bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhanced transport of plant‐produced rabies single‐chain antibody‐RVG peptide fusion protein across an in cellulo blood–brain barrier device
Authors: Phoolcharoen Waranyoo , Prehaud Christophe , van Dolleweerd Craig J. , Both Leonard , da Costa Anaelle , Lafon Monique , Ma Julian K‐C. 
Published: March 2017

SummaryThe biomedical applications of antibody engineering are developing rapidly and have been expanded to plant expression platforms. In this study, we have generated a novel antibody molecule in planta for targeted delivery across the blood–brain barrier (BBB). Rabies virus (RABV) is a neurotropic virus for which there is no effective treatment after entry into the central nervous system. This study investigated the use of a RABV glycoprotein peptide sequence to assist delivery of a rabies neutralizing single‐chain antibody (ScFv) across an in cellulo model of human BBB. The 29 amino acid rabies virus peptide (RVG) recognizes the nicotinic acetylcholine receptor (nAchR) at neuromuscular junctions and the BBB. ScFv and ScFv‐RVG fusion proteins were produced in Nicotiana benthamiana by transient expression. Both molecules were successfully expressed and purified, but the ScFv expression level was significantly higher than that of ScFv‐RVG fusion. Both ScFv and ScFv‐RVG fusion molecules had potent neutralization activity against RABVin cellulo. The ScFv‐RVG fusion demonstrated increased binding to nAchR and entry into neuronal cells, compared to ScFv alone. Additionally, a human brain endothelial cell line BBB model was used to demonstrate that plant‐produced ScFv‐RVGP fusion could translocate across the cells. This study indicates that the plant‐produced ScFv‐RVGP fusion protein was able to cross the in celluloBBB and neutralize RABV.
Pheomelanogenesis is promoted at a weakly acidic pH
Authors: Wakamatsu Kazumasa , Nagao Ayano , Watanabe Miu , Nakao Kenta , Ito Shosuke 
Published: March 2017

SummaryThe diversity of pigmentation in the skin, hair, and eyes of humans has been largely attributed to the diversity of pH in melanosomes with an acidic pH being proposed to suppress melanin production, especially eumelanogenesis. We previously showed that an acidic pH greatly suppresses the late stage of eumelanogenesis after the dopachrome stage. The oxidation of tyrosine by tyrosinase in the presence of cysteine forms cysteinyldopa isomers, which are further oxidized to give rise to pheomelanin via benzothiazine intermediates. However, how those steps are controlled by pH has not been characterized. We therefore examined whether pheomelanin synthesis is chemically promoted at an acidic pH. We found that pheomelanin production either from dopa or tyrosine in the presence of cysteine by tyrosinase was greatest at pH values of 5.8–6.3, while eumelanin production was suppressed at pH 5.8. This suggests that mixed melanogenesis is chemically shifted to more pheomelanic states at a weakly acidic pH.
Sectoral determinants of foreign affiliate sales employing European data
Authors: Bekkers Eddy , Macskasi Indre 
Published: March 2017

AbstractWe test theories on sectoral determinants of foreign affiliate sales employing European foreign affiliate sales statistics (FATS). On the one hand, we test hypotheses that foreign affiliate sales are less likely in sectors with complex tasks and more likely in sectors where communication with customers is important. On the other hand, we test the hypothesis that the force of gravity is stronger in more complex sectors. Employing Poisson and negative binomial estimators, we find support for the first hypotheses and contradict the second hypothesis. We show that the interaction effect between distance and complexity changes sign from negative to positive when complexity is included as a separate regressor. We propose an explanation to reconcile our findings with the basic assertion in the second hypothesis that the force of gravity is stronger in more complex sectors, based on a composition effect between horizontal and vertical affiliate sales.
Siglec‐9 is upregulated in rheumatoid arthritis and suppresses collagen‐induced arthritis through reciprocal regulation of Th17‐/Treg‐cell differentiation
Authors: Wang X. , Liu D. , Ning Y. , Liu J. , Wang X. , Tu R. , Shen H. , Chen Q. , Xiong Y. 
Published: March 2017

AbstractSialic acid‐binding Ig‐like lectin‐9 (Siglec‐9) is a novel sialic acid‐binding member of the immunoglobulin superfamily and is broadly expressed on immune cells, which can inhibit both innate and adaptive immune responses through immunoreceptor tyrosine‐based inhibitory motifs. However, the exact role of Siglec‐9 in the pathogenesis of rheumatoid arthritis (RA) remains unknown. In this study, we determined soluble Siglec‐9 (sSiglec‐9) levels in the serum and synovial fluid of patients with RA and evaluated the relation between sSiglec‐9 levels and clinical factors. In addition, we investigated whether Siglec‐9 could alleviate collagen‐induced arthritis (CIA) development in mice and explored the molecular mechanisms involved. The results showed that, in the serum and synovial fluid of patients with RA, sSiglec‐9 levels were elevated. Thus, high sSiglec‐9 serum levels associated with disease severity in patients with RA. Furthermore, administration of recombinant human Siglec‐9 Fc chimera protein significantly attenuated collagen‐induced arthritis development in vivo and in vitro by reciprocal regulation of the differentiation of Th17 and Treg cells. Our findings collectively indicate that Siglec‐9 plays a potent immunosuppressive role in the pathogenesis of RA by reciprocal regulation of Th17‐/Treg‐cell differentiation. In conclusion, Siglec‐9 may serve as a potential diagnostic and therapeutic target for RA.
Computational Prediction of Usutu Virus E Protein B Cell and T Cell Epitopes for Potential Vaccine Development
Authors: Palanisamy N. , Lennerstrand J. 
Published: March 2017

AbstractUsutu virus (family Flaviviridae), once confined to Africa, has emerged in Europe a decade ago. The virus has been spreading throughout Europe at a greater pace mostly affecting avian species. While most bird species remain asymptomatic carriers of this virus, few bird species are highly susceptible. Lately, Usutu virus (USUV) infections in humans were reported sporadically with severe neuroinvasive symptoms like meningoencephalitis. As so much is unknown about this virus, which potentially may cause severe diseases in humans, there is a need for more studies of this virus. In this study, we have used computational tools to predict potential B cell and T cell epitopes of USUV envelope (E) protein. We found that amino acids between positions 68 and 84 could be a potential B cell epitope, while amino acids between positions 53 and 69 could be a potential major histocompatibility complex (MHC) class I‐ and class II‐restricted T cell epitope. By homology 3D modeling of USUV E protein, we found that the predicted B cell epitope was predominantly located in the coil region, while T cell epitope was located in the beta‐strand region of the E protein. Additionally, the potential MHC class I T cell epitope (LAEVRSYCYL) was predicted to bind to nearly 24 human leucocyte antigens (HLAs) (IC50 ≤5000 nm) covering nearly 86.44% of the Black population and 96.90% of the Caucasoid population. Further in vivo studies are needed to validate the predicted epitopes.
PTEN/PI3k/AKT Regulates Macrophage Polarization in Emphysematous mice
Authors: Lu J. , Xie L. , Liu C. , Zhang Q. , Sun S. 
Published: March 2017

AbstractMacrophages play an important role in the pathogenesis of COPD. Macrophage polarization towards the M2 phenotype has been observed in the lung tissues of COPD patients and cigarette smokers. The molecular basis of this process remains unclear, and it has not been completely illuminated in animal models of emphysema. In our study, we combined cigarette smoke (CS) exposure with intraperitoneal injection of cigarette smoke extract (CSE) to build an emphysema model. We found by immunohistochemical staining and flow cytometry that the expression level of CD206 and the ratio of M2 to M1 macrophages was increased in emphysematous mice. We also demonstrated that decreased protein level for phosphatase and tensin homology deleted on chromosome ten (PTEN) and increased total protein levels for phosphorylation ‐protein kinase B (p‐AKT) in the lung tissue of emphysematous mice and in CSE‐treated RAW264.7 cells. In both bone marrow‐derived macrophages (BMDMs) from emphysematous mice and CSE‐treated RAW264.7 cells, we observed by RT‐PCR that the mRNA levels of M2 macrophage‐related markers and cytokines were increased. Furthermore, M1 macrophage‐related markers and cytokines were decreased. Meanwhile we treated BMDMs from emphysematous mice and CSE‐treated RAW264.7 cells with the phosphoinositide 3‐kinase (PI3K)/Akt inhibitor (LY294002), we observed a reduction in RNA levels of M2 macrophage‐related markers and cytokines. In conclusion, we confirmed that macrophage M2 polarization was induced in emphysematous mice generated by CS exposure combined with intraperitoneal injection of CSE. We also showed that M2 polarization was mediated through PTEN/PI3k/AKT pathway activation.
Weed growth and crop yield responses to tillage and mulching under different crop rotation sequences in semi‐arid conditions
Authors: Mashingaidze N. , Twomlow S. , Madakadze I.C. , Mupangwa W. , Mavunganidze Z. 
Published: March 2017

AbstractConservation agriculture (CA) is thought to reduce weed pressure from the third year of adoption, when recommended practices are followed. Weed growth and crop yield were assessed during the third and fourth year of maize–cowpea–sorghum rotation, second and third year of maize–cowpea rotation and first and second year of maize monocropping on a clay loam soil at Matopos Research Station (annual rainfall, 573 mm) following recommended CA management practices. Each experiment had a split‐plot randomized complete block design with mouldboard plough (CONV), minimum tillage (MT) with ripper tine and planting basins as main‐plot factor and maize residue mulch rate (0, 2 and 4 t/ha) as a subplot factor, with threefold replication. All subplots were surface mulched and weeded by hoe at the same time. We hypothesized that under MT weed growth would be considerable with maize monocropping but from year 3 of CA, weed growth would decrease and crop yield increase relative to values from unmulched CONV. Minimum tillage increased weed growth in 2nd year of maize monocropping. Under the maize–cowpea rotation, the considerable weed growth in planting basins was likely due to the large intrarow spacing and poor light competiveness of the cowpea variety. Mulch contributed to weed growth being suppressed by up to 36% under CA in the maize–cowpea–sorghum rotation relative to unmulched CONV. When planted on the same date, crop yield did not differ between CA and unmulched CONV. Maize–cowpea–sorghum rotation grain yield (3143 kg/ha) was double that under monocropping, probably due to improvements in soil physical and chemical conditions.
Purpureocillium lilacinum tattoo‐related skin infection in a kidney transplant recipient
Authors: Trinh Sonya A. , Angarone Michael P. 
Published: March 2017

AbstractPurpureocillium lilacinum is an emerging pathogenic mold among immunocompromised hosts that causes cutaneous infections related to skin breakdown. We present the first reported case of P. lilacinum tattoo‐related skin infection, to our knowledge. A kidney transplant recipient recently treated for acute cellular rejection presented with skin papules overlying a tattoo. Diagnosis was confirmed on culture, histology, and 18S ribosomal RNA polymerase chain reaction. The morphological features on culture characteristic of P. lilacinum included violet colonies on malt extract agar, long tapering brush‐like phialides, and elliptical conidia attached in chains. P. lilacinum has intrinsic resistance to many antifungal agents including amphotericin B, but voriconazole and posaconazole have good in vitro activity. The patient was treated with voriconazole with subsequent resolution of the papules after 3 months of therapy.
The Association Between Spanish Physical Education Teachers’ Self-Efficacy Expectations and Their Attitudes Toward Overweight and Obese Students
Authors: Martínez-López Emilio J. , Zamora-Aguilera Nestor , Grao-Cruces Alberto , De la Torre-Cruz Manuel J. 
Published: March 2017

Purpose:The aim of this study was to investigate the association between Spanish physical education teachers’ perceived self-efficacy toward including overweight and obese students and their attitudes toward overweight and obese students.Method:Four hundred and seventy-one physical education teachers filled out questionnaires to assess their self-efficacy expectations to meet overweight and obese students’ educational needs, and to identify physical education teachers’ beliefs and attitudes toward these students.Results:The physical education teachers with a higher perceived self-efficacy in fostering participation and in assessing and promoting overweight and obese students’ learning were more sensitive toward these students’ fitness and healthcare and showed less pejorative attitudes toward overweight and obesity.Conclusions:These results highlight the need for teaching education programs capable of increasing the physical education teachers’ perceived self-efficacy in this area. The results also show that there is a need for training for teachers and students in strategies aimed at reducing the cases of victimization of overweight and obese students.
Robin’s Story: Life History of an Exemplary American Female Physical Education Teacher
Authors: Cazers Gunars , Curtner-Smith Matthew D. 
Published: March 2017

Purpose:The purpose was to construct the life history of Robin, an exemplary female physical educator, to hear her voice, and to explore ways in which she experienced marginalization. Few life histories of exemplary physical educators have been recounted.Method:Robin’s life history was investigated in light of the theory of occupational socialization (Lawson, 1983 a, b). Three semistructured interviews were conducted, and data were analyzed deductively according to categories in the occupational socialization literature.Results:The study found that Robin experienced marginalization based on gender, lack of support, and being unaccepted. Occupational socialization explained how Robin’s induction into teaching helped her both teach as she had been trained and to be innovative.Discussion/Conclusion:The study suggests ways in which Robin persevered in her career and gives suggestions based upon her story. The sharing of this story may serve to empower other teachers not just to survive, but to challenge the status quo in their professional life.
Extracurricular School-Based Sports as a Stepping Stone Toward an Active Lifestyle? Differences in Physical Activity and Sports-Motivation Between Extracurricular School-Based Sports Participants and Non-Participants
Authors: De Meester An , Cardon Greet , De Bourdeaudhuij Ilse , Haerens Leen 
Published: March 2017

Purpose:The goals were to investigate whether extracurricular school-based sports reach students not engaging in community sports and whether extracurricular school-based sports participants are more physically active and/or autonomously motivated toward sports than nonparticipants.Method:1526 students (48.0% boys; 85.9% Belgian natives; age = 15.34 ± 1.83y) completed validated questionnaires to assess sports participation, physical activity (PA) and sports-motivation. Multilevel regression analyses were conducted.Results:Only 28.7% of all students (n = 438), and 19.7% of students not engaging in community sports (n = 123), participated in extracurricular school-based sports. Participants were significantly more physically active [β=44.19, S.E.=17.34, χ2(1)=6.50, p = .01] and autonomously motivated [β=.18, S.E.=.04, χ2(1)=25.62, p < .001] than nonparticipants, even after controlling for community sports participation. Boys were more physically active and autonomously motivated than girls (p < .001).Conclusion:As participation is linked to higher PA-levels and autonomous motivation, increasing overall participation rates may contribute to children developing a more physically active lifestyle and achieving the PA guidelines.
To Move More and Sit Less: Does Physical Activity/Fitness Knowledge Matter in Youth?
Authors: Chen Senlin , Liu Yang , Schaben Jodee 
Published: March 2017

Purpose:The purpose of this study was to examine physical activity (PA)/fitness knowledge and its association with PA and sedentary behavior in youth.Method:Eighth grade students from five schools (N = 660) in a midwestern state completed a PE Metrics written test and the Youth Activity Profile to assess PA/fitness knowledge, PA (at school and after school) and sedentary behavior, respectively.Results:Participants were clustered into high, medium, and low knowledge groups. Students in the high knowledge group reported higher level of PA after school (p < .05, d = .28) but lower level of sedentary behavior than the low knowledge group (p = .001, d = -.45). The low knowledge group also reported higher PA at school (p < .05, d = .25). PA/Fitness knowledge significantly predicted sedentary behavior, particularly in the low knowledge group (β = -.32, t = -2.46, p < .05, R2 = .105), after controlling for gender and race/ethnicity.Conclusion:Physical education focused on conveying PA/fitness knowledge is warranted to educate youth to move more and sit less.
Human Cytomegalovirus MicroRNAs miR-US5-1 and miR-UL112-3p Block Proinflammatory Cytokine Production in Response to NF-κB-Activating Factors through Direct Downregulation of IKKα and IKKβ
Authors: Hancock Meaghan H. , Hook Lauren M. , Mitchell Jennifer , Nelson Jay A. 
Published: March 2017

ABSTRACTEmerging evidence indicates that human cytomegalovirus (HCMV) manipulates host cell signaling pathways using both proteins and noncoding RNAs. Several studies have shown that HCMV induces NF-κB signaling early in infection, resulting in the induction of antiviral proinflammatory cytokines with a subsequent reduction of these cytokines late in infection. The mechanism for late cytokine reduction is unknown. In this study, we show that HCMV microRNAs (miRNAs) miR-US5-1 and miR-UL112-3p target the IκB kinase (IKK) complex components IKKα and IKKβ to limit production of proinflammatory cytokines in response to interleukin 1β (IL-1β) and tumor necrosis factor alpha (TNF-α). Transfection of miR-UL112-3p and miR-US5-1 mimics reduced endogenous IKKα and IKKβ protein levels, and site-directed mutagenesis of the 3′ untranslated regions (UTRs) identified the binding sites for each miRNA. Infection with mutant viruses lacking these miRNAs resulted in increased levels of IKKα and IKKβ proteins, an impaired ability to control NF-κB signaling at late times of lytic infection, and increased production of proinflammatory cytokines compared to wild-type virus in cell types relevant to HCMV infectionin vivo. These phenotypes were rescued by preexpression of miR-US5-1 and miR-UL112-3p in infected cells or by a miR-US5-1/miR-UL112-3p double mutant virus that expresses short hairpin RNAs (shRNAs) targeting IKKα and IKKβ, demonstrating the gene specificity of the miRNAs. These observations describe a mechanism through which HCMV miRNAs expressed late in the infectious cycle downregulate proinflammatory cytokine production to create a cellular proviral environment.IMPORTANCEHuman cytomegalovirus (HCMV) is a significant cause of morbidity and mortality in transplant recipients and causes hearing loss and mental retardation when acquired congenitally. Initial events during HCMV infection result in the activation of NF-κB signaling, which culminates in the production of IL-6, CCL5, and TNF-α. Several viruses have developed mechanisms to block the antiviral effects of these cytokines. We show here that two HCMV miRNAs, miR-US5-1 and miR-UL112-3p, specifically downregulate IKKα and IKKβ signaling factors necessary to propagate NF-κB signaling and subsequent IL-6, CCL5, and TNF-α production. Regulation of these proinflammatory cytokines during lytic infection and during latency is critical to viral survival in the host.
Microevolution of Serial Clinical Isolates ofCryptococcus neoformansvar.grubiiandC. gattii
Authors: Chen Yuan , Farrer Rhys A. , Giamberardino Charles , Sakthikumar Sharadha , Jones Alexander , Yang Timothy , Tenor Jennifer L. , Wagih Omar , Van Wyk Marelize , Govender Nelesh P. , Mitchell Thomas G. , Litvintseva Anastasia P. , Cuomo Christina A. , Perfect John R. 
Published: March 2017

ABSTRACTThe pathogenic species ofCryptococcusare a major cause of mortality owing to severe infections in immunocompromised as well as immunocompetent individuals. Although antifungal treatment is usually effective, many patients relapse after treatment, and in such cases, comparative analyses of the genomes of incident and relapse isolates may reveal evidence of determinative, microevolutionary changes within the host. Here, we analyzed serial isolates cultured from cerebrospinal fluid specimens of 18 South African patients with recurrent cryptococcal meningitis. The time between collection of the incident isolates and collection of the relapse isolates ranged from 124 days to 290 days, and the analyses revealed that, during this period within the patients, the isolates underwent several genetic and phenotypic changes. Considering the vast genetic diversity of cryptococcal isolates in sub-Saharan Africa, it was not surprising to find that the relapse isolates had acquired different genetic and correlative phenotypic changes. They exhibited various mechanisms for enhancing virulence, such as growth at 39°C, adaptation to stress, and capsule production; a remarkable amplification ofERG11at the native and unlinked locus may provide stable resistance to fluconazole. Our data provide a deeper understanding of the microevolution ofCryptococcusspecies under pressure from antifungal chemotherapy and host immune responses. This investigation clearly suggests a promising strategy to identify novel targets for improved diagnosis, therapy, and prognosis.IMPORTANCEOpportunistic infections caused by species of the pathogenic yeastCryptococcuslead to chronic meningoencephalitis and continue to ravage thousands of patients with HIV/AIDS. Despite receiving antifungal treatment, over 10% of patients develop recurrent disease. In this study, we collected isolates ofCryptococcusfrom cerebrospinal fluid specimens of 18 patients at the time of their diagnosis and when they relapsed several months later. We then sequenced and compared the genomic DNAs of each pair of initial and relapse isolates. We also tested the isolates for several key properties related to cryptococcal virulence as well as for their susceptibility to the antifungal drug fluconazole. These analyses revealed that the relapsing isolates manifested multiple genetic and chromosomal changes that affected a variety of genes implicated in the pathogenicity ofCryptococcusor resistance to fluconazole. This application of comparative genomics to serial clinical isolates provides a blueprint for identifying the mechanisms whereby pathogenic microbes adapt within patients to prolong disease.