bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rational drug-design approach supported with thermodynamic studies — a peptide leader for the efficient bi-substrate inhibitor of protein kinase CK2
Authors: Winiewska-Szajewska Maria , Płonka Dawid , Zhukov Igor , Poznański Jarosław 
Published: July 2019

AbstractNumerous inhibitors of protein kinases act on the basis of competition, targeting the ATP binding site. In this work, we present a procedure of rational design of a bi-substrate inhibitor, complemented with biophysical assays. The inhibitors of this type are commonly engineered by combining ligands carrying an ATP-like part with a peptide or peptide-mimicking fragment that determines specificity. Approach presented in this paper led to generation of a specific system for independent screening for efficient ligands and peptides, by means of thermodynamic measurements, that assessed the ability of the identified ligand and peptide to combine into a bi-substrate inhibitor. The catalytic subunit of human protein kinase CK2 was used as the model target. Peptide sequence was optimized using peptide libraries [KGDE]-[DE]-[ST]-[DE]3–4-NH2, originated from the consensus CK2 sequence. We identified KESEEE-NH2 peptide as the most promising one, whose binding affinity is substantially higher than that of the reference RRRDDDSDDD peptide. We assessed its potency to form an efficient bi-substrate inhibitor using tetrabromobenzotriazole (TBBt) as the model ATP-competitive inhibitor. The formation of ternary complex was monitored using Differential Scanning Fluorimetry (DSF), Microscale Thermophoresis (MST) and Isothermal Titration Calorimetry (ITC).
The Role of Visual Experience in Auditory Space Perception around the Legs
Authors: Aggius-Vella Elena , Campus Claudio , Kolarik Andrew Joseph , Gori Monica 
Published: July 2019

AbstractIt is widely accepted that vision plays a key role in the development of spatial skills of the other senses. Recent works have shown that blindness is often associated with auditory spatial deficits. The majority of previous studies have focused on understanding the representation of the upper frontal body space where vision and actions have a central role in mapping the space, however less research has investigated the back space and the space around the legs. Here we investigate space perception around the legs and the role of previous visual experience, by studying sighted and blind participants in an audio localization task (front-back discrimination). Participants judged if a sound was delivered in their frontal or back space. The results showed that blindfolded sighted participants were more accurate than blind participants in the frontal space. However, both groups were similarly accurate when auditory information was delivered in the back space. Blind individuals performed the task with similar accuracy for sounds delivered in the frontal and back space, while sighted people performed better in the frontal space. These results suggest that visual experience influences auditory spatial representations around the legs. Moreover, these results suggest that hearing and vision play different roles in different spaces.
Comparative genomics suggests loss of keratin K24 in three evolutionary lineages of mammals
Authors: Ehrlich Florian , Laggner Maria , Langbein Lutz , Burger Pamela , Pollreisz Andreas , Tschachler Erwin , Eckhart Leopold 
Published: July 2019

AbstractKeratins are the main cytoskeletal proteins of epithelial cells and changes in the expression of keratins have contributed to the evolutionary adaptation of epithelia to different environments. Keratin K24 was proposed to be a differentiation marker of epidermal keratinocytes but the significance of K24 expression in the epidermis versus other tissues has remained elusive. Here, we show by RT-PCR, western blot, and immunofluorescence analyses that K24 is highly expressed in the epithelium of the cornea whereas its expression levels are significantly lower in other stratified epithelia including in the epidermis. To investigate the evolutionary history of K24, we screened the genome sequences of vertebrates for orthologs of the human KRT24 gene. The results of this comparative genomics study suggested that KRT24 originated in a common ancestor of amniotes and that it was lost independently in three clades of mammals, i.e. camels, cetaceans, and a subclade of pinnipeds comprising eared seals and the walrus. Together, the results of this study identify K24 as component of the cytoskeleton in the human corneal epithelium and reveal previously unknown differences of keratin gene content among mammalian species.
Serum PlGF and EGF are independent prognostic markers in non-metastatic colorectal cancer
Authors: Schölch Sebastian , Bogner Andreas , Bork Ulrich , Rahbari Mohammad , Győrffy Balázs , Schneider Martin , Reissfelder Christoph , Weitz Jürgen , Rahbari Nuh N. 
Published: July 2019

AbstractThe aim of this study was to determine the prognostic value of circulating angiogenic cytokines in non-metastatic colorectal cancer (CRC) patients. Preoperative serum samples of a training (TC) (n = 219) and a validation cohort (VC) (n = 168) were analyzed via ELISA to determine PlGF, EGF, VEGF, Ang1, PDGF-A, PDGF-B, IL-8 and bFGF levels. In addition, survival was correlated with PlGF and EGF expression measured by microarray and RNAseq in two publicly available, independent cohorts (n = 550 and n = 463, respectively). Prognostic values for overall (OS) and disease-free survival (DFS) were determined using uni- and multivariate Cox proportional hazard analyses. Elevated PlGF is predictive for impaired OS (TC: HR 1.056; p = 0.046; VC: HR 1.093; p = 0.001) and DFS (TC: HR 1.052; p = 0.029; VC: HR 1.091; p = 0.009). Conversely, elevated EGF is associated with favorable DFS (TC: HR 0.998; p = 0.045; VC: HR 0.998; p = 0.018) but not OS (TC: p = 0.201; VC: p = 0.453). None of the other angiogenic cytokines correlated with prognosis. The prognostic value of PlGF (OS + DFS) and EGF (DFS) was confirmed in both independent retrospective cohorts. Serum PlGF and EGF may serve as prognostic markers in non-metastatic CRC.
Thermal damage in three-dimensional vivo bio-tissues induced by moving heat sources in laser therapy
Authors: Ma Jingxuan , Yang Xianfeng , Sun Yuxin , Yang Jialing 
Published: July 2019

AbstractThe thermal damage of a three-dimensional bio-tissue model irradiated by a movable laser beam was studied in this work. By employing the DPL biological heat conduction model and Henriques’ thermal damage assessment model, the distribution of burn damage of vivo human tissue during laser therapy was analytically obtained. The influences of laser moving velocity, laser spot size, phase lags of heat flux and temperature gradient were discussed. It was found that the laser moving speed and the laser spot size greatly influence the thermal damage degree by affecting the energy concentration degree. The increases of the laser moving speed and laser spot size can enlarge the irradiated region and reduce the burn degree. A greater phase lag of temperature gradient led to lower accumulation of thermal energy and lower burn degree. However, the increment of heat flux phase lag leads to the thermal energy accumulation and more serious burn degree in the irradiated region.
Hybrid nanocomposite as a chest wall graft with improved integration by adipose-derived stem cells
Authors: Buschmann Johanna , Yamada Yoshito , Schulz-Schönhagen Konstantin , Hess Samuel C. , Stark Wendelin J. , Opelz Christine , Bürgisser Gabriella Meier , Weder Walter , Jungraithmayr Wolfgang 
Published: July 2019

AbstractSurgery of the chest wall is potentially required to cover large defects after removal of malignant tumours. Usually, inert and non-degradable Gore-Tex serves to replace the missing tissue. However, novel biodegradable materials combined with stem cells are available that stimulate the healing. Based on poly-lactic-co-glycolic acid and amorphous calcium phosphate nanoparticles (PLGA/aCaP) and pure PLGA, a dual layer biodegradable hybrid nanocomposite was generated. Mouse adipose-derived stem cells were cultered on electrospun disks (ASCs of C57BL/6), and biomechanical tests were performed. The cell-seeded scaffolds were engrafted in C57BL/LY5.1 mice to serve as a chest wall substitute. Cell invasion into the bi-layered material, extent of CD45+ cells, inflammatory response, neo-vascularization and ECM composition were determined at 1 and 2 months post-surgery, respectively. The bi-layered hybrid nanocomposite was stable after a 2-week in vitro culture, in contrast to PLGA/aCaP without a PLGA layer. There was a complete biointegration and good vascularization in vivo. The presence of ASCs attracted more CD45+ cells (hematopoietic origin) compared to cell-free scaffolds. Inflammatory reaction was similar for both groups (±ASCs) at 8 weeks. A bi-layered hybrid nanocomposite fabricated of electrospun PLGA/aCaP and a reinforcing layer of pristine PLGA is an ideal scaffold for chest wall reconstruction. It is stable and allows a proper host tissue integration. If ASCs are seeded, they attract more CD45+ cells, supporting the regeneration process.
Comparative study on the catalytic activity of Fe-doped ZrO2 nanoparticles without significant toxicity through chemical treatment under various pH conditions
Authors: Song Hye-in , Hong Jung A. , Lee Hangil , Lim Kwang-il 
Published: July 2019

AbstractDespite advances in the construction of catalysts based on metal oxide nanoparticles (MO NPs) for various industrial, biomedical, and daily-life applications, the biosafety concerns about these NPs still remain. Recently, the need to analyze and improve the safety of MO NPs along with attempts to enhance their catalytic performance has been strongly perceived. Here, we prepared multiple variants of Fe-doped zirconium oxide (Fe@ZrO2) NPs under different pH conditions; then, we assessed their toxicity and finally screened the variant that exhibited the best catalytic performance. To assess the NP toxicity, the prepared NPs were introduced into three types of human cells originally obtained from different body parts likely to be most affected by NPs (skin, lung, and kidney). Experimental results from conventional cellular toxicity assays including recently available live-cell imaging indicated that none of the variants exerted severe negative effects on the viability of the human cells and most NPs were intracellular localized outside of nucleus, by which severe genotoxicity is unexpected. In contrast, Fe@ZrO2 NPs synthesized under a basic condition (pH = 13.0), exhibited the highest catalytic activities for three different reactions; each was biochemical (L-cysteine oxidation) or photochemical one (4-chlorophenol degradation and OH radical formation with benzoic acid). This study demonstrates that catalytic Fe@ZrO2 NPs with enhanced activities and modest or insignificant toxicity can be effectively developed and further suggests a potential for the use of these particles in conventional chemical reactions as well as in recently emerging biomedical and daily-life nanotechnology applications.
Adiponectin levels among individuals with varied employment status in Japan: a cross-sectional analysis of the J-SHINE study
Authors: Amano Hoichi , Shirakawa Yoshimi , Hashimoto Hideki 
Published: July 2019

AbstractThe purpose of this study was to examine the association between employment status and adiponectin levels. This cross-sectional study was a part of the Japanese Stratification, Health, Income, and Neighborhood study, a population-based survey in metropolitan Japan. The analysis included data from 848 individuals. A one-way analysis of variance was used to assess differences in log-transformed adiponectin levels among individuals according to their employment status. Multiple linear regression analysis was used to assess these differences after adjusting for other cardiovascular disease risk factors. The main outcome was log-transformed adiponectin. Of the participants, 6.2% of the men and 15.1% of the women were precarious workers. Mean adiponectin values differed significantly by employment status in men, but not in women. In men, multiple regression analysis showed that precarious workers had significantly lower adiponectin levels than permanent workers (β = −0.16, P = 0.02). However, in women, adiponectin levels were significantly lower only in precarious workers with low household incomes (β = −0.35, P = 0.02). Male precarious workers and their female counterparts with low annual household incomes had significantly lower levels of adiponectin. These results might help us to understand mechanisms underlying the relationship between employment status and cardiovascular disease.
CETP, LIPC, and SCARB1 variants in individuals with extremely high high-density lipoprotein-cholesterol levels
Authors: Lee Chan Joo , Park Mun Su , Kim Miso , Ann Soo-jin , Lee Jaeho , Park Sungha , Kang Seok-Min , Jang Yangsoo , Lee Ji Hyun , Lee Sang-Hak 
Published: July 2019

AbstractThe concentration of high-density lipoprotein-cholesterol (HDL-C) in humans is partially determined by genetic factors; however, the role of these factors is incompletely understood. The aim of this study was to examine the prevalence and characteristics of CETP, LIPC, and SCARB1 variants in Korean individuals with extremely high HDL-C levels. We also analysed associations between these variants and cholesterol efflux capacity (CEC), reactive oxygen species (ROS) generation, and vascular cell adhesion molecule-1 (VCAM-1) expression. Of 13,545 participants in the cardiovascular genome cohort, 42 subjects with HDL-C levels >100 mg/dL were analysed. The three target genes were sequenced by targeted next-generation sequencing, the functional effects of detected variants were predicted, and CEC was assessed using a radioisotope and apolipoprotein B-depleted sera. We observed two rare variants of CETP in 13 individuals (rare variant c.A1196G [p.D399G] of CETP was discovered in 12 subjects) and one rare variant of SCARB1 in one individual. Furthermore, all subjects had at least one of four common variants (one CETP and three LIPC variants). Two additional novel CETP variants of unknown frequency were found in two subjects. However, the identified variants did not show significant associations with CEC, ROS generation, or VCAM-1 expression. Our study provides additional insights into the role of genetics in individuals with extremely high HDL-C.
Tinospora cordifolia protects against inflammation associated anemia by modulating inflammatory cytokines and hepcidin expression in male Wistar rats
Authors: Ghatpande Niraj S. , Misar Ashwini V. , Waghole Ravindra J. , Jadhav Sachin H. , Kulkarni Prasad P. 
Published: July 2019

AbstractSystemic iron homeostasis dysregulation is primarily associated with inflammation- associated anemia (AI) due to hepcidin up-regulation. Tinospora cordifolia (TC) has shown remarkable anti-inflammatory properties and has been found useful in the treatment of inflammatory disorders. However, the effects and mechanisms of TC on AI have not been studied yet. We conducted in vivo and in vitro studies to evaluate the effect of TC on AI. HPLC studies were also carried out to find out active constituents in TC extract. Model system exhibiting AI was developed by repeated injections of HKBA in Wistar rats. TC treated groups showed significantly higher levels of Hb and RBC count compared to the inflammatory control group. TC treatment showed reduction in the expression of the HAMP (hepcidin) gene in the rat liver. TC extract also inhibited gene expression of inflammatory cytokines (TNF-α, IL-1β) and decreased NO production in RAW 264.7 cells. The HPLC analysis revealed the presence of tinosporaside, which could have synergistically contributed to the above findings. Overall results indicate that TC therapy was able to maintain circulating iron through reduction of inflammatory cytokines and expression of hepcidin in rats.
Astrocyte Specific Remodeling of Plasmalemmal Cholesterol Composition by Ketamine Indicates a New Mechanism of Antidepressant Action
Authors: Lasič Eva , Lisjak Marjeta , Horvat Anemari , Božić Mićo , Šakanović Aleksandra , Anderluh Gregor , Verkhratsky Alexei , Vardjan Nina , Jorgačevski Jernej , Stenovec Matjaž , Zorec Robert 
Published: July 2019

AbstractKetamine is an antidepressant with rapid therapeutic onset and long-lasting effect, although the underlying mechanism(s) remain unknown. Using FRET-based nanosensors we found that ketamine increases [cAMP]i in astrocytes. Membrane capacitance recordings, however, reveal fundamentally distinct mechanisms of effects of ketamine and [cAMP]i on vesicular secretion: a rise in [cAMP]i facilitated, whereas ketamine inhibited exocytosis. By directly monitoring cholesterol-rich membrane domains with a fluorescently tagged cholesterol-specific membrane binding domain (D4) of toxin perfringolysin O, we demonstrated that ketamine induced cholesterol redistribution in the plasmalemma in astrocytes, but neither in fibroblasts nor in PC 12 cells. This novel mechanism posits that ketamine affects density and distribution of cholesterol in the astrocytic plasmalemma, consequently modulating a host of processes that may contribute to ketamine’s rapid antidepressant action.
Deletion of NFKB1 enhances canonical NF-κB signaling and increases macrophage and myofibroblast content during tendon healing
Authors: Best Katherine T. , Lee Fredella K. , Knapp Emma , Awad Hani A. , Loiselle Alayna E. 
Published: July 2019

AbstractFlexor tendon injuries heal with excessive scar tissue that limits range of motion and increases incidence of re-rupture. The molecular mechanisms that govern tendon healing are not well defined. Both the canonical nuclear factor kappa B (NF-κB) and mitogen activated protein kinase (MAPK) pathways have been implicated in tendon healing. The gene NFKB1 (proteins p105/p50) is involved in both NF-κB and MAPK signaling cascades. In the present study, we tested the hypothesis that global NFKB1 deletion would increase activation of both NF-κB and MAPK through loss of signaling repressors, resulting in increased matrix deposition and altered biomechanical properties. As hypothesized, NFKB1 deletion increased activation of both NF-κB and MAPK signaling. While gliding function was not affected, NFKB1 deletion resulted in tendons that were significantly stiffer and trending towards increased strength by four weeks post-repair. NFKB1 deletion resulted in increased collagen deposition, increase macrophage recruitment, and increased presence of myofibroblasts. Furthermore, NFKB1 deletion increased expression of matrix-related genes (Col1a1, Col3a1), macrophage-associated genes (Adgre1, Ccl2), myofibroblast markers (Acta2), and general inflammation (Tnf). Taken together, these data suggest that increased activation of NF-κB and MAPK via NFKB1 deletion enhance macrophage and myofibroblast content at the repair, driving increased collagen deposition and biomechanical properties.
Particle coating alters mucociliary transit in excised rat trachea: A synchrotron X-ray imaging study
Authors: Gardner Mark , McCarron Alexandra , Morgan Kaye , Parsons David , Donnelley Martin 
Published: July 2019

AbstractWe have previously developed non-invasive in vivo mucociliary transport (MCT) monitoring methods using synchrotron phase contrast X-ray imaging (PCXI) to evaluate potential therapies for cystic fibrosis (CF). However, previous in vivo measurements of MCT velocity using this method were lower than those from alternate methods. We hypothesise this was due to the surface chemistry of the uncoated particles. We investigated the effect of particle surface coating on MCT marker performance by measuring the velocity of uncoated, positively-charged (aminated; NH2), and negatively-charged (carboxylated; COOH) particles. The effect of aerosolised hypertonic saline (HS) was also investigated, as previous in vivo measurements showed HS significantly increased MCT rate. PCXI experiments were performed using an ex vivo rat tracheal imaging setup. Prior to aerosol delivery there was little movement of the uncoated particles, whilst the NH2 and COOH particles moved with MCT rates similar to those previously reported. After application of HS the uncoated and COOH particle velocity increased and NH2 decreased. This experiment validated the use of COOH particles as MCT marker particles over the uncoated and NH2 coated particles. Our results suggest that future experiments measuring MCT using synchrotron PCXI should use COOH coated marker particles for more accurate MCT quantification.
Comprehensive feature selection for classifying the treatment outcome of high-intensity ultrasound therapy in uterine fibroids
Authors: Suomi Visa , Komar Gaber , Sainio Teija , Joronen Kirsi , Perheentupa Antti , Blanco Sequeiros Roberto 
Published: July 2019

AbstractThe study aim was to utilise multiple feature selection methods in order to select the most important parameters from clinical patient data for high-intensity focused ultrasound (HIFU) treatment outcome classification in uterine fibroids. The study was retrospective using patient data from 66 HIFU treatments with 89 uterine fibroids. A total of 39 features were extracted from the patient data and 14 different filter-based feature selection methods were used to select the most informative features. The selected features were then used in a support vector classification (SVC) model to evaluate the performance of these parameters in predicting HIFU therapy outcome. The therapy outcome was defined as non-perfused volume (NPV) ratio in three classes: <30%, 30–80% or >80%. The ten most highly ranked features in order were: fibroid diameter, subcutaneous fat thickness, fibroid volume, fibroid distance, Funaki type I, fundus location, gravidity, Funaki type III, submucosal fibroid type and urinary symptoms. The maximum F1-micro classification score was 0.63 using the top ten features from Mutual Information Maximisation (MIM) and Joint Mutual Information (JMI) feature selection methods. Classification performance of HIFU therapy outcome prediction in uterine fibroids is highly dependent on the chosen feature set which should be determined prior using different classifiers.