bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterizing the original anti‐C5 function‐blocking antibody, BB5.1, for species specificity, mode of action and interactions with C5
Authors: Zelek Wioleta M. , Menzies Georgina E. , Brancale Andrea , Stockinger Brigitta , Morgan Bryan Paul 
Published: June 2020

SummaryThe implication of complement in multiple diseases over the last 20 years has fuelled interest in developing anti‐complement drugs. To date, the focus has been on C5; blocking cleavage of C5 prevents formation of two pro‐inflammatory activities, C5a anaphylatoxin and membrane attack complex. The concept of C5 blockade to inhibit inflammation dates back 30 years to the description of BB5.1, an anti‐C5 blocking monoclonal antibody raised in C5‐deficient mice. This antibody proved an invaluable tool to demonstrate complement involvement in mouse disease models and catalysed enthusiasm for anti‐complement drug development, culminating in the anti‐human C5 monoclonal antibody eculizumab, the most successful anti‐complement drug to date, already in clinical use for several rare diseases. Despite its key role in providing proof‐of‐concept for C5 blockade, the mechanism of BB5.1 inhibition remains poorly understood. Here, we characterized BB5.1 cross‐species inhibition, C5 binding affinity and chain specificity. BB5.1 efficiently inhibited C5 in mouse serum but not in human or other rodent sera; it prevented C5 cleavage and C5a generation. BB5.1 bound the C5 α‐chain with high affinity and slow off‐rate. BB5.1 complementarity‐determining regions were obtained and docking algorithms were used to predict the likely binding interface on mouse C5.
lncRNA NR2F1‐AS1 promotes breast cancer angiogenesis through activating IGF‐1/IGF‐1R/ERK pathway
Authors: Zhang Qi , Li Tianfu , Wang Zhecun , Kuang Xiaying , Shao Nan , Lin Ying 
Published: June 2020

AbstractLong non‐coding RNAs (lncRNAs) take various effects in cancer mostly through sponging with microRNAs (miRNAs). lncRNA NR2F1‐AS1 is found to promote tumour progression in hepatocellular carcinoma, endometrial cancer and thyroid cancer. However, the role of lncRNA NR2F1‐AS1 in breast cancer angiogenesis remains unknown. In this study, we found lncRNA NR2F1‐AS1 was positively related with CD31 and CD34 in breast cancer through Pearson's correlation analysis, while lncRNA NR2F1‐AS1 transfection promoted human umbilical vascular endothelial cell (HUVEC) tube formation. In breast cancer cells, lncRNA NR2F1‐AS1 enhanced the HUVEC proliferation, tube formation and migration ability through tumour‐conditioned medium (TCM). In zebrafish model, lncRNA NR2F1‐AS1 increased the breast cancer cell‐related neo‐vasculature and subsequently promoted the breast cancer cell metastasis. In mouse model, lncRNA NR2F1‐AS1 promoted the tumour vessel formation, increased the micro vessel density (MVD) and then induced the growth of primary tumour. Mechanically, lncRNA NR2F1‐AS1 increased insulin‐like growth factor‐1 (IGF‐1) expression through sponging miRNA‐338‐3p in breast cancer cells and then activated the receptor of IGF‐1 (IGF‐1R) and extracellular signal‐regulated kinase (ERK) pathway in HUVECs. These results indicated that lncRNA NR2F1‐AS1 could promote breast cancer angiogenesis through IGF‐1/IGF‐1R/ERK pathway.
Assessment of clinical inertia in people with diabetes within primary care
Authors: Meredith Ashley H. , Buatois Emily M. , Krenz James R. , Walroth Todd , Shenk McKenzie , Triboletti Jessica S. , Pence Lauren , Gonzalvo Jasmine D. 
Published: June 2020

AbstractRationale, aims and objectivesClinical inertia, defined as a delay in treatment intensification, is prevalent in people with diabetes. Treatment intensification rates are as low as 37.1% in people with haemoglobin A1c (HbA1c) values >7%. Intensification by addition of medication therapy may take 1.6 to more than 7 years. Clinical inertia increases the risk of cardiovascular events. The primary objective was to evaluate rates of clinical inertia in people whose diabetes is managed by both pharmacists and primary care providers (PCPs). Secondary objectives included characterizing types of treatment intensification, HbA1c reduction, and time between treatment intensifications.MethodRetrospective chart review of persons with diabetes managed by pharmacists at an academic, safety‐net institution. Eligible subjects were referred to a pharmacist‐managed cardiovascular risk reduction clinic while continuing to see their PCP between October 1, 2016 and June 30, 2018. All progress notes were evaluated for treatment intensification, HbA1c value, and type of medication intensification.ResultsThree hundred sixty‐three eligible patients were identified; baseline HbA1c 9.6% (7.9, 11.6) (median interquartile range [IQR]). One thousand one hundred ninety‐two pharmacist and 1739 PCP visits were included in data analysis. Therapy was intensified at 60.5% (n = 721) pharmacist visits and 39.3% (n = 684) PCP visits (P < .001). The median (IQR) time between interventions was 49 (28, 92) days for pharmacists and 105 (38, 182) days for PCPs (P < .001). Pharmacists more frequently intensified treatment with glucagon‐like peptide‐1 agonists and sodium glucose cotransporter‐2 inhibitors.ConclusionPharmacist involvement in diabetes management may reduce the clinical inertia patients may otherwise experience in the primary care setting.
Research and application of an intelligent networking model for flood forecasting in the arid mountainous basins
Authors: Yuan Ximin , Zhang Xingyuan , Tian Fuchang 
Published: June 2020

AbstractStorm floods occur frequently and have complex characteristics in arid mountainous areas, which for a long time has been a weak link in flood forecasting. The application of an artificial intelligent model and physically‐based hydrological model has some limitations on flood forecasting in arid mountainous areas with scarce data. In this article, the ANN model and Muskingum‐Cunge method are combined to propose an intelligent networking model for flood forecasting (FFIN model) in arid mountainous areas with scarce data, which BR‐ANN model is used to forecast the flood in the catchment sub‐basin with runoff data, while the General Regression Neural Network model is used to carry out flood parallel forecast in the catchment sub‐basin without runoff data. The Muskingum‐Cunge method is used to connect the sub‐basins and form a confluence network, so as to simulate the flood routing process in river. The verification and comparison results in study area show that the FFIN model has a superior overall forecasting ability. For the forecasting period, the evaluation index Kling‐Gupta efficiency is 0.88, Nash efficiency coefficient is 0.982 and forecasting deviation of flood peak flow is 7.15%. The FFIN model can be effectively applied to flood forecasting in arid mountainous areas with scarce runoff data.
AtHAP5A regulates iron translocation in iron‐deficient Arabidopsis thaliana
Authors: Zhu Xiao Fang , Wu Qi , Meng Yu Ting , Tao Ye , Shen Ren Fang 
Published: June 2020

AbstractIron (Fe) deficient plants employ multiple strategies to increase root uptake and root‐to‐shoot translocation of Fe. The identification of genes that are responsible for these processes, and a comprehensive understanding of the regulatory effects of transcriptional networks on their expression, including transcription factors (TFs), is underway in Arabidopsis thaliana. Here, we show that a Histone‐ or heme‐associated proteins (HAP) transcription factor (TF), HAP5A, is necessary for the response to Fe deficiency in Arabidopsis. Its expression was induced under Fe deficiency, and the lack of HAP5A significantly decreased Fe translocation from the root to the shoot, resulting in substantial chlorosis of the newly expanded leaves, compared with the wild‐type (WT, Col‐0). Further analysis found that the expression of a gene encoding nicotianamine (NA) synthase (NAS1) was dramatically decreased in the hap5a mutant, regardless of the Fe status. Yeast‐one‐hybrid and ChIP analyses suggested that HAP5A directly binds to the promoter region of NAS1. Moreover, overexpression of NAS1 could rescue the chlorosis phenotype of hap5a in Fe deficient conditions. In summary, a novel pathway was elucidated, showing that NAS1‐dependent translocation of Fe from the root to the shoot is controlled by HAP5A in Fe‐deficient Arabidopsis thaliana.
Anterior pituitary gland synthesises dopamine from l‐3,4‐dihydroxyphenylalanine (l‐dopa)
Authors: Orrillo Santiago Jordi , de Dios Nataly , Asad Antonela Sofía , De Fino Fernanda , Imsen Mercedes , Romero Ana Clara , Zárate Sandra , Ferraris Jimena , Pisera Daniel 
Published: June 2020

AbstractProlactin (PRL) is a hormone principally secreted by lactotrophs of the anterior pituitary gland. Although the synthesis and exocytosis of this hormone are mainly under the regulation of hypothalamic dopamine (DA), the possibility that the anterior pituitary synthesises this catecholamine remains unclear. The present study aimed to determine if the anterior pituitary produces DA from the precursor l‐3,4‐dihydroxyphenylalanine (l‐dopa). Accordingly, we investigated the expression of aromatic l‐amino acid decarboxylase (AADC) enzyme and the transporter vesicular monoamine transporter 2 (VMAT2) in the anterior pituitary, AtT20 and GH3 cells by immunofluorescence and western blotting. Moreover, we investigated the production of DA from l‐dopa and its release in vitro. Then, we explored the effects of l‐dopa with respect to the secretion of PRL from anterior pituitary fragments. We observed that the anterior pituitary, AtT20 and GH3 cells express both AADC and VMAT2. Next, we detected an increase in DA content after anterior pituitary fragments were incubated with l‐dopa. Also, the presence of l‐dopa increased DA levels in incubation media and reduced PRL secretion. Likewise, the content of cellular DA increased after AtT20 cells were incubated with l‐dopa. In addition, l‐dopa reduced corticotrophin‐releasing hormone‐stimulated adrenocorticotrophic hormone release from these cells after AADC activity was inhibited by NSD‐1015. Moreover, DA formation from l‐dopa increased apoptosis and decreased proliferation. However, in the presence of NSD‐1015, l‐dopa decreased apoptosis and increased proliferation rates. These results suggest that the anterior pituitary synthesises DA from l‐dopa by AADC and this catecholamine can be released from this gland contributing to the control of PRL secretion. In addition, our results suggest that l‐dopa exerts direct actions independently from its metabolisation to DA.
Intraspecific variation in nutritional traits of neighbouring plants generates a continuum of associational effects
Authors: Champagne Emilie , Moore Ben D , Côté Steeve D , Tremblay Jean‐Pierre 
Published: June 2020

AbstractAimsWhen deciding whether or not to eat a plant, herbivores are influenced by the nutritional value of potential foods, but also indirectly by neighbouring plants (associational effects). We aimed to investigate how the abundance and nutritional quality of neighbours of balsam firs (Abies balsamea) affects browsing on balsam firs by white‐tailed deer. We sought to distinguish the effects of conspecific and heterospecific neighbour abundance, and to evaluate whether intraspecific variation in nutritional traits produces associational effects.LocationAnticosti Island, QC, Canada.MethodsWe measured the abundance of stems in 4‐m2 plots centred on a focal balsam fir and evaluated nutritional value (nitrogen content and digestibility) of focal firs and neighbouring plants. We used generalized linear models to explain browsing on firs as a function of the neighbouring stem abundance (conspecific and heterospecific), and of the nutritional value of firs and neighbouring stems.ResultsFir abundance only affected browsing of firs after accounting for fir nutritional value, e.g., browsing in plots of low fir digestibility decreased as the number of fir stems increased (resource dilution effect). The associational effects of heterospecific neighbour abundance, especially birch stem and shoot abundance, were also contingent on neighbour nutritional value. For example, at low birch digestibility, browsing on the focal fir increased with the number of neighbouring birches. Browsing on fir also increased as the number of spruce stems of high nutritional value increased.ConclusionsBy taking into account the abundance of all species, we could discriminate between conspecific effects and associational effects caused by heterospecifics. Our study suggests that the strength of associational effects varies in a continuous fashion in response to relative nutritional value. We propose that future studies should not only consider the identity of neighbours but also the nutritional traits of plant communities.
“Catching butterflies”: Marion Milner and stream of consciousness writing
Authors: Tyson Helen 
Published: June 2020

AbstractThis article explores the use of stream of consciousness writing in the early work of the British psychoanalyst, life writer, and artist, Marion Milner. Focusing on Milner's 1934 book,A Life of One's Own(first published under the pen name Joanna Field), the first part of the article situates Milner's use of stream of consciousness writing alongside the work of her contemporaries Virginia Woolf, May Sinclair, and Dorothy Richardson. Building on Vanessa Smith's recent archival work on Milner's reading of Woolf, this article provides further insight into previously unpublished archival material that reveals Milner explicitly identifying her “method” with that of T. S. Eliot inThe Waste Landand commenting on Dorothy Richardson's rejection of the “omniscient observer” while she worked onA Life of One's Own. ReadingA Life of One's Ownalongside the writing of Milner's modernist contemporaries, I argue not only that Milner's writing contains striking formal and thematic echoes of modernist stream of consciousness prose but also that she uses forms of free writing as the basis for her own distinctive experiment in disentangling her own wants and desires from those manufactured by the forces of patriarchal capitalist modernity. The second part of the article demonstrates how Milner's experiments with stream of consciousness writing became, in the political context of the 1930s, fraught with an uncertainty about the boundaries of the individual mind. Examining Milner's anxieties about the forms of personal surrender solicited by modernist artworks, I show how Milner's own experiments with stream of consciousness writing became, increasingly in the 1930s, part of an experiment in trying to extricate the individual from the rising currents of fascism. Tracking Milner's, Richardson's, and Woolf's dramatisation of the pleasures and perils of aesthetic abandon, I argue that, although Milner struggles to negotiate her own immersion within the rising sociopolitical currents of history, the significance of her writing lies not only in the vividness with which it dramatises this fragile encounter but also in the argument that it makes for the value of creative and critical processes in an age of fascism.
Oxidative stress is associated with suspected non‐alcoholic fatty liver disease and all‐cause mortality in the general population
Authors: Damba Turtushikh , Bourgonje Arno R. , Abdulle Amaal E. , Pasch Andreas , Sydor Svenja , van den Berg Eline H. , Gansevoort Ron T. , Bakker Stephan J. L. , Blokzijl Hans , Dullaart Robin P. F. , van Goor Harry , Moshage Han 
Published: June 2020

AbstractBackground & AimsNon‐alcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation, inflammation and an imbalanced redox homeostasis. We hypothesized that systemic free thiol levels, as a proxy of systemic oxidative stress, are associated with NAFLD.MethodsProtein‐adjusted serum free thiol concentrations were determined in participants from the Prevention of Renal and Vascular End‐Stage Disease (PREVEND) cohort study (n = 5562). Suspected NAFLD was defined by the Fatty Liver Index (FLI ≥ 60) and Hepatic Steatosis Index (HSI > 36).ResultsProtein‐adjusted serum free thiols were significantly reduced in subjects with FLI ≥ 60 (n = 1651). In multivariable logistic regression analyses, protein‐adjusted serum free thiols were associated with NAFLD (FLI ≥ 60) (OR per doubling of concentration: 0.78 [95% CI 0.64‐0.96], P = .016) even when adjusted for potential confounding factors, including systolic blood pressure, diabetes, current smoking, use of alcohol and total cholesterol (OR 0.80 [95% CI 0.65‐0.99], P = .04). This association lost its significance (OR 0.94 [95% CI 0.73‐1.21], P = .65) after additional adjustment for high‐sensitive C‐reactive protein. Stratified analyses showed significantly differential associations of protein‐adjusted serum free thiol concentrations with suspected NAFLD for gender (P < .02), hypertension (P < .001) and hypercholesterolemia (P < .003). Longitudinally, protein‐adjusted serum free thiols were significantly associated with the risk of all‐cause mortality in subjects with NAFLD (FLI ≥ 60) (HR 0.27 [95% CI 0.17‐0.45], P < .001).ConclusionProtein‐adjusted serum free thiol levels are reduced and significantly associated with all‐cause mortality in subjects with suspected NAFLD. Quantification of free thiols may be a promising, minimally invasive strategy to improve detection of NAFLD and associated risk of all‐cause mortality in the general population.
Calcium homeostasis plays important roles in the internalization and activities of the small synthetic antifungal peptide PAF26
Authors: Alexander Akira J. T. , Muñoz Alberto , Marcos Jose F. , Read Nick D. 
Published: June 2020

AbstractFungal diseases are responsible for the deaths of over 1.5 million people worldwide annually. Antifungal peptides represent a useful source of antifungals with novel mechanisms‐of‐action, and potentially provide new methods of overcoming resistance. Here we investigate the mode‐of‐action of the small, rationally designed synthetic antifungal peptide PAF26 using the model fungus Neurospora crassa. Here we show that the cell killing activity of PAF26 is dependent on extracellular Ca2+ and the presence of fully functioning fungal Ca2+ homeostatic/signaling machinery. In a screen of mutants with deletions in Ca2+‐signaling machinery, we identified three mutants more tolerant to PAF26. The Ca2+ ATPase NCA‐2 was found to be involved in the initial interaction of PAF26 with the cell envelope. The vacuolar Ca2+ channel YVC‐1 was shown to be essential for its accumulation and concentration within the vacuolar system. The Ca2+ channel CCH‐1 was found to be required to prevent the translocation of PAF26 across the plasma membrane. In the wild type, Ca2+ removal from the medium resulted in the peptide remaining trapped in small vesicles as in the Δyvc‐1 mutant. It is, therefore, apparent that cell killing by PAF26 is complex and unusually dependent on extracellular Ca2+ and components of the Ca2+‐regulatory machinery.
Raymond Williams' Reading of Newman's The Idea of a University
Authors: Phillips Jacob 
Published: June 2020

AbstractThis article engages with an example of Newman's reception in 20th Century thought, in Raymond Williams's Culture and Society from 1958. Williams considers that Newman's wording in The Idea of a University demonstrates a particular moment in the development of the semantic field of the word ‘culture’, which is indicated by the fact Newman does not use the word at an important juncture in his text. Williams also locates Newman in a developing trajectory of English understandings of culture at a point when (what we now term) culture was presented as a surrogate religion. Both of these points are responded to by showing that the word ‘culture’ would not have served the purpose Williams apportions to it for Newman's argument, and that Newman should not be associated with those for whom the domain of culture was emerging as an alternative to religion in the 19th Century. Moreover, this analysis will show that Newman's understanding of what we today term ‘culture’ should be understood in terms of a broader semantic cluster best captured by the word “sensibility”: a set of pervasive tendencies, predispositions, and qualities.
Imaging Approaches for Accurate Determination of the Quadriceps Angle
Authors: Wu Chi‐chuan , Yeow Kee‐min , Yeow Yun‐jen 
Published: June 2020

ObjectivesA retrospective study was conducted using magnetic resonance image (MRI) and a full‐length standing scanogram (FLSS) to measure the quadriceps angle (Q‐angle) while avoiding soft tissue interference.MethodsTwo steps were retrospectively carried out in two case series. The first step involved using MRI to define the standardized patellar center (PC) and the tibial tubercle (TT) on the frontal plane of the MRI in one group of 60 consecutive patients (from July 2016 to December 2016, 29 men and 31 women, average of 46 years). The next step was transferring the location of the standardized PC and the TT from the MRI to the FLSS in another group of 100 consecutive patients (from April 2009 to March 2014, 50 men and 50 women, average of 36 years). The pelvis and intact femur, knee, and tibia were used to determine the Q‐angle on the FLSS.ResultsThe standardized PC was positioned 42% from the lateral end of femur trans‐epicondylar line. The TT was 2 cm distal to the tibial articular surface and 37% from the lateral end of tibial width. The average Q‐angle was 9.5° in 100 patients (8.8° in 50 men and 10.1° in 50 women, P = 0.02). The average femoral length was 42.9 cm in 100 patients (44.7 cm in 50 men and 41.1 cm in 50 women, P < 0.001). Women and men had similar pelvic width (27.9 vs 27.8 cm, P = 0.89).ConclusionUsing the FLSS may help to accurately determine the Q‐angle. Men and women have similar pelvic width. A larger Q‐angle in women may be mainly due to the shorter femur.
Branding as a Public Governance Strategy: A Q Methodological Analysis of How Companies React to Place Branding Strategies
Authors: Stevens Vidar , Klijn Erik Hans , Warsen Rianne 
Published: June 2020

AbstractPublic branding is a new governance strategy in the public sector.Local governments,for instance,use brands to attract target groups to the city,such companies,tourists,or citizens.But how do target groups actually value this governance strategy?This article zooms in on the purpose of branding,as perceived by companies as a target group in a branding campaign.Q methodology is used to study the subjective viewpoints of 33 company owners in a neighborhood in Rotterdam,the Netherlands,that was branded as the Rotterdam Makers District.The analysis reveals that company owners prefer a transparent branding process in which they are recognized as coproducers of the brand and can add their story to the brand message that is conveyed to target audiences.These findings add to the resonating call in the literature to make more use of governance theories in the field of branding.
Do you really need it? Educational mismatch and earnings in Ghana
Authors: Darko Christian K. , Abrokwa Kennedy K. 
Published: June 2020

AbstractThis study examines the effects of educational mismatch on earnings using cross‐sectional data from three rounds of the Ghana Living Standards Survey. There are gender‐earnings differentials, with women suffering a penalty for undereducation that is almost twice that paid by men for having less than the required years of education, although the premium associated with overeducation is higher for women. While the penalty associated with deficit schooling decreases for men over time, this penalty increases for women. Women but not men experience significant increases in returns for attaining the required education. On the contrary, the lack of significance of returns to overeducation over time suggests that human capital beyond the required level is unproductive and may represent a waste of public resources.