bluuebunny/crossref_metadata_2025_split huggingface dataset:
Erianin induces G2/M-phase arrest, apoptosis, and autophagy via the ROS/JNK signaling pathway in human osteosarcoma cells in vitro and in vivo
Authors: Wang H , Zhang T , Sun W , Wang Z , Zuo D , Zhou Z , Li S , Xu J , Yin F , Hua Y , Cai Z 
Published: June 2016

AbstractErianin, a natural product derived from Dendrobium chrysotoxum, has exhibited potential antitumor activity in various malignancies, including hepatocarcinoma, melanoma, and promyelocytic leukemia. Here we explored the effects of erianin on osteosarcoma (OS) in vitro and in vivo and further elucidated the underlying molecule mechanisms. In this study, we found that erianin potently suppressed cell viability in various OS cell lines. Treatment with erianin induced G2/M-phase arrest, apoptosis, and autophagy in OS cells. Further studies showed that erianin-induced apoptosis and autophagy was attributed to reactive oxygen species (ROS), as N-acetyl cysteine (NAC), an ROS scavenger, attenuated them. Moreover, we found that erianin induced activation of c-Jun N-terminal kinase (JNK) signal pathway, which was also blocked by NAC. Downregulation of JNK by its specific inhibitor SP600125 could attenuate apoptosis and autophagy induced by erianin. Finally, erianin in vivo markedly reduced the growth with little organ-related toxicity. In conclusion, erianin induced cell cycle G2/M-phase arrest, apoptosis, and autophagy via the ROS/JNK signaling pathway in human OS. In light of these results, erianin may be a promising agent for anticancer therapy against OS.
TMEM2 inhibits hepatitis B virus infection in HepG2 and HepG2.2.15 cells by activating the JAK–STAT signaling pathway
Authors: Zhu X , Xie C , Li Y-m , Huang Z-l , Zhao Q-y , Hu Z-x , Wang P-p , Gu Y-r , Gao Z-l , Peng L 
Published: June 2016

AbstractWe have previously observed the downregulation of TMEM2 in the liver tissue of patients with chronic hepatitis B virus (HBV) infection and in HepG2.2.15 cells with HBV genomic DNA. In the present study, we investigated the role and mechanism of TMEM2 in HepG2 and HepG2.2.15 during HBV infection HepG2 and HepG2.2.15. HepG2 shTMEM2 cells with stable TMEM2 knockdown and HepG2 TMEM2 and HepG2.2.15 TMEM2 cells with stable TMEM2 overexpression were established using lentivirus vectors. We observed reduced expression of TMEM2 in HBV-infected liver tissues and HepG2.2.15 cells. HBsAg, HBcAg, HBV DNA, and HBV cccDNA levels were significantly increased in HepG2 shTMEM2 cells but decreased in HepG2 TMEM2 and HepG2.2.15 TMEM2 cells compared with naive HepG2 cells. On the basis of the western blotting results, the JAK–STAT signaling pathway was inhibited in HepG2 shTMEM2 cells but activated in HepG2 TMEM2 and HepG2.2.15 TMEM2 cells. In addition, reduced and increased expression of the antiviral proteins MxA and OAS1 was observed in TMEM2-silenced cells (HepG2 shTMEM2 cells) and TMEM2-overexpressing cells (HepG2 TMEM2 and HepG2.2.15 TMEM2 cells), respectively. The expression of Interferon regulatory factor 9 (IRF9) was not affected by TMEM2. However, we found that overexpression and knockdown of TMEM2, respectively, promoted and inhibited importation of IRF9 into nuclei. The luciferase reporter assay showed that IRF9 nuclear translocation affected interferon-stimulated response element activities. In addition, the inhibitory effects of TMEM2 on HBV infection in HepG2 shTMEM2 cells was significantly enhanced by pre-treatment with interferon but significantly inhibited in HepG2.2.15 TMEM2 cells by pre-treatment with JAK1 inhibitor. TMEM2 inhibits HBV infection in HepG2 and HepG2.2.15 by activating the JAK–STAT signaling pathway.
A ribosome-related signature in peripheral blood CLL B cells is linked to reduced survival following treatment
Authors: Sbarrato T , Horvilleur E , Pöyry T , Hill K , Chaplin L C , Spriggs R V , Stoneley M , Wilson L , Jayne S , Vulliamy T , Beck D , Dokal I , Dyer M J S , Yeomans A M , Packham G , Bushell M , Wagner S D , Willis A E 
Published: June 2016

AbstractWe have used polysome profiling coupled to microarray analysis to examine the translatome of a panel of peripheral blood (PB) B cells isolated from 34 chronic lymphocytic leukaemia (CLL) patients. We have identified a ‘ribosome-related’ signature in CLL patients with mRNAs encoding for ribosomal proteins and factors that modify ribosomal RNA, e.g. DKC1 (which encodes dyskerin, a pseudouridine synthase), showing reduced polysomal association and decreased expression of the corresponding proteins. Our data suggest a general impact of dyskerin dysregulation on the translational apparatus in CLL and importantly patients with low dyskerin levels have a significantly shorter period of overall survival following treatment. Thus, translational dysregulation of dyskerin could constitute a mechanism by which the CLL PB B cells acquire an aggressive phenotype and thus have a major role in oncogenesis.
Toll-like receptor 4 modulates the cochlear immune response to acoustic injury
Authors: Vethanayagam R R , Yang W , Dong Y , Hu B H 
Published: June 2016

AbstractAcoustic overstimulation traumatizes the cochlea, resulting in auditory dysfunction. As a consequence of acoustic injury, the immune system in the cochlea is activated, leading to the production of inflammatory mediators and the infiltration of immune cells. However, the molecular mechanisms responsible for initiating these immune responses remain unclear. Here, we investigate the functional role of Toll-like receptor 4 (Tlr4), a cellular receptor that activates the innate immune system, in the regulation of cochlear responses to acoustic overstimulation. Using a Tlr4 knockout mouse model, we examined how Tlr4 deficiency affects sensory cell pathogenesis, auditory dysfunction and cochlear immune activity. We demonstrate that Tlr4 knockout does not affect sensory cell viability under physiological conditions, but reduces the level of sensory cell damage and cochlear dysfunction after acoustic injury. Together, these findings suggest that Tlr4 promotes sensory cell degeneration and cochlear dysfunction after acoustic injury. Acoustic injury provokes a site-dependent inflammatory response in both the organ of Corti and the tissues of the lateral wall and basilar membrane. Tlr4 deficiency affects these inflammatory responses in a site-dependent manner. In the organ of Corti, loss of Tlr4 function suppresses the production of interleukin 6 (Il6), a pro-inflammatory molecule, after acoustic injury. By contrast, the production of inflammatory mediators, including Il6, persists in the lateral wall and basilar membrane. In addition to immune molecules, Tlr4 knockout inhibits the expression of major histocompatibility complex class II, an antigen-presenting molecule, in macrophages, suggesting that Tlr4 participates in the antigen-presenting function of macrophages after acoustic trauma. Together, these results suggest that Tlr4 regulates multiple aspects of the immune response in the cochlea and contributes to cochlear pathogenesis after acoustic injury.
The dynamic transcriptional and translational landscape of the model antibiotic producer Streptomyces coelicolor A3(2)
Authors: Jeong Yujin , Kim Ji-Nu , Kim Min Woo , Bucca Giselda , Cho Suhyung , Yoon Yeo Joon , Kim Byung-Gee , Roe Jung-Hye , Kim Sun Chang , Smith Colin P. , Cho Byung-Kwan 
Published: June 2016

AbstractIndividual Streptomyces species have the genetic potential to produce a diverse array of natural products of commercial, medical and veterinary interest. However, these products are often not detectable under laboratory culture conditions. To harness their full biosynthetic potential, it is important to develop a detailed understanding of the regulatory networks that orchestrate their metabolism. Here we integrate nucleotide resolution genome-scale measurements of the transcriptome and translatome of Streptomyces coelicolor, the model antibiotic-producing actinomycete. Our systematic study determines 3,570 transcription start sites and identifies 230 small RNAs and a considerable proportion (∼21%) of leaderless mRNAs; this enables deduction of genome-wide promoter architecture. Ribosome profiling reveals that the translation efficiency of secondary metabolic genes is negatively correlated with transcription and that several key antibiotic regulatory genes are translationally induced at transition growth phase. These findings might facilitate the design of new approaches to antibiotic discovery and development.
LRP6 acts as a scaffold protein in cardiac gap junction assembly
Authors: Li Jun , Li Changming , Liang Dandan , Lv Fei , Yuan Tianyou , The Erlinda , Ma Xiue , Wu Yahan , Zhen Lixiao , Xie Duanyang , Wang Shiyi , Liu Yuan , Huang Jian , Shi Jingyi , Liu Yi , Shi Dan , Xu Liang , Lin Li , Peng Luying , Cui Jianmin , Zhu Weidong , Chen Yi-Han 
Published: June 2016

AbstractLow-density lipoprotein receptor-related protein 6 (LRP6) is a Wnt co-receptor in the canonical Wnt/β-catenin signalling. Here, we report the scaffold function of LRP6 in gap junction formation of cardiomyocytes. Cardiac LRP6 is spatially restricted to intercalated discs and binds to gap junction protein connexin 43 (Cx43). A deficiency in LRP6 disrupts Cx43 gap junction formation and thereby impairs the cell-to-cell coupling, which is independent of Wnt/β-catenin signalling. The defect in Cx43 gap junction resulting from LRP6 reduction is attributable to the defective traffic of de novo Cx43 proteins from the endoplasmic reticulum to the Golgi apparatus, leading to the lysosomal degradation of Cx43 proteins. Accordingly, the hearts of conditional cardiac-specific Lrp6-knockout mice consistently exhibit overt reduction of Cx43 gap junction plaques without any abnormality in Wnt signalling and are predisposed to lethal arrhythmias. These findings uncover a distinct role of LRP6 as a platform for intracellular protein trafficking.
Improving GENCODE reference gene annotation using a high-stringency proteogenomics workflow
Authors: Wright James C. , Mudge Jonathan , Weisser Hendrik , Barzine Mitra P. , Gonzalez Jose M. , Brazma Alvis , Choudhary Jyoti S. , Harrow Jennifer 
Published: June 2016

AbstractComplete annotation of the human genome is indispensable for medical research. The GENCODE consortium strives to provide this, augmenting computational and experimental evidence with manual annotation. The rapidly developing field of proteogenomics provides evidence for the translation of genes into proteins and can be used to discover and refine gene models. However, for both the proteomics and annotation groups, there is a lack of guidelines for integrating this data. Here we report a stringent workflow for the interpretation of proteogenomic data that could be used by the annotation community to interpret novel proteogenomic evidence. Based on reprocessing of three large-scale publicly available human data sets, we show that a conservative approach, using stringent filtering is required to generate valid identifications. Evidence has been found supporting 16 novel protein-coding genes being added to GENCODE. Despite this many peptide identifications in pseudogenes cannot be annotated due to the absence of orthogonal supporting evidence.
Demonstration of a positron beam-driven hollow channel plasma wakefield accelerator
Authors: Gessner Spencer , Adli Erik , Allen James M. , An Weiming , Clarke Christine I. , Clayton Chris E. , Corde Sebastien , Delahaye J. P. , Frederico Joel , Green Selina Z. , Hast Carsten , Hogan Mark J. , Joshi Chan , Lindstrøm Carl A. , Lipkowitz Nate , Litos Michael , Lu Wei , Marsh Kenneth A. , Mori Warren B. , O’Shea Brendan , Vafaei-Najafabadi Navid , Walz Dieter , Yakimenko Vitaly , Yocky Gerald 
Published: June 2016

AbstractPlasma wakefield accelerators have been used to accelerate electron and positron particle beams with gradients that are orders of magnitude larger than those achieved in conventional accelerators. In addition to being accelerated by the plasma wakefield, the beam particles also experience strong transverse forces that may disrupt the beam quality. Hollow plasma channels have been proposed as a technique for generating accelerating fields without transverse forces. Here we demonstrate a method for creating an extended hollow plasma channel and measure the wakefields created by an ultrarelativistic positron beam as it propagates through the channel. The plasma channel is created by directing a high-intensity laser pulse with a spatially modulated profile into lithium vapour, which results in an annular region of ionization. A peak decelerating field of 230 MeV m−1 is inferred from changes in the beam energy spectrum, in good agreement with theory and particle-in-cell simulations.
Wafer-scale fabrication and growth dynamics of suspended graphene nanoribbon arrays
Authors: Suzuki Hiroo , Kaneko Toshiro , Shibuta Yasushi , Ohno Munekazu , Maekawa Yuki , Kato Toshiaki 
Published: June 2016

AbstractAdding a mechanical degree of freedom to the electrical and optical properties of atomically thin materials can provide an excellent platform to investigate various optoelectrical physics and devices with mechanical motion interaction. The large scale fabrication of such atomically thin materials with suspended structures remains a challenge. Here we demonstrate the wafer-scale bottom–up synthesis of suspended graphene nanoribbon arrays (over 1,000,000 graphene nanoribbons in 2 × 2 cm2 substrate) with a very high yield (over 98%). Polarized Raman measurements reveal graphene nanoribbons in the array can have relatively uniform-edge structures with near zigzag orientation dominant. A promising growth model of suspended graphene nanoribbons is also established through a comprehensive study that combined experiments, molecular dynamics simulations and theoretical calculations with a phase-diagram analysis. We believe that our results can contribute to pushing the study of graphene nanoribbons into a new stage related to the optoelectrical physics and industrial applications.
Creation of a library of induced pluripotent stem cells from Parkinsonian patients
Authors: Holmqvist Staffan , Lehtonen Šárka , Chumarina Margarita , Puttonen Katja A , Azevedo Carla , Lebedeva Olga , Ruponen Marika , Oksanen Minna , Djelloul Mehdi , Collin Anna , Goldwurm Stefano , Meyer Morten , Lagarkova Maria , Kiselev Sergei , Koistinaho Jari , Roybon Laurent 
Published: June 2016

AbstractInduced pluripotent stem cells (iPSCs) are becoming an important source of pre-clinical models for research focusing on neurodegeneration. They offer the possibility for better understanding of common and divergent pathogenic mechanisms of brain diseases. Moreover, iPSCs provide a unique opportunity to develop personalized therapeutic strategies, as well as explore early pathogenic mechanisms, since they rely on the use of patients’ own cells that are otherwise accessible only post-mortem, when neuronal death-related cellular pathways and processes are advanced and adaptive. Neurodegenerative diseases are in majority of unknown cause, but mutations in specific genes can lead to familial forms of these diseases. For example, mutations in the superoxide dismutase 1 gene lead to the motor neuron disease amyotrophic lateral sclerosis (ALS), while mutations in the SNCA gene encoding for alpha-synuclein protein lead to familial Parkinson’s disease (PD). The generations of libraries of familial human ALS iPSC lines have been described, and the iPSCs rapidly became useful models for studying cell autonomous and non-cell autonomous mechanisms of the disease. Here we report the generation of a comprehensive library of iPSC lines of familial PD and an associated synucleinopathy, multiple system atrophy (MSA). In addition, we provide examples of relevant neural cell types these iPSC can be differentiated into, and which could be used to further explore early disease mechanisms. These human cellular models will be a valuable resource for identifying common and divergent mechanisms leading to neurodegeneration in PD and MSA.
Predictive value of the composition of the vaginal microbiota in bacterial vaginosis, a dynamic study to identify recurrence-related flora
Authors: Xiao Bingbing , Niu Xiaoxi , Han Na , Wang Ben , Du Pengcheng , Na Risu , Chen Chen , Liao Qinping 
Published: June 2016

AbstractBacterial vaginosis (BV) is a highly prevalent disease in women and increases the risk of pelvic inflammatory disease. It has been given wide attention because of the high recurrence rate. Traditional diagnostic methods based on microscope providing limited information on the vaginal microbiota increase the difficulty in tracing the development of the disease in bacteria resistance condition. In this study, we used deep-sequencing technology to observe dynamic variation of the vaginal microbiota at three major time points during treatment, at D0 (before treatment), D7 (stop using the antibiotics) and D30 (the 30-day follow-up visit). Sixty-five patients with BV were enrolled (48 were cured and 17 were not cured) and their bacterial composition of the vaginal microbiota was compared. Interestingly, we identified 9 patients might be recurrence. We also introduced a new measurement point of D7, although its microbiota were significantly inhabited by antibiotic and hard to be observed by traditional method. The vaginal microbiota in deep-sequencing-view present a strong correlation to the final outcome. Thus, coupled with detailed individual bioinformatics analysis and deep-sequencing technology, we may illustrate a more accurate map of vaginal microbial to BV patients, which provide a new opportunity to reduce the rate of recurrence of BV.
Magnetic Trapping of Bacteria at Low Magnetic Fields
Authors: Wang Z. M. , Wu R. G. , Wang Z. P. , Ramanujan R. V. 
Published: June 2016

AbstractA suspension of non-magnetic entities in a ferrofluid is referred to as an inverse ferrofluid. Current research to trap non-magnetic entities in an inverse ferrofluid focuses on using large permanent magnets to generate high magnetic field gradients, which seriously limits Lab-on-a-Chip applications. On the other hand, in this work, trapping of non-magnetic entities, e.g., bacteria in a uniform external magnetic field was studied with a novel chip design. An inverse ferrofluid flows in a channel and a non-magnetic island is placed in the middle of this channel. The magnetic field was distorted by this island due to the magnetic susceptibility difference between this island and the surrounding ferrofluid, resulting in magnetic forces applied on the non-magnetic entities. Both the ferromagnetic particles and the non-magnetic entities, e.g., bacteria were attracted towards the island, and subsequently accumulate in different regions. The alignment of the ferrimagnetic particles and optical transparency of the ferrofluid was greatly enhanced by the bacteria at low applied magnetic fields. This work is applicable to lab-on-a-chip based detection and trapping of non-magnetic entities bacteria and cells.
Cotesia vestalis teratocytes express a diversity of genes and exhibit novel immune functions in parasitism
Authors: Gao Fei , Gu Qi-juan , Pan Jing , Wang Ze-hua , Yin Chuan-lin , Li Fei , Song Qi-sheng , Strand Michael R. , Chen Xue-xin , Shi Min 
Published: June 2016

AbstractSome endoparasitoid wasps lay eggs that produce cells called teratocytes. In this study, we sequenced and analyzed the transcriptome of teratocytes from the solitary endoparasitoid Cotesia vestalis (Braconidae), which parasitizes larval stage Plutella xylostella (Plutellidae). Results identified many teratocyte transcripts with potential functions in affecting host immune defenses, growth or metabolism. Characterization of teratocyte-secreted venom-like protein 8 (TSVP-8) indicated it inhibits melanization of host hemolymph in vitro, while two predicted anti-microbial peptides (CvT-def 1 and 3) inhibited the growth of bacteria. Results also showed the parasitized hosts lacking teratocytes experienced higher mortality after immune challenge by pathogens than hosts with teratocytes. Taken together, these findings indicate that C. vestalis teratocytes secrete products that alter host immune functions while also producing anti-microbial peptides with functions that help protect the host from infection by other organisms.
Global gene expression analysis using RNA-seq uncovered a new role for SR1/CAMTA3 transcription factor in salt stress
Authors: Prasad Kasavajhala V. S. K. , Abdel-Hameed Amira A. E. , Xing Denghui , Reddy Anireddy S. N. 
Published: June 2016

AbstractAbiotic and biotic stresses cause significant yield losses in all crops. Acquisition of stress tolerance in plants requires rapid reprogramming of gene expression. SR1/CAMTA3, a member of signal responsive transcription factors (TFs), functions both as a positive and a negative regulator of biotic stress responses and as a positive regulator of cold stress-induced gene expression. Using high throughput RNA-seq, we identified ~3000 SR1-regulated genes. Promoters of about 60% of the differentially expressed genes have a known DNA binding site for SR1, suggesting that they are likely direct targets. Gene ontology analysis of SR1-regulated genes confirmed previously known functions of SR1 and uncovered a potential role for this TF in salt stress. Our results showed that SR1 mutant is more tolerant to salt stress than the wild type and complemented line. Improved tolerance of sr1 seedlings to salt is accompanied with the induction of salt-responsive genes. Furthermore, ChIP-PCR results showed that SR1 binds to promoters of several salt-responsive genes. These results suggest that SR1 acts as a negative regulator of salt tolerance by directly repressing the expression of salt-responsive genes. Overall, this study identified SR1-regulated genes globally and uncovered a previously uncharacterized role for SR1 in salt stress response.
Immuno-targeting the multifunctional CD38 using nanobody
Authors: Li Ting , Qi Shali , Unger Mandy , Hou Yun Nan , Deng Qi Wen , Liu Jun , Lam Connie M. C. , Wang Xian Wang , Xin Du , Zhang Peng , Koch-Nolte Friedrich , Hao Quan , Zhang Hongmin , Lee Hon Cheung , Zhao Yong Juan 
Published: June 2016

AbstractCD38, as a cell surface antigen is highly expressed in several hematologic malignancies including multiple myeloma (MM) and has been proven to be a good target for immunotherapy of the disease. CD38 is also a signaling enzyme responsible for the metabolism of two novel calcium messenger molecules. To be able to target this multifunctional protein, we generated a series of nanobodies against CD38 with high affinities. Crystal structures of the complexes of CD38 with the nanobodies were solved, identifying three separate epitopes on the carboxyl domain. Chromobodies, engineered by tagging the nanobody with fluorescence proteins, provide fast, simple and versatile tools for quantifying CD38 expression. Results confirmed that CD38 was highly expressed in malignant MM cells compared with normal white blood cells. The immunotoxin constructed by splicing the nanobody with a bacterial toxin, PE38 shows highly selective cytotoxicity against patient-derived MM cells as well as the cell lines, with half maximal effective concentration reaching as low as 10−11 molar. The effectiveness of the immunotoxin can be further increased by stimulating CD38 expression using retinoid acid. These results set the stage for the development of clinical therapeutics as well as diagnostic screening for myeloma.