bluuebunny/crossref_metadata_2025_split huggingface dataset:
A deleterious role for Th9/IL-9 in hepatic fibrogenesis
Authors: Qin Shan-yu , Lu Dong-hong , Guo Xiao-yun , Luo Wei , Hu Bang-li , Huang Xiao-li , Chen Mei , Wang Jia-xu , Ma Shi-Jia , Yang Xian-wen , Jiang Hai-xing , Zhou You 
Published: January 2016

AbstractT helper 9 (Th9) cells, a recently recognized Th cell subset, are involved in autoimmune diseases. We aimed to investigate the role of Th9/interleukin-9 (IL-9) in the pathogenesis of hepatic fibrosis. Th9 and Th17 cells were quantified in chronic hepatitis B (CHB) patients with hepatic fibrosis, HBV-associated liver cirrhosis (LC) patients and healthy controls (HC). The percentages of Th9 and Th17 cells, concentrations of IL-9 and IL-17, as well as expression of IL-17, TNF-α, IL-6, IL-4, IL-21, TGF-β1 and IFN-γ were significantly increased in plasma of CHB and LC patients compared with those in HC. Splenic Th9 and Th17 cells, plasma concentrations and liver expression of IL-9 and IL-17A were significantly elevated in mice with hepatic fibrosis compared with controls. Neutralization of IL-9 in mice ameliorated hepatic fibrosis, attenuated the activation of hepatic stellate cells, reduced frequencies of Th9, Th17 and Th1 cells in spleen and suppressed expression of IL-9, IL-17A, IFN-γ, TGF-β1, IL-6, IL-4 and TNF-α in plasma and liver respectively. Our data suggest a deleterious role of Th9/IL-9 in increasing hepatic fibrosis and exacerbating disease endpoints, indicating that Th9/IL9 based immunotherapy may be a promising approach for treating hepatic fibrosis.
Protein oxidation mediated by heme-induced active site conversion specific for heme-regulated transcription factor, iron response regulator
Authors: Kitatsuji Chihiro , Izumi Kozue , Nambu Shusuke , Kurogochi Masaki , Uchida Takeshi , Nishimura Shin-Ichiro , Iwai Kazuhiro , O’Brian Mark R. , Ikeda-Saito Masao , Ishimori Koichiro 
Published: January 2016

AbstractThe Bradyrhizobium japonicum transcriptional regulator Irr (iron response regulator) is a key regulator of the iron homeostasis, which is degraded in response to heme binding via a mechanism that involves oxidative modification of the protein. Here, we show that heme-bound Irr activates O2 to form highly reactive oxygen species (ROS) with the “active site conversion” from heme iron to non-heme iron to degrade itself. In the presence of heme and reductant, the ROS scavenging experiments show that Irr generates H2O2 from O2 as found for other hemoproteins, but H2O2 is less effective in oxidizing the peptide and further activation of H2O2 is suggested. Interestingly, we find a time-dependent decrease of the intensity of the Soret band and appearance of the characteristic EPR signal at g = 4.3 during the oxidation, showing the heme degradation and the successive formation of a non-heme iron site. Together with the mutational studies, we here propose a novel “two-step self-oxidative modification” mechanism, during which O2 is activated to form H2O2 at the heme regulatory motif (HRM) site and the generated H2O2 is further converted into more reactive species such as ·OH at the non-heme iron site in the His-cluster region formed by the active site conversion.
Farnesoid X receptor activation promotes cell proliferation via PDK4-controlled metabolic reprogramming
Authors: Xie Yang , Wang Hong , Cheng Xuefang , Wu Yuzheng , Cao Lijuan , Wu Mengqiu , Xie Wen , Wang Guangji , Hao Haiping 
Published: January 2016

AbstractFarnesoid X receptor (FXR) plays a pivotal role in the regulation of various metabolic pathways as well as liver regeneration. However, the casual link between cell proliferative effects during liver regeneration and metabolic regulation of FXR was elusive. In this study, we found that FXR activation significantly promotes HepG2 cell proliferation accompanied with metabolic switch towards the excessive accumulation of aerobic glycolytic intermediates including lactic acid, pyruvate and the subsequently increased biosynthesis of glycine. This FXR-induced metabolic switch was found dependent on an up-regulation of pyruvate dehydrogenate kinase 4 (PDK4), a FXR target gene. FXR agonists were found to promote liver regeneration in the murine model of APAP induced liver injury, which was associated with a metabolic switch favoring the accumulation of glycolytic intermediates as precursors for generation of biomass. However, FXR activation has little effect on the glycolytic metabolism in healthy primary hepatocytes in vitro and the liver of healthy mice in vivo. Therefore, we conclude that FXR may promote the proliferation of tumor cells and the hepatocytes in the process of liver regeneration by activating the PDK4-mediated metabolic reprogramming to generate glycolytic intermediates essential for rapid biomass generation, establishing a mechanistic link between cell proliferation and metabolic switch.
Topographic confinement of epithelial clusters induces epithelial-to-mesenchymal transition in compliant matrices
Authors: Nasrollahi Samila , Pathak Amit 
Published: January 2016

AbstractEpithelial cells disengage from their clusters and become motile by undergoing epithelial-to-mesenchymal transition (EMT), an essential process for both embryonic development and tumor metastasis. Growing evidence suggests that high extracellular matrix (ECM) stiffness induces EMT. In reality, epithelial clusters reside in a heterogeneous microenvironment whose mechanical properties vary not only in terms of stiffness, but also topography, dimensionality and confinement. Yet, very little is known about how various geometrical parameters of the ECM might influence EMT. Here, we adapt a hydrogel-microchannels based matrix platform to culture mammary epithelial cell clusters in ECMs of tunable stiffness and confinement. We report a previously unidentified role of ECM confinement in EMT induction. Surprisingly, confinement induces EMT even in the cell clusters surrounded by a soft matrix, which otherwise protects against EMT in unconfined environments. Further, we demonstrate that stiffness-induced and confinement-induced EMT work through cell-matrix adhesions and cytoskeletal polarization, respectively. These findings highlight that both the structure and the stiffness of the ECM can independently regulate EMT, which brings a fresh perspective to the existing paradigm of matrix stiffness-dependent dissemination and invasion of tumor cells.
Potency of umbilical cord blood- and Wharton’s jelly-derived mesenchymal stem cells for scarless wound healing
Authors: Doi Hanako , Kitajima Yuriko , Luo Lan , Yan Chan , Tateishi Seiko , Ono Yusuke , Urata Yoshishige , Goto Shinji , Mori Ryoichi , Masuzaki Hideaki , Shimokawa Isao , Hirano Akiyoshi , Li Tao-Sheng 
Published: January 2016

AbstractPostnatally, scars occur as a consequence of cutaneous wound healing. Scarless wound healing is highly desired for patients who have undergone surgery or trauma, especially to exposed areas. Based on the properties of mesenchymal stem cells (MSCs) for tissue repair and immunomodulation, we investigated the potential of MSCs for scarless wound healing. MSCs were expanded from umbilical cord blood (UCB-MSCs) and Wharton’s jelly (WJ-MSCs) from healthy donors who underwent elective full-term pregnancy caesarean sections. UCB-MSCs expressed lower levels of the pre-inflammatory cytokines IL1A and IL1B, but higher levels of the extracellular matrix (ECM)-degradation enzymes MMP1 and PLAU compared with WJ-MSCs, suggesting that UCB-MSCs were more likely to favor scarless wound healing. However, we failed to find significant benefits for stem cell therapy in improving wound healing and reducing collagen deposition following the direct injection of 1.0 × 105 UCB-MSCs and WJ-MSCs into 5 mm full-thickness skin defect sites in nude mice. Interestingly, the implantation of UCB-MSCs tended to increase the expression of MMP2 and PLAU, two proteases involved in degradation of the extracellular matrix in the wound tissues. Based on our data, UCB-MSCs are more likely to be a favorable potential stem cell source for scarless wound healing, although a better experimental model is required for confirmation.
Pigeons home faster through polluted air
Authors: Li Zhongqiu , Courchamp Franck , Blumstein Daniel T. 
Published: January 2016

AbstractAir pollution, especially haze pollution, is creating health issues for both humans and other animals. However, remarkably little is known about how animals behaviourally respond to air pollution. We used multiple linear regression to analyse 415 pigeon races in the North China Plain, an area with considerable air pollution and found that while the proportion of pigeons successfully homed was not influenced by air pollution, pigeons homed faster when the air was especially polluted. Our results may be explained by an enhanced homing motivation and possibly an enriched olfactory environment that facilitates homing. Our study provides a unique example of animals’ response to haze pollution; future studies are needed to identify proposed mechanisms underlying this effect.
Absence of IFNγ promotes hippocampal plasticity and enhances cognitive performance
Authors: Monteiro S , Ferreira F M , Pinto V , Roque S , Morais M , de Sá-Calçada D , Mota C , Correia-Neves M , Cerqueira J J 
Published: January 2016

AbstractCognitive functioning can be differentially modulated by components of the immune system. Interferon-γ (IFNγ) is a pro-inflammatory cytokine whose production is altered in many conditions displaying some degree of cognitive deficits, although its role in cognitive functioning is still unclear. Here we show that the absence of IFNγ selectively enhances cognitive behaviours in tasks in which the hippocampus is implicated. Moreover, the absence of IFNγ leads to volumetric and cell density changes that are restricted to the dorsal part of the hippocampus. In the dorsal hippocampus, the absence of this pro-inflammatory cytokine leads to an increase in the numbers of newly born neurons in the subgranular zone of the dentate gyrus (DG), an adult neurogenic niche known to support learning and memory, and to an enlargement of the dendritic arborization of DG granule and cornu ammonis (CA)1 pyramidal neurons. Moreover, it also modestly impacts synaptic plasticity, by decreasing the paired-pulse facilitation in the Schaffer collateral to CA1 pyramidal cell synapses. Taken together, our results provide evidence that IFNγ is a negative regulator of hippocampal functioning, as its absence positively impacts on dorsal hippocampus structure, cell density, neuronal morphology and synaptic plasticity. Importantly, these neuroplastic changes are associated with improved performance in learning and memory tasks. Therefore, blockage of the IFNγ signalling may present as promising therapeutic targets for the treatment of inflammation-associated cognitive dysfunction.
A comprehensive analysis of NDST3 for schizophrenia and bipolar disorder in Han Chinese
Authors: Zhang C , Lu W , Wang Z , Ni J , Zhang J , Tang W , Fang Y 
Published: January 2016

AbstractA novel susceptibility locus (rs11098403) for schizophrenia and bipolar disorder (BD) was identified in an Ashkenazi Jewish population by a recent large-scale genome-wide association study. The rs11098403 is located in the vicinity of the gene encoding N-deacetylase/N-sulfotransferase (heparan glucosaminyl) 3, (NDST3). This study aimed to replicate the results in a Han Chinese population and then potentially extend these findings. We performed a two-stage study to investigate the association of NDST3 with the schizophrenia and BD risk in the Han Chinese. In stage 1, a total of 632 patients with schizophrenia, 654 patients with BD and 684 healthy controls were recruited from the Shanghai region. In stage 2, 522 schizophrenia patients and 547 normal subjects were enrolled from the Hangzhou region. Then, we conducted a meta-analysis based on the present literature. In stage 1, the single nucleotide polymorphism (SNP) rs11098403 showed a significant association with schizophrenia (corrected P=0.005). The frequency of the rs11098403 G allele was significantly lower among schizophrenia patients than among the controls (odds ratio (OR)=0.68, 95% confidence interval (CI): 0.55−0.84, corrected P=0.002). No significant difference was observed in individual SNP marker genotypes or allele distributions between the BD and control groups. In stage 2, the association of rs11098403 with schizophrenia could be validated (genotypic P=0.001 and allelic P=0.0003). After pooling all data from 1861 patients with schizophrenia and 2081 controls, we observed a significant association of the rs11098403 G allele with schizophrenia (Z=5.56, P<0.001), with an OR=0.70 (95% CI: 0.61−0.79). Then, we performed an expression quantitative trait loci analysis to investigate the functional effect of rs11098403 on NDST3 expression in the brain. We observed a significant association of rs11098403 with NDST3 expression in the hippocampus (P=0.027), although the significance did not survive after multiple testing correction. Our findings provided preliminary evidence that rs11098403 might modify the genetic risk of schizophrenia in the Han Chinese. Further investigations are warranted to identify the precise mechanism regulating brain NDST3 expression in the Han Chinese. These results would help to explain the pathophysiological mechanism of schizophrenia.
Dysfunction in the coagulation system and schizophrenia
Authors: Hoirisch-Clapauch S , Amaral O B , Mezzasalma M A U , Panizzutti R , Nardi A E 
Published: January 2016

AbstractAlthough different hypotheses have been formulated to explain schizophrenia pathogenesis, the links between them are weak. The observation that five psychotic patients on chronic warfarin therapy for deep-vein thrombosis showed long-term remission of psychotic symptoms made us suspect that abnormalities in the coagulation pathway, specifically low tissue plasminogen activator (tPA) activity, could be one of the missing links. Our hypothesis is supported by a high prevalence of conditions affecting tPA activity in drug-naive schizophrenia, such as antiphospholipid antibodies, elevated cytokine levels, hyperinsulinemia and hyperhomocysteinemia. We recently screened a group of schizophrenia patients and controls for conditions affecting tPA activity. Free-protein S deficiency was highly prevalent among patients, but not found in controls. Free-protein S and functional protein C are natural anticoagulants that form complexes that inhibit tPA inhibitors. All participants had normal protein C levels, suggesting that protein S could have a role in schizophrenia, independent of protein C. Chronic patients and those studied during acute episodes had between three and six conditions affecting tPA and/or protein S activity, while patients in remission had up to two, which led us to postulate that multiple conditions affecting tPA and/or protein S activity could contribute to the full expression of schizophrenia phenotype. This paper describes the physiological roles of tPA and protein S, reviewing how their activity influences pathogenesis and comorbidity of schizophrenia. Next, it analyzes how activity of tPA and protein S is influenced by biochemical abnormalities found in schizophrenia. Last, it suggests future directions for research, such as studies on animal models and on therapeutic approaches for schizophrenia aiming at increasing tPA and protein S activity.
Broadband circularly‐polarised chifre‐shaped monopole antenna with asymmetric feed
Authors: Han Rong‐Cang , Zhong Shun‐Shi 
Published: January 2016

A broadband circularly‐polarised monopole antenna is proposed. The broadband property of the antenna is basically achieved not only by the chifre‐shaped monopole radiator, but also its asymmetric feed. The circular‐polarisation characteristics are greatly enhanced by adjusting the location of the monopole microstrip‐feed. The antenna delivers good performance on impedance matching and circular polarisation. The measured results demonstrate that the impedance bandwidth is 72% and the 3‐dB axial‐ratio bandwidth reaches 41.6% with a central frequency of 2.5 GHz.
Return to Play in Athletes Receiving Cervical Surgery: A Systematic Review
Authors: Molinari Robert W. , Pagarigan Krystle , Dettori Joseph R. , Molinari Robert , Dehaven Kenneth E. 
Published: January 2016

Study Design Systematic review. Clinical Questions Among athletes who undergo surgery of the cervical spine, (1) What proportion return to play (RTP) after their cervical surgery? (2) Does the proportion of those cleared for RTP depend on the type of surgical procedure (artificial disk replacement, fusion, nonfusion foraminotomies/laminoplasties), number of levels (1, 2, or more levels), or type of sport? (3) Among those who return to their presurgery sport, how long do they continue to play? (4) Among those who return to their presurgery sport, how does their postoperative performance compare with their preoperative performance? Objectives To evaluate the extent and quality of published literature on the topic of return to competitive athletic completion after cervical spinal surgery. Methods Electronic databases and reference lists of key articles published up to August 19, 2015, were searched to identify studies reporting the proportion of athletes who RTP after cervical spine surgery. Results Nine observational, retrospective series consisting of 175 patients were included. Seven reported on professional athletes and two on recreational athletes. Seventy-five percent (76/102) of professional athletes returned to their respective sport following surgery for mostly cervical herniated disks. Seventy-six percent of recreational athletes (51/67) age 10 to 42 years RTP in a variety of sports following surgery for mostly herniated disks. No snowboarder returned to snowboarding (0/6) following surgery for cervical fractures. Most professional football players and baseball pitchers returned to their respective sport at their presurgery performance level. Conclusions RTP decisions after cervical spine surgery remain controversial, and there is a paucity of existing literature on this topic. Successful return to competitive sports is well described after single-level anterior cervical diskectomy and fusion surgery for herniated disk. RTP outcomes involving other cervical spine diagnoses and surgical procedures remain unclear. Additional quality research is needed on this topic.
The spreading of misinformation online
Authors: Del Vicario Michela , Bessi Alessandro , Zollo Fabiana , Petroni Fabio , Scala Antonio , Caldarelli Guido , Stanley H. Eugene , Quattrociocchi Walter 
Published: January 2016

SignificanceThe wide availability of user-provided content in online social media facilitates the aggregation of people around common interests, worldviews, and narratives. However, the World Wide Web is a fruitful environment for the massive diffusion of unverified rumors. In this work, using a massive quantitative analysis of Facebook, we show that information related to distinct narratives––conspiracy theories and scientific news––generates homogeneous and polarized communities (i.e., echo chambers) having similar information consumption patterns. Then, we derive a data-driven percolation model of rumor spreading that demonstrates that homogeneity and polarization are the main determinants for predicting cascades’ size.
Micronucleus formation causes perpetual unilateral chromosome inheritance in mouse embryos
Authors: Vázquez-Diez Cayetana , Yamagata Kazuo , Trivedi Shardul , Haverfield Jenna , FitzHarris Greg 
Published: January 2016

Significance
Early mammalian embryos frequently constitute a mixture of euploid and aneuploid cells, termed embryo mosaicism. Although this is considered a major cause of fertility problems, the mechanistic explanation for the mitotic errors that give rise to the aneuploid cells within mosaic embryos remains mysterious. Here using long-term live imaging of chromosome segregation in mouse embryos we show that individual chromosomes are frequently encapsulated within small nucleus-like structures called micronuclei. We show that micronucleus-enclosed chromosomes lack proper kinetochores and are therefore unable to be correctly segregated, causing them to be randomly inherited by just one of the daughter cells during subsequent embryonic cell divisions. This unexpected pattern of chromosome inheritance provides a novel explanation for mosaicism in early embryos.
Quantum violation of the pigeonhole principle and the nature of quantum correlations
Authors: Aharonov Yakir , Colombo Fabrizio , Popescu Sandu , Sabadini Irene , Struppa Daniele C. , Tollaksen Jeff 
Published: January 2016

Significance
We show that quantum mechanics violates one of the fundamental principles of nature: If you put three particles in two boxes, necessarily two particles will end up in the same box. We find instances when three quantum particles are put in two boxes, yet no two particles are in the same box, a seemingly impossible and absurd effect. This is only one of a host of related quantum effects which we discovered and which point to a very interesting structure of quantum mechanics that was hitherto unnoticed and has major implications for our understanding of nature. It requires us to revisit some of the most basic notions of quantum physics––the notions of separability, of correlations, and of interactions.
Economic Performance and Political Trust: The impact of the financial crisis on European citizens
Authors: Kroknes Veronica Fagerland , Jakobsen Tor Georg , Grønning Lisa-Marie 
Published: January 2016

ABSTRACT
Trust links ordinary citizens to the institutions that are intended to represent them, and thereby enhances both the legitimacy and the effectiveness of democratic government. In this article we investigate whether economic performance affects political trust and if the 2007–2008 financial crisis has decreased confidence levels due to the severity of its consequences. We employ multilevel modeling to analyze data from 25 European countries taken from the European Social Survey, combined with economic indicators from the World Bank and the international Monetary Fund. Our results show that economic performance is an important decider of people's levels of trust. We are also able to conclude that the financial crisis has reduced citizen's trust in political institutions in those countries where the crisis has had a severe impact on the economy.
Cash for childcare schemes in the Nordic welfare states: diverse paths, diverse outcomes
Authors: Duvander Ann-Zofie , Ellingsæter Anne Lise 
Published: January 2016

ABSTRACT
Recent family policy developments may blur conventional family policy typologies. While policies in some European welfare states are shifting away from strong male breadwinner regimes towards work–family reconciliation, the adding of cash for childcare (CFC) benefits in Nordic earner-carer welfare states points in the opposite direction. How can we understand growing family policy hybridisation? Comparison of CFC schemes in the five Nordic countries is the empirical basis of the discussion here – what does the insertion of such a familistic policy measure actually mean? The analysis displays diverse national policy processes and policy outputs and wide variation in parents’ responses to this policy incentive. Reforms have been subject to conflicts and amendments to different degrees, and impact has been shaped by their institution at different times distinguished by mothers’ varying access to childcare services and labour markets. We conclude that conceptualisation of CFC schemes needs to be contextualised in relation to political dynamisms and opportunity structures.