bluuebunny/crossref_metadata_2025_split huggingface dataset:
DNMT1 mediates metabolic reprogramming induced by Epstein–Barr virus latent membrane protein 1 and reversed by grifolin in nasopharyngeal carcinoma
Authors: Luo Xiangjian , Hong Liping , Cheng Can , Li Namei , Zhao Xu , Shi Feng , Liu Jikai , Fan Jia , Zhou Jian , Bode Ann M. , Cao Ya 
Published: May 2018

AbstractCancer cells frequently adapt fundamentally altered metabolism to support tumorigenicity and malignancy. Epigenetic and metabolic networks are closely interactive, in which DNA methyltransferases (DNMTs) play important roles. Epstein–Barr virus (EBV)-encoded latent membrane protein 1 (EBV-LMP1) is closely associated with nasopharyngeal carcinoma (NPC) pathogenesis because it can trigger multiple cell signaling pathways that promote cell transformation, proliferation, immune escape, invasiveness, epigenetic modification, and metabolic reprogramming. Our current findings reveal for the first time that LMP1 not only upregulates DNMT1 expression and activity, but also promotes its mitochondrial translocation. This induces epigenetic silencing of pten and activation of AKT signaling as well as hypermethylation of the mtDNA D-loop region and downregulation of oxidative phosphorylation (OXPHOS) complexes, consequently, leading to metabolic reprogramming in NPC. Furthermore, we demonstrate that grifolin, a natural farnesyl phenolic compound originated from higher fungi, is able to attenuate glycolytic flux and recover mitochondrial OXPHOS function by inhibiting DNMT1 expression and activity as well as its mitochondrial retention in NPC cells. Therefore, our work establishes a mechanistic connection between epigenetics and metabolism in EBV-positive NPC and provides further evidence for pathological classification based on CpG island methylator phenotype (CIMP) in EBV-associated malignancies. In addition, grifolin might be a promising lead compound in the intervention of high-CIMP tumor types. The availability of this natural product could hamper tumor cell metabolic reprogramming by targeting DNMT1.
Renal inhibition of miR-181a ameliorates 5-fluorouracil-induced mesangial cell apoptosis and nephrotoxicity
Authors: Liu Xiao-Yun , Zhang Fei-Ran , Shang Jin-Yan , Liu Ying-Ying , Lv Xiao-Fei , Yuan Jia-Ni , Zhang Ting-Ting , Li Kai , Lin Xiao-Chun , Liu Xiu , Lei Qingqing , Fu Xiao-Dong , Zhou Jia-Guo , Liang Si-Jia 
Published: May 2018

AbstractThe development of nephrotoxicity largely limits the clinical use of chemotherapy. MiRNAs are able to target various genes and involved in the regulation of diverse cellular processes, including cell apoptosis and death. Our study showed that miR-181a expression was significantly increased after 5-fluorouracil (5-FU) treatment in renal mesangial cells and kidney tissue, which was associated with decreased baculoviral inhibition of apoptosis protein repeat-containing 6 (BIRC6) expression and increased apoptotic rate. Enforced miR-181a expression enhanced 5-FU-induced p53-dependent mitochondrial apoptosis, including declined Bcl-2/Bax ratio, loss of mitochondrial membrane potential, cytochrome c release, and caspase-9 and caspase-3 activation. However, inhibition of miR-181a was associated with reduced p53-mediated mitochondrial apoptosis induced by 5-FU. Moreover, miR-181a increased BIRC6 downstream gene p53 protein expression and transcriptional activity by reducing ubiquitin-mediated protein degradation. We found that miR-181a directly targeted 3′-UTR of BIRC6 mRNA and negatively regulated BIRC6 expression. In vivo study, knockdown of miR-181a with adeno-associated virus harboring miR-181a-tough decoy attenuated 5-FU-induced renal cell apoptosis, inflammation and kidney injury. In conclusion, these results demonstrate that miR-181a increases p53 protein expression and transcriptional activity by targeting BIRC6 and promotes 5-FU-induced apoptosis in mesangial cells. Inhibition of miR-181a ameliorates 5-FU-induced nephrotoxicity, suggesting that miR-181a may be a novel therapeutic target for nephrotoxicity treatment during chemotherapy.
Pharmacologic inhibition of protein phosphatase-2A achieves durable immune-mediated antitumor activity when combined with PD-1 blockade
Authors: Ho Winson S. , Wang Herui , Maggio Dominic , Kovach John S. , Zhang Qi , Song Qi , Marincola Francesco M. , Heiss John D. , Gilbert Mark R. , Lu Rongze , Zhuang Zhengping 
Published: May 2018

AbstractMounting evidence suggests that inhibition of protein phosphatase-2A (PP2A), a serine/threonine phosphatase, could enhance anticancer immunity. However, drugs targeting PP2A are not currently available. Here, we report that a PP2A inhibitor, LB-100, when combined with anti-PD-1 (aPD-1) blockade can synergistically elicit a durable immune-mediated antitumor response in a murine CT26 colon cancer model. This effect is T-cell dependent, leading to regression of a significant proportion of tumors. Analysis of tumor lymphocytes demonstrates enhanced effector T-cell and reduced suppressive regulatory T-cell infiltration. Clearance of tumor establishes antigen-specific secondary protective immunity. A synergistic effect of LB-100 and aPD-1 blockade is also observed in B16 melanoma model. In addition, LB-100 activates the mTORC1 signaling pathway resulting in decreased differentiation of naive CD4 cells into regulatory T cells. There is also increased expression of Th1 and decreased expression of Th2 cytokines. These data highlight the translational potential of PP2A inhibition in combination with checkpoint inhibition.
Different combination strategies for prophylaxis of venous thromboembolism in patients: A prospective multicenter randomized controlled study
Authors: Sang Cui-Qin , Zhao Na , Zhang Jian , Wang Shu-Zhen , Guo Shu-Li , Li Shu-Hong , Jiang Ying , Li Bin , Wang Jian-Liu , Song Lei , Zhai Jian-Jun , Zhang Zhen-Yu 
Published: May 2018

AbstractThe aim was to evaluate the efficacy and safety of different combination strategies for prophylaxis of venous thromboembolism (VTE) after gynecologic surgery in patients at different levels of risk. This was a prospective multicenter randomized controlled study, in which 625 women who would undergo pelvic surgery for gynecologic diseases were stratified into three risk groups and then randomized into four groups to receive graduated compression stockings (GCS) alone (group A), GCS + low molecular weight heparin (LMWH) (group B), GCS + intermittent pneumatic compression (IPC) (group C), and GCS + IPC + LMWH (group C), respectively. The overall incidence of DVT was 5.1%. Group A had the highest incidence of DVT (8.8%), followed by group C (5.2%), group B (3.8%), and group D (2.6%). There was a significant difference in the incidence of DVT between groups A and D. The incidence of DVT was significantly lower in LMWH-treated patients (group B + group D) than in non-LMWH-treated patients (group A + group C). In conclusion, combination prophylaxis, especially LMWH-containing strategies, is better than monoprophylaxis in reducing VTE after gynecologic surgery. Risk-stratified prophylactic strategies should be implemented in patients undergoing gynecologic surgery, with LMWH-containing strategies being recommended for high-risk and very-high-risk patients.
The Evolution of Molecular Compatibility between Bacteriophage ΦX174 and its Host
Authors: Kula Alexander , Saelens Joseph , Cox Jennifer , Schubert Alyxandria M. , Travisano Michael , Putonti Catherine 
Published: May 2018

AbstractViruses rely upon their hosts for biosynthesis of viral RNA, DNA and protein. This dependency frequently engenders strong selection for virus genome compatibility with potential hosts, appropriate gene regulation and expression necessary for a successful infection. While bioinformatic studies have shown strong correlations between codon usage in viral and host genomes, the selective factors by which this compatibility evolves remain a matter of conjecture. Engineered to include codons with a lesser usage and/or tRNA abundance within the host, three different attenuated strains of the bacterial virus ФX174 were created and propagated via serial transfers. Molecular sequence data indicate that biosynthetic compatibility was recovered rapidly. Extensive computational simulations were performed to assess the role of mutational biases as well as selection for translational efficiency in the engineered phage. Using bacteriophage as a model system, we can begin to unravel the evolutionary processes shaping codon compatibility between viruses and their host.
The effect of N-acetyl-l-cysteine (NAC) on liver toxicity and clinical outcome after hematopoietic stem cell transplantation
Authors: El-Serafi Ibrahim , Remberger Mats , El-Serafi Ahmed , Benkessou Fadwa , Zheng Wenyi , Martell Eva , Ljungman Per , Mattsson Jonas , Hassan Moustapha 
Published: May 2018

AbstractBusulphan (Bu) is a myeloablative drug used for conditioning prior to hematopoietic stem cell transplantation. Bu is predominantly metabolized through glutathione conjugation, a reaction that consumes the hepatic glutathione. N-acetyl-l-cysteine (NAC) is a glutathione precursor used in the treatment of acetaminophen hepatotoxicity. NAC does not interfere with the busulphan myeloablative effect. We investigated the effect of NAC concomitant treatment during busulphan conditioning on the liver enzymes as well as the clinical outcome. Prophylactic NAC treatment was given to 54 patients upon the start of busulphan conditioning. These patients were compared with 54 historical matched controls who did not receive NAC treatment. In patients treated with NAC, aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) were significantly (P < 0.05) decreased after conditioning compared to their start values. Within the NAC-group, liver enzymes were normalized in those patients (30%) who had significantly high start values. No significant decrease in enzyme levels was observed in the control group. Furthermore, NAC affected neither Bu kinetics nor clinical outcome (sinusoidal obstruction syndrome incidence, graft-versus-host disease and/or graft failure). In conclusion: NAC is a potential prophylactic treatment for hepatotoxicity during busulphan conditioning. NAC therapy did not alter busulphan kinetics or affect clinical outcome.
Induction of ganglioside synthesis in Drosophila brain accelerates assembly of amyloid β protein
Authors: Yamasaki Yasutoyo , Tsuda Leo , Suzuki Akemi , Yanagisawa Katsuhiko 
Published: May 2018

AbstractThe assembly and deposition of amyloid β protein (Aβ) is a fundamental event during the early stages of Alzheimer’s disease (AD) and cerebral amyloid angiopathy. A growing body of evidence indicates that gangliosides form a pathological platform for the generation of ganglioside-bound Aβ, which facilitates the assembly of soluble Aβs; however, the molecular mechanisms underlying the binding of Aβ to gangliosides in the brain remain unclear due to the lack of an in vivo system that may address this issue. In insects, including the fruit fly Drosophila melanogaster, gangliosides are not intrinsically present at a detectable level. We herein demonstrate that ganglioside expression is inducible in Drosophila via the expression of transgenes of ganglioside synthesis enzymes and the feeding of exogenous sialic acid, and also that the induction of ganglioside synthesis significantly accelerates Aβ assembly in vivo. Our results support the hypothesis that gangliosides are responsible for Aβ assembly in vivo and also provide an opportunity to develop a valuable model for basic research as well as a therapeutic strategy for AD.
Metagenomic insights into the microbial diversity in manganese-contaminated mine tailings and their role in biogeochemical cycling of manganese
Authors: Ghosh Shreya , Das Alok Prasad 
Published: May 2018

AbstractTo extend the knowledge on the microbial diversity of manganese rich environments, we performed a clone library based study using metagenomic approach. Pyrosequencing based analysis of 16S rRNA genes were carried out on an Illumina platform to gain insights into the bacterial community inhabiting in a manganese mining site and the taxonomic profiles were correlated with the inherent capacities of these strains to solubilise manganese. The application of shot gun sequencing in this study yielded results which revealed the highest prevalence of Proteobacteria (42.47%), followed by Actinobacteria (23.99%) in the area of study. Cluster of orthologous group (COG) functional category has 85,066 predicted functions. Out of which 11% are involved in metabolism of amino acid, 9% are involved in production and conversion of energy while Keto Encyclopedia of Gene and Genomes (KEGG) functional category has 107,388 predicted functions, out of which 55% are involved in cellular metabolism, 15% are environmental and information processing and 12% are genetic information processing in nature. The isolated microbial consortia demonstrated visible growth in presence of high concentrations of Mn. Solubilisation studies resulted in 86% of manganese recovery after 20 days. The result presented in this study has important implications in understanding the microbial diversity in manganese contaminated mine tailings and their role in natural geochemical cycling of Mn.
Temperature and the vertical movements of oceanic whitetip sharks, Carcharhinus longimanus
Authors: Andrzejaczek Samantha , Gleiss Adrian C. , Jordan Lance K. B. , Pattiaratchi Charitha B. , Howey Lucy A. , Brooks Edward J. , Meekan Mark G. 
Published: May 2018

AbstractLarge-bodied pelagic ectotherms such as sharks need to maintain internal temperatures within a favourable range in order to maximise performance and be cost-efficient foragers. This implies that behavioural thermoregulation should be a key feature of the movements of these animals, although field evidence is limited. We used depth and temperature archives from pop-up satellite tags to investigate the role of temperature in driving vertical movements of 16 oceanic whitetip sharks,Carcharhinus longimanus, (OWTs). Spectral analysis, linear mixed modelling, segmented regression and multivariate techniques were used to examine the effect of mean sea surface temperature (SST) and mixed layer depth on vertical movements. OWTs continually oscillated throughout the upper 200 m of the water column. In summer when the water column was stratified with high SSTs, oscillations increased in amplitude and cycle length and sharks reduced the time spent in the upper 50 m. In winter when the water column was cooler and well-mixed, oscillations decreased in amplitude and cycle length and sharks frequently occupied the upper 50 m. SSTs of 28 oC marked a distinct change in vertical movements and the onset of thermoregulation strategies. Our results have implications for the ecology of these animals in a warming ocean.
Characterizing co-expression networks underpinning maize stalk rot virulence in Fusarium verticillioides through computational subnetwork module analyses
Authors: Kim Man S. , Zhang Huan , Yan Huijuan , Yoon Byung-Jun , Shim Won Bo 
Published: May 2018

AbstractFusarium verticillioidesis recognized as an important stalk rot pathogen of maize worldwide, but our knowledge of genetic mechanisms underpinning this pathosystem is limited. Previously, we identified a striatin-like protein Fsr1 that plays an important role in stalk rot. To further characterize transcriptome networks downstream of Fsr1, we performed next-generation sequencing (NGS) to investigate relative read abundance and also to infer co-expression networks utilizing the preprocessed expression data through partial correlation. We used a probabilistic pathway activity inference strategy to identify functional subnetwork modules likely involved in virulence. Each subnetwork modules consisted of multiple correlated genes with coordinated expression patterns, but the collective activation levels were significantly different inF. verticillioideswild type versusfsr1mutant. We also identified putative hub genes from predicted subnetworks for functional validation and network robustness studies through mutagenesis, virulence and qPCR assays. Our results suggest that these genes are important virulence genes that regulate the expression of closely correlated genes, demonstrating that these are important hubs of their respective subnetworks. Lastly, we used keyF. verticillioidesvirulence genes to computationally predict a subnetwork of maize genes that potentially respond to fungal genes by applying cointegration-correlation-expression strategy.
Quality control of the traditional Chinese medicine Ruyi jinhuang powder based on high-throughput sequencing and real-time PCR
Authors: Li Qiang , Sun Ying , Guo Huijun , Sang Feng , Ma Hongyu , Peng Hai , Zheng Na , Xu Liran 
Published: May 2018

AbstractTraditional Chinese medicine (TCM) has been practiced for thousands of years, although concerns about the efficacy, legality, and safety of TCM continue to be raised. Chromatographic studies have detected the presence of heavy metals and plant toxins within some TCM preparations. However, chromatography is not able to identify all of the compounds of TCM, particularly those items that are not clearly labeled on the packaging. The present study aimed to establish a supplemental method that better assesses the ingredient components of TCM preparations.We established an effective approach to screen the biological and toxical composition of TCM based on high-throughput sequencing (HTS), as well as fast detection and validation of the toxical species by real-time PCR, based on ITS2 DNA barcoding. Ruyi jinhuang powder (RHP), a classical herbal prescription containing the toxical herb Arisaematis rhizoma, was chosen to test the method. This method could determine whether the Arisaematis Rhizoma had been replaced by Pinellia pedatisecta in the RHP. The results were validated by real-time PCR. 90% compositions of RHP were identified by ITS2 DNA barcoding, suggesting that more DNA barcoding markers are needed for TCM identification. The strategy of high-throughput sequencing has the potential for comprehensive ingredient profiling for TCM preparations. Real-time PCR provides a expeditious metehod for monitoring the safety and legality of TCM preparations.
Dexamethasone-induced Intra-Uterine Growth Restriction impacts NOSTRIN and its downstream effector genes in the rat mesometrial uterus
Authors: Chakraborty Shreeta , Islam Safirul , Saha Sarbani , Ain Rupasri 
Published: May 2018

AbstractIntra-Uterine Growth Restriction (IUGR) is a major cause of fetal and neonatal mortality. Understanding the impact of IUGR on utero-placental gene expression is key to developing effective therapy. In this report we elucidated the impact of IUGR on NOSTRIN and its downstream effector gene expression in the utero-placental compartments. We showed here that induction of IUGR by maternal dexamethasone administration in rats led to up-regulation of NOSTRIN transcript and protein in the mesometrial triangle of the uterus (MG) and not in other utero-placental compartments as compared to control. This was associated with down-regulation of twelve genes and four cytokines that were known to be regulated by NOSTRIN and also required for maintenance of pregnancy. Interestingly, there was remarkable decrease in phosphorylation of RelA transcription factor in the MG during IUGR in line with the fact that the down regulated genes harbour RelA transcription activation domain in their promoters. Furthermore, HIF-1α level was reciprocal to NOSTRIN expression pattern in the mesometrial compartment during IUGR and also in CoCl2 treated endothelial cells. Over-expression of HIF-1α led to a decrease in NOSTRIN levels suggesting inhibition of Nostrin transcription by HIF-1α. Our findings highlight the importance of NOSTRIN in uterine pathophysiology during IUGR.
Asymmetric distribution of biomolecules of maternal origin in the Xenopus laevis egg and their impact on the developmental plan
Authors: Sindelka Radek , Abaffy Pavel , Qu Yanyan , Tomankova Silvie , Sidova Monika , Naraine Ravindra , Kolar Michal , Peuchen Elizabeth , Sun Liangliang , Dovichi Norman , Kubista Mikael 
Published: May 2018

AbstractAsymmetric cell division is a ubiquitous feature during the development of higher organisms. Asymmetry is achieved by differential localization or activities of biological molecules such as proteins, and coding and non-coding RNAs. Here, we present subcellular transcriptomic and proteomic analyses along the animal-vegetal axis of Xenopus laevis eggs. More than 98% of the maternal mRNAs could be categorized into four localization profile groups: animal, vegetal, extremely vegetal, and a newly described group of mRNAs that we call extremely animal, which are mRNAs enriched in the animal cortex region. 3′UTRs of localized mRNAs were analyzed for localization motifs. Several putative motifs were discovered for vegetal and extremely vegetal mRNAs, while no distinct conserved motifs for the extremely animal mRNAs were identified, suggesting different localization mechanisms. Asymmetric profiles were also found for proteins, with correlation to those of corresponding mRNAs. Based on unexpected observation of the profiles of the homoeologous genes exd2 we propose a possible mechanism of genetic evolution.
Extended investigation of tube-gel sample preparation: a versatile and simple choice for high throughput quantitative proteomics
Authors: Muller Leslie , Fornecker Luc , Chion Marie , Van Dorsselaer Alain , Cianférani Sarah , Rabilloud Thierry , Carapito Christine 
Published: May 2018

AbstractSample preparation for quantitative proteomics is a crucial step to ensure the repeatability and the accuracy of the results. However, there is no universal method compatible with the wide variety of protein extraction buffers currently used. We have recently demonstrated the compatibility of tube-gel with SDS-based buffers and its efficiency for label-free quantitative proteomics by comparing it to stacking gel and liquid digestion. Here, we investigated the compatibility of tube-gel with alternatives to SDS-based buffers allowing notably the extraction of proteins in various pH conditions. We also explored the use of photopolymerization to extend the number of possibilities, as it is compatible with a wide range of pH and is non-oxidative. To achieve this goal, we compared six extraction buffers in combination with two polymerization conditions to further optimize the tube-gel protocol and evaluate its versatility. Identification and quantitative results demonstrated the compatibility of tube-gel with all tested conditions by overall raising quite comparable results. In conclusion, tube-gel is a versatile and simple sample preparation method for large-scale quantitative proteomics applications. Complete datasets are available via ProteomeXchange with identifier PXD008656.