bluuebunny/crossref_metadata_2025_split huggingface dataset:
Doxycycline, metronidazole and isotretinoin: Do they modify microRNA/mRNA expression profiles and function in murine T-cells?
Authors: Becker Eugenia , Bengs Susan , Aluri Sirisha , Opitz Lennart , Atrott Kirstin , Stanzel Claudia , Castro Pedro A. Ruiz , Rogler Gerhard , Frey-Wagner Isabelle 
Published: November 2016

AbstractInflammatory bowel disease (IBD) may develop due to an inflammatory response to commensal gut microbiota triggered by environmental factors in a genetically susceptible host. Isotretinoin (acne therapy) has been inconsistently associated with IBD onset and flares but prior treatment with antibiotics, also associated with IBD development, complicates the confirmation of this association. Here we studied in mice whether doxycycline, metronidazole or isotretinoin induce epigenetic modifications, and consequently change T-cell mRNA expression and/or function directly after treatment and after a 4 week recovery period. Isotretinoin induced IL-10 signaling in Tregs and naive T-cells directly after treatment and reduced effector T-cell proliferation alone and in co-culture with Tregs. Metronidazole activated processes associated with anti-inflammatory pathways in both T-cell subsets directly after the treatment period whereas doxycycline induced an immediate pro-inflammatory expression profile that resolved after the recovery period. Long-term changes indicated an inhibition of proliferation by doxycycline and induction of beneficial immune and metabolic pathways by metronidazole. Persistent alterations in microRNA and mRNA expression profiles after the recovery period indicate that all three medications may induce long-term epigenetic modifications in both T-cell subsets. Yet, our data do not support the induction of a long-term pro-inflammatory phenotype in murine Tregs and naive T-cells.
The Lnc RNA SPRY4-IT1 Modulates Trophoblast Cell Invasion and Migration by Affecting the Epithelial-Mesenchymal Transition
Authors: Zuo Qing , Huang Shiyun , Zou Yanfen , Xu Yetao , Jiang Ziyan , Zou Shan , Xu Haoqing , Sun Lizhou 
Published: November 2016

AbstractPreeclampsia is a common, pregnancy-specific disease and a major contributor to maternal and foetal morbidity and mortality. Some placental abnormalities, including deficient implantation, abnormal trophoblast cell function, and improper placental vascular development, are believed to lead to preeclampsia. The long noncoding RNA SPRY4-IT1 is more highly expressed in preeclamptic human placentas than in normal placentas. We assessed the role of epithelial-mesenchymal transition (EMT)-associated invasion and migration in HTR-8/SVneo trophoblast cells. Overexpression of SPRY4-IT1 suppressed trophoblast cell migration and invasion, whereas reduced expression of SPRY4-IT1 prevented the EMT process. Mechanistically, an RNA immunoprecipitation experiment showed that SPRY4-IT1 bound directly to HuR and mediated the β-catenin expression associated with EMT in HTR-8/SVneo cells. Moreover, the expression levels of genes in the WNT family, such as WNT3 and WNT5B, were changed after transfection of HTR-8/SVneo with SPRY4-IT1. Together, our results highlight the roles of SPRY4-IT1 in causing trophoblast cell dysfunction by acting through the Wnt/β-catenin pathway, and consequently in impairing spiral artery remodelling. These results suggest a new potential therapeutic target for intervention against preeclampsia.
Selective sweep on human amylase genes postdates the split with Neanderthals
Authors: Inchley Charlotte E. , Larbey Cynthia D. A. , Shwan Nzar A. A. , Pagani Luca , Saag Lauri , Antão Tiago , Jacobs Guy , Hudjashov Georgi , Metspalu Ene , Mitt Mario , Eichstaedt Christina A. , Malyarchuk Boris , Derenko Miroslava , Wee Joseph , Abdullah Syafiq , Ricaut François-Xavier , Mormina Maru , Mägi Reedik , Villems Richard , Metspalu Mait , Jones Martin K. , Armour John A. L. , Kivisild Toomas 
Published: November 2016

AbstractHumans have more copies of amylase genes than other primates. It is still poorly understood, however, when the copy number expansion occurred and whether its spread was enhanced by selection. Here we assess amylase copy numbers in a global sample of 480 high coverage genomes and find that regions flanking the amylase locus show notable depression of genetic diversity both in African and non-African populations. Analysis of genetic variation in these regions supports the model of an early selective sweep in the human lineage after the split of humans from Neanderthals which led to the fixation of multiple copies of AMY1 in place of a single copy. We find evidence of multiple secondary losses of copy number with the highest frequency (52%) of a deletion of AMY2A and associated low copy number of AMY1 in Northeast Siberian populations whose diet has been low in starch content.
Foetal programming by methyl donor deficiency produces steato-hepatitis in rats exposed to high fat diet
Authors: Bison Anaïs , Marchal-Bressenot Aude , Li Zhen , Elamouri Ilef , Feigerlova Eva , Peng Lu , Houlgatte Remi , Beck Bernard , Pourié Gregory , Alberto Jean-Marc , Umoret Remy , Conroy Guillaume , Bronowicki Jean-Pierre , Guéant Jean-Louis , Guéant-Rodriguez Rosa-Maria 
Published: November 2016

AbstractNon-alcoholic steatohepatitis (NASH) is a manifestation of metabolic syndrome, which emerges as a major public health problem. Deficiency in methyl donors (folate and vitamin B12) during gestation and lactation is frequent in humans and produces foetal programming effects of metabolic syndrome, with small birth weight and liver steatosis at day 21 (d21), in rat pups. We investigated the effects of fetal programming on liver of rats born from deficient mothers (iMDD) and subsequently subjected to normal diet after d21 and high fat diet (HF) after d50. We observed increased abdominal fat, ASAT/ALAT ratio and angiotensin blood level, but no histological liver abnormality in d50 iMDD rats. In contrast, d185 iMDD/HF animals had hallmarks of steato-hepatitis, with increased markers of inflammation and fibrosis (caspase1, cleaved IL-1β, α1(I) and α2(I) collagens and α-SMA), insulin resistance (HOMA-IR and Glut 2) and expression of genes involved in stellate cell stimulation and remodelling and key genes triggering NASH pathomechanisms (transforming growth factor beta super family, angiotensin and angiotensin receptor type 1). Our data showed a foetal programming effect of MDD on liver inflammation and fibrosis, which suggests investigating whether MDD during pregnancy is a risk factor of NASH in populations subsequently exposed to HF diet.
Gastrodin protects against chronic inflammatory pain by inhibiting spinal synaptic potentiation
Authors: Xiao Mei-Mei , Zhang Yu-Qi , Wang Wen-Ting , Han Wen-Juan , Lin Zhen , Xie Rou-Gang , Cao Zhi , Lu Na , Hu San-Jue , Wu Sheng-Xi , Dong Hui , Luo Ceng 
Published: November 2016

AbstractTissue injury is known to produce inflammation and pain. Synaptic potentiation between peripheral nociceptors and spinal lamina I neurons has been proposed to serve as a trigger for chronic inflammatory pain. Gastrodin is a main bioactive constituent of the traditional Chinese herbal medicine Gastrodia elata Blume, which has been widely used as an analgesic since ancient times. However, its underlying cellular mechanisms have remained elusive. The present study demonstrated for the first time that gastrodin exhibits an analgesic effect at the spinal level on spontaneous pain, mechanical and thermal pain hypersensitivity induced by peripheral inflammation, which is not dependent on opioid receptors and without tolerance. This analgesia by gastrodin is at least in part mediated by depressing spinal synaptic potentiation via blockade of acid-sensing ion channels. Further studies with miniature EPSCs and paired-pulse ratio analysis revealed the presynaptic origin of the action of gastrodin, which involves a decrease in transmitter release probability. In contrast, neither basal nociception nor basal synaptic transmission was altered. This study revealed a dramatic analgesic action of gastrodin on inflammatory pain and uncovered a novel spinal mechanism that could underlie the analgesia by gastrodin, pointing the way to a new analgesic for treating chronic inflammatory pain.
A High-Fat High-Sucrose Diet Rapidly Alters Muscle Integrity, Inflammation and Gut Microbiota in Male Rats
Authors: Collins Kelsey H. , Paul Heather A. , Hart David A. , Reimer Raylene A. , Smith Ian C. , Rios Jaqueline L. , Seerattan Ruth A. , Herzog Walter 
Published: November 2016

AbstractThe chronic low-level inflammation associated with obesity is known to deleteriously affect muscle composition. However, the manner in which obesity leads to muscle loss has not been explored in detail or in an integrated manner following a short-term metabolic challenge. In this paper, we evaluated the relationships between compromised muscle integrity, diet, systemic inflammatory mediators, adipose tissue, and gut microbiota in male Sprague-Dawley rats. We show that intramuscular fat, fibrosis, and the number of pro-inflammatory cells increased by 3-days and was sustained across 28-days of high-fat high-sugar feeding compared to control-diet animals. To understand systemic contributors to muscle damage, dynamic changes in gut microbiota and serum inflammatory markers were evaluated. Data from this study links metabolic challenge to persistent compromise in muscle integrity after just 3-days, a finding associated with altered gut microbiota and systemic inflammatory changes. These data contribute to our understanding of early consequences of metabolic challenge on multiple host systems, which are important to understand as obesity treatment options are developed. Therefore, intervention within this early period of metabolic challenge may be critical to mitigate these sustained alterations in muscle integrity.
Lent-On-Plus Lentiviral vectors for conditional expression in human stem cells
Authors: Benabdellah Karim , Muñoz Pilar , Cobo Marién , Gutierrez-Guerrero Alejandra , Sánchez-Hernández Sabina , Garcia-Perez Angélica , Anderson Per , Carrillo-Gálvez Ana Belén , Toscano Miguel G. , Martin Francisco 
Published: November 2016

AbstractConditional transgene expression in human stem cells has been difficult to achieve due to the low efficiency of existing delivery methods, the strong silencing of the transgenes and the toxicity of the regulators. Most of the existing technologies are based on stem cells clones expressing appropriate levels of tTA or rtTA transactivators (based on the TetR-VP16 chimeras). In the present study, we aim the generation of Tet-On all-in-one lentiviral vectors (LVs) that tightly regulate transgene expression in human stem cells using the original TetR repressor. By using appropriate promoter combinations and shielding the LVs with the Is2 insulator, we have constructed the Lent-On-Plus Tet-On system that achieved efficient transgene regulation in human multipotent and pluripotent stem cells. The generation of inducible stem cell lines with the Lent-ON-Plus LVs did not require selection or cloning, and transgene regulation was maintained after long-term cultured and upon differentiation toward different lineages. To our knowledge, Lent-On-Plus is the first all-in-one vector system that tightly regulates transgene expression in bulk populations of human pluripotent stem cells and its progeny.
Genetic determination of the enhanced drought resistance of rice maintainer HuHan2B by pedigree breeding
Authors: Wei Haibin , Feng Fangjun , Lou Qiaojun , Xia Hui , Ma Xiaosong , Liu Yunhua , Xu Kai , Yu Xinqiao , Mei Hanwei , Luo Lijun 
Published: November 2016

AbstractThe ongoing deficit of fresh water resource in rice growing regions has made the selection of water-saving and drought-resistance rice (WDR) a crucial factor in developing sustainable cultivation. HuHan2B, a new japonica maintainer for WDR breeding, had the same yield potential as recurrent parent HanFengB but showed improved drought resistance in fields. We investigated the genomic content accumulation and candidate genes passed from parent to offspring using the genomic and transcriptomic approaches. The genomic constitution indicated that the genetic similarity was 84% between HuHan2B and HanFengB; additionally, 7,256 genes with specific alleles were inherited by HuHan2B from parents other than HanFengB. The differentially expressed genes (DEGs) under drought stress showed that biological function was significantly enriched for transcript regulation in HuHan2B, while the oxidation-reduction process was primarily enriched in HanFengB. Furthermore, 36 DEGs with specific inherited alleles in HuHan2B were almost involved in the regulatory network of TFs and target genes. These findings suggested that major-effect genes were congregated and transformed into offspring in manner of interacting network by breeding. Thus, exploiting the potential biological function of allelic-influencing DEGs would be of great importance for improving selection efficiency and the overall genetic gain of multiple complex traits.
Novel Podophyllotoxin Derivatives as Partial PPARγ Agonists and their Effects on Insulin Resistance and Type 2 Diabetes
Authors: Zhang Xiangming , Liu Huijuan , Sun Bo , Sun Yan , Zhong Weilong , Liu Yanrong , Chen Shuang , Ling Honglei , Zhou Lei , Jing Xiangyan , Qin Yuan , Xiao Ting , Sun Tao , Zhou Honggang , Yang Cheng 
Published: November 2016

AbstractPeroxisome proliferator-activated receptor γ (PPARγ) is recognized as a key regulator of insulin resistance. In this study, we searched for novel PPARγ agonists in a library of structurally diverse organic compounds and determined that podophyllotoxin exhibits partial agonist activity toward PPARγ. Eight novel podophyllotoxin-like derivatives were synthesized and assayed for toxicity and functional activity toward PPARγ to reduce the possible systemic toxic effects of podophyllotoxin and to maintain partial agonist activity toward PPARγ. Cell-based transactivation assays showed that compounds (E)-3-(hydroxy(3,4,5-trimethoxyphenyl)methyl)-4-(4(trifluoromethyl)styryl)dihydrofuran-2(3H)-one (3a) and (E)-4-(3-acetylstyryl)-3-(hydroxyl (3,4,5-trimethoxyphenyl)methyl)dihydrofuran-2(3H)-one (3f) exhibited partial agonist activity. An experiment using human hepatocarcinoma cells (HepG2) that were induced to become an insulin-resistant model showed that compounds 3a and 3f improved insulin sensitivity and glucose consumption. In addition, compounds 3a and 3f significantly improved hyperglycemia and insulin resistance in high-fat diet-fed streptozotocin (HFD-STZ)-induced type 2 diabetic rats at a dose of 15 mg/kg/day administered orally for 45 days, without significant weight gain. Cell toxicity testing also showed that compounds 3a and 3f exhibited weaker toxicity than pioglitazone. These findings suggested that compounds 3a and 3f improved insulin resistance in vivo and in vitro and that the compounds exhibited potential for the treatment of type 2 diabetes mellitus.
Atomic Layering, Intermixing and Switching Mechanism in Ge-Sb-Te based Chalcogenide Superlattices
Authors: Yu Xiaoming , Robertson John 
Published: November 2016

AbstractGeSbTe-based chalcogenide superlattice (CSLs) phase-change memories consist of GeSbTe layer blocks separated by van der Waals bonding gaps. Recent high resolution electron microscopy found two types of disorder in CSLs, a chemical disorder within individual layers, and SbTe bilayer stacking faults connecting one block to an adjacent block which allows individual block heights to vary. The disorder requires a generalization of the previous switching models developed for CSL systems. Density functional calculations are used to describe the stability of various types of intra-layer disorder, how the block heights can vary by means of SbTe-based stacking faults and using a vacancy-mediated kink motion, and also to understand the nature of the switching process in more chemically disordered CSLs.
Genome wide transcriptome profiling of Fusarium oxysporum f sp. ciceris conidial germination reveals new insights into infection-related genes
Authors: Sharma Mamta , Sengupta Anindita , Ghosh Raju , Agarwal Gaurav , Tarafdar Avijit , Nagavardhini A , Pande Suresh , Varshney Rajeev K 
Published: November 2016

AbstractVascular wilt caused by Fusarium oxysporum f. sp. ciceris (Foc) is a serious disease of chickpea (Cicer arietinum L.) accounting for approximately 10–15% annual crop loss. The fungus invades the plant via roots, colonizes the xylem vessels and prevents the upward translocation of water and nutrients. Infection is initiated by conidia that invade the host tissue often by penetration of intact epidermal cells. Here, we report the characterization of the transcriptome of Foc sequenced using Illumina Hiseq technology during its conidial germination at different time points. Genome-wide expression profiling revealed that genes linked to fungal development are transcribed in successive ways. Analysis showed that Foc have large sets of germination-related genes and families of genes encoding secreted effectors, cell wall/pectin-degrading enzymes, metabolism related enzymes, transporters and peptidases. We found that metabolism related enzymes are up-regulated at early time point whereas most transporters and secondary metabolites important for tissue colonization and pathogenicity are up-regulated later as evident from the qRT-PCR. The study demonstrated that early conidial germination in Foc is accompanied by rapid shifts in gene expression that prepare the fungus for germ tube outgrowth, host cell invasion and pathogenesis. This work lays the foundation for facilitating further research towards understanding this host-pathogen interaction.
Acidic pH promotes intervertebral disc degeneration: Acid-sensing ion channel -3 as a potential therapeutic target
Authors: Gilbert Hamish T. J. , Hodson Nathan , Baird Pauline , Richardson Stephen M. , Hoyland Judith A. 
Published: November 2016

AbstractThe aetiology of intervertebral disc (IVD) degeneration remains poorly understood. Painful IVD degeneration is associated with an acidic intradiscal pH but the response of NP cells to this aberrant microenvironmental factor remains to be fully characterised. The aim here was to address the hypothesis that acidic pH, similar to that found in degenerate IVDs, leads to the altered cell/functional phenotype observed during IVD degeneration, and to investigate the involvement of acid-sensing ion channel (ASIC) -3 in the response. Human NP cells were treated with a range of pH, from that of a non-degenerate (pH 7.4 and 7.1) through to mildly degenerate (pH 6.8) and severely degenerate IVD (pH 6.5 and 6.2). Increasing acidity of pH caused a decrease in cell proliferation and viability, a shift towards matrix catabolism and increased expression of proinflammatory cytokines and pain-related factors. Acidic pH resulted in an increase in ASIC-3 expression. Importantly, inhibition of ASIC-3 prevented the acidic pH induced proinflammatory and pain-related phenotype in NP cells. Acidic pH causes a catabolic and degenerate phenotype in NP cells which is inhibited by blocking ASIC-3 activity, suggesting that this may be a useful therapeutic target for treatment of IVD degeneration.
The structure and dynamics of Nano Particles encapsulated by the SDS monolayer collapse at the water/TCE interface
Authors: Shi Wenxiong 
Published: November 2016

AbstractThe super-saturated surfactant monolayer collapses with the nanoparticles (NPs) at the water/trichloroethylene (TCE) interface are investigated using molecular dynamics (MD) simulations. The results show that sodium alkyl sulfate (SDS) monolayer collapse is initiated by buckling and followed primarily by budding and the bud encapsulating the NPs and oil molecules. The developed bud detaches from the monolayer into a water phase and forms the swollen micelle emulsion with NPs and oil molecules. We investigate the wavelength of the initial budding and the theoretical description of the budding process. The wavelength of the monolayer increases with bending modulus. The energy barrier of the budding can be easily overcome by thermal fluctuation energy, which indicates that budding process proceeds rapidly.
Tunable high-performance microwave absorption for manganese dioxides by one-step Co doping modification
Authors: Lv Guocheng , Xing Xuebing , Wu Limei , Jiang Wei-Teh , Li Zhaohui , Liao Libing 
Published: November 2016

AbstractThe frequencies of microwave absorption can be affected by the permanent electric dipole moment which could be adjusted by modifying the crystal symmetry of the microwave absorbing materials. Herein, we corroborate this strategy experimentally and computationally to the microwave absorption of manganese dioxides. Nanosized Co-doped cryptomelane (Co-Cryp) was successfully synthesized by a one-step reaction. The introduction of Co(III) induced a change of crystal symmetry from tetragonal to monlclinic, which could lead to an increase of its permanent electric dipole moment. As a result, the frequencies of maximum microwave absorption were regulated in the range of 7.4 to 13.9 GHz with a broadened bandwidths. The results suggested that microwave absorption of manganese dioxides can be tailored with Co doping to expand their potential uses for abatement of various microwave pollutions.
Killing in Self-Defense
Authors: Miller Seumas 
Published: November 2016

Abstract
In this chapter the main contemporary theories of justifiable killing in self-defense are criticized and an alternative account elaborated: the fault-based internalist suspendable-rights theory (FIST). FIST is a partialist account. The rights not to be killed are such that when one member of the set of rights is suspended, the other rights remain in force. Thus, if A’s right not to be killed by B is suspended, then B no longer has an obligation not to kill A. However, A still has a right not to be killed by C, and thus C’s obligation not to kill A remains in force. In addition, on FIST, a culpable attacker suspends his or her right not to be killed by a defender even in cases in which it is not necessary (necessity condition) for the defender to kill the attacker to save his or her own life.
Becoming Conquered (The 1560s)
Authors: Townsend Camilla 
Published: November 2016

Abstract
The 1560s were a pivotal decade for the Nahuas. For the first time, the urban Indians had to pay a head tax like all other Mexican indigenous peoples. They made extraordinary efforts to prevent this change, which they foresaw would impoverish them, and they recorded for their posterity traditional histories or annals recounting their efforts. Because of high unrest, a plot against the Crown by don Martín Cortés, son of Hernando Cortés, reverberated in terrible ways. Several indigenous texts illuminate not only the political moment but also the traditional indigenous notions of historiography, among them the Codex Aubin, the Codex Osuna, and the Annals of Juan Bautista.
Forging Friendship with Franciscans (1560s–1580s)
Authors: Townsend Camilla 
Published: November 2016

Abstract
Franciscan friars at missions established by the Spanish conquerors taught the Nahuas the roman alphabet. As some of their earliest students attained adulthood and became intellectuals in their own right, they occasionally found themselves arguing with their former mentors. Two indigenous men in this position were don Mateo Sánchez of Tecamachalco, a friend of fray Francisco Toral, and don Pedro de San Buenaventura of Cuauhtitlan, a friend of fray Bernardino de Sahagún. The sets of annals they wrote reveal both their knowledge of their people’s past and present and also their participation in dialog with Europeans. As intermediaries, they suffered and were empowered in unique ways.