bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of the sirohaem biosynthesis pathway in Staphylococcus aureus
Authors: Videira Marco A. M. , Lobo Susana A. L. , Sousa Filipa L. , Saraiva Lígia M. 
Published: October 2019

Sirohaem is a modified tetrapyrrole and a key prosthetic group of several enzymes involved in nitrogen and sulfur metabolisms. This work shows that Staphylococcus aureus produces sirohaem through a pathway formed by three independent enzymes. Of the two putative sirohaem synthases encoded in the S. aureus genome and annotated as cysG, one is herein shown to be a uroporphyrinogen III methyltransferase that converts uroporphyrinogen III to precorrin‐2, and was renamed as UroM. The second cysG gene encodes a precorrin‐2 dehydrogenase that converts precorrin‐2 to sirohydrochlorin, and was designated as P2D. The last step was found to be performed by the gene nirR that, in fact, codes for a protein with sirohydrochlorin ferrochelatase activity, labelled as ShfC. Additionally, site‐directed mutagenesis studies of S. aureus ShfC revealed that residues H22 and H87, which are predicted by homology modelling to be located at the active site, control the ferrochelatase activity. Within bacteria, sirohaem synthesis may occur via one, two or three enzymes, and we propose to name the correspondent pathways as Types 1, 2 and 3, respectively. A phylogenetic analysis revealed that Type 1 is the most used pathway in Gammaproteobacteria and Streptomycetales, Type 2 predominates in Fibrobacteres and Vibrionales, and Type 3 predominates in Firmicutes of the Bacillales order. Altogether, we concluded that the current distribution of sirohaem pathways within bacteria, which changes at the genus or species level and within taxa, seems to be the result of evolutionary multiple fusion/fission events.
Label‐free superresolution effect of nonlinear reverse saturation absorption thin films through difference method
Authors: DING C. , WEI J. 
Published: October 2019

SummaryLabel‐free superresolution effect of nonlinear reverse saturation absorption (NRSA) thin films was investigated through difference method, where a subdiffraction‐limit spot signal was constructed by intensity subtraction of two spots obtained under different laser intensities. By using annealed InSb films as the NRSA thin films, we experimentally obtained the subdiffraction‐limit spot signal, and the optimal reduction ratio was approximately 52.5% of the original spot. Experimental results agreed well with theoretical simulations. The simulation results of a 9‐point array sample showed the capability to achieve nonfluorescence superresolution imaging using the NRSA effect.
A multicenter study of oral sarcomas in Brazil
Authors: de Carvalho Waldner Ricardo Souza , de Souza Lucas Lacerda , Pontes Flávia Sirotheau Corrêa , Uchôa Daniel Cavallero Colares , Corrêa Davi Lavareda , de Cáceres Cinthia Verónica Bardalez López , Lopes Márcio Ajudarte , Santos‐Silva Alan Roger , Vargas Pablo Agustin , de Andrade Bruno Augusto Benevenuto , Romañach Mário , Gomez Ricardo Santiago , Costa Sara Ferreira dos Santos , Batista Aline Carvalho , Mendonça Elismauro Francisco , Pinto Décio dos Santos , Gondak Rogério , da Cruz Perez Danyel Elias , Nonaka Cassiano , dos Santos Jean Nunes , Libório‐Kimura Tatiana Nayara , Câmara Jeconias , Ramôa Pires Fábio , de Souza Lélia Batista , Martins Manoela Domingues , de Almeida Oslei Paes , Fonseca Felipe Paiva , Pontes Hélder Antônio Rebelo 
Published: October 2019

AbstractObjectivesThe aim of this study was to investigate the prevalence of oral sarcomas from geographic regions of Brazil.Materials and methodsA cross‐sectional study was conducted on biopsies obtained from January 2007 to December 2016 at twelve Brazilian oral and maxillofacial pathology centres. Gender, age, evolution time, clinical aspects, tumour location, tumour size at diagnosis, radiographic aspects and histopathological diagnosis were evaluated. Data were analysed using descriptive statistical methods.ResultsFrom 176,537, a total of 200 (0.11%) oral sarcomas were reported, and the most prevalent were osteosarcomas (74 cases; 37%) and Kaposi's sarcomas (52 cases; 26%). Males were more affected than females at a mean age of 32.2 years old (range of 3–87 years). The most common symptoms were swelling¸ localised pain and bleeding at a mean evolution time of 5.14 months (range <1–156 months). The lesions were mostly observed in the mandible (90 cases; 45%), with a mean tumour size of 3.4 cm (range of 0.3–15 cm). Radiographically, the lesions presented a radiolucent aspect showing cortical bone destruction and ill‐defined limits.ConclusionsOral sarcomas are rare lesions with more than 50 described subtypes. Osteosarcomas and Kaposi's sarcomas were the main sarcomas of the oral cavity in Brazil.
Which factors determine treatment choices in patients with advanced kidney failure? a protocol for a co-productive, mixed methods study
Authors: Roberts Gareth , Chess James A , Howells Teri , Mc Laughlin Leah , Williams Gail , Charles Joanna M , Dallimore D J , Edwards Rhiannon Tudor , Noyes Jane 
Published: October 2019

IntroductionKidney disease is common, affecting up to 1 in 10 of the adult population, and the numbers are expected to rise over the next decade. There are three main treatments that are available to patients with kidney disease: transplantation, dialysis and supportive care without dialysis. Dialysis can occur in a dialysis unit or in a person’s home, but unit-based dialysis remains the most common initial treatment for patients in Wales. This is a cause for concern as most studies suggest that it is associated with the lowest quality of life and the highest mortality, and is a more expensive treatment option.This study aims to identify the factors that lead to patients choosing unit-based haemodialysis rather than home-based dialysis with a view to informing future changes in patient education and service commissioning in Wales. A secondary aim is to determine if the co-production of research leads to more sustainable services.Methods and analysisThis mixed-method study taking place between October 2018 and September 2020 will use a sequential explanatory design whereby the descriptive quantitative cross-sectional analysis of linked health and administrative data sets inform qualitative data collection from patients, carers and health and care professionals. Qualitative findings will be used to interpret or explain quantitative descriptive results. Additional strands to the study include a review of materials and education provided to patients and an economic review of treatment modalities.Ethics and disseminationThe study will be conducted in accordance with the principles expressed in the Declaration of Helsinki. It has full approval from Health and Care Research Wales Research Ethics Committee #5. As a co-productive study involving patients, clinicians, third sector partners and academics, findings from this study will be shared on a continual basis. Study results will be published in peer-reviewed journals and presented at national and international conferences.
The Platonist Absurd Accumulation of Geometrical Objects: Metaphysics Μ.2
Authors: González-Varela José Edgar 
Published: October 2019

Abstract
In the first argument of Metaphysics Μ.2 against the Platonist introduction of separate mathematical objects, Aristotle purports to show that positing separate geometrical objects to explain geometrical facts generates an ‘absurd accumulation’ of geometrical objects. Interpretations of the argument have varied widely. I distinguish between two types of interpretation, corrective and non-corrective interpretations. Here I defend a new, and more systematic, non-corrective interpretation that takes the argument as a serious and very interesting challenge to the Platonist.
Engaging with the Bible in Visual Culture
Authors: Beaumont Sheona 
Published: October 2019

Abstract
Increasingly articulate contemporary art practices are engaging with biblical representation, revealing new relationships with religion through the availability of the word in image. Taking as exemplary the photographic publication of Adam Broomberg and Oliver Chanarin’s Holy Bible (2013), this essay considers the evidence for their hermeneutics between image and word that is characterized by open awareness of and expansive participation in the (rereading of the) Bible. Discussing this engagement, I explore imagistic readings of the Bible through the artists’ strategies of interpolation and repetition, as well as examining their chosen theme—catastrophe—for its revelatory power. Through the artists’ self-reflexive hermeneutics of indeterminacy, I argue that the discussion of the return of religion in art needs attuning to this kind of specific practitioner experience: a hermeneutical circle of imaginative, dialogical, and dynamic interpretative positions in which the notion of indeterminacy is persuasive for interpretative grist, historical accountability, and theological horizon.
Proclo commentatore del Timeo: esegesi procliana, esegesi a Proclo, e vettori materiali (Patmos Eileton 897)
Authors: Menchelli Mariella 
Published: October 2019

Abstract
Proclus’ Commentary on Plato’s Timaeus has been preserved in several manuscripts from the IX to the XVI centuries and in a paper scroll of the XI century, Patmos Eileton 897, containing two large parts of Book III (on the world’s body, on the recto, and on the world’s soul, on the verso of the scroll) and a large corpus of scholia vetera to it. This paper aims to examine the two main branches of the tradition of the Commentary and to give some observations on the exegetical apparatus to Proclus in the different forms of scholia figurata (and/or schemata), exegetical scholia, scholia to Proclus.
La terra di mezzo del commentario umanistico ai testi classici
Authors: Abbamonte Giancarlo 
Published: October 2019

Abstract
Scholars have lengthy debated on the originality of the humanistic commentary on the classical authors with respect to the medieval commentaries on the same authors. If the question can be regarded as still open for the works written in the first half of the 15th century, the birth of the printing determined a dramatic change in the contents and the form of the commentaries. From the point of view of the content the humanists are much more interested in the different readings transmitted by the manuscripts, whilst the printing allows both to have different layouts of the commentaries and to insert new tools as indexes and page numbers for consulting them. The present paper will present the new aspects of the printed commentaries and will try to explain the reasons which produced each change.
Intellectual Captivity
Authors: Bar-Itzhak Chen 
Published: October 2019

Abstract
This essay concerns the unequal distribution of epistemic capital in the academic field of World Literature and calls for an epistemic shift: a broadening of our theoretical canon and the epistemologies through which we read and interpret world literature. First, this epistemic inequality is discussed through a sociological examination of the “world republic of literary theory,” addressing the limits of circulation of literary epistemologies. The current situation, it is argued, creates an “intellectual captivity,” the ethical and political implications of which are demonstrated through a close reading of the acts of reading world literature performed by scholars at the center of the field. A few possible solutions are then suggested, drawing on recent developments in anthropology, allowing for a redistribution of epistemic capital within the discipline of World Literature: awareness of positionality, reflexivity as method, promotion of marginal scholarship, and a focus on “points of interaction.”
Secular Liturgies
Authors: Somerville-Wong Anastasia E. 
Published: October 2019

Abstract
This paper, by the founder of the UK based Secular Liturgies Network and Forum, explores the concept and purpose of secular liturgy, and the potential for liturgical events in modern secular societies. It examines the practice of writing secular liturgy, discusses potential contributions from atheists, agnostics, humanists and religious progressives, and considers the new pastoral roles that may evolve alongside a secular liturgies movement. The author argues that secular liturgies and liturgical events have the potential to enrich secular culture, nurture community, facilitate healthy social interaction, advance ethical thought, promote creative writing and other arts, and galvanise people in their efforts towards sustainability and the creation of cultures and environments of health.
Improved Detection of FV Leiden Patients Using a Novel Snake-Venom-Based Activated Protein C Resistance Assay.
Authors: Wilmer Marianne , Stocker Christoph , Buehler Beatrice , Conell Brigitte , Calatzis Andreas 
Published: October 2019

Abstract
A new functional prothrombin-based activated protein C (APC) resistance (APC-R) test (Pefakit® APC-R Factor V Leiden, Pentapharm, Basel, Switzerland) is presented.
Methods: The plasma sample is mixed with a reagent containing APC and snake venom specifically activating FV (RVV-V, Daboia russelli) and plasma that has been depleted of FV. During an incubation period of 180 sec the activated FV is inactivated by APC. Subsequently a reagent that contains a FV dependent prothrombin activator (Noscarin, Notechis scutatus) and EDTA is added. The clotting time is recorded. A second determination is performed under identical conditions, with the exception that no APC is added to the first reagent. A ratio between the two measurements is calculated. 703 samples of patients undergoing thrombophilia screening were analysed. Results were correlated to PCR based FVL testing, aPTT, PT, and to levels of Protein C, Protein S, Fibrinogen, FVIII and lupus anticoagulant index.
Results: Using a predefined cut-off of a ratio of 2.5 a 100% sensitivity and specificity for the detection of a FVL mutation was found. Using a cut-off ratio of 1.2 a complete but narrow distinction of FVL heterozygous (n=192) and FVL homozygous samples (n=27) was determined. No interference by sample’s INR and aPTT, PS, fibrinogen and FVIII levels and lupus anticoagulant ratio was detected.
Conclusion: The new snake-venom-based APC-R assay provides an improved distinction of FV wild-type and FVL carriers compared to the data reported for the aPTT based methods. The use of a FV dependent prothrombin activator eliminates effects of FVIII concentration or lupus anticoagulants in the sample.
Identification of a Novel Stromal Cell Membrane Protein that Binds to Megakaryocytes.
Authors: Tamashiro Kazuki , Fujimoto Tetsur-Takahiro , Fujimura Kingo 
Published: October 2019

Abstract
In bone marrow, hematopoiesis-supporting cells or stromal cells govern the growth, survival and differentiation of hematopoietic stem cells. We previously reported the method to produce the functional platelets from murine embryonic stem (ES) cells in vitro, using the coculture system with OP9 stromal cells. Also in this system, the cell contact between ES-derived cells and stromal cells is essential for megakaryocyte differentiation, and even after growth factors including TPO were supplied, ES-derived megakaryocytes cannot be maintained without stromal cells. In this study, we searched membrane proteins that were expressed in the stromal cells and were involved in the cell contact with megakaryocytes. We employed the retrovirus-based signal sequence trap (SST) method to identify such membrane proteins from murine stromal cells. 117 signal sequence-containing clones were identified, and the clones were further screened by the binding capacity to megakaryocytic cell lines. We finally identified a novel protein that contains two Ig domains and belongs to the transmembrane-type immunoglobulin superfamily. RT-PCR analysis showed that this protein is expressed in bone marrow stromal cell lines including OP9, and vascular endothelial cell lines, whereas no expression was detected in any hematopoietic cell lines. We next created a cDNA construct in which the extracellular domain of the protein was linked to IgG Fc domain, and the construct was transfected into 293 cells. The fusion protein was purified from the culture supernatant. By flow cytometer, the purified recombinant protein bound to megakaryocytic cell lines and CD41-positive bone marrow megakaryocytes. The binding to murine Sca-1-positive and human CD34-positive immature cells was also detected. The binding was dependent on calcium, but was not inhibited by RGD peptide. The effect on in vitro differentiation system of ES cells was further tested. The addition of the fusion protein showed no influences on the maintenance of undifferentiated state of ES cells. However, after the differentiation induction, the protein facilitated morphological change of the ES cells. Further analysis will contribute to understanding of the mechanisms by which the stromal cell contact regulates megakaryocyte differentiation and platelet production.
Determination of Soluble MICA in Serum as a Novel Marker for Tumor Stage and Metastasis.
Authors: Salih Helmut R. , Stieber Petra , Peterfi Andrea , Nagel Dorothea , Kanz Lothar , Steinle Alexander L. , Holdenrieder Stefan 
Published: October 2019

Abstract
The human NKG2D ligands (NKG2DL) MICA and MICB have been shown to be expressed on tumors of epithelial and hematopoietic origin in vivo. Recently we reported that MICA is shed from the cell surface of tumor cells and is present in sera of tumor patients (J Immunol169:4098 (2002), Blood102:1389 (2003)). Since the strength of an anti-tumor response by NK cells and CD8 T cells is critically depending on NKG2DL expression levels, down-regulation of MICA-expression on tumor cells represents an immune escape mechanism that diminishes anti-tumor reactivity of NKG2D-bearing lymphocytes. However, no data are yet available regarding the correlation of soluble MICA (sMICA) levels with specific tumor entities, aggressiveness of the disease, and hence the potential implementation of sMICA as novel marker in differential diagnosis and prognosis of cancer. In this study, we determined sMICA levels in sera of 512 individuals including 296 patients with various cancers, 154 patients with benign disorders and 62 healthy individuals. Healthy individuals revealed significantly lower sMICA values (median<30pg/mL) than patients with benign diseases (84pg/mL; p=0.005) and cancer patients (161pg/mL; p<0.0001). In addition, sMICA levels differed significantly between cancer patients and patients with benign disorders (p<0.0001) that represent the most relevant control group for differential diagnosis. In cancer patients, while there was no association between sMICA levels and tumor size (p=0.456), cell differentiation (p=0.271), or lymph node involvement (p=0.674), sMICA correlated significantly with cancer stage and metastasis (p=0.015 and p=0.007, respectively). Our data indicate that release of MICA might play a role in late stages of tumor progression by overcoming the confining effect of NK cells and CD8 T cells. Thus, determination of sMICA levels provides valuable information for cancer staging, and sMICA in serum seems to be an indicator for systemic manifestation of malignancy rather than for local tumor extent.
Human Monoclonal Cryocrystalglobulinemia: First Complete Heavy and Light Chain Variable Region Nucleotide Sequences.
Authors: Perfetti Vittorio , Navazza Valentina , Giorgietti Sofia , Marchese Loredana , Palladini Giovanni , Caporali Roberto , Montecucco Claudio , Merlini Giampaolo 
Published: October 2019

Abstract
Cryocrystalglobulinemia is characterized by a monoclonal immunoglobulin that is both cryoprecipitable and crystalforming (cryocrystalglobulin). It occours in humans as a rare complication of lymphoproliferative disorders. The monoclonal immunoglobulins may crystallize in serum and synovial fluid and are responsible for both microcrystalline synovial inflammation and occlusive vasculopathy in kidneys and skin. At present, there are no reports on sequence analysis and tertiary structure of human cryocrystalglobulins. In this study, we established the first complete light and heavy chain variable region sequences of a human cryocrystalglobulin (BEL) from a patient with severe microcrystalline arthropathy, cutaneous purpura and sacroiliitis. Serum cryoprecipitate was composed of unbound monoclonal IgGk at immunofixation (type I cryoglobulinemia) and revealed homogeneous crystals under light microscopy. Extra and intracellular crystals were also found in synovial fluid. Analysis of bone marrow aspirate showed 4% monoclonal plasma cell infiltration. Total RNA was extracted from Ficoll-separated bone marrow mononuclear cells and complete heavy (VH) and light chain (Vk) variable domain sequences of monoclonal Ig were obtained by means of an unbiased inverse-PCR strategy. Sequences were then matched in databases to identify rearranged germline V, D and J segments. The heavy chain sequence belonged to the g2 class and its variable region was most closely related (94% identity) to the VH3-30 germline gene (VH3 family) rearranged to D2-2 and JH4b segments, whereas the Vk region was derived (97% identity) from the germline VkL6 (VkIII) rearranged to Jk5. Partial protein sequence of serum cryocrystalprecipitate confirmed the correct identification of the monoclonal sequences. A previously reported murine model of cryocrystalglobulinemia suggested that acquisition of specific amino acids at critical positions within the VH domain (positions 6 and 23) could influence cryoprecipitation (Rengers J-U et al, Blood2000;95:3467–72). Analysis of BEL VH domain did not confirm these observations. Protein modelling and site-directed mutagenesis studies are undergoing to clarify the role of amino acid substitutions and interactions in immunoglobulin crystal-like aggregation and cryoprecipitation.