bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preoperative red cell distribution width and neutrophil-to-lymphocyte ratio predict survival in patients with epithelial ovarian cancer
Authors: Li Zheng , Hong Na , Robertson Melissa , Wang Chen , Jiang Guoqian 
Published: February 2017

AbstractSeveral parameters of preoperative complete blood count (CBC) and inflammation-associated blood cell markers derived from them have been reported to correlate with prognosis in patients with epithelial ovarian cancer (EOC), but their prognostic importance and optimal cutoffs are still needed be elucidated. Clinic/pathological parameters, 5-year follow-up data and preoperative CBC parameters were obtained retrospectively in 654 EOC patients underwent primary surgery at Mayo Clinic. Cutoffs for neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) were optimized by receiver operating characteristic (ROC) curve. Prognostic significance for overall survival (OS) and recurrence free survival (RFS) were determined by Cox proportional hazards models and Kaplan-Meier method. Associations of RDW and NLR with clinic/pathological parameters were analyzed using non-parametric tests. RDW with cutoff 14.5 and NLR with cutoff 5.25 had independent prognostic significance for OS, while combined RDW and NLR scores stratified patients into low (RDW-low and NLR-low), intermediate (RDW-high or NLR-high) and high risk (RDW-high and NLR-high) groups, especially in patients with high-grade serous ovarian cancer (HGSOC). Moreover, high NLR was associated with poor RFS as well. Elevated RDW was strongly associated with age, whereas high NLR was strongly associated with stage, preoperative CA125 level and ascites at surgery.
Cellular glycosylation affects Herceptin binding and sensitivity of breast cancer cells to doxorubicin and growth factors
Authors: Peiris Diluka , Spector Alexander F. , Lomax-Browne Hannah , Azimi Tayebeh , Ramesh Bala , Loizidou Marilena , Welch Hazel , Dwek Miriam V. 
Published: February 2017

AbstractAlterations in protein glycosylation are a key feature of oncogenesis and have been shown to affect cancer cell behaviour perturbing cell adhesion, favouring cell migration and metastasis. This study investigated the effect of N-linked glycosylation on the binding of Herceptin to HER2 protein in breast cancer and on the sensitivity of cancer cells to the chemotherapeutic agent doxorubicin (DXR) and growth factors (EGF and IGF-1). The interaction between Herceptin and recombinant HER2 protein and cancer cell surfaces (on-rate/off-rate) was assessed using a quartz crystal microbalance biosensor revealing an increase in the accessibility of HER2 to Herceptin following deglycosylation of cell membrane proteins (deglycosylated cells Bmax: 6.83 Hz; glycosylated cells Bmax: 7.35 Hz). The sensitivity of cells to DXR and to growth factors was evaluated using an MTT assay. Maintenance of SKBR-3 cells in tunicamycin (an inhibitor of N-linked glycosylation) resulted in an increase in sensitivity to DXR (0.1 μM DXR P < 0.001) and a decrease in sensitivity to IGF-1 alone and to IGF-1 supplemented with EGF (P < 0.001). This report illustrates the importance of N-linked glycosylation in modulating the response of cancer cells to chemotherapeutic and biological treatments and highlights the potential of glycosylation inhibitors as future combination treatments for breast cancer.
Radiation exposure in the remote period after the Chernobyl accident caused oxidative stress and genetic effects in Scots pine populations
Authors: Volkova Polina Yu. , Geras’kin Stanislav A. , Kazakova Elizaveta A. 
Published: February 2017

AbstractEven 30 years after the Chernobyl accident, biological effects of irradiation are observed in the chronically exposed Scots pine populations. Chronic radiation exposure at dose rates above 50 mGy∙yr−1caused oxidative stress and led to the increase of antioxidants concentrations in these populations. Genetic variability was examined for 6 enzymes and 14 enzymatic loci of 6 Scots pine populations. Dose rates over 10 mGy∙yr−1caused the increased frequency of mutations and changes in genetic structure of Scots pine populations. However, the same dose rates had no effect on enzymatic activities. The results indicate that even relatively low dose rates of radiation can be considered as an ecological factor which should be taken into account for ecological management and radiation protection of biota species.
Identification of novel cancer therapeutic targets using a designed and pooled shRNA library screen
Authors: Oliver David , Ji Hao , Liu Piaomu , Gasparian Alexander , Gardiner Ellen , Lee Samuel , Zenteno Adrian , Perinskaya Lillian O. , Chen Mengqian , Buckhaults Phillip , Broude Eugenia , Wyatt Michael D. , Valafar Homayoun , Peña Edsel , Shtutman Michael 
Published: February 2017

AbstractTargeted cancer therapeutics aim to exploit tumor-specific, genetic vulnerabilities specifically affecting neoplastic cells without similarly affecting normal cells. Here we performed sequencing-based screening of an shRNA library on a panel of cancer cells of different origins as well as normal cells. The shRNA library was designed to target a subset of genes previously identified using a whole genome screening approach. This focused shRNA library was infected into cells followed by analysis of enrichment and depletion of the shRNAs over the course of cell proliferation. We developed a bootstrap likelihood ratio test for the interpretation of the effects of multiple shRNAs over multiple cell line passages. Our analysis identified 44 genes whose depletion preferentially inhibited the growth of cancer cells. Among these genes ribosomal protein RPL35A, putative RNA helicase DDX24, and coatomer complex I (COPI) subunit ARCN1 most significantly inhibited growth of multiple cancer cell lines without affecting normal cell growth and survival. Further investigation revealed that the growth inhibition caused by DDX24 depletion is independent of p53 status underlining its value as a drug target. Overall, our study establishes a new approach for the analysis of proliferation-based shRNA selection strategies and identifies new targets for the development of cancer therapeutics.
The miRNAome of Catharanthus roseus: identification, expression analysis, and potential roles of microRNAs in regulation of terpenoid indole alkaloid biosynthesis
Authors: Shen Ethan M. , Singh Sanjay K. , Ghosh Jayadri S. , Patra Barunava , Paul Priyanka , Yuan Ling , Pattanaik Sitakanta 
Published: February 2017

AbstractMicroRNAs (miRNAs) regulate numerous crucial biological processes in plants. However, information is limited on their involvement in the biosynthesis of specialized metabolites in plants, including Catharanthus roseus that produces a number of pharmaceutically valuable, bioactive terpenoid indole alkaloids (TIAs). Using small RNA-sequencing, we identified 181 conserved and 173 novel miRNAs (cro-miRNAs) in C. roseus seedlings. Genome-wide expression analysis revealed that a set of cro-miRNAs are differentially regulated in response to methyl jasmonate (MeJA). In silico target prediction identified 519 potential cro-miRNA targets that include several auxin response factors (ARFs). The presence of cleaved transcripts of miRNA-targeted ARFs in C. roseus cells was confirmed by Poly(A) Polymerase-Mediated Rapid Amplification of cDNA Ends (PPM-RACE). We showed that auxin (indole acetic acid, IAA) repressed the expression of key TIA pathway genes in C. roseus seedlings. Moreover, we demonstrated that a miRNA-regulated ARF, CrARF16, binds to the promoters of key TIA pathway genes and repress their expression. The C. roseus miRNAome reported here provides a comprehensive account of the cro-miRNA populations, as well as their abundance and expression profiles in response to MeJA. In addition, our findings underscore the importance of miRNAs in posttranscriptional control of the biosynthesis of specialized metabolites.
High-Intensity Aerobic Exercise Improves Both Hepatic Fat Content and Stiffness in Sedentary Obese Men with Nonalcoholic Fatty Liver Disease
Authors: Oh Sechang , So Rina , Shida Takashi , Matsuo Tomoaki , Kim Bokun , Akiyama Kentaro , Isobe Tomonori , Okamoto Yoshikazu , Tanaka Kiyoji , Shoda Junichi 
Published: February 2017

AbstractWe compared the effects of 12-week programs of resistance training (RT), high-intensity interval aerobic training (HIAT), and moderate-intensity continuous aerobic training (MICT). The primary goal was to evaluate the therapeutic effects of the exercise modalities for the management of nonalcoholic fatty liver disease (NAFLD). A total of 61 sedentary obese men with NAFLD were randomized into one of the following exercise regimens (RT, HIAT, or MICT). Hepatic fat content was decreased to a similar extent in the RT, HIAT, and MICT groups (−14.3% vs. −13.7% vs. −14.3%) without significant changes in weight and visceral fat. The gene expression levels of fatty acid synthesis were significantly decreased in the subjects’ monocytes. Hepatic stiffness was decreased only in the HIAT group (−16.8%). The stiffness change was associated with restored Kupffer cell phagocytic function (+17.8%) and decreased levels of inflammation such as leptin (−13.2%) and ferritin (−14.1%). RT, HIAT, and MICT were equally effective in reducing hepatic fat content, but only HIAT was effective in improving hepatic stiffness and restoring Kupffer cell function. These benefits appeared to be independent of detectable weight and visceral fat reductions; the benefits were acquired through the modulation ofin vivofatty acid metabolism and obesity-related inflammatory conditions.
Metabolic profiling of presymptomatic Huntington’s disease sheep reveals novel biomarkers
Authors: Skene Debra J. , Middleton Benita , Fraser Cara K. , Pennings Jeroen L. A. , Kuchel Timothy R. , Rudiger Skye R. , Bawden C. Simon , Morton A. Jennifer 
Published: February 2017

AbstractThe pronounced cachexia (unexplained wasting) seen in Huntington’s disease (HD) patients suggests that metabolic dysregulation plays a role in HD pathogenesis, although evidence of metabolic abnormalities in HD patients is inconsistent. We performed metabolic profiling of plasma from presymptomatic HD transgenic and control sheep. Metabolites were quantified in sequential plasma samples taken over a 25 h period using a targeted LC/MS metabolomics approach. Significant changes with respect to genotype were observed in 89/130 identified metabolites, including sphingolipids, biogenic amines, amino acids and urea. Citrulline and arginine increased significantly in HD compared to control sheep. Ten other amino acids decreased in presymptomatic HD sheep, including branched chain amino acids (isoleucine, leucine and valine) that have been identified previously as potential biomarkers of HD. Significant increases in urea, arginine, citrulline, asymmetric and symmetric dimethylarginine, alongside decreases in sphingolipids, indicate that both the urea cycle and nitric oxide pathways are dysregulated at early stages in HD. Logistic prediction modelling identified a set of 8 biomarkers that can identify 80% of the presymptomatic HD sheep as transgenic, with 90% confidence. This level of sensitivity, using minimally invasive methods, offers novel opportunities for monitoring disease progression in HD patients.
PVN Blockade of p44/42 MAPK Pathway Attenuates Salt-induced Hypertension through Modulating Neurotransmitters and Attenuating Oxidative Stress
Authors: Gao Hong-Li , Yu Xiao-Jing , Liu Kai-Li , Shi Xiao-Lian , Qi Jie , Chen Yan-Mei , Zhang Yan , Bai Juan , Yi Qiu-Yue , Feng Zhi-Peng , Chen Wen-Sheng , Cui Wei , Liu Jin-Jun , Zhu Guo-Qing , Kang Yu-Ming 
Published: February 2017

AbstractThe imbalance of neurotransmitters and excessive oxidative stress responses contribute to the pathogenesis of hypertension. In this study, we determined whether blockade of p44/42 MAPK pathway in the hypothalamic paraventricular nucleus (PVN) ameliorates the development of hypertension through modulating neurotransmitters and attenuating oxidative stress. Dahl salt-sensitive (S) rats received a high-salt diet (HS, 8% NaCl) or a normal-salt diet (NS, 0.3% NaCl) for 6 weeks and were treated with bilateral PVN infusion of PD-98059 (0.025 μg/h), a p44/42 MAPK inhibitor, or vehicle via osmotic minipump. HS resulted in higher mean arterial pressure (MAP) and Fra-like (Fra-LI) activity, and plasma and PVN levels of norepinephrine (NE), tyrosine hydroxylase (TH), NOX2 and NOX4, lower PVN levels of gamma-aminobutyric acid (GABA), copper/zinc superoxide dismutase (Cu/Zn-SOD) and the 67-kDa isoform of glutamate decarboxylase (GAD67), as compared with NS group. PD-98059 infusion reduced NE, TH, NOX2 and NOX4 in the PVN, and induced Cu/Zn-SOD and GAD67 in the PVN. It suggests that PVN blockade of p44/42 MAPK attenuates hypertension through modulating neurotransmitters and attenuating oxidative stress.
Antitumorigenic effect of atmospheric-pressure dielectric barrier discharge on human colorectal cancer cells via regulation of Sp1 transcription factor
Authors: Han Duksun , Cho Jin Hyoung , Lee Ra Ham , Bang Woong , Park Kyungho , Kim Minseok S. , Shim Jung-Hyun , Chae Jung-Il , Moon Se Youn 
Published: February 2017

AbstractHuman colorectal cancer cell lines (HT29 and HCT116) were exposed to dielectric barrier discharge (DBD) plasma at atmospheric pressure to investigate the anticancer capacity of the plasma. The dose- and time-dependent effects of DBDP on cell viability, regulation of transcription factor Sp1, cell-cycle analysis, and colony formation were investigated by means of MTS assay, DAPI staining, propidium iodide staining, annexin V–FITC staining, Western blot analysis, RT-PCR analysis, fluorescence microscopy, and anchorage-independent cell transformation assay. By increasing the duration of plasma dose times, significant reductions in the levels of both Sp1 protein and Sp1 mRNA were observed in both cell lines. Also, expression of negative regulators related to the cell cycle (such as p53, p21, and p27) was increased and of the positive regulator cyclin D1 was decreased, indicating that the plasma treatment led to apoptosis and cell-cycle arrest. In addition, the sizes and quantities of colony formation were significantly suppressed even though two cancer promoters, such as TPA and epidermal growth factor, accompanied the plasma treatment. Thus, plasma treatment inhibited cell viability and colony formation by suppressing Sp1, which induced apoptosis and cell-cycle arrest in these two human colorectal cancer cell lines.
Prevention of tumorigenesis in mice by exercise is dependent on strain background and timing relative to carcinogen exposure
Authors: Kelly Scott A. , Zhao Liyang , Jung Kuo-Chen , Hua Kunjie , Threadgill David W. , Kim Yunjung , de Villena Fernando Pardo Manuel , Pomp Daniel 
Published: February 2017

AbstractAmong cancer diagnoses, colorectal cancer (CRC) is prevalent, with a lifetime risk of developing CRC being approximately 5%. Population variation surrounding the mean risk of developing CRCs has been associated with both inter-individual differences in genomic architecture and environmental exposures. Decreased risk of CRC has been associated with physical activity, but protective responses are variable. Here, we utilized a series of experiments to examine the effects of genetic background (strain), voluntary exercise (wheel running), and their interaction on azoxymethane (AOM)-induced intestinal tumor number and size in mice. Additionally, we investigated how the timing of exercise relative to AOM exposure, and amount of exercise, affected tumor number and size. Our results indicated that voluntary exercise significantly reduced tumor number in a strain dependent manner. Additionally, among strains where exercise reduced tumor number (A/J, CC0001/Unc) the timing of voluntary exercise relative to AOM exposure was crucial. Voluntary exercise prior to or during AOM treatment resulted in a significant reduction in tumor number, but exercise following AOM exposure had no effect. The results indicate that voluntary exercise should be used as a preventative measure to reduce risk for environmentally induced CRC with the realization that the extent of protection may depend on genetic background.
Three TFL1 homologues regulate floral initiation in the biofuel plant Jatropha curcas
Authors: Li Chaoqiong , Fu Qiantang , Niu Longjian , Luo Li , Chen Jianghua , Xu Zeng-Fu 
Published: February 2017

AbstractRecent research revealed that TERMINAL FLOWER 1 (TFL1) homologues are involved in the critical developmental process of floral initiation in several plant species. In this study, the functions of three putative TFL1 homologues (JcTFL1a, JcTFL1b and JcTFL1c) in the biofuel plant Jatropha curcas were analysed using the transgenic approach. JcTFL1b and JcTFL1c, but not JcTFL1a, could complement the TFL1 function and rescue early flowering and determinate inflorescence phenotype in tfl1-14 Arabidopsis mutant, thus suggesting that JcTFL1b and JcTFL1c may be homologues of TFL1. Transgenic Jatropha overexpressing JcTFL1a, JcTFL1b or JcTFL1c showed late flowering, whereas only JcTFL1b and JcTFL1c overexpression delayed flowering in transgenic Arabidopsis. JcTFL1b-RNAi transgenic Jatropha consistently exhibited moderately early flowering phenotype. JcFT and JcAP1 were significantly downregulated in transgenic Jatropha overexpressing JcTFL1a, JcTFL1b or JcTFL1c, which suggested that the late flowering phenotype of these transgenic Jatropha may result from the repressed expression of JcFT and JcAP1. Our results indicate that these three JcTFL1 genes play redundant roles in repressing flowering in Jatropha.
The scaling and allometry of organ size associated with miniaturization in insects: A case study for Coleoptera and Hymenoptera
Authors: Polilov Alexey A. , Makarova Anastasia A. 
Published: February 2017

AbstractThe study of the influence of body size on structure in animals, as well as scaling of organs, is one of the key areas of functional and evolutionary morphology of organisms. Most studies in this area treated mammals or birds; comparatively few studies are available on other groups of animals. Insects, because of the huge range of their body sizes and because of their colossal diversity, should be included in the discussion of the problem of scaling and allometry in animals, but to date they remain insufficiently studied. In this study, а total of 28 complete (for all organs) and 24 partial 3D computer reconstructions of body and organs have been made for 23 insect species of 11 families and five orders. The relative volume of organs was analyzed based on these models. Most insect organs display a huge potential for scaling and for retaining their organization and constant relative volume. By contrast, the relative volume of the reproductive and nervous systems increases by a considerable factor as body size decreases. These systems can geometrically restrain miniaturization in insects and determine the limits to the smallest possible body size.
High-fidelity self-assembly pathways for hydrogen-bonding molecular semiconductors
Authors: Lin Xu , Suzuki Mika , Gushiken Marina , Yamauchi Mitsuaki , Karatsu Takashi , Kizaki Takahiro , Tani Yuki , Nakayama Ken-ichi , Suzuki Mitsuharu , Yamada Hiroko , Kajitani Takashi , Fukushima Takanori , Kikkawa Yoshihiro , Yagai Shiki 
Published: February 2017

AbstractThe design of molecular systems with high-fidelity self-assembly pathways that include several levels of hierarchy is of primary importance for the understanding of structure-function relationships, as well as for controlling the functionality of organic materials. Reported herein is a high-fidelity self-assembly system that comprises two hydrogen-bonding molecular semiconductors with regioisomerically attached short alkyl chains. Despite the availability of both discrete cyclic and polymeric linear hydrogen-bonding motifs, the two regioisomers select one of the two motifs in homogeneous solution as well as at the 2D-confined liquid-solid interface. This selectivity arises from the high directionality of the involved hydrogen-bonding interactions, which renders rerouting to other self-assembly pathways difficult. In thin films and in the bulk, the resulting hydrogen-bonded assemblies further organize into the expected columnar and lamellar higher-order architectures via solution processing. The contrasting organized structures of these regioisomers are reflected in their notably different miscibility with soluble fullerene derivatives in the solid state. Thus, electron donor-acceptor blend films deliver a distinctly different photovoltaic performance, despite their virtually identical intrinsic optoelectronic properties. Currently, we attribute this high-fidelity control via self-assembly pathways to the molecular design of these supramolecular semiconductors, which lacks structure-determining long aliphatic chains.
Rumination and Default Mode Network Subsystems Connectivity in First-episode, Drug-Naive Young Patients with Major Depressive Disorder
Authors: Zhu Xueling , Zhu Qiuling , Shen Huaizhen , Liao Weihua , Yuan Fulai 
Published: February 2017

AbstractNeuroimaging evidence implicates the association between rumination and default mode network (DMN) in major depressive disorder (MDD). However, the relationship between rumination and DMN subsystems remains incompletely understood, especially in patients with MDD. Thirty-three first-episode drug-naive patients with MDD and thirty-three healthy controls (HCs) were enrolled and underwent resting-sate fMRI scanning. Functional connectivity analysis was performed based on 11 pre-defined regions of interest (ROIs) for three DMN subsystems: the midline core, dorsal medial prefrontal cortex (dMPFC) and medial temporal lobe (MTL). Compared with HCs group, patients with MDD exhibited increased within-system connectivity in the dMPFC subsystem and inter-system connectivity between the dMPFC and MTL subsystems. Decreased inter-system connectivity was identified between the midline core and dMPFC subsystem in MDD patients. Depressive rumination was positively correlated with within-system connectivity in the dMPFC subsystem (dMPFC-TempP) and with inter-system connectivity between the dMPFC and MTL subsystems (LTC-PHC). Our results suggest MDD may be characterized by abnormal DMN subsystems connectivity, which may contribute to the pathophysiology of the maladaptive self-focus in MDD patients.