bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of GXXXXG motif in Chrysophsin-1 and its implication in the design of analogs with cell-selective antimicrobial and anti-endotoxin activities
Authors: Tripathi Amit Kumar , Kumari Tripti , Harioudh Munesh Kumar , Yadav Pranjal Kumar , Kathuria Manoj , Shukla P. K. , Mitra Kalyan , Ghosh Jimut Kanti 
Published: June 2017

AbstractMarine fish antimicrobial peptide, chrysophsin-1 possesses versatile biological activities but its non-selective nature restricts its therapeutic possibilities. Often small alterations in structural motifs result in significant changes in the properties of concerned proteins/peptides. We have identified GXXXXG motif in chrysophsin-1. Glycine residue(s) of this motif in Chrysophsin-1 was/were replaced with alanine, valine and proline residue(s). Of these, proline-substituted Chrysophsin-1 analogs exhibited significantly reduced cytotoxicity towards mammalian cells. Further, these analogs showed broad-spectrum activity against Gram-positive, Gram-negative bacteria, Methicillin-resistant Staphylococcus aureus strains and fungi and also retained antibacterial activity in presence of physiological salts, serum and at elevated temperatures indicative of their therapeutic potential. These Chrysophsin-1 analogs also inhibited lipopolysaccharide (LPS) induced pro-inflammatory responses in THP-1 cells and in murine primary macrophages. One of these single proline-substituted Chrysophsin-1 analogs inhibited LPS-stimulated pro-inflammatory cytokine production in BALB/c mice and elicited appreciable survival of mice administered with a lethal dose of LPS in a model of severe sepsis. The data for the first time showed the implication of GXXXXG motifs in functional and biological properties of an antimicrobial peptide and could be useful to design novel anti-microbial and anti-endotoxin peptides by employing this motif.
Enhanced chondrogenesis of bone marrow-derived stem cells by using a combinatory cell therapy strategy with BMP-2/TGF-β1, hypoxia, and COL1A1/HtrA1 siRNAs
Authors: Legendre Florence , Ollitrault David , Gomez-Leduc Tangni , Bouyoucef Mouloud , Hervieu Magalie , Gruchy Nicolas , Mallein-Gerin Frédéric , Leclercq Sylvain , Demoor Magali , Galéra Philippe 
Published: June 2017

AbstractMesenchymal stem cells (MSCs) hold promise for cartilage engineering. Here, we aimed to determine the best culture conditions to induce chondrogenesis of MSCs isolated from bone marrow (BM) of aged osteoarthritis (OA) patients. We showed that these BM-MSCs proliferate slowly, are not uniformly positive for stem cell markers, and maintain their multilineage potential throughout multiple passages. The chondrogenic lineage of BM-MSCs was induced in collagen scaffolds, under normoxia or hypoxia, by BMP-2 and/or TGF-β1. The best chondrogenic induction, with the least hypertrophic induction, was obtained with the combination of BMP-2 and TGF-β1 under hypoxia. Differentiated BM-MSCs were then transfected with siRNAs targeting two markers overexpressed in OA chondrocytes, type I collagen and/or HtrA1 protease. siRNAs significantly decreased mRNA and protein levels of type I collagen and HtrA1, resulting in a more typical chondrocyte phenotype, but with frequent calcification of the subcutaneously implanted constructs in a nude mouse model. Our 3D culture model with BMP-2/TGF-β1 andCOL1A1/HtrA1siRNAs was not effective in producing a cartilage-like matrixin vivo. Further optimization is needed to stabilize the chondrocyte phenotype of differentiated BM-MSCs. Nevertheless, this study offers the opportunity to develop a combinatory cellular therapy strategy for cartilage tissue engineering.
Raman micro-spectroscopy as a viable tool to monitor and estimate the ionic transport in epithelial cells
Authors: Puppulin Leonardo , Pezzotti Giuseppe , Sun Hongxin , Hosogi Shigekuni , Nakahari Takashi , Inui Toshio , Kumamoto Yasuaki , Tanaka Hideo , Marunaka Yoshinori 
Published: June 2017

AbstractThe typical response to the lowering of plasma Na+ concentration and blood pressure in our body involves the release of aldosterone from the adrenal glands, which triggers the reabsorption of sodium in the kidney. Although the effects of aldosterone on this physiological mechanism were extensively studied in the past decades, there are still some aspects to be fully elucidated. In the present study, we propose for the first time a new approach based on Raman spectroscopy to monitor the ionic activity in aldosterone-treated A6 renal epithelial cells. This spectroscopic technique is capable of probing the cells through their thickness in a non-destructive and nimble way. The spectroscopic variations of the Raman bands associated to the O-H stretching of water were correlated to the variations of ionic concentration in the intracellular and extracellular fluids. The increase of Na+ concentration gradients was clearly visualized in the cytosol of aldosterone-treated cells. The enhancement of the Na+ current density induced by aldosterone was estimated from the variation of the ionic chemical potential across the intracellular space. In addition, the variation of the O-H Raman bands of water was used to quantify the cell thickness, which was not affected by aldosterone.
Temporal trends in initiation of VKA, rivaroxaban, apixaban and dabigatran for the treatment of venous thromboembolism - A Danish nationwide cohort study
Authors: Sindet-Pedersen Caroline , Pallisgaard Jannik Langtved , Staerk Laila , Berger Jeffrey S. , Lamberts Morten , Torp-Pedersen Christian , Gislason Gunnar H. , Olesen Jonas Bjerring 
Published: June 2017

AbstractDanish nationwide registries were used to investigate temporal trends in initiation of rivaroxaban or apixaban or dabigatran versus vitamin K antagonists (VKA) in patients with venous thromboembolism (VTE). Patients treated with one of the NOACs (rivaroxaban, dabigatran, apixaban) or VKA were identified between February 2012 and September 2016. A total of 19,578 patients were included of which 10,844 (55.4%) were treated with VKA and 8,734 (44.6%) were treated with NOACs (rivaroxaban 7,572, apixaban 1,066, and dabigatran 96). Temporal trends showed a decrease in the initiation of VKA (p-value for decreasing trend, p < 0001) and an increase in the initiation of rivaroxaban and apixaban (p-value for increasing trend, p < 0001). By September 2016, 12%, 70%, 16%, and 2% of patients with VTE were initiated on VKA, rivaroxaban, apixaban, and dabigatran. Patients with previous VTE, chronic kidney disease, liver disease, cancer, and thrombophilia were more likely to be initiated on VKA compared with one of the NOACs. In conclusion the initiation of rivaroxaban and apixaban is increasing significantly over time in patients with VTE. Patients with previous VTE, chronic kidney disease, liver disease, cancer, and thrombophilia were more likely to be initiated on VKA compared with rivaroxaban or apixaban.
3D ultra-high resolution seismic imaging of shallow Solfatara crater in Campi Flegrei (Italy): New insights on deep hydrothermal fluid circulation processes
Authors: De Landro Grazia , Serlenga Vincenzo , Russo Guido , Amoroso Ortensia , Festa Gaetano , Bruno Pier Paolo , Gresse Marceau , Vandemeulebrouck Jean , Zollo Aldo 
Published: June 2017

AbstractSeismic tomography can be used to image the spatial variation of rock properties within complex geological media such as volcanoes. Solfatara is a volcano located within the Campi Flegrei, a still active caldera, so it is of major importance to characterize its level of activity and potential danger. In this light, a 3D tomographic high-resolution P-wave velocity image of the shallow central part of Solfatara crater is obtained using first arrival times and amultiscaleapproach. The retrieved images, integrated with the resistivity section and temperature and the CO2flux measurements, define the following characteristics: 1. A depth-dependent P-wave velocity layer down to 14 m, with Vp < 700 m/s typical of poorly-consolidated tephra and affected by CO2degassing; 2. An intermediate layer, deepening towards the mineralized liquid-saturated area (Fangaia), interpreted as permeable deposits saturated with condensed water; 3. A deep, confined high velocity anomaly associated with a CO2reservoir. These features are expression of an area located between the Fangaia, water saturated and replenished from deep aquifers, and the main fumaroles, superficial relief of the deep rising CO2flux. Therefore, the changes in the outgassing rate greatly affect the shallow hydrothermal system, which can be used as a “mirror” of fluid migration processes occurring at depth.
Insights into enterotoxigenic Escherichia coli diversity in Bangladesh utilizing genomic epidemiology
Authors: Sahl Jason W. , Sistrunk Jeticia R. , Baby Nabilah Ibnat , Begum Yasmin , Luo Qingwei , Sheikh Alaullah , Qadri Firdausi , Fleckenstein James M. , Rasko David A. 
Published: June 2017

AbstractEnterotoxigenicEscherichia coli(ETEC) cause more than 500,000 deaths each year in the developing world and are characterized on a molecular level by the presence of genes that encode the heat-stable (ST) and/or heat-labile (LT) enterotoxins, as well as surface structures, known as colonization factors (CFs). Genome sequencing and comparative genomic analyses of 94 previously uncharacterized ETEC isolates demonstrated remarkable genomic diversity, with 28 distinct sequence types identified in three phylogenomic groups. Interestingly, there is a correlation between the genomic sequence type and virulence factor profiles based on prevalence of the isolate, suggesting that there is an optimal combination of genetic factors required for survival, virulence and transmission in the most successful clones. A large-scale BLAST score ratio (LS-BSR) analysis was further applied to identify ETEC-specific genomic regions when compared to non-ETEC genomes, as well as genes that are more associated with clinical presentations or other genotypic markers. Of the strains examined, 21 of 94 ETEC isolates lacked any previously identified CF. Homology searches with the structural subunits of known CFs identified 6 new putative CF variants. These studies provide a roadmap to exploit genomic analyses by directing investigations of pathogenesis, virulence regulation and vaccine development.
Integrin α2β1 in nonactivated conformation can induce focal adhesion kinase signaling
Authors: Salmela Maria , Jokinen Johanna , Tiitta Silja , Rappu Pekka , Cheng R. Holland , Heino Jyrki 
Published: June 2017

AbstractConformational activation of integrins is generally required for ligand binding and cellular signalling. However, we have previously reported that the nonactivated conformation of α2β1 integrin can also bind to large ligands, such as human echovirus 1. In this study, we show that the interaction between the nonactivated integrin and a ligand resulted in the activation of focal adhesion kinase (FAK) in a protein kinase C dependent manner. A loss-of-function mutation, α2E336A, in the α2-integrin did not prevent the activation of FAK, nor did EDTA-mediated inactivation of the integrin. Full FAK activation was observed, since phosphorylation was not only confirmed in residue Y397, but also in residues Y576/7. Furthermore, initiation of downstream signaling by paxillin phosphorylation in residue Y118 was evident, even though this activation was transient by nature, probably due to the lack of talin involvement in FAK activation and the absence of vinculin in the adhesion complexes formed by the nonactivated integrins. Altogether these results indicate that the nonactivated integrins can induce cellular signaling, but the outcome of the signaling differs from conventional integrin signaling.
Electron-band theory inspired design of magnesium–precious metal bulk metallic glasses with high thermal stability and extended ductility
Authors: Laws Kevin J. , Shamlaye Karl F. , Granata Davide , Koloadin Leah S. , Löffler Jörg F. 
Published: June 2017

AbstractMagnesium-based bulk metallic glasses (BMGs) exhibit high specific strengths and excellent glass-forming ability compared to other metallic systems, making them suitable candidates for next-generation materials. However, current Mg-based BMGs tend to exhibit low thermal stability and are prone to structural relaxation and brittle failure. This study presents a range of new magnesium–precious metal-based BMGs from the ternary Mg–Ag–Ca, Mg–Ag–Yb, Mg–Pd–Ca and Mg–Pd–Yb alloy systems with Mg content greater than 67 at.%. These alloys were designed for high ductility by utilising atomic bond-band theory and a topological efficient atomic packing model. BMGs from the Mg–Pd–Ca alloy system exhibit high glass-forming ability with critical casting sizes of up to 3 mm in diameter, the highest glass transition temperatures (>200 °C) of any reported Mg-based BMG to date, and sustained compressive ductility. Alloys from the Mg–Pd–Yb family exhibit critical casting sizes of up to 4 mm in diameter, and the highest compressive plastic (1.59%) and total (3.78%) strain to failure of any so far reported Mg-based glass. The methods and theoretical approaches presented here demonstrate a significant step forward in the ongoing development of this extraordinary class of materials.
In-depth method assessments of differentially expressed protein detection for shotgun proteomics data with missing values
Authors: Wang Jinxia , Li Liwei , Chen Tao , Ma Jie , Zhu Yunping , Zhuang Jujuan , Chang Cheng 
Published: June 2017

AbstractConsidering as one of the major goals in quantitative proteomics, detection of the differentially expressed proteins (DEPs) plays an important role in biomarker selection and clinical diagnostics. There have been plenty of algorithms and tools focusing on DEP detection in proteomics research. However, due to the different application scopes of these methods, and various kinds of experiment designs, it is not very apparent about the best choice for large-scale proteomics data analyses. Moreover, given the fact that proteomics data usually contain high percentage of missing values (MVs), but few replicates, a systematic evaluation of the DEP detection methods combined with the MV imputation methods is essential and urgent. Here, we analyzed a total of four representative imputation methods and five DEP methods on different experimental and simulated datasets. The results showed that (i) MV imputation could not always improve the performances of DEP detection methods and the imputation effects differed in the missing value percentages; (ii) the DEP detection methods had different statistical powers affected by the percentage of MVs. Two statistical methods (i.e. the empirical Bayesian random censoring threshold model, and the significance analysis of microarray) performed better than the other evaluated methods in terms of accuracy and sensitivity.
Streptococcus sp. in neonatal endotracheal tube biofilms is associated with ventilator-associated pneumonia and enhanced biofilm formation of Pseudomonas aeruginosa PAO1
Authors: Pan Yun , Song Sijie , Tang Xiaoli , Ai Qing , Zhu Danping , Liu Zhenqiu , Yu Jialin 
Published: June 2017

AbstractVentilator-associated pneumonia (VAP) is a serious complication of mechanical ventilation leading to high morbidity and mortality among intubated neonates in neonatal intensive care units (NICUs). Endotracheal tube (ETT) biofilm flora were considered to be responsible for the occurrence of VAP as a reservoir of pathogens. However, regarding neonates with VAP, little is known about the complex microbial signatures in ETT biofilms. In the present study, a culture-independent approach based on next generation sequencing was performed as an initial survey to investigate the microbial communities in ETT biofilms of 49 intubated neonates with and without VAP. Our results revealed a far more complex microflora in ETT biofilms from intubated neonates compared to a previous culture-based study. The abundance of Streptococci in ETT biofilms was significantly related to the onset of VAP. By isolating Streptococci in ETT biofilms, we found that Streptococci enhanced biofilm formation of the common nosocomial pathogenPseudomonas aeruginosaPAO1 and decreased IL-8 expression of airway epithelia cells exposed to the biofilm conditioned medium of PAO1. This study provides new insight into the pathogenesis of VAP among intubated neonates. More studies focusing on intubated neonates are warranted to develop strategies to address this important nosocomial disease in NICUs.
Determination of arsenic and lead in single hair strands by laser ablation inductively coupled plasma mass spectrometry
Authors: Luo Ruxin , Su Xiaohong , Xu Weicong , Zhang Sujing , Zhuo Xianyi , Ma Dong 
Published: June 2017

AbstractThe purpose of this study was to develop matrix-matched hair standards and a LA-ICP-MS technique for determination of the As and Pb in a single human hair using single spot scan mode. These results could subsequently be used to infer when the element entered the body. This study was conducted in two parts. First, a method was developed and validated for the elemental analysis of hair by LA-ICP-MS. A calibration strategy in LA-ICP-MS was developed using prepared matrix-matched laboratory hair standards doped with analytes of interest at a defined concentration. The use of hair strand standards enables calibration curves to be obtained by plotting the analyte ion (M+) intensity normalized to34S+(the ratio M+/34S+) as a function of the concentration determined by ICP-MS of the acidic digests. The linear correlation coefficients (R2) of the calibration curves for the analytes As and Pb were typically between 0.9970 and 0.9998, respectively. Second, an actual hair was measured using the developed method. The spatial distribution of As along the hair was observed in a hair sample from a leukaemia patient treated with arsenic trioxide (As2O3). The actual and estimated times over which the drug entered the body were compared and discussed.
Protective and therapeutic effect of felodipine against bleomycin-induced pulmonary fibrosis in mice
Authors: Tanaka Ken-ichiro , Niino Tomomi , Ishihara Tomoaki , Takafuji Ayaka , Takayama Takahiro , Kanda Yuki , Sugizaki Toshifumi , Tamura Fumiya , Kurotsu Shota , Kawahara Masahiro , Mizushima Tohru 
Published: June 2017

AbstractIdiopathic pulmonary fibrosis (IPF) involves alveolar epithelial injury and abnormal collagen production caused by activated fibroblasts; transforming growth factor (TGF)-β1 is implicated in this activation. In this study, we screened for chemicals capable of inhibiting TGF-β1-induced collagen production in cultured fibroblasts from medicines already in clinical use. We selected felodipine based on its extent of collagen production inhibition, clinical safety profile, and other pharmacological activity. Felodipine is a dihydropyridine Ca2+ channel blocker that has been used clinically to treat patients with high blood pressure. Felodipine suppressed collagen production within LL29 cells in the presence of TGF-β1, but not in its absence. Intratracheal administration of felodipine prevented bleomycin-induced pulmonary fibrosis, alteration of lung mechanics and respiratory dysfunction. Felodipine also improved pulmonary fibrosis, as well as lung and respiratory function when administered after fibrosis development. Furthermore, administration of felodipine suppressed a bleomycin-induced increase in activated fibroblasts in the lung. We also found other dihydropyridine Ca2+ channel blockers (nifedipine and benidipine) inhibited collagen production in vitro and partially prevented bleomycin-induced pulmonary fibrosis, alteration of lung mechanics and respiratory dysfunction in vivo. We propose that these Ca2+ channel blockers may be therapeutically beneficial for IPF patients.
Competing Factors Link to Bone Health in Polycystic Ovary Syndrome: Chronic Low-Grade Inflammation Takes a Toll
Authors: Kalyan Shirin , Patel Millan S. , Kingwell Elaine , Côté Hélène C. F. , Liu Danmei , Prior Jerilynn C. 
Published: June 2017

AbstractChronic inflammation predisposes to poor bone health. Women with polycystic ovary syndrome (PCOS) experience androgen excess, ovulatory disturbances, insulin resistance, abdominal adiposity and chronic inflammation. Our objective was to investigate the relationships among bone health parameters, chronic subclinical inflammation and anthropometric measures in premenopausal women with and without PCOS. In 61 premenopausal women, 22 women with PCOS and 39 controls, we assessed bone parameters (total hip bone mineral density [BMD] by dual-energy X-ray absorptiometry and radius strength-strain index [SSI] by peripheral quantitative computed tomography), inflammation (C-reactive protein/albumin), oxidative stress (leukocyte telomere length, urinary 8-hydroxydeoxyguanosine); hemoglobin A1c; anthropometric measures (body mass index, waist-to-height ratio, cross-sectional muscle area). A diagnosis of PCOS negatively predicted (beta = −0.251, p = 0.022) hip BMD in a regression model including weight. In women with PCOS, inflammation, which was predicted by increased waist-to-height ratio and current use of oral contraceptives, attenuated the positive influences of increased weight and muscle mass on bone strength and was inversely associated with radial SSI (R2 = 0.25, p = 0.018). In conclusion, chronic subclinical inflammation may negatively impact bone physiology in women with PCOS. Strategies focused on reducing abdominal adiposity and avoiding medications that increase inflammation may counter this effect.
Performance of four modern whole genome amplification methods for copy number variant detection in single cells
Authors: Deleye Lieselot , Tilleman Laurentijn , Vander Plaetsen Ann-Sophie , Cornelis Senne , Deforce Dieter , Van Nieuwerburgh Filip 
Published: June 2017

AbstractWhole genome amplification (WGA) has become an invaluable tool to perform copy number variation (CNV) detection in single, or a limited number of cells. Unfortunately, current WGA methods introduce representation bias that limits the detection of small CNVs. New WGA methods have been introduced that might have the potential to reduce this bias. We compared the performance of PicoPLEX DNA-Seq (Picoseq), DOPlify, REPLI-g and Ampli-1 WGA for aneuploidy screening and copy number analysis using shallow whole genome massively parallel sequencing (MPS), starting from single or a limited number of cells. Although the four WGA methods perform differently, they are all suited for this application.
Local immunization impacts the response of dairy cows to Escherichia coli mastitis
Authors: Herry Vincent , Gitton Christophe , Tabouret Guillaume , Répérant Maryline , Forge Laurine , Tasca Christian , Gilbert Florence B. , Guitton Edouard , Barc Céline , Staub Christophe , Smith David G. E. , Germon Pierre , Foucras Gilles , Rainard Pascal 
Published: June 2017

AbstractCurrent vaccines to Escherichia coli mastitis have shown some albeit limited efficacy. Their mode of action has not been documented, and immune responses protecting the mammary gland against E. coli are not completely understood. To improve our knowledge of mammary gland immune protection, cows immunized either intramuscularly or intramammarily with the E. coli P4 were submitted to a homologous mastitis challenge. A third group of mock-immunized cows serve as challenge controls. Local immunization modified favorably the course of infection, by improving bacterial clearance while limiting inflammation. Systemic clinical signs and reduction in milk secretion were also contained. This occurred with a modification of the cytokine profile, such as an increase in IFN-γ and a reduction in TNF-α concentrations in milk. Concentrations of IL-17A and IL-22 increased in milk at the onset of the inflammatory response and remained high up to the elimination of bacteria, but concentrations did not differ between groups. Accelerated bacteriological cure was not linked to an increase in the initial efficiency of phagocytosis in milk. Results support the idea that antibodies did not play a major role in the improvement, and that cell-mediated immunity is the key to understanding E. coli vaccine-induced protection of the mammary gland.