bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coupling optogenetic stimulation with NanoLuc-based luminescence (BRET) Ca++ sensing
Authors: Yang Jie , Cumberbatch Derrick , Centanni Samuel , Shi Shu-qun , Winder Danny , Webb Donna , Johnson Carl Hirschie 
Published: October 2016

AbstractOptogenetic techniques allow intracellular manipulation of Ca++ by illumination of light-absorbing probe molecules such as channelrhodopsins and melanopsins. The consequences of optogenetic stimulation would optimally be recorded by non-invasive optical methods. However, most current optical methods for monitoring Ca++ levels are based on fluorescence excitation that can cause unwanted stimulation of the optogenetic probe and other undesirable effects such as tissue autofluorescence. Luminescence is an alternate optical technology that avoids the problems associated with fluorescence. Using a new bright luciferase, we here develop a genetically encoded Ca++ sensor that is ratiometric by virtue of bioluminescence resonance energy transfer (BRET). This sensor has a large dynamic range and partners optimally with optogenetic probes. Ca++ fluxes that are elicited by brief pulses of light to cultured cells expressing melanopsin and to neurons-expressing channelrhodopsin are quantified and imaged with the BRET Ca++ sensor in darkness, thereby avoiding undesirable consequences of fluorescence irradiation.
Mesenchymal state of intimal cells may explain higher propensity to ascending aortic aneurysm in bicuspid aortic valves
Authors: Maleki Shohreh , Kjellqvist Sanela , Paloschi Valentina , Magné Joelle , Branca Rui Miguel Mamede , Du Lei , Hultenby Kjell , Petrini Johan , Fuxe Jonas ,   MIBAVA Leducq Consortium, Dietz Harry C. , Loeys Bart , Van Laer Lut , McCallion Andrew S. , Mertens Luc , Mital Seema , Mohamed Salah A. , Andelfinger Gregor , Lehtiö Janne , Franco-Cereceda Anders , Eriksson Per , Björck Hanna M. 
Published: October 2016

AbstractIndividuals with a bicuspid aortic valve (BAV) are at significantly higher risk of developing aortic complications than individuals with tricuspid aortic valves (TAV) and defective signaling during the embryonic development and/or life time exposure to abnormal hemodynamic have been proposed as underlying factors. However, an explanation for the molecular mechanisms of aortopathy in BAV has not yet been provided. We combined proteomics, RNA analyses, immunohistochemistry, and electron microscopy to identify molecular differences in samples of non-dilated ascending aortas from BAV (N = 62) and TAV (N = 54) patients. Proteomic analysis was also performed for dilated aortas (N = 6 BAV and N = 5 TAV) to gain further insight into the aortopathy of BAV. Our results collectively showed the molecular signature of an endothelial/epithelial-mesenchymal (EndMT/EMT) transition-like process, associated with instability of intimal cell junctions and activation of RHOA pathway in the intima and media layers of ascending aorta in BAV patients. We propose that an improper regulation of EndMT/EMT during the spatiotemporally related embryogenesis of semilunar valves and ascending aorta in BAV individuals may result in aortic immaturity and instability prior to dilation. Exasperation of EndMT/EMT state in post embryonic life and/or exposure to non-physiological hemodynamic could lead to the aneurysm of ascending aorta in BAV individuals.
Two flagellar BAR domain proteins in Trypanosoma brucei with stage-specific regulation
Authors: Cicova Zdenka , Dejung Mario , Skalicky Tomas , Eisenhuth Nicole , Hanselmann Steffen , Morriswood Brooke , Figueiredo Luisa M. , Butter Falk , Janzen Christian J. 
Published: October 2016

AbstractTrypanosomes are masters of adaptation to different host environments during their complex life cycle. Large-scale proteomic approaches provide information on changes at the cellular level, and in a systematic way. However, detailed work on single components is necessary to understand the adaptation mechanisms on a molecular level. Here, we have performed a detailed characterization of a bloodstream form (BSF) stage-specific putative flagellar host adaptation factor Tb927.11.2400, identified previously in a SILAC-based comparative proteome study. Tb927.11.2400 shares 38% amino acid identity with TbFlabarin (Tb927.11.2410), a procyclic form (PCF) stage-specific flagellar BAR domain protein. We named Tb927.11.2400 TbFlabarin-like (TbFlabarinL), and demonstrate that it originates from a gene duplication event, which occurred in the African trypanosomes. TbFlabarinL is not essential for the growth of the parasites under cell culture conditions and it is dispensable for developmental differentiation from BSF to the PCF in vitro. We generated TbFlabarinL-specific antibodies, and showed that it localizes in the flagellum. Co-immunoprecipitation experiments together with a biochemical cell fractionation suggest a dual association of TbFlabarinL with the flagellar membrane and the components of the paraflagellar rod.
Comparative venomics of Psyttalia lounsburyi and P. concolor, two olive fruit fly parasitoids: a hypothetical role for a GH1 β-glucosidase
Authors: Mathé-Hubert Hugo , Colinet Dominique , Deleury Emeline , Belghazi Maya , Ravallec Marc , Poulain Julie , Dossat Carole , Poirié Marylène , Gatti Jean-Luc 
Published: October 2016

AbstractVenom composition of parasitoid wasps attracts increasing interest – notably molecules ensuring parasitism success on arthropod pests – but its variation within and among taxa is not yet understood. We have identified here the main venom proteins of two braconid wasps, Psyttalia lounsburyi (two strains from South Africa and Kenya) and P. concolor, olive fruit fly parasitoids that differ in host range. Among the shared abundant proteins, we found a GH1 β-glucosidase and a family of leucine-rich repeat (LRR) proteins. Olive is extremely rich in glycoside compounds that are hydrolyzed by β-glucosidases into defensive toxic products in response to phytophagous insect attacks. Assuming that Psyttalia host larvae sequester ingested glycosides, the injected venom GH1 β-glucosidase could induce the release of toxic compounds, thus participating in parasitism success by weakening the host. Venom LRR proteins are similar to truncated Toll-like receptors and may possibly scavenge the host immunity. The abundance of one of these LRR proteins in the venom of only one of the two P. lounsburyi strains evidences intraspecific variation in venom composition. Altogether, venom intra- and inter-specific variation in Psyttalia spp. were much lower than previously reported in the Leptopilina genus (Figitidae), suggesting it might depend upon the parasitoid taxa.
Variation in structure of proteins by adjusting reactive oxygen and nitrogen species generated from dielectric barrier discharge jet
Authors: Park Ji Hoon , Kim Minsup , Shiratani Masaharu , Cho Art. E. , Choi Eun Ha , Attri Pankaj 
Published: October 2016

AbstractOver the last few years, the variation in liquid chemistry due to the development of radicals generated by cold atmospheric plasma (CAP) has played an important role in plasma medicine. CAP direct treatment or CAP activated media treatment in cancer cells shows promising anticancer activity for both in vivo and in vitro studies. However, the anticancer activity or antimicrobial activity varies between plasma devices due to the different abilities among plasma devices to generate the reactive oxygen and nitrogen species (RONS) at different ratios and in different concentrations. While the generation of RONS depends on many factors, the feeding gas plays the most important role among the factors. Hence, in this study we used different compositions of feeding gas while fixing all other plasma characteristics. We used Ar, Ar-O2 (at different ratios), and Ar-N2 (at different ratios) as the working gases for CAP and investigated the structural changes in proteins (Hemoglobin (Hb) and Myoglobin (Mb)). We then analyzed the influence of RONS generated in liquid on the conformations of proteins. Additionally, to determine the influence of H2O2 on the Hb and Mb structures, we used molecular dynamic simulation.
Crystal structures and inhibition of Trypanosoma brucei hypoxanthine–guanine phosphoribosyltransferase
Authors: Terán David , Hocková Dana , Česnek Michal , Zíková Alena , Naesens Lieve , Keough Dianne T. , Guddat Luke W. 
Published: October 2016

AbstractHuman African Trypanosomiasis (HAT) is a life-threatening infectious disease caused by the protozoan parasite, Trypanosoma brucei (Tbr). Due to the debilitating side effects of the current therapeutics and the emergence of resistance to these drugs, new medications for this disease need to be developed. One potential new drug target is 6-oxopurine phosphoribosyltransferase (PRT), an enzyme central to the purine salvage pathway and whose activity is critical for the production of the nucleotides (GMP and IMP) required for DNA/RNA synthesis within this protozoan parasite. Here, the first crystal structures of this enzyme have been determined, these in complex with GMP and IMP and with three acyclic nucleoside phosphonate (ANP) inhibitors. The Ki values for GMP and IMP are 30.5 μM and 77 μM, respectively. Two of the ANPs have Ki values considerably lower than for the nucleotides, 2.3 μM (with guanine as base) and 15.8 μM (with hypoxanthine as base). The crystal structures show that when two of the ANPs bind, they induce an unusual conformation change to the loop where the reaction product, pyrophosphate, is expected to bind. This and other structural differences between the Tbr and human enzymes suggest selective inhibitors for the Tbr enzyme can be designed.
Plasma Ang2 and ADAM17 levels are elevated during clinical malaria; Ang2 level correlates with severity and expression of EPCR-binding PfEMP1
Authors: Petersen Jens E. V. , Mkumbaye Sixbert I. , Vaaben Anna V. , Manjurano Alphaxard , Lyimo Eric , Kavishe Reginald A. , Mwakalinga Steven B. , Mosha Jacklin , Minja Daniel T. R. , Lusingu John P. A. , Theander Thor G. , Lavstsen Thomas , Wang Christian W. 
Published: October 2016

AbstractThe pathogenesis ofPlasmodium falciparummalaria involves a complex interplay between parasite adhesion and inflammatory response that includes release of cytokines and activation of the endothelium with accompanying release of Angiopoitin 2 (Ang2) to the plasma. A-disintegrin and metalloproteinase 17 (ADAM17) is a protein responsible for releasing cytokines, including Tumor Necrosis Factor α (TNFα), and shedding of adhesion proteins. In this study, we show that plasma levels of ADAM17 are increased in Tanzanian children hospitalized with a malaria infection compared with asymptomatic children but similar to children hospitalized with other infectious diseases. The plasma levels of ADAM17 decreased during recovery after an acute malaria episode. Plasma levels of Ang2 were associated with markers of malaria severity and levels ofvartranscripts encodingP. falciparumErythrocyte Membrane Protein 1 (PfEMP1) containing Cysteine Rich Inter Domain Region α1 (CIDRα1) domains predicted to bind Endothelial Protein C receptor (EPCR). ADAM17 levels were not associated with expression ofvargenes encoding different PfEMP1 types when controlling for age. These data are the first to report ADAM17 plasma levels in malaria-exposed individuals, and support the notion that parasite sequestration mediated by EPCR-binding PfEMP1 is associated with endothelial activation and pathology in severe paediatric malaria.
One compound of saponins from Disocorea zingiberensis protected against experimental acute pancreatitis by preventing mitochondria-mediated necrosis
Authors: Zhang Rui , Wen Li , Shen Yan , Shi Na , Xing Zhihua , Xia Qing , Niu Hai , Huang Wen 
Published: October 2016

AbstractAcute pancreatitis (AP) is a painful inflammatory disorder of the exocrine pancreas, ranking as the most common gastrointestinal reasons for hospitalization with no specific therapy currently. Diosgenyl saponins extracted from natural products and diosgenin or its derivatives have been shown to exert anti-inflammatory effects in various diseases. However, the therapeutic effects of diosgenyl saponins from Dioscorea zingiberensis C. H. Wright in AP have not yet been determined. Five compounds were extracted and screened for taurocholate-induced necrosis in mouse pancreatic acinar cells. Particularly, 26-O-β-d-glucopyranosyl-3β, 22α, 26-trihydroxy-25(R)-furosta-5-en-3-O-[α-L-rhamnopyranosyl-(1 → 4)]-β-d-glucopyranoside (compound 1) exhibited the best protective effects with no toxicity observed. Next, we showed compound 1 concentration-dependently inhibited necrotic cell death pathway activation and 2.5 mM compound 1 also prevented the loss of mitochondrial membrane potential, adenosine triphosphate production, and reactive oxygen species generation in mouse pancreatic acinar cells. Finally, we showed compound 1 protected against three clinically representative murine models of AP and significantly improved pancreatitis-associated acute lung injury. These data provide in vitro and in vivo evidence that one compound of diosgenyl saponins can be potential treatment for AP. This study suggests natural saponins may serve as fruitful sources for exploring/identifying potential therapies for inflammatory diseases.
Critical scaling of icosahedral medium-range order in CuZr metallic glass-forming liquids
Authors: Wu Z. W. , Li F. X. , Huo C. W. , Li M. Z. , Wang W. H. , Liu K. X. 
Published: October 2016

AbstractThe temperature evolution of icosahedral medium-range order formed by interpenetrating icosahedra in CuZr metallic glassforming liquids was investigated via molecular dynamics simulations. Scaling analysis based on percolation theory was employed, and it is found that the size distribution of clusters formed by the central atoms of icosahedra at various temperatures follows a very good scaling law with the cluster number density scaled by S−τ and the cluster size S scaled by |1 − Tc/T|−1/σ, respectively. Here Tc is scaling crossover-temperature. τ and σ are scaling exponents. The critical scaling behaviour suggests that there would be a structural phase transition manifested by percolation of locally favoured structures underlying the glass transition, if the liquid could be cooled slowly enough but without crystallization intervening. Furthermore, it is revealed that when icosahedral short-range order (ISRO) extends to medium-range length scale by connection, the atomic configurations of ISROs will be optimized from distorted ones towards more regular ones gradually, which significantly lowers the energies of ISROs and introduces geometric frustration simultaneously. Both factors make key impacts on the drastic dynamic slow-down of supercooled liquids. Our findings provide direct structure-property relationship for understanding the nature of glass transition.
Advanced Raman Spectroscopy of Methylammonium Lead Iodide: Development of a Non-destructive Characterisation Methodology
Authors: Pistor Paul , Ruiz Alejandro , Cabot Andreu , Izquierdo-Roca Victor 
Published: October 2016

AbstractIn recent years, there has been an impressively fast technological progress in the development of highly efficient lead halide perovskite solar cells. However, the stability of perovskite films and respective solar cells is still an open point of concern and calls for advanced characterization methods. In this work, we identify appropriate measurement conditions for a meaningful analysis of spin-coated absorber-grade perovskite thin films based on methylammonium (MA) lead iodide (MAPbI3) by Raman spectroscopy. The material under investigation and its derivates is the most commonly used for high efficiency devices in the literatures and has yielded working solar cell devices with efficiencies around 10% in our laboratory. We report highly detailed Raman spectra obtained with excitation at 532 nm and 633 nm and their deconvolution taking advantage of the simultaneous fitting of spectra obtained with varying excitation wavelengths. Finally, we propose a fast and contactless methodology based on Raman to probe composition variations and/or degradation of these perovskite thin films and discuss the potential of the presented technique as quality control and degradation monitoring tool in other organic-inorganic perovskite materials and complete solar cell devices.
Network Consistency Projection for Human miRNA-Disease Associations Inference
Authors: Gu Changlong , Liao Bo , Li Xiaoying , Li Keqin 
Published: October 2016

AbstractPrediction and confirmation of the presence of disease-related miRNAs is beneficial to understand disease mechanisms at the miRNA level. However, the use of experimental verification to identify disease-related miRNAs is expensive and time-consuming. Effective computational approaches used to predict miRNA-disease associations are highly specific. In this study, we develop the Network Consistency Projection for miRNA-Disease Associations (NCPMDA) method to reveal the potential associations between miRNAs and diseases. NCPMDA is a non-parametric universal network-based method that can simultaneously predict miRNA-disease associations in all diseases but does not require negative samples. NCPMDA can also confirm the presence of miRNAs in isolated diseases (diseases without any known miRNA association). Leave-one-out cross validation and case studies have shown that the predictive performance of NCPMDA is superior over that of previous method.
Linearized texture of three-dimensional extracellular matrix is mandatory for bladder cancer cell invasion
Authors: Alfano Massimo , Nebuloni Manuela , Allevi Raffaele , Zerbi Pietro , Longhi Erika , Lucianò Roberta , Locatelli Irene , Pecoraro Angela , Indrieri Marco , Speziali Chantal , Doglioni Claudio , Milani Paolo , Montorsi Francesco , Salonia Andrea 
Published: October 2016

AbstractIn the fields of biomaterials and tissue engineering simulating the native microenvironment is of utmost importance. As a major component of the microenvironment, the extracellular matrix (ECM) contributes to tissue homeostasis, whereas modifications of native features are associated with pathological conditions. Furthermore, three-dimensional (3D) geometry is an important feature of synthetic scaffolds favoring cell stemness, maintenance and differentiation. We analyzed the 3D structure, geometrical measurements and anisotropy of the ECM isolated from (i) human bladder mucosa (basal lamina and lamina propria) and muscularis propria; and, (ii) bladder carcinoma (BC). Next, binding and invasion of bladder metastatic cell line was observed on synthetic scaffold recapitulating anisotropy of tumoral ECM, but not on scaffold with disorganized texture typical of non-neoplastic lamina propria. This study provided information regarding the ultrastructure and geometry of healthy human bladder and BC ECMs. Likewise, using synthetic scaffolds we identified linearization of the texture as a mandatory feature for BC cell invasion. Integrating microstructure and geometry with biochemical and mechanical factors could support the development of an innovative synthetic bladder substitute or a tumoral scaffold predictive of chemotherapy outcomes.
S100A8 promotes migration and infiltration of inflammatory cells in acute anterior uveitis
Authors: Wang Yuqin , Zhang Zuhui , Zhang Laihe , Li Xinxin , Lu Rui , Xu Peipei , Zhang Xuhong , Dai Mali , Dai Xiaodan , Qu Jia , Lu Fan , Chi Zailong 
Published: October 2016

AbstractUveitis, the pathologic condition of inflammation of the uvea, frequently leads to severe vision loss and blindness. S100A8 is a calcium-binding protein which mainly expresses in granulocytes and monocytes and plays a prominent role in the regulation of inflammatory processes and immune response. Here, we determined the role of S100A8-positive cells in acute anterior uveitis (AAU) and keratitis. In rat models of endotoxin (lipopolisaccharide, LPS) -induced uveitis (EIU) and keratitis, S100A8-positive granulocytes and monocytes increased significantly in the iris-ciliary body and cornea as well as in the blood. Interestingly, Glucocorticoids slightly increased S100A8 levels in leukocytes, but reduced its presence significantly in the iris-ciliary body after LPS injection. Moreover, inhibition of NF-kB activation remarkably suppressed both progression of AAU and total S100A8 levels in leukocytes and the iris-ciliary body after LPS administration. Additionally, S100A8 protein level was also found to be elevated in the serum of AAU patients parallel with the progression of AAU through the designated clinical stages. Thus, S100A8 plays a pivotal role in the processes of AAU through involvement in migration and infiltration of S100A8-positive cells. Our findings suggest that serum levels of S100A8 protein can be used to monitor inflammatory activity in AAU.
SNP-based heritability estimates of the personality dimensions and polygenic prediction of both neuroticism and major depression: findings from CONVERGE
Authors: Docherty A R , Moscati A , Peterson R , Edwards A C , Adkins D E , Bacanu S A , Bigdeli T B , Webb B T , Flint J , Kendler K S 
Published: October 2016

AbstractBiometrical genetic studies suggest that the personality dimensions, including neuroticism, are moderately heritable (~0.4 to 0.6). Quantitative analyses that aggregate the effects of many common variants have recently further informed genetic research on European samples. However, there has been limited research to date on non-European populations. This study examined the personality dimensions in a large sample of Han Chinese descent (N=10 064) from the China, Oxford, and VCU Experimental Research on Genetic Epidemiology study, aimed at identifying genetic risk factors for recurrent major depression among a rigorously ascertained cohort. Heritability of neuroticism as measured by the Eysenck Personality Questionnaire (EPQ) was estimated to be low but statistically significant at 10% (s.e.=0.03, P=0.0001). In addition to EPQ, neuroticism based on a three-factor model, data for the Big Five (BF) personality dimensions (neuroticism, openness, conscientiousness, extraversion and agreeableness) measured by the Big Five Inventory were available for controls (n=5596). Heritability estimates of the BF were not statistically significant despite high power (>0.85) to detect heritabilities of 0.10. Polygenic risk scores constructed by best linear unbiased prediction weights applied to split-half samples failed to significantly predict any of the personality traits, but polygenic risk for neuroticism, calculated with LDpred and based on predictive variants previously identified from European populations (N=171 911), significantly predicted major depressive disorder case–control status (P=0.0004) after false discovery rate correction. The scores also significantly predicted EPQ neuroticism (P=6.3 × 10−6). Factor analytic results of the measures indicated that any differences in heritabilities across samples may be due to genetic variation or variation in haplotype structure between samples, rather than measurement non-invariance. Findings demonstrate that neuroticism can be significantly predicted across ancestry, and highlight the importance of studying polygenic contributions to personality in non-European populations.