bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cavity filling mutations at the thyroxine-binding site dramatically increase transthyretin stability and prevent its aggregation
Authors: Sant’Anna Ricardo , Almeida Maria Rosário , Varejāo Nathalia , Gallego Pablo , Esperante Sebastian , Ferreira Priscila , Pereira-Henriques Alda , Palhano Fernando L. , de Carvalho Mamede , Foguel Debora , Reverter David , Saraiva Maria João , Ventura Salvador 
Published: March 2017

AbstractMore than a hundred different Transthyretin (TTR) mutations are associated with fatal systemic amyloidoses. They destabilize the protein tetrameric structure and promote the extracellular deposition of TTR as pathological amyloid fibrils. So far, only mutations R104H and T119M have been shown to stabilize significantly TTR, acting as disease suppressors. We describe a novel A108V non-pathogenic mutation found in a Portuguese subject. This variant is more stable than wild type TTR both in vitro and in human plasma, a feature that prevents its aggregation. The crystal structure of A108V reveals that this stabilization comes from novel intra and inter subunit contacts involving the thyroxine (T4) binding site. Exploiting this observation, we engineered a A108I mutation that fills the T4 binding cavity, as evidenced in the crystal structure. This synthetic protein becomes one of the most stable TTR variants described so far, with potential application in gene and protein replacement therapies.
The miR-24-3p/p130Cas: a novel axis regulating the migration and invasion of cancer cells
Authors: Kang Hoin , Rho Jun Gi , Kim Chongtae , Tak Hyosun , Lee Heejin , Ji Eunbyul , Ahn Sojin , Shin A-Ri , Cho Hyun-Il , Huh Yun Hyun , Song Woo Keun , Kim Wook , Lee Eun Kyung 
Published: March 2017

AbstractMicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression by suppressing translation or facilitating mRNA decay. Differential expression of miRNAs is involved in the pathogenesis of several diseases including cancer. Here, we investigated the role of-miR-24-3p as a downregulated miRNA in metastatic cancer. miR-24-3p was decreased in metastatic cancer and lower expression of miR-24-3p was related to poor survival of cancer patients. Consistently, ectopic expression of miR-24-3p suppressed the cell migration, invasion, and proliferation of MCF7, Hep3B, B16F10, SK-Hep1, and PC-3 cells by directly targeting p130Cas. Stable expression of p130Cas restored miR-24-3p-mediated inhibition of cell migration and invasion. These results suggest that miR-24-3p functions as a tumor suppressor and the miR-24-3p/p130Cas axis is a novel factor of cancer progression by regulating cell migration and invasion.
Protein interaction evolution from promiscuity to specificity with reduced flexibility in an increasingly complex network
Authors: Alhindi T. , Zhang Z. , Ruelens P. , Coenen H. , Degroote H. , Iraci N. , Geuten K. 
Published: March 2017

AbstractA key question regarding protein evolution is how proteins adapt to the dynamic environment in which they function and how in turn their evolution shapes the protein interaction network. We used extant and resurrected ancestral plant MADS-domain transcription factors to understand how SEPALLATA3, a protein with hub and glue properties, evolved and takes part in network organization. Although the density of dimeric interactions was saturated in the network, many new interactions became mediated by SEPALLATA3 after a whole genome triplication event. By swapping SEPALLATA3 and its ancestors between dimeric networks of different ages, we found that the protein lost the capacity of promiscuous interaction and acquired specificity in evolution. This was accompanied with constraints on conformations through proline residue accumulation, which made the protein less flexible. SHORT VEGETATIVE PHASE on the other hand (non-hub) was able to gain protein-protein interactions due to a C-terminal domain insertion, allowing for a larger interaction interface. These findings illustrate that protein interaction evolution occurs at the level of conformational dynamics, when the binding mechanism concerns an induced fit or conformational selection. Proteins can evolve towards increased specificity with reduced flexibility when the complexity of the protein interaction network requires specificity.
Septin 9_i2 is downregulated in tumors, impairs cancer cell migration and alters subnuclear actin filaments
Authors: Verdier-Pinard P. , Salaun D. , Bouguenina H. , Shimada S. , Pophillat M. , Audebert S. , Agavnian E. , Coslet S. , Charafe-Jauffret E. , Tachibana T. , Badache A. 
Published: March 2017

AbstractFunctions of septin cytoskeletal polymers in tumorigenesis are still poorly defined. Their role in the regulation of cytokinesis and cell migration were proposed to contribute to cancer associated aneuploidy and metastasis. Overexpression of Septin 9 (Sept9) promotes migration of cancer cell lines. SEPT9 mRNA and protein expression is increased in breast tumors compared to normal and peritumoral tissues and amplification of SEPT9 gene was positively correlated with breast tumor progression. However, the existence of multiple isoforms of Sept9 is a confounding factor in the analysis of Sept9 functions. In the present study, we analyze the protein expression of Sept9_i2, an uncharacterized isoform, in breast cancer cell lines and tumors and describe its specific impact on cancer cell migration and Sept9 cytoskeletal distribution. Collectively, our results showed that, contrary to Sept9_i1, Sept9_i2 did not support cancer cell migration, and induced a loss of subnuclear actin filaments. These effects were dependent on Sept9_i2 specific N-terminal sequence. Sept9_i2 was strongly down-regulated in breast tumors compared to normal mammary tissues. Thus our data indicate that Sept9_i2 is a negative regulator of breast tumorigenesis. We propose that Sept9 tumorigenic properties depend on the balance between Sept9_i1 and Sept9_i2 expression levels.
Post-Hoc Study: Intravenous Hydration Treatment in Chinese Patients with High Risk of Contrast-Induced Nephropathy Following Percutaneous Coronary Intervention
Authors: Bei Weijie , Li Hualong , Lin Kaiyang , Wang Kun , Chen Shiqun , Guo Xiaosheng , Liu Yong , Tan Ning , Chen Jiyan ,   TRUST investigators, Yang Xiangtai , Su Xi , Du Zhimin , Zeng Qiutang , Fang Zhenfei , Wang Yan , Jiang Hong , Xiong Longgen , Hou Yuqing , Yuan Yong , Li Tianfa , Hong Lang , Wu Yanqing , Liu Yin , Lin Wenhua , Jiang Tiemin , Fu Junhua , An Yi , Yu Bo , Tian Ye , Zheng Yang , Liu Bin , Yang Ping , Jiang Xianyan , Wang Hao , Qu Peng , Cui Lianqun , Li Xueqi , Qi Xiaoyong , Ma Zengcai , Li Jifu , Zhang Lili , Liu Shengquan , Pang Wenyue , Li Yibo , Yang Manguang , Ji Zheng , Zhao Pitian , Li Lu , Ge Junbo , Jin Huigen , Pan Weimin , Song Yaoming , Li Jianmei , Xiao Jianming , Liu Hanxiong , Tao Jianhong , Wu Zhongdong , Tuo Buxiong , Li Wei , Xu Yixian , Zhang Zhaoqi , Chen Yundai , Wang Lefeng , Zhang Jinying , Wang Fengling , Jia Yongping , Wang Bin , Tang Fakuan , Tang Qiang , Wang Wei , Sun Yuemin , Su Weiqing 
Published: March 2017

AbstractContrast-induced nephropathy (CIN) develops after the injection of iodinated contrast media. This is a post hoc analysis of the data obtained from the TRUST study, which was a prospective, multicentre, observational study conducted to evaluate the safety and tolerability of the contrast medium iopromide in patients undergoing cardiac catheterization from August 2010 to September 2011 in China, conducted to explore the current status, trends and risk predictors of hydration treatment. The status of hydration to prevent CIN in each patient was recorded. Of the total 17,139 patients from the TRUST study (mean age, 60.33 ± 10.38 years), the overall hydration usage was 46.1% in patients undergoing percutaneous coronary intervention (PCI) and 77.4%, 51.7%, and 48.5% in patients with pre-existing renal disease, diabetes mellitus, and hypertension, respectively. The proportion of hydration use increased from 36.5% to 55.5% from August 2010 to September 2011, which was independently associated with risk predictors like older age, pre-existing renal disease, hypertension, diabetes mellitus, prior myocardial infarction, ST segment elevation MI, high contrast dose, multi-vessel disease and reduced LVEF (<45%). Overall, the usage of intravenous hydration treatment for patients with a high risk of CIN following PCI was high in China.
Ghrelin Facilitates GLUT2-, SGLT1- and SGLT2-mediated Intestinal Glucose Transport in Goldfish (Carassius auratus)
Authors: Blanco Ayelén Melisa , Bertucci Juan Ignacio , Ramesh Naresh , Delgado María Jesús , Valenciano Ana Isabel , Unniappan Suraj 
Published: March 2017

AbstractGlucose homeostasis is an important biological process that involves a variety of regulatory mechanisms. This study aimed to determine whether ghrelin, a multifunctional gut-brain hormone, modulates intestinal glucose transport in goldfish (Carassius auratus). Three intestinal glucose transporters, the facilitative glucose transporter 2 (GLUT2), and the sodium/glucose co-transporters 1 (SGLT1) and 2 (SGLT2), were studied. Immunostaining of intestinal sections found colocalization of ghrelin and GLUT2 and SGLT2 in mucosal cells. Some cells containing GLUT2, SGLT1 and SGLT2 coexpressed the ghrelin/growth hormone secretagogue receptor 1a (GHS-R1a). Intraperitoneal glucose administration led to a significant increase in serum ghrelin levels, as well as an upregulation of intestinal preproghrelin, ghrelin O-acyltransferase and ghs-r1 expression. In vivo and in vitro ghrelin treatment caused a concentration- and time-dependent modulation (mainly stimulatory) of GLUT2, SGLT1 and SGLT2. These effects were abolished by the GHS-R1a antagonist [D-Lys3]-GHRP-6 and the phospholipase C inhibitor U73122, suggesting that ghrelin actions on glucose transporters are mediated by GHS-R1a via the PLC/PKC signaling pathway. Finally, ghrelin stimulated the translocation of GLUT2 into the plasma membrane of goldfish primary intestinal cells. Overall, data reported here indicate an important role for ghrelin in the modulation of glucoregulatory machinery and glucose homeostasis in fish.
Microvasculature on a chip: study of the Endothelial Surface Layer and the flow structure of Red Blood Cells
Authors: Tsvirkun Daria , Grichine Alexei , Duperray Alain , Misbah Chaouqi , Bureau Lionel 
Published: March 2017

AbstractMicrovasculatures-on-a-chip,i.e. in vitromodels that mimic important features of microvessel networks, have gained increasing interest in recent years. Such devices have allowed investigating pathophysiological situations involving abnormal biophysical interactions between blood cells and vessel walls. Still, a central question remains regarding the presence, in such biomimetic systems, of the endothelial glycocalyx. The latter is a glycosaminoglycans-rich surface layer exposed to blood flow, which plays a crucial role in regulating the interactions between circulating cells and the endothelium. Here, we use confocal microscopy to characterize the layer expressed by endothelial cells cultured in microfluidic channels. We show that, under our culture conditions, endothelial cells form a confluent layer on all the walls of the circuit and display a glycocalyx that fully lines the lumen of the microchannels. Moreover, the thickness of this surface layer is found to be on the order of 600 nm, which compares well with measurements performedexorin vivoon microcapillaries. Furthermore, we investigate how the presence of endothelial cells in the microchannels affects their hydrodynamic resistance and the near-wall motion of red blood cells. Our study thus provides an important insight into the physiological relevance ofin vitromicrovasculatures.
In-situ Raman spectroscopy to elucidate the influence of adsorption in graphene electrochemistry
Authors: van den Beld Wesley T. E. , Odijk Mathieu , Vervuurt René H. J. , Weber Jan-Willem , Bol Ageeth A. , van den Berg Albert , Eijkel Jan C. T. 
Published: March 2017

AbstractElectrochemistry on graphene is of particular interest due to graphene’s high surface area, high electrical conductivity and low interfacial capacitance. Because the graphene Fermi level can be probed by its strong Raman signal, information on the graphene doping can be obtained which in turn can provide information on adsorbed atoms or molecules. For this paper, the adsorption analysis was successfully performed using three electroactive substances with different electrode interaction mechanisms: hexaammineruthenium(III) chloride (RuHex), ferrocenemethanol (FcMeOH) and potassium ferricyanide/potassium ferrocyanide (Fe(CN)6). The adsorption state was probed by analysing the G-peak position in the measured in-situ Raman spectrum during electrochemical experiments. We conclude that electrochemical Raman spectroscopy on graphene is a valuable tool to obtain in-situ information on adsorbed species on graphene, isolated from the rest of the electrochemical behaviour.
Identification of hexose kinase genes in Kluyveromyces marxianus and thermo-tolerant one step producing glucose-free fructose strain construction
Authors: Zhang Guorong , Lu Min , Wang Jichao , Wang Dongmei , Gao Xiaolian , Hong Jiong 
Published: March 2017

AbstractIn yeast, the hexose assimilation is started at hexose phosphorylation. However, in Kluyveromyces marxianus, the hexokinase (HXK) and glucokinase (GLK) genes were not identified by experiments. Meanwhile, the glucose-free fructose product requires more cost-efficient method. In this study, the KmHXK1 and KmGLK1 genes were functionally identified through gene disruption, over-expression and recombinant enzymes characterization. Both glucose and fructose assimilation ability decreased significantly in KmHXK1 disrupted strain YLM001, however, this ability was not changed obviously in KmGLK1 disrupted strain YLM002. When over-expressing KmGLK1 in YLM001, only the glucose assimilation ability was recovered in obtained strain (YLM005). The kinetic constant analysis of recombinant enzymes also proved that KmHXK1 could phosphorylate glucose (Vmax 553.01 U/mg, Km 0.83 mM) and fructose (Vmax 609.82 U/mg, Km 0.52 mM), and KmGLK1 only phosphorylate glucose with a Vmax of 0.73 U/mg and a Km 4.09 mM. A thermo-tolerant strain YGR003 which produced glucose-free fructose from Jerusalem artichoke tuber in one step was constructed based on the obtained information. The highest production and fastest productivity were 234.44 g/L and 10.26 g/L/h, respectively, which were several folds of the results in previous reports.
Intermediate filament reorganization dynamically influences cancer cell alignment and migration
Authors: Holle Andrew W. , Kalafat Melih , Ramos Adria Sales , Seufferlein Thomas , Kemkemer Ralf , Spatz Joachim P. 
Published: March 2017

AbstractThe interactions between a cancer cell and its extracellular matrix (ECM) have been the focus of an increasing amount of investigation. The role of the intermediate filament keratin in cancer has also been coming into focus of late, but more research is needed to understand how this piece fits in the puzzle of cytoskeleton-mediated invasion and metastasis. In Panc-1 invasive pancreatic cancer cells, keratin phosphorylation in conjunction with actin inhibition was found to be sufficient to reduce cell area below either treatment alone. We then analyzed intersecting keratin and actin fibers in the cytoskeleton of cyclically stretched cells and found no directional correlation. The role of keratin organization in Panc-1 cellular morphological adaptation and directed migration was then analyzed by culturing cells on cyclically stretched polydimethylsiloxane (PDMS) substrates, nanoscale grates, and rigid pillars. In general, the reorganization of the keratin cytoskeleton allows the cell to become more ‘mobile’- exhibiting faster and more directed migration and orientation in response to external stimuli. By combining keratin network perturbation with a variety of physical ECM signals, we demonstrate the interconnected nature of the architecture inside the cell and the scaffolding outside of it, and highlight the key elements facilitating cancer cell-ECM interactions.
The Effect Of microbial Mats In The Decay Of Anurans With Implications For Understanding Taphonomic Processes In The Fossil Record
Authors: Iniesto M. , Villalba I. , Buscalioni A. D. , Guerrero M. C. , López-Archilla A. I. 
Published: March 2017

AbstractThe pattern and sequence of the decomposition of the Pipidae African dwarf frog (Hymenochirusboettgeri) is tracked in an experiment with microbial mats in order to explore soft tissue preservation over three years. Frog decay in microbial mats is preceded by rapid entombment (25–30 days) and mediated by the formation of a sarcophagus, which is built by a complex microbial community. The frog carcasses maintained a variety of soft tissues for years. Labile organic structures show greater durability within the mat, cells maintain their general shape (bone marrow cells and adipocytes), and muscles and connective tissues (adipose and fibrous tendons) exhibit their original organic structures. In addition, other soft tissues are promptly mineralized (day 540) in a Ca-rich carbonate phase (encephalic tectum) or enriched in sulphur residues (integumentary system). The result is coherent with a bias in soft-tissue preservation, as some tissues are more likely to be conserved than others. The outcomes support observations of exceptionally preserved fossil anurans (adults and tadpoles). Decomposition in mats shows singular conditions of pH and dissolved oxygen. Mineralization processes could be more diverse than in simple heterotrophic biofilms, opening new taphonomic processes that have yet to be explored.
Schisandrin A inhibits dengue viral replication via upregulating antiviral interferon responses through STAT signaling pathway
Authors: Yu Jung-Sheng , Wu Yu-Hsuan , Tseng Chin-Kai , Lin Chun-Kuang , Hsu Yao-Chin , Chen Yen-Hsu , Lee Jin-Ching 
Published: March 2017

AbstractDengue virus (DENV) infects 400 million people worldwide annually. Infection of more than one serotype of DENV highly corresponds to dengue hemorrhagic fever and dengue shock syndrome, which are the leading causes of high mortality. Due to lack of effective vaccines and unavailable therapies against DENV, discovery of anti-DENV agents is urgently needed. We first characterize that Schisandrin A can inhibit the replication of four serotypes of DENV in a concentration- and time-dependent manner, with an effective half-maximal effective concentration 50% (EC50) value of 28.1 ± 0.42 μM against DENV serotype type 2 without significant cytotoxicity. Furthermore, schisandrin A can effectively protect mice from DENV infection by reducing disease symptoms and mortality of DENV-infected mice. We demonstrate that STAT1/2-mediated antiviral interferon responses contribute to the action of schisandrin A against DENV replication. Schisandrin A represents a potential antiviral agent to block DENV replication in vitro and in vivo. In conclusion, stimulation of STAT1/2-mediated antiviral interferon responses is a promising strategy to develop antiviral drug.
Entropic stabilization of a deubiquitinase provides conformational plasticity and slow unfolding kinetics beneficial for functioning on the proteasome
Authors: Lee Yun-Tzai Cloud , Chang Chia-Yun , Chen Szu-Yu , Pan Yun-Ru , Ho Meng-Ru , Hsu Shang-Te Danny 
Published: March 2017

AbstractHuman ubiquitin C-terminal hydrolyase UCH-L5 is a topologically knotted deubiquitinase that is activated upon binding to the proteasome subunit Rpn13. The length of its intrinsically disordered cross-over loop is essential for substrate recognition. Here, we showed that the catalytic domain of UCH-L5 exhibits higher equilibrium folding stability with an unfolding rate on the scale of 10−8 s−1, over four orders of magnitudes slower than its paralogs, namely UCH-L1 and -L3, which have shorter cross-over loops. NMR relaxation dynamics analysis confirmed the intrinsic disorder of the cross-over loop. Hydrogen deuterium exchange analysis further revealed a positive correlation between the length of the cross-over loop and the degree of local fluctuations, despite UCH-L5 being thermodynamically and kinetically more stable than the shorter UCHs. Considering the role of UCH-L5 in removing K48-linked ubiquitin to prevent proteasomal degradation of ubiquitinated substrates, our findings offered mechanistic insights into the evolution of UCH-L5. Compared to its paralogs, it is entropically stabilized to withstand mechanical unfolding by the proteasome while maintaining structural plasticity. It can therefore accommodate a broad range of substrate geometries at the cost of unfavourable entropic loss.
Non-thermal air plasma promotes the healing of acute skin wounds in rats
Authors: Kubinova S. , Zaviskova K. , Uherkova L. , Zablotskii V. , Churpita O. , Lunov O. , Dejneka A. 
Published: March 2017

AbstractNon-thermal plasma (NTP) has nonspecific antibacterial effects, and can be applied as an effective tool for the treatment of chronic wounds and other skin pathologies. In this study we analysed the effect of NTP on the healing of the full-thickness acute skin wound model in rats. We utilised a single jet NTP system generating atmospheric pressure air plasma, with ion volume density 5 · 1017 m−3 and gas temperature 30–35 °C. The skin wounds were exposed to three daily plasma treatments for 1 or 2 minutes and were evaluated 3, 7 and 14 days after the wounding by histological and gene expression analysis. NTP treatment significantly enhanced epithelization and wound contraction on day 7 when compared to the untreated wounds. Macrophage infiltration into the wound area was not affected by the NTP treatment. Gene expression analysis did not indicate an increased inflammatory reaction or a disruption of the wound healing process; transient enhancement of inflammatory marker upregulation was found after NTP treatment on day 7. In summary, NTP treatment had improved the healing efficacy of acute skin wounds without noticeable side effects and concomitant activation of pro-inflammatory signalling. The obtained results highlight the favourability of plasma applications for wound therapy in clinics.
Genome-wide random regression analysis for parent-of-origin effects of body composition allometries in mouse
Authors: Zhao Jingli , Li Shuling , Wang Lijuan , Jiang Li , Yang Runqing , Cui Yuehua 
Published: March 2017

AbstractGenomic imprinting underlying growth and development traits has been recognized, with a focus on the form of absolute or pure growth. However, little is known about the effect of genomic imprinting on relative growth. In this study, we proposed a random regression model to estimate genome-wide imprinting effects on the relative growth of multiple tissues and organs to body weight in mice. Joint static allometry scaling equation as sub-model is nested within the genetic effects of markers and polygenic effects caused by a pedigree. Both chromosome-wide and genome-wide statistical tests were conducted to identify imprinted quantitative trait nucleotides (QTNs) associated with relative growth of individual tissues and organs to body weight. Real data analysis showed that three of six analysed tissues and organs are significantly associated with body weight in terms of phenotypic relative growth. At the chromosome-wide level, a total 122 QTNs were associated with allometries of kidney, spleen and liver weights to body weight, 36 of which were imprinted with different imprinting fashions. Further, only two imprinted QTNs responsible for relative growth of spleen and liver were verified by genome-wide test. Our approach provides a general framework for statistical inference of genomic imprinting underlying allometry scaling in animals.