bluuebunny/crossref_metadata_2025_split huggingface dataset:
LMP2 immunoproteasome promotes lymphocyte survival by degrading apoptotic BH3‐only proteins
Authors: Zanker Damien , Pang Kenneth , Oveissi Sara , Lu Chunni , Faou Pierre , Nowell Cameron , Mbogo George W , Carotta Sebastian , Quillici Cathy , Karupiah Guna , Hibbs Margaret L. , Nutt Stephen L , Neeson Paul , Puthalakath Hamsa , Chen Weisan 
Published: May 2018

AbstractThe role of the immunoproteasome is perceived as confined to adaptive immune responses given its ability to produce peptides ideal for MHC Class‐I binding. Here, we demonstrate that the immunoproteasome subunit, LMP2, has functions beyond its immunomodulatory role. Using LMP2‐deficient mice, we demonstrate that LMP2 is crucial for lymphocyte development and survival in the periphery. Moreover, LMP2‐deficient lymphocytes show impaired degradation of key BH3‐only proteins, resulting in elevated levels of pro‐apoptotic BIM and increased cell death. Interestingly, LMP2 is the sole immunoproteasome subunit required for BIM degradation. Together, our results suggest LMP2 has important housekeeping functions and represents a viable therapeutic target for cancer.
What Triggers the Intention to Use the European Citizens’ Initiative? The Role of Benefits, Values and Efficacy
Authors: Kandyla Anna , Gherghina Sergiu 
Published: May 2018

AbstractThe European Citizens’ Initiative (ECI) is a European Union instrument that aspires to encourage citizens to participate in EU policy‐making. Although scholarly interest in the ECI is strong, only isolated studies have examined the factors that shape the intention to use it. This article fills a gap in the literature by examining how personal benefits from the EU, value‐based assessments of the EU, and political efficacy (internal and external) may trigger potential use of the ECI. It develops a model that is tested with recent Eurobarometer data. Results show that personal benefits from the EU are key determinants of the intention to use the ECI while considerations based on democratic values play a less important role. In addition, internal political efficacy emerges as a strong predictor of potential use. The results challenge the expectation that the ECI could broaden public engagement with EU affairs.
Keratin 4 regulates the development of human white sponge nevus
Authors: Zhang Jianming , Quan Jingjing , Ren Yongyuan , Chen Mengshan , Yang Jie , Zhang Xu 
Published: May 2018

BackgroundThe aim of this study was to investigate the roles of keratin 4 (KRT4) gene in the development of human white sponge nevus (WSN).MethodsTransgenic mice were created using the microinjection method with pcDNA3.1 vectors expressing KRT4 wild‐type (WT) gene and E520K mutation. Polymerase chain reaction (PCR) and Western blotting were used to identify the genotype of transgenic founders and their filial generations. Expression of KRT4 in mouse oral mucosa was characterized by immunohistochemistry (IHC), and the whole epithelium layer of transgenic mice was observed using transmission electron microscope (TEM).ResultsThe positive rate of KRT4 transgenic mice in F1 generation was 45.5%. Expression level of KRT4 protein was significantly higher in 2‐month‐old transgenic mice than WT mice. Furthermore, all the epithelial lamina of 3‐month‐old transgenic mice showed reduced staining of KRT4. The surface and spinous layers were full of hyalocytes and bubble cells, which are similar to the clinical symptoms of WSN. For the ultrastructure, both tonofilaments and Odland bodies increased.ConclusionsOur study indicated the mutated KRT4 gene may play important roles in the pathogenesis of WSN.
Exploration of gender differences in bottled mineral water consumption: A projective study of consumer's perception in Brazil
Authors: Pacheco Marcelo H. S. , Kuriya Shigeno P. , Capobiango Carla S. C. , Pimentel Tatiana Colombo , Cruz Adriano Gomes , Esmerino Erick A. , Freitas Mônica Q. 
Published: May 2018

AbstractThe bottled mineral water sector is strategic to countries like Brazil and understanding the factors that guides the purchase and consumption by men and women becomes vital to the product's commercial success. In this context, projective techniques are important tools to comprehend the consumers' perception and to the development of target strategies of marketing. Therefore, the objective of this study was to investigate the gender differences about the bottled mineral water's perception through using Word Association (WA) alongside with the Partial Least Squares—Discriminant Analysis (PLS‐DA). The results demonstrated that from the 12 listed categories for the product, the most common were: “necessity,” “well‐being,” “quality,” and “appearance,” and it was possible to identify through PLS‐DA the main differences (p < .05) between genders. The bottled mineral water consumption by the female public is possibly directed to necessity and well‐being, despite practicality, while the male public made the purchase and consumption of the product associated to brand and informal places. Yet, it was realized that the product's presentation and quality parameter were highly impactful in the consumers' attitudes from both sexes. It is highlighted that the WA and PLS‐DA tools, used together in an innovative way, contribute to the deep acknowledgment about the bottled mineral water's consumption, and their application can be expanded and adopted routinely in marketing research and in the new marketing strategies.Practical applicationsThis study brings relevant information about the factors which should be considered by consumers at the moment of purchase and consumption of bottled water, emphasizing the differences by gender, with the advantage of the results being obtained using simple sensory methodologies, as the Word association task which taken in account the consumers' perception and evaluated for multivariate approaches, as Partial Least Squares—Discrimination Analysis. These findings should be considered to bottled water industry to elaborate marketing messages to increase their sales in an effective way.
Public goods and public bads
Authors: Buchholz Wolfgang , Cornes Richard , Rübbelke Dirk 
Published: May 2018

AbstractIn many empirically relevant situations agents in different groups are affected by the provision of a public characteristic in divergent ways. Whereas for one group it represents a public good, it is a public bad for another group. Applying Cornes and Hartley's aggregative game approach, we analyze a general model in which such contentious public characteristics are present and are provided cooperatively. In particular, we establish neutrality results with respect to redistribution and growth of income, infer the effects of preference changes and coalition formation, and present a technology paradox. Finally, we compare the outcome of voluntary provision of the contentious public characteristic with the Pareto‐optimal solution, highlighting a potential conflict between equity and efficiency in this case.
Delayed asymptomatic progressive intraventricular pneumocephalus in a dog following craniotomy
Authors: Hicks J. , Stewart G. , Kent M. , Platt S. 
Published: May 2018

Delayed pneumocephalus developed in a 9‐year‐old dog following transfrontal craniotomy and implantation of an experimental local chemotherapy into a partially resected oligodendroglioma, but the animal appeared to be asymptomatic. MRI evidence of increasing intracranial pressure, including progressive ventricular dilatation and compression of periventricular parenchyma, led to the recommendation for exploratory craniotomy. The barrier between the intracranial cavity and frontal sinus was enhanced, and pneumocephalus resolved on MRI at both 1 and 3 months following the repair.
Risk of hepatitis B virus reactivation with direct‐acting antivirals against hepatitis C virus: A cohort study from Egypt and meta‐analysis of published data
Authors: El Kassas Mohamed , Shimakawa Yusuke , Ali‐Eldin Zainab , Funk Anna‐Louise , Wifi Mohamed Naguib , Zaky Samy , El‐Raey Fathiya , Esmat Gamal , Fontanet Arnaud 
Published: May 2018

AbstractBackground & AimsHepatitis B virus (HBV) reactivation in chronic hepatitis C (CHC) patients treated with direct‐acting antivirals (DAAs) became an issue. However, its frequency has been poorly estimated, because of the varying definitions used and evaluation of heterogeneous study populations, including those concurrently treated for HBV.MethodsWe prospectively followed HBV surface antigen (HBsAg)‐positive Egyptians undergoing interferon‐free DAAs, to estimate the risk of HBV reactivation and HBV‐related hepatitis. We also conducted a meta‐analysis to estimate the reactivation risk using published data obtained from a systematic review of PubMed/Embase, in addition to our Egyptian data. We applied a standard definition of HBV reactivation proposed by the international liver associations (APASL and AASLD).ResultsOf 4471 CHC patients, 35 HBsAg‐positive patients started interferon‐free DAAs without HBV nucleos(t)ide analogues in our Egyptian cohort. Ten experienced HBV reactivation (28.6%), of whom 1 developed hepatitis (10.0%). Our systematic review identified 18 papers. The pooled reactivation risk in HBsAg‐positive patients was 18.2% (95% CI: 7.9%‐30.7%) without HBV therapy and 0.0% (95% CI: 0.0%‐0.0%) with HBV nucleos(t)ide analogue. The pooled risk of hepatitis in those with HBV reactivation was 12.6% (95% CI: 0.0%‐34.7%). The pooled reactivation risk in HBsAg‐negative, antibody to HBV core antigen‐positive (anti‐HBc‐positive) patients was negligible (0.1%, 95% CI: 0.0%‐0.3%), irrespective of the presence of antibody to HBsAg (anti‐HBs).ConclusionsWe confirmed high HBV reactivation risk in HBsAg‐positive patients undergoing DAAs, with only a minority developing clinically important hepatitis. The risk is negligible for HBsAg‐negative anti‐HBc‐positive patients.
Toxoplasma gondii TFP1 is an essential transporter family protein critical for microneme maturation and exocytosis
Authors: Hammoudi Pierre‐Mehdi , Maco Bohumil , Dogga Sunil Kumar , Frénal Karine , Soldati‐Favre Dominique 
Published: May 2018

SummaryInvasion and egress are two key steps in the lytic cycle of Apicomplexa that are governed by the sequential discharge of proteins from two apical secretory organelles called micronemes and rhoptries. In Toxoplasma gondii, the biogenesis of these specialized organelles depends on the post Golgi trafficking machinery, forming an endosomal‐like compartment (ELC) resembling endomembrane systems found in eukaryotes. In this study, we have characterized four phylogenetically related Transporter Facilitator Proteins (TFPs) conserved among the apicomplexans. TFP1 localises to the micronemes and ELC, TFP2 and TFP3 to the rhoptries and TFP4 to the Golgi. TFP1 crucially contributes to parasite fitness and survival while the other members of this family are dispensable. Conditional depletion of TFP1 impairs microneme biogenesis and leads to a complete block in exocytosis, which hampers gliding motility, attachment, invasion and egress. Morphological investigations revealed that TFP1 participates in the condensation of the microneme content, suggesting the transport of a relevant molecule for maintaining the intraluminal microenvironment necessary for organelle maturation and exocytosis. In absence of TFP2, rhoptries adopt a considerable elongated shape, but the abundance, processing or secretion of the rhoptry content are not affected. These findings establish the relevance of TFPs in organelle maturation of T. gondii.
Early‐life dietary and epigenetic influences on childhood musculoskeletal health: Update on the UK component of the ALPHABET project
Authors: Curtis E. M. , Suderman M. , Phillips C. M. , Relton C. , Harvey N. C. 
Published: May 2018

AbstractThe ALPHABET project, funded through the European Research Area Healthy Diet for a Healthy Life Biomarkers call, aims to expand the knowledge base regarding interactions between diet, epigenetics and offspring health, characterising biomarkers that may inform future health strategies. This review focuses on the UK Biotechnology and Biological Sciences Research Council (BBSRC)‐funded component in which the aim was to (1) generate and collate early‐life epigenetic data and (2) investigate early diet and epigenetic marks as predictors of later bone health. The project builds on a wealth of evidence implicating environmental factors, such as maternal diet and body composition, as influences on the long‐term health and development of the offspring, and that these relationships might be mediated at least in part through epigenetic signals. Experimental studies in animal models have demonstrated that manipulation of maternal diet during pregnancy leads to altered offspring epigenetic marking and phenotype. Human studies convincingly demonstrate associations between early environment and later health and disease for outcomes across musculoskeletal, respiratory, neurodevelopmental and cardiometabolic health. The priority now is to find ways in which such observations can be translated into improved lifelong health. A key approach is to identify early biomarkers of adverse health outcomes and then to test these, and subsequent interventions, in trials aimed at identifying strategies to optimise health throughout the life course. The ALPHABET project will inform this process for musculoskeletal outcomes, and the project as a whole should help elucidate not only novel mechanisms, but also potential strategies to reduce the burden of musculoskeletal, respiratory, neurodevelopmental and cardiometabolic disease in future generations.
Enhancing mineral bioavailability from cereals: Current strategies and future perspectives
Authors: Aslam M. F. , Ellis P. R. , Berry S. E. , Latunde‐Dada G. O. , Sharp P. A. 
Published: May 2018

AbstractInadequate intake of essential minerals such as iron and zinc is a public health concern in the UK, particularly for girls and young women. Approximately 30% and 50% of the zinc and iron, respectively, in the UK diet is provided by cereals. In wheat, most of the iron and zinc is contained within the aleurone cell layer; however, aleurone is removed during processing of wheat into white flour. While elemental iron powder is added back into white flour at the milling stage, there is no restoration of zinc. Elemental iron powder has very low bioavailability, and therefore, in our current Biotechnology and Biological Sciences Research Council Diet and Health Research Industry Club‐funded project, we are investigating the potential use of aleurone as a bioavailable source of minerals that could be added to wheat‐based foods. This work has relevance for the food industry and may establish the use of aleurone as a functional food ingredient for fortification of a range of cereal‐based food products.
Determinants of regret in elderly dialysis patients
Authors: Tan Edlyn G F , Teo Irene , Finkelstein Eric A , Meng Chan C 
Published: May 2018

ABSTRACTAimsIn Singapore, most elderly end‐stage renal disease (ESRD) patients choose dialysis over palliative management. However, dialysis may not be the optimal treatment option given only moderate survival benefits and high costs and treatment burden compared to non‐dialysis management. Elderly patients may therefore come to regret this decision. This study investigated: (i) extent of patients’ decision regret after starting dialysis, and (ii) potentially modifiable predictors of regret: satisfaction with chronic kidney disease education, decisional conflict, and decision‐making involvement.MethodsThe present study was a cross‐sectional study of 103 dialysis patients above 70 years of age, surveyed at Singapore General Hospital's renal medicine clinics between March and June 2017. Participants reported their levels of decision regret on the Decision Regret Scale (DRS), retrospective decisional conflict on the Decisional Conflict Scale, information satisfaction, and decision‐making involvement.ResultsIn total, 81% of participants reported no decision regret (DRS score < 50), 11% ambivalence (DRS = 50), and 8% regret (DRS >50). In individual DRS items, 19% felt dialysis had done them harm and 16% would not make the same decision again. In multivariable analyses, lower information satisfaction [b = −0.07 (95% CI: −0.13, −0.01)] and decisional conflict [b = 0.004 (95% CI: 0.002, 0.006)] were significantly associated with decision regret.ConclusionAlthough the majority of elderly dialysis patients were comfortable with their decision to start dialysis, a proportion was ambivalent or regretted this choice. Regret was more likely among those who experienced decisional conflict and/or expressed poorer information satisfaction. Healthcare professionals should recognize these risk factors and take steps to minimize chances of regret among this population subset.
Two‐dimensional simulation of eccentric photorefraction images for ametropes: factors influencing the measurement
Authors: Wu Yifei , Thibos Larry N. , Candy T. Rowan 
Published: May 2018

AbstractPurposeEccentric photorefraction and Purkinje image tracking are used to estimate refractive state and eye position simultaneously. Beyond vision screening, they provide insight into typical and atypical visual development. Systematic analysis of the effect of refractive error and spectacles on photorefraction data is needed to gauge the accuracy and precision of the technique.MethodsSimulation of two‐dimensional, double‐pass eccentric photorefraction was performed (Zemax). The inward pass included appropriate light sources, lenses and a single surface pupil plane eye model to create an extended retinal image that served as the source for the outward pass. Refractive state, as computed from the luminance gradient in the image of the pupil captured by the model's camera, was evaluated for a range of refractive errors (−15D to +15D), pupil sizes (3 mm to 7 mm) and two sets of higher‐order monochromatic aberrations. Instrument calibration was simulated using −8D to +8D trial lenses at the spectacle plane for: (1) vertex distances from 3 mm to 23 mm, (2) uncorrected and corrected hyperopic refractive errors of +4D and +7D, and (3) uncorrected and corrected astigmatism of 4D at four different axes. Empirical calibration of a commercial photorefractor was also compared with a wavefront aberrometer for human eyes.ResultsThe pupil luminance gradient varied linearly with refractive state for defocus less than approximately 4D (5 mm pupil). For larger errors, the gradient magnitude saturated and then reduced, leading to under‐estimation of refractive state. Additional inaccuracy (up to 1D for 8D of defocus) resulted from spectacle magnification in the pupil image, which would reduce precision in situations where vertex distance is variable. The empirical calibration revealed a constant offset between the two clinical instruments.ConclusionsComputational modelling demonstrates the principles and limitations of photorefraction to help users avoid potential measurement errors. Factors that could cause clinically significant errors in photorefraction estimates include high refractive error, vertex distance and magnification effects of a spectacle lens, increased higher‐order monochromatic aberrations, and changes in primary spherical aberration with accommodation. The impact of these errors increases with increasing defocus.
Development of molecular markers linked to the Leptosphaeria maculans resistance gene Rlm6 and inheritance of SCAR and CAPS markers in Brassica napus × Brassica juncea interspecific hybrids
Authors: Rashid M. Harunur , Zou Zhongwei , Fernando W. G. Dilantha 
Published: May 2018

AbstractLeptosphaeria maculans causes blackleg disease on Brassica napus, an economically important oilseed crop. Brassica juncea has high resistance to blackleg and is a source for the development of resistant B. napus varieties. To transfer the Rlm6 resistance gene from B. juncea into B. napus, an interspecific cross between B. napus “Topas DH16516” and B. juncea “Forge” was produced, followed by the development of F2 and F3 generations. Sequence characterized amplified region (SCAR) and cleaved amplified polymorphic sequence (CAPS) markers linked to the L. maculans resistance gene Rlm6 were developed. Segregation of SCAR and CAPS markers linked to Rlm6 were confirmed by genotyping of F2 and F3 progeny. Segregation of CAPS markers and phenotypes for blackleg disease severity in F2 plants had a Mendelian ratio of 3:1 in resistant vs. susceptible plants, respectively, supporting the assumption that genetic control of resistance was by a single dominant gene. The molecular markers developed in this study, which show linkage with the L. maculans resistance gene Rlm6, would facilitate marker‐assisted backcross breeding in a variety development programme.
Oncogenic signaling in uveal melanoma
Authors: Park John J. , Diefenbach Russell J. , Joshua Anthony M. , Kefford Richard F. , Carlino Matteo S. , Rizos Helen 
Published: May 2018

AbstractUveal melanoma is the most common primary cancer of the eye, and despite rapidly emerging insights into the molecular profile of this disease, prognosis of patients with metastatic uveal melanoma remains poor with mortality rates unchanged in over 35 years. Early genetic events activate G protein‐coupled receptor signaling in nearly all uveal tumors via mutually exclusive mutations in the GNAQ, GNA11, CYSLTR2, or PLCB4 genes. A multitude of signaling cascades downstream of G protein activation, including protein kinase C and mitogen‐activated protein kinase activity, are actionable, and many ongoing clinical trials are targeting these pathways. Additional cytogenetic and genetic changes, however, including chromosome 3 monosomy, mutations in the BAP1 tumor suppressor gene, alterations in the splicing factors SRSF2/SF3B1, and mutations in the translation initiation factor EIF1AX, modulate signaling output in uveal tumors and modify the risk of metastases. Here, we review the complex interactions between genetic, molecular signaling, and prognostic profiles in uveal melanoma; the clinical implications of these interactions; and the latest potential targets for rational therapy.