bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long noncoding RNA CRNDE promotes colorectal cancer cell proliferation via epigenetically silencing DUSP5/CDKN1A expression
Authors: Ding Jie , Li Juan , Wang HaiYan , Tian Yun , Xie Min , He XueZhi , Ji Hao , Ma Zhonghua , Hui Bingqing , Wang Keming , Ji Guozhong 
Published: August 2017

AbstractEvidence indicates that long non-coding RNAs (lncRNAs) play a critical role in the regulation of tumor cellular processes, such as proliferation, apoptosis, and metastasis. LncRNA CRNDE (Colorectal Neoplasia Differentially Expressed) is located at human chromosome 16 and has been found overexpressed in a variety of cancers including colorectal cancer (CRC). In this paper, we report that lncRNA CRNDE expression was remarkably upregulated in CRC tissues and that lncRNA CRNDE overexpression was positively correlated with advanced pathological stages and larger tumor sizes. In addition, the knockdown of CRNDE significantly suppressed proliferation and caused apoptosis of CRC cells both in vitro and in vivo. Furthermore, RNA immunoprecipitation and chromatin immunoprecipitation assays demonstrated that lncRNA CRNDE could epigenetically suppress the expressions of dual-specificity phosphatase 5 (DUSP5) and CDKN1A by binding to EZH2 (the key components of Polycomb repressive complex 2 (PRC2)), thus promoting CRC development. In conclusion, our data suggest that the lncRNA CRNDE promotes the progression of CRC and is a potential therapeutic target for CRC intervention.
MiR-30c regulates cisplatin-induced apoptosis of renal tubular epithelial cells by targeting Bnip3L and Hspa5
Authors: Du Bin , Dai Xiao-meng , Li Shuang , Qi Guo-long , Cao Guang-xu , Zhong Ying , Yin Pei-di , Yang Xue-song 
Published: August 2017

AbstractAs a common anticancer drug, cisplatin has been widely used for treating tumors in the clinic. However, its side effects, especially its nephrotoxicity, noticeably restrict the application of cisplatin. Therefore, it is imperative to investigate the mechanism of renal injury and explore the corresponding remedies. In this study, we showed the phenotypes of the renal tubules and epithelial cell death as well as elevated cleaved-caspase3- and TUNEL-positive cells in rats intraperitoneally injected with cisplatin. Similar cisplatin-induced cell apoptosis was found in HK-2 and NRK-52E cells exposed to cisplatin as well. In both models of cisplatin-induced apoptosis in vivo and in vitro, quantitative PCR data displayed reductions in miR-30a-e expression levels, indicating that miR-30 might be involved in regulating cisplatin-induced cell apoptosis. This was further confirmed when the effects of cisplatin-induced cell apoptosis were found to be closely correlated with alterations in miR-30c expression, which were manipulated by transfection of either the miR-30c mimic or miR-30c inhibitor in HK-2 and NRK-52E cells. Using bioinformatics tools, including TargetScan and a gene expression database (Gene Expression Omnibus), Adrb1, Bnip3L, Hspa5 and MAP3K12 were predicted to be putative target genes of miR-30c in cisplatin-induced apoptosis. Subsequently, Bnip3L and Hspa5 were confirmed to be the target genes after determining the expression of these putative genes following manipulation of miR-30c expression levels in HK-2 cells. Taken together, our current experiments reveal that miR-30c is certainly involved in regulating the renal tubular cell apoptosis induced by cisplatin, which might supply a new strategy to minimize cisplatin-induced nephrotoxicity.
Linker histone H1 prevents R-loop accumulation and genome instability in heterochromatin
Authors: Bayona-Feliu Aleix , Casas-Lamesa Anna , Reina Oscar , Bernués Jordi , Azorín Fernando 
Published: August 2017

AbstractLinker histone H1 is an important structural component of chromatin that stabilizes the nucleosome and compacts the nucleofilament into higher-order structures. The biology of histone H1 remains, however, poorly understood. Here we show thatDrosophilahistone H1 (dH1) prevents genome instability as indicated by the increased γH2Av (H2AvS137P) content and the high incidence of DNA breaks and sister-chromatid exchanges observed in dH1-depleted cells. Increased γH2Av occurs preferentially at heterochromatic elements, which are upregulated upon dH1 depletion, and is due to the abnormal accumulation of DNA:RNA hybrids (R-loops). R-loops accumulation is readily detectable in G1-phase, whereas γH2Av increases mainly during DNA replication. These defects induce JNK-mediated apoptosis and are specific of dH1 depletion since they are not observed when heterochromatin silencing is relieved by HP1a depletion. Altogether, our results suggest that histone H1 prevents R-loops-induced DNA damage in heterochromatin and unveil its essential contribution to maintenance of genome stability.
The Microbial Ecosystem Distinguishes Chronically Diseased Tissue from Adjacent Tissue in the Sigmoid Colon of Chronic, Recurrent Diverticulitis Patients
Authors: Schieffer Kathleen M. , Sabey Kate , Wright Justin R. , Toole David R. , Drucker Rebecca , Tokarev Vasily , Harris Leonard R. , Deiling Sue , Eshelman Melanie A. , Hegarty John P. , Yochum Gregory S. , Koltun Walter A. , Lamendella Regina , Stewart David B. 
Published: August 2017

AbstractDiverticular disease is commonly associated with the older population in the United States. As individual’s age, diverticulae, or herniation of the mucosa through the colonic wall, develop. In 10–25% of individuals, the diverticulae become inflamed, resulting in diverticulitis. The gut ecosystem relies on the interaction of bacteria and fungi to maintain homeostasis. Although bacterial dysbiosis has been implicated in the pathogenesis of diverticulitis, associations between the microbial ecosystem and diverticulitis remain largely unstudied. This study investigated how the cooperative network of bacteria and fungi differ between a diseased area of the sigmoid colon chronically affected by diverticulitis and adjacent non-affected tissue. To identify mucosa-associated microbes, bacterial 16S rRNA and fungal ITS sequencing were performed on chronically diseased sigmoid colon tissue (DT) and adjacent tissue (AT) from the same colonic segment. We found that Pseudomonas and Basidiomycota OTUs were associated with AT while Microbacteriaceae and Ascomycota were enriched in DT. Bipartite co-occurrence networks were constructed for each tissue type. The DT and AT networks were distinct for each tissue type, with no microbial relationships maintained after intersection merge of the groups. Our findings indicate that the microbial ecosystem distinguishes chronically diseased tissue from adjacent tissue.
Molecular dynamics simulations of heterogeneous cell membranes in response to uniaxial membrane stretches at high loading rates
Authors: Zhang Lili , Zhang Zesheng , Jasa John , Li Dongli , Cleveland Robin O. , Negahban Mehrdad , Jérusalem Antoine 
Published: August 2017

AbstractThe chemobiomechanical signatures of diseased cells are often distinctively different from that of healthy cells. This mainly arises from cellular structural/compositional alterations induced by disease development or therapeutic molecules. Therapeutic shock waves have the potential to mechanically destroy diseased cells and/or increase cell membrane permeability for drug delivery. However, the biomolecular mechanisms by which shock waves interact with diseased and healthy cellular components remain largely unknown. By integrating atomistic simulations with a novel multiscale numerical framework, this work provides new biomolecular mechanistic perspectives through which many mechanosensitive cellular processes could be quantitatively characterised. Here we examine the biomechanical responses of the chosen representative membrane complexes under rapid mechanical loadings pertinent to therapeutic shock wave conditions. We find that their rupture characteristics do not exhibit significant sensitivity to the applied strain rates. Furthermore, we show that the embedded rigid inclusions markedly facilitate stretch-induced membrane disruptions while mechanically stiffening the associated complexes under the applied membrane stretches. Our results suggest that the presence of rigid molecules in cellular membranes could serve as “mechanical catalysts” to promote the mechanical destructions of the associated complexes, which, in concert with other biochemical/medical considerations, should provide beneficial information for future biomechanical-mediated therapeutics.
MEPicides: potent antimalarial prodrugs targeting isoprenoid biosynthesis
Authors: Edwards Rachel L. , Brothers Robert C. , Wang Xu , Maron Maxim I. , Ziniel Peter D. , Tsang Patricia S. , Kraft Thomas E. , Hruz Paul W. , Williamson Kim C. , Dowd Cynthia S. , John Audrey R. Odom 
Published: August 2017

AbstractThe emergence of Plasmodium falciparum resistant to frontline therapeutics has prompted efforts to identify and validate agents with novel mechanisms of action. MEPicides represent a new class of antimalarials that inhibit enzymes of the methylerythritol phosphate (MEP) pathway of isoprenoid biosynthesis, including the clinically validated target, deoxyxylulose phosphate reductoisomerase (Dxr). Here we describe RCB-185, a lipophilic prodrug with nanomolar activity against asexual parasites. Growth of P. falciparum treated with RCB-185 was rescued by isoprenoid precursor supplementation, and treatment substantially reduced metabolite levels downstream of the Dxr enzyme. In addition, parasites that produced higher levels of the Dxr substrate were resistant to RCB-185. Notably, environmental isolates resistant to current therapies remained sensitive to RCB-185, the compound effectively treated sexually-committed parasites, and was both safe and efficacious in malaria-infected mice. Collectively, our data demonstrate that RCB-185 potently and selectively inhibits Dxr in P. falciparum, and represents a promising lead compound for further drug development.
Evolutionary shifts in gene expression decoupled from gene duplication across functionally distinct spider silk glands
Authors: Clarke Thomas H. , Garb Jessica E. , Haney Robert A. , Chaw R. Crystal , Hayashi Cheryl Y. , Ayoub Nadia A. 
Published: August 2017

AbstractSpider silk synthesis is an emerging model for the evolution of tissue-specific gene expression and the role of gene duplication in functional novelty, but its potential has not been fully realized. Accordingly, we quantified transcript (mRNA) abundance in seven silk gland types and three non-silk gland tissues for three cobweb-weaving spider species. Evolutionary analyses based on expression levels of thousands of homologous transcripts and phylogenetic reconstruction of 605 gene families demonstrated conservation of expression for each gland type among species. Despite serial homology of all silk glands, the expression profiles of the glue-forming aggregate glands were divergent from fiber-forming glands. Also surprising was our finding that shifts in gene expression among silk gland types were not necessarily coupled with gene duplication, even though silk-specific genes belong to multi-paralog gene families. Our results challenge widely accepted models of tissue specialization and significantly advance efforts to replicate silk-based high-performance biomaterials.
Lignin Valorization: Two Hybrid Biochemical Routes for the Conversion of Polymeric Lignin into Value-added Chemicals
Authors: Wu Weihua , Dutta Tanmoy , Varman Arul M. , Eudes Aymerick , Manalansan Bianca , Loqué Dominique , Singh Seema 
Published: August 2017

AbstractNaturally, many aerobic organisms degrade lignin-derived aromatics through conserved intermediates including protocatechuate and catechol. Employing this microbial approach offers a potential solution for valorizing lignin into valuable chemicals for a potential lignocellulosic biorefinery and enabling bioeconomy. In this study, two hybrid biochemical routes combining lignin chemical depolymerization, plant metabolic engineering, and synthetic pathway reconstruction were demonstrated for valorizing lignin into value-added products. In the biochemical route 1, alkali lignin was chemically depolymerized into vanillin and syringate as major products, which were further bio-converted into cis, cis-muconic acid (ccMA) and pyrogallol, respectively, using engineered Escherichia coli strains. In the second biochemical route, the shikimate pathway of Tobacco plant was engineered to accumulate protocatechuate (PCA) as a soluble intermediate compound. The PCA extracted from the engineered Tobacco was further converted into ccMA using the engineered E. coli strain. This study reports a direct process for converting lignin into ccMA and pyrogallol as value-added chemicals, and more importantly demonstrates benign methods for valorization of polymeric lignin that is inherently heterogeneous and recalcitrant. Our approach also validates the promising combination of plant engineering with microbial chassis development for the production of value added and speciality chemicals.
Quantification of lactate from various metabolic pathways and quantification issues of lactate isotopologues and isotopmers
Authors: Zhang Wei , Guo Cheng , Jiang Kezhi , Ying Minfeng , Hu Xun 
Published: August 2017

Abstract13C-labeled glucose combined with chromatography and mass spectrometry enables us to decipher the percentage of lactate generated from various metabolic pathways. We showed that lactate derived from glycolysis, pentose phosphate pathway, Krebs cycle, and other sources accounted for 82–90%, 6.0–11%, 0.67–1.8% and 1.5–7.9%, respectively, depending on different types of cells. When using glucose isotopomers ([1-13C]-, [3-13C]-, [4-13C]-, and [6-13C]glucose) or isotopologues ([1,2-13C2]- and [1,2,3-13C3]glucose) for tracing, the ratio of lactate derived from glucose carbon 1, 2, 3 over 4, 5, 6 via glycolysis varied significantly, ranging from 1.6 (traced with [1,2-13C2]glucose) to 0.85 (traced with [6-13C]glucose), but the theoretical ratio should be 1. The odd results might be caused by intramolecular 13C, which may significantly affect lactate fragmentation under tandem mass spectrometry condition, leading to erroneous quantification. Indeed, the fragmentation efficiency of [U-13C]lactate, [2,3-13C]lactate, and [3-13C]lactate were 1.4, 1.5 and 1.2 folds higher than lactate, respectively, but [1-13C]lactate was similar to lactate, suggesting that carbon-13 at different positions could differentially influence lactate fragmentation. This observed phenomenon was inconsistent with the data based on theoretical calculation, according to which activation energies for all lactate isotopomers and isotopologues are nearly identical. The inconsistency suggested a need for further investigation. Our study suggests that calibration is required for quantifying metabolite isotopolugues and isotopomers.
Susceptibility of influenza A(H1N1)/pdm2009, seasonal A(H3N2) and B viruses to Oseltamivir in Guangdong, China between 2009 and 2014
Authors: Liu Shan-shan , Jiao Xiao-yang , Wang Sheng , Su Wen-zhe , Jiang Ling-zhi , Zhang Xin , Ke Chang-wen , Xiong Ping 
Published: August 2017

AbstractNasopharyngeal swabs were collected from patients through the influenza surveillance network of the CDC of Guangdong. All specimens between 2009 and 2014 were checked for influenza virus using MDCK cells and further subtyped. Of those collected, 542 H1N1pdm09, 230 A(H3N2)and 448 B viruses selected at random were subjected to fluorescence-based NAI assays. Viral RNA was extracted from resistant isolates, and their NA genes were amplified by RT-PCR. Alignment of nucleotides and amino acids was performed. We performed structural modelling and simulations of mutants using Modeller 9.x and AutoDock and analyzed conformations and binding affinities. All tested seasonal type B and H3N2 viruses from 2009 to 2014 remained sensitive to oseltamivir. However, there were five strains (out of 198 tested isolates acquired between June and September 2013) that were resistant to oseltamivir. Another three resistant strains were identified among isolates from March to April 2014. We found that 2013/2014 oseltamivir-resistant strains and 2012/2013/2014 oseltamivir-sensitive strains had all or some of the following mutations: N44S, N200S,V241I, I321V,N369K, N386 K and K432E. MutationsV241I, N369K, N386K and K432E, alone or in conjunction with H275Y, had a significant impact on the binding pattern and affinity of oseltamivir for neuraminidase, rendering neuraminidase less susceptible.
CRISPR-Cas9 Mediated Labelling Allows for Single Molecule Imaging and Resolution
Authors: Khan Abdullah O. , Simms Victoria A. , Pike Jeremy A. , Thomas Steven G. , Morgan Neil V. 
Published: August 2017

AbstractSingle molecule imaging approaches like dSTORM and PALM resolve structures at 10–20 nm, and allow for unique insights into protein stoichiometry and spatial relationships. However, key obstacles remain in developing highly accurate quantitative single molecule approaches. The genomic tagging of PALM fluorophores through CRISPR-Cas9 offers an excellent opportunity for generating stable cell lines expressing a defined single molecule probe at endogenous levels, without the biological disruption and variability inherent to transfection. A fundamental question is whether these comparatively low levels of expression can successfully satisfy the stringent labelling demands of super-resolution SMLM. Here we apply CRISPR-Cas9 gene editing to tag a cytoskeletal protein (α-tubulin) and demonstrate a relationship between expression level and the subsequent quality of PALM imaging, and that spatial resolutions comparable to dSTORM can be achieved with CRISPR-PALM. Our approach shows a relationship between choice of tag and the total expression of labelled protein, which has important implications for the development of future PALM tags. CRISPR-PALM allows for nanoscopic spatial resolution and the unique quantitative benefits of single molecule localization microscopy through endogenous expression, as well as the capacity for super-resolved live cell imaging.
The genetic variation rs12143842 in NOS1AP increases idiopathic ventricular tachycardia risk in Chinese Han populations
Authors: Zhang Ronfeng , Chen Feifei , Yu Honjiu , Gao Lianjun , Yin Xiaomeng , Dong Yingxue , Yang Yanzong , Xia Yunlong 
Published: August 2017

AbstractGenome-wide association studies identified that the common T of rs12143842 in NOS1AP is associated with a QT/QTc interval in European populations. In this study, we test the association between the variation rs12143842 in NOS1AP and idiopathic ventricular tachycardia (IVT). A case-control association study examining rs12143842 was performed in two independent cohorts. The Northern cohort enrolled 277 IVT patients and 728 controls from a Chinese Gene ID population. The Central cohort enrolled 301 IVT patients and 803 matched controls. Genotyping was performed using high-resolution melt analysis. The minor T allele of the rs12143842 SNP was significantly associated with decreased IVT risk in the Northern cohort (adjusted P = 0.024, OR 0.71(0.52~0.96)), and this association was replicated in an independent Central Gene ID cohort (adjusted P = 0.029, OR 0.78 (0.62~0.97)). The association was more significant in the combined population (adjusted P = 0.001, OR 0.76 (0.64~0.90)). The P values for the genotypic association were significant for the dominant (P < 0.001) and additive (P = 0.001) models. The minor T allele for the SNP rs12143842 in NOS1AP is significantly associated with IVT. NOS1AP might be a novel gene affecting IVT, and further functional studies should be performed.
Non-thermal plasma-treated solution demonstrates antitumor activity against pancreatic cancer cells in vitro and in vivo
Authors: Liedtke Kim Rouven , Bekeschus Sander , Kaeding André , Hackbarth Christine , Kuehn Jens-Peter , Heidecke Claus-Dieter , von Bernstorff Wolfram , von Woedtke Thomas , Partecke Lars Ivo 
Published: August 2017

AbstractPancreatic cancer is associated with a high mortality rate. In advanced stage, patients often experience peritoneal carcinomatosis. Using a syngeneic murine pancreatic cancer cell tumor model, the effect of non-thermal plasma (NTP) on peritoneal metastatic lesions was studied. NTP generates reactive species of several kinds which have been proven to be of relevance in cancer. In vitro, exposure to both plasma and plasma-treated solution significantly decreased cell viability and proliferation of 6606PDA cancer cells, whereas mouse fibroblasts were less affected. Repeated intraperitoneal treatment of NTP-conditioned medium decreased tumor growth in vivo as determined by magnetic resonance imaging, leading to reduced tumor mass and improved median survival (61 vs 52 days; p < 0.024). Tumor nodes treated by NTP-conditioned medium demonstrated large areas of apoptosis with strongly inhibited cell proliferation. Contemporaneously, no systemic effects were found. Apoptosis was neither present in the liver nor in the gut. Also, the concentration of different cytokines in splenocytes or blood plasma as well as the distribution of various hematological parameters remained unchanged following treatment with NTP-conditioned medium. These results suggest an anticancer role of NTP-treated solutions with little to no systemic side effects being present, making NTP-treated solutions a potential complementary therapeutic option for advanced tumors.
Micron-scale mapping of megagauss magnetic fields using optical polarimetry to probe hot electron transport in petawatt-class laser-solid interactions
Authors: Chatterjee Gourab , Singh Prashant Kumar , Robinson A. P. L. , Blackman D. , Booth N. , Culfa O. , Dance R. J. , Gizzi L. A. , Gray R. J. , Green J. S. , Koester P. , Kumar G. Ravindra , Labate L. , Lad Amit D. , Lancaster K. L. , Pasley J. , Woolsey N. C. , Rajeev P. P. 
Published: August 2017

AbstractThe transport of hot, relativistic electrons produced by the interaction of an intense petawatt laser pulse with a solid has garnered interest due to its potential application in the development of innovative x-ray sources and ion-acceleration schemes. We report on spatially and temporally resolved measurements of megagauss magnetic fields at the rear of a 50-μm thick plastic target, irradiated by a multi-picosecond petawatt laser pulse at an incident intensity of ~1020 W/cm2. The pump-probe polarimetric measurements with micron-scale spatial resolution reveal the dynamics of the magnetic fields generated by the hot electron distribution at the target rear. An annular magnetic field profile was observed ~5 ps after the interaction, indicating a relatively smooth hot electron distribution at the rear-side of the plastic target. This is contrary to previous time-integrated measurements, which infer that such targets will produce highly structured hot electron transport. We measured large-scale filamentation of the hot electron distribution at the target rear only at later time-scales of ~10 ps, resulting in a commensurate large-scale filamentation of the magnetic field profile. Three-dimensional hybrid simulations corroborate our experimental observations and demonstrate a beam-like hot electron transport at initial time-scales that may be attributed to the local resistivity profile at the target rear.