bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of Teriparatide in Glucocorticoid‐induced Osteoporosis through Regulating Cellular Reactive Oxygen Species
Authors: Wang Tao , Han Chao , Tian Peng , Li Peng‐fei , Ma Xin‐long
Published: May 2018

Objective

To determine the signaling pathways mediated by teriparatide in MLO‐Y4 cell lines based on the evaluation of reactive oxygen species (ROS) through AKT pathways, which regulate apoptosis of bone cells.

Methods

We performed the DCFH‐DA assay to investigate the role of ROS in MLO‐Y4 cells caused by dexamethasone (Dex). Four groups were included: Dex group, Dex+NAC, Dex+ teriparatide group and control group (without any dispose). Real‐time reverse transcriptase polymerase chain reaction was used to test the SOD2 and Cat mRNA expression. Western blot (WB) was used to investigate the AKT and caspase‐3 protein expression. A Cell Counting Kit‐8 (CCK‐8) assay test was conducted to explore the cell viability, and we also studied the apoptosis through western blot assay. A glucocorticoid‐induced osteoporosis (GIOP) model was used to confirm the anti‐ROS and anti‐apoptosis ability of teriparatide.

Results

The CCK‐8 assay revealed that Dex reduced the proliferative capability of cells significantly, whereas incubation with teriparatide resulted in a remarkable increase in the proliferation of osteocytes. In addition, teriparatide can rescue the effect of inhibiting cell proliferation due to Dex treatment. Immunofluorescence analysis showed that ROS levels increased in Dex‐treated MLO‐Y4 cells when compared with control groups. However, the Dex+Teriparatide group showed less ROS when compared with the Dex group. The expression of Sod2 and Cat, two antioxidant enzymes crucial for ROS elimination, was decreased in the Dex group, indicating a defect of the enzymatic antioxidant system. Compared to the Dex group, incubation with teriparatide resulted in a significant decrease in caspase‐3 level; when compared with the control group, the caspase‐3 level was not significantly different, indicating that teriparatide can rescue apoptosis during Dex exposure. Moreover, teriparatide promotes the expression of AKT, and rescues the apoptosis effect caused by Dex. The results of immunofluorescence also showed that Akt was highly expressed in the teriparatide group when compared with the Dex group. The microstructural parameters Tb.Th, BV/TV, and Tb.N in the methylprednisolone (MPS) group were markedly reduced compared with the control group, but additional treatment with teriparatide could remarkably reverse the methylprednisolone‐induced reduction of these parameters. Moreover, the parameter Tb.Sp was significantly increased in the methylprednisolone group compared to the control group, and this increase could be inhibited by teriparatide.

Conclusions

Teriparatide can reduce the cellular ROS level caused by glucocorticoids to facilitate the proliferation of osteocytes through activating the AKT pathway. Meanwhile, the activated AKT can inhibit the activity of proteolytic enzyme caspase‐3 and prevent the activation of apoptosis cascade.
A simple technique for relocating chronic CIED leads to a subpectoral position for relief of erosion and pain
Authors: Hesselson Aaron B.
Published: May 2018

Background

Methodology specific for moving superficial chronically implanted transvenous pacing leads to a subpectoral pocket is not described in the literature. Relocation of prepectoral leads and generator to a submuscular pocket for relief of erosion and pain with minimal pectoral trauma is possible by applying a variant of a previously described submammary tunneling technique.

Methods

All patients presenting for device follow‐up, elective battery replacement, or system upgrade over an 8‐month period were considered for relocation if experiencing significant thinning or pain over their prepectoral implant. Those selected for relocation then had their system moved subpectorally via the tunneling technique. Patients were followed for 6 months postoperatively for procedurally related complications and resolution of preprocedure symptoms.

Results

Thirty‐two leads in 14 patients were all successfully relocated. Of the relocated leads, five (16%) were a three‐pin connector implantable cardioverter defibrillator lead. Three patients (21%) in the group required short‐term prescription analgesia in the immediate postdischarge period. Pain and erosion concerns abated in the study group by the 3‐month follow‐up.

Conclusions

Relocation of superficial pacing leads with CIED generator to a subpectoral pocket facilitated by this tunneling method is successful, safe, and can accommodate single and multipin leads with minimal pectoral trauma and no nerve damage.
Genes for seed longevity in barley identified by genomic analysis on near isogenic lines
Authors: Wozny Dorothee , Kramer Katharina , Finkemeier Iris , Acosta Ivan F. , Koornneef Maarten
Published: May 2018

Genes controlling differences in seed longevity between 2 barley (Hordeum vulgare) accessions were identified by combining quantitative genetics “omics” technologies in near isogenic lines (NILs). The NILs were derived from crosses between the spring barley landraces L94 from Ethiopia and Cebada Capa from Argentina. A combined transcriptome and proteome analysis on mature, nonaged seeds of the 2 parental lines and the L94 NILs by RNA‐sequencing and total seed proteomic profiling identified the UDP‐glycosyltransferase MLOC_11661.1 as candidate gene for the quantitative trait loci on 2H, and the NADP‐dependent malic enzyme (NADP‐ME) MLOC_35785.1 as possible downstream target gene. To validate these candidates, they were expressed in Arabidopsis under the control of constitutive promoters to attempt complementing the T‐DNA knockout line nadp‐me1. Both the NADP‐ME MLOC_35785.1 and the UDP‐glycosyltransferase MLOC_11661.1 were able to rescue the nadp‐me1 seed longevity phenotype. In the case of the UDP‐glycosyltransferase, with high accumulation in NILs, only the coding sequence of Cebada Capa had a rescue effect.
Internal Whistle‐Blowing in the Public Service: A Matter of Trust
Authors: Taylor Jeannette
Published: May 2018

Although employee reporting of workplace ethical violations is recognized as an important measure for managing the integrity of the public service, not many public employees who have observed ethical violations actually report them. This article examines and compares the links between employee perceptions of trustworthiness of different organizational members and internal whistle‐blowing. It differentiates between trustworthy coworkers, supervisors, and senior managers. It uses cross‐sectional data from 10,850 employees in the Australian Public Service in 2013 and 2016, which are aggregated to construct longitudinal data for 60 organizations. Among the three groups examined, perceptions of trustworthy senior managers are found to be most strongly related to internal whistle‐blowing.
The Physical Characteristics of Specific Phases of Play During Rugby Union Match Play
Authors: Read Dale B. , Jones Ben , Williams Sean , Phibbs Padraic J. , Darrall-Jones Josh D. , Roe Greg A.B. , Weakley Jonathon J.S. , Rock Andrew , Till Kevin
Published: May 2018

Purpose: To quantify the frequencies and timings of rugby union match-play phases (ie, attacking, defending, ball in play [BIP], and ball out of play [BOP]) and then compare the physical characteristics of attacking, defending, and BOP between forwards and backs. Methods: Data were analyzed from 59 male rugby union academy players (259 observations). Each player wore a microtechnology device (OptimEye S5; Catapult, Melbourne, Australia) with video footage analyzed for phase timings and frequencies. Dependent variables were analyzed using a linear mixed-effects model and assessed with magnitude-based inferences and Cohen d effect sizes (ES). Results: Attack, defense, BIP, and BOP times were 12.7 (3.1), 14.7 (2.5), 27.4 (2.9), and 47.4 (4.1) min, respectively. Mean attack (26 [17] s), defense (26 [18] s), and BIP (33 [24] s) phases were shorter than BOP phases (59 [33] s). The relative distance in attacking phases was similar (112.2 [48.4] vs 114.6 [52.3] m·min−1, ES = 0.00 ± 0.23) between forwards and backs but greater in forwards (114.5 [52.7] vs 109.0 [54.8] m·min−1, ES = 0.32 ± 0.23) during defense and greater in backs during BOP (ES = −0.66 ± 0.23). Conclusions: Total time in attack, defense, and therefore BIP was less than BOP. Relative distance was greater in forwards during defense, whereas it was greater in backs during BOP and similar between positions during attack. Players should be exposed to training intensities from in-play phases (ie, attack and defense) rather than whole-match data and practice technical skills during these intensities.
Is the Functional Threshold Power a Valid Surrogate of the Lactate Threshold?
Authors: Valenzuela Pedro L. , Morales Javier S. , Foster Carl , Lucia Alejandro , de la Villa Pedro
Published: May 2018

Purpose: To analyze the relationship between functional threshold power (FTP) and the lactate threshold (LT). Methods: A total of 20 male cyclists performed an incremental test in which LT was determined. At least 48 h later, they performed a 20-min time trial, and 95% of the mean power output was defined as FTP. Participants were divided into recreational (peak power output < 4.5 W·kg−1; n = 11) or trained cyclists (peak power output > 4.5 W·kg−1; n = 9) according to their fitness status. Results: The FTP (240 [35] W) was overall not significantly different (effect size = 0.20; limits of agreement = −2.4% [11.5%]) from the LT (246 [24] W), and both markers were strongly correlated (r = .95; P < .0001). Accounting for the participants’ fitness status, no significant differences were found between FTP and LT (effect size = 0.22; limits of agreement =2.1% [7.8%]) in trained cyclists, but FTP was significantly lower than the LT (P = .0004, effect size = 0.81; limits of agreement =−6.5% [8.3%]) in recreational cyclists. A significant relationship was found between relative peak power output and the bias between FTP and the LT markers (r = .77; P < .0001). Conclusions: FTP is a valid field test-based marker for the assessment of endurance fitness. However, caution should be taken when using FTP interchangeably with LT, as the bias between markers seems to depend on the athlete’s fitness status. Whereas FTP provides a good estimate of LT in trained cyclists, in recreational cyclists, it may underestimate LT.
NASA cancels carbon monitoring research program
Authors: Voosen Paul
Published: May 2018

Move undermines efforts to use satellite and aircraft observations to verify greenhouse gas reduction treaties.
A different animal
Authors: Langin Katie
Published: May 2018

One gene separates spring- and fall-run Chinook salmon. Is that enough to justify an endangered species listing?
How does temperature determine sex?
Authors: Georges Arthur , Holleley Clare E.
Published: May 2018

Temperature-responsive epigenetic regulation clarifies a 50-year-old mystery in reptiles
Energy powerhouses of cells come into focus
Authors: Kane Patricia M.
Published: May 2018

High-resolution structures reveal core design features of rotary ATP synthases and ATPases
Backing up nuclear disarmament
Authors: Zerbo Lassina
Published: May 2018

Who could have imagined the possibility of an inter-Korean Summit this year, let alone one between the United States and North Korea? Recent news that North Korea may suspend nuclear tests and dismantle its test site is a startling about-face, given the country's multitude of missile and nuclear weapons tests over the past decade. Those incidents increased tensions at a time when questions were being raised about the instruments, approaches, and mechanisms that nations collectively strive to use to rid the world of weapons of mass destruction. At the end of this month, the Comprehensive Nuclear-Test-Ban Treaty Organization (CTBTO) will convene a symposium in Vienna to emphasize what brings real security to the world—negotiated agreements that are effectively verifiable and credibly enforceable. These include the Treaty on the Non-Proliferation of Nuclear Weapons (NPT) and the Comprehensive Nuclear-Test-Ban Treaty (CTBT). The issue is not whether such current institutions and instruments are failing, but rather, preserving their integrity and building further trust in and around them.
Utility of a Stressed Single Nucleotide Polymorphism (SNP) Real-Time PCR Assay for Rapid Identification of Measles Vaccine Strains in Patient Samples
Authors: Tran Thomas , Kostecki Renata , Catton Michael , Druce Julian
Published: May 2018

Rapid differentiation of wild-type measles virus from measles vaccine strains is crucial during a measles outbreak and in a measles elimination setting. A real-time reverse transcription-PCR (rRT-PCR) for the rapid detection of measles vaccine strains was developed with high specificity and sensitivity equivalent to that of traditional measles genotyping methods.
Parents’ experience when their child has chronic abdominal pain: a qualitative study in Norway
Authors: Brodwall Anne , Glavin Kari , Lagerløv Per
Published: May 2018

Objective

Functional abdominal pain occurs frequently in children and adolescents. It is an exclusion diagnosis; somatic diseases have to be ruled out. However little explanation is given for why the child is experiencing pain. The aim was to explore the experiences of parents of children with chronic abdominal pain discharged from hospital without a somatic explanation.

Design

The study has a qualitative design. The open questions concerned pain experiences and management. Interviews were conducted at the hospital, at the parents’ workplace or in their homes, audiotape recorded and transcribed. A descriptive content analysis was used to analyse the transcribed text.

Setting

Parents of children referred from general practice located in urban and rural areas in two municipals in Norway.

Participants

Fourteen parents of children with functional abdominal pain aged 5–15 years.

Results

Fourteen parents participated. Some explained that their child’s disability glued the parents together on a common project to help the child. Other parents could tell that siblings got less attention and complained about too much fuss during pain. Parents wished for diagnosis that could be treated efficiently. Some were still anxious that an undetected condition triggered pain. They prompted their doctor to do further examinations. However, some parents knew that social factors could inflict pain and were concerned that their child was unable to distinguish sensations like anxiety and ‘butterfly’ tensions from physical pain. The parents and children needed professional guidance on how to manage the pain .

Conclusion

The doctor’s consultation should not end at the diagnosis of functional abdominal pain. Doctors may help these families further by focusing on pain management strategies.
Bivalirudin versus heparin in primary PCI: clinical outcomes and cost analysis
Authors: Deharo Pierre , Johnson Thomas W , Rahbi Hazim , Kandan Raveen , Bowles Ruth , Mozid Abdul , Dorman Stephen , Strange Julian W , Baumbach Andreas
Published: May 2018

Background

The evidence for benefits of bivalirudin over heparin has recently been challenged. We aimed to analyse the safety and cost-effectiveness following reintroduction of heparin instead of bivalirudin as the standard anticoagulation for primary percutaneous coronary intervention (PPCI) in a high-volume centre.

Methods and results

This analysis was an open-label, prospective registry including all patients admitted to our centre for PPCI from April 2014 to April 2016. Heparin was reintroduced as standard anticoagulant in April 2015. During the 2 years, 1291 patients underwent a PPCI, 662 in the Bivalirudin protocol period (Cohort B) and 629 in the Heparin protocol period (Cohort H). Baseline and procedural characteristics were not significantly different, except for a higher use of thromboaspiration and femoral access in the earlier Cohort B. Glycoprotein 2b3a (Gp2b3a) antagonists were used in 24% of the patients in Cohort B versus 28% in Cohort H (P<0.01). We did not observe any differences in death at 180 days (11.03% in Cohort B vs 11.29% in Cohort H)(HR 95% CI 0.98 (0.72 to 1.33), P=0.88). The incidence of any bleeding complications at 30 days did not differ between the two periods (21.9% vs 21.9%, P=0.99). The cost related to the anticoagulants amounted to £246 236 in Cohort B versus £4483 in Cohort H (£324 406 vs £102 347 when adding Gp2b3a antagonists).

Conclusion

We did not find clinically relevant changes in patient outcomes, including bleeding complications with reintroduction of heparin in our PPCI protocol. However, the use of heparin was associated with a major reduction in treatment costs.
Data from the US and UK cystic fibrosis registries support disease modification by CFTR modulation with ivacaftor
Authors: Bessonova Leona , Volkova Nataliya , Higgins Mark , Bengtsson Leif , Tian Simon , Simard Christopher , Konstan Michael W , Sawicki Gregory S , Sewall Ase , Nyangoma Stephen , Elbert Alexander , Marshall Bruce C , Bilton Diana
Published: May 2018

Background

Ivacaftor is the first cystic fibrosis transmembrane conductance regulator (CFTR) modulator demonstrating clinical benefit in patients with cystic fibrosis (CF). As ivacaftor is intended for chronic, lifelong use, understanding long-term effects is important for patients and healthcare providers.

Objective

This ongoing, observational, postapproval safety study evaluates clinical outcomes and disease progression in ivacaftor-treated patients using data from the US and the UK CF registries following commercial availability.

Methods

Annual analyses compare ivacaftor-treated and untreated matched comparator patients for: risks of death, transplantation, hospitalisation, pulmonary exacerbation; prevalence of CF-related complications and microorganisms and lung function changes in a subset of patients who initiated ivacaftor in the first year of commercial availability. Results from the 2014 analyses (2 and 3 years following commercial availability in the UK and USA, respectively) are presented here.

Results

Analyses included 1256 ivacaftor-treated and 6200 comparator patients from the USA and 411 ivacaftor-treated and 2069 comparator patients from the UK. No new safety concerns were identified based on the evaluation of clinical outcomes included in the analyses. As part of safety evaluations, ivacaftor-treated US patients were observed to have significantly lower risks of death (0.6% vs 1.6%, p=0.0110), transplantation (0.2% vs 1.1%, p=0.0017), hospitalisation (27.5% vs 43.1%, p<0.0001) and pulmonary exacerbation (27.8% vs 43.3%, p<0.0001) relative to comparators; trends were similar in the UK. In both registries, ivacaftor-treated patients had a lower prevalence of CF-related complications and select microorganisms and had better preserved lung function.

Conclusions

While general limitations of observational research apply, analyses revealed favourable results for clinically important outcomes among ivacaftor-treated patients, adding to the growing body of literature supporting disease modification by CFTR modulation with ivacaftor.

EU PAS registration number

EUPAS4270
Antifungal activity of essential oils against azole-resistant and azole-susceptible vaginal Candida glabrata strains
Authors: Massa N. , Cantamessa S. , Novello G. , Ranzato E. , Martinotti S. , Pavan M. , Rocchetti A. , Berta G. , Gamalero E. , Bona E.
Published: May 2018

Candida glabrata is an opportunistic pathogen, associated with endocarditis, meningitis, and disseminated disease, and also with complicated vaginitis. Essential oils derived from aromatic plants are known in traditional medicine as antimicrobial agents and have antifungal properties. The aim of this work was to evaluate whether 12 tested essential oils (tea tree, laurel, anise, basil, bergamot, lavender, mint, oregano, grapefruit, rosemary, winter savory, and ginger) could have a transverse effect on C. glabrata sensitive strains but above all on strains resistant to the three main azole antifungals used (clotrimazole, fluconazole, itraconazole). For this reason, different strains of C. glabrata, vaginal isolated, were characterized (disk diffusion assay, minimal inhibitory concentration) with respect to their response to such antifungals. Electron microscopy analyses were performed to examine cellular damages in depth. Subsequently, we wanted to evaluate the effect of the oils on human cells to estimate their potential cytotoxicity. Oregano and winter savory were the two most effective essential oils, inducing growth inhibition, cell damage of C. glabrata strains (both sensitive and resistant to azole antifungal drugs), and medium–high level of toxicity against human keratinocytes. The results of this work support the research for new alternatives or complementary therapies against vaginal candidiasis.
Controlling the interference between localized and delocalized surface plasmons via incident polarization for optical switching
Authors: Song Wen-Bo , Qi Yun , Zhang Xiao-Peng , Wan Ming-Li , He Jinna
Published: May 2018

Surface plasmons supported by various metallic nanostructures have given rise to several significant breakthroughs in the field of integrated photonic devices due to its ability to effectively confine and enhance optical field in subwavelength volume. In particular, the demand to actively control optical responses of plasmonic systems becomes urgent for the miniaturization of signal processing devices, surface-enhanced Raman scattering (SERS) substrates and biochemical sensors. In this paper, we systematically investigate the plasmon modes as well as their interaction in a layered nanostructure composed of a periodically-arranged radiative nanoring and a metallic ground plane, as well as a thin insulating spacer. A tunable transparent peak on the background of the broadband plasmon resonance emerges in the reflection spectrum as changing the periodicity of nanoparticle array, a plasmonic analogue of electromagnetically induced transparency (EIT). Owing to the structural symmetry of the rings, we demonstrate a new scheme of controlling the interference between localized and delocalized plasmons by means of incident polarization and believe that the proposed metasurface may find applications in optical switching if the polarization-controlled components are introduced.
Knowledge Transition: A Conceptual Model of Knowledge Transfer for Cross-Industry Innovation
Authors: Lyng Hilda Bø , Brun Eric Christian
Published: May 2018

There is a gap in research literature between cross-industry innovation (CII), knowledge transfer, and relational proximities. In this study, we analyze contributions from these three streams of literature and an empirical case of CII, and propose a conceptual model for knowledge transfer in CII, which also incorporates the influences of proximities. The focus of our study is on CII from the petroleum industry to the medical industry. Theoretical and practical implications are discussed in the paper.
Encapsulating silicon nanoparticles into N-doped carbon film as a high-performance anode for lithium ion batteries
Authors: Xing Zheng , Huang Chunlai , Deng Yichen , Zhao Yulong , Ju Zhicheng
Published: May 2018

A flexible strategy is to exploit encapsulating Si nanoparticles into N-doping carbon film (Si-NC) that can effectively localize the Si nanoparticles, thereby solving the problem of serious volume change during cycling as well as facilitating the fast diffusion of Li[Formula: see text], and thus achieving improved anode performance. A maximum capacity of 883.1[Formula: see text]mAh[Formula: see text]g[Formula: see text] at the current density of 100[Formula: see text]mA[Formula: see text]g[Formula: see text] after 50 charge and discharge processes is achieved for Si-NC. Even at a large current density of 2000[Formula: see text]mA[Formula: see text]g[Formula: see text], a specific capacity of 415[Formula: see text]mAh[Formula: see text]g[Formula: see text] is maintained. Moreover, the charge capacity can still almost recover the initial capacity as the current density is reverted to 100[Formula: see text]mA[Formula: see text]g[Formula: see text], indicating that Si-NC has a superior rate performance in lithium storage. This facile synthesis route provides a new perspective to produce Si/C composite at a low cost and large scale with good electrochemical performance.
Pharmacological decrease of liver stiffness is pressure-related and predicts long-term clinical outcome
Authors: Piecha Felix , Mandorfer Mattias , Peccerella Teresa , Ozga Ann-Kathrin , Poth Tanja , Vonbank Anna , Seitz Helmut Karl , Rausch Vanessa , Reiberger Thomas , Mueller Sebastian
Published: May 2018

Liver stiffness (LS) as measured by transient elastography is increasingly used to noninvasively assess liver fibrosis. However, LS is efficiently modulated by confounders like arterial and portal pressure (PP). We here study the effect of acute hemodynamic changes on LS (measured by µFibroscan) in a rodent model of cirrhosis in response to pharmacological modulation of PP by losartan, nitric oxide donors, and propranolol. Additionally, changes of LS and the hepatic venous pressure gradient (HVPG) under propranolol therapy were assessed with regard to clinical outcomes in a human cohort of n = 38 cirrhotic patients. In the animal model, cirrhosis induction resulted in a significant increase of LS and PP. After losartan or NO application, a LS decrease of 25% was strongly correlated with a concomitant decrease of mean arterial pressure (MAP) and PP. In contrast, acute propranolol administration decreased heart rate but not MAP resulting in stable LS. In the human cohort, most patients ( n = 25, 66%) showed a LS decrease after propranolol treatment initiation which significantly correlated to HVPG ( r = 0.518, P < 0.01) but was not accompanied by statistically significant changes in transaminases or model of end-stage liver disease (MELD). On multivariate analysis, patients with decreasing LS on propranolol had a decreased risk for experiencing a transplantation or death than patients with increasing LS irrespective of HVPG. In conclusion, LS changes after pharmacological interventions are influenced by hemodynamic effects on arterial and portal pressure. In humans, a LS decrease may be predictive of improved outcome irrespective of MELD scores and may serve as an additional follow-up tool in the future.

NEW & NOTEWORTHY Liver stiffness (LS) is efficiently modulated by changes in portal venous and systemic pressures in an animal model of liver cirrhosis irrespective of baseline LS and portal pressure values. In humans, most patients show a decrease in LS after propranolol treatment initiation without statistically significant changes in transaminases or model of end-stage liver disease (MELD) scores. A decrease in LS may be associated with improved outcome and thus another valuable tool in the follow-up of patients after propranolol treatment initiation.
Filaggrin and tight junction proteins are crucial for IL-13-mediated esophageal barrier dysfunction
Authors: Wu Liping , Oshima Tadayuki , Li Min , Tomita Toshihiko , Fukui Hirokazu , Watari Jiro , Miwa Hiroto
Published: May 2018

Eosinophilic esophagitis (EoE) is an allergy-mediated disease that is accompanied by IL-13 overexpression and an impaired esophageal barrier. Filaggrin (FLG) and tight junction (TJ) proteins are considered to contribute to epithelial barrier function. However, their functional involvement in EoE has not been elucidated. Here, we aimed to determine the IL-13-mediated barrier dysfunction and expression of TJ-related proteins in EoE and to characterize interactions among TJ-related proteins involved in the barrier function of the esophageal epithelium. Biopsy specimens from EoE patients were analyzed. Primary human esophageal epithelial cells (HEECs) were cultured using an air-liquid interface (ALI) system. The permeability of TJs was assayed by biotinylation. Transepithelial electrical resistance (TEER) was measured after stimulation with IL-13 and after siRNA silencing of FLG expression. FLG and TJ genes and proteins were assessed by quantitative RT-PCR, Western blot analysis, and immunofluorescent staining. The biotinylation reagent diffused through the paracellular spaces of whole stratified epithelial layers in EoE biopsy samples. The TEER decreased in ALI-cultured HEECs after IL-13 stimulation. Although the protein level of FLG decreased, that of the TJ proteins increased in the mucosa of EoE biopsy samples and in ALI-cultured HEECs after IL-13 stimulation. IL-13 altered the staining patterns of TJ proteins and the epithelial morphology. FLG siRNA transfection significantly decreased TEER. The IL-13-mediated reduced esophageal barrier is associated with the altered expression pattern but not with the levels of TJ-associated proteins. A deficiency of FLG altered the stratified epithelial barrier.

NEW & NOTEWORTHY Esophageal permeability to small molecules was increased in patients with eosinophilic esophagitis (EoE) and could be induced by IL-13 in our unique air-liquid interface-cultured primary multilayer human esophageal epithelial cells in vitro. A deficiency of filaggrin disrupted the esophageal stratified epithelial barrier. The decreased esophageal barrier in EoE was associated with the altered staining pattern of tight junction proteins, although the levels of the proteins themselves do not appear to be changed.
Pannexin-1 channels on endothelial cells mediate vascular inflammation during lung ischemia-reperfusion injury
Authors: Sharma Ashish K. , Charles Eric J. , Zhao Yunge , Narahari Adishesh K. , Baderdinni Pranav K. , Good Miranda E. , Lorenz Ulrike M. , Kron Irving L. , Bayliss Douglas A. , Ravichandran Kodi S. , Isakson Brant E. , Laubach Victor E.
Published: May 2018

Ischemia-reperfusion (I/R) injury (IRI), which involves inflammation, vascular permeability, and edema, remains a major challenge after lung transplantation. Pannexin-1 (Panx1) channels modulate cellular ATP release during inflammation. This study tests the hypothesis that endothelial Panx1 is a key mediator of vascular inflammation and edema after I/R and that IRI can be blocked by Panx1 antagonism. A murine hilar ligation model of IRI was used whereby left lungs underwent 1 h of ischemia and 2 h of reperfusion. Treatment of wild-type mice with Panx1 inhibitors (carbenoxolone or probenecid) significantly attenuated I/R-induced pulmonary dysfunction, edema, cytokine production, and neutrophil infiltration versus vehicle-treated mice. In addition, VE-Cad-CreERT2+/Panx1fl/fl mice (tamoxifen-inducible deletion of Panx1 in vascular endothelium) treated with tamoxifen were significantly protected from IRI (reduced dysfunction, endothelial permeability, edema, proinflammatory cytokines, and neutrophil infiltration) versus vehicle-treated mice. Furthermore, extracellular ATP levels in bronchoalveolar lavage fluid is Panx1-mediated after I/R as it was markedly attenuated by Panx1 antagonism in wild-type mice and by endothelial-specific Panx1 deficiency. Panx1 gene expression in lungs after I/R was also significantly elevated compared with sham. In vitro experiments demonstrated that TNF-α and/or hypoxia-reoxygenation induced ATP release from lung microvascular endothelial cells, which was attenuated by Panx1 inhibitors. This study is the first, to our knowledge, to demonstrate that endothelial Panx1 plays a key role in mediating vascular permeability, inflammation, edema, leukocyte infiltration, and lung dysfunction after I/R. Pharmacological antagonism of Panx1 activity may be a novel therapeutic strategy to prevent IRI and primary graft dysfunction after lung transplantation.
AMD3100 ameliorates cigarette smoke-induced emphysema-like manifestations in mice
Authors: Barwinska Daria , Oueini Houssam , Poirier Christophe , Albrecht Marjorie E. , Bogatcheva Natalia V. , Justice Matthew J. , Saliba Jacob , Schweitzer Kelly S. , Broxmeyer Hal E. , March Keith L. , Petrache Irina
Published: May 2018

We have shown that cigarette smoke (CS)-induced pulmonary emphysema-like manifestations are preceded by marked suppression of the number and function of bone marrow hematopoietic progenitor cells (HPCs). To investigate whether a limited availability of HPCs may contribute to CS-induced lung injury, we used a Food and Drug Administration-approved antagonist of the interactions of stromal cell-derived factor 1 (SDF-1) with its chemokine receptor CXCR4 to promote intermittent HPC mobilization and tested its ability to limit emphysema-like injury following chronic CS. We administered AMD3100 (5mg/kg) to mice during a chronic CS exposure protocol of up to 24 wk. AMD3100 treatment did not affect either lung SDF-1 levels, which were reduced by CS, or lung inflammatory cell counts. However, AMD3100 markedly improved CS-induced bone marrow HPC suppression and significantly ameliorated emphysema-like end points, such as alveolar airspace size, lung volumes, and lung static compliance. These results suggest that antagonism of SDF-1 binding to CXCR4 is associated with protection of both bone marrow and lungs during chronic CS exposure, thus encouraging future studies of potential therapeutic benefit of AMD3100 in emphysema.
Mechanical properties of the airway tree: heterogeneous and anisotropic pseudoelastic and viscoelastic tissue responses
Authors: Eskandari Mona , Arvayo Alberto L. , Levenston Marc E.
Published: May 2018

Airway obstruction and pulmonary mechanics remain understudied despite lung disease being the third cause of death in the United States. Lack of relevant data has led computational pulmonary models to infer mechanical properties from available material data for the trachea. Additionally, the time-dependent, viscoelastic behaviors of airways have been largely overlooked, despite their potential physiological relevance and utility as metrics of tissue remodeling and disease progression. Here, we address the clear need for airway-specific material characterization to inform biophysical studies of the bronchial tree. Specimens from three airway levels (trachea, large bronchi, and small bronchi) and two orientations (axial and circumferential) were prepared from five fresh pig lungs. Uniaxial tensile tests revealed substantial heterogeneity and anisotropy. Overall, the linear pseudoelastic modulus was significantly higher axially than circumferentially (30.5 ± 3.1 vs. 8.4 ± 1.1 kPa) and significantly higher among circumferential samples for small bronchi than for the trachea and large bronchi (12.5 ± 1.9 vs. 6.0 ± 0.6 and 6.6 ± 0.9 kPa). Circumferential samples exhibited greater percent stress relaxation over 300 s than their axial counterparts (38.0 ± 1.4 vs. 23.1 ± 1.5%). Axial and circumferential trachea samples displayed greater percent stress relaxation (26.4 ± 1.6 and 42.5 ± 1.7%) than corresponding large and small bronchi. This ex vivo pseudoelastic and viscoelastic characterization reveals novel anisotropic and heterogeneous behaviors and equips us to construct airway-specific constitutive relations. Our results establish necessary fundamentals for airway mechanics, laying the groundwork for future studies to extend to clinical questions surrounding lung injury, and further directly enables computational tools for lung disease obstruction predictions.

NEW & NOTEWORTHY Understanding the mechanics of the lung is necessary for investigating disease progression. Trachea mechanics comprises the vast majority of ex vivo airway tissue characterization despite distal airways being the site of disease manifestation and occlusion. Furthermore, viscoelastic studies are scarce, whereas time-dependent behaviors could be potential physiological metrics of tissue remodeling. In this study, the critical need for airway-specific material properties is addressed, reporting bronchial tree anisotropic and heterogeneous material properties.
NADPH Oxidase Signaling Pathway Mediates Mesenchymal Stem Cell-Induced Inhibition of Hepatic Stellate Cell Activation
Authors: Qiao Haowen , Zhou Yu , Qin Xingping , Cheng Jing , He Yun , Jiang Yugang
Published: May 2018

Background. Bone marrow-derived mesenchymal stem cells (BMSCs) have blossomed into an effective approach with great potential for the treatment of liver fibrosis. The aim of this study was to investigate the underlying antifibrosis mechanisms by which the BMSC inhibit activated hepatic stellate cells (HSCs) in vivo and in vitro. Methods. To study the effect of human bone marrow-derived mesenchymal stem cells (hBM-MSCs) on activated HSCs, we used HSCs and the coculture systems to evaluate the inhibition of activated HSCs from the aspects of the apoptosis of activated HSCs. In addition, activation of NADPH oxidase pathway and the changes in liver histopathology were tested by using the carbon tetrachloride- (CCl4-) induced liver fibrosis in mice. Results. Introduction of hBM-MSCs significantly inhibited the proliferation of activated HSCs by inducing the apoptosis process of activated HSCs. The effect of hBM-MSCs reduced the signaling pathway of NADPH oxidase in activated HSCs. Besides, the signaling pathway of NADPH oxidase mediated hBM-MSC upregulation of the expression of the peroxisome proliferator-activated receptor γ and downregulation of the expression of α1(I) collagen and alpha-smooth muscle actin (α-SMA) in activated HSCs. Moreover, the hBM-MSC-induced decrease in the signaling pathway of NADPH oxidase was accompanied by the decrease of the activated HSC number and liver fibrosis in a mouse model of CCl4-induced liver fibrosis. Conclusion. The hBM-MSCs act as a promising drug source against liver fibrosis development with respect to hepatopathy as a therapeutic target.
Comparative Genomics Analysis of Plasmid pPV989-94 from a Clinical Isolate ofPantoea vagansPV989
Authors: Xu Lei , Yin Min , Zhu Tingyuan , Liu Yabo , Ying Yuanyuan , Lu Junwan , Lin Chaoqing , Ying Jianchao , Xu Teng , Ni Liyan , Bao Qiyu , Lu Shunfei
Published: May 2018

Pantoea vagans, a gram-negative bacterium from the genusPantoeaand familyEnterobacteriaceae, is present in various natural environments and considered to be plant endophytes. We isolated thePantoea vagansPV989 strain from the clinic and sequenced its whole genome. Besides a chromosome DNA molecule, it also harboured three large plasmids. A comparative genomics analysis was performed for the smallest plasmid, pPV989-94. It can be divided into four regions, including three conservative regions related to replication (R1), transfer conjugation (R2), and transfer leading (R3), and one variable region (R4). Further analysis showed that pPV989-94 is most similar to plasmids LA637P2 and pEA68 ofErwinia amylovorastrains isolated from fruit trees. These three plasmids share three conservative regions (R1, R2, and R3). Interestingly, a fragment (R4′) in R4, mediated by phage integrase and phage integrase family site-specific recombinase and encoding 9 genes related to glycometabolism, resistance, and DNA repair, was unique in pPV989-94. Homologues of R4′were found in other plasmids or chromosomes, suggesting that horizontal gene transfer (HGT) occurred among different bacteria of various species or genera. The acquired functional genes may play important roles in the adaptation of bacteria to different hosts or environmental conditions.
Multilevel Seismic Damage Behavior Correlation Analysis for RC Framed Structures
Authors: Yue Jianguang
Published: May 2018

Five structural levels, that is, material level, section level, member level, storey level, and structure level, were proposed to analyze the multilevel nonlinear mechanism of the reinforced concrete (RC) framed structures. Based on the presented deformation equivalent principle, a generalized stiffness damage model was developed for each structural level. At each structural level, the stiffness damage value can be calculated by the integration of the material stiffness damage. Furthermore, an impact factor was proposed to reflect the damage correlations between different structural levels. In order to verify this method, the proposed method was used to study the damage evolutions at various structural levels of a 12‐storey frame structure. The numerical model utilizing the proposed analysis method produces results in good agreement with the test results of the 12‐storey frame structure. It shows that the proposed method is useful to assess the structure multilevel damage performance and to design a new structure.
Syngeneic Transplantation of Olfactory Ectomesenchymal Stem Cells Restores Learning and Memory Abilities in a Rat Model of Global Cerebral Ischemia
Authors: Veron Antoine D. , Bienboire-Frosini Cécile , Girard Stéphane D. , Sadelli Kevin , Stamegna Jean-Claude , Khrestchatisky Michel , Alexis Jennifer , Pageat Patrick , Asproni Pietro , Mengoli Manuel , Roman François S.
Published: May 2018

Stem cells are considered as promising tools to repair diverse tissue injuries. Among the different stem cell types, the “olfactory ectomesenchymal stem cells” (OE-MSCs) located in the adult olfactory mucosa stand as one of the best candidates. Here, we evaluated if OE-MSC grafts could decrease memory impairments due to ischemic injury. OE-MSCs were collected from syngeneic F344 rats. After a two-step global cerebral ischemia, inducing hippocampal lesions, learning abilities were evaluated using an olfactory associative discrimination task. Cells were grafted into the hippocampus 5 weeks after injury and animal’s learning abilities reassessed. Rats were then sacrificed and the brains collected for immunohistochemical analyses. We observed significant impairments in learning and memory abilities following ischemia. However, 4 weeks after OE-MSC grafts, animals displayed learning and memory performances similar to those of controls, while sham rats did not improve them. Immunohistochemical analyses revealed that grafts promoted neuroblast and glial cell proliferation, which could permit to restore cognitive functions. These results demonstrated, for the first time, that syngeneic transplantations of OE-MSCs in rats can restore cognitive abilities impaired after brain injuries and provide support for the development of clinical studies based on grafts of OE-MSCs in amnesic patients following brain injuries.
Study of the Press Fit Bearing‐Shaft Joint Dimensional Parameters by Analytical and Numerical Approach
Authors: Murčinková Zuzana , Baron Petr , Pollák Martin
Published: May 2018

The study of press fit bearing‐shaft joint dimensional parameters by means of analytical and numerical calculations in order to identify those parameters of the press fit joints which significantly influence the life of the bearings fitted by pressing is dealt in this paper. The mounting and conditions of fit joint are the significant factors affecting the operability and life of the bearings and consequently that of rotating machines and the whole technical units. The aim of the analysis and study is to determine the tangential and radial stress, the radial displacement, and the influence of the shape features and the size of the interference on the change of the radii in the press fit bearing‐shaft joint, in particular, the ball bearings of 6014 2RSR C3 type. Moreover, on the basis of obtained results, the paper discusses the impact of shaft dimensional and geometrical accuracy on the bearing lifetime.
Benralizumab: From the Basic Mechanism of Action to the Potential Use in the Biological Therapy of Severe Eosinophilic Asthma
Authors: Pelaia Corrado , Calabrese Cecilia , Vatrella Alessandro , Busceti Maria Teresa , Garofalo Eugenio , Lombardo Nicola , Terracciano Rosa , Pelaia Girolamo
Published: May 2018

Asthma is a very frequent chronic airway disease that includes many different clinical phenotypes and inflammatory patterns. In particular, eosinophilic bronchial inflammation is often associated with allergic as well as nonallergic asthma. The most important cytokine involved in the induction, maintenance, and amplification of airway eosinophilia in asthma is interleukin-5 (IL-5), released by both T helper 2 (Th2) lymphocytes and group 2 innate lymphoid cells (ILC2). Hence, IL-5 and its receptor are suitable targets for selective biologic drugs which can play a key role in add-on treatment of severe eosinophilic asthma refractory to corticosteroids. Within such a context, the anti-IL-5 monoclonal antibodies mepolizumab and reslizumab have been developed and approved for biological therapy of uncontrolled eosinophilic asthma. In this regard, on the basis of several successful randomized controlled trials, the anti-IL-5 receptor benralizumab has also recently obtained the approval from US Food and Drug Administration (FDA).
Performance Analysis of Network-RTK Techniques for Drone Navigation considering Ionospheric Conditions
Authors: Bae Tae-Suk , Kim Minho
Published: May 2018

Recently, an accurate positioning has become the kernel of autonomous navigation with the rapid growth of drones including mapping purpose. The Network-based Real-time Kinematic (NRTK) system was predominantly used for precision positioning in many fields such as surveying and agriculture, mostly in static mode or low-speed operation. The NRTK positioning, in general, shows much better performance with the fixed integer ambiguities. However, the success rate of the ambiguity resolution is highly dependent on the ionospheric condition and the surrounding environment of Global Navigation Satellite System (GNSS) positioning, which particularly corresponds to the low-cost GNSS receivers. We analyzed the effects of the ionospheric conditions on the GNSS NRTK, as well as the possibility of applying the mobile NRTK to drone navigation for mapping. Two NRTK systems in operation were analyzed during a period of high ionospheric conditions, and the accuracy and the performance were compared for several operational cases. The test results show that a submeter accuracy is available even with float ambiguity under a favorable condition (i.e., visibility of the satellites as well as stable ionosphere). We still need to consider how to deal with ionospheric disturbances which may prevent NRTK positioning.
Assessment of Transient Stability through Coherent Machine Identification by Using Least-Square Support Vector Machine
Authors: Soni Bhanu Pratap , Saxena Akash , Gupta Vikas , Surana S. L.
Published: May 2018

Transient stability assessment (TSA) of the power system is a crucial issue with escalating demands and large operational constraints. Real-time TSA allows for deciding and monitoring of the relevant preventive/corrective control actions depending on the dynamic behavior of the system components. To assess this, coherency of generating machines is to be found. After determination of the coherent machines, any corrective or preventive action can be initiated by the system operator to maintain stability of the system during occurrence of any severe contingency. The Transient Severity Index (TSI) introduced in this paper has proven to be an interesting alternative for determining generator coherency. Furthermore, the numerical values of this index are employed to construct a supervised learning-based classifier and the ranking method with the help of system load and generation as input features. This framework employs the support vector machine (SVM) to perform the ranking of the generators based on severity and classify them into vulnerable and nonvulnerable machines. The results are validated on the IEEE 10-generator, 39-bus test (New England) system. It is observed that the proposed index and the supervised learning engine give satisfactory results and both are aligned with the published approaches.