bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phenotype and Functional Features of Human Telomerase Reverse Transcriptase Immortalized Human Airway Smooth Muscle Cells from Asthmatic and Non-Asthmatic Donors
Authors: Burgess J. K. , Ketheson A. , Faiz A. , Limbert Rempel K. A. , Oliver B. G. , Ward J. P. T. , Halayko A. J. 
Published: January 2018

AbstractAsthma is an obstructive respiratory disease characterised by chronic inflammation with airway hyperresponsiveness. In asthmatic airways, there is an increase in airway smooth muscle (ASM) cell bulk, which differs from non-asthmatic ASM in characteristics. This study aimed to assess the usefulness of hTERT immortalisation of human ASM cells as a research tool. Specifically we compared proliferative capacity, inflammatory mediator release and extracellular matrix (ECM) production in hTERT immortalised and parent primary ASM cells from asthmatic and non-asthmatic donors. Our studies revealed no significant differences in proliferation, IL-6 and eotaxin-1 production, or CTGF synthesis between donor-matched parent and hTERT immortalised ASM cell lines. However, deposition of ECM proteins fibronectin and fibulin-1 was significantly lower in immortalised ASM cells compared to corresponding primary cells. Notably, previously reported differences in proliferation and inflammatory mediator release between asthmatic and non-asthmatic ASM cells were retained, but excessive ECM protein deposition in asthmatic ASM cells was lost in hTERT ASM cells. This study shows that hTERT immortalised ASM cells mirror primary ASM cells in proliferation and inflammatory profile characteristics. Moreover, we demonstrate both strengths and weaknesses of this immortalised cell model as a representation of primary ASM cells for future asthma pathophysiological research.
Detection of antimicrobial resistance genes associated with the International Space Station environmental surfaces
Authors: Urbaniak C. , Sielaff A. Checinska , Frey K. G. , Allen J. E. , Singh N. , Jaing C. , Wheeler K. , Venkateswaran K. 
Published: January 2018

AbstractAntimicrobial resistance (AMR) is a global health issue. In an effort to minimize this threat to astronauts, who may be immunocompromised and thus at a greater risk of infection from antimicrobial resistant pathogens, a comprehensive study of the ISS “resistome’ was conducted. Using whole genome sequencing (WGS) and disc diffusion antibiotic resistance assays, 9 biosafety level 2 organisms isolated from the ISS were assessed for their antibiotic resistance. Molecular analysis of AMR genes from 24 surface samples collected from the ISS during 3 different sampling events over a span of a year were analyzed with Ion AmpliSeq™ and metagenomics. Disc diffusion assays showed that Enterobacter bugandensis strains were resistant to all 9 antibiotics tested and Staphylococcus haemolyticus being resistant to none. Ion AmpliSeq™ revealed that 123 AMR genes were found, with those responsible for beta-lactam and trimethoprim resistance being the most abundant and widespread. Using a variety of methods, the genes involved in antimicrobial resistance have been examined for the first time from the ISS. This information could lead to mitigation strategies to maintain astronaut health during long duration space missions when return to Earth for treatment is not possible.
A tissue-mimetic nano-fibrillar hybrid injectable hydrogel for potential soft tissue engineering applications
Authors: Latifi Neda , Asgari Meisam , Vali Hojatollah , Mongeau Luc 
Published: January 2018

AbstractWhile collagen type I (Col-I) is commonly used as a structural component of biomaterials, collagen type III (Col-III), another fibril forming collagen ubiquitous in many soft tissues, has not previously been used. In the present study, the novel concept of an injectable hydrogel with semi-interpenetrating polymeric networks of heterotypic collagen fibrils, with tissue-specific Col-III to Col-I ratios, in a glycol-chitosan matrix was investigated. Col-III was introduced as a component of the novel hydrogel, inspired by its co-presence with Col-I in many soft tissues, its influence on the Col-I fibrillogenesis in terms of diameter and mechanics, and its established role in regulating scar formation. The hydrogel has a nano-fibrillar porous structure, and is mechanically stable under continuous dynamic stimulation. It was found to provide a longer half-life of about 35 days than similar hyaluronic acid-based hydrogels, and to support cell implantation in terms of viability, metabolic activity, adhesion and migration. The specific case of pure Col-III fibrils in a glycol-chitosan matrix was investigated. The proposed hydrogels meet many essential requirements for soft tissue engineering applications, particularly for mechanically challenged tissues such as vocal folds and heart valves.
SLAF-based high-density genetic map construction and QTL mapping for major economic traits in sea urchin Strongylocentrotus intermedius
Authors: Chang Yaqing , Ding Jun , Xu Yuhui , Li Dan , Zhang Weijie , Li Lei , Song Jian 
Published: January 2018

AbstractSea urchin (Strongylocentrotus intermedius) has long been a model species for developmental and evolutionary research, but only a few studies have focused on gene mapping. Here, we reported a high-density genetic map containing 4,387 polymorphism specific-length amplified fragment (SLAF) markers spanning 21 linkage groups (LG) for sea urchin. Based on this genetic map and phenotyping data for eight economic traits, 33 potentially significant QTLs were detected on ten different LGs with explanations ranging from 9.90% to 46.30%, partly including 10 QTLs for test diameter, six QTLs for body weight and eight QTLs for Aristotle’s lantern weight. Moreover, we found a QTL enrichment LG, LG15, gathering QTLs for test diameter, body weight, gonad weight, light orange-yellow color difference (≥E1) and light yellow color difference (≥E2). Among all QTLs, we genotyped four QTLs for test diameter, Aristotle’s lantern weight and body weight using High Resolution Melting (HRM) technology. Finally, we used the verified SNP marker (detected using SLAF sequencing) to explore their marker-assisted selection (MAS) breeding application potential and found that SNP-29 associated tightly with body weight and that heterozygous genotype was a dominant genotype, indicating that SNP-29 was a promising marker for MAS.
Band gap maps beyond the delocalization limit: correlation between optical band gaps and plasmon energies at the nanoscale
Authors: Zhan Wei , Venkatachalapathy Vishnukanthan , Aarholt Thomas , Kuznetsov Andrej Yu. , Prytz Øystein 
Published: January 2018

AbstractRecent progresses in nanoscale semiconductor technology have heightened the need for measurements of band gaps with high spatial resolution. Band gap mapping can be performed through a combination of probe-corrected scanning transmission electron microscopy (STEM) and monochromated electron energy-loss spectroscopy (EELS), but are rare owing to the complexity of the experiments and the data analysis. Furthermore, although this method is far superior in terms of spatial resolution to any other techniques, it is still fundamentally resolution-limited due to inelastic delocalization of the EELS signal. In this work we have established a quantitative correlation between optical band gaps and plasmon energies using the Zn1−xCd
x
O/ZnO system as an example, thereby side-stepping the fundamental resolution limits of band gap measurements, and providing a simple and convenient approach to achieve band gap maps with unprecedented spatial resolution.
Error-related cardiac response as information for visibility judgements
Authors: Łukowska Marta , Sznajder Michał , Wierzchoń Michał 
Published: January 2018

AbstractInteroception provides information about the saliency of external or internal sensory events and thus may inform perceptual decision-making. Error in performance is an example of a motivationally significant internal event that evokes autonomic nervous system response resembling the orienting response: heart rate deceleration, increased skin conductance response, and pupil dilation. Here, we investigate whether error-related cardiac activity may serve as a source of information when making metacognitive judgments in an orientation discrimination backward masking task. In the first experiment, we found that the heart accelerates less after an incorrect stimuli discrimination than after a correct one. Moreover, this difference becomes more pronounced with increasing subjective visibility of the stimuli. In the second experiment, this accuracy-dependent pattern of cardiac activity was found only when participants listened to their own heartbeats, but not someone else’s. We propose that decision accuracy coded in cardiac activity may be fed as a cue to subjective visibility judgments.
Oxidative stress via inhibition of the mitochondrial electron transport and Nrf-2-mediated anti-oxidative response regulate the cytotoxic activity of plumbagin
Authors: Kapur Arvinder , Beres Thomas , Rathi Kavya , Nayak Amruta P. , Czarnecki Austin , Felder Mildred , Gillette Amani , Ericksen Spencer S. , Sampene Emmanuel , Skala Melissa C. , Barroilhet Lisa , Patankar Manish S. 
Published: January 2018

AbstractPlumbagin, an anti-cancer agent, is toxic to cells of multiple species. We investigated if plumbagin targets conserved biochemical processes. Plumbagin induced DNA damage and apoptosis in cells of diverse mutational background with comparable potency. A 3–5 fold increase in intracellular oxygen radicals occurred in response to plumbagin. Neutralization of the reactive oxygen species by N-acetylcysteine blocked apoptosis, indicating a central role for oxidative stress in plumbagin-mediated cell death. Plumbagin docks in the ubiquinone binding sites (Q0 and Qi) of mitochondrial complexes I–III, the major sites for oxygen radicals. Plumbagin decreased oxygen consumption rate, ATP production and optical redox ratio (NAD(P)H/FAD) indicating interference with electron transport downstream of mitochondrial Complex II. Oxidative stress induced by plumbagin triggered an anti-oxidative response via activation of Nrf2. Plumbagin and the Nrf2 inhibitor, brusatol, synergized to inhibit cell proliferation. These data indicate that while inhibition of electron transport is the conserved mechanism responsible for plumbagin’s chemotoxicity, activation of Nrf2 is the resulting anti-oxidative response that allows plumbagin to serve as a chemopreventive agent. This study provides the basis for designing potent and selective plumbagin analogs that can be coupled with suitable Nrf2 inhibitors for chemotherapy or administered as single agents to induce Nrf2-mediated chemoprevention.
Glucocorticoid receptor GRβ regulates glucocorticoid-induced ocular hypertension in mice
Authors: Patel Gaurang C. , Liu Yang , Millar J. Cameron , Clark Abbot F. 
Published: January 2018

AbstractProlonged glucocorticoid (GC) therapy can cause GC-induced ocular hypertension (OHT), which if left untreated progresses to iatrogenic glaucoma and permanent vision loss. The alternatively spliced isoform of glucocorticoid receptor GRβ acts as dominant negative regulator of GR activity, and it has been shown that overexpressing GRβ in trabecular meshwork (TM) cells inhibits GC-induced glaucomatous damage in TM cells. The purpose of this study was to use viral vectors to selectively overexpress the GRβ isoform in the TM of mouse eyes treated with GCs, to precisely dissect the role of GRβ in regulating steroid responsiveness. We show that overexpression of GRβ inhibits GC effects on MTM cells in vitro and GC-induced OHT in mouse eyes in vivo. Ad5 mediated GRβ overexpression reduced the GC induction of fibronectin, collagen 1, and myocilin in TM of mouse eyes both in vitro and in vivo. GRβ also reversed DEX-Ac induced IOP elevation, which correlated with increased conventional aqueous humor outflow facility. Thus, GRβ overexpression reduces effects caused by GCs and makes cells more resistant to GC treatment. In conclusion, our current work provides the first evidence of the in vivo physiological role of GRβ in regulating GC-OHT and GC-mediated gene expression in the TM.
Cardiac glycoside/aglycones inhibit HIV-1 gene expression by a mechanism requiring MEK1/2-ERK1/2 signaling
Authors: Wong Raymond W. , Lingwood Clifford A. , Ostrowski Mario A. , Cabral Tyler , Cochrane Alan 
Published: January 2018

AbstractThe capacity of HIV-1 to develop resistance to current drugs calls for innovative strategies to control this infection. We aimed at developing novel inhibitors of HIV-1 replication by targeting viral RNA processing—a stage dependent on conserved host processes. We previously reported that digoxin is a potent inhibitor of this stage. Herein, we identify 12 other cardiac glycoside/aglycones or cardiotonic steroids (CSs) that impede HIV growth in HIV-infected T cells from clinical patients at IC50s (1.1–1.3 nM) that are 2–26 times below concentrations used in patients with heart conditions. We subsequently demonstrate that CSs inhibit HIV-1 gene expression in part through modulation of MEK1/2-ERK1/2 signaling via interaction with the Na+/K+-ATPase, independent of alterations in intracellular Ca2+. Supporting this hypothesis, depletion of the Na+/K+-ATPase or addition of a MEK1/2-ERK1/2 activator also impairs HIV-1 gene expression. Similar to digoxin, all CSs tested induce oversplicing of HIV-1 RNAs, reducing unspliced (Gag) and singly spliced RNAs (Env/p14-Tat) encoding essential HIV-1 structural/regulatory proteins. Furthermore, all CSs cause nuclear retention of genomic/unspliced RNAs, supporting viral RNA processing as the underlying mechanism for their disruption of HIV-1 replication. These findings call for further in vivo validation and supports the targeting of cellular processes to control HIV-1 infection.
New virulence factor CSK29544_02616 as LpxA binding partner in Cronobacter sakazakii
Authors: Kim Seongok , Yoon Hyunjin , Ryu Sangryeol 
Published: January 2018

AbstractCronobacter sakazakii is an opportunistic pathogen that can cause meningitis and necrotizing enterocolitis in premature infants, but its virulence determinants remain largely unknown. In this study, a transposon-mediated random-mutant library of C. sakazakii was used to identify new virulence factors. Compared to wild-type bacteria, a mutant lacking CSK29544_02616 (referred to as labp) was defective in invasion into intestinal epithelial cells (by at least 1000-fold) and showed less phagocytosis by macrophages (by at least 50-fold). The lack of labp in C. sakazakii changed the profile of outer membrane proteins, decreased the production of lipopolysaccharides, and increased the production of membrane phospholipids. Bacterial physiological characteristics including surface hydrophobicity and motility were also altered in the absence of labp, presumably because of changes in the bacterial-envelope structure. To systematically determine the role of labp, ligand fishing was conducted using Labp as a bait, which revealed LpxA as a binding partner of Labp. LpxA is UDP-N-acetylglucosamine (GlcNAc) acyltransferase, the first enzyme in the pathway of lipid A biosynthesis. Labp increased the enzymatic activity of LpxA without influencing lpxA expression. Considering multifaceted roles of lipopolysaccharides in virulence regulation, Labp is a novel virulence factor that promotes the production of lipid A by LpxA in Cronobacter.
Quail egg homogenate alleviates food allergy induced eosinophilic esophagitis like disease through modulating PAR-2 transduction pathway in peanut sensitized mice
Authors: Lianto Priscilia , Han Shiwen , Li Xinrui , Ogutu Fredrick Onyango , Zhang Yani , Fan Zhuoyan , Che Huilian 
Published: January 2018

AbstractThe present pharmacotherapy for eosinophilic esophagitis (EoE) fundamentally depend on inhaled corticosteroids. Despite the fact that oral intake of topical steroids can be successful in restricting EoE-related inflammation, there are concerns with respect to the long term utilization of steroids, especially in kids. In the current research, we assess the effect of quail egg, which is reportedly a known serine protease inhibitor, on symptomatology and immune responses in a peanut-sensitized mouse model of food allergy induced EoE. Daily oral treatment with quail egg attenuated mice symptomatology and immune response. Treatment with quail egg inhibited antigen-prompted increments in mouse tryptase and eosinophil cationic protein (ECP) in serum and eosinophil in inflamed tissues like oesophagus, lung, and digestive system. Quail egg treatment resulted in decreased antibody specific IgE and IgG1 and a variety of inflammatory genes that were abnormally expressed in EoE. Other effects included increased IL-10, decreased PAR-2 activation and NF-kB p65 in inflamed tissues. Our results suggest that quail egg treatment may have therapeutic potential in attenuating the symptoms of food allergy induced EoE like disease through regulating PAR-2 downstream pathway by blocking the activation of the transcription factor NF-kB p65 activity.
Relationship between brachial-ankle and heart-femoral pulse wave velocities and the rapid decline of kidney function
Authors: Lee Sung Woo , Han Seung Hyeok , Yoo Tae Hyun , Chung Wookyung , Park Sue K. , Chae Dong Wan , Ahn Curie , Oh Kook-Hwan 
Published: January 2018

AbstractThe impact of brachial-ankle pulse wave velocity (baPWV) and heart-femoral pulse wave velocity (hfPWV) on rapid decline of estimated glomerular filtration rate (eGFR) has been inconclusive. The database of a multicenter prospective study of 2238 patients in Korea enrolled from 2011 to 2016 was reviewed. After excluding patients with missing baPWV (n = 257) and eGFR change (n = 180), the study included 1801 non-dialysis chronic kidney disease (CKD) patients. The eGFR change <−5ml/min/1.73 m2/year was defined as rapid decline. During a mean of 2.2 years, the mean eGFR change was −3.6 ml/min/1.73 m2/year, and 31.6% of patients were classified as having rapid decline. Older age, causes of CKD, increased heart rate, systolic blood pressures, and proteinuria were associated with the highest baPWV quintile. In multivariate logistic regression analyses, the odds of a rapid decline in eGFR was 1.9 times higher in the fifth quintile than in the first quintile (P = 0.013). In a subset with baPWV and hfPWV (n = 1182), high baPWV was associated with rapid eGFR decline only when accompanied by a high hfPWV. These findings suggest that central and peripheral PWVs may simultaneously affect rapid eGFR decline.
High strength nanostructured Al-based alloys through optimized processing of rapidly quenched amorphous precursors
Authors: Kim Song-Yi , Lee Gwang-Yeob , Park Gyu-Hyeon , Kim Hyeon-Ah , Lee A-Young , Scudino Sergio , Prashanth Konda Gokuldoss , Kim Do-Hyang , Eckert Jürgen , Lee Min-Ha 
Published: January 2018

AbstractWe report the methods increasing both strength and ductility of aluminum alloys transformed from amorphous precursor. The mechanical properties of bulk samples produced by spark-plasma sintering (SPS) of amorphous Al-Ni-Co-Dy powders at temperatures above 673 K are significantly enhanced by in-situ crystallization of nano-scale intermetallic compounds during the SPS process. The spark plasma sintered Al84Ni7Co3Dy6 bulk specimens exhibit 1433 MPa compressive yield strength and 1773 MPa maximum strength together with 5.6% plastic strain, respectively. The addition of Dy enhances the thermal stability of primary fcc Al in the amorphous Al-TM -RE alloy. The precipitation of intermetallic phases by crystallization of the remaining amorphous matrix plays important role to restrict the growth of the fcc Al phase and contributes to the improvement of the mechanical properties. Such fully crystalline nano- or ultrafine-scale Al-Ni-Co-Dy systems are considered promising for industrial application because their superior mechanical properties in terms of a combination of very high room temperature strength combined with good ductility.
The effect of foreign language in fear acquisition
Authors: García-Palacios Azucena , Costa Albert , Castilla Diana , del Río Eva , Casaponsa Aina , Duñabeitia Jon Andoni 
Published: January 2018

AbstractEmotions are at the core of human nature. There is evidence that emotional reactivity in foreign languages compared to native languages is reduced. We explore whether this emotional distance could modulate fear conditioning, an essential mechanism for the understanding and treatment of anxiety disorders. A group of participants was verbally informed (either in a foreign or in a native language) that two different stimuli could be either cueing the potential presence of a threat stimulus or its absence. We registered pupil size and electrodermal activity and calculated the difference in psychophysiological responses to conditioned and to unconditioned stimuli. Our findings provided evidence that verbal conditioning processes are affected by language context in this paradigm. We report the first experimental evidence regarding how the use of a foreign language may reduce fear conditioning. This observation opens the avenue to the potential use of a foreign language in clinical contexts.
Stress-induced TRBP phosphorylation enhances its interaction with PKR to regulate cellular survival
Authors: Chukwurah Evelyn , Patel Rekha C. 
Published: January 2018

AbstractTransactivation response element RNA-binding protein (TRBP or TARBP2) initially identified to play an important role in human immunodeficiency virus (HIV) replication also has emerged as a regulator of microRNA biogenesis. In addition, TRBP functions in signaling pathways by negatively regulating the interferon-induced double-stranded RNA (dsRNA)-activated protein kinase (PKR) during viral infections and cell stress. During cellular stress, PKR is activated and phosphorylates the α subunit of the eukaryotic translation factor eIF2, leading to the cessation of general protein synthesis. TRBP inhibits PKR activity by direct interaction as well as by binding to PKR’s two known activators, dsRNA and PACT, thus preventing their interaction with PKR. In this study, we demonstrate for the first time that TRBP is phosphorylated in response to oxidative stress and upon phosphorylation, inhibits PKR more efficiently promoting cell survival. These results establish that PKR regulation through stress-induced TRBP phosphorylation is an important mechanism ensuring cellular recovery and preventing apoptosis due to sustained PKR activation.