bluuebunny/crossref_metadata_2025 huggingface dataset:
Membrane Targeting of Disheveled Can Bypass the Need for Arrow/LRP5
Authors: Kaur Prameet , Lam Vanessa Yuk Man , Mannava Anirudh Gautam , Suresh Jahnavi , Jenny Andreas , Tolwinski Nicholas S.
Published: July 2017

The highly conserved Wnt signaling pathway regulates cell proliferation and differentiation in vertebrates and invertebrates. Upon binding of a Wnt ligand to a receptor of the Fz family, Disheveled (Dsh/Dvl) transduces the signal during canonical and non-canonical Wnt signaling. The specific details of how this process occurs have proven difficult to study, especially as Dsh appears to function as a switch between different branches of Wnt signaling. Here we focus on the membrane-proximal events that occur once Dsh is recruited to the membrane. We show that membrane-tethering of the Dsh protein is sufficient to induce canonical Wnt signaling activation even in the absence of the Wnt co-receptor Arrow/LRP5/6. We map the protein domains required for pathway activation in membrane tethered constructs finding that both the DEP and PDZ domains are dispensable for canonical signaling only in membrane-tethered Dsh, but not in untethered/normal Dsh. These data lead to a signal activation model, where Arrow is required to localize Dsh to the membrane during canonical Wnt signaling placing Dsh downstream of Arrow.
Modified Western blotting for insulin and other diabetes-associated peptide hormones
Authors: Okita Naoyuki , Higami Yoshikazu , Fukai Fumio , Kobayashi Masaki , Mitarai Miku , Sekiya Takao , Sasaki Takashi
Published: July 2017

Now, the quantification of proinsulin/insulin contents within organisms tends to be evaluated only by enzyme-linked immunosorbent assay (ELISA), although assessing the adequacy of results by some quantification method is important. Remarkably, few scientific papers use detection by Western blotting (WB), another immunological assay, of proinsulin/insulin. We found two problems with quantification of insulin and proinsulin by general WB: the shape of an insulin band in gel electrophoresis is distorted, and the retention potency to a blotting membrane of the peptide hormones (mainly insulin) is low. We solved the first problem by optimizing the sodium dodecyl sulfate concentration in the sample buffer and the second problem by glutaraldehyde fixation following treatment with a blocking solution for a short time. The improvements were confirmed by quantification of proinsulin/insulin in standards, MIN6c4 cell lysates, and MIN6c4 culture supernatants. Furthermore, we showed that the modified WB is applicable to other diabetes-associated peptide hormones: insulin analogs, glucagon, GLP-1s, somatostatins, ghrelins, and pancreatic polypeptide. Our data showed that the modified WB can contribute to qualitative or quantitative analyses of diabetes-associated peptides by providing analytical information based on electrophoresis, although ELISA, which is an almost exclusive method in the quantification of peptide hormones, supplies only numerical data.
Erratum: Perfluorooctanesulfonate (PFOS)-induced Sertoli cell injury through a disruption of F-actin and microtubule organization is mediated by Akt1/2
Authors: Gao Ying , Chen Haiqi , Xiao Xiang , Lui Wing-yee , Lee Will M. , Mruk Dolores D. , Cheng C. Yan
Published: July 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.
Biosynthesis of brain cytoplasmic 200 RNA
Authors: Kim Youngmi , Lee Jungmin , Shin Heegwon , Jang Seonghui , Kim Sun Chang , Lee Younghoon
Published: July 2017

Brain cytoplasmic 200 RNA (BC200 RNA), a neuron-specific non-coding RNA, is also highly expressed in a number of tumors of non-neuronal origin. However, the biosynthesis of BC200 RNA remains poorly understood. In this study, we show that the efficient transcription of BC200 RNA requires both internal and upstream promoter elements in cancer cells. The transcription complex seems to interact with a broad range of sequences within the upstream 100-bp region. The cellular levels and half-lives of BC200 RNA were found to differ across various cancer cell types, but there was no significant correlation between these parameters. Exogenously expressed BC200 RNA had a shorter half-life than that observed for the endogenous version in cancer cells, suggesting that BC200 RNA might be protected by some limiting factor(s) in cancer cells. Transient transfection experiments showed that the transcriptional activity of the exogenous BC200 RNA promoter element varied depending on the cancer cell type. However, the promoter activities together with the half-life data could not explain the differences in the levels of BC200 RNA among different cell types, suggesting that there is another level of transcriptional regulation beyond that detected by our transient transfection experiments.
Ethylene, an early marker of systemic inflammation in humans
Authors: Paardekooper Laurent M. , van den Bogaart Geert , Kox Matthijs , Dingjan Ilse , Neerincx Anne H. , Bendix Maura B. , Beest Martin ter , Harren Frans J. M. , Risby Terence , Pickkers Peter , Marczin Nandor , Cristescu Simona M.
Published: July 2017

Ethylene is a major plant hormone mediating developmental processes and stress responses to stimuli such as infection. We show here that ethylene is also produced during systemic inflammation in humans and is released in exhaled breath. Traces of ethylene were detected by laser spectroscopy bothin vitroin isolated blood leukocytes exposed to bacterial lipopolysaccharide (LPS) as well asin vivofollowing LPS administration in healthy volunteers. Exposure to LPS triggers formation of ethylene as a product of lipid peroxidation induced by the respiratory burst. In humans, ethylene was detected prior to the increase of blood levels of inflammatory cytokines and stress-related hormones. Our results highlight that ethylene release is an early and integral component ofin vivolipid peroxidation with important clinical implications as a breath biomarker of bacterial infection.
Serotonin hormonally regulates lacrimal gland secretory function via the serotonin type 3a receptor
Authors: Imada Toshihiro , Nakamura Shigeru , Hisamura Ryuji , Izuta Yusuke , Jin Kai , Ito Masataka , Kitamura Naoki , Tanaka Kenji F. , Mimura Masaru , Shibuya Izumi , Tsubota Kazuo
Published: July 2017

Tears are extracellular fluid secreted from the lacrimal gland (LG). Tears consist of a dynamic tri-layered film composed of secretions from the LG, Meibomian gland, and conjunctival goblet cells. The LG secretes the aqueous component of the tear, the Meibomian gland secretes the lipid component, and conjunctival goblet cells secrete mucin. The regulation of LG activity via the autonomic nervous system has been recognized as fundamental to maintaining aqueous tear flow. Here, we describe the role of a hormone, peripheral serotonin, in tear secretion. We found that blood serotonin concentration, changed by feeding a diet deprived of the serotonin precursor tryptophan, correlated with tear secretion, and that a sustained decrease in serotonin resulted in LG atrophy and autophagy. The combination of a decrease in serotonin with the interruption of autonomic neural stimuli to the LG preceded these alterations. Furthermore, we found that the serotonin type 3a receptor expressed in LG acinar cells is involved in tear secretion via intracellular calcium mobilization. Our findings demonstrate that hormonal regulation by serotonin, in cooperation with the autonomic nervous system, regulates tear secretion.
Protected State Transfer via an Approximate Quantum Adder
Authors: Gatti G. , Barberena D. , Sanz M. , Solano E.
Published: July 2017

We propose a decoherence protected protocol for sending single photon quantum states through depolarizing channels. This protocol is implemented via an approximate quantum adder engineered through spontaneous parametric down converters, and shows higher success probability than distilled quantum teleportation protocols for distances below a threshold depending on the properties of the channel.
Diurnal preference, mood and the response to morning light in relation to polymorphisms in the human clock gene PER3
Authors: Turco M. , Biscontin A. , Corrias M. , Caccin L. , Bano M. , Chiaromanni F. , Salamanca M. , Mattei D. , Salvoro C. , Mazzotta G. , De Pittà C. , Middleton B. , Skene D. J. , Montagnese S. , Costa R.
Published: July 2017

PER3gene polymorphisms have been associated with differences in human sleep-wake phenotypes, and sensitivity to light. The aims of this study were to assess:i) the frequency of allelic variants at twoPER3polymorphic sites (rs57875989 length polymorphism:PER34,PER35; rs228697 SNP:PER3C,PER3G) in relation to sleep-wake timing;ii) the effect of morning light on behavioural/circadian variables inPER34/PER34andPER35/PER35homozygotes. 786 Caucasian subjects living in Northern Italy donated buccal DNA and completed diurnal preference, sleep quality/timing and sleepiness/mood questionnaires. 19PER34/PER34and 11PER35/PER35homozygotes underwent morning light administration, whilst monitoring sleep-wake patterns and the urinary 6-sulphatoxymelatonin (aMT6s) rhythm. No significant relationship was observed between the length polymorphism and diurnal preference. By contrast, a significant association was observed between thePER3Gvariant and morningness (OR = 2.10), and between thePER3G-PER34haplotype and morningness (OR = 2.19), for which a mechanistic hypothesis is suggested. No significant differences were observed in sleep timing/aMT6s rhythms betweenPER35/PER35andPER34/PER34subjects at baseline. After light administration,PER34/PER34subjects advanced their aMT6s acrophase (p < 0.05), and showed a trend of advanced sleep-wake timing. In conclusion, significant associations were observed betweenPER3polymorphic variants/their combinations and both diurnal preference and the response to light.
Characterisation and pharmacological analysis of a crustacean G protein-coupled receptor: the red pigment-concentrating hormone receptor of Daphnia pulex
Authors: Marco Heather G. , Verlinden Heleen , Vanden Broeck Jozef , Gäde Gerd
Published: July 2017

This is the first pharmacological characterisation of a neuropeptide G protein-coupled receptor (GPCR) in a crustacean. We cloned the ORF of the red pigment-concentrating hormone from a German strain of Daphnia pulex (Dappu-RPCH), as well as that of the cognate receptor (Dappu-RPCHR). Dappu-RPCHR has the hallmarks of the rhodopsin superfamily of GPCRs, and is more similar to insect adipokinetic hormone (AKH) receptor sequences than to receptor sequences for AKH/corazonin-like peptide or corazonin. We provide experimental evidence that Dappu-RPCH specifically activates the receptor (EC50 value of 65 pM) in a mammalian cell-based bioluminescence assay. We further characterised the properties of the ligands for the Dappu-RPCHR by investigating the activities of a variety of naturally-occurring peptides (insect AKH and crustacean RPCH peptides). The insect AKHs had lower EC50 values than the crustacean RPCHs. In addition, we tested a series of Dappu-RPCH analogues, where one residue at a time is systematically replaced by an alanine to learn about the relative importance of the termini and side chains for activation. Mainly amino acids in positions 1 to 4 and 8 of Dappu-RPCH appear responsible for effective activation of Dappu-RPCHR. The substitution of Phe4 in Dappu-RPCH had the most damaging effect on its agonistic activity.
Laser induced strong-field ionization gas jet tomography
Authors: Tchulov Oshrat , Negro Matteo , Stagira Salvatore , Devetta Michele , Vozzi Caterina , Frumker Eugene
Published: July 2017

We introduce a novel in-situ strong field ionization tomography approach for characterizing the spatial density distribution of gas jets. We show that for typical intensities in high harmonic generation experiments, the strong field ionization mechanism used in our approach provides an improvement in the resolution close to factor of 2 (resolving about 8 times smaller voxel volume), when compared to linear/single-photon imaging modalities. We find, that while the depth of scan in linear tomography is limited by resolution loss due to the divergence of the driving laser beam, in the proposed approach the depth of focus is localized due to the inherent physical nature of strong-field interaction and discuss implications of these findings. We explore key aspects of the proposed method and compare it with commonly used single- and multi-photon imaging mechanisms. The proposed method will be particularly useful for strong field and attosecond science experiments.
Combined serum levels of multiple proteins in tPA-BDNF pathway may aid the diagnosis of five mental disorders
Authors: Chen Suzhen , Jiang Haitang , Liu Yang , Hou Zhenhua , Yue Yingying , Zhang Yuqun , Zhao Fuying , Xu Zhi , Li Yinghui , Mou Xiaodong , Li Lei , Wang Tianyu , Zhao Jingjing , Han Chongyang , Sui Yuxiu , Wang Ming , Yang Zhong , Lu Yan , Zhu Yifeng , Li Jianhua , Shen Xinhua , Sun Fei , Chen Qingsong , Chen Huanxin , Yuan Yonggui
Published: July 2017

Mental disorders are severe, disabling conditions with unknown etiology and are commonly misdiagnosed when clinical symptomology criteria are solely used. Our previous work indicated that combination of serum levels of multiple proteins in tissue plasminogen activator (tPA)-brain-derived neurotrophic factor (BDNF) pathway improved accuracy of diagnosis of major depressive disorder (MDD). Here, we measured serum levels of tPA, plasminogen activator inhibitor-1 (PAI-1), BDNF, precursor-BDNF (proBDNF), tropomyosin-related kinase B (TrkB) and neurotrophin receptor p75 (p75NTR) in patients with paranoid schizophrenia (SZ, n = 34), MDD (n = 30), bipolar mania (BM, n = 30), bipolar depression (BD, n = 22), panic disorder (PD, n = 30), and healthy controls (HCs, n = 30) by Enzyme-linked immunosorbent assay kits. We used receiver operating characteristic (ROC) curve to analyze diagnostic potential of these proteins. We found, compared with HCs, that serum tPA and proBDNF were lower in SZ, BM and BD; TrkB was lower in SZ and BD; and p75NTR was declined in SZ and BM. ROC analysis showed that combined serum level of tPA, PAI-1, BDNF, proBDNF, TrkB and p75NTR was better than any single protein in accuracy of diagnosis and differentiation, suggesting that the combination of multiple serum proteins levels in tPA-BDNF pathway may have a potential for a diagnostic panel in mental disorders.
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(4.2 K, 31.2 T) beyond 1 kA/mm2 of a ~3.2 μm thick, 20 mol% Zr-added MOCVD REBCO coated conductor
Authors: Xu A. , Zhang Y. , Gharahcheshmeh M. Heydari , Yao Y. , Galstyan E. , Abraimov D. , Kametani F. , Polyanskii A. , Jaroszynski J. , Griffin V. , Majkic G. , Larbalestier D. C. , Selvamanickam V.
Published: July 2017

A main challenge that significantly impedes REBa2Cu3Ox (RE = rare earth) coated conductor applications is the low engineering critical current density J
e
because of the low superconductor fill factor in a complicated layered structure that is crucial for REBa2Cu3Ox to carry supercurrent. Recently, we have successfully achieved engineering critical current density beyond 2.0 kA/mm2 at 4.2 K and 16 T, by growing thick REBa2Cu3Ox layer, from ∼1.0 μm up to ∼3.2 μm, as well as controlling the pinning microstructure. Such high engineering critical current density, the highest value ever observed so far, establishes the essential role of REBa2Cu3Ox coated conductors for very high field magnet applications. We attribute such excellent performance to the dense c-axis self-assembled BaZrO3 nanorods, the elimination of large misoriented grains, and the suppression of big second phase particles in this ~3.2 μm thick REBa2Cu3Ox film.
The basal translation rate of authentic HIV-1 RNA is regulated by 5’UTR nt-pairings at junction of R and U5
Authors: Boeras I. , Seufzer B. , Brady S. , Rendahl A. , Heng X. , Boris-Lawrie K.
Published: July 2017

The paradigm protein synthesis rate is regulated by structural complexity of the 5′untranslated region (UTR) derives from bacterial and other riboswitches. In-solution, HIV-1 5′UTR forms two interchangeable long-range nucleotide (nt) -pairings, one sequesters the gag start codon promoting dimerization while the other sequesters the dimer initiation signal preventing dimerization. While the effect of these nt-pairings on dimerization and packaging has been documented their effect on authentic HIV translation in cellulo has remained elusive until now. HIVNL4-3 5′UTR substitutions were designed to individually stabilize the dimer-prone or monomer-prone conformations, validated in-solution, and introduced to molecular clones. The effect of 5′UTR conformation on ribosome loading to HIV unspliced RNA and rate of Gag polypeptide synthesis was quantified in cellulo. Monomer- and dimer-prone 5′UTRs displayed equivalent, basal rate of translation. Gain-of-function substitution U103, in conjunction with previously defined nt-pairings that reorient AUG to flexible nt-pairing, significantly activated the translation rate, indicating the basal translation rate is under positive selection. The observed translation up-mutation focuses attention to nt-pairings at the junction of R and U5, a poorly characterized structure upstream of the characterized HIV riboswitch and demonstrates the basal translation rate of authentic HIV RNA is regulated independently of monomer:dimer equilibrium of the 5′UTR.
A Glucose Sensing System Based on Transmission Measurements at Millimetre Waves using Micro strip Patch Antennas
Authors: Saha Shimul , Cano-Garcia Helena , Sotiriou Ioannis , Lipscombe Oliver , Gouzouasis Ioannis , Koutsoupidou Maria , Palikaras George , Mackenzie Richard , Reeve Thomas , Kosmas Panagiotis , Kallos Efthymios
Published: July 2017

We present a sensing system operating at millimetre (mm) waves in transmission mode that can measure glucose level changes based on the complex permittivity changes across the signal path. The permittivity of a sample can change significantly as the concentration of one of its substances varies: for example, blood permittivity depends on the blood glucose levels. The proposed sensing system uses two facing microstrip patch antennas operating at 60 GHz, which are placed across interrogated samples. The measured transmission coefficient depends on the permittivity change along the signal path, which can be correlated to the change in concentration of a substance. Along with theoretical estimations, we experimentally demonstrate the sensing performance of the system using controlled laboratory samples, such as water-based glucose-loaded liquid samples. We also present results of successful glucose spike detection in humans during an in-vivo Intravenous Glucose Tolerance Test (IVGTT). The system could eventually be developed into a non-invasive glucose monitor for continuous monitoring of glucose levels for people living with diabetes, as it can detect as small as 1.33 mmol/l (0.025 wt%) glucose concentrations in the controlled water-based samples satisfactorily, which is well below the typical human glucose levels of 4 mmol/l.
Exendin-4 reduces food intake via the PI3K/AKT signaling pathway in the hypothalamus
Authors: Yang Yan , Choi Pique P. , Smith Wanli W. , Xu Weijie , Ma Delin , Cordner Zachary A. , Liang Nu-Chu , Moran Timothy H.
Published: July 2017

Exendin-4 (EX-4), a glucagon-like peptide-1 (GLP-1) receptor agonist, has been shown to reduce food intake and to increase proopiomelanocortin (POMC) gene expression in the hypothalamus. In this study, we examined the potential neural mechanisms by which these effects occur. Male Sprague Dawley rats were implanted with a cannula in the third ventricle of the brain through which an inhibitor of phosphatidylinositol-3 kinase (PI3K) (wortmannin) was administered, and EX-4 or vehicle was administered via intraperitoneal (IP) injection. The activity of PI3K/protein kinase B (AKT) and insulin receptor substrate-1 (IRS-1) in the hypothalamic arcuate was determined. We found that EX-4 treatment significantly decreased food intake and body weight. However, there were almost no changes in food intake and body weight when wortmannin injection (into the third ventricle) occurred prior to EX-4 IP injection. EX-4 not only increased the activity of PI3K/AKT, but it also increased IRS-1 activity. These results show that EX-4 likely suppresses food intake due to its ability to enhance insulin signaling.
Approach of automatic 3D geological mapping: the case of the Kovdor phoscorite-carbonatite complex, NW Russia
Authors: Kalashnikov A. O. , Ivanyuk G. Yu , Mikhailova J. A. , Sokharev V. A.
Published: July 2017

We have developed an approach for automatic 3D geological mapping based on conversion of chemical composition of rocks to mineral composition by logical computation. It allows to calculate mineral composition based on bulk rock chemistry, interpolate the mineral composition in the same way as chemical composition, and, finally, build a 3D geological model. The approach was developed for the Kovdor phoscorite-carbonatite complex containing the Kovdor baddeleyite-apatite-magnetite deposit. We used 4 bulk rock chemistry analyses – Femagn, P2O5, CO2 and SiO2. We used four techniques for prediction of rock types – calculation of normative mineral compositions (norms), multiple regression, artificial neural network and developed by logical evaluation. The two latter became the best. As a result, we distinguished 14 types of phoscorites (forsterite-apatite-magnetite-carbonate rock), carbonatite and host rocks. The results show good convergence with our petrographical studies of the deposit, and recent manually built maps. The proposed approach can be used as a tool of a deposit genesis reconstruction and preliminary geometallurgical modelling.
Towards Picogram Detection of Superparamagnetic Iron-Oxide Particles Using a Gradiometric Receive Coil
Authors: Graeser Matthias , Knopp Tobias , Szwargulski Patryk , Friedrich Thomas , von Gladiss Anselm , Kaul Michael , Krishnan Kannan M , Ittrich Harald , Adam Gerhard , Buzug Thorsten M.
Published: July 2017

Superparamagnetic iron-oxide nanoparticles can be used in medical applications like vascular or targeted imaging. Magnetic particle imaging (MPI) is a promising tomographic imaging technique that allows visualizing the 3D nanoparticle distribution concentration in a non-invasive manner. The two main strengths of MPI are high temporal resolution and high sensitivity. While the first has been proven in the assessment of dynamic processes like cardiac imaging, it is unknown how far the detection limit of MPI can be lowered. Within this work, we will present a highly sensitive gradiometric receive-coil unit combined with a noise-matching network tailored for the imaging of mice. The setup is capable of detecting 5 ng of iron in-vitro with an acquisition time of 2.14 sec. In terms of iron concentration we are able to detect 156 μg/L marking the lowest value that has been reported for an MPI scanner so far. In-vivo MPI mouse images of a 512 ng bolus and a 21.5 ms acquisition time allow for capturing the flow of an intravenously injected tracer through the heart of a mouse. Since it has been rather difficult to compare detection limits across MPI publications we propose guidelines to improve the comparability of future MPI studies.
PLA2R binds to the annexin A2-S100A10 complex in human podocytes
Authors: Fresquet Maryline , Jowitt Thomas A. , McKenzie Edward A. , Ball Matthew D. , Randles Michael J. , Lennon Rachel , Brenchley Paul E.
Published: July 2017

Phospholipase A2 receptor (PLA2R) is a member of the mannose receptor family found in podocytes in human kidney. PLA2R is the target of the autoimmune disease, membranous nephropathy, characterised by production of anti-PLA2R autoantibodies which bind to the podocyte. However the function of PLA2R in health and in disease remains unclear. To gain insight into the molecular mechanisms of PLA2R function, we searched for its endogenous binding partners. Proteomic analysis identified annexinA2 as a potential interactor with the extracellular domains of PLA2R. We confirmed that PLA2R binds to annexinA2-S100A10 (A2t) complex with specific high affinity to the S100A10 component. The binding occured within the PLA2R NC3 fragment and was increased in acidic pH. Furthermore Ca2+ promoted the association of the PLA2R-A2t complex with phospholipid membranes in vitro. Within the podocyte, all three proteins were enriched in the plasma membrane and organelle membrane compartments. PLA2R co-localised with S100A10 at the cell surface and in extracellular vesicles. This novel interaction between PLA2R and the A2t complex offers insights into the role of PLA2R in podocytes and how autoantibodies might disrupt PLA2R function. The ability of podocytes to secrete vesicles containing PLA2R provides a route for engagement of PLA2R with the immune system.
Interface-induced spontaneous positive and conventional negative exchange bias effects in bilayer La0.7Sr0.3MnO3/Eu0.45Sr0.55MnO3 heterostructures
Authors: Murthy J. Krishna , Kumar P. S. Anil
Published: July 2017

We report zero-field-cooled spontaneous-positive and field-cooled conventional-negative exchange bias effects in epitaxial bilayer composed of La0.7Sr0.3MnO3 (LSMO) with ferromagnetic (FM) and Eu0.45Sr0.55MnO3 (ESMO) with A-type antiferromagnetic (AF) heterostructures respectively. A temperature dependent magnetization study of LSMO/ESMO bilayers grown on SrTiO3 (001) manifest FM ordering (TC) of LSMO at ~320 K, charge/orbital ordering of ESMO at ~194 K and AF ordering (TN) of ESMO at ~150 K. The random field Ising model has demonstrated an interesting observation of inverse dependence of exchange bias effect on AF layer thickness due to the competition between FM-AF interface coupling and AF domain wall energy. The isothermally field induced unidirectional exchange anisotropy formed at the interface of FM-LSMO layer and the kinetically phase-arrested magnetic phase obtained from the metamagnetic AF-ESMO layer could be responsible for the spontaneous exchange bias effect. Importantly, no magnetic poling is needed, as necessary for the applications. The FM-AF interface exchange interaction has been ascribed to the AF coupling with $$\sum {J}_{ex}\vec{{S}_{{\rm{FM}}}}\cdot \vec{{S}_{{\rm{AF}}}}$$
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, coupling constant between AF spins) for the spontaneous positive hysteresis loop shift, and the field-cooled conventional exchange bias has been attributed to the ferromagnetically exchanged interface with $${J}_{ex}\approx {J}_{F}$$

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(coupling constant between FM spins).
Plant survival and keystone pollinator species in stochastic coextinction models: role of intrinsic dependence on animal-pollination
Authors: Traveset Anna , Tur Cristina , Eguíluz Víctor M.
Published: July 2017

Coextinction models are useful to understand community robustness to species loss and resilience to disturbances. We simulated pollinator extinctions in pollination networks by using a hybrid model that combined a recently developed stochastic coextinction model (SCM) for plant extinctions and a topological model (TCM) for animal extinctions. Our model accounted for variation in interaction strengths and included empirical estimates of plant dependence on pollinators to set seeds. The stochastic nature of such model allowed us determining plant survival to single (and multiple) extinction events, and identifying which pollinators (keystone species) were more likely to trigger secondary extinctions. Consistently across three different pollinator removal sequences, plant robustness was lower than in a pure TCM, and plant survival was more determined by dependence on the mutualism than by interaction strength. As expected, highly connected and dependent plants were the most sensitive to pollinator loss and collapsed faster in extinction cascades. We predict that the relationship between dependence and plant connectivity is crucial to determine network robustness to interaction loss. Finally, we showed that honeybees and several beetles were keystone species in our communities. This information is of great value to foresee consequences of pollinator losses facing current global change and to identify target species for effective conservation.
Elevated levels of the stress hormone, corticosterone, cause ‘pessimistic’ judgment bias in broiler chickens
Authors: Iyasere Oluwaseun S. , Beard Andrew P. , Guy Jonathan H. , Bateson Melissa
Published: July 2017

Pessimistic judgment biases, whereby humans or non-human animals interpret ambiguous information negatively, are hypothesised to be one of the suite of adaptive changes that comprise the vertebrate stress response. To test this hypothesis, we asked whether experimentally elevating levels of the glucocorticoid stress hormone, corticosterone, in broiler chickens produced a pessimistic judgment bias. We trained young chickens to discriminate a stimulus (paper cone) placed at two locations in an arena, one associated with reward (mealworms) and one with punishment (air puff). During seven days of non-invasive administration of either corticosterone or vehicle control, we tested the birds’ responses to the cone placed at ambiguous locations between the trained locations. Corticosterone-treated birds were more likely than controls to respond as if punishment was likely when the cone was placed near to the punished location. The degree of this ‘pessimism’ was associated with smaller relative spleen weight, which is a documented consequence of chronic stress in chickens. We conclude that changes in corticosterone levels in chickens are sufficient to cause a specific change in decision making, dubbed ‘pessimism’, whereby corticosterone-treated birds showed an increased expectation of punishment in the face of ambiguous information. Pessimism could be a useful welfare indicator in chickens.
Durability and Self-healing Effects of Hydrogel Coatings with respect to Contact Condition
Authors: Kim Chang-Lae , Kim Dae-Eun
Published: July 2017

The self-healing property of a hydrogel applied to a glass substrate as a thin polymer coating was assessed. The motivation was to develop a durable hydrogel coating that may be used to protect the surface of precision components from surface damage and scratches. The intrinsic swelling behavior of hydrogel fibers when they are exposed to moisture was exploited to attain the self-healing effect. The mechanical and self-healing properties of the dehydrated hydrogel coating by the freeze-drying process and the hydrated hydrogel coating that was reconstituted by the addition of water were analyzed. After conducting sliding tests with different loads and sliding distances, the wear area was hydrated with water to successfully induce self-healing of the hydrogel coating. It was also found that both the dehydrated hydrogel coating and the hydrated hydrogel coating had improved friction characteristics. In particular, the hydrated hydrogel coating had a much higher durability than the dehydrated coating.
Homocysteine induces mitochondrial dysfunction involving the crosstalk between oxidative stress and mitochondrial pSTAT3 in rat ischemic brain
Authors: Chen Shuang , Dong Zhiping , Zhao Yaqian , Sai Na , Wang Xuan , Liu Huan , Huang Guowei , Zhang Xumei
Published: July 2017

Homocysteine (Hcy) has been shown to have a neurotoxic effect on ischemic brain cells; however, the underlying mechanisms remain incompletely understood. Here, we examined whether Hcy treatment influences mitochondria injury, oxidative stress, and mitochondrial STAT3 (mitoStat3) expression in rat ischemic brain. Our results demonstrated that Hcy treatment aggravated the damage of mitochondrial ultrastructure in the brain cortex and the dentate gyrus region of the hippocampus after focal cerebral ischemia. An elevated Hcy level was also accompanied by the significant inhibition of mitochondrial complex I–III enzymatic activities in addition to an increase in cytochrome c release. 8-Hydroxy-2′-deoxyguanosine (8-OHdG) content and mitoStat3 protein phosphorylation level were increased in Hcy-treated animals, whereas AG490, a Jak2 inhibitor, inhibited mitoStat3 phosphorylation as well as 8-OHdG levels induced by Hcy. In vitro studies revealed that Hcy also markedly increased reactive oxygen species (ROS) and mitoStat3 levels. In addition, the inhibition of pSTAT3 reduced Hcy-mediated increase in ROS levels, whereas quenching ROS using the ROS inhibitor glutathione ethyl ester inhibited Hcy-mediated pSTAT3 overactivation in Neuro2a cells. These findings suggest that the development of therapies that interfere with the ROS/pSTAT3 pathway may be helpful for treating cerebral infarction-related diseases associated with Hcy.
Associations between subjective well-being and subcortical brain volumes
Authors: Van ‘t Ent D. , den Braber A. , Baselmans B. M. L. , Brouwer R. M. , Dolan C. V. , Hulshoff Pol H. E. , de Geus E. J. C. , Bartels M.
Published: July 2017

To study the underpinnings of individual differences in subjective well-being (SWB), we tested for associations of SWB with subcortical brain volumes in a dataset of 724 twins and siblings. For significant SWB-brain associations we probed for causal pathways using Mendelian Randomization (MR) and estimated genetic and environmental contributions from twin modeling. Another independent measure of genetic correlation was obtained from linkage disequilibrium (LD) score regression on published genome-wide association summary statistics. Our results indicated associations of SWB with hippocampal volumes but not with volumes of the basal ganglia, thalamus, amygdala, or nucleus accumbens. The SWB-hippocampus relations were nonlinear and characterized by lower SWB in subjects with relatively smaller hippocampal volumes compared to subjects with medium and higher hippocampal volumes. MR provided no evidence for an SWB to hippocampal volume or hippocampal volume to SWB pathway. This was in line with twin modeling and LD-score regression results which indicated non-significant genetic correlations. We conclude that low SWB is associated with smaller hippocampal volume, but that genes are not very important in this relationship. Instead other etiological factors, such as exposure to stress and stress hormones, may exert detrimental effects on SWB and the hippocampus to bring about the observed association.
ROCK1 is a novel Rac1 effector to regulate tubular endocytic membrane formation during clathrin-independent endocytosis
Authors: Soriano-Castell David , Chavero Albert , Rentero Carles , Bosch Marta , Vidal-Quadras Maite , Pol Albert , Enrich Carlos , Tebar Francesc
Published: July 2017

Clathrin-dependent and -independent pathways contribute for β1-integrin endocytosis. This study defines a tubular membrane clathrin-independent endocytic network, induced with the calmodulin inhibitor W13, for β1-integrin internalization. This pathway is dependent on increased phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) levels and dynamin activity at the plasma membrane. Exogenous addition of PI(4,5)P2 or phosphatidylinositol-4-phosphate 5-kinase (PIP5K) expression mimicked W13-generated-tubules which are inhibited by active Rac1. Therefore, the molecular mechanisms downstream of Rac1, that controls this plasma membrane tubulation, were analyzed biochemically and by the expression of different Rac1 mutants. The results indicate that phospholipase C and ROCK1 are the main Rac1 effectors that impair plasma membrane invagination and tubule formation, essentially by decreasing PI(4,5)P2 levels and promoting cortical actomyosin assembly respectively. Interestingly, among the plethora of proteins that participate in membrane remodeling, this study revealed that ROCK1, the well-known downstream RhoA effector, has an important role in Rac1 regulation of actomyosin at the cell cortex. This study provides new insights into Rac1 functioning on plasma membrane dynamics combining phosphatidylinositides and cytoskeleton regulation.
Effects of pulpotomy using mineral trioxide aggregate on prostaglandin transporter and receptors in rat molars
Authors: Ohkura Naoto , Edanami Naoki , Takeuchi Ryosuke , Tohma Aiko , Ohkura Mariko , Yoshiba Nagako , Yoshiba Kunihiko , Ida-Yonemochi Hiroko , Ohshima Hayato , Okiji Takashi , Noiri Yuichiro
Published: July 2017

Mineral trioxide aggregate (MTA) is a commonly used dental pulp-capping material with known effects in promoting reparative dentinogenesis. However, the mechanism by which MTA induces dentine repair remains unclear. The aim of the present study was to investigate the role of prostaglandin E2(PGE2) in dentine repair by examining the localisation and mRNA expression levels of its transporter (Pgt) and two of its receptors (Ep2 and Ep4) in a rat model of pulpotomy with MTA capping. Ep2 expression was detected in odontoblasts, endothelial cells, and nerve fibres in normal and pulpotomised tissues, whereas Pgt and Ep4 were immunolocalised only in the odontoblasts. Moreover, mRNA expression ofSlco2a1(encoding Pgt),Ptger2(encoding Ep2), andPtger4(encoding Ep4) was significantly upregulated in pulpotomised dental pulp and trigeminal ganglia after MTA capping. Our results provide insights into the functions of PGE2via Pgt and Ep receptors in the healing dentine/pulp complex and may be helpful in developing new therapeutic targets for dental disease.
Regulatory T-cells from pancreatic lymphnodes of patients with type-1 diabetes express increased levels of microRNA miR-125a-5p that limits CCR2 expression
Authors: Sebastiani Guido , Ventriglia Giuliana , Stabilini Angela , Socci Carlo , Morsiani Cristina , Laurenzi Andrea , Nigi Laura , Formichi Caterina , Mfarrej Bechara , Petrelli Alessandra , Fousteri Georgia , Brusko Todd M. , Dotta Francesco , Battaglia Manuela
Published: July 2017

Autoimmune type 1 diabetes (T1D) is thought to be caused by a defective immune regulation with regulatory T (Treg) cells playing a fundamental role in this process. Tolerance mechanisms depend on tunable responses that are sensitive to minor perturbations in the expression of molecules that can be carried out by multiple epigenetic mechanisms, including regulation by microRNAs. In this study, microRNA expression profile was investigated in Treg cells isolated from peripheral blood (PB) and from pancreatic draining lymph nodes (PLN) of T1D patients and non-diabetic subjects. Among 72 microRNAs analyzed, miR-125a-5p resulted specifically hyper-expressed in Treg cells purified from PLN of T1D patients. TNFR2 and CCR2 were identified as miR-125a-5p target genes. Elevated miR-125a-5p was detected in Treg cells isolated from PLN but not from PB of donors with T1D and was associated with reduced CCR2 expression. A specific beta-cell expression of the CCR2-ligand (CCL2) was observed in the pancreata of cadaveric donors, suggesting that beta-cells are prone to attract CCR2+ Treg cells. These novel data propose a mechanism, occurring in PLNs of T1D patients, involving increased expression of miR-125a-5p on Treg cells which results into reduced expression of CCR2, thus limiting their migration and eventual function in the pancreas.
The advantages of endophyte-infected over uninfected tall fescue in the growth and pathogen resistance are counteracted by elevated CO2
Authors: Chen Wei , Liu Hui , Wurihan  , Gao Yubao , Card Stuart D. , Ren Anzhi
Published: July 2017

Atmospheric CO2 concentrations are predicted to double within the next century. Despite this trend, the extent and mechanisms through which elevated CO2 affects grass-endophyte symbionts remain uncertain. In the present study, the growth, chemical composition and pathogen resistance of endophyte-infected (E+) and uninfected (E−) tall fescue were compared under elevated CO2 conditions. The results showed that the effect of endophyte infection on the growth of tall fescue was significantly affected by elevated CO2. Significant advantage of E+ over E− tall fescue in tiller number, maximum net photosynthetic rate and shoot biomass occurred only under ambient CO2. With CO2 concentration elevated, the beneficial effect of endophyte infection on the growth disappeared. Similarly, endophyte infection reduced lesion number and spore concentration of Curvularia lunata only under ambient CO2. These results suggest that the beneficial effect of endophyte infection on the growth and pathogen resistance of tall fescue could be counteracted by elevated CO2. An explanation for the counteraction may be found in a change in photosynthesis and nutritive quality of leaf tissue.
A novel pharmacodynamic assay to evaluate the effects of crystallization inhibitors on calcium phosphate crystallization in human plasma
Authors: Ferrer M. D. , Pérez M. M. , Cànaves M. M. , Buades J. M. , Salcedo C. , Perelló J.
Published: July 2017

Cardiovascular calcification (CVC) is a progressive complication of chronic kidney disease and a predictor of CV events and mortality. The use of biomarkers to predict CV risk and activities of potential or current treatment drugs in these patients could have a crucial impact on therapeutic approaches. Our aim was to develop a novel assay for measurement of the rate of calcium phosphate crystallization in human plasma and provide a tool to evaluate the effects of crystallization inhibitors. The efficacy of inhibitors was determined by adding inhibitory compounds (polyphosphates, fetuin-A, sodium thiosulfate or citrate) to control samples. The assay was additionally validated for SNF472, an experimental formulation of phytate being developed for the treatment of calciphylaxis and CVC in patients with end-stage renal disease (ESRD) undergoing hemodialysis (HD). The method was repeatable and reproducible. The plasma crystallization rate was reduced up to 80% in a concentration-dependent manner following treatment with inhibitors in vitro, among which SNF472 was the most potent. This method appears beneficial in evaluating and discriminating between inhibitory activities of compounds such as polyphosphates on calcium phosphate crystallization, which present a novel therapeutic approach to treat CVC in ESRD patients.
Restricted regions of enhanced growth of Antarctic krill in the circumpolar Southern Ocean
Authors: Murphy Eugene J. , Thorpe Sally E. , Tarling Geraint A. , Watkins Jonathan L. , Fielding Sophie , Underwood Philip
Published: July 2017

Food webs in high-latitude oceans are dominated by relatively few species. Future ocean and sea-ice changes affecting the distribution of such species will impact the structure and functioning of whole ecosystems. Antarctic krill (Euphausia superba) is a key species in Southern Ocean food webs, but there is little understanding of the factors influencing its success throughout much of the ocean. The capacity of a habitat to maintain growth will be crucial and here we use an empirical relationship of growth rate to assess seasonal spatial variability. Over much of the ocean, potential for growth is limited, with three restricted oceanic regions where seasonal conditions permit high growth rates, and only a few areas around the Scotia Sea and Antarctic Peninsula suitable for growth of the largest krill (>60 mm). Our study demonstrates that projections of impacts of future change need to account for spatial and seasonal variability of key ecological processes within ocean ecosystems.
Electronic structure and its external electric field modulation of PbPdO2 ultrathin slabs with (002) and (211) preferred orientations
Authors: Yang Yanmin , Zhong Kehua , Xu Guigui , Zhang Jian-Min , Huang Zhigao
Published: July 2017

The Electronic structure of PbPdO2 with (002) and (211) preferred orientations were investigated using first-principles calculation. The calculated results indicate that, (002) and (211) orientations exhibit different electric field dependence of band-gap and carrier concentration. The small band gap and more sensitive electric field modulation of band gap were found in (002) orientation. Moreover, the electric field modulation of the resistivity up to 3–4 orders of magnitude is also observed in (002) slab, which reveals that origin of colossal electroresistance. Lastly, electric field modulation of band gap is well explained. This work should be significant for repeating the colossal electroresistance.
T2DiACoD: A Gene Atlas of Type 2 Diabetes Mellitus Associated Complex Disorders
Authors: Rani Jyoti , Mittal Inna , Pramanik Atreyi , Singh Namita , Dube Namita , Sharma Smriti , Puniya Bhanwar Lal , Raghunandanan Muthukurussi Varieth , Mobeen Ahmed , Ramachandran Srinivasan
Published: July 2017

We performed integrative analysis of genes associated with type 2 Diabetes Mellitus (T2DM) associated complications by automated text mining with manual curation and also gene expression analysis from Gene Expression Omnibus. They were analysed for pathogenic or protective role, trends, interaction with risk factors, Gene Ontology enrichment and tissue wise differential expression. The database T2DiACoD houses 650 genes, and 34 microRNAs associated with T2DM complications. Seven genes AGER, TNFRSF11B, CRK, PON1, ADIPOQ, CRP and NOS3 are associated with all 5 complications. Several genes are studied in multiple years in all complications with high proportion in cardiovascular (75.8%) and atherosclerosis (51.3%). T2DM Patients’ skeletal muscle tissues showed high fold change in differentially expressed genes. Among the differentially expressed genes, VEGFA is associated with several complications of T2DM. A few genes ACE2, ADCYAP1, HDAC4, NCF1, NFE2L2, OSM, SMAD1, TGFB1, BDNF, SYVN1, TXNIP, CD36, CYP2J2, NLRP3 with details of protective role are catalogued. Obesity is clearly a dominant risk factor interacting with the genes of T2DM complications followed by inflammation, diet and stress to variable extents. This information emerging from the integrative approach used in this work could benefit further therapeutic approaches. The T2DiACoD is available at www.http://t2diacod.igib.res.in/.
Single vector non-leaky gene expression system for Drosophila melanogaster
Authors: Akmammedov Arslan , Geigges Marco , Paro Renato
Published: July 2017

An ideal transgenic gene expression system is inducible, non-leaky, and well tolerated by the target organism. While the former has been satisfactorily realized, leakiness and heavy physiological burden imposed by the existing systems are still prominent hurdles in their successful implementation. Here we describe a new system for non-leaky expression of transgenes in Drosophila. PRExpress is based on a single transgenic construct built from endogenous components, the inducible hsp70 promoter and a multimerized copy of a Polycomb response element (PRE) controlled by epigenetic chromatin regulators of the Polycomb group. We show that this system is non-leaky, rapidly and strongly inducible, and reversible. To make the application of PRExpress user-friendly, we deliver the construct via site-specific integration.