bluuebunny/crossref_metadata_2025 huggingface dataset:
MYC regulates ductal-neuroendocrine lineage plasticity in pancreatic ductal adenocarcinoma associated with poor outcome and chemoresistance
Authors: Farrell Amy S. , Joly Meghan Morrison , Allen-Petersen Brittany L. , Worth Patrick J. , Lanciault Christian , Sauer David , Link Jason , Pelz Carl , Heiser Laura M. , Morton Jennifer P. , Muthalagu Nathiya , Hoffman Megan T. , Manning Sara L. , Pratt Erica D. , Kendsersky Nicholas D. , Egbukichi Nkolika , Amery Taylor S. , Thoma Mary C. , Jenny Zina P. , Rhim Andrew D. , Murphy Daniel J. , Sansom Owen J. , Crawford Howard C. , Sheppard Brett C. , Sears Rosalie C.
Published: November 2017

Intratumoral phenotypic heterogeneity has been described in many tumor types, where it can contribute to drug resistance and disease recurrence. We analyzed ductal and neuroendocrine markers in pancreatic ductal adenocarcinoma, revealing heterogeneous expression of the neuroendocrine marker Synaptophysin within ductal lesions. Higher percentages of Cytokeratin-Synaptophysin dual positive tumor cells correlate with shortened disease-free survival. We observe similar lineage marker heterogeneity in mouse models of pancreatic ductal adenocarcinoma, where lineage tracing indicates that Cytokeratin-Synaptophysin dual positive cells arise from the exocrine compartment. Mechanistically, MYC binding is enriched at neuroendocrine genes in mouse tumor cells and loss of MYC reduces ductal-neuroendocrine lineage heterogeneity, while deregulated MYC expression in KRAS mutant mice increases this phenotype. Neuroendocrine marker expression is associated with chemoresistance and reducing MYC levels decreases gemcitabine-induced neuroendocrine marker expression and increases chemosensitivity. Altogether, we demonstrate that MYC facilitates ductal-neuroendocrine lineage plasticity in pancreatic ductal adenocarcinoma, contributing to poor survival and chemoresistance.
Long-lived unipotent Blimp1-positive luminal stem cells drive mammary gland organogenesis throughout adult life
Authors: Elias Salah , Morgan Marc A. , Bikoff Elizabeth K. , Robertson Elizabeth J.
Published: November 2017

The hierarchical relationships between various stem and progenitor cell subpopulations driving mammary gland morphogenesis and homoeostasis are poorly understood. Conditional inactivation experiments previously demonstrated that expression of the zinc finger transcriptional repressor Blimp1/PRDM1 is essential for the establishment of epithelial cell polarity and functional maturation of alveolar cells. Here we exploit a Prdm1.CreERT2-LacZ reporter allele for lineage tracing experiments. Blimp1 expression marks a rare subpopulation of unipotent luminal stem cells that initially appear in the embryonic mammary gland at around E17.5 coincident with the segregation of the luminal and basal compartments. Fate mapping at multiple time points in combination with whole-mount confocal imaging revealed these long-lived unipotent luminal stem cells survive consecutive involutions and retain their identity throughout adult life. Blimp1+ luminal stem cells give rise to Blimp1− progeny that are invariably Elf5+ERα−PR−. Thus, Blimp1 expression defines a mammary stem cell subpopulation with unique functional characteristics.
Molecular changes in premenopausal oestrogen receptor-positive primary breast cancer in Vietnamese women after oophorectomy
Authors: Haynes Ben P. , Ginsburg Ophira , Gao Qiong , Folkerd Elizabeth , Afentakis Maria , Quang Le Hong , Han Pham Thi , Khoa Pham Hong , Dinh Nguyen Van , To Ta Van , Clemons Mark , Smith Ian E. , Dowsett Mitch
Published: November 2017

For premenopausal women with primary ER + breast cancer, oophorectomy (OvX) is an evidence-based cost-effective option and is standard treatment in many countries. However, there is virtually no data describing the effects of OvX on breast tumour biology. We therefore, characterised the endocrine and genome-wide transcriptional impact of OvX in 56 premenopausal women with ER + breast cancer for 2 weeks prior to mastectomy. Plasma estradiol concentrations decreased from 406 ± 41 to 20.7 ± 2.6 pmol/l (mean ± sem) 24 h after OvX, and to 8.1 ± 0.8 pmol/l 2 weeks later at mastectomy. Ki67 decreased in 33/36 (91.7%) tumours. The expression of 655 genes changed significantly (FDR < 1%) with an absolute mean fold-change (FC) ≥ 1.25 (257 up, 398 down). Archetypal oestrogen-regulated genes (TFF1, GREB1, PGR and PDZK1) showed large decreases in expression (FC = 0.20–0.69; p < 1e-6-1e-7). Proliferation-associated genes (e.g. TOP2A, AURKA and UBE2C) were also strongly downregulated (FC = 0.38–0.56; p < 1e-7) along with putative progesterone-regulated genes (e.g. FKBP4, MYB; FC = 0.64–0.68; p < 1e-4-1e-7). The gene expression changes did not differ according to HER2 status and correlated strongly with the changes reported previously after aromatase inhibitor (AI) treatment in postmenopausal women (rho = 0.55, p < 1e-04). However, after OvX the mean FC was significantly higher compared to AI (p < 1e-04). In conclusion, changes in tumoural gene expression after OvX were largely similar, but of a greater magnitude to those observed after AI in postmenopausal patients; however, OvX appeared to have a greater effect on progesterone-regulated genes than AI.
Author Correction: Metabolic Biomarkers for Prognostic Prediction of Pre-diabetes: results from a longitudinal cohort study
Authors: Zeng Hailuan , Tong Renchao , Tong Wenxin , Yang Qiaoling , Qiu Miaoyan , Xiong Aizhen , Sun Siming , Ding Lili , Zhang Hongli , Yang Li , Tian Jingyan
Published: November 2017

A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.
Neural bases of ingroup altruistic motivation in soccer fans
Authors: Bortolini Tiago , Bado Patrícia , Hoefle Sebastian , Engel Annerose , Zahn Roland , de Oliveira Souza Ricardo , Dreher Jean-Claude , Moll Jorge
Published: November 2017

Humans have a strong need to belong to social groups and a natural inclination to benefit ingroup members. Although the psychological mechanisms behind human prosociality have extensively been studied, the specific neural systems bridging group belongingness and altruistic motivation remain to be identified. Here, we used soccer fandom as an ecological framing of group membership to investigate the neural mechanisms underlying ingroup altruistic behaviour in male fans using event-related functional magnetic resonance. We designed an effort measure based on handgrip strength to assess the motivation to earn money (i) for oneself, (ii) for anonymous ingroup fans, or (iii) for a neutral group of anonymous non-fans. While overlapping valuation signals in the medial orbitofrontal cortex (mOFC) were observed for the three conditions, the subgenual cingulate cortex (SCC) exhibited increased functional connectivity with the mOFC as well as stronger hemodynamic responses for ingroup versus outgroup decisions. These findings indicate a key role for the SCC, a region previously implicated in altruistic decisions and group affiliation, in dovetailing altruistic motivations with neural valuation systems in real-life ingroup behaviour.
Methylomic and phenotypic analysis of the ModH5 phasevarion of Helicobacter pylori
Authors: Srikhanta Yogitha N. , Gorrell Rebecca J. , Power Peter M. , Tsyganov Kirill , Boitano Matthew , Clark Tyson A. , Korlach Jonas , Hartland Elizabeth L. , Jennings Michael P. , Kwok Terry
Published: November 2017

The Helicobacter pylori phase variable gene modH, typified by gene HP1522 in strain 26695, encodes a N6-adenosine type III DNA methyltransferase. Our previous studies identified multiple strain-specific modH variants (modH1 – modH19) and showed that phase variation of modH5 in H. pylori P12 influenced expression of motility-associated genes and outer membrane protein gene hopG. However, the ModH5 DNA recognition motif and the mechanism by which ModH5 controls gene expression were unknown. Here, using comparative single molecule real-time sequencing, we identify the DNA site methylated by ModH5 as 5′-Gm6ACC-3′. This motif is vastly underrepresented in H. pylori genomes, but overrepresented in a number of virulence genes, including motility-associated genes, and outer membrane protein genes. Motility and the number of flagella of H. pylori P12 wild-type were significantly higher than that of isogenic modH5 OFF or ΔmodH5 mutants, indicating that phase variable switching of modH5 expression plays a role in regulating H. pylori motility phenotypes. Using the flagellin A (flaA) gene as a model, we show that ModH5 modulates flaA promoter activity in a GACC methylation-dependent manner. These findings provide novel insights into the role of ModH5 in gene regulation and how it mediates epigenetic regulation of H. pylori motility.
Microstructural Development in a Laser-Remelted Al-Zn-Si-Mg Coating
Authors: Godec M. , Podgornik B. , Nolan D.
Published: November 2017

In the last five decades, there has been intense development in the field of Zn-Al galvanic coating modification. Recently, Mg was added to improve corrosion properties. Further improvements to the coating are possible with additional laser surface treatment. In this article, we focus on remelting the Al-Zn-Mg-Si layer, using a diode laser with a wide-beam format, concentrating on the microstructure development during extreme cooling rates. Laser remelting of the Al-Zn-Mg-Si coating and rapid self-quenching produces a finer grain size, and a microstructure that is substantially refined and homogenized with respect to the phase distribution. Using EBSD results, we are able to understand microstructure modification. The laser modified coating has some porosity and intergranular cracking which are difficult to avoid, however this does not seem to be detrimental to mechanical properties, such as ductility on bending. The newly developed technology has a high potential for improved corrosion performance due to highly refined microstructure.
Statistics and simulation of growth of single bacterial cells: illustrations with B. subtilis and E. coli
Authors: van Heerden Johan H. , Kempe Hermannus , Doerr Anne , Maarleveld Timo , Nordholt Niclas , Bruggeman Frank J.
Published: November 2017

The inherent stochasticity of molecular reactions prevents us from predicting the exact state of single-cells in a population. However, when a population grows at steady-state, the probability to observe a cell with particular combinations of properties is fixed. Here we validate and exploit existing theory on the statistics of single-cell growth in order to predict the probability of phenotypic characteristics such as cell-cycle times, volumes, accuracy of division and cell-age distributions, using real-time imaging data for Bacillus subtilis and Escherichia coli. Our results show that single-cell growth-statistics can accurately be predicted from a few basic measurements. These equations relate different phenotypic characteristics, and can therefore be used in consistency tests of experimental single-cell growth data and prediction of single-cell statistics. We also exploit these statistical relations in the development of a fast stochastic-simulation algorithm of single-cell growth and protein expression. This algorithm greatly reduces computational burden, by recovering the statistics of growing cell-populations from the simulation of only one of its lineages. Our approach is validated by comparison of simulations and experimental data. This work illustrates a methodology for the prediction, analysis and tests of consistency of single-cell growth and protein expression data from a few basic statistical principles.
Preventive effect of Agnucastoside C against Isoproterenol-induced myocardial injury
Authors: Panda Sunanda , Kar Anand , Biswas Sagarika
Published: November 2017

An iridoid glycoside, agnucastoside C (ACC) was isolated from the leaves of Moringa oliefera and its cardio protective potential was investigated in adult rats by examining the effects of this test compound, ACC at 30 mg/kg for 14 days in isoproterenol (100 mg/kg)-induced myocardial injury. Isoproterenol (ISO) administration induced the myocardial injury as evidenced by the altered ECG pattern with ST-segment elevation and an increase in the levels of cardiac injury markers including troponin-I, creatine kinase-MB, alanine transaminase, aspartate transaminase, lactate dehydrogenase; inflammatory markers, interleukine-6 and tumor necrosis factor. In this group, there was also an increase in cardiac lipid peroxidation and a decrease in cellular antioxidants. However, pretreatment with ACC maintained the normal ECG pattern and nearly normal levels of all the cardiac markers in ISO-induced animals. Electron microscopic and histological studies also showed marked reduction in ISO-induced cardiac damages including infarct size by ACC. Analysis by 2-DE revealed the involvement of 19 different cardiac proteins, associated with energy metabolism, oxidative stress and maintenance of cytoskeleton. The expression of those proteins were altered by ISO, but maintained in ACC pretreated rats. Our findings reveal the potential of isolated ACC in the prevention of myocardial damage.
Stochastic evolutionary voluntary public goods game with punishment in a Quasi-birth-and-death process
Authors: Quan Ji , Liu Wei , Chu Yuqing , Wang Xianjia
Published: November 2017

Traditional replication dynamic model and the corresponding concept of evolutionary stable strategy (ESS) only takes into account whether the system can return to the equilibrium after being subjected to a small disturbance. In the real world, due to continuous noise, the ESS of the system may not be stochastically stable. In this paper, a model of voluntary public goods game with punishment is studied in a stochastic situation. Unlike the existing model, we describe the evolutionary process of strategies in the population as a generalized quasi-birth-and-death process. And we investigate the stochastic stable equilibrium (SSE) instead. By numerical experiments, we get all possible SSEs of the system for any combination of parameters, and investigate the influence of parameters on the probabilities of the system to select different equilibriums. It is found that in the stochastic situation, the introduction of the punishment and non-participation strategies can change the evolutionary dynamics of the system and equilibrium of the game. There is a large range of parameters that the system selects the cooperative states as its SSE with a high probability. This result provides us an insight and control method for the evolution of cooperation in the public goods game in stochastic situations.
Rapid changes in Atlantic grey seal milk from birth to weaning – immune factors and indicators of metabolic strain
Authors: Lowe Amanda D. , Bawazeer Sami , Watson David G. , McGill Suzanne , Burchmore Richard J. S. , Pomeroy P. P , Kennedy Malcolm W.
Published: November 2017

True seals have the shortest lactation periods of any group of placental mammal. Most are capital breeders that undergo short, intense lactations, during which they fast while transferring substantial proportions of their body reserves to their pups, which they then abruptly wean. Milk was collected from Atlantic grey seals (Halichoerus grypus) periodically from birth until near weaning. Milk protein profiles matured within 24 hours or less, indicating the most rapid transition from colostrum to mature phase lactation yet observed. There was an unexpected persistence of immunoglobulin G almost until weaning, potentially indicating prolonged trans-intestinal transfer of IgG. Among components of innate immune protection were found fucosyllactose and siallylactose that are thought to impede colonisation by pathogens and encourage an appropriate milk-digestive and protective gut microbiome. These oligosaccharides decreased from early lactation to almost undetectable levels by weaning. Taurine levels were initially high, then fell, possibly indicative of taurine dependency in seals, and progressive depletion of maternal reserves. Metabolites that signal changes in the mother’s metabolism of fats, such as nicotinamide and derivatives, rose from virtual absence, and acetylcarnitines fell. It is therefore possible that indicators of maternal metabolic strain exist that signal the imminence of weaning.
Synthesis of uniform single layer WS2 for tunable photoluminescence
Authors: Park Juhong , Kim Min Su , Cha Eunho , Kim Jeongyong , Choi Wonbong
Published: November 2017

Two-dimensional transition metal dichalcogenides (2D TMDs) have gained great interest due to their unique tunable bandgap as a function of the number of layers. Especially, single-layer tungsten disulfides (WS2) is a direct band gap semiconductor with a gap of 2.1 eV featuring strong photoluminescence and large exciton binding energy. Although synthesis of MoS2 and their layer dependent properties have been studied rigorously, little attention has been paid to the formation of single-layer WS2 and its layer dependent properties. Here we report the scalable synthesis of uniform single-layer WS2 film by a two-step chemical vapor deposition (CVD) method followed by a laser thinning process. The PL intensity increases six-fold, while the PL peak shifts from 1.92 eV to 1.97 eV during the laser thinning from few-layers to single-layer. We find from the analysis of exciton complexes that both a neutral exciton and a trion increases with decreasing WS2 film thickness; however, the neutral exciton is predominant in single-layer WS2. The binding energies of trion and biexciton for single-layer WS2 are experimentally characterized at 35 meV and 60 meV, respectively. The tunable optical properties by precise control of WS2 layers could empower a great deal of flexibility in designing atomically thin optoelectronic devices.
A New Approach to Deliver Anti-cancer Nanodrugs with Reduced Off-target Toxicities and Improved Efficiency by Temporarily Blunting the Reticuloendothelial System with Intralipid
Authors: Liu Li , Ye Qing , Lu Maggie , Chen Shih-Ta , Tseng Hsiang-Wen , Lo Ya-Chin , Ho Chien
Published: November 2017

We have developed a new strategy to temporarily blunt the reticuloendothelial system uptake of nanodrugs, a major challenge for nanodrug delivery and causing off-target toxicities, using an FDA approved nutrition supplement, Intralipid. We have tested our methodology in rats using an experimental platinum-containing anti-cancer nanodrug and three FDA approved nanodrugs, Abraxane, Marqibo, and Onivyde, to determine their toxicities in liver, spleen, and kidney, with and without the addition of Intralipid. Our method illustrates its potentials to deliver nanodrugs with an increase in the bioavailability and a decrease in toxicities. Our study shows that Intralipid treatment exhibits no harmful effect on tumor growing and no negative effect on the anti-tumor efficacy of the platinum-containing nanodrug, as well as animal survival rate in a HT-29 xenograft mouse model. Our methodology could also be a valuable complement/supplement to the “stealth” strategies. Our approach is a general one applicable to any approved and in-development nanodrugs without additional modification of the nanodrugs, thus facilitating its translation to clinical settings.
Ocular effects of virtual reality headset wear in young adults
Authors: Turnbull Philip R. K. , Phillips John R.
Published: November 2017

Virtual Reality (VR) headsets create immersion by displaying images on screens placed very close to the eyes, which are viewed through high powered lenses. Here we investigate whether this viewing arrangement alters the binocular status of the eyes, and whether it is likely to provide a stimulus for myopia development. We compared binocular status after 40-minute trials in indoor and outdoor environments, in both real and virtual worlds. We also measured the change in thickness of the ocular choroid, to assess the likely presence of signals for ocular growth and myopia development. We found that changes in binocular posture at distance and near, gaze stability, amplitude of accommodation and stereopsis were not different after exposure to each of the 4 environments. Thus, we found no evidence that the VR optical arrangement had an adverse effect on the binocular status of the eyes in the short term. Choroidal thickness did not change after either real world trial, but there was a significant thickening (≈10 microns) after each VR trial (p < 0.001). The choroidal thickening which we observed suggest that a VR headset may not be a myopiagenic stimulus, despite the very close viewing distances involved.
Structural, electronic, magnetic, half-metallic, mechanical, and thermodynamic properties of the quaternary Heusler compound FeCrRuSi: A first-principles study
Authors: Wang Xiaotian , Khachai Houari , Khenata Rabah , Yuan Hongkuan , Wang Liying , Wang Wenhong , Bouhemadou Abdelmadjid , Hao Liyu , Dai Xuefang , Guo Ruikang , Liu Guodong , Cheng Zhenxiang
Published: November 2017

In this paper, we have investigated the structural, electronic, magnetic, half-metallic, mechanical, and thermodynamic properties of the equiatomic quaternary Heusler (EQH) compound FeCrRuSi using the density functional theory (DFT) and the quasi-harmonic Debye model. Our results reveal that FeCrRuSi is a half-metallic material (HMM) with a total magnetic moment of 2.0 μB in agreement with the well-known Slater-Pauling rule Mt = Zt − 24. Furthermore, the origin of the half-metallic band gap in FeCrRuSi is well studied through a schematic diagram of the possible d-d hybridization between Fe, Cr and Ru elements. The half-metallic behavior of FeCrRuSi can be maintained in a relatively wide range of variations of the lattice constant (5.5–5.8 Å) under uniform strain and the c/a ratio (0.96–1.05) under tetragonal distortion. The calculated phonon dispersion, cohesive and formation energies, and mechanical properties reveal that FeCrRuSi is stable with an EQH structure. Importantly, the compound of interest has been prepared and is found to exist in an EQH type structure with the presence of some B2 disorder. Moreover, the thermodynamic properties, such as the thermal expansion coefficient α, the heat capacity CV, the Grüneisen constant γ, and the Debye temperature ΘD are calculated.
The Robustness and the Doubly-Preferential Attachment Simulation of the Consensus Connectome Dynamics of the Human Brain
Authors: Szalkai Balázs , Varga Bálint , Grolmusz Vince
Published: November 2017

Consensus Connectome Dynamics (CCD) is a remarkable phenomenon of the human connectomes (braingraphs) that was discovered by continuously decreasing the minimum confidence-parameter at the graphical interface of the Budapest Reference Connectome Server, which depicts the cerebral connections of n = 418 subjects with a frequency-parameter k: For any k = 1, 2, …, n one can view the graph of the edges that are present in at least k connectomes. If parameter k is decreased one-by-one from k = n through k = 1 then more and more edges appear in the graph, since the inclusion condition is relaxed. The surprising observation is that the appearance of the edges is far from random: it resembles a growing, complex structure. We hypothesize that this growing structure copies the axonal development of the human brain. Here we show the robustness of the CCD phenomenon: it is almost independent of the particular choice of the set of underlying connectomes. This result shows that the CCD phenomenon is most likely a biological property of the human brain and not just a property of the data sets examined. We also present a simulation that well-describes the growth of the CCD structure: in our random graph model a doubly-preferential attachment distribution is found to mimic the CCD.
Metabolic Differences in Glutamine Utilization Lead to Metabolic Vulnerabilities in Prostate Cancer
Authors: Zacharias Niki Marie , McCullough Christopher , Shanmugavelandy Sriram , Lee Jaehyuk , Lee Youngbok , Dutta Prasanta , McHenry James , Nguyen Linda , Norton William , Jones Lawrence W. , Bhattacharya Pratip K.
Published: November 2017

The new oncologic paradigm of precision medicine is focused on identifying metabolic, proteomic, transcriptomic and genomic variabilities in tumors that can be exploited to tailor treatments and improve patient outcomes. Metabolic changes are a hallmark of cancer, and inhibition of metabolic pathways is now a major strategy in medicinal chemistry for targeting cancers. However, non-invasive biomarkers to categorize metabolic subtypes are in short supply. The purpose of this study was to characterize the intracellular and extracellular metabolic profiles of four prostate cancer cell lines with varying degrees of aggressiveness. We observed metabolic differences between the aggressive prostate cancer cell line PC3 and the even more aggressive, metastatic subline PC3M assessed by hyperpolarized in vivo pyruvate studies, nuclear magnetic resonance spectroscopy, and carbon-13 feeding studies. On further examination of the differences between these two cell lines, we found increased glutamine utilization in the metastatic PC3M subline that led directly to sensitivity to glutaminase inhibitor CB-839. Our study supports the theory that metastatic progression increases glutamine utilization and the inhibition of glutaminolysis could have clinical implications.
Flavonoids from Pterogyne nitens Inhibit Hepatitis C Virus Entry
Authors: Shimizu Jacqueline Farinha , Lima Caroline Sprengel , Pereira Carina Machado , Bittar Cintia , Batista Mariana Nogueira , Nazaré Ana Carolina , Polaquini Carlos Roberto , Zothner Carsten , Harris Mark , Rahal Paula , Regasini Luis Octávio , Jardim Ana Carolina Gomes
Published: November 2017

Hepatitis C virus (HCV) is one of the leading causes of liver diseases and transplantation worldwide. The current available therapy for HCV infection is based on interferon-α, ribavirin and the new direct-acting antivirals (DAAs), such as NS3 protease and NS5B polymerase inhibitors. However, the high costs of drug design, severe side effects and HCV resistance presented by the existing treatments demonstrate the need for developing more efficient anti-HCV agents. This study aimed to evaluate the antiviral effects of sorbifolin (1) and pedalitin (2), two flavonoids from Pterogyne nitens on the HCV replication cycle. These compounds were investigated for their anti-HCV activities using genotype 2a JFH-1 subgenomic replicons and infectious virus systems. Flavonoids 1 and 2 inhibited virus entry up to 45.0% and 78.7% respectively at non-cytotoxic concentrations. The mechanism of the flavonoid 2 block to virus entry was demonstrated to be by both the direct action on virus particles and the interference on the host cells. Alternatively, the flavonoid 1 activity was restricted to its virucidal effect. Additionally, no inhibitory effects on HCV replication and release were observed by treating cells with these flavonoids. These data are the first description of 1 and 2 possessing in vitro anti-HCV activity.
First-trimester vaginal microbiome diversity: A potential indicator of preterm delivery risk
Authors: Haque Mohammed Monzoorul , Merchant Mitali , Kumar Pinna Nishal , Dutta Anirban , Mande Sharmila S.
Published: November 2017

Preterm birth is a leading cause of global neonate mortality. Hospitalization costs associated with preterm deliveries present a huge economic burden. Existing physical/biochemical markers for predicting preterm birth risk are mostly suited for application at mid/late pregnancy stages, thereby leaving very short time (between diagnosis and delivery) for adopting appropriate intervention strategies. Recent studies indicating correlations between pre/full-term delivery and the composition of vaginal microbiota in pregnant women have opened new diagnostic possibilities. In this study, we performed a thorough meta-analysis of vaginal microbiome datasets to evaluate the utility of popular diversity and inequality measures for predicting, at an early stage, the risk of preterm delivery. Results indicate significant differences (in diversity measures) between ‘first-trimester’ vaginal microbiomes obtained from women with term and preterm outcomes, indicating the potential diagnostic utility of these measures. In this context, we introduce a novel diversity metric that has significantly better diagnostic ability as compared to established diversity measures. The metric enables ‘early’ and highly accurate prediction of preterm delivery outcomes, and can potentially be deployed in clinical settings for preterm birth risk-assessment. Our findings have potentially far reaching implications in the fight against neonatal deaths due to preterm birth.
TRADD mediates the tumor necrosis factor-induced apoptosis of L929 cells in the absence of RIP3
Authors: Chang Xixi , Wang Lili , Wang Zicheng , Wu Shuai , Zhu Xiaoming , Hu Shiping , Wang Yu , Yu Jiyun , Chen Guozhu
Published: November 2017

Receptor-interacting protein kinase 3 (RIP3) is a critical initiator in mediating necroptosis induced by tumor necrosis factor alpha (TNFα) in L929 cells, so knockdown of RIP3 inhibits TNFα-induced L929 cell necroptosis. However, RIP3 knockdown was shown to switch TNFα-induced necroptosis to apoptosis in L929 cells in other studies. Therefore, whether RIP3 knockdown blocks the TNFα-induced death of L929 cells is controversial. In this study, TNFα activated caspase pathway and induced cell death in RIP3 knockdown L929 cells, and the RIP3-independent cell death had been blocked by Z-VAD-FMK (pan-caspase inhibitor) or caspase 8 knockdown, demonstrating that RIP3 knockdown switched TNFα-induced necroptosis to caspase-dependent apoptosis. Although both TNF receptor type 1-associated death domain protein (TRADD) and RIP1 have been reported to mediate TNFα-induced apoptosis, the knockdown of TRADD, but not RIP1, suppressed TNFα-induced activation of the caspase pathway and subsequent apoptosis in RIP3 knockdown L929 cells. In addition, TRADD bound and activated caspase 8 during the RIP3-independent apoptosis process, indicating that TRADD initiates RIP3-independent apoptosis by activating the caspase pathway. Collectively, we identified the target and mechanism underlying RIP3-independent apoptosis and elucidated the coordinated roles of RIP3 and TRADD in mediating the programmed cell death of L929 cells following TNFα stimulation.
Active Sites of M(IV)-incorporated Zeolites (M = Sn, Ti, Ge, Zr)
Authors: Yang Gang , Zhou Lijun
Published: November 2017

M(IV)-incorporated zeolites have recently aroused wide interest due to outstanding catalytic effects while their active sites remain largely elusive. Here periodic density functional theory calculations are conducted finding that active sites are determined jointly by identity of M(IV) ions, topology of zeolites, type of framework species and choice of T sites. All M2(IV) active sites in BEA zeolites are penta-coordinated with chemisorption of one water while subsequent water molecules that form only H-bonds promote chemisorption of the first water, especially the second water possessing comparable or even higher adsorption strengths as the first water; Ti(IV) and Ge(IV) active sites at the intersection remain penta-coordinated and Sn(IV) and Zr(IV) active sites prefer to hexa-coordination although potentially expanded to hepta-coordination. Different from other zeolites, Ti(IV) active sites in FER zeolites are hexa-coordinated as Sn(IV) active sites, due to the promoting effect of the first water. Lewis acidic defects expand Ti(IV) active sites to hexa-coordination while inhibit the formation of hepta-coordinated Sn(IV) species. Two forms of Brϕnsted acidic defects exist for Sn(IV) sites instead of only one for Ti(IV) sites, and all M(IV) Brϕnsted acidic defects, regardless of different acidic forms and M(IV) ions, can chemisorb only one water.
Giant Anisotropic Magnetocaloric Effect in Double-perovskite Gd2CoMnO6 Single Crystals
Authors: Moon J. Y. , Kim M. K. , Choi Y. J. , Lee N.
Published: November 2017

The magnetocaloric effect (MCE) is described by the change in temperature of a material by magnetic field variation and is a crucial subject in magnetism; it is motivated by the desire to enhance energy-efficient magnetic refrigeration for clean technology. Despite the recent discovery of the giant cryogenic MCE in double perovskites, the role of magnetic anisotropy has not yet been clearly discussed, because of the averaging effect of polycrystalline samples. Here, we investigated the anisotropic MCE in the single-crystal double perovskite Gd2CoMnO6. In addition to the ferromagnetic order of the Co2+ and Mn4+ moments, the large Gd3+ moments align below TGd = 21 K, exhibiting an isotropic nature. Because of the intricate temperature development of magnetically hysteretic behaviour and metamagnetism, the change in magnetic entropy along the c-axis appears to be relatively small. On the contrary, the smaller but almost reversible magnetization perpendicular to the c-axis leads to a large MCE with a maximum entropy change of 25.4 J/kg·K. The anisotropic MCE generates a giant rotational MCE, estimated as 16.6 J/kg·K. Our results demonstrate the importance of magnetic anisotropy for understanding the MCE and reveal essential clues for exploring suitable magnetic refrigerant compounds aiming at magnetic functional applications.
Randomness-induced quantum spin liquid on honeycomb lattice
Authors: Yamaguchi Hironori , Okada Masataka , Kono Yohei , Kittaka Shunichiro , Sakakibara Toshiro , Okabe Toshiki , Iwasaki Yoshiki , Hosokoshi Yuko
Published: November 2017

Quantum entanglement in magnetic materials is expected to yield a quantum spin liquid (QSL), in which strong quantum fluctuations prevent magnetic ordering even at zero temperature. This topic has been one of the primary focuses of condensed-matter science since Anderson first proposed the resonating valence bond state in a certain spin-1/2 frustrated magnet in 1973. Since then, several candidate materials featuring frustration, such as triangular and kagome lattices, have been reported to exhibit liquid-like behavior. However, the mechanisms that stabilize the liquid-like states have remained elusive. Here, we present a QSL state in a spin-1/2 honeycomb lattice with randomness in the exchange interaction. That is, we successfully introduce randomness into the organic radial-based complex and realize a random-singlet (RS) state (or valence bond glass). All magnetic and thermodynamic experimental results indicate the liquid-like behaviors, which are consistent with those expected in the RS state. Our results suggest that the randomness or inhomogeneity in the actual systems stabilize the RS state and yield liquid-like behavior.
Evidence for unconscious regulation of performance in fatigue
Authors: Ishii Akira , Tanaka Masaaki , Yoshikawa Takahiro , Watanabe Yasuyoshi
Published: November 2017

Since fatigue is prevalent in modern societies, it is necessary to clarify the neural mechanisms of fatigue. The regulation of performance through fatigue sensation is one of the mechanisms that decreases performance in fatigue. However, it is unknown whether subjective feeling of fatigue is necessary for the regulation of performance. Here, we examined whether decreased performance occurs without increased fatigue sensation through the experiment which was designed to test if fatigue can be learned unconsciously. Healthy male volunteers performed a fatigue-inducing hand-grip task for 10 min while viewing a target image presented without awareness. On the next day, they viewed a control and the target images presented with awareness and the neural activity caused by viewing the images was measured using magnetoencephalography. Results showed the level of fatigue sensation was not altered but grip-strength was decreased by viewing the target image on the second day. The level of beta band power in Brodmann’s area 31 was increased by viewing the target image and this increase was negatively associated with the decrease of grip-strength caused in the hand-grip task. These findings demonstrated that fatigue can be learned unconsciously and that there is a mechanism to decrease performance without fatigue sensation.
Increased light penetration due to ultrasound-induced air bubbles in optical scattering media
Authors: Kim Haemin , Chang Jin Ho
Published: November 2017

Light is an attractive tool for high spatial- and contrast-resolution imaging, highly sensitive molecular imaging, and target-selective therapy, and it does not exhibit the risks associated with ionizing radiation. The main limitation of using light in clinical applications is its superficial imaging and therapeutic depth caused by high optical scattering in biological media. Here, we demonstrate that the scattering and thus defocusing of the incident light can be alleviated when simultaneously delivered ultrasound generates air bubbles in the pathway of the incident light, thus increasing the light penetration. The bubbles are temporally induced by ultrasound with an intensity that is sufficiently low to avoid tissue damage and act as a Mie scattering medium in which light is scattered predominantly in the forward direction. The change in the optical scattering property caused by the ultrasound is undone after cessation of the insonification. From the results, it is expected that this proposed method will open a new route for overcoming the limitations of current optical imaging and therapeutic techniques.
Equilibrium folding dynamics of meACP in water, heavy water, and low concentration of urea
Authors: Zhou Yang , Yang Daiwen
Published: November 2017

Many proteins fold in apparent two-state behavior, as partially folded intermediates only transiently accumulate and easily escape detection. Besides a native form and a mainly unfolded form, we captured a partially unfolded form of an acyl carrier protein from Micromonospora echinospora (meACP) in the folding/unfolding equilibrium using chemical exchange saturation transfer NMR experiments. The C-terminal region of the partially unfolded form is mainly folded and the N-terminal is unfolded. Furthermore, to understand how the folding process of meACP is influenced by solvent environments, we compared the folding dynamics of meACP in D2O, H2O and low concentration of urea. As the environment becomes more denaturing from D2O to H2O and then to urea, the unfolded state becomes increasingly populated, and the folding rate decreases. Adding a small amount of urea, which does not change solvent viscosity, has little effects on the unfolding rates, while changing H2O to D2O reduces the unfolding rates possibly due to the increase of solvent viscosity. The quantified solvent effects on the protein folding Gibbs energy and activation energy suggest that the transition state of folding may have a similar structure to the native state of the protein.
Ilizarov external fixation versus plate internal fixation in the treatment of end-stage ankle arthritis: decision analysis of clinical parameters
Authors: Li Jun , Li Bohua , Zhang Zhengdong , Wang Shanxi , Liu Lei
Published: November 2017

The purpose of this study was to evaluate the effect of Ilizarov external fixation (IEF) and plate internal fixation (PIF) in the treatment of end-stage ankle arthritis on pain relieving and function improvement. The study cohort consisted of 59 patients with end-stage ankle arthritis underwent ankle arthrodesis with IEF or PIF between June 2011 and June 2015. Standard radiographs and computed tomography (CT) scans were obtained before surgery and during the follow-up. Functional assessments were performed using Foot and Ankle pain score of American Orthopedics Foot and Ankle Society (AOFAS) and Visual Analogue Scale (VAS). The average AOFAS scores in both IEF group and PIF groups increased significantly after operation, from 45.5 ± 6.3 to 84.8 ± 4.9 and from 45.9 ± 6.6 to 86.6 ± 5.4, respectively. The average VAS scores in both groups decreased significantly after operation, from 8.4 ± 1.9 to 2.5 ± 0.6 and from 8.2 ± 1.5 to 2.3 ± 0.7, respectively. Nevertheless, there was no significant difference for preoperative or postoperative AOFAS and VAS scores between the two groups. The IEF would result in comparable postoperative functional recovery and pain relieving to PIF and may be an effective substitute to PIF in the treatment of end-stage ankle arthritis.
p300-mediated acetylation increased the protein stability of HIPK2 and enhanced its tumor suppressor function
Authors: Choi Jong-Ryoul , Lee Seo-Young , Shin Ki Soon , Choi Cheol Yong , Kang Shin Jung
Published: November 2017

Homeodomain-interacting protein kinase 2 (HIPK2) is a nuclear serine/threonine kinase that functions in development and tumor suppression. One of the prominent features of this kinase is that it is tightly regulated by proteasomal degradation. In the present study, we present evidence suggesting that the protein stability of HIPK2 can be regulated by p300-mediated acetylation. p300 increased the protein level of HIPK2 via its acetyltransferase activity. p300 increased the acetylation of HIPK2 while decreased polyubiquitination and its proteasomal degradation. We also observed that DNA damage induced acetylation of HIPK2 along with an increase in the protein amount, which was inhibited by p300 RNAi. Importantly, p300 promoted p53 activation and the HIPK2-mediated suppression of cell proliferation, suggesting acetylation-induced HIPK2 stabilization contributed to the enhanced activation of HIPK2. Overexpression of p300 promoted the HIPK2-mediated suppression of tumor growth in mouse xenograft model as well. Taken together, our data suggest that p300-mediated acetylation of HIPK2 increases the protein stability of HIPK2 and enhances its tumor suppressor function.
Advanced glycation endproducts link inflammatory cues to upregulation of galectin-1 in diabetic retinopathy
Authors: Kanda Atsuhiro , Dong Yoko , Noda Kousuke , Saito Wataru , Ishida Susumu
Published: November 2017

Diabetic retinopathy (DR) is an inflammatory and progressive vaso-occlusive disease resulting in angiogenesis. Galectin-1 is a hypoxia-induced angiogenic factor associated with cancer and proliferative DR. Here we reveal a significant upregulation of galectin-1 in eyes of DR patients along with progression of clinical stages beginning from the pre-ischemic, inflammatory stage with diabetic macular edema, but not in eyes with non-diabetic retinal vascular occlusions. As for its regulatory mechanism unrelated to hypoxia but selective to DR, in vitro galectin-1/LGALS1 expression was shown to increase after application to Müller glial cells with interleukin (IL)-1β, which was induced in monocyte-derived macrophages and microglial cells via toll-like receptor (TLR) 4 signaling stimulated by advanced glycation endproducts (AGE). In vivo inhibition of AGE generation with aminoguanidine, macrophage depletion with clodronate liposomes, and antibody-based blockade of Il-1β and Tlr4 attenuated diabetes-induced retinal Lgals1 expression in mice. Fibrovascular tissues from proliferative DR eyes were immunoreactive for AGE, TRL4 and IL-1β in macrophages, and IL-1β receptor-positive glial cells expressed galectin-1. Therefore, diabetes-induced retinal AGE accumulation was suggested to activate IL-1β-related inflammatory cues in macrophages followed by Müller cells, linking to galectin-1 upregulation in human DR with time. Our data highlight AGE-triggered inflammation as the DR-selective inducer of galectin-1.
Rapid Detection of Prunus Necrotic Ringspot Virus by Reverse Transcription-cross-priming Amplification Coupled with Nucleic Acid Test Strip Cassette
Authors: Huo Ya-Yun , Li Gui-Fen , Qiu Yan-Hong , Li Wei-Min , Zhang Yong-Jiang
Published: November 2017

Prunus necrotic ringspot virus (PNRSV) is one of the most devastating viruses to Prunus spp. In this study, we developed a diagnostic system RT-CPA-NATSC, wherein reverse transcription-cross-priming amplification (RT-CPA) is coupled with nucleic acid test strip cassette (NATSC), a vertical flow (VF) visualization, for PNRSV detection. The RT-CPA-NATSC assay targets the encoding gene of the PNRSV coat protein with a limit of detection of 72 copies per reaction and no cross-reaction with the known Prunus pathogenic viruses and viroids, demonstrating high sensitivity and specificity. The reaction is performed on 60 °C and can be completed less than 90 min with the prepared template RNA. Field sample test confirmed the reliability of RT-CPA-NATSC, indicating the potential application of this simple and rapid detection method in routine test of PNRSV.
Phosphate-Solubilizing Bacteria Nullify the Antagonistic Effect of Soil Calcification on Bioavailability of Phosphorus in Alkaline Soils
Authors: Adnan Muhammad , Shah Zahir , Fahad Shah , Arif Muhamamd , Alam Mukhtar , Khan Imtiaz Ali , Mian Ishaq Ahmad , Basir Abdul , Ullah Hidayat , Arshad Muhammad , Rahman Inayat-Ur , Saud Shah , Ihsan Muhammad Zahid , Jamal Yousaf , Amanullah  , Hammad Hafiz Mohkum , Nasim Wajid
Published: November 2017

Phosphate-solubilizing bacteria (PSB) reduce the negative effects of soil calcification on soil phosphorus (P) nutrition. In this incubation study, we explored the ability of PSB (control and inoculated) to release P from different P sources [single super phosphate (SSP), rock phosphate (RP), poultry manure (PM) and farm yard manure (FYM)] with various soil lime contents (4.78, 10, 15 and 20%) in alkaline soil. PSB inoculation progressively enriched Olsen extractable P from all sources compared to the control over the course of 56 days; however, this increase was greater from organic sources (PM and FYM) than from mineral P sources (SSP and RP). Lime addition to the soil decreased bioavailable P, but this effect was largely neutralized by PSB inoculation. PSB were the most viable in soil inoculated with PSB and amended with organic sources, while lime addition decreased PSB survival. Our findings imply that PSB inoculation can counteract the antagonistic effect of soil calcification on bioavailable P when it is applied using both mineral and organic sources, although organic sources support this process more efficiently than do mineral P sources. Therefore, PSB inoculation combined with organic manure application is one of the best options for improving soil P nutrition.
Transient Ischemic Attack, Traumatic Brain Injury, and Ischemic Stroke: Risk Factors and Treatments
Authors: Peplow Philip V. , Liaw Jacqueline J. T.
Published: November 2017

A stroke or traumatic brain injury (TBI) has multiple consequences for patients and their families, as well as healthcare providers and society. This chapter reviews the incidence and risk factors of transient ischemic attack (TIA; ‘mini-stroke’), stroke, and TBI. Treatments of TIA, ischemic stroke, and TBI are also presented, as well as possible hemorrhagic complications arising from thrombolytic therapy for ischemic stroke.
Biomarkers of Acute Brain Injury and Surrogate Endpoints in Traumatic Brain Injury and Stroke Translational Studies
Authors: Papa Linda
Published: November 2017

The diagnosis of acute brain injury in the acute care setting is based on neurological examination and neuroimaging tools such as computed tomography scanning and magnetic resonance imaging. Clinicians have not been afforded the opportunity to use blood-based biomarkers for these conditions acutely. There are numerous blood-based biomarkers being used in medicine today, but no blood-based biomarker has been approved by the FDA for clinical use, nor has one been validated as a surrogate measure for clinical trials. Although there is an abundance of papers being published, many lack the rigorous methods and reporting required to adequately evaluate these markers for clinical use or as surrogate endpoints. Given all of this research, there is now an important need to validate these biomarkers. This chapter will review some of the most widely studied protein biomarkers for acute brain injury in the clinical setting, with an emphasis on traumatic brain injury and stroke. Also highlighted will be the gaps in the current state of knowledge and the role for blood-based biomarkers in future clinical trials.