bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human rhinovirus internal ribosome entry site element enhances transgene expression in transfected CHO-S cells
Authors: Chai Yu-rong , Ge Meng-meng , Wei Ting-ting , Jia Yan-long , Guo Xiao , Wang Tian-yun 
Published: April 2018

AbstractChinese hamster ovary (CHO) cells are mainly used for recombinant protein production. However, the unstable transgene expression and lower transgene copy numbers are the major issues need to be resolved. Here, eleven internal ribosome entry site (IRES) elements from viral and cellular IRES were evaluated for foreign gene expression in CHO-S cells. We constructed eleven fusing plasmids containing different IRES sequences downstream of the enhanced green fluorescent protein (EGFP) gene. EGFP expression was detected by flow cytometry and the transgene copy number was evaluated by quantitative PCR. The erythropoietin (EPO) protein was also used to assess the stronger IRES. The results showed that IRES from human rhinovirus (HRV) exhibited the highest EGFP expression level under transient and stable transfections. The EGFP expression level of vector with IRES from HRV was related to the gene copy number in stably transfected CHO-S cells. Moreover, IRES from HRV induced higher expression level of EPO compared with one mutant IRES from EMCV in transfected cells. In conclusion, IRES from HRV can function as a strong IRES element for stable expression in CHO-S cells, which could potentially guide more effective foreign gene expression in CHO-S cells.
Opto-mechanical lab-on-fibre seismic sensors detected the Norcia earthquake
Authors: Pisco Marco , Bruno Francesco Antonio , Galluzzo Danilo , Nardone Lucia , Gruca Grzegorz , Rijnveld Niek , Bianco Francesca , Cutolo Antonello , Cusano Andrea 
Published: April 2018

AbstractWe have designed and developed lab-on-fibre seismic sensors containing a micro-opto-mechanical cavity on the fibre tip. The mechanical cavity is designed as a double cantilever suspended on the fibre end facet and connected to a proof mass to tune its response. Ground acceleration leads to displacement of the cavity length, which in turn can be remotely detected using an interferometric interrogation technique. After the sensors characterization, an experimental validation was conducted at the Italian National Institute of Geophysics and Volcanology (INGV), which is responsible for seismic surveillance over the Italian country. The fabricated sensors have been continuously used for long periods to demonstrate their effectiveness as seismic accelerometer sensors. During the tests, fibre optic seismic accelerometers clearly detected the seismic sequence that culminated in the severe Mw6.5 Norcia earthquake that struck central Italy on October 30, 2016. The seismic data provided by the optical sensors were analysed by specialists at the INGV. The wave traces were compared with state-of-the-art traditional sensors typically incorporated into the INGV seismic networks. The comparison verifies the high fidelity of the optical sensors in seismic wave detection, indicating their suitability for a novel class of seismic sensors to be employed in practical scenarios.
Transient peak-strain matching partially recovers the age-impaired mechanoadaptive cortical bone response
Authors: Javaheri Behzad , Carriero Alessandra , Wood Maria , De Souza Roberto , Lee Peter D. , Shefelbine Sandra , Pitsillides Andrew A. 
Published: April 2018

AbstractMechanoadaptation maintains bone mass and architecture; its failure underlies age-related decline in bone strength. It is unclear whether this is due to failure of osteocytes to sense strain, osteoblasts to form bone or insufficient mechanical stimulus. Mechanoadaptation can be restored to aged bone by surgical neurectomy, suggesting that changes in loading history can rescue mechanoadaptation. We use non-biased, whole-bone tibial analyses, along with characterisation of surface strains and ensuing mechanoadaptive responses in mice at a range of ages, to explore whether sufficient load magnitude can activate mechanoadaptation in aged bone. We find that younger mice adapt when imposed strains are lower than in mature and aged bone. Intriguingly, imposition of short-term, high magnitude loading effectively primes cortical but not trabecular bone of aged mice to respond. This response was regionally-matched to highest strains measured by digital image correlation and to osteocytic mechanoactivation. These data indicate that aged bone’s loading response can be partially recovered, non-invasively by transient, focal high strain regions. Our results indicate that old murine bone does respond to load when the loading is of sufficient magnitude, and bones’ age-related adaptation failure may be due to insufficient mechanical stimulus to trigger mechanoadaptation.
RNA-sequencing reveals long-term effects of silver nanoparticles on human lung cells
Authors: Gliga Anda R. , Di Bucchianico Sebastiano , Lindvall Jessica , Fadeel Bengt , Karlsson Hanna L. 
Published: April 2018

AbstractDespite a considerable focus on the adverse effects of silver nanoparticles (AgNPs) in recent years, studies on the potential long-term effects of AgNPs are scarce. The aim of this study was to explore the effects of AgNPs following repeated low-dose, long-term exposure of human bronchial epithelial cells. To this end, the human BEAS-2B cell line was exposed to 1 µg/mL AgNPs (10 nm) for 6 weeks followed by RNA-sequencing (RNA-Seq) as well as genome-wide DNA methylation analysis. The transcriptomics analysis showed that a substantial number of genes (1717) were differentially expressed following AgNP exposure whereas only marginal effects on DNA methylation were observed. Downstream analysis of the transcriptomics data identified several affected pathways including the ‘fibrosis’ and ‘epithelial-mesenchymal transition’ (EMT) pathway. Subsequently, functional validation studies were performed using AgNPs of two different sizes (10 nm and 75 nm). Both NPs increased collagen deposition, indicative of fibrosis, and induced EMT, as evidenced by an increased invasion index, anchorage independent cell growth, as well as cadherin switching. In conclusion, using a combination of RNA-Seq and functional assays, our study revealed that repeated low-dose, long-term exposure of human BEAS-2B cells to AgNPs is pro-fibrotic, induces EMT and cell transformation.
Hydrogen-mediated magnetic domain formation and domain wall motion in Co30Pd70 alloy films
Authors: Chang Po-Chun , Liu Chak-Ming , Hsu Chuan-Che , Lin Wen-Chin 
Published: April 2018

AbstractIn this study, the microscopic origin of the hydrogen effect on magnetic materials was explored through the characterization of time-dependent magnetic domain evolution. We prepared 25-nm Co30Pd70 alloy films with canted magnetic moment on SiO2/Si(001) substrates. From macroscopic Kerr hysteresis loops, considerable hydrogen-induced reduction of magnetic coercivity by a factor of 1/5 in a longitudinal direction and enhancement of magnetic remanence to saturation ratio from 60% to 100% were observed. The magnetic reversal behavior of the Co30Pd70 alloy films gradually transformed from nucleation- to domain-wall-motion dominance when H2 pressure was increased from a vacuum of 1 × 10−5 mbar to 0.8 bar. Domain size also increased considerably with H2 pressure. When H2 pressure was above 0.4 bar, the domain wall (DW) motion was clear to observe and the DW velocity was approximately 10−6–10−5 m/s. Greater hydrogen content in the Co30Pd70 alloy films promoted DW motion that was closer to the behavior of a thermally activated model. The hydrogen effects on magnetism were observed to be reversible and could have valuable future application in spintronic devices for hydrogen sensing.
Contribution of multidrug and toxin extrusion protein 1 (MATE1) to renal secretion of trimethylamine-N-oxide (TMAO)
Authors: Gessner A. , König J. , Fromm M. F. 
Published: April 2018

AbstractTrimethylamine-N-oxide (TMAO) gained considerable attention because of its role as a cardiovascular risk biomarker. Organic cation transporter 2 (OCT2) mediates TMAO uptake into renal proximal tubular cells. Here we investigated the potential role of multidrug and toxin extrusion protein 1 (MATE1) for translocation of TMAO across the luminal membrane of proximal tubular cells. HEK293 cells stably expressing OCT2 (HEK-OCT2) or MATE1 (HEK-MATE1) were used for uptake studies. Transcellular transport of TMAO was investigated using monolayers of MDCK control cells (MDCK-Co) as well as single- (MDCK-OCT2, MDCK-MATE1) and double-transfected cells (MDCK-OCT2-MATE1). In line with previous studies, HEK-OCT2 cells revealed a 2.4-fold uptake of TMAO compared to control cells (p < 0.001), whereas no significant uptake was observed in HEK-MATE1. In monolayers of MDCK cells, polarised TMAO transcellular transport was not significantly different between MDCK-Co and MDCK-OCT2 cells, but significantly increased in MDCK-MATE1 (p < 0.05) and MDCK-OCT2-MATE1 cells (p < 0.001). The OCT/MATE inhibitor trimethoprim abolished TMAO translocation in MDCK-OCT2-MATE1 cells (p < 0.05). The present data suggest that MATE1 contributes to renal elimination of TMAO. For selected MATE substrates, such as TMAO, uptake studies using non-polarised MATE-expressing cells can reveal false negative results compared to studies using polarised monolayers.
Ketogenic diet enhances neurovascular function with altered gut microbiome in young healthy mice
Authors: Ma David , Wang Amy C. , Parikh Ishita , Green Stefan J. , Hoffman Jared D. , Chlipala George , Murphy M. Paul , Sokola Brent S. , Bauer Björn , Hartz Anika M. S. , Lin Ai-Ling 
Published: April 2018

AbstractNeurovascular integrity, including cerebral blood flow (CBF) and blood-brain barrier (BBB) function, plays a major role in determining cognitive capability. Recent studies suggest that neurovascular integrity could be regulated by the gut microbiome. The purpose of the study was to identify if ketogenic diet (KD) intervention would alter gut microbiome and enhance neurovascular functions, and thus reduce risk for neurodegeneration in young healthy mice (12–14 weeks old). Here we show that with 16 weeks of KD, mice had significant increases in CBF and P-glycoprotein transports on BBB to facilitate clearance of amyloid-beta, a hallmark of Alzheimer’s disease (AD). These neurovascular enhancements were associated with reduced mechanistic target of rapamycin (mTOR) and increased endothelial nitric oxide synthase (eNOS) protein expressions. KD also increased the relative abundance of putatively beneficial gut microbiota (Akkermansia muciniphila and Lactobacillus), and reduced that of putatively pro-inflammatory taxa (Desulfovibrio and Turicibacter). We also observed that KD reduced blood glucose levels and body weight, and increased blood ketone levels, which might be associated with gut microbiome alteration. Our findings suggest that KD intervention started in the early stage may enhance brain vascular function, increase beneficial gut microbiota, improve metabolic profile, and reduce risk for AD.
Pilot study with IBAT inhibitor A4250 for the treatment of cholestatic pruritus in primary biliary cholangitis
Authors: Al-Dury Samer , Wahlström Annika , Wahlin Staffan , Langedijk Jacqueline , Elferink Ronald Oude , Ståhlman Marcus , Marschall Hanns-Ulrich 
Published: April 2018

AbstractPruritus is a common complication of cholestatic liver diseases. Inhibition of the ileal bile acid transporter (IBAT/ASBT) may emerge as treatment option. Our aim was to assess tolerability and effect on pruritus of the selective IBAT inhibitor A4250 in patients with primary biliary cholangitis (PBC). Ten patients with PBC and bile acid sequestrant treatment of cholestatic pruritus were after a two-week wash out of the bile acid sequestrant treated with either 0.75 mg (n = 4) or 1.5 mg (n = 5) of A4250 for four weeks. Patients’ pruritus was assessed by Visual Analogue Scale (VAS), 5-D itch scale and the pruritus module of the PBC40 questionnaire. Plasma bile acids and 7α-hydroxy-4-cholesten-3-one were measured by UPLC-MS/MS, plasma fibroblast growth factor 19 by ELISA, and serum autotaxin activity by homemade assay. All nine patients exposed to A4250 reported a remarkable improvement in pruritus, until none or mild according to 5-D itch, VAS and PBC40 pruritus. Five patients finished the study prematurely due to abdominal pain (5/5) and diarrhoea (4/5). The high incidence of probably bile acid malabsorption-related diarrhoea and abdominal pain in the bile acid sequestrant pre-treated population indicates that the start dose of A4250 may have been too high for adult patients.
Dietary polyphenols enhance optogenetic recall of fear memory in hippocampal dentate gyrus granule neuron subpopulations
Authors: Smith Chad , Frolinger Tal , Brathwaite Justin , Sims Steven , Pasinetti Giulio M. 
Published: April 2018

AbstractGrape-derived polyphenols have been investigated for their role in promoting memory in model systems of stress, but little is known about select subpopulations of neurons that are influenced by polyphenols to improve memory performance. Granule neurons in the hippocampal dentate gyrus are vulnerable to stressors that impair contextual memory function and can be influenced by dietary polyphenols. We utilized a c-fos-tTA/TRE-ChR2 optogenetics model in which neurons activated during fear learning are labeled with ChR2-mCherry and can be optically reactivated in a different context to recapitulate the behavioral output of a related memory. Treatment with dietary polyphenols increased fear memory recall and ChR2-mCherry expression in dentate gyrus neurons, suggesting that dietary polyphenols promote recruitment of neurons to a fear memory engram. We show that dietary polyphenols promote memory function and offer a general method to map cellular subpopulations influenced by dietary polyphenols, in part through the mechanism of c-Fos expression enhancement.
Cobalt-Catalyzed Hydroboration and Borylation of Alkenes and Alkynes
Authors: Huang Zheng , Zuo Ziqing , Wen Huanan , Liu Guixia 
Published: April 2018

Incorporation of the boryl moiety across a carbon–carbon multiple bond is a powerful method for the synthesis of organoboron compounds. This kind of transformation could be realized with high chemo-, regio-, and stereoselectivity by using an appropriate transition-metal catalyst. This account summarizes the latest advances from our group in the area of cobalt-catalyzed hydroboration and borylation of alkenes and alkynes, which lead to the formation of a variety of organoboron compounds, including alkylboronates, 1,1,1-tris(boronates), 1,1-diborylalkenes, and 1,1-diboronates.1	Introduction2	Cobalt-Catalyzed Hydroboration of Alkenes3	Cobalt-Catalyzed Dehydrogenative Borylations-Hydroboration4	Cobalt-Catalyzed Double Dehydrogenative Borylations of
1-Alkenes5	Cobalt-Catalyzed Hydroboration of Terminal Alkynes6	Summary and Outlook
Comparison between Hemilaminectomy with either Anulectomy or Partial Discectomy for Treatment of Thoracolumbar Intervertebral Disc Protrusion in Dogs
Authors: De Decker Steven , Crawford Abbe 
Published: April 2018

Objectives The aim of this study was to compare the clinical outcome of dogs undergoing a hemilaminectomy with anulectomy (HA) or a hemilaminectomy with partial discectomy (HPD) for treatment of thoracolumbar intervertebral disc protrusion.
Methods Medical records from 2006 to 2015 were retrospectively reviewed. Dogs were included if they had clinical signs and imaging findings consistent with thoracolumbar intervertebral disc protrusion and had undergone surgical treatment with a HA or HPD. Outcome data were obtained via veterinary records and owner questionnaires. Recorded variables included age, sex, body weight, neurological deficits, surgical time, perioperative complications, postoperative neurological deterioration and recurrence of clinical signs.
Results The two treatment groups showed no significant difference in signalment, clinical presentation and imaging findings. However, significant differences were detected in outcome. Early postoperative neurological deterioration was recorded in 16/29 dogs in the HA group and 7/24 dogs in the HPD group (p = 0.037). Sustained clinical improvement for a minimum of 18 months postoperatively was reported in 9/22 dogs in the HA group compared with 17/23 dogs in the HPD group (p = 0.019).
Clinical Significance Hemilaminectomy with partial discectomy for decompression of thoracolumbar intervertebral disc protrusion was associated with decreased postoperative neurological deterioration and increased sustained clinical improvement compared with hemilaminectomy with anulectomy.
Häufigkeit und Vorkommen multiresistenter gramnegativer Erreger: 3MRGN/4MRGN
Authors: Hamprecht Axel , Göttig Stephan 
Published: April 2018

AbstractThe increase of multidrug-resistant Gram-negative bacilli (MRGN) is a great threat for both the health system and patients. Challenges of MRGN for physicians are limited therapeutic options, the need of infection control measures and the danger of outbreaks. In this article, the prevalence of MRGN, risk factors, the background and definitions of multidrug-resistant organisms are presented.
Dysphagie aus gastroenterologischer Sicht
Authors: Hollenbach Marcus , Feisthammel Jürgen , Mössner Joachim , Hoffmeister Albrecht 
Published: April 2018

AbstractSwallowing disorders (dysphagia) comprise a common cause of medical consultation and are defined as a subjective sensation of difficulty or abnormality of swallowing. In the initial step, a clear differentiation of dysphagia from odynophagia and globus sensation for further diagnostic procedures is mandatory. The careful questioning of patients symptoms and complaints is often helpful for the differentiation of oropharyngeal and esophageal dysphagia. Oropharyngeal dysphagia is mainly caused by neurological disorders (cerebral ischemia, Parkinson’s disease, dementia) or local compression of malignancies, thyroid gland or lymph nodes. In contrast, stenosis of the tubular esophagus (peptic stricture, rings and webs, diverticula, malignancies, infections) can lead to esophageal dysphagia, mostly only after ingestion of solids. Esophageal dysphagia after ingestion of solids and liquids is often caused by motility disorders of the esophagus (achalasia, hypertensive or hypercontractile esophagus). Important diagnostic procedures comprise endoscopy, barium swallow and high-resolution manometry. Overlap syndromes are frequent and need to be supervised interdisciplinary. The diagnostic algorithm and interpretation of exam results is complex. If the results are ambiguous, a reevaluation and, when appropriate, repetition of diagnostics are recommended. Whereas oropharyngeal dysphagia is treated by neurologists or ENT physicians, diagnostic and treatment of esophageal dysphagia is a challenging role for gastroenterologists.
Environmental selection during the last ice age on the mother-to-infant transmission of vitamin D and fatty acids through breast milk
Authors: Hlusko Leslea J. , Carlson Joshua P. , Chaplin George , Elias Scott A. , Hoffecker John F. , Huffman Michaela , Jablonski Nina G. , Monson Tesla A. , O’Rourke Dennis H. , Pilloud Marin A. , Scott G. Richard 
Published: April 2018

SignificanceThe frequency of the human-specificEDAR V370Aisoform is highly elevated in North and East Asian populations. The gene is known to have several pleiotropic effects, among which are sweat gland density and ductal branching in the mammary gland. The former has led some geneticists to argue that the near-fixation of this allele was caused by selection for modulation of thermoregulatory sweating. We provide an alternative hypothesis, that selection instead acted on the allele’s effect of increasing ductal branching in the mammary gland, thereby amplifying the transfer of critical nutrients to infants via mother’s milk. This is likely to have occurred during the Last Glacial Maximum when a human population was genetically isolated in the high-latitude environment of the Beringia.
Lifetime of muscarinic receptor–G-protein complexes determines coupling efficiency and G-protein subtype selectivity
Authors: Ilyaskina Olga S. , Lemoine Horst , Bünemann Moritz 
Published: April 2018

Significance
The family of G-protein–coupled receptors (GPCRs) is the largest receptor family, and each member detects specific ligands, which in turn, activate selected members of one or more G-protein families. We developed a broadly applicable assay to study the specificity of GPCR–G-protein interaction in a subtype selective manner. We were able to quantitatively measure both association and dissociation rates of G proteins from agonist-activated GPCRs. We found that the stability of the receptor–G-protein complex is an inherent property of both interaction partners independent on the agonist used. Furthermore, its lifetime correlated closely with the ability of the receptor to activate the corresponding G-protein subtype.
Efficient models of polymerization applied to FtsZ ring assembly in
Escherichia coli
Authors: Ruiz-Martínez Álvaro , Bartol Thomas M. , Sejnowski Terrence J. , Tartakovsky Daniel M. 
Published: April 2018

Significance
Our modeling framework yields accurate and computationally efficient quantitative predictions of complex kinetics of polymerization processes in biological systems. The resulting model consists of 10 differential equations, regardless of the total concentration of proteins. This is in contrast to previous polymerization models, in which the number of equations increases with the total concentrations, reaching into the thousands. Consequently, our model is orders of magnitude faster than its existing alternatives. It can be used to predict polymerization kinetics at high concentrations characteristic of in vivo processes and, especially, their compartmentalized and spatially distributed representations.
Sporadic sampling, not climatic forcing, drives observed early hominin diversity
Authors: Maxwell Simon J. , Hopley Philip J. , Upchurch Paul , Soligo Christophe 
Published: April 2018

SignificancePaleoanthropologists have long been intrigued by the observed patterns of human evolution, including species diversity, and often invoked climatic change as the principal driver of evolutionary change. Here, we investigate whether the early hominin fossil record is of suitable quality to test these climate-forcing hypotheses. Specifically, we compare early hominin diversity to sampling metrics that quantify changes in fossil preservation and sampling intensity between 7 and 1 million years ago. We find that observed diversity patterns are governed by sporadic sampling and do not yield a genuine evolutionary signal. Many more fossil discoveries are required before existing hypotheses linking climate and evolution can be meaningfully tested.
Protection from cytomegalovirus viremia following glycoprotein B vaccination is not dependent on neutralizing antibodies
Authors: Baraniak Ilona , Kropff Barbara , Ambrose Lyn , McIntosh Megan , McLean Gary R. , Pichon Sylvie , Atkinson Claire , Milne Richard S. B. , Mach Michael , Griffiths Paul D. , Reeves Matthew B. 
Published: April 2018

Significance
Conventionally, vaccines are screened for induction of a neutralizing antibody response in human volunteers before proceeding to late-stage clinical trials. We present results from a human cytomegalovirus (HCMV) challenge study suggesting that this paradigm may not apply universally to all viruses. Instead, viruses like HCMV, which establish lifelong infections and grow both cell-free and cell-associated, may be controlled independently of a potent neutralizing antibody response. Our results suggest that more detailed laboratory studies are required to identify correlates of immune protection for such viruses and that failure of a vaccine to induce a neutralizing antibody response should not necessarily be considered as a key go-no-go decision point in the design of future vaccine studies.