bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide bisulphite-sequencing reveals organ-specific methylation patterns in chickpea
Authors: Bhatia Himanshi , Khemka Niraj , Jain Mukesh , Garg Rohini 
Published: June 2018

AbstractDNA methylation is widely known to regulate gene expression in eukaryotes. Here, we unraveled DNA methylation patterns in cultivated chickpea to understand the regulation of gene expression in different organs. We analyzed the methylation pattern in leaf tissue of wild chickpea too, and compared it with cultivated chickpea. Our analysis indicated abundant CG methylation within gene-body and CHH methylation in intergenic regions of the chickpea genome in all the organs examined. Analysis of differentially methylated regions (DMRs) demonstrated a higher number of CG context DMRs in wild chickpea and CHH context DMRs in cultivated chickpea. We observed increased preponderance of hypermethylated DMRs in the promoter regions and hypomethylated DMRs in the genic regions in cultivated chickpea. Genomic location and context of the DMRs correlated well with expression of proximal genes. Our results put forth a positive correlation of promoter hypermethylation with increased transcript abundance via identification of DMR-associated genes involved in flower development in cultivated chickpea. The atypical correlation observed between promoter hypermethylation and increased transcript abundance might be dependent on 24-nt small RNAs and transcription factors binding to the promoter region. This study provides novel insights into DNA methylation patterns in chickpea and their role in regulation of gene expression.
2-carba cyclic phosphatidic acid suppresses inflammation via regulation of microglial polarisation in the stab-wounded mouse cerebral cortex
Authors: Hashimoto Kei , Nakashima Mari , Hamano Ayana , Gotoh Mari , Ikeshima-Kataoka Hiroko , Murakami-Murofushi Kimiko , Miyamoto Yasunori 
Published: June 2018

AbstractTraumatic brain injury (TBI) is caused by physical damage to the brain and it induces blood-brain barrier (BBB) breakdown and inflammation. To diminish the sequelae of TBI, it is important to decrease haemorrhage and alleviate inflammation. In this study, we aimed to determine the effects of 2-carba-cyclic phosphatidic acid (2ccPA) on the repair mechanisms after a stab wound injury as a murine TBI model. The administration of 2ccPA suppressed serum immunoglobulin extravasation after the injury. To elucidate the effects of 2ccPA on inflammation resulting from TBI, we analysed the mRNA expression of inflammatory cytokines. We found that 2ccPA prevents a TBI-induced increase in the mRNA expression of Il-1β, Il-6, Tnf-α and Tgf-β1. In addition, 2ccPA reduces the elevation of Iba1 levels. These data suggest that 2ccPA attenuates the inflammation after a stab wound injury via the modulation of pro-inflammatory cytokines release from microglial cells. Therefore, we focused on the function of 2ccPA in microglial polarisation towards M1 or M2 phenotypes. The administration of 2ccPA decreased the number of M1 and increased the number of M2 type microglial cells, indicating that 2ccPA modulates the microglial polarisation and shifts them towards M2 phenotype. These data suggest that 2ccPA treatment suppresses the extent of BBB breakdown and inflammation after TBI.
Activation of the p53-MDM4 regulatory axis defines the anti-tumour response to PRMT5 inhibition through its role in regulating cellular splicing
Authors: Gerhart Sarah V. , Kellner Wendy A. , Thompson Christine , Pappalardi Melissa B. , Zhang Xi-Ping , Montes de Oca Rocio , Penebre Elayne , Duncan Kenneth , Boriack-Sjodin Ann , Le BaoChau , Majer Christina , McCabe Michael T. , Carpenter Chris , Johnson Neil , Kruger Ryan G. , Barbash Olena 
Published: June 2018

AbstractEvasion of the potent tumour suppressor activity of p53 is one of the hurdles that must be overcome for cancer cells to escape normal regulation of cellular proliferation and survival. In addition to frequent loss of function mutations, p53 wild-type activity can also be suppressed post-translationally through several mechanisms, including the activity of PRMT5. Here we describe broad anti-proliferative activity of potent, selective, reversible inhibitors of protein arginine methyltransferase 5 (PRMT5) including GSK3326595 in human cancer cell lines representing both hematologic and solid malignancies. Interestingly, PRMT5 inhibition activates the p53 pathway via the induction of alternative splicing of MDM4. The MDM4 isoform switch and subsequent p53 activation are critical determinants of the response to PRMT5 inhibition suggesting that the integrity of the p53-MDM4 regulatory axis defines a subset of patients that could benefit from treatment with GSK3326595.
Viscoelastic properties of Pseudomonas aeruginosa variant biofilms
Authors: Gloag Erin S. , German Guy K. , Stoodley Paul , Wozniak Daniel J. 
Published: June 2018

AbstractPseudomonas aeruginosa evolves during chronic pulmonary infections of cystic fibrosis (CF) patients, forming pathoadapted variants that are persistent. Mucoid and rugose small-colony variants (RSCVs) are typically isolated from sputum of CF patients. These variants overproduce exopolysaccharides in the biofilm extracellular polymeric substance (EPS). Currently, changes to the biophysical properties of RSCV and mucoid biofilms due to variations in EPS are not well understood. This knowledge may reveal how lung infections resist host clearance mechanisms. Here, we used mechanical indentation and shear rheometry to analyse the viscoelasticity of RSCV and mucoid colony-biofilms compared to their isogenic parent at 2-, 4-, and 6-d. While the viscoelasticity of parental colony-biofilms underwent fluctuating temporal changes, in contrast, RSCV and mucoid colony-biofilms showed a gradual progression to more elastic-solid behaviour. Theoretical indices of mucociliary and cough clearance predict that mature 6-d parental and RSCV biofilms may show reduced cough clearance from the lung, while early mucoid biofilms may show reduced clearance by both mechanisms. We propose that viscoelasticity be considered a virulence property of biofilms.
Consistent signatures of selection from genomic analysis of pairs of temporal and spatial Plasmodium falciparum populations from The Gambia
Authors: Amambua-Ngwa Alfred , Jeffries David , Amato Roberto , Worwui Archibald , Karim Mane , Ceesay Sukai , Nyang Haddy , Nwakanma Davis , Okebe Joseph , Kwiatkowski Dominic , Conway David J. , D’Alessandro Umberto 
Published: June 2018

AbstractGenome sequences of 247 Plasmodium falciparum isolates collected in The Gambia in 2008 and 2014 were analysed to identify changes possibly related to the scale-up of antimalarial interventions that occurred during this period. Overall, there were 15 regions across the genomes with signatures of positive selection. Five of these were sweeps around known drug resistance and antigenic loci. Signatures at antigenic loci such as thrombospodin related adhesive protein (Pftrap) were most frequent in eastern Gambia, where parasite prevalence and transmission remain high. There was a strong temporal differentiation at a non-synonymous SNP in a cysteine desulfarase (Pfnfs) involved in iron-sulphur complex biogenesis. During the 7-year period, the frequency of the lysine variant at codon 65 (Pfnfs-Q65K) increased by 22% (10% to 32%) in the Greater Banjul area. Between 2014 and 2015, the frequency of this variant increased by 6% (20% to 26%) in eastern Gambia. IC50 for lumefantrine was significantly higher in Pfnfs-65K isolates. This is probably the first evidence of directional selection on Pfnfs or linked loci by lumefantrine. Given the declining malaria transmission, the consequent loss of population immunity, and sustained drug pressure, it is important to monitor Gambian P. falciparum populations for further signs of adaptation.
Click communication in wild harbour porpoises (Phocoena phocoena)
Authors: Sørensen P. M. , Wisniewska D. M. , Jensen F. H. , Johnson M. , Teilmann J. , Madsen P. T. 
Published: June 2018

AbstractSocial delphinids employ a vocal repertoire of clicks for echolocation and whistles for communication. Conversely, the less social and acoustically cryptic harbour porpoises (Phocoena phocoena) only produce narrow-band high-frequency (NBHF) clicks with properties that appear poorly suited for communication. Nevertheless, these small odontocetes likely mediate social interactions, such as mate choice and mother-calf contact, with sound. Here, we deployed six tags (DTAG3) on wild porpoises in Danish waters for a total of 96 hours to investigate if the patterns and use of stereotyped NBHF click trains are consistent with a communication function. We show that wild porpoises produce frequent (up to 27 $$\bullet $$

∙

min−1), high-repetition rate click series with repetition rates and output levels different from those of foraging buzzes. These sounds are produced in bouts and frequently co-occur with emission of similar sounds by nearby conspecifics, audible on the tags for >10% of the time. These results suggest that social interactions are more important to this species than their limited social encounters at the surface may indicate and that these interactions are mediated by at least two broad categories of calls composed of short, high-repetition rate click trains that may encode information via the repetition rate of their stereotyped NBHF clicks.
A new technique for nanoparticle transport and its application in a novel nano-sieve
Authors: Wang Shuai , Wang Chao , Peng Zhilong , Chen Shaohua 
Published: June 2018

AbstractA new technique is proposed to transport and further classify nanoparticles of different sizes. A graphene sheet is used as the substrate; a nanoparticle is placed on the substrate and a sliding block is located below the substrate. As the sliding block moves under the graphene substrate, a driving force is yielded from the van der Waals interaction between the sliding block and the nanoparticle. The effects of the pre-tension of the graphene substrate, size and number of layers of the nanoparticle, slip velocity, the interface commensurability and temperature on nanoparticle transportation are systematically investigated. It is found that a pre-tensioned graphene substrate could provide easier nanoparticle transport. The initial movement of the nanoparticle depends on the competition between the in-plane force and the driving force, while the subsequent transport depends on the slip velocity of the sliding block and the viscous damping force. Based on such a new transport mechanism, a novel nano-sieve can be designed, with which nanoparticles of different sizes can be screened and classified spontaneously. Our findings may be useful for promising designs of transportation, manipulation and classification of nanoparticles.
A sensitive electrochemical immunosensor for label-free detection of Zika-virus protein
Authors: Kaushik Ajeet , Yndart Adriana , Kumar Sanjeev , Jayant Rahul Dev , Vashist Arti , Brown Ashley N. , Li Chen-Zhong , Nair Madhavan 
Published: June 2018

AbstractThis work, as a proof of principle, presents a sensitive and selective electrochemical immunosensor for Zika-virus (ZIKV)-protein detection using a functionalized interdigitated micro-electrode of gold (IDE-Au) array. A miniaturized IDE-Au immunosensing chip was prepared via immobilization of ZIKV specific envelop protein antibody (Zev-Abs) onto dithiobis(succinimidyl propionate) i.e., (DTSP) functionalized IDE-Au (electrode gap/width of 10 µm). Electrochemical impedance spectroscopy (EIS) was performed to measure the electrical response of developed sensing chip as a function of ZIKV-protein concentrations. The results of EIS studies confirmed that sensing chip detected ZIKV-protein selectively and exhibited a detection range from 10 pM to 1 nM and a detection limit of 10 pM along with a high sensitivity of 12 kΩM−1. Such developed ZIKV immune-sensing chip can be integrated with a miniaturized potentiostat (MP)-interfaced with a smartphone for rapid ZIKV-infection detection required for early stage diagnostics at point-of-care application.
The atypical subunit composition of respiratory complexes I and IV is associated with original extra structural domains in Euglena gracilis
Authors: Miranda-Astudillo H. V. , Yadav K. N. S. , Colina-Tenorio L. , Bouillenne F. , Degand H. , Morsomme P. , Boekema E. J. , Cardol P. 
Published: June 2018

AbstractIn mitochondrial oxidative phosphorylation, electron transfer from NADH or succinate to oxygen by a series of large protein complexes in the inner mitochondrial membrane (complexes I–IV) is coupled to the generation of an electrochemical proton gradient, the energy of which is utilized by complex V to generate ATP. In Euglena gracilis, a non-parasitic secondary green alga related to trypanosomes, these respiratory complexes totalize more than 40 Euglenozoa-specific subunits along with about 50 classical subunits described in other eukaryotes. In the present study the Euglena proton-pumping complexes I, III, and IV were purified from isolated mitochondria by a two-steps liquid chromatography approach. Their atypical subunit composition was further resolved and confirmed using a three-steps PAGE analysis coupled to mass spectrometry identification of peptides. The purified complexes were also observed by electron microscopy followed by single-particle analysis. Even if the overall structures of the three oxidases are similar to the structure of canonical enzymes (e.g. from mammals), additional atypical domains were observed in complexes I and IV: an extra domain located at the tip of the peripheral arm of complex I and a “helmet-like” domain on the top of the cytochrome c binding region in complex IV.
Nonlinear associations between working hours and overwork-related cerebrovascular and cardiovascular diseases (CCVD)
Authors: Lin Ro-Ting , Chien Lung-Chang , Kawachi Ichiro 
Published: June 2018

AbstractLong working hours are recognized as a risk factor for cerebrovascular and cardiovascular diseases (CCVD). We investigated the relationship between working hours and different CCVD severity outcomes—death, disability, and illness—across industries in Taiwan from 2006 to 2016. We applied a generalized additive mixed model to estimate the association between working hours and the rate of each severity outcome, adjusted for salary, unemployment rate, time, and a random intercept. Industry-average working hours were significantly associated with each outcome level of overwork-related CCVD, especially when monthly working hours increased from 169 (relative risk [RR] = 1.46, 95% confidence interval [CI] 1.002–2.12) to 187 (RR = 5.73, 95% CI 3.61–9.08). Although RR trends declined after monthly working hours exceeded 187, excess risks remained statistically significant. Each 1-hour increase in working hours had a stronger effect on the RR increase in death and disability than on illness. Variations in CCVD risks existed across industries, with the highest risk in transportation and information. Reducing working hours is essential to preventing overwork-related CCVD, especially the more severe outcomes. We recommend further research to address possible underreporting of less severe cases, and to explore actions to narrow the gaps in risk across industries.
C3a triggers formation of sub-retinal pigment epithelium deposits via the ubiquitin proteasome pathway
Authors: Fernandez-Godino Rosario , Pierce Eric A. 
Published: June 2018

AbstractThe mechanisms that connect complement system activation and basal deposit formation in early stages of age-related macular degeneration (AMD) are insufficiently understood, which complicates the design of efficient therapies to prevent disease progression. Using human fetal (hf) retinal pigment epithelial (RPE) cells, we have established anin vitromodel to investigate the effect of complement C3a on RPE cells and its role in the formation of sub-RPE deposits. The results of these studies revealed that C3a produced after C3 activation is sufficient to induce the formation of sub-RPE deposits via complement-driven proteasome inhibition. C3a binds the C3a receptor (C3aR), stimulates deposition of collagens IV and VI underneath the RPE, and impairs the extracellular matrix (ECM) turnover by increased MMP-2 activity, all mediated by downregulation of the ubiquitin proteasome pathway (UPP). The formation of basal deposits can be prevented by the addition of a C3aR antagonist, which restores the UPP activity and ECM turnover. These findings indicate that the cell-based model can be used to test potential therapeutic agentsin vitro. The data suggest that modulation of C3aR-mediated events could be a therapeutic approach for treatment of early AMD.
Eine Längsschnittstudie zu Arbeitsmarktübergängen und Beschäftigungsnachhaltigkeit nach beruflichen Weiterbildungsmaßnahmen im Rahmen von Leistungen zur Teilhabe am Arbeitsleben
Authors: Reims Nancy , Tophoven Silke 
Published: June 2018

Zusammenfassung
Ziel der Studie Die Studie untersuchte die Beschäftigungsperspektiven von Personen, die im Rahmen von Leistungen zur Teilhabe am Arbeitsleben (LTA) in Kostenträgerschaft der Bundesagentur für Arbeit (BA) Weiterbildungsmaßnahmen absolviert haben.
Methodik Auf Basis administrativer Daten der BA (LTA-RehaPro) wurden Weiterbildungsteilnehmende betrachtet, die zwischen 2009 und 2012 eine berufliche Rehabilitation beendet haben (N=21 772). Mithilfe ereignisdatenanalytischer Verfahren wurden Beschäftigungseintritte und Beschäftigungsdauern ausgewiesen und auf multivariater Ebene Einflussfaktoren der Beschäftigungsaufnahme aufgezeigt.
Ergebnisse Es zeigt sich, dass innerhalb von 500 Tagen 70% eine sozialversicherungspflichtige Beschäftigung aufnehmen – sehr häufig direkt im Anschluss an die Rehabilitation. Der Median der Beschäftigungsdauer im Beobachtungszeitraum liegt bei 670 Tagen.
Schlussfolgerung Für Personen mit gesundheitlichen Einschränkungen sind Weiterbildungsmaßnahmen eine wichtige Möglichkeit zur Wiedereingliederung in den Arbeitsmarkt.
Kieferorthopädie bei Parodontitispatienten – Worauf sollte man achtgeben?
Authors: Bertl Kristina , Melsen Birte , Stavropoulos Andreas 
Published: June 2018

Zusammenfassung
Zielsetzung Ein Überblick zu der Thematik „Kieferorthopädie bei Parodontitispatienten“ anhand folgender 3 Fragestellungen: (1) Wann kann man mit der kieferorthopädischen Therapie starten? (2) Worauf muss man während der kieferorthopädischen Therapie achten? (3) Kann das Ergebnis nach abgeschlossener Kieferorthopädie aufrechterhalten werden?
Ergebnis Generell basiert die wissenschaftliche Evidenz zu dieser Thematik hauptsächlich auf präklinischen und retrospektiven Studien sowie Fallberichtserien; kontrollierte Studien liegen kaum vor. Jedoch unumstritten ist, dass Zahnbewegungen nur im entzündungsfreien Zustand erfolgen sollten, da es ansonsten zu vermehrtem Attachmentverlust kommen kann. Vorab sollte stets eine ursachenbezogene Parodontaltherapie erfolgen sowie in weiterer Folge eine regelmäßige Erhaltungstherapie. In Bezug auf Zeitpunkt und Art einer allfälligen chirurgischen Therapie vor Beginn der Kieferorthopädie lässt sich anhand der Literatur keine klare Therapieempfehlung geben. Bei vertikalen Knochendefekten scheint diese vorteilhaft; ob aber eine offene Kürettage ausreichend ist oder zusätzlich regenerative Materialien verwendet werden sollten, ist nach wie vor unklar. Nach Abschluss der kieferorthopädischen Therapie kann mit entsprechender Stabilisierung auch in einem reduzierten Parodont ein ansprechendes Langzeitoutcome erzielt werden.
Schlussfolgerung Kieferorthopädische Zahnbewegungen führen in einem reduzierten, aber entzündungsfreien Parodont zu keinem Attachmentverlust, und ein ansprechendes Langzeitoutcome ist möglich. Daher sollte vor Beginn der Kieferorthopädie stets eine ursachenbezogene Parodontaltherapie erfolgen, um entzündungsfreie Verhältnisse zu etablieren. Jedoch kann in Bezug auf Zeitpunkt und Art allfälliger parodontal- chirurgischer Eingriffe bislang keine eindeutige Therapieempfehlung gegeben werden.
External Quality Monitoring of the Cervical Cytopathological Exams in the Rio de Janeiro City
Authors: Rocha Vânia Stiepanowez de Oliveira , Malfacini Solange da Silva , Gomes Alex Moreira , Rocha Cláudia Ramos Marques da 
Published: June 2018

Objective To discuss the implementation and contributions of the External Quality Monitoring in the city of Rio de Janeiro and to analyze the performance of the main providers of cervical cytopathology in this city from September 2013 to March 2017, here referred to as “Alpha laboratory” and “Beta laboratory.”
Methods Observational, cross-sectional, retrospective study using information from the Cervical Cancer Control Information System (SISCOLO, in the Portuguese acronym), municipal coordination module, External Quality Monitoring report. The proportions of false positives, false negatives, unsatisfactory samples and rejected samples were estimated. The agreement among the observers was analyzed through the Kappa index and the reduction of disagreements in the period for each laboratory studied, comparing the results of each cycle.
Results A total of 19,158 examinations were selected, of which 19,130 (99.85%) were monitored, 16.649 (87, 03%) were reviewed by the External Quality Monitoring Unit, 2,481 (12,97%) were rejected and 441 (2,65%) were considered unsatisfactory. The “Beta laboratory” presented excellent concordance in all cycles; the “Alpha laboratory” had good concordance in the first two cycles (K = 0.76 and 0.79), becoming excellent in the following four cycles. The average Kappa index was 0.85, with median of 0.86. The percentage of diagnostic disagreement was 6.63% of the reviewed exams, of which 5.38% required a change of conduct
Conclusion External Quality Monitoring is an exercise in diagnostic improvement, and its implementation was fundamental to ensure the reliability of the cytopathological exams in the city of Rio de Janeiro.
Right TKR Patients Treated with Enhanced Pain and Rehabilitation Protocols Can Drive at 2 Weeks
Authors: Dalury David F. , Chapman Danielle M. 
Published: June 2018

AbstractAn important milestone in the recovery following total knee replacement (TKR) is the ability to return to driving. With advances in pain control and the widespread introduction of rapid rehab programs, we hypothesized that the ability to drive would also return sooner than had been traditionally observed. In our group of consecutive right TKR patients, using a driving simulator, we showed that at the 2-week mark, 36 of the 40 patients tested had returned to their preoperative driving capabilities and the other 4 had reached baseline at 3 weeks. While the eventual decision to return to driving is complex and dependent on many factors, we conclude that one of the benefits of enhanced pain and rehab protocols is that patients undergoing right TKR can return to driving in most instances at the 2-week mark rather than the traditional 6-week mark.