bluuebunny/crossref_metadata_2025_split huggingface dataset:
Solute carriers affect Anopheles stephensi survival and Plasmodium berghei infection in the salivary glands
Authors: Couto J. , Antunes S. , Pinheiro-Silva R. , do Rosário V. , de la Fuente J. , Domingos A. 
Published: July 2017

AbstractMalaria is caused by mosquito-bornePlasmodiumspp. parasites that must infect and survive within mosquito salivary glands (SGs) prior to host transmission. Recent advances in transcriptomics and the complete genome sequencing of mosquito vectors have increased our knowledge of the SG genes and proteins involved in pathogen infection and transmission. Membrane solute carriers are key proteins involved in drug transport and are useful in the development of new interventions for transmission blocking. Herein, we applied transcriptomics analysis to compare SGs mRNA levels inAnopheles stephensifed on non-infected andP. berghei-infected mice. TheA. stephensisolute carriersprestinAandNDAE1were up-regulated in response to infection. These molecules are predicted to interact with each other, and are reportedly involved in the maintenance of cell homeostasis. To further evaluate their functions in mosquito survival and parasite infection, these genes were knocked down by RNA interference. Knockdown ofprestinAandNDAE1resulted in reduction of the number of sporozoites in mosquito SGs. Moreover,NDAE1knockdown strongly impacted mosquito survival, resulting in the death of half of the treated mosquitoes. Overall, our findings indicate the importance of prestinA and NDAE1 in interactions between mosquito SGs andPlasmodium, and suggest the need for further research.
Integrin α6β4 Upregulates Amphiregulin and Epiregulin through Base Excision Repair-Mediated DNA Demethylation and Promotes Genome-wide DNA Hypomethylation
Authors: Carpenter Brittany L. , Liu Jinpeng , Qi Lei , Wang Chi , O’Connor Kathleen L. 
Published: July 2017

AbstractAberrant DNA methylation patterns are a common theme across all cancer types. Specific DNA demethylation of regulatory sequences can result in upregulation of genes that are critical for tumor development and progression. Integrin α6β4 is highly expressed in pancreatic carcinoma and contributes to cancer progression, in part, through the specific DNA demethylation and upregulation of epidermal growth factor receptor (EGFR) ligands amphiregulin (AREG) and epiregulin (EREG). Whole genome bisulfite sequencing (WGBS) revealed that integrin α6β4 signaling promotes an overall hypomethylated state and site specific DNA demethylation of enhancer elements within the proximal promoters of AREG and EREG. Additionally, we find that the base excision repair (BER) pathway is required to maintain expression of AREG and EREG, as blocking DNA repair molecules, TET1 GADD45A, TDG, or PARP-1 decreased gene expression. Likewise, we provide the novel finding that integrin α6β4 confers an enhanced ability on cells to repair DNA lesions and survive insult. Therefore, while many known signaling functions mediated by integrin α6β4 that promote invasive properties have been established, this study demonstrates that integrin α6β4 can dramatically impact the epigenome of cancer cells, direct global DNA methylation levels toward a hypomethylated state, and impact DNA repair and subsequent cell survival.
Human intrahepatic CD69 + CD8+ T cells have a tissue resident memory T cell phenotype with reduced cytolytic capacity
Authors: Stelma Femke , de Niet Annikki , Sinnige Marjan J. , van Dort Karel A. , van Gisbergen Klaas P. J. M. , Verheij Joanne , van Leeuwen Ester M. M. , Kootstra Neeltje A. , Reesink Hendrik W. 
Published: July 2017

AbstractTissue resident memory T cells (TRM) have been identified in various tissues, however human liver TRM to date remain unidentified. TRM can be recognized by CD69 and/or CD103 expression and may play a role in the pathology of chronic hepatitis B (CHB) and hepatitis C virus infection (CHC). Liver and paired blood mononuclear cells from 17 patients (including 4 CHB and 6 CHC patients) were isolated and CD8+ T cells were comprehensively analysed by flowcytometry, immunohistochemistry and qPCR. The majority of intrahepatic CD8+ T cells expressed CD69, a marker used to identify TRM, of which a subset co-expressed CD103. CD69 + CD8+ T cells expressed low levels of S1PR1 and KLF2 and a large proportion (>90%) was CXCR6+, resembling liver TRM in mice and liver resident NK cells in human. Cytotoxic proteins were only expressed in a small fraction of liver CD69 + CD8+ T cells in patients without viral hepatitis, however, in livers from CHB patients more CD69 + CD8+ T cells were granzyme B+. In CHC patients, less intrahepatic CD69 + CD8+ T cells were Hobit+ as compared to CHB and control patients. Intrahepatic CD69 + CD8+ T cells likely TRM which have a reduced cytolytic potential. In patients with chronic viral hepatitis TRM have a distinct phenotype.
An In Vitro Model for the Ocular Surface and Tear Film System
Authors: Lu Qiaozhi , Yin Hongbo , Grant Michael P. , Elisseeff Jennifer H. 
Published: July 2017

AbstractDry eye is a complicated ocular surface disease whose exact pathogenesis is not yet fully understood. For the therapeutic evaluation and pathogenesis study of dry eye, we established an in vitro three-dimensional (3D) coculture model for the ocular surface. It is composed of rabbit conjunctival epithelium and lacrimal gland cell spheroids, and recapitulates the aqueous and mucin layers of the tear film. We first investigated the culture conditions for both cell types to optimize their secretory functions, by employing goblet cell enrichment, air-lifting culture, and 3D spheroid formation techniques. The coculture of the two cell components leads to elevated secretion and higher expression of tear secretory markers. We also compared several coculture systems, and found that direct cell contact between the two cell types significantly increased tear secretion. Inflammation was induced to mimic dry eye disease in the coculture model system. Our results showed that the coculture system provides a more physiologically relevant therapeutic response compared to monocultures. Our work provides a complex 3D model as a recapitulation of the ocular surface and tear film system, which can be further developed as a model for dry eye disease and therapeutic evaluation.
Tumor-targeted delivery of siRNA using fatty acyl-CGKRK peptide conjugates
Authors: Sharma Meenakshi , El-Sayed Naglaa Salem , Do Hung , Parang Keykavous , Tiwari Rakesh Kumar , Aliabadi Hamidreza Montazeri 
Published: July 2017

AbstractTumor-targeted carriers provide efficient delivery of chemotherapeutic agents to tumor tissue. CGKRK is one of the well-known tumor targeting peptides with significant specificity for angiogenic blood vessels and tumor cells. Here, we designed fatty acyl conjugated CGKRK peptides, based on the hypothesis that hydrophobically-modified CGKRK peptide could enhance cellular permeation and delivery of siRNA targeted to tumor cells for effective silencing of selected proteins. We synthesized six fatty acyl-peptide conjugates, using a diverse chain of saturated and unsaturated fatty acids to study the efficiency of this approach. At peptide:siRNA weight/weight ratio of 10:1 (N/P ≈ 13.6), almost all the peptides showed complete binding with siRNA, and at a w/w ratio of 20:1 (N/P ≈ 27.3), complete protection of siRNA from early enzymatic degradation was observed. Conjugated peptides and peptide/siRNA complexes did not show significant cytotoxicity in selected cell lines. The oleic acid-conjugated peptide showed the highest efficiency in siRNA uptake and silencing of kinesin spindle protein at peptide:siRNA w/w ratio of 80:1 (N/P ≈ 109). The siRNA internalization into non-tumorigenic kidney cells was negligible with all fatty acyl-peptide conjugates. These results indicate that conjugation of fatty acids to CGKRK could create an efficient delivery system for siRNA silencing specifically in tumor cells.
Anti-tubercular Activity of Pyrazinamide is Independent of trans-Translation and RpsA
Authors: Dillon Nicholas A. , Peterson Nicholas D. , Feaga Heather A. , Keiler Kenneth C. , Baughn Anthony D. 
Published: July 2017

AbstractPyrazinamide (PZA) is a first line anti-tubercular drug for which the mechanism of action remains unresolved. Recently, it was proposed that the active form of PZA, pyrazinoic acid (POA), disrupts the ribosome rescue process of trans-translation in Mycobacterium tuberculosis. This model suggested that POA binds within the carboxy-terminal domain of ribosomal protein S1 (RpsA) and inhibits trans-translation leading to accumulation of stalled ribosomes. Here, we demonstrate that M. tuberculosis RpsA interacts with single stranded RNA, but not with POA. Further, we show that an rpsA polymorphism previously identified in a PZA resistant strain does not confer PZA resistance when reconstructed in a laboratory strain. Finally, by utilizing an in vitro trans-translation assay with purified M. tuberculosis ribosomes we find that an interfering oligonucleotide can inhibit trans-translation, yet POA does not inhibit trans-translation. Based on these findings, we conclude that the action of PZA is entirely independent of RpsA and trans-translation in M. tuberculosis.
Helical Phase Structure of Radiation from an Electron in Circular Motion
Authors: Katoh M. , Fujimoto M. , Mirian N. S. , Konomi T. , Taira Y. , Kaneyasu T. , Hosaka M. , Yamamoto N. , Mochihashi A. , Takashima Y. , Kuroda K. , Miyamoto A. , Miyamoto K. , Sasaki S. 
Published: July 2017

AbstractWe theoretically show that a single free electron in circular motion radiates an electromagnetic wave possessing helical phase structure, which is closely related to orbital angular momentum carried by it. We experimentally demonstrate it by interference and double-slit diffraction experiments on radiation from relativistic electrons in spiral motion. Our results indicate that photons carrying orbital angular momentum should be created naturally by cyclotron/synchrotron radiations or Compton scatterings in various situations in cosmic space. We propose promising laboratory vortex photon sources in various wavelengths ranging from radio wave to gamma-rays.
A novel proton transfer mechanism in the SLC11 family of divalent metal ion transporters
Authors: Pujol-Giménez Jonai , Hediger Matthias A. , Gyimesi Gergely 
Published: July 2017

AbstractIn humans, the H+-coupled Fe2+ transporter DMT1 (SLC11A2) is essential for proper maintenance of iron homeostasis. While X-ray diffraction has recently unveiled the structure of the bacterial homologue ScaDMT as a LeuT-fold transporter, the exact mechanism of H+-cotransport has remained elusive. Here, we used a combination of molecular dynamics simulations, in silico pK
a
calculations and site-directed mutagenesis, followed by rigorous functional analysis, to discover two previously uncharacterized functionally relevant residues in hDMT1 that contribute to H+-coupling. E193 plays a central role in proton binding, thereby affecting transport properties and electrogenicity, while N472 likely coordinates the metal ion, securing an optimally “closed” state of the protein. Our molecular dynamics simulations provide insight into how H+-translocation through E193 is allosterically linked to intracellular gating, establishing a novel transport mechanism distinct from that of other H+-coupled transporters.
Radiation loss of planar surface plasmon polaritons transmission lines at microwave frequencies
Authors: Xu Zhixia , Li Shunli , Yin Xiaoxing , Zhao Hongxin , Liu Leilei 
Published: July 2017

AbstractRadiation loss of a typical spoof surface plasmon polaritons (SSPPs) transmission line (TL) is investigated in this paper. A 325 mm-long SSPPs TL is designed and fabricated. Simulated results show that radiation loss contributes more to transmission loss than dielectric loss and conductor loss from 2 GHz to 10 GHz. Radiation loss of the SSPPs TL could be divided into two parts, one is caused by the input mode converter, and the other is caused by the corrugated metallic strip. This paper explains mechanisms of radiation loss from different parts, designs a loaded SSPPs TL with a series of resistors to absorb electromagnetic energy on corrugated metallic strip, and then discriminates radiation loss from the input mode converter, proposes the concept of average radiation length (ARL) to evaluate radiation loss from SSPPs of finite length, and concludes that radiation loss is mainly caused by corrugated structure of finite length at low frequency band and by the input mode converter at high frequency band. To suppress radiation loss, a mixed slow wave TL based on the combination of coplanar waveguides (CPWs) and SSPPs is presented. The designed structure, sample fabrication and experimental verification are discussed.
PI3K p85α Subunit-deficient Macrophages Protect Mice from Acute Colitis due to the Enhancement of IL-10 Production
Authors: Hayashi Shusaku , Hamada Takayuki , Zinsou Donald G. A. , Oshiro Momoe , Itoi Kana , Yamamoto Takeshi , Kadowaki Makoto 
Published: July 2017

AbstractWe investigated the role of the PI3K p85α subunit in the development of acute colitis with a focus on intestinal macrophages. Experimental acute colitis was induced using 3% dextran sulfate sodium (DSS) in drinking water for 7 days. The severity of DSS-induced acute colitis was significantly attenuated in p85α hetero-deficient (p85α+/−) mice compared with WT mice. The expression of proinflammatory mediators in intestinal macrophages isolated from the inflamed colonic mucosa was significantly suppressed in p85α+/− colitis mice compared with WT colitis mice. Interestingly, we found that bone marrow-derived macrophages (BMDMs) from p85α+/− mice produced a significantly higher amount of IL-10 than BMDMs from WT mice. The adoptive transfer of p85α+/− BMDMs, but not WT BMDMs, significantly improved the severity in WT colitis mice, and this effect was reversed by anti-IL-10 antibody. Furthermore, the expression of IL-10 in the intestinal macrophages of p85α+/− normal colonic mucosa was significantly higher than that in the intestinal macrophages of WT normal colonic mucosa. The present results demonstrate that p85α+/− mice exhibit a reduced susceptibility to DSS-induced acute colitis. Our study suggests that a deficiency of PI3K p85α enhances the production of IL-10 in intestinal macrophages, thereby suppressing the development of DSS-induced acute colitis.
Prognostic role of Glasgow prognostic score in patients with colorectal cancer: evidence from population studies
Authors: Liu Yangyang , He Xingkang , Pan Jie , Chen Shujie , Wang Liangjing 
Published: July 2017

AbstractGlasgow prognostic score (GPS) has been reported to be an indicator of prognosis for various cancers. However, the relationship between GPS and colorectal cancers (CRC) remains unclear. A comprehensive search of Pubmed, Embase, Cochrane library, Web of Science, ChinaInfo and Chinese National Knowledge Infrastructure was performed to identify eligible studies, from which the risk of overall survival (OS) and cancer-specific survival (CSS) were extracted. A random-effect model was adopted to combine hazard ratio (HR) and 95% confidence interval (CI). 25 articles with a total of 5660 participants were included. The pooled results indicated that elevated GPS was associated with poor OS (HR = 2.83, 95%CI: 2.00–4.00, P < 0.01) and CSS (HR = 1.94, 95%CI: 1.51–2.49, P < 0.01). This correlation was confirmed both in primary operable and advanced inoperable patients. Increased GPS was also closely related to advanced tumour-node-metastasis (TNM) stage (odds ratio [OR] = 1.44, 95% CI: 1.010–2.065, P < 0.05) and elevated level of serum carcinoembryonic antigen (OR = 2.252, 95% CI: 1.508–3.362, P < 0.01). Subgroup analysis revealed a significant association between high GPS and poor survival outcome according to the factors of sample size, study of region and cut-off value of GPS level. These findings suggest that GPS may serve as a reliable predictive index for patients with CRC.
C26-Ceramide as highly sensitive biomarker for the diagnosis of Farber Disease
Authors: Cozma Claudia , Iurașcu Marius-Ionuț , Eichler Sabrina , Hovakimyan Marina , Brandau Oliver , Zielke Susanne , Böttcher Tobias , Giese Anne-Katrin , Lukas Jan , Rolfs Arndt 
Published: July 2017

AbstractFarber disease (FD) is a rare autosomal recessive disease caused by mutations in the acid ceramidase gene (ASAH1). Low ceramidase activity results in the accumulation of fatty substances, mainly ceramides. Hallmark symptoms at clinical level are periarticular nodules, lipogranulomas, swollen and painful joints and a hoarse voice. FD phenotypes are heterogeneous varying from mild to very severe cases, with the patients not surviving past their first year of life. The diagnostic aspects of FD are poorly developed due to the rarity of the disease. In the present study, the screening for ceramides and related molecules was performed in Farber affected patients (n = 10), carriers (n = 11) and control individuals (n = 192). This study has the highest number of enrolled Farber patients and carriers reported to present. Liquid chromatography multiple reaction mass spectrometry (LC/MRM-MS) studies revealed that the ceramide C26:0 and especially its isoform 1 is a highly sensitive and specific biomarker for FD (p < 0.0001). The new biomarker can be determined directly in the dried blood spot extracts with low sample consumption. This allows for easy sample preparation, high reproducibility and use in high throughput screenings.
Critical behavior of the van der Waals bonded high T

C
ferromagnet Fe3GeTe2
Authors: Liu Bingjie , Zou Youming , Zhou Shiming , Zhang Lei , Wang Zhe , Li Hexuan , Qu Zhe , Zhang Yuheng 
Published: July 2017

AbstractFe3GeTe2 is a promising candidate for van der Waals bonded ferromagnet because of its high Curie temperature and the prediction that its ferromagnetism can maintain upon exfoliating down to single layer. Here, we have reported the critical behavior to understand its ferromagnetic exchange. Based on various techniques including modified Arrott plot, Kouvel-Fisher plot, and critical isotherm analysis, a set of reliable critical exponents (β = 0.327 ± 0.003, γ = 1.079 ± 0.005, and δ = 4.261 ± 0.009) has been obtained. The critical behavior suggests a three-dimensional long-range magnetic coupling with the exchange distance decaying as J(r) ≈ r−4.6 in Fe3GeTe2. The possible origin of three-dimensional magnetic characteristics in van der Waals bonded magnets is discussed.
Trainees’ Knowledge, Attitudes, and Practices Towards Caring for the Substance-Exposed Mother-Infant Dyad
Authors: Schiff Davida M. , Zuckerman Barry , Wachman Elisha M. , Bair-Merritt Megan 
Published: July 2017

Background As rates of substance use disorder during pregnancy rise, pediatric trainees are increasingly caring for infants with neonatal abstinence syndrome (NAS). This study evaluated the knowledge, attitudes, and practices of trainees caring for substance-exposed newborns and their families, comparing differences by level and type of training, and personal experience with addiction or trauma. Methods A cross-sectional survey of medical students and pediatric, medicine/pediatric, and family medicine residents in 2015–2106. Measures included knowledge about NAS, attitudes towards mothers who use drugs, and practices around discussing addiction and trauma with families. Descriptive and bivariate analyses were conducted. Results The overall response rate was 70%, with 229 trainees included in the final sample (99 students, 130 residents). Fifty percent of trainees endorsed personal experience with addiction, 50% with trauma, and 35% with both addiction and trauma. Increasing years of pediatric training was associated with greater comfort in managing symptoms of NAS but decreased comfort discussing addiction and trauma. Family medicine and medicine/pediatric residents were more comfortable discussing addiction and trauma than categorical pediatric residents ( P < .01). Twenty-two percent of trainees felt confident that mothers would disclose illicit drug use, 39% felt that they would actively care for their infants with NAS, and 43% felt that mothers would not make unreasonable demands. Personal experience with addiction or trauma did not significantly impact trainees’ attitudes towards women with substance use disorder. Conclusions Trainees may benefit from educational interventions focused on developing a 2-generational model of trauma-informed care to improve attitudes and ultimately the care of substance-exposed infants and their families.
Analytical Solution for Peristaltic Transport of Viscous Nanofluid in an Asymmetric Channel with Full Slip and Convective Conditions
Authors: Ebaid Abdelhalim , Aly Emad H. , Vajravelu K. 
Published: July 2017

AbstractThe peristaltic flow of nanofluids is a relatively new area of research. Scientists are of the opinion that the no-slip conditions at the boundaries are no longer valid and consequently, the first and the second order slip conditions should be addressed. In this paper, the effects of slip conditions and the convective boundary conditions at the boundary walls on the peristaltic flow of a viscous nanofluid are investigated for. Also, the exact analytical solutions are obtained for the model. The obtained results are presented through graphs and discussed. The results reveal that the two slip parameters have strong effects on the temperature and the nanoparticles volume fraction profiles. Moreover, it has been seen that the temperature and nanoparticles volume fraction profiles attain certain values when the first slip condition exceeds a specified value. However, no limit value for the second slip parameter has been detected. Further, the effects of the various emerging parameters on the flow and heat transfer characteristics have been presented.
Costs and Benefits of Land Fragmentation: Evidence from Rwanda
Authors: Ali Daniel Ayalew , Deininger Klaus , Ronchi Loraine 
Published: July 2017

Abstract
Panel data from Rwanda allow us to explore costs and benefits from land fragmentation in a non-mechanized setting using two methodological improvements, namely (i) a terrain-adjusted measure of travel time/cost required to visit all parcels to measure fragmentation; and (ii) instrumental variable (IV) approaches that use measures for inherited/allocated parcels and past displacement as instruments. Results suggest that fragmentation as measured by travel cost negatively affect yield, intensity of labor use, and technical efficiency while reducing yield variability. With some 7 percent increase in yields, the size of the estimated impact of potential consolidation remains modest, suggesting that in an unmechanized setting such as the one studied here, the costs of programs to reduce fragmentation may outweigh the benefits.
Complexity-Entropy maps as a tool for the characterization of the clinical electrophysiological evolution of patients under pharmacological treatmentwith psychotropic drugs
Authors: Diaz J. M. , Mateos D. M. , Boyallian C. 
Published: July 2017

AbstractIn the clinical electrophisiologic practice, the reading and comparing electroencephalographic (EEG) recordings some times is insufficient and take to much time. That is why in the last years it has begun to introduce new methods of EEG analysis, that give a better and faster understanding of the EEG dynamics and allow a rapid intervention in the patient’s treatment. Tools coming from the information theory or nonlinear system as an entropy and complexity have been shown to be a very good alternative to address this problem. In this work we introduce a novel method -the permutation Lempel-ziv complexity vs permutation entropy map. This method was applied to EEG of two patients with specific diagnosed pathologies during respective follow up processes of pharmacological changes in order to detect changes that are not evident with the usual inspection method. Our results show that the proposed method are useful for observing an evolutionary retrospective clinical effects of pharmacological interventions in both patients, and from these, to follow the clinical response to the proposed treatment.