bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contractile forces at tricellular contacts modulate epithelial organization and monolayer integrity
Authors: Salomon Julie , Gaston Cécile , Magescas Jérémy , Duvauchelle Boris , Canioni Danielle , Sengmanivong Lucie , Mayeux Adeline , Michaux Grégoire , Campeotto Florence , Lemale Julie , Viala Jérôme , Poirier Françoise , Minc Nicolas , Schmitz Jacques , Brousse Nicole , Ladoux Benoit , Goulet Olivier , Delacour Delphine 
Published: January 2017

AbstractMonolayered epithelia are composed of tight cell assemblies that ensure polarized exchanges. EpCAM, an unconventional epithelial-specific cell adhesion molecule, is assumed to modulate epithelial morphogenesis in animal models, but little is known regarding its cellular functions. Inspired by the characterization of cellular defects in a rare EpCAM-related human intestinal disease, we find that the absence of EpCAM in enterocytes results in an aberrant apical domain. In the course of this pathological state, apical translocation towards tricellular contacts (TCs) occurs with striking tight junction belt displacement. These unusual cell organization and intestinal tissue defects are driven by the loss of actomyosin network homoeostasis and contractile activity clustering at TCs, yet is reversed by myosin-II inhibitor treatment. This study reveals that adequate distribution of cortical tension is crucial for individual cell organization, but also for epithelial monolayer maintenance. Our data suggest that EpCAM modulation protects against epithelial dysplasia and stabilizes human tissue architecture.
K48-linked KLF4 ubiquitination by E3 ligase Mule controls T-cell proliferation and cell cycle progression
Authors: Hao Zhenyue , Sheng Yi , Duncan Gordon S. , Li Wanda Y. , Dominguez Carmen , Sylvester Jennifer , Su Yu-Wen , Lin Gloria H.Y. , Snow Bryan E. , Brenner Dirk , You-Ten Annick , Haight Jillian , Inoue Satoshi , Wakeham Andrew , Elford Alisha , Hamilton Sara , Liang Yi , Zúñiga-Pflücker Juan C. , He Housheng Hansen , Ohashi Pamela S. , Mak Tak W. 
Published: January 2017

AbstractT-cell proliferation is regulated by ubiquitination but the underlying molecular mechanism remains obscure. Here we report that Lys-48-linked ubiquitination of the transcription factor KLF4 mediated by the E3 ligase Mule promotes T-cell entry into S phase. Mule is elevated in T cells upon TCR engagement, and Mule deficiency in T cells blocks proliferation because KLF4 accumulates and drives upregulation of its transcriptional targets E2F2 and the cyclin-dependent kinase inhibitors p21 and p27. T-cell-specific Mule knockout (TMKO) mice develop exacerbated experimental autoimmune encephalomyelitis (EAE), show impaired generation of antigen-specific CD8+ T cells with reduced cytokine production, and fail to clear LCMV infections. Thus, Mule-mediated ubiquitination of the novel substrate KLF4 regulates T-cell proliferation, autoimmunity and antiviral immune responses in vivo.
Structural basis for the recognition and degradation of host TRIM proteins by Salmonella effector SopA
Authors: Fiskin Evgenij , Bhogaraju Sagar , Herhaus Lina , Kalayil Sissy , Hahn Marcel , Dikic Ivan 
Published: January 2017

AbstractThe hallmark of Salmonella Typhimurium infection is an acute intestinal inflammatory response, which is mediated through the action of secreted bacterial effector proteins. The pro-inflammatory Salmonella effector SopA is a HECT-like E3 ligase, which was previously proposed to activate host RING ligases TRIM56 and TRIM65. Here we elucidate an inhibitory mechanism of TRIM56 and TRIM65 targeting by SopA. We present the crystal structure of SopA in complex with the RING domain of human TRIM56, revealing the atomic details of their interaction and the basis for SopA selectivity towards TRIM56 and TRIM65. Structure-guided biochemical analysis shows that SopA inhibits TRIM56 E3 ligase activity by occluding the E2-interacting surface of TRIM56. We further demonstrate that SopA ubiquitinates TRIM56 and TRIM65, resulting in their proteasomal degradation during infection. Our results provide the basis for how a bacterial HECT ligase blocks host RING ligases and exemplifies the multivalent power of bacterial effectors during infection.
Topological frustration of artificial spin ice
Authors: Drisko Jasper , Marsh Thomas , Cumings John 
Published: January 2017

AbstractFrustrated systems, typically characterized by competing interactions that cannot all be simultaneously satisfied, display rich behaviours not found elsewhere in nature. Artificial spin ice takes a materials-by-design approach to studying frustration, where lithographically patterned bar magnets mimic the frustrated interactions in real materials but are also amenable to direct characterization. Here, we introduce controlled topological defects into square artificial spin ice lattices in the form of lattice edge dislocations and directly observe the resulting spin configurations. We find the presence of a topological defect produces extended frustration within the system caused by a domain wall with indeterminate configuration. Away from the dislocation, the magnets are locally unfrustrated, but frustration of the lattice persists due to its topology. Our results demonstrate the non-trivial nature of topological defects in a new context, with implications for many real systems in which a typical density of dislocations could fully frustrate a canonically unfrustrated system.
TNFα drives pulmonary arterial hypertension by suppressing the BMP type-II receptor and altering NOTCH signalling
Authors: Hurst Liam A. , Dunmore Benjamin J. , Long Lu , Crosby Alexi , Al-Lamki Rafia , Deighton John , Southwood Mark , Yang Xudong , Nikolic Marko Z. , Herrera Blanca , Inman Gareth J. , Bradley John R. , Rana Amer A. , Upton Paul D. , Morrell Nicholas W. 
Published: January 2017

AbstractHeterozygous germ-line mutations in the bone morphogenetic protein type-II receptor (BMPR-II) gene underlie heritable pulmonary arterial hypertension (HPAH). Although inflammation promotes PAH, the mechanisms by which inflammation and BMPR-II dysfunction conspire to cause disease remain unknown. Here we identify that tumour necrosis factor-α (TNFα) selectively reduces BMPR-II transcription and mediates post-translational BMPR-II cleavage via the sheddases, ADAM10 and ADAM17 in pulmonary artery smooth muscle cells (PASMCs). TNFα-mediated suppression of BMPR-II subverts BMP signalling, leading to BMP6-mediated PASMC proliferation via preferential activation of an ALK2/ACTR-IIA signalling axis. Furthermore, TNFα, via SRC family kinases, increases pro-proliferative NOTCH2 signalling in HPAH PASMCs with reduced BMPR-II expression. We confirm this signalling switch in rodent models of PAH and demonstrate that anti-TNFα immunotherapy reverses disease progression, restoring normal BMP/NOTCH signalling. Collectively, these findings identify mechanisms by which BMP and TNFα signalling contribute to disease, and suggest a tractable approach for therapeutic intervention in PAH.
Hydrogenation of iron in the early stage of Earth’s evolution
Authors: Iizuka-Oku Riko , Yagi Takehiko , Gotou Hirotada , Okuchi Takuo , Hattori Takanori , Sano-Furukawa Asami 
Published: January 2017

AbstractDensity of the Earth’s core is lower than that of pure iron and the light element(s) in the core is a long-standing problem. Hydrogen is the most abundant element in the solar system and thus one of the important candidates. However, the dissolution process of hydrogen into iron remained unclear. Here we carry out high-pressure and high-temperature in situ neutron diffraction experiments and clarify that when the mixture of iron and hydrous minerals are heated, iron is hydrogenized soon after the hydrous mineral is dehydrated. This implies that early in the Earth’s evolution, as the accumulated primordial material became hotter, the dissolution of hydrogen into iron occurred before any other materials melted. This suggests that hydrogen is likely the first light element dissolved into iron during the Earth’s evolution and it may affect the behaviour of the other light elements in the later processes.
Effects of childhood and adolescence physical activity patterns on psychosis risk—a general population cohort study
Authors: Sormunen Elina , Saarinen Maiju M. , Salokangas Raimo K. R. , Telama Risto , Hutri-Kähönen Nina , Tammelin Tuija , Viikari Jorma , Raitakari Olli , Hietala Jarmo 
Published: January 2017

AbstractSchizophrenia spectrum disorders are associated with high morbidity and mortality in somatic diseases. The risk factors of this excess mortality include, e.g., obesity, dietary factors, and physical inactivity, especially after the onset of psychosis, but there are limited early developmental data on these factors in individuals who later develop psychosis. A population-based cohort study “Cardiovascular Risk of Young Finns” started in 1980 with 3596 children and adolescents from six different age groups (3, 6, 9, 12, 15, and 18 years). Cardiovascular health parameters, including questionnaire of physical activity before first hospitalization (≤18 years), were studied in 1980, 1983, and 1986. All psychiatric diagnoses of the participants were derived from the Finnish Hospital Discharge Register up to the year 2012. We identified diagnostic groups of non-affective psychosis (n = 68, including a schizophrenia subgroup, n = 41), personality disorders (n = 43), affective disorders (n = 111), and substance-related disorders (n = 49), based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Ed﻿ition (DSM-IV). Groups were compared with controls with no psychiatric diagnoses (n = 3325). Sex, age, body mass index, birth weight, non-preterm birth, and mother’s mental disorders were included in the statistical model. Low physical activity in childhood and adolescence (9–18 years) independently predicted later development of non-affective psychosis. Lower physical activity index (relative risk 1.26 [1.1–1.5]), lower level of common activity during leisure time (relative risk 1.71 [1.2–2.5]), and non-participation in sports competitions (relative risk 2.58 [1.3–5.3]) were associated with a higher risk for later non-affective psychosis (expressed as increase in relative risk per physical activity unit). The findings were even stronger for schizophrenia, but no such link was observed for other diagnoses. The cause of low physical activity in premorbid/prodromal phase is likely to be multifactorial, including deviant motor and cognitive development. The results provide a rationale for including exercise and physical activity interventions as a part of psychosis prevention programs.
Significantly improved photovoltaic performance in polymer bulk heterojunction solar cells with graphene oxide /PEDOT:PSS double decked hole transport layer
Authors: Rafique Saqib , Abdullah Shahino Mah , Shahid Muhammad Mehmood , Ansari Mohammad Omaish , Sulaiman Khaulah 
Published: January 2017

AbstractThis work demonstrates the high performance graphene oxide (GO)/PEDOT:PSS doubled decked hole transport layer (HTL) in the PCDTBT:PC71BM based bulk heterojunction organic photovoltaic device. The devices were tested on merits of their power conversion efficiency (PCE), reproducibility, stability and further compared with the devices with individual GO or PEDOT:PSS HTLs. Solar cells employing GO/PEDOT:PSS HTL yielded a PCE of 4.28% as compared to either of individual GO or PEDOT:PSS HTLs where they demonstrated PCEs of 2.77 and 3.57%, respectively. In case of single GO HTL, an inhomogeneous coating of ITO caused the poor performance whereas PEDOT:PSS is known to be hygroscopic and acidic which upon direct contact with ITO reduced the device performance. The improvement in the photovoltaic performance is mainly ascribed to the increased charge carriers mobility, short circuit current, open circuit voltage, fill factor, and decreased series resistance. The well matched work function of GO and PEDOT:PSS is likely to facilitate the charge transportation and an overall reduction in the series resistance. Moreover, GO could effectively block the electrons due to its large band-gap of ~3.6 eV, leading to an increased shunt resistance. In addition, we also observed the improvement in the reproducibility and stability.
Optimum Leaf Removal Increases Nitrogen Accumulation in Kernels of Maize Grown at High Density
Authors: Liu Tiening , Huang Rundong , Cai Tie , Han Qingfang , Dong Shuting 
Published: January 2017

AbstractIncreasing plant density is one of the main approaches of achieving higher yields for modern maize crop. However, there exists leaf redundancy for high-density maize, and leaves of the upper canopy shade more competent leaves at the middle strata. In a two-year field experiments, Jinhai5, a semi-compact corn cultivar, was grown at a density of 105,000 plants ha−1 grown until 3 days after silking (3DAS), when plants were subjected to removal of the uppermost two leaves (S2), four leaves (S4) or six leaves (S6), with no leaf removal as control (S0). We evaluated the effects of leaf removal on N remobilization, photosynthetic capacity of the remaining leaves for N uptake, and N accumulation in kernels. Our present results concluded that, under high plant density, excising the uppermost two leaves promoted N remobilization from vegetative organs to kernels and enhanced photosynthetic capacity for N uptake, leading to an increased N accumulation in kernels (19.6% higher than control). However, four or six uppermost leaves removal reduced N remobilization from stem and photosynthesis for poor N uptake, resulting in 37.5 and 50.2% significantly reduced N accumulation in kernels, respectively.
Soluble ectodomain CD163 and extracellular vesicle-associated CD163 are two differently regulated forms of ‘soluble CD163’ in plasma
Authors: Etzerodt Anders , Berg Ronan M. G. , Plovsing Ronni R. , Andersen Morten N. , Bebien Magali , Habbeddine Mohamed , Lawrence Toby , Møller Holger J. , Moestrup Søren K. 
Published: January 2017

AbstractCD163 is the macrophage receptor for uptake of hemoglobin-haptoglobin complexes. The human receptor can be shed from the macrophage surface owing to a cleavage site for the inflammation-inducible TACE/ADAM17 enzyme. Accordingly, plasma ‘soluble CD163’ (sCD163) has become a biomarker for macrophage activity and inflammation. The present study disclosed that 10% of sCD163 in healthy persons is actually extracellular vesicle (EV)-associated CD163 not being cleaved and shed. Endotoxin injection of human volunteers caused a selective increase in the ectodomain CD163, while septic patients exhibited high levels of both soluble ectodomain CD163 and extracellular vesicle (EV) CD163, the latter representing up 60% of total plasma CD163. A poor prognosis of septic patients measured as the sequential organ failure assessment (SOFA) score correlated with the increase in membrane-associated CD163. Our results show that soluble ectodomain CD163 and EV CD163 in plasma are part of separate macrophage response in the context of systemic inflammation. While that soluble ectodomain CD163 is released during the acute systemic inflammatory response, this is not the case for EV CD163 that instead may be released during a later phase of the inflammatory response. A separate measurement of the two forms of CD163 constituting ‘soluble CD163’ in plasma may therefore add to the diagnostic and prognostic value.
Regulation of sleep plasticity by a thermo-sensitive circuit in Drosophila
Authors: Lamaze Angelique , Öztürk-Çolak Arzu , Fischer Robin , Peschel Nicolai , Koh Kyunghee , Jepson James E. C. 
Published: January 2017

AbstractSleep is a highly conserved and essential behaviour in many species, including the fruit fly Drosophila melanogaster. In the wild, sensory signalling encoding environmental information must be integrated with sleep drive to ensure that sleep is not initiated during detrimental conditions. However, the molecular and circuit mechanisms by which sleep timing is modulated by the environment are unclear. Here we introduce a novel behavioural paradigm to study this issue. We show that in male fruit flies, onset of the daytime siesta is delayed by ambient temperatures above 29 °C. We term this effect Prolonged Morning Wakefulness (PMW). We show that signalling through the TrpA1 thermo-sensor is required for PMW, and that TrpA1 specifically impacts siesta onset, but not night sleep onset, in response to elevated temperatures. We identify two critical TrpA1-expressing circuits and show that both contact DN1p clock neurons, the output of which is also required for PMW. Finally, we identify the circadian blue-light photoreceptor CRYPTOCHROME as a molecular regulator of PMW, and propose a model in which the Drosophila nervous system integrates information encoding temperature, light, and time to dynamically control when sleep is initiated. Our results provide a platform to investigate how environmental inputs co-ordinately regulate sleep plasticity.
LPS promotes Th2 dependent sensitisation leading to anaphylaxis in a Pru p 3 mouse model
Authors: Rodriguez Maria J. , Aranda Ana , Fernandez Tahia D. , Cubells-Baeza Nuria , Torres Maria J. , Gomez Francisca , Palomares Francisca , Perkins James R. , Rojo Javier , Diaz-Perales Araceli , Mayorga Cristobalina 
Published: January 2017

AbstractPru p 3 is the major peach allergen in the Mediterranean area. It frequently elicits severe reactions, limiting its study in humans, raising the need for animal models to investigate the immunological mechanisms involved. However, no anaphylaxis model exists for Pru p 3. We aimed to develop a model of peach anaphylaxis by sensitising mice with Pru p 3 in combination with lipopolysaccharide (LPS) as an adjuvant. Four groups of mice were sensitised intranasally: untreated; treated with Pru p 3; treated with LPS; treated with Pru p 3 + LPS. After sensitisation mice were intraperitoneally challenged with Pru p 3 and in vivo and in vitro parameters were evaluated. Only mice in the Pru p 3 + LPS group showed anaphylaxis symptoms, including a decrease in temperature. Determination of in vitro parameters showed a Th2 response with an increase of Pru p 3-specific IgE and IgG1. Moreover, at the cellular level, we found increased levels of IgE and IgG1 secreting Pru p 3-specific cells and a proliferative CD4+ T-cell response. These results demonstrate that Pru p 3-specific anaphylaxis can be generated after nasal sensitisation to Pru p 3 in combination with LPS. This is a promising model for evaluating food allergy immunotherapies.
Improvement of Uveal and Capsular Biocompatibility of Hydrophobic Acrylic Intraocular Lens by Surface Grafting with 2-Methacryloyloxyethyl Phosphorylcholine-Methacrylic Acid Copolymer
Authors: Tan Xuhua , Zhan Jiezhao , Zhu Yi , Cao Ji , Wang Lin , Liu Sa , Wang Yingjun , Liu Zhenzhen , Qin Yingyan , Wu Mingxing , Liu Yizhi , Ren Li 
Published: January 2017

AbstractBiocompatibility of intraocular lens (IOL) is critical to vision reconstruction after cataract surgery. Foldable hydrophobic acrylic IOL is vulnerable to the adhesion of extracellular matrix proteins and cells, leading to increased incidence of postoperative inflammation and capsule opacification. To increase IOL biocompatibility, we synthesized a hydrophilic copolymer P(MPC-MAA) and grafted the copolymer onto the surface of IOL through air plasma treatment. X-ray photoelectron spectroscopy, atomic force microscopy and static water contact angle were used to characterize chemical changes, topography and hydrophilicity of the IOL surface, respectively. Quartz crystal microbalance with dissipation (QCM-D) showed that P(MPC-MAA) modified IOLs were resistant to protein adsorption. Moreover, P(MPC-MAA) modification inhibited adhesion and proliferation of lens epithelial cells (LECs)in vitro. To analyze uveal and capsular biocompatibilityin vivo, we implanted the P(MPC-MAA) modified IOLs into rabbits after phacoemulsification. P(MPC-MAA) modification significantly reduced postoperative inflammation and anterior capsule opacification (ACO), and did not affect posterior capsule opacification (PCO). Collectively, our study suggests that surface modification by P(MPC-MAA) can significantly improve uveal and capsular biocompatibility of hydrophobic acrylic IOL, which could potentially benefit patients with blood-aqueous barrier damage.
Repair of osteochondral defects with in vitro engineered cartilage based on autologous bone marrow stromal cells in a swine model
Authors: He Aijuan , Liu Lina , Luo Xusong , Liu Yu , Liu Yi , Liu Fangjun , Wang Xiaoyun , Zhang Zhiyong , Zhang Wenjie , Liu Wei , Cao Yilin , Zhou Guangdong 
Published: January 2017

AbstractFunctional reconstruction of large osteochondral defects is always a major challenge in articular surgery. Some studies have reported the feasibility of repairing articular osteochondral defects using bone marrow stromal cells (BMSCs) and biodegradable scaffolds. However, no significant breakthroughs have been achieved in clinical translation due to the instability ofin vivocartilage regeneration based on direct cell-scaffold construct implantation. To overcome the disadvantages of direct cell-scaffold construct implantation, the current study proposed anin vitrocartilage regeneration strategy, providing relatively mature cartilage-like tissue with superior mechanical properties. Our strategy involvedin vitrocartilage engineering, repair of osteochondral defects, and evaluation ofin vivorepair efficacy. The results demonstrated that BMSC engineered cartilagein vitro(BEC-vitro) presented a time-depended maturation process. The implantation of BEC-vitro alone could successfully realize tissue-specific repair of osteochondral defects with both cartilage and subchondral bone. Furthermore, the maturity level of BEC-vitro had significant influence on the repaired results. These results indicated thatin vitrocartilage regeneration using BMSCs is a promising strategy for functional reconstruction of osteochondral defect, thus promoting the clinical translation of cartilage regeneration techniques incorporating BMSCs.
Inference of immune cell composition on the expression profiles of mouse tissue
Authors: Chen Ziyi , Huang Anfei , Sun Jiya , Jiang Taijiao , Qin F. Xiao-Feng , Wu Aiping 
Published: January 2017

AbstractMice are some of the widely used experimental animal models for studying human diseases. Defining the compositions of immune cell populations in various tissues from experimental mouse models is critical to understanding the involvement of immune responses in various physiological and patho-physiological conditions. However, non-lymphoid tissues are normally composed of vast and diverse cellular components, which make it difficult to quantify the relative proportions of immune cell types. Here we report the development of a computational algorithm, ImmuCC, to infer the relative compositions of 25 immune cell types in mouse tissues using microarray-based mRNA expression data. The ImmuCC algorithm showed good performance and robustness in many simulated datasets. Remarkable concordances were observed when ImmuCC was used on three public datasets, one including enriched immune cells, one with normal single positive T cells, and one with leukemia cell samples. To validate the performance of ImmuCC objectively, thorough cross-comparison of ImmuCC predicted compositions and flow cytometry results was done with in-house generated datasets collected from four distinct mouse lymphoid tissues and three different types of tumor tissues. The good correlation and biologically meaningful results demonstrate the broad utility of ImmuCC for assessing immune cell composition in diverse mouse tissues under various conditions.