bluuebunny/crossref_metadata_2025_split huggingface dataset:
From general base to general acid catalysis in a sodium-specific DNAzyme by a guanine-to-adenine mutation
Authors: Ma Lingzi , Kartik Sanjana , Liu Biwu , Liu Juewen 
Published: June 2019

Abstract
Recently, a few Na+-specific RNA-cleaving DNAzymes were reported, where nucleobases are likely to play critical roles in catalysis. The NaA43 and NaH1 DNAzymes share the same 16-nt Na+-binding motif, but differ in one or two nucleotides in a small catalytic loop. Nevertheless, they display an opposite pH-dependency, implicating distinct catalytic mechanisms. In this work, rational mutation studies locate a catalytic adenine residue, A22, in NaH1, while previous studies found a guanine (G23) to be important for the catalysis of NaA43. Mutation with pKa-perturbed analogs, such as 2-aminopurine (∼3.8), 2,6-diaminopurine (∼5.6) and hypoxanthine (∼8.7) affected the overall reaction rate. Therefore, we propose that the N1 position of G23 (pKa ∼6.6) in NaA43 functions as a general base, while that of A22 (pKa ∼6.3) in NaH1 as a general acid. Further experiments with base analogs and a phosphorothioate-modified substrate suggest that the exocyclic amine in A22 and both of the non-bridging oxygens at the scissile phosphate are important for catalysis for NaH1. This is an interesting example where single point mutations can change the mechanism of cleavage from general base to general acid, and it can also explain this Na+-dependent DNAzyme scaffold being sensitive to a broad range of metal ions and molecules.
The role of ZAP and OAS3/RNAseL pathways in the attenuation of an RNA virus with elevated frequencies of CpG and UpA dinucleotides
Authors: Odon Valerie , Fros Jelke J , Goonawardane Niluka , Dietrich Isabelle , Ibrahim Ahmad , Alshaikhahmed Kinda , Nguyen Dung , Simmonds Peter 
Published: June 2019

AbstractZinc finger antiviral protein (ZAP) is a powerful restriction factor for viruses with elevated CpG dinucleotide frequencies. We report that ZAP similarly mediates antiviral restriction against echovirus 7 (E7) mutants with elevated frequencies of UpA dinucleotides. Attenuation of both CpG- and UpA-high viruses and replicon mutants was reversed in ZAP k/o cell lines, and restored by plasmid-derived reconstitution of expression in k/o cells. In pull-down assays, ZAP bound to viral RNA transcripts with either CpG- and UpA-high sequences inserted in the R2 region. We found no evidence that attenuation of CpG- or UpA-high mutants was mediated through either translation inhibition or accelerated RNA degradation. Reversal of the attenuation of CpG-high, and UpA-high E7 viruses and replicons was also achieved through knockout of RNAseL and oligodenylate synthetase 3 (OAS3), but not OAS1. WT levels of replication of CpG- and UpA-high mutants were observed in OAS3 k/o cells despite abundant expression of ZAP, indicative of synergy or complementation of these hitherto unconnected pathways. The dependence on expression of ZAP, OAS3 and RNAseL for CpG/UpA-mediated attenuation and the variable and often low level expression of these pathway proteins in certain cell types, such as those of the central nervous system, has implications for the use of CpG-elevated mutants as attenuated live vaccines against neurotropic viruses.
Pharmacogenomics of Nicotine Metabolism: Novel CYP2A6 and CYP2B6 Genetic Variation Patterns in Alaska Native and American Indian Populations
Authors: Claw Katrina G , Beans Julie A , Lee Seung-Been , Avey Jaedon P , Stapleton Patricia A , Scherer Steven E , El-Boraie Ahmed , Tyndale Rachel F , Nickerson Deborah A , Dillard Denise A , Thummel Kenneth E , Robinson Renee F 
Published: June 2019

Abstract

Introduction
Alaska Native and American Indian (AN/AI) populations have higher tobacco use prevalence than other ethnic/racial groups. Pharmacogenetic testing to tailor tobacco cessation treatment may improve cessation rates. This study characterized polymorphic variations among AN/AI people in genes associated with metabolism of nicotine and drugs used for tobacco cessation.

Methods
Recruitment of AN/AI individuals represented six subgroups, five geographic subgroups throughout Alaska and a subgroup comprised of AIs from the lower 48 states living in Alaska. We sequenced the CYP2A6 and CYP2B6 genes to identify known and novel gain, reduced, and loss-of-function alleles, including structural variation (eg, gene deletions, duplications, and hybridizations).

Results
Variant allele frequencies differed substantially between AN/AI subgroups. The gene deletion CYP2A6*4 and reduced function CYP2A6*9 alleles were found at high frequency in Northern/Western subgroups and in Lower 48/Interior subgroups, respectively. The reduced function CYP2B6*6 allele was observed in all subgroups and a novel, predicted reduced function CYP2B6 variant was found at relatively high frequency in the Southeastern subgroup.

Conclusions
Diverse CYP2A6 and CYP2B6 variation among the subgroups highlight the need for comprehensive pharmacogenetic testing to guide tobacco cessation therapy for AN/AI populations.

Implications
Nicotine metabolism is largely determined by CYP2A6 genotype, and variation in CYP2A6 activity has altered the treatment success in other populations. These findings suggest pharmacogenetic-guided smoking cessation drug treatment could provide benefit to this unique population seeking tobacco cessation therapy.
Nicolò de’ Rossi
Authors: Sangiovanni Fabio 
Published: June 2019

Nicolò de’ Rossi (c. 1295–c. post-1348) was born in Treviso, Italy, toward the end of the 13th century and died in Venice after 1348. Beyond a preeminent legal activity that allowed him to take part as a Guelph to the unstable political events of those years, he was one of the most important literary personalities of his age in northern Italy. His cultural renown within the Trevisan area is confirmed by the fact that after the completion of his law studies in Bologna in 1318, he was preferred over Cino da Pistoia as professor of civil law at the academic Studium of Treviso, and he was often chosen as one of the members of diplomatic missions in several troublesome circumstances (in particular during the war against Cangrande della Scala). However, his name is primarily remembered because of his fervent literary activity: his poetic production includes more than 400 poems (sonnets and four canzoni, one associated to a Latin commentary) written between 1317 and 1329, collected, almost as a lyric canzoniere, in the manuscript Colombino 7.1.32 preserved at the Biblioteca Capitular in Seville. These poems mainly deal with love subjects (he experienced all the possibilities offered by the coeval tradition, from Guittone’s style to Stilnovo styles), as well as with political, moral, realistic, and religious themes. Furthermore, thanks to the testimony of this manuscript, we are able to recognize him as the author of the first vernacular examples of figurative poetry: by renewing the model of the Latin carmina figurata, he integrated the phonic element into the graphic one through the elaboration of complex visual architectures for four poems. His importance in the Veneto region is also due to his activity as a veritable editor of the Italian lyric tradition, as witnessed by another manuscript (Barberiniano lat. 3953 of the Vatican Library), collecting a wide series of Tuscan texts (by Dante, Cavalcanti, Cino da Pistoia, Cecco Angiolieri, etc.) that constitute a remarkable anthology based on particular criteria of selection and inner order.
Stephen Fry, the Meaning of Life, and the Problem with Irish Blasphemy Law
Authors: Cox Neville 
Published: June 2019

Abstract
In May 2017, news broke that comedian Stephen Fry was, briefly, under investigation in Ireland, for blasphemy, leading to a reaction of outrage that a blasphemy law existed in Ireland in 2017. This mirrored the equivalent reaction in 2009 when Ireland, in fulfilment of a constitutional obligation, defined the crime in a piece of legislation. A blasphemy law must, by definition, be predicated on a religious public morality that regards certain kinds of irreverence as being ‘unsayable’ and, because Irish public morality is now secular in nature, the law, even though it can have no substantive impact, carried an embarrassingly erroneous message about the nature of modern Ireland. The impact of the law was, therefore, symbolic, and the reaction was against what was seen as an embarrassing and inaccurate symbolic message about the nature of modern Ireland. The disconnect between Irish public morality and the existence of a blasphemy law is the strongest reason why the law should be abolished, and is also the reason why it is unjustifiable as a matter of International Human Rights Law.
Damage accrual and mortality over long-term follow-up in 300 patients with systemic lupus erythematosus in a multi-ethnic British cohort
Authors: Segura Beatriz Tejera , Bernstein Brett Sydney , McDonnell Thomas , Wincup Chris , Ripoll Vera M , Giles Ian , Isenberg David , Rahman Anisur 
Published: June 2019

Abstract

Objective
Damage in patients with systemic lupus erythematosus is irreversible change in organs due to disease activity, concomitant disease or medication side-effects. It is measured using the Systemic Lupus International Collaborative Clinics Damage Index (SDI) and is associated with increased mortality. Previous reports have suggested associations between damage accrual and various ethnic, disease and treatment factors, but there is a dearth of long-term follow-up data from large multi-ethnic cohorts. We describe a study of damage and mortality in 300 patients from London, UK followed for up to 40 years.

Methods
We carried out retrospective analysis of medical records and SDI scores of 300 patients followed for up to 40 years (median 13.3 years). Characteristics of the groups who did and did not develop damage and those who died or survived to the end of follow-up were compared using univariable and multivariable analysis. Kaplan-Meier analysis was used to analyse factors affecting mortality and accrual of damage.

Results
Damage developed in 231/300 (77%) of patients. There was a linear accrual of damage over 40 years follow-up. Factors associated with damage were African/Caribbean ethnicity, renal and cerebral involvement, early use of high-dose corticosteroids or immunosuppressants, anti-RNP and antiphospholipid antibodies. Damage was strongly associated with mortality. Of 87 patients who died, 93% had damage compared with 70% of survivors (P < 0.001).

Conclusion
Development of damage is strongly associated with increased mortality. We identified groups at increased risk of developing damage, including those treated with high-dose steroids and immunosuppressants within the first two years.
What I have heard: conference summary and thoughts for the future1
Authors: Galyean Michael L 
Published: June 2019

Abstract
Twenty-nine presentations by 28 speakers at the California Net Energy System (CNES) 50th Anniversary Symposium provided an informative overview of the past, present, and future of the CNES. The Symposium was divided into eight sessions, with each one or two sessions followed by a lively discussion period. This article provides a summary of key points made by the speakers in each session as provided at the conclusion of the Symposium. Additional thoughts about future directions for research related to the CNES are offered.
Assessment of nociception and related quality-of-life measures in a porcine model of neurofibromatosis type 1
Authors: Khanna Rajesh , Moutal Aubin , White Katherine A. , Chefdeville Aude , Negrao de Assis Pedro , Cai Song , Swier Vicki J. , Bellampalli Shreya S. , Giunta Marissa D. , Darbro Benjamin W. , Quelle Dawn E. , Sieren Jessica C. , Wallace Margaret R. , Rogers Christopher S. , Meyerholz David K. , Weimer Jill M. 
Published: June 2019

Abstract
Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder resulting from germline mutations in the NF1 gene, which encodes neurofibromin. Patients experience a variety of symptoms, but pain in the context of NF1 remains largely underrecognized. Here, we characterize nociceptive signaling and pain behaviors in a miniswine harboring a disruptive NF1 mutation (exon 42 deletion). We present the first characterization of pain-related behaviors in a pig model of NF1, identifying unchanged agitation scores, lower tactile thresholds (allodynia), and decreased response latencies to thermal laser stimulation (hyperalgesia) in NF1

+/ex42del
(females only) pigs. Male NF1

+/ex42del
pigs with tumors showed reduced sleep quality and increased resting, 2 health-related quality-of-life symptoms found to be comorbid in people with NF1 pain. We explore these phenotypes in relationship to suppression of the increased activity of the N-type voltage-gated calcium (CaV2.2) channel by pharmacological antagonism of phosphorylation of a regulatory protein—the collapsin response mediator protein 2 (CRMP2), a known interactor of neurofibromin, and by targeting the interface between the α subunit of CaV2.2 and the accessory β-subunits with small molecules. Our data support the use of NF1

+/ex42del
pigs as a large animal model for studying NF1-associated pain and for understanding the pathophysiology of NF1. Our findings demonstrate the translational potential of 2 small molecules in reversing ion channel remodeling seen in NF1. Interfering with CaV2.2, a clinically validated target for pain management, might also be a promising therapeutic strategy for NF1-related pain management.
Incidence and Prevalence of Borrelia burgdorferi Antibodies in Male Professional Football Players
Authors: Breitbart Philipp , Meister Steffen , Meyer Tim , Gärtner Barbara C. 
Published: June 2019

Objective:
Infections with Borrelia burgdorferi can cause Lyme disease with multiorganic involvement such as (myo)carditis or joint manifestations. Musculoskeletal complaints possibly mimicking some of these symptoms are common among elite athletes. This study aimed to determine seroprevalence and incidence of B. burgdorferi antibodies in professional football players.

Design:
Prospective observational study.

Setting:
Healthy professional football players.

Participants:
Five hundred thirty-five men in the first and second German league.

Interventions:
Two screening assays were used to examine immunoglobulin M (IgM) and immunoglobulin G (IgG) against B. burgdorferi: an enzyme immunoassay (EIA) and a chemiluminescence assay (CLIA). In case of a positive or equivocal result, an immunoblot including in vivo antigens was performed.

Main Outcome Measures:
Course of IgM and IgG against B. burgdorferi in overall 1529 blood samples.

Results:
A total of 96.4% of all results were concordant between EIA and CLIA. Considering only samples with identical results in both assays, prevalence was 1.6%. A positive IgM was detected in 2.3%. No player showed any symptoms of Lyme disease. A seroconversion to IgG was not found. Three players developed a positive IgM corresponding to an incidence of 1032/100 000 person-years. Depending on the assay, 49% to 75% of positive or equivocal screening results could not be confirmed by immunoblot.

Conclusions:
Seroprevalence and incidence of B. burgdorferi among healthy male professional football players are low. Therefore, infections with B. burgdorferi have to be regarded a rare differential diagnosis in professional football in Central Europe. The low confirmation rate of positive screening assays points to an unspecific immune activation.
Crohn’s disease and ulcerative colitis patient perspectives on clinical trials and participation
Authors: Ehrlich Orna , Testaverde James , Heller Caren , Daman Stuart , Anderson Annick , Higgins Peter D.R. 
Published: June 2019

AbstractBackgroundClinical trial recruitment is often the rate-limiting step in the development of new treatments reaching patients across all disease states. With more than 1500 currently available clinical trials for inflammatory bowel diseases (IBD) patients, it is important to understand patient perceptions of clinical trial participation to improve recruitment and retention. This study aimed to examine the specific challenges and barriers that might be reducing IBD patient enrollment and potential methods to overcome these barriers.MethodsFive in-person patient focus groups were conducted from February through May 2016 using two facilitation guides. Participants self-reported a diagnosis of Crohn’s disease or ulcerative colitis.ResultsThe five focus groups included a total of 34 participants. Participants discussed several barriers, including fears, disease severity at trial onset, potential adverse effects, time constraints, and the influence of both their primary IBD provider and support network. Methods to improve participation included better communication to prospective patients, reduced length of trial and time commitment, lower placebo rates, the option of open label extension, and support of the patient’s primary IBD provider.ConclusionsThis is the first study to examine patient perceptions for IBD clinical trial enrollment, including barriers to participation and methods to improve participation. Fear and misunderstanding of clinical trials, engagement with providers, limiting time demands, and limiting the impact on work and family were found to be barriers to participation. Creative solutions to these problems could lead to greater participation in trials and more rapid advancement of new therapies to clinical approval and use.
Formation of synthetic RNA protein granules using engineered phage-coat-protein -RNA complexes
Authors: Granik Naor , Katz Noa , Willinger Or , Goldberg Sarah , Amit Roee 
Published: June 2019

AbstractLiquid-solid transition, also known as gelation, is a specific form of phase separation in which molecules cross-link to form a highly interconnected compartment with solid – like dynamical properties. Here, we utilize RNA hairpin coat-protein binding sites to form synthetic RNA based gel-like granules via liquid-solid phase transition. We show bothin-vitroandin-vivothat hairpin containing synthetic long non-coding RNA (slncRNA) molecules granulate into bright localized puncta. We further demonstrate that upon introduction of the coat-proteins, less-condensed gel-like granules form with the RNA creating an outer shell with the proteins mostly present inside the granule. Moreover, by tracking puncta fluorescence signals over time, we detected addition or shedding events of slncRNA-CP nucleoprotein complexes. Consequently, our granules constitute a genetically encoded storage compartment for protein and RNA with a programmable controlled release profile that is determined by the number of hairpins encoded into the RNA. Our findings have important implications for the potential regulatory role of naturally occurring granules and for the broader biotechnology field.
Thirty years of Doi Moi in the museum
Authors: Were Graeme 
Published: June 2019

PurposeThe purpose of this paper is to describe an exhibition that celebrated 30 years of reform in the Vietnamese National Museum of History, which opened in 2016. It contributes to anthropological understandings of the way exhibitions create new forms of cultural heritage, and so operate as a kind of technology of governance for legitimising state transformations that seek to celebrate neoliberal ideologies and the rise of the individual.Design/methodology/approachUsing an ethnographic methodology, it explores some of the behind-the-scenes decisions involved in producing a narrative of national development since the Doi Moi reforms of 1986.FindingsIn analysing how imported memory approaches were innovatively employed alongside conventional historical facts, this paper reveals ways in which old revolutionary narratives make way for expansive and more acceptable concepts of development that embrace well-being and quality of life as well as national achievements.Originality/valueThis research is based on original ethnographic research conducted by the author and contributes to an emerging field of museum and heritage studies in East and South-East Asia.
Assessing consumer attitudes and perceptions towards food authenticity
Authors: Chousou Charoula , Mattas Konstadinos 
Published: June 2019

PurposeThe purpose of this paper is to identify and assess the factors that consumers evaluate significant in the assessment of food authenticity and guide them to make safe food choices.Design/methodology/approachIn this respect, a mixture model for consumer preferences, namely CUB, was employed due to the ability of discriminate features that are rated similarly allowing the detection of significant similarities and differences in consumers’ judgments. Moreover, introducing covariates in CUB models allow studying the influence that consumers’ socio-demographic characteristics have on the importance of the attributes used in the assessment of food authenticity.FindingsThe results demonstrate that organic certificate, traditional and homemade production practices, origin certificate as well as information about product’s origin country and raw materials production region are significant quality cues enable consumers to judge food authenticity. In addition, consumers further segmentation according to socio-demographic characteristics indicate that country of origin information are mainly used by middle-aged consumers, highly educated and paid, whereas production techniques and organic certification constitute the most effective indicators for judging food authenticity by older consumers.Originality/valueThe paper confirms that consumers can use extrinsic and intrinsic quality cues to judge food’s authenticity.
Sustainability and human competences: a systematic literature review
Authors: Galleli Barbara , Hourneaux Jr Flavio , Munck Luciano 
Published: June 2019

PurposeThe purpose of this paper is to identify and discuss human competences required for sustainability management in organisations.Design/methodology/approachThe research is based on a systematic review of the literature, through qualitative thematic analysis.FindingsThe research covered 15 years of scientific publications and was summarised in 43 articles. It revealed that education, more than management, was the field of knowledge with more references in human competences, through exploratory methodological approaches. The competences found were plenty, but there is still some misunderstanding regarding their conceptual and theoretical bases.Research limitations/implicationsThis research provides evidence that the academic knowledge on the subject is still at its initial stage, and it exposes the debility of the management area in addressing the subject.Practical implicationsThe authors intend to indicate to managers some fundamentals for the adoption of human competences for sustainability aiming at a more sustainable performance in organisations.Social implicationsThe results may instigate studies concerning the fit of sustainability competences developed on higher education institutions and the job market. From it, curricula and pedagogical projects can be proposed and revised with better alignment to the organisational context.Originality/valueThis paper presents a theoretical contribution by building bridges among different perspectives and fields of knowledge on the topic. The paper also offers a managerial contribution by stimulating practical discussions to develop sustainability in organisations through individuals.