bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic variants in ERCC1 and XPC predict survival outcome of non-small cell lung cancer patients treated with platinum-based therapy
Authors: Zhang Ruoxin , Jia Ming , Xue Huijing , Xu Yuan , Wang Mengyun , Zhu Meiling , Sun Menghong , Chang Jianhua , Wei Qingyi 
Published: August 2017

AbstractNucleotide excision repair (NER) plays a vital role in platinum-induced DNA damage during chemotherapy. We hypothesize that regulatory single nucleotide polymorphisms (rSNPs) of the core NER genes modulate clinical outcome of patients with advanced non-small cell lung cancer (NSCLC) treated with platinum-based chemotherapy (PBS). We investigated associations of 25 rSNPs in eight NER genes with progression free survival (PFS) and overall survival (OS) in 710 NSCLC patients. We found that ERCC1 rs3212924 AG/GG and XPC rs2229090 GC/CC genotypes were associated with patients’ PFS (HRadj = 1.21, 95% CI = 1.03–1.43, Padj = 0.021 for ERCC1 and HRadj = 0.80, 95% CI = 0.68–0.94, Padj = 0.007 for XPC), compared with the AA and GG genotypes, respectively. The association of XPC rs2229090 was more apparent in adenocarcinoma than in squamous cell carcinoma patients. Additionally, ERCC4 rs1799798 GA/AA genotypes were associated with poorer OS (HRadj = 1.32, 95% CI = 1.04–1.69, Padj = 0.026), compared with the GG genotype. The expression quantitative trait loci analysis revealed that ERCC1 rs3212924 and XPC rs2229090 might regulate transcription of their genes, which is consistent with their associations with survival. Larger studies are needed to validate our findings with further functional studies to elucidate the mechanisms underlying these observed associations.
Plasmid transfection influences the readout of nonsense-mediated mRNA decay reporter assays in human cells
Authors: Gerbracht Jennifer V. , Boehm Volker , Gehring Niels H. 
Published: August 2017

AbstractMessenger RNA (mRNA) turnover is a crucial and highly regulated step of gene expression in mammalian cells. This includes mRNA surveillance pathways such as nonsense-mediated mRNA decay (NMD), which assesses the fidelity of transcripts and eliminates mRNAs containing a premature translation termination codon (PTC). When studying mRNA degradation pathways, reporter mRNAs are commonly expressed in cultivated cells. Traditionally, the molecular mechanism of NMD has been characterized using pairs of reporter constructs that express the same mRNA with (“PTC-containing mRNA”) or without (“wild-type mRNA”) a PTC. Cell lines stably expressing an NMD reporter have been reported to yield very robust and highly reproducible results, but establishing the cell lines can be very time-consuming. Therefore, transient transfection of such reporter constructs is frequently used and allows analysis of many samples within a short period of time. However, the behavior of transiently and stably transfected NMD constructs has not been systematically compared so far. Here, we report that not all commonly used human cell lines degrade NMD targets following transient transfection. Furthermore, the degradation efficiency of NMD substrates can depend on the manner of transfection within the same cell line. This has substantial implications for the interpretation of NMD assays based on transient transfections.
A Novel Benzocoumarin-Stilbene Hybrid as a DNA ligase I inhibitor with in vitro and in vivo anti-tumor activity in breast cancer models
Authors: Hussain Mohd. Kamil , Singh Deependra Kumar , Singh Akhilesh , Asad Mohd. , Ansari Mohd. Imran , Shameem Mohammad , Krishna Shagun , Valicherla Guru R. , Makadia Vishal , Meena Sanjeev , Deshmukh Amit Laxmikant , Gayen Jiaur R. , Imran Siddiqi Mohammad , Datta Dipak , Hajela Kanchan , Banerjee Dibyendu 
Published: August 2017

AbstractExisting cancer therapies are often associated with drug resistance and toxicity, which results in poor prognosis and recurrence of cancer. This necessitates the identification and development of novel therapeutics against existing as well as novel cellular targets. In this study, a novel class of Benzocoumarin-Stilbene hybrid molecules were synthesized and evaluated for their antiproliferative activity against various cancer cell lines followed by in vivo antitumor activity in a mouse model of cancer. The most promising molecule among the series, i.e. compound (E)-4-(3,5-dimethoxystyryl)-2H-benzo[h]chromen-2-one (19) showed maximum antiproliferative activity in breast cancer cell lines (MDA-MB-231 and 4T1) and decreased the tumor size in the in-vivo 4T1 cell-induced orthotopic syngeneic mouse breast cancer model. The mechanistic studies of compound 19 by various biochemical, cell biology and biophysical approaches suggest that the compound binds to and inhibits the human DNA ligase I enzyme activity that might be the cause for significant reduction in tumor growth and may constitute a promising next-generation therapy against breast cancers.
Some sustained improvements in pneumonia case management four and five years following implementation of paediatric hospital guidelines in Lao PDR
Authors: Gray Amy , Chhor Louis , Sanyalack Saysanasongkham , Lim Ruth , Lai Jana , Vilivong Keo , Morpeth Melinda , Soukaloun Douangdao , Russell Fiona 
Published: August 2017

AbstractIn 2010, WHO paediatric hospital guidelines were implemented in Lao PDR, along with training workshops and feedback audits, achieving significant improvements in pneumonia case management when assessed one-year post-intervention. The sustainability of these improvements is hereby assessed, four and five years post-intervention. Medical records of children aged 1–59 months, diagnosed with pneumonia in 2010, 2011, 2014 and 2015 from a central Lao hospital were reviewed. Information relating to clinical steps in pneumonia case management was extracted and a scoring system applied based on the documentation of each clinical step, producing a pneumonia assessment score for each case. Comparisons of clinical steps and mean assessment score across study years were performed using Pearson’s chi-squared and t-tests, respectively. Of 231 pneumonia cases, the mean assessment scores in 2010, 2011, 2014 and 2015 were 57%, 96%, 69% and 69% respectively, showing a significant reduction from the immediate post-intervention period (2011) to 2015 (p < 0.01). Mean assessment score in 2014/2015 was significantly higher than in 2010 (p < 0.01). The high standards of pneumonia case management in 2011 were not observed in 2014/2015 in the absence of ongoing intervention but overall quality of care remained higher than pre-intervention levels, suggesting some degree of sustainability in the long-term.
Halotolerant aminopeptidase M29 from Mesorhizobium SEMIA 3007 with biotechnological potential and its impact on biofilm synthesis
Authors: Sierra Elwi Machado , Pereira Mariana Rangel , Maester Thaís Carvalho , Gomes-Pepe Elisangela Soares , Mendoza Elkin Rodas , Lemos Eliana G. de Macedo 
Published: August 2017

AbstractThe aminopeptidase gene from Mesorhizobium SEMIA3007 was cloned and overexpressed in Escherichia coli. The enzyme called MesoAmp exhibited optimum activity at pH 8.5 and 45 °C and was strongly activated by Co2+ and Mn2+. Under these reaction conditions, the enzyme displayed Km and kcat values of 0.2364 ± 0.018 mM and 712.1 ± 88.12 s−1, respectively. Additionally, the enzyme showed remarkable stability in organic solvents and was active at high concentrations of NaCl, suggesting that the enzyme might be suitable for use in biotechnology. MesoAmp is responsible for 40% of the organism’s aminopeptidase activity. However, the enzyme’s absence does not affect bacterial growth in synthetic broth, although it interfered with biofilm synthesis and osmoregulation. To the best of our knowledge, this report describes the first detailed characterization of aminopeptidase from Mesorhizobium and suggests its importance in biofilm formation and osmotic stress tolerance. In summary, this work lays the foundation for potential biotechnological applications and/or the development of environmentally friendly technologies and describes the first solvent- and halo-tolerant aminopeptidases identified from the Mesorhizobium genus and its importance in bacterial metabolism.
Maximum extent and decay of the Laurentide Ice Sheet in Western Baffin Bay during the Last glacial episode
Authors: Brouard Etienne , Lajeunesse Patrick 
Published: August 2017

AbstractReconstructing the extent, flow and decay of the Laurentide Ice Sheet (LIS) on the continental shelves of North America during the last glaciation provides paleoglaciological analogues that are essential for understanding and predicting how modern marine-based ice-sheets will respond to future climate change and sea level fluctuations. The geometry of the LIS during Marine isotope stage 2 (MIS-2; 29–14 ka BP) is one key element for ice-sheet modelling. The maximum extent of the LIS during this stage is well constrained for most sectors of the ice sheet, but major uncertainties remain, especially along the continental shelves of Arctic Canada. Despite a series of recent papers, the extent of the LIS in Western Baffin Bay, an area draining large volumes of glacial ice through multiple ice streams and likely characterized by ice shelves, remains highly speculative. Here we present unequivocal marine geophysical evidence that during the MIS-2 the LIS extended to the edge of the continental shelf, seaward of the previously proposed limits and subsequently retreated episodically westward during deglaciation. These data support interpretations of deep glacial ice grounding in Western Baffin Bay.
Impact of nutritional supplements on cognitive development of children in developing countries: A meta-analysis
Authors: Ip Patrick , Ho Frederick Ka Wing , Rao Nirmala , Sun Jin , Young Mary Eming , Chow Chun Bong , Tso Winnie , Hon Kam Lun 
Published: August 2017

AbstractNutritional supplements may be important on cognition but the evidence is heterogeneous. This meta-analysis aimed (1) to determine whether nutritional supplements provided to pregnant women or young children could improve cognitive development of children in developing countries, and (2) to explore how supplementation characteristics could improve children’s cognitive outcomes. This meta-analysis examined nutritional supplementation studies in 9 electronic databases and 13 specialist websites. Experimental studies were included if they were published from 1992 to 2016, were conducted in developing countries, had nutritional supplementation for pregnant women or children aged ≤8, and reported effect sizes on cognitive outcomes. Interventions with confounded components, such as stimulation and parenting, were excluded. 67 interventions (48 studies) for 29814 children from 20 developing countries were evaluated. Childhood nutritional supplementation could improve children’s cognitive development (d 0.08, 95% CI 0.03–0.13) and those with ≥5 nutrients was particularly beneficial (0.15, 0.08–0.22). Antenatal supplementation did not improve cognitive development (0.02, -0.01 to 0.06) except for those implemented in the first trimester (0.15, 0.03–0.28). In conclusion, childhood nutritional supplementation was beneficial to cognitive development but could be optimised by providing multiple nutrients; antenatal supplementation should target pregnancy women in the first trimester for better cognitive benefits.
Structural basis for CRMP2-induced axonal microtubule formation
Authors: Niwa Shinsuke , Nakamura Fumio , Tomabechi Yuri , Aoki Mari , Shigematsu Hideki , Matsumoto Takashi , Yamagata Atsushi , Fukai Shuya , Hirokawa Nobutaka , Goshima Yoshio , Shirouzu Mikako , Nitta Ryo 
Published: August 2017

AbstractMicrotubule associated protein Collapsin response mediator protein 2 (CRMP2) regulates neuronal polarity in developing neurons through interactions with tubulins or microtubules. However, how CRMP2 promotes axonal formation by affecting microtubule behavior remains unknown. This study aimed to obtain the structural basis for CRMP2–tubulin/microtubule interaction in the course of axonogenesis. The X-ray structural studies indicated that the main interface to the soluble tubulin-dimer is the last helix H19 of CRMP2 that is distinct from the known C-terminal tail-mediated interaction with assembled microtubules. In vitro structural and functional studies also suggested that the H19-mediated interaction promoted the rapid formation of GTP-state microtubules directly, which is an important feature of the axon. Consistently, the H19 mutants disturbed axon elongation in chick neurons, and failed to authorize the structural features for axonal microtubules in Caenorhabditis elegans. Thus, CRMP2 induces effective axonal microtubule formation through H19-mediated interactions with a soluble tubulin-dimer allowing axonogenesis to proceed.
High temperature in-situ synchrotron-based XRD study on the crystal structure evolution of C/C composite impregnated by FLiNaK molten salt
Authors: Feng Shanglei , Yang Yingguo , Li Li , Zhang Dongsheng , Yang Xinmei , Xia Huihao , Yan Long , Tsang Derek K. L. , Huai Ping , Zhou Xingtai 
Published: August 2017

AbstractAn in-situ real-time synchrotron-based grazing incidence X-ray diffraction was systematically used to investigate the crystal structural evolution of carbon fiber reinforced carbon matrix (C/C) composite impregnated with FLiNaK molten salt during the heat-treatment process. It was found that the crystallographic thermal expansion and contraction rate of interlayer spacing d002 in C/C composite with FLiNaK salt impregnation is smaller than that in the virgin sample, indicating the suppression on interlayer spacing from FLiNaK salt impregnated. Meanwhile the crystallite size LC002 of C/C composite with FLiNaK salt impregnation is larger than the virgin one after whole heat treatment process, indicating that FLiNaK salt impregnation could facilitate the crystallization of C/C composite after heat treatment process. This improved crystallization in C/C composite with FLiNaK salt impregnation suggests the synthetic action of the salt squeeze effect on crooked carbon layer and the release of internal residual stress after heating-cooling process. Thus, the present study not only contribute to reveal the interaction mechanism between C/C composite and FLiNaK salt in high temperature environment, but also promote the design of safer and more reliable C/C composite materials for the next generation molten salt reactor.
Oxidative damage and impairment of protein quality control systems in keratinocytes exposed to a volatile organic compounds cocktail
Authors: Dezest Marlène , Le Bechec Mickael , Chavatte Laurent , Desauziers Valérie , Chaput Benoît , Grolleau Jean-Louis , Descargues Pascal , Nizard Carine , Schnebert Sylvianne , Lacombe Sylvie , Bulteau Anne-Laure 
Published: August 2017

AbstractCompelling evidence suggests that volatile organic compounds (VOCs) have potentially harmful effects to the skin. However, knowledge about cellular signaling events and toxicity subsequent to VOC exposure to human skin cells is still poorly documented. The aim of this study was to focus on the interaction between 5 different VOCs (hexane, toluene, acetaldehyde, formaldehyde and acetone) at doses mimicking chronic low level environmental exposure and the effect on human keratinocytes to get better insight into VOC-cell interactions. We provide evidence that the proteasome, a major intracellular proteolytic system which is involved in a broad array of processes such as cell cycle, apoptosis, transcription, DNA repair, protein quality control and antigen presentation, is a VOC target. Proteasome inactivation after VOC exposure is accompanied by apoptosis, DNA damage and protein oxidation. Lon protease, which degrades oxidized, dysfunctional, and misfolded proteins in the mitochondria is also a VOC target. Using human skin explants we found that VOCs prevent cell proliferation and also inhibit proteasome activity in vivo. Taken together, our findings provide insight into potential mechanisms of VOC-induced proteasome inactivation and the cellular consequences of these events.
A complete investigation of monocular and binocular functions in clinically treated amblyopia
Authors: Zhao Wuxiao , Jia Wu-Li , Chen Ge , Luo Yan , Lin Borong , He Qing , Lu Zhong-Lin , Li Min , Huang Chang-Bing 
Published: August 2017

AbstractThe gold standard of a successful amblyopia treatment is full recovery of visual acuity (VA) in the amblyopic eye, but there has been no systematic study on both monocular and binocular visual functions. In this research, we aimed to quantify visual qualities with a variety of perceptual tasks in subjects with treated amblyopia. We found near stereoacuity and pAE dominance in binocular rivalry in “treated” amblyopia were largely comparable to those of normal subjects. CSF of the pAE remained deficient in high spatial frequencies. The binocular contrast summation ratio is significantly lower than normal standard. The interocular balance point is 34%, indicating that contrast in pAE is much less effective as the same contrast in pFE in binocular phase combination. Although VA, stereoacuity and binocular rivalry at low spatial frequency in treated amblyopes were normal or nearly normal, the pAE remained “lazy” in high frequency domain, binocular contrast summation, and interocular phase combination. Our results suggest that structured monocular and binocular training are necessary to fully recover deficient functions in amblyopia.
A TCR-based Chimeric Antigen Receptor
Authors: Walseng Even , Köksal Hakan , Sektioglu Ibrahim M. , Fåne Anne , Skorstad Gjertrud , Kvalheim Gunnar , Gaudernack Gustav , Inderberg Else Marit , Wälchli Sébastien 
Published: August 2017

AbstractEffector T cells equipped with engineered antigen receptors specific for cancer targets have proven to be very efficient. Two methods have emerged: the Chimeric Antigen Receptors (CARs) and T-cell Receptor (TCR) redirection. Although very potent, CAR recognition is limited to membrane antigens which represent around 1% of the total proteins expressed, whereas TCRs have the advantage of targeting any peptide resulting from cellular protein degradation. However, TCRs depend on heavy signalling machinery only present in T cells which restricts the type of eligible therapeutic cells. Hence, an introduced therapeutic TCR will compete with the endogenous TCR for the signalling proteins and carries the potential risk of mixed dimer formation giving rise to a new TCR with unpredictable specificity. We have fused a soluble TCR construct to a CAR-signalling tail and named the final product TCR-CAR. We here show that, if expressed, the TCR-CAR conserved the specificity and the functionality of the original TCR. In addition, we demonstrate that TCR-CAR redirection was not restricted to T cells. Indeed, after transduction, the NK cell line NK-92 became TCR positive and reacted against pMHC target. This opens therapeutic avenues combing the killing efficiency of NK cells with the diversified target recognition of TCRs.
RNA Sequencing and Co-expressed Long Non-coding RNA in Modern and Wild Wheats
Authors: Cagirici Halise Busra , Alptekin Burcu , Budak Hikmet 
Published: August 2017

AbstractThere is an urgent need for the improvement of drought-tolerant bread and durum wheat. The huge and complex genome of bread wheat (BBAADD genome) stands as a vital obstruction for understanding the molecular mechanism underlying drought tolerance. However, tetraploid wheat (Triticum turgidum ssp., BBAA genome) is an ancestor of modern bread wheat and offers an important model for studying the drought response due to its less complex genome. Additionally, several wild relatives of tetraploid wheat have already shown a significant drought tolerance. We sequenced root transcriptome of three tetraploid wheat varieties with varying stress tolerance profiles, and built differential expression library of their transcripts under control and drought conditions. More than 5,000 differentially expressed transcripts were identified from each genotype. Functional characterization of transcripts specific to drought-tolerant genotype, revealed their association with osmolytes production and secondary metabolite pathways. Comparative analysis of differentially expressed genes and their non-coding RNA partners, long noncoding RNAs and microRNAs, provided valuable insight to gene expression regulation in response to drought stress. LncRNAs as well as coding transcripts share similar structural features in different tetraploid species; yet, lncRNAs slightly differ from coding transcripts. Several miRNA-lncRNA target pairs were detected as differentially expressed in drought stress. Overall, this study suggested an important pool of transcripts where their manipulations confer a better performance of wheat varieties under drought stress.
Peroxisome Proliferator-Activated Receptor Gamma in Obesity and Colorectal Cancer: the Role of Epigenetics
Authors: Motawi T. K. , Shaker O. G. , Ismail M. F. , Sayed N. H. 
Published: August 2017

AbstractPeroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor that is deregulated in obesity. PPARγ exerts diverse antineoplastic effects. Attempting to determine the clinical relevance of the epigenetic mechanisms controlling the expression PPARγ and susceptibility to colorectal cancer (CRC) in obese subjects, this study investigated the role of some microRNAs and DNA methylation on the deregulation of PPARγ. Seventy CRC patients (34 obese and 36 lean), 22 obese and 24 lean healthy controls were included. MicroRNA levels were measured in serum. PPARγ promoter methylation was evaluated in peripheral blood mononuclear cells (PBMC). PPARγ level was evaluated by measuring mRNA level in PBMC and protein level in serum. The tested microRNAs (miR-27b, 130b and 138) were significantly upregulated in obese and CRC patients. Obese and CRC patients had significantly low levels of PPARγ. A significant negative correlation was found between PPARγ levels and the studied microRNAs. There was a significant PPARγ promoter hypermethylation in CRC patients that correlated to low PPARγ levels. Our results suggest that upregulation of microRNAs 27b, 130b and 138 is associated with susceptibility to CRC in obese subjects through PPARγ downregulation. Hypermethylation of PPARγ gene promoter is associated with CRC through suppression of PPARγ regardless of BMI.
Genetic Mechanisms Contribute to the Development of Heart Failure in Patients with Atrioventricular Block and Right Ventricular Apical Pacing
Authors: Liu Nana , Zheng Min , Li Shijie , Bai Hui , Liu Zhouying , Hou Cui hong , Zhang Shu , Pu Jielin 
Published: August 2017

AbstractRight ventricular apical (RVA) pacing can lead to progressive left ventricular dysfunction and heart failure (HF), even in patients with normal cardiac structure and function. Our study conducted candidate gene screening and lentivirus transfected neonatal rat cardiomyocytes (NRCMs) to explore the genetic and pathogenic mechanisms of RVA pacing induced cardiomyopathy in third degree atrioventricular block (III AVB) patients. We followed 887 III AVB patients with baseline normal cardiac function and RVA pacing. After a median follow-up of 2.5 years, 10 patients (four males, mean age 47.6 ± 10.0 years) were diagnosed with RVA pacing induced HF with left ventricular ejection fraction (LVEF) reducing dramatically to 37.8 ± 7.1% (P  < 0.05). Candidate genes sequencing found cardiomyopathy associated genetic variations in all ten HF patients and six SCN5A variations in 6 of 20 control patients. Transfected NRCMs of Lamin A/C mutations (R216C and L379F) disrupted Lamin A/C location on nucleus membrane and finally resulted in increased apoptotic rate after serum starvation. In conclusion, cardiomyopathy associated genetic variations play an essential role in occurrence of newly onset HF in the III AVB patients with RVA pacing. RVA pacing, serving as extra stimulator, might accelerate the deterioration of cardiac structure and function.