bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anisotropic engineered heart tissue made from laser-cut decellularized myocardium
Authors: Schwan Jonas , Kwaczala Andrea T. , Ryan Thomas J. , Bartulos Oscar , Ren Yongming , Sewanan Lorenzo R. , Morris Aaron H. , Jacoby Daniel L. , Qyang Yibing , Campbell Stuart G. 
Published: August 2016

AbstractWe have developed an engineered heart tissue (EHT) system that uses laser-cut sheets of decellularized myocardium as scaffolds. This material enables formation of thin muscle strips whose biomechanical characteristics are easily measured and manipulated. To create EHTs, sections of porcine myocardium were laser-cut into ribbon-like shapes, decellularized and mounted in specialized clips for seeding and culture. Scaffolds were first tested by seeding with neonatal rat ventricular myocytes. EHTs beat synchronously by day five and exhibited robust length-dependent activation by day 21. Fiber orientation within the scaffold affected peak twitch stress, demonstrating its ability to guide cells toward physiologic contractile anisotropy. Scaffold anisotropy also made it possible to probe cellular responses to stretch as a function of fiber angle. Stretch that was aligned with the fiber direction increased expression of brain natriuretic peptide, but off-axis stretches (causing fiber shear) did not. The method also produced robust EHTs from cardiomyocytes derived from human embryonic stem cells and induced pluripotent stem cells (hiPSC). hiPSC-EHTs achieved maximum peak stress of 6.5 mN/mm2 and twitch kinetics approaching reported values from adult human trabeculae. We conclude that laser-cut EHTs are a viable platform for novel mechanotransduction experiments and characterizing the biomechanical function of patient-derived cardiomyoctyes.
Expression and Functional Analysis of a Novel Group of Legume-specific WRKY and Exo70 Protein Variants from Soybean
Authors: Wang Ze , Li Panfeng , Yang Yan , Chi Yingjun , Fan Baofang , Chen Zhixiang 
Published: August 2016

AbstractLegumes fix atmospheric nitrogen through symbiosis with microorganisms and contain special traits in nitrogen assimilation and associated processes. Recently, we have reported a novel WRKY-related protein (GmWRP1) and a new clade of Exo70 proteins (GmExo70J) from soybean with homologs found only in legumes. GmWRP1 and some of the GmExo70J proteins are localized to Golgi apparatus through a novel N-terminal transmembrane domain. Here, we report further analysis of expression and functions of the novel GmWRP1 and GmExo70J genes. Promoter-GUS analysis in Arabidopsis revealed distinct tissue-specific expression patterns of the GmExo70J genes not only in vegetative but also in reproductive organs including mature tissues, where expression of previously characterized Exo70 genes is usually absent. Furthermore, expression of some GmExo70J genes including GmExo70J1, GmExo70J6 and GmExo70J7 increases greatly in floral organ-supporting receptacles during the development and maturation of siliques, indicating a possible role in seed development. More importantly, suppression of GmWRP1, GmExo70J7, GmExo70J8 and GmExo70J9 expression in soybean using virus- or artificial microRNA-mediated gene silencing resulted in accelerated leaf senescence and reduced nodule formation. These results strongly suggest that legume-specific GmWRP1 and GmExo70J proteins play important roles not only in legume symbiosis but also in other processes critical for legume growth and development.
The antifungal plant defensin AtPDF2.3 from Arabidopsis thaliana blocks potassium channels
Authors: Vriens Kim , Peigneur Steve , De Coninck Barbara , Tytgat Jan , Cammue Bruno P. A. , Thevissen Karin 
Published: August 2016

AbstractScorpion toxins that block potassium channels and antimicrobial plant defensins share a common structural CSαβ-motif. These toxins contain a toxin signature (K-C4-X-N) in their amino acid sequence, and based on in silico analysis of 18 plant defensin sequences, we noted the presence of a toxin signature (K-C5-R-G) in the amino acid sequence of the Arabidopsis thaliana defensin AtPDF2.3. We found that recombinant (r)AtPDF2.3 blocks Kv1.2 and Kv1.6 potassium channels, akin to the interaction between scorpion toxins and potassium channels. Moreover, rAtPDF2.3[G36N], a variant with a KCXN toxin signature (K-C5-R-N), is more potent in blocking Kv1.2 and Kv1.6 channels than rAtPDF2.3, whereas rAtPDF2.3[K33A], devoid of the toxin signature, is characterized by reduced Kv channel blocking activity. These findings highlight the importance of the KCXN scorpion toxin signature in the plant defensin sequence for blocking potassium channels. In addition, we found that rAtPDF2.3 inhibits the growth of Saccharomyces cerevisiae and that pathways regulating potassium transport and/or homeostasis confer tolerance of this yeast to rAtPDF2.3, indicating a role for potassium homeostasis in the fungal defence response towards rAtPDF2.3. Nevertheless, no differences in antifungal potency were observed between the rAtPDF2.3 variants, suggesting that antifungal activity and Kv channel inhibitory function are not linked.
Presynaptic DLG regulates synaptic function through the localization of voltage-activated Ca2+ Channels
Authors: Astorga César , Jorquera Ramón A. , Ramírez Mauricio , Kohler Andrés , López Estefanía , Delgado Ricardo , Córdova Alex , Olguín Patricio , Sierralta Jimena 
Published: August 2016

AbstractThe DLG-MAGUK subfamily of proteins plays a role on the recycling and clustering of glutamate receptors (GLUR) at the postsynaptic density. discs-large1 (dlg) is the only DLG-MAGUK gene in Drosophila and originates two main products, DLGA and DLGS97 which differ by the presence of an L27 domain. Combining electrophysiology, immunostaining and genetic manipulation at the pre and postsynaptic compartments we study the DLG contribution to the basal synaptic-function at the Drosophila larval neuromuscular junction. Our results reveal a specific function of DLGS97 in the regulation of the size of GLUR fields and their subunit composition. Strikingly the absence of any of DLG proteins at the presynaptic terminal disrupts the clustering and localization of the calcium channel DmCa1A subunit (Cacophony), decreases the action potential-evoked release probability and alters short-term plasticity. Our results show for the first time a crucial role of DLG proteins in the presynaptic function in vivo.
EF24 inhibits tumor growth and metastasis via suppressing NF-kappaB dependent pathways in human cholangiocarcinoma
Authors: Yin Da-long , Liang Ying-jian , Zheng Tong-sen , Song Rui-peng , Wang Jia-bei , Sun Bo-shi , Pan Shang-ha , Qu Lian-dong , Liu Jia-ren , Jiang Hong-chi , Liu Lian-xin 
Published: August 2016

AbstractA synthetic monoketone analog of curcumin, termed 3, 5-bis (2-flurobenzylidene) piperidin-4-one (EF24), has been reported to inhibit the growth of a variety of cancer cells both in vitro and in vivo. However, whether EF24 has anticancer effects on cholangiocarcinoma (CCA) cells and the mechanisms remain to be investigated. The aim of our study was to evaluate the molecular mechanisms underlying the anticancer effects of EF24 on CCA tumor growth and metastasis. Cell proliferation, apoptosis, migration, invasion, tumorigenesis and metastasis were examined. EF24 exhibited time- and dose-dependent inhibitory effects on HuCCT-1, TFK-1 and HuH28 human CCA cell lines. EF24 inhibited CCA cell proliferation, migration, and induced G2/M phase arrest. EF24 induced cell apoptosis along with negative regulation of NF-κB- X-linked inhibitor of apoptosis protein (XIAP) signaling pathway. XIAP inhibition by lentivirus mediated RNA interference enhanced EF24-induced apoptosis, while XIAP overexpression reduced it in CCA cells. In vivo, EF24 significantly suppressed the growth of CCA tumor xenografts and tumor metastasis while displaying low toxicity levels. Our findings indicate that EF24 is a potent antitumor agent that inhibits tumor growth and metastasis by inhibiting NF-κB dependent signaling pathways. EF24 may represent a novel approach for CCA treatment.
Long noncoding RNA linc00598 regulates CCND2 transcription and modulates the G1 checkpoint
Authors: Jeong Oh-Seok , Chae Yun-Cheol , Jung Hyeonsoo , Park Soon Cheol , Cho Sung-Jin , Kook Hyun , Seo SangBeom 
Published: August 2016

AbstractData derived from genomic and transcriptomic analyses have revealed that long noncoding RNAs (lncRNAs) have important roles in the transcriptional regulation of various genes. Recent studies have identified the mechanism underlying this function. To date, a variety of noncoding transcripts have been reported to function in conjunction with epigenetic regulator proteins. In this study, we investigated the function of linc00598, which is transcribed by a genomic sequence on chromosome 13, downstream of FoxO1 and upstream of COG6. Microarray analysis showed that linc00598 regulates the transcription of specific target genes, including those for cell cycle regulators. We discovered that linc00598 regulates CCND2 transcription through modulation of the transcriptional regulatory effect of FoxO1 on the CCND2 promoter. Moreover, we observed that knockdown of linc00598 induced G0/G1 cell cycle arrest and inhibited proliferation. These data indicate that linc00598 plays an important role in cell cycle regulation and proliferation through its ability to regulate the transcription of CCND2.
Decreased demand for olfactory periglomerular cells impacts on neural precursor cell viability in the rostral migratory stream
Authors: Langenfurth Anika , Gu Song , Bautze Verena , Zhang Caiyi , Neumann Julia E. , Schüller Ulrich , Stock Kristin , Wolf Susanne A. , Maier Anna-Maria , Mastrella Giorgia , Pak Andrew , Cheng Hongwei , Kälin Roland E. , Holmbeck Kenn , Strotmann Jörg , Kettenmann Helmut , Glass Rainer 
Published: August 2016

AbstractThe subventricular zone (SVZ) provides a constant supply of new neurons to the olfactory bulb (OB). Different studies have investigated the role of olfactory sensory input to neural precursor cell (NPC) turnover in the SVZ but it was not addressed if a reduced demand specifically for periglomerular neurons impacts on NPC-traits in the rostral migratory stream (RMS). We here report that membrane type-1 matrix metalloproteinase (MT1-MMP) deficient mice have reduced complexity of the nasal turbinates, decreased sensory innervation of the OB, reduced numbers of olfactory glomeruli and reduced OB-size without alterations in SVZ neurogenesis. Large parts of the RMS were fully preserved in MT1-MMP-deficient mice, but we detected an increase in cell death-levels and a decrease in SVZ-derived neuroblasts in the distal RMS, as compared to controls. BrdU-tracking experiments showed that homing of NPCs specifically to the glomerular layer was reduced in MT1-MMP-deficient mice in contrast to controls while numbers of tracked cells remained equal in other OB-layers throughout all experimental groups. Altogether, our data show the demand for olfactory interneurons in the glomerular layer modulates cell turnover in the RMS, but has no impact on subventricular neurogenesis.
Phosphate enhance recovery from wastewater by mechanism analysis and optimization of struvite settleability in fluidized bed reactor
Authors: Fang Ci , Zhang Tao , Jiang Rongfeng , Ohtake Hisao 
Published: August 2016

AbstractSince phosphorus, a non-renewable and non-substitutable resource, has become the principal contributor and limiting factor to water eutrophication, achieving phosphorus removal and recovery from wastewater is pretty essential. Even though struvite crystallization process has been widely used for phosphate (P) recovery in wastewater treatment, its application is hampered by difficulties controlling small particle size and crystal growth. This study was conducted to control the settleability of struvite by calculating and predicting the struvite-settling percentage (Ps), which is always affected by the initial concentration of P (CP), solution pH (pH), reaction time (t), reaction temperature (T), agitation rate (Ar) and inlet flow velocity (vf) of the fluidized bed reactor. The results showed that the settleability of struvite could be enhanced by increasing T and decreasing pH, Ar, or vf and would perform worse with overlong t or excessive CP. The dynamic variation process of the solution supersaturated index (SI) combined with the phase equilibrium theory and Ostwald ripening mechanism explained the above results sufficiently. The logistic model was chosen to predict the Ps under multi-factors, but the accuracy needs to be improved.
Exploring tight junction alteration using double fluorescent probe combination of lanthanide complex with gold nanoclusters
Authors: Wang Xinyi , Wang Na , Yuan Lan , Li Na , Wang Junxia , Yang Xiaoda 
Published: August 2016

AbstractTight junctions play a key role in restricting or regulating passage of liquids, ions and large solutes through various biological barriers by the paracellular route. Changes in paracellular permeation indicate alteration of the tight junction. However, it is very difficult to obtain the structural change information by measuring paracellular flux based on transepithelial electrical resistance or using fluorescein-labeled dextrans. Here we show that the BSA and GSH stabilized gold nanoclusters exhibit marginal cytotoxicity and pass through the MDCK monolayer exclusively through the paracellular pathway. We propose a double fluorescence probe strategy, the combination of a proven paracellular indicator (europium complex) with fluorescent gold nanoclusters. We calculate changes of structural parameters in tight junctions based on determination of the diffusion coefficients of the probes. Two different types of tight junction openers are used to validate our strategy. Results show that EDTA disrupts tight junction structures and induces large and smooth paracellular pore paths with an average radius of 17 nm, but vanadyl complexes induce paths with the radius of 6 nm. The work suggests that the double fluorescence probe strategy is a useful and convenient approach for in vitro investigation of tight junction structural alternations caused by pharmacological or pathological events.
Galectin-4 expression is down-regulated in response to autophagy during differentiation of rat trophoblast cells
Authors: Arikawa Tomohiro , Liao Shengjun , Shimada Hiroki , Inoue Tomoki , Sakata-Haga Hiromi , Nakamura Takanori , Hatta Toshihisa , Shoji Hiroki 
Published: August 2016

AbstractPlacental development and trophoblast invasion of the maternal endometrium establish the maternal-fetal interface, which is critical for the developing embryo and fetus. Herein we show that overexpression of Galectin-4 (Gal-4) during trophoblast differentiation inhibited the enlargement of Rcho-1 cells (a model for rat trophoblast differentiation) and promoted cell-cell adhesion, whereas trophoblast specific markers and MMP-9 activity were not affected. In the rat placenta, microtubule associated protein 1 light chain 3 alpha (LC3) protein, an autophagy marker, is highly expressed on the maternal side of the decidua where Gal-4 expression is weak. In vitro assays showed that the expression of trophoblast-specific differentiation markers was reduced by 3-Methyladenine (3-MA) and Bafilomycin A1, known as autophagy inhibitors, compared to control cells. Furthermore, Gal-4 expression in Rcho-1 cells, which is normally down-regulated during differentiation, was not attenuated in the presence of autophagy inhibitors, suggesting that autophagy is upstream of Gal-4 expression. We herein describe a possible mechanism by which autophagy regulates trophoblast differentiation via regulation of Gal-4 expression in order to establish the maternal-fetal interface.
Influence of tacrolimus metabolism rate on BKV infection after kidney transplantation
Authors: Thölking Gerold , Schmidt Christina , Koch Raphael , Schuette-Nuetgen Katharina , Pabst Dirk , Wolters Heiner , Kabar Iyad , Hüsing Anna , Pavenstädt Hermann , Reuter Stefan , Suwelack Barbara 
Published: August 2016

AbstractImmunosuppression is the major risk factor for BK virus nephropathy (BKVN) after renal transplantation (RTx). As the individual tacrolimus (Tac) metabolism rate correlates with Tac side effects, we hypothesized that Tac metabolism might also influence the BKV infection risk. In this case-control study RTx patients with BK viremia within 4 years after RTx (BKV group) were compared with a BKV negative control group. The Tac metabolism rate expressed as the blood concentration normalized by the daily dose (C/D ratio) was applied to assess the Tac metabolism rate. BK viremia was detected in 86 patients after a median time of 6 (0–36) months after RTx. BKV positive patients showed lower Tac C/D ratios at 1, 3 and 6 months after RTx and were classified as fast Tac metabolizers. 8 of 86 patients with BK viremia had histologically proven BKN and a higher median maximum viral load than BKV patients without BKN (441,000 vs. 18,572 copies/mL). We conclude from our data that fast Tac metabolism (C/D ratio <1.05) is associated with BK viremia after RTx. Calculation of the Tac C/D ratio early after RTx, may assist transplant clinicians to identify patients at risk and to choose the optimal immunosuppressive regimen.
Time-dependent X-ray diffraction studies on urea/hen egg white lysozyme complexes reveal structural changes that indicate onset of denaturation
Authors: Raskar Tushar , Khavnekar Sagar , Hosur Madhusoodan 
Published: August 2016

AbstractTemporal binding of urea to lysozyme was examined using X-ray diffraction of single crystals of urea/lysozyme complexes prepared by soaking native lysozyme crystals in solutions containing 9 M urea. Four different soak times of 2, 4, 7 and 10 hours were used. The five crystal structures (including the native lysozyme), refined to 1.6 Å resolution, reveal that as the soaking time increased, more and more first-shell water molecules are replaced by urea. The number of hydrogen bonds between urea and the protein is similar to that between protein and water molecules replaced by urea. However, the number of van der Waals contacts to protein from urea is almost double that between the protein and the replaced water. The hydrogen bonding and van der Waals interactions are initially greater with the backbone and later with side chains of charged residues. Urea altered the water-water hydrogen bond network both by replacing water solvating hydrophobic residues and by shortening the first-shell intra-water hydrogen bonds by 0.2 Å. These interaction data suggest that urea uses both ‘direct’ and ‘indirect’ mechanisms to unfold lysozyme. Specific structural changes constitute the first steps in lysozyme unfolding by urea.
Circulating intestine-derived exosomal miR-328 in plasma, a possible biomarker for estimating BCRP function in the human intestines
Authors: Gotanda Keisuke , Hirota Takeshi , Saito Jumpei , Fukae Masato , Egashira Yu , Izumi Noritomo , Deguchi Mariko , Kimura Miyuki , Matsuki Shunji , Irie Shin , Ieiri Ichiro 
Published: August 2016

AbstractA variant in the breast cancer resistance protein (BCRP) gene, 421C> A is a useful biomarker for describing large inter-individual differences in the pharmacokinetics of sulfasalazine (SASP), a BCRP substrate. However, large intra-genotypic variability still exists in spite of the incorporation of this variant into the pharmacokinetics of SASP. Since miR-328 negatively regulates BCRP expression in human tissues, we hypothesized that exosomal miR-328 in plasma, which leaks from the intestines, is a possible biomarker for estimating BCRP activity in the human intestines. We established an immunoprecipitation-based quantitative method for circulating intestine-derived miR-328 in plasma using an anti-glycoprotein A33 antibody. A clinical study was conducted with an open-label, non-randomized and single-arm design involving 33 healthy participants. Intestine-derived exosomal miR-328 levels positively correlated (P < 0.05) with SASP AUC0-48, suggesting that subjects with high miR-328 levels have low intestinal BCRP activity, resulting in the high AUC of SASP. Circulating intestine-derived exosomal miR-328 in plasma has potential as a possible biomarker for estimating BCRP function in the human intestines.
Crystal Structure of Major Envelope Protein VP24 from White Spot Syndrome Virus
Authors: Sun Lifang , Su Yintao , Zhao Yanhe , Fu Zheng-qing , Wu Yunkun 
Published: August 2016

AbstractWhite spot syndrome virus (WSSV) is one of the major and most serious pathogen in the shrimp industry. As one of the most abundant envelope protein, VP24 acts as a core protein interacting with other structure proteins and plays an important role in virus assembly and infection. Here, we have presented the crystal structure of VP24 from WSSV. In the structure, VP24 consists of a nine-stranded β–barrel fold with mostly antiparallel β-strands and the loops extending out the β–barrel at both N-terminus and C-terminus, which is distinct to those of the other two major envelope proteins VP28 and VP26. Structural comparison of VP24 with VP26 and VP28 reveals opposite electrostatic surface potential properties of them. These structural differences could provide insight into their differential functional mechanisms and roles for virus assembly and infection. Moreover, the structure reveals a trimeric assembly, suggesting a likely natural conformation of VP24 in viral envelope. Therefore, in addition to confirming the evolutionary relationship among the three abundant envelope proteins of WSSV, our structural studies also facilitate a better understanding of the molecular mechanism underlying special roles of VP24 in WSSV assembly and infection.
Broad Spectrum Anti-Influenza Agents by Inhibiting Self-Association of Matrix Protein 1
Authors: Mosier Philip D. , Chiang Meng-Jung , Lin Zhengshi , Gao Yamei , Althufairi Bashayer , Zhou Qibing , Musayev Faik , Safo Martin K. , Xie Hang , Desai Umesh R. 
Published: August 2016

AbstractThe matrix protein 1 (M1) of influenza A virus (IAV) exists as a three-dimensional oligomeric structure in mature virions with high sequence conservation across different IAV subtypes, which makes it a potential broad spectrum antiviral target. We hypothesized that impairing self-association of M1 through a small molecule ‘wedge’, which avidly binds to an M1-M1 interface, would result in a completely new class of anti-influenza agents. To establish this proof-of-principle, we performed virtual screening on a library of >70,000 commercially available small molecules that resulted in several plausible ‘wedges’. Biophysical studies showed that the best molecule bound the M1 protein potently and weakened M1-M1 self-association. Most importantly, the agent reduced the thickness of the M1 layer in mature virions and inhibited in ovo propagation of multiple IAV strains including H1N1, pandemic H1N1, H3N2 and H5N1, which supports the “wedge” hypothesis. These results demonstrate that M1 is a promising druggable target for the discovery of a completely new line of broad spectrum anti-IAV agents.
Introducing Mg-4Zn-3Gd-1Ca/ZnO nanocomposite with compressive strengths matching/exceeding that of mild steel
Authors: Chen Y. , Tekumalla S. , Guo Y. B. , Gupta M. 
Published: August 2016

AbstractThis work introduces Mg-4Zn-3Gd-1Ca/2ZnO (wt.%) nanocomposite fabricated using the technique of disintegrated melt deposition and extrusion. Addition of ZnO nanoparticles enhanced the compressive strengths of alloy by ~100 MPa. Nanocomposite samples display high strength and good ductility: 0.2% compressive yield stress of 355 MPa, ultimate compressive stress of 703 MPa and compressive failure strain of 10.6%. The significant enhancement of compressive yield stress is mainly attributed to the grain refinement by adding nanoparticles. The strength levels exceed that of commercial magnesium alloys (i.e. WE43, WE54, ZK60 and ME21) and mild steels (i.e. S275 and S355), making Mg-4Zn-3Gd-1Ca/2ZnO a very promising material for multiple engineering and biomedical applications.