bluuebunny/crossref_metadata_2025_split huggingface dataset:
Network Pharmacology-Based identification of pharmacological mechanism of SQFZ injection in combination with Docetaxel on lung cancer
Authors: Li Tan , Baochen Zhu , Yue Zhang , Cheng Wang , Yali Wu , Zongxi Sun , Wantong Zhang , Yang Lu , Shouying Du 
Published: March 2019

AbstractDocetaxel is the widely-used first-line therapy to treat lung cancer around the world. However, tumor progression and severe side effect occurred in some patients with docetaxel treatment. Most of the side effects were caused by immunocompromise, which limits the long-term use of docetaxel. Shenqi Fuzheng (SQFZ) injection has been used as adjuvant therapy to treat lung cancer which may enhance immunity as well. Owing to the complexity of drug combination, the mechanism of SQFZ injection in combination with docetaxel on lung cancer remains unclear. Therefore, a network pharmacology-based strategy was proposed in this study to help solve this problem. Network pharmacology approach comprising multiple components, candidate targets of component and therapeutic targets, has been used in this study. Also, in vivo and in vitro experiment was applied to verify the predicted targets from network pharmacology We established mouse lung cancer model and inject with docetaxel and SQFZ injection. Tumour weight, spleen index, thymus index, immunohistochemical staining and ELISA were conducted to evaluate the effect and underlying mechanisms of docetaxel and SQFZ injection. Besides A549 cells were also administrated by docetaxel and SQFZ.The indexes BCL2, CASP3 and CASP9 were determined after administration. The results indicated that combination of SQFZ and docetaxel could reduce tumour weight, enhance the spleen index, thymus index. Meanwhile, it could improve the activity of caspase-3 and IL-2 in mice and caspase-3, caspase-9 in A549 cell and inhibit the activity of BCL-2 in A549 cell, which verified the potential protective targets predicted by network pharmacology. In conclusion, combination of SQFZ and docetaxel could increase the curative effect by inducing tumour to apoptosis and play a key role on immunoprotection to reduce side effects.
Draft genome of the brown alga, Nemacystus decipiens, Onna-1 strain: Fusion of genes involved in the sulfated fucan biosynthesis pathway
Authors: Nishitsuji Koki , Arimoto Asuka , Higa Yoshimi , Mekaru Munekazu , Kawamitsu Mayumi , Satoh Noriyuki , Shoguchi Eiichi 
Published: March 2019

AbstractThe brown alga, Nemacystus decipiens (“ito-mozuku” in Japanese), is one of the major edible seaweeds, cultivated principally in Okinawa, Japan. N. decipiens is also a significant source of fucoidan, which has various physiological activities. To facilitate brown algal studies, we decoded the ~154 Mbp draft genome of N. decipiens Onna-1 strain. The genome is estimated to contain 15,156 protein-coding genes, ~78% of which are substantiated by corresponding mRNAs. Mitochondrial genes analysis showed a close relationship between N. decipiens and Cladosiphon okamuranus. Comparisons with the C. okamuranus and Ectocarpus siliculosus genomes identified a set of N. decipiens-specific genes. Gene ontology annotation showed more than half of these are classified as molecular function, enzymatic activity, and/or biological process. Extracellular matrix analysis revealed domains shared among three brown algae. Characterization of genes that encode enzymes involved in the biosynthetic pathway for sulfated fucan showed two sets of genes fused in the genome. One is a fusion of l-fucokinase and GDP-fucose pyrophosphorylase genes, a feature shared with C. okamuranus. Another fusion is between an ST-domain-containing gene and an alpha/beta hydrolase gene. Although the function of fused genes should be examined in future, these results suggest that N. decipiens is another promising source of fucoidan.
DNA methylation signature of smoking in lung cancer is enriched for exposure signatures in newborn and adult blood
Authors: Bakulski K. M. , Dou J. , Lin N. , London S. J. , Colacino J. A. 
Published: March 2019

AbstractSmoking impacts DNA methylation genome-wide in blood of newborns from maternal smoking during pregnancy and adults from personal smoking. We compared smoking-related DNA methylation in lung adenocarcinoma (61 never smokers, 91 current smokers, and 238 former smokers) quantified with the Illumina450k BeadArray in The Cancer Genome Atlas with published large consortium meta-analyses of newborn and adult blood. We assessed whether CpG sites related to smoking in blood from newborns and adults were enriched in the lung adenocarcinoma methylation signal. Testing CpGs differentially methylated by smoke exposure, we identified 296 in lung adenocarcinoma meeting a P < 10−4 cutoff, while previous meta-analyses identified 3,042 in newborn blood, and 8,898 in adult blood meeting the same P < 10−4 cutoff. Lung signals were highly enriched for those seen in newborn (24 overlapping CpGs, Penrichment = 1.2 × 10−18) and adult blood (66 overlapping CpGs, Penrichment = 1.2 × 10−48). The 105 genes annotated to CpGs differentially methylated in lung tumors, but not blood, were enriched for RNA processing ontologies. Some epigenetic alterations associated with cigarette smoke exposure are tissue specific, but others are common across tissues. These findings support the value of blood-based methylation biomarkers for assessing exposure effects in target tissues.
Virus-triggered spinal cord demyelination is followed by a peripheral neuropathy resembling features of Guillain-Barré Syndrome
Authors: Leitzen Eva , Raddatz Barbara B. , Jin Wen , Goebbels Sandra , Nave Klaus-Armin , Baumgärtner Wolfgang , Hansmann Florian 
Published: March 2019

AbstractTheiler’s murine encephalomyelitis virus (TMEV)-induces a demyelinating disease in the spinal cord (SC) of susceptible but not in resistant (B6) mouse strains. The aim of the present study was to induce SC demyelination and a peripheral neuropathy in resistant mice by switching the infection site from cerebrum to SC. B6 mice were intraspinally inoculated with TMEV. Infected mice showed clinical signs starting at 7 days post infection (dpi). Histopathology revealed a mononuclear myelitis, centred on the injection site at 3 dpi with subsequent antero- and retrograde spread, accompanied by demyelination and axonal damage within the SC. Virus protein was detected in the SC at all time points. SC inflammation decreased until the end of the investigation period (28 dpi). Concurrent with the amelioration of SC inflammation, the emergence of a peripheral neuropathy, characterized by axonal damage, demyelination and macrophage infiltration, contributing to persistent clinical sings, was observed. Intraspinal TMEV infection of resistant mice induced inflammation, demyelination and delayed viral clearance in the spinal cord and more interestingly, subsequent, virus-triggered inflammation and degeneration within the PN associated with dramatic and progressive clinical signs. The lesions observed in the PN resemble important features of Guillain-Barré syndrome, especially of acute motor/motor-sensory axonal forms.
Probing Membrane Association of α-Synuclein Domains with VDAC Nanopore Reveals Unexpected Binding Pattern
Authors: Jacobs Daniel , Hoogerheide David P. , Rovini Amandine , Jiang Zhiping , Lee Jennifer C. , Rostovtseva Tatiana K. , Bezrukov Sergey M. 
Published: March 2019

AbstractIt is well established that α-synuclein (α-syn) binding from solution to the surface of membranes composed of negatively charged and/or non-lamellar lipids can be characterized by equilibrium dissociation constants of tens of micromolar. Previously, we have found that a naturally occurring nanopore of the mitochondrial voltage-dependent anion channel (VDAC), reconstituted into planar bilayers of a plant-derived lipid, responds to α-syn at nanomolar solution concentrations. Here, using lipid mixtures that mimic the composition of mitochondrial outer membranes, we show that functionally important binding does indeed take place in the nanomolar range. We demonstrate that the voltage-dependent rate at which a membrane-embedded VDAC nanopore captures α-syn is a strong function of membrane composition. Comparison of the nanopore results with those obtained by the bilayer overtone analysis of membrane binding demonstrates a pronounced correlation between the two datasets. The stronger the binding, the larger the on-rate, but with some notable exceptions. This leads to a tentative model of α-syn-membrane interactions, which assigns different lipid-dependent roles to the N- and C-terminal domains of α-syn accounting for both electrostatic and hydrophobic effects. As a result, the rate of α-syn capture by the nanopore is not simply proportional to the α-syn concentration on the membrane surface but found to be sensitive to the specific interactions of each domain with the membrane and nanopore.
Association of C-Reactive Protein with Risk of Developing Type 2 Diabetes Mellitus, and Role of Obesity and Hypertension: A Large Population-Based Korean Cohort Study
Authors: Kanmani Suganya , Kwon Minji , Shin Moon-Kyung , Kim Mi Kyung 
Published: March 2019

AbstractThis study was undertaken to assess the associations of C-reactive protein (CRP) with incident type-2 diabetes mellitus (T2DM) and to determine the joint effect of obesity and hypertension on them in the large-scale population-based Korean cohort of the Korean Genome and Epidemiology study (KoGES). We included 22,946 men and women from 11 rural communities at baseline (2005–2011). Epidemiological data and blood samples were collected. Incident physician-diagnosed T2DM cases (130 men and 148 women) were self-reported or based on fasting glucose ≥126 mg/dL or HbA1c level ≥6.5% during a median follow-up of 3.0 years (58,916 person-years) between 2007 and 2014. After multivariate adjustment for T2DM risk factors, the hazard ratios for developing T2DM in the highest CRP tertile (T3), compared with the lowest (T1), was 2.80 (1.73–4.52;pfor trend <0.0001) in women and 1.67 (1.00–2.45;pfor trend 0.02) in men. The associations between CRP and incident T2DM were more prominent among the older group (≥50 years). And CRP and its combination with obesity and hypertension were associated with increased risk of T2DM. In conclusion, we found positive associations between CRP and incident T2DM in a large population-based Korean cohort.
Effects of Neonicotinoid Insecticides on Physiology and Reproductive Characteristics of Captive Female and Fawn White-tailed Deer
Authors: Berheim Elise Hughes , Jenks Jonathan A. , Lundgren Jonathan G. , Michel Eric S. , Grove Daniel , Jensen William F. 
Published: March 2019

AbstractOver the past decade, abnormalities have been documented in white-tailed deer (Odocoileus virginianus) in west-central Montana. Hypotheses proposed to explain these anomalies included contact with endocrine disrupting pesticides, such as imidacloprid. We evaluated the effects of imidacloprid experimentally at the South Dakota State University Wildlife and Fisheries Captive Facility where adult white-tailed deer females and their fawns were administered aqueous imidacloprid (an untreated control, 1,500 ng/L, 3,000 ng/L, and 15,000 ng/L). Water consumption, thyroid hormone function, behavioral responses, and skull and jawbone measurements were compared among treatments. Additionally, liver, spleen, genital, and brain imidacloprid concentrations were determined by an enzyme-linked immunosorbent assay (ELISA). Results indicated that 1) control deer consumed more water than treatment groups, 2) imidacloprid was present in the organs of our control group, indicating environmental contamination, 3) as imidacloprid increased in the spleen, fawn survival, thyroxine levels, jawbone lengths, body weight, and organ weights decreased, 4) adult female imidacloprid levels in the genitals were negatively correlated with genital organ weight and, 5) behavioral observations indicated that imidacloprid levels in spleens were negatively correlated with activity levels in adult females and fawns. Results demonstrate that imidacloprid has direct effects on white-tailed deer when administered at field–relevant doses.
A Peptide-Nanoparticle System with Improved Efficacy against Multidrug Resistant Bacteria
Authors: Pal Indrani , Bhattacharyya Dipita , Kar Rajiv Kumar , Zarena D. , Bhunia Anirban , Atreya Hanudatta S. 
Published: March 2019

AbstractThe recent rise of multidrug resistant microbial strains requires development of new and novel therapeutic alternatives. In this study, we present a novel antibacterial system that comprises of modified naturally abundant antimicrobial peptides in conjugation with silver nanoparticles. Further, we propose a simple route to incorporate a cysteine residue either at the N- or C-terminal of the parent peptide. Tagging a cysteine residue at the terminals not only enhances the binding propensity of the resultant peptide with the silver nanoparticle, but also increases its antimicrobial property against several pathogenic bacterial strains including K. pneumoniae. The minimum inhibitory concentration (MIC) values of the cysteine tagged nanoconjugates were obtained in the range of 5–15 μM compared to 50 μM for peptides devoid of the cysteines. The origin and mechanism of such improved activity of the conjugates were investigated using NMR spectroscopy and molecular dynamics (MD) simulations. The application of 13C-isotope labelled media to track the metabolic lifecycle of E. coli cells provided further insights into the system. MD simulations showed that pore formation in membrane bilayer is mediated through a hydrophobic collapse mechanism. The design strategy described herein opens up new-avenues for using biocompatible nanomedicines as a potential alternative to conventional antibiotics.
A model-guided dissociation between subcortical and cortical contributions to word recognition
Authors: Braun Mario , Kronbichler Martin , Richlan Fabio , Hawelka Stefan , Hutzler Florian , Jacobs Arthur M. 
Published: March 2019

AbstractNeurocognitive studies of visual word recognition have provided information about brain activity correlated with orthographic processing. Some of these studies related the orthographic neighborhood density of letter strings to the amount of hypothetical global lexical activity (GLA) in the brain as simulated by computational models of word recognition. To further investigate this issue, we used GLA of words and nonwords from the multiple read-out model of visual word recognition (MROM) and related this activity to neural correlates of orthographic processing in the brain by using functional magnetic resonance imaging (fMRI). Words and nonwords elicited linear effects in the cortex with increasing BOLD responses for decreasing values of GLA. In addition, words showed increasing linear BOLD responses for increasing GLA values in subcortical regions comprising the hippocampus, globus pallidus and caudate nucleus. We propose that these regions are involved in the matching of orthographic input onto representations in long-term memory. The results speak to a potential involvement of the basal ganglia in visual word recognition with globus pallidus and caudate nucleus activity potentially reflecting maintenance of orthographic input in working memory supporting the matching of the input onto stored representations by selection of appropriate lexical candidates and the inhibition of orthographically similar but non-matching candidates.
Climate- and gateway-driven cooling of Late Eocene to earliest Oligocene sea surface temperatures in the North Sea Basin
Authors: Śliwińska Kasia K. , Thomsen Erik , Schouten Stefan , Schoon Petra L. , Heilmann-Clausen Claus 
Published: March 2019

AbstractDuring the late Eocene, the Earth’s climate experienced several transient temperature fluctuations including the Vonhof cooling event (C16n.1n; ~35.8 Ma) hitherto known mainly from the southern oceans. Here we reconstruct sea-surface temperatures (SST) and provide δ18O and δ13C foraminiferal records for the late Eocene and earliest Oligocene in the North Sea Basin. Our data reveal two main perturbations: (1), an abrupt brief cooling of ~4.5 °C dated to ~35.8 Ma and synchronous with the Vonhof cooling, which thus may be a global event, and (2) a gradual nearly 10 °C temperature fall starting at 36.1 Ma and culminating near the Eocene-Oligocene transition at ~33.9 Ma. The late Priabonian temperature trend in the North Sea shows some resemblance IODP Site U1404 from the North Atlantic, offshore Newfoundland; and is in contrast to the more abrupt change observed in the deep-sea δ18O records from the southern oceans. The cooling in the North Sea is large compared to the pattern seen in the North Atlantic record. This difference may be influenced by a late Eocene closure of the warm gateways connecting the North Sea with the Atlantic and Tethys oceans.
Strategies of the invasive tropical fire ant (Solenopsis geminata) to minimize inbreeding costs
Authors: Lenancker Pauline , Hoffmann Benjamin D. , Tay Wee Tek , Lach Lori 
Published: March 2019

AbstractHow invasive species overcome challenges associated with low genetic diversity is unclear. Invasive ant populations with low genetic diversity sometimes produce sterile diploid males, which do not contribute to colony labour or reproductive output. We investigated how inbreeding affects colony founding and potential strategies to overcome its effects in the invasive tropical fire ant, Solenopsis geminata. Our genetic analyses of field samples revealed that 13–100% of males per colony (n = 8 males per 10 colonies) were diploid, and that all newly mated queens (n = 40) were single-mated. Our laboratory experiment in which we assigned newly mated queens to nests consisting of 1, 2, 3, or 5 queens (n = 95 ± 9 replicates) revealed that pleometrosis (queens founding their nest together) and diploid male larvae execution can compensate for diploid male load. The proportion of diploid male producing (DMP) colonies was 22.4%, and DMP colonies produced fewer pupae and adult workers than non-DMP colonies. Pleometrosis significantly increased colony size. Queens executed their diploid male larvae in 43.5% of the DMP colonies, and we hypothesize that cannibalism benefits incipient colonies because queens can redirect nutrients to worker brood. Pleometrosis and cannibalism of diploid male larvae represent strategies through which invasive ants can successfully establish despite high inbreeding.
Isolation and identification of a male-produced aggregation-sex pheromone for the velvet longhorned beetle, Trichoferus campestris
Authors: Ray Ann M. , Francese Joseph A. , Zou Yunfan , Watson Kristopher , Crook Damon J. , Millar Jocelyn G. 
Published: March 2019

AbstractThe velvet longhorned beetle,Trichoferus campestris(Faldermann) (“VLB”; Coleoptera: Cerambycidae), is native to eastern Asia where it infests and damages a wide range of deciduous and coniferous tree species, including orchard and timber species. Immature stages of VLB are transported to new countries via international commerce, and populations have established outside the native range of the species. Here, we show that identification of pheromones of invasive pest species can be expedited by knowledge of the semiochemistry of related taxa. Histological sectioning revealed subcuticular, male-specific prothoracic glands connected to pits in the cuticle, which, in related species, are diagnostic for production of male-produced aggregation-sex pheromones, usually characterized by 2,3-alkanediol/hydroxyketone structural motifs. However, in preliminary field bioassays, beetles were not attracted by any known cerambycid pheromones. Subsequently, we identified a novel variant of the hydroxyketone motif (“trichoferone”) from headspace volatiles of males. In field bioassays, synthetic trichoferone was more attractive to both sexes of VLB than previously developed high-release-rate ethanol lures, and attraction was strongly female biased. This study demonstrated the utility of the prothoracic gland trait for predicting pheromone use in cerambycid species in the subfamily Cerambycinae, and that identification of pheromones of novel species can be expedited by knowledge of pheromones of related species. Trichoferone should prove to be a valuable tool for detection of VLB in regions where the beetle is or may become established.
Resveratrol, lunularin and dihydroresveratrol do not act as caloric restriction mimetics when administered intraperitoneally in mice
Authors: Pallauf Kathrin , Chin Dawn , Günther Ilka , Birringer Marc , Lüersen Kai , Schultheiß Gerald , Vieten Sarah , Krauß Jürgen , Bracher Franz , Danylec Nicolas , Soukup Sebastian T. , Kulling Sabine E. , Rimbach Gerald 
Published: March 2019

AbstractResveratrol as well as caloric restriction were shown to extend lifespan in some model organisms and may possibly delay onset of ageing-related diseases in humans. Yet, resveratrol supplementation does not always extend lifespan of animal models or improve health status of humans. Because of interindividual differences in human microbiota, resveratrol metabolite production in the gut differs. While some individuals produce lunularin and dihydroresveratrol in their gut, others produce dihydroresveratrol only. Therefore, we addressed the question whether these metabolites differ in their biological impact on ageing and intraperitoneally injected 13-month-old C57BL/6JRj mice on an ad-libitum (AL) HFD with resveratrol, dihydroresveratrol or lunularin (24 mg/kg bodyweight; 3 times/week). Compared to mice injected with vehicle (AL-control), resveratrol and dihydroresveratrol did not change bodyweight and had no impact on insulin or glucose levels while lunularin slightly reduced feed intake and bodyweight gain. CR-mice showed lowered cholesterol, insulin and leptin levels, elevated adiponectin and phosphorylated AMPK levels in liver as well as increased transcription of Pck1 and Pgc1α when compared to the AL-control. In contrast, injections with the test substances did not change these parameters. We therefore conclude that in our model, resveratrol, lunularin and dihydroresveratrol did not act as CR mimetics.
Rapid and reversible suppression of ALT by DAXX in osteosarcoma cells
Authors: Yost Kathryn E. , Clatterbuck Soper Sarah F. , Walker Robert L. , Pineda Marbin A. , Zhu Yuelin J. , Ester Corbin D. , Showman Soyeon , Roschke Anna V. , Waterfall Joshua J. , Meltzer Paul S. 
Published: March 2019

AbstractMany tumors maintain chromosome-ends through a telomerase-independent, DNA-templated mechanism called alternative lengthening of telomeres (ALT). While ALT occurs in only a subset of tumors, it is strongly associated with mutations in the genes ATRX and DAXX, which encode components of an H3.3 histone chaperone complex. The role of ATRX and DAXX mutations in potentiating the mechanism of ALT remains incompletely understood. Here we characterize an osteosarcoma cell line, G292, with wild-type ATRX but a unique chromosome translocation resulting in loss of DAXX function. While ATRX and DAXX form a complex in G292, this complex fails to localize to nuclear PML bodies. We demonstrate that introduction of wild type DAXX suppresses the ALT phenotype and restores the localization of ATRX/DAXX to PML bodies. Using an inducible system, we show that ALT-associated PML bodies are disrupted rapidly following DAXX induction and that ALT is again restored following withdrawal of DAXX.