HepG2-xenografts and DEN-induced-HCC in C57BL/6 mice. Analyses of WA-treated HepG2-xenografts and DEN-induced-HCC tumors showed elevated levels of ERK, RSK, ELK1 and DR5 along with decreased expression of Ki67. In silico analyses of HCC, utilizing published profiling studies showed an inverse correlation between DR5 and Ki67. These data showed the efficacy of WA as an effective agent for HCC inhibition and provided first in vitro and in vivo evidence supporting the key role of a novel crosstalk between WA, ERK/RSK, ELK1, and DR5 in HCC inhibition.
Long-term impact of intrauterine neuroinflammation and treatment with magnesium sulphate and betamethasone: Sex-specific differences in a preterm labor murine model
Authors: Thagard Andrew S. , Slack Jessica L. , Estrada Sarah M. , Kazanjian Avedis A. , Chan Sem , Burd Irina , Napolitano Peter G. , Ieronimakis Nicholas 
Published: December 2017

AbstractPreterm infants are at significantly increased risk for lifelong neurodevelopmental disability with male offspring disproportionately affected. Corticosteroids (such as betamethasone) and magnesium sulphate (MgSO4) are administered to women in preterm labor to reduce neurologic morbidity. Despite widespread use of MgSO4 in clinical practice, its effects on adult offspring are not well known nor have sex-specific differences in therapeutic response been explored. The objective of our study was to examine the long-term effects of perinatal neuroinflammation and the effectiveness of prenatal MgSO4/betamethasone treatments between males and females in a murine model via histologic and expression analyses. Our results demonstrate that male but not female offspring exposed to intrauterine inflammation demonstrated impaired performance in neurodevelopmental testing in early life assessed via negative geotaxis, while those exposed to injury plus treatment fared better. Histologic analysis of adult male brains identified a significant reduction in hippocampal neural density in the injured group compared to controls. Evaluation of key neural markers via qRT-PCR demonstrated more profound differences in gene expression in adult males exposed to injury and treatment compared to female offspring, which largely showed resistance to injury. Prenatal treatment with MgSO4/betamethasone confers long-term benefits beyond cerebral palsy prevention with sex-specific differences in response.
Atomistic study of the solid state inside graphene nanobubbles
Authors: Iakovlev Evgeny , Zhilyaev Petr , Akhatov Iskander 
Published: December 2017

AbstractA two-dimensional (2D) material placed on an atomically flat substrate can lead to the formation of surface nanobubbles trapping different types of substances. In this paper graphene nanobubbles of the radius of 7–34 nm with argon atoms inside are studied using molecular dynamics (MD). All modeled graphene nanobubbles except for the smallest ones exhibit an universal shape, i.e., a constant ratio of a bubble height to its footprint radius, which is in an agreement with experimental studies and their interpretation using the elastic theory of membranes. MD simulations reveal that argon does exist in a solid close-packed phase, although the internal pressure in the nanobubble is not sufficiently high for the ordinary crystallization that would occur in a bulk system. The smallest graphene bubbles with a radius of 7 nm exhibit an unusual “pancake” shape. Previously, nanobubbles with a similar pancake shape were experimentally observed in completely different systems at the interface between water and a hydrophobic surface.
Identification and characterization of the structure–activity relationships involved in UGT1A1 inhibition by anthraquinone and dianthrone constituents of Polygonum multiflorum
Authors: Wang Qi , Wang Yadan , Li Yong , Wen Binyu , Dai Zhong , Ma Shuangcheng , Zhang Yujie 
Published: December 2017

AbstractThe adverse effects of Polygonum (P.) multiflorum, including abnormal bilirubin metabolism, are a serious public health issue. As uridine diphosphate (UDP)-glucuronosyltransferase 1A1 (UGT1A1) is the only enzyme responsible for bilirubin metabolism, we investigated the inhibitory effect of a P. multiflorum extract and 10 anthraquinone and dianthrone compounds on UGT1A1 in rat liver microsomes in vitro. The P. multiflorum extract exhibited the strongest inhibitory effect on UGT1A1 activity (inhibition constant [Ki] = 0.3257 μM, 1422 μg of material/mL), followed by cis-emodin dianthrones (Ki = 0.8630 μM), trans-emodin dianthrones (Ki = 1.083 μM), emodin-8-O-glc (Ki = 3.425 μM), and polygonumnolide C2 (Ki = 4.291 μM). Analysis of the structure–activity relationships of these compounds suggested that the spatial orientation of the molecules and the presence of particular functional groups affect UGT1A1 inhibition. A mechanistic analysis showed that all the tested compounds docked into two of the nine active sites of UGT1A1 and suggested that hydrophobic interactions and hydrogen bonds are important for the affinity of the tested compounds for UGT1A1; moreover, their interaction energies were generally in agreement with the Ki values. These findings provide insight into adverse reactions to P. multiflorum and identify the pharmacophores involved in inhibition of UGT1A1.
Formation of Cell Membrane Component Domains in Artificial Lipid Bilayer
Authors: Tero Ryugo , Fukumoto Kohei , Motegi Toshinori , Yoshida Miyu , Niwano Michio , Hirano-Iwata Ayumi 
Published: December 2017

AbstractThe lipid bilayer environment around membrane proteins strongly affects their structure and functions. Here, we aimed to study the fusion of proteoliposomes (PLs) derived from cultured cells with an artificial lipid bilayer membrane and the distribution of the PL components after the fusion. PLs, which were extracted as a crude membrane fraction from Chinese hamster ovary (CHO) cells, formed isolated domains in a supported lipid bilayer (SLB), comprising phosphatidylcholine (PC), phosphatidylethanolamine (PE), and cholesterol (Chol), after the fusion. Observation with a fluorescence microscope and an atomic force microscope showed that the membrane fusion occurred selectively at microdomains in the PC + PE + Chol-SLB, and that almost all the components of the PL were retained in the domain. PLs derived from human embryonic kidney 293 (HEK) cells also formed isolated domains in the PC + PE + Chol-SLB, but their fusion kinetics was different from that of the CHO-PLs. We attempted to explain the mechanism of the PL-SLB fusion and the difference between CHO- and HEK-PLs, based on a kinetic model. The domains that contained the whole cell membrane components provided environments similar to that of natural cell membranes, and were thus effective for studying membrane proteins using artificial lipid bilayer membranes.
Agarose capsules as new tools for protecting denuded mouse oocytes/embryos during handling and freezing-thawing and supporting embryonic development in vivo
Authors: Nagatomo Hiroaki , Yao Tatsuma , Araki Yasuyuki , Mizutani Eiji , Wakayama Teruhiko 
Published: December 2017

AbstractOocytes without a zona pellucida (ZP) often occur as a result of congenital or operational effects, but they are difficult to handle, and embryonic survival is low. Such zona-free (ZF) oocytes are therefore not used in clinics or laboratories. Furthermore, in the laboratory, removal of the ZP is often necessary for genetic manipulation by viral infection or twin production by blastomere separation, but adverse effects on development have been reported. It would therefore be extremely valuable if the embryo could be covered with a structure similar to that of the ZP. In this study, we sought to determine whether an agarose capsule could serve as a substitute for the ZP. Our results indicate that embryos derived from these agarose capsules were able to develop normally, and could be transplanted to obtain viable offspring, without having to remove the agarose capsule. Furthermore, before compaction, the agarose capsule embryos exhibited good freezing tolerance, and survival rate was extremely high compared to ZF embryos. Thus, agarose capsules represent a valuable tool for utilizing oocytes and embryos that lack a ZP, both in a clinical and livestock setting.
Confocal laser feedback microscopy for in‐depth imaging applications
Authors: Mowla A. , Taimre T. , Bertling K. , Wilson S. , Rakić A. D. 
Published: December 2017

We propose confocal laser feedback microscopy for in‐depth imaging of highly scattering samples. This technique provides a compact configuration for microscopy in reflectance mode; it is based on laser feedback interferometry which is a sensing technique where the laser acts as both transmitter and receiver of the beam. Operating at 850 nm, it offers an ideal platform for non‐invasive and in vivo imaging of soft biological tissues. To explore the technique, the authors performed microscopic imaging of micro‐glass‐spheres (with diameter sizes of 10–20 µm) deep within an agar gel sample, at depth of 0.43 mm from the surface. Experimental results show the feasibility of a compact, low‐cost, and simple laser‐scanning microscope with possible biomedical imaging applications.
Synthesis of Tricyclic Marine Alkaloids, Cylindricines, Lepadiformines, Fasicularin, and Polycitorols: A Recent Update
Authors: Chiba Shunsuke , Kaga Atsushi 
Published: December 2017

Cylindricines, lepadiformines, and fasicularin are tricyclic marine alkaloids bearing perhydropyrrolo- and pyrido[2,1-j] frameworks having divergent chemical functionalities. They have been isolated from marine tunicates over the last two decades and found to have a range of cytotoxicity such as DNA-alkylating ability. Recently, polycitorols have emerged as a new member of this alkaloid family. Their unique structural features and biological activities have intrigued many researchers and challenged them in their synthesis. This review describes recent syntheses of the tricyclic alkaloids based on key synthetic approaches.1	Introduction2	Total and Formal Syntheses2.1	Overview of Synthetic Strategies2.2	Azaspirocycle (BC Ring) Approaches2.3	Indolizidine (AC Ring) Approaches2.4	Azadecalin (AB Ring) Approaches2.5	Tandem Cyclization Approaches3	Summary and Future Perspective
Continuous Flow Conversion of Glycerol into Chemicals: An Overview
Authors: Len Christophe , Delbecq Frederic , Cara Corpas Cristobal , Ruiz Ramos Encarnacion 
Published: December 2017

This report highlights the recent advances for glycerol valorization to valuable products in liquid phase continuous flow systems using different types of catalysts and processes. The main biobased chemicals obtained from glycerol, such as acrolein, lactic acid, dihydroxyacetone, propanediols, glycerol carbonate, solketal, acetin, alkyl ethers, and oligomers, will be presented.1	Introduction2	Continuous Dehydration2.1	Without Added Catalyst2.2	With Acid Catalyst3	Continuous Oxidation4	Continuous Hydrogenolysis5	Continuous Carbonatation6	Continuous Ketalization7	Continuous Esterification8	Continuous Etherification9	Continuous Oligomerization10	Outlook11	Conclusion
Outcomes of the Ulnar Shortening Osteotomy Using a Dynamic Compression Plate on the Ulnar Surface of the Ulna
Authors: Rozée Bernhard , Elgammal Ahmed 
Published: December 2017

Background The purpose of this study is to evaluate the results of patients with ulnar impaction syndrome treated with diaphyseal osteotomy using freehand technique and fixation with ulnar osteotomy compression plate placed on the ulnar surface of the ulna.
Materials and Methods A retrospective chart review of patients with ulnar impaction syndrome between 2010 and 2014 identified 38 patients. The following clinical data were observed: patient age, sex, range of motion, grip strength, visual analog scale (VAS), Disabilities of the Arm, Shoulder, and Hand (DASH) score, radiological assessment, and complications. The mean follow-up period is 30 months. Eleven patients were excluded from the study.
Results Compared with the contralateral side, the 27 patients included in this study attained 93 to 96% of wrist and forearm motion and 81% of the grip strength. The average DASH score was 18 in a mean follow-up period of 30 months. Three patients required plate removal and one case showed nonunion and a further operation was needed. Two patients reported persistent ulnar-sided wrist pain.
Conclusion We concluded that placing the ulnar osteotomy plate on the ulnar surface of the ulna is a quicker procedure, with less soft tissue dissection and irritation, and very high union rate.
Level of Evidence Level IV.
Tumor Vascularity Does Not Predict Response to Yttrium-90 Radioembolization for Hepatic Metastases from Colorectal Cancer
Authors: Naydenov Alipi , Harris William , Johnson Guy , Hippe Daniel , Padia Siddharth 
Published: December 2017

AbstractThe purpose of this study was to determine whether the degree of tumor vascularity based on imaging has an impact on tumor response and survival in patients with metastatic colorectal cancer (mCRC) to the liver undergoing yttrium-90 radioembolization. A retrospective study of 75 mCRC patients from a single-institution undergoing radioembolization was performed over a 7-year period. Tumors were categorized as hypo- or hypervascular based on digital subtraction angiography (DSA) and C-arm CT during mapping angiography. Tumor response and survival were compared between each group, after undergoing radioembolization. Hypervascular tumors were present in 37 of 75 (49%) patients according to DSA. Of 37 patients who underwent C-arm CT during the procedure, 22 (59%) had tumors classified as hypervascular. There were no significant differences in tumor response rates when vascularity was stratified by DSA or C-arm CT. Median progression-free survival (PFS) was 111 versus 128 days (p = 0.41) between DSA hypervascular and hypovascular cases, and median overall survival (OS) was 439 versus 342 days (p = 0.96). When stratified by C-arm CT, median PFS was 313 versus 244 days (p = 0.83) and median OS was 489 versus 342 days (p = 0.74) for hypervascular and hypovascular cases, respectively. Tumor vascularity based on DSA or C-arm CT does not predict imaging response or survival after radioembolization and should not be used as a criterion for selecting candidates for radioembolization for hepatic mCRC.