bluuebunny/crossref_metadata_2025_split huggingface dataset:
A French History of ‘Most Shamefull Villanie’
Authors: Patterson Jonathan 
Published: June 2021

Abstract
By the 1580s, fragments of individual suffering in France’s Wars of Religion were being pieced together to form a larger picture within English cultural memory. A significant contribution came from Anne Dowriche’s The French Historie (1589), ostensibly based on the testimonies of Huguenot exiles. The French Historie reverses the villain–hero pairing of Chantelouve’s tragedy (Chapter 11): Charles IX becomes a consummate dissembler, while Coligny (in keeping with Protestant polemical discourse) becomes a blessed martyr. However, Dowriche’s underlying concern is to promote a selective kind of epistemic vigilance (in Relevance Theory, an ‘alertness to error’) in her readers: they must not be blind to the presence of ‘a strange Italian weede’—the villainy of Machiavelli and Catherine de’ Medici—proliferating like a rhizome across European culture.
The Nature and Significance of Culpability
Authors: Brink David O. 
Published: June 2021

AbstractNarrow culpability is the elemental sense of mens rea, which provides the mental or subjective dimension of criminal wrongdoing. Broad culpability is the responsibility condition in virtue of which the agent’s wrongdoing is blameworthy and without which she would be excused. Inclusive culpability is the combination of wrongdoing and responsibility that together make the agent blameworthy and deserving of blame and punishment. Each kind of culpability plays an important role in a broadly retributive rationale for the criminal law that predicates blame and punishment on the fair opportunity to avoid wrongdoing. Different kinds of culpability align with attributability and accountability. Strict liability crimes that permit liability without culpability are rejected.
Countering Public Misinformation
Authors: Lepoutre Maxime 
Published: June 2021

Abstract
This chapter examines how we should counteract the dangers posed by misinformation (such as fake news and conspiracy theories) in public discourse. Legal norms suppressing misinformation are an even less promising response here than with hate speech. Yet speech-based responses also face grave difficulties: the damage wrought by misinformation is often ‘sticky’, or difficult to reverse. The chapter offers two recommendations for counterspeech that targets misinformation. The first draws on the negative/positive distinction introduced in Chapter 3: unlike negative counterspeech, positive counterspeech can rebut misinformation without triggering the properties that render it sticky. This insight casts doubt on the popular practice of online fact-checking. Second, the chapter recommends adopting a diachronic conception of counterspeech: verbally responding to misinformation should be a continuous process, which pre-empts as well as follows misinformation. Only if it takes this diachronic form can counterspeech keep the most resilient types of misinformation, like conspiracy theories, from taking root.
Introduction
Authors: Lyman R. Lee 
Published: June 2021

Abstract
Graphs of quantitative data are analytical tools that facilitate visual thinking. In many disciplines, the use of graphs was preceded by tables summarizing quantitative data. Graphs known by North American archaeologists as “battleship curves” are temporal frequency distributions of relative abundances of specimens in each of several artifact types. They are unimodal frequency distributions known as spindle graphs. In the early 1950s, it was suggested that the idea of spindle graphs was borrowed by archaeologists from paleontology. Archaeologists occasionally used bar graphs and line graphs to diagram change in artifact inventories in the early twentieth century. The questions addressed in this volume are: (i) did North American archaeologists borrow the idea of spindle graphs from paleontology, and (ii) what was the frequency of use by North American archaeologists of each of the various graph types to diagram culture change during the early and middle twentieth century?
Observations on Graphing Prehistory
Authors: Lyman R. Lee 
Published: June 2021

Abstract
Despite years of graphing culture change using different types and styles of diagram, there is minimal discussion of graph grammar—how to construct an effective and efficient graph, and how to decipher a graph of change. Part of the difficulty attending graph decipherment resided in (and continues to reside in) unclear distinction of transformational change from variational change. Models reflecting the former tend to be commonsensical and are similar to Petrie’s classic sequence dating graphs. The difficulty of graph decipherment is exacerbated by parsing temporally continuous variation into discontinuous spatio-temporally bounded units known as artifact types, cultures, phases, periods, stages, etc. These units are reified and (implicitly) conceived as real entities to be discovered for want of a well-developed theory of change and an attendant ontology of how continuously variable phenomena should be parsed into types for analysis. Archaeologists did perfect models of diffusion—the movement of culture traits (ideas or norms manifest as artifact types) across space over time—and built models of how it should be reflected in the archaeological record. A majority of introductory archaeology textbooks published since 1965 typically present graphs of culture change in the form of a spindle graph but with minimal discussion of graph grammar. Texts on regional or continental prehistory typically summarize culture change in spatio-temporal rectangle diagrams, which for pedagogical reasons may be reasonable. A few spindle graphs have been published in other disciplines and, like archaeological spindles, display temporally shifting frequencies.
Social Proximity, Information, and Incentives in Local Bank Lending
Authors: Wang Junbo , Wang Yun , Wu Chunchi , Yang Xiaoguang , Zhao Lin 
Published: June 2021

Abstract
Exploring the role of social proximity in bank lending using a proprietary data set, we uncover evidence of a significant social proximity effect on private information acquisition. Local loan officers have better information to identify higher-quality borrowers through improved screening. This advantage is greater when firms have higher information asymmetry and lower ratings. Results suggest that sociocultural resources drive locals’ informational advantages and improve their lending performance. Importantly, we find that the social proximity advantage interacts with loan officer incentives. Strong evidence suggests that loan officers can be incentivized to use their social proximity advantage to make better loans. (JEL G12, G13)
Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
Nitrogen-influenced competition between the genders of Salix rehderiana
Authors: Song Haifeng , Chen Yao , Cai Zeyu , Wu Xinxin , Zhang Sheng 
Published: June 2021

Abstract
Male and female willow plants show spatial segregation of genders along the environmental gradients. The skewed gender ratio of willows is related not only to altitude, but also to nutrient status and sexual competition, which can affect their growth and defense by altering secondary metabolite production. The relationship between metabolites and nutrients in the two genders of Salix rehderiana was explored in the Gongga Mountain. We found that the gender ratio was altered with a change in soil nitrogen (N) status; in the high N habitats, secondary metabolites accumulated in males. Furthermore, a pot experiment was conducted to test the effect of N supply on gender competition in S. rehderiana. Sufficient N supply stimulated females to produce amino acids and carbon (C)-containing secondary metabolites for maintaining their C-N balance, but extra N for males was used for growth to occupy more space. Nitrogen supply induced foliar nutrient imbalances and growth of opportunistic species, allowing them to outcompete neighbors. Better C allocation and storage in male than female willows would benefit intersexual competitiveness of males if environment N increases. Competition between the genders has a significant correlation with skewed gender ratio, spatial separation and resource utilization. Female willows would suffer fiercer competition for space by males with the increased soil N, which would result in the gender ratio alteration. Therefore, gender ratio of willows is likely to convert to gender balance from female-biased with long-term N deposition in the future.
Can a b/delta fusion protein replace individual b and delta subunits of ATP synthase in Escherichia coli?
Authors: Gajadeera Chathurada Sugeeshvarie , Weber Joachim 
Published: June 2021

ATP synthase is a ubiquitous membrane protein that plays a key role in biological energy metabolism. In Escherichia coli, ATP synthase contains eight different subunits, with a stoichiometry of α3β3γδεab2c10. The stator stalk which is composed of two copies of subunit b and one copy of subunit delta (δ) is the least well understood part of ATP synthase. To get a clearer picture of the role of individual b subunits, construction of a fusion protein between one of the b subunits and δ was the main intention of the project. Such a fusion protein does exist in mycobacteria.A b/δ fusion protein in E. coli ATP synthase was functional and could replace the individual b and δ subunits. If no additional b subunit is present, the fusion protein forms a homodimer, as dimerization of b or the b segment of the fusion protein is necessary to obtain a functional enzyme. Deletion of the N‐terminal transmembrane region in the strain that carries only the bδ fusion protein failed to give ATP synthase, whereas active ATP synthase was seen in the strain that carries both bδ and a second b subunit, showing that not both transmembrane helices are required for activity. Finally, the generation of a C‐terminal truncation in the second b, b’, gave active ATP synthase, showing that, as seen in mycobacteria, also in E. coli the C‐ terminal helix of the second b subunit is expendable. This data suggest that the b subunit is responsible for binding to F1, the b’ subunit for binding to Fo.
Develop Spatially‐ Interactive Multienzyme Complex on Selfassembled DNA Nanostructures
Authors: Fu Jinglin 
Published: June 2021

Cellular activities are directed by complex, multi‐step synthetic pathways. Many of the enzymes in these pathways are spatially organized to improve both the speed and specificity. This abstracts presents a DNA scaffold‐directed strategy to assemble multienzyme systems with precisely controlled orientations and positions. It has increased our understanding of the enzymology for biological metabolic pathways and also provided the tools and design principles for creating efficient man‐made catalytic complexes.As shown in Figure 1, a two‐enzyme Glucose Oxidase (GOx) ‐ Horseradish Peroxidase (HRP) cascade was assembled on rectangular DNA origami tiles with inter‐enzyme distances ranging from 10 to 65 nm. It was observed that the rate of coupled reactions dramatically increased when the two enzymes were positioned very close together (e.g. 10‐nm in Figure 1B) so that the hydration shells of enzymes overlapped. Further, a protein bridge structure was constructed to facilitate the transfer of intermediates between enzymes (Figure 1C). This opens the door for the design of much more efficient multi‐enzyme systems which should find utility in the development of catalysts for the production of high‐value products in industry and bioenergy, as well as diagnostic applications in biomedicine.
Regio‐ and stereo‐selective oxidation of fluorinated substrates by recombinant cytochrome P450 BM3 variants
Authors: Yu Steve S.‐F. , Wu Li‐Lan , Chiang Chih‐Hsiang , Ramu Ravirala , Yang Chung‐Ling , Ng Kok Yaoh , Luo Wen‐I , Chan Sunney I. 
Published: June 2021

We recently showed that, upon the addition of fluorine substituents on n‐octane, van der Waals interactions including dispersion between a ‐CF2‐ and an aromatic π system account for changes in the alkane hydroxylation mediated by variants of recombinant cytochrome P450 BM3. Here, for the first time, we demonstrate that P450 BM3 also recognizes fluorinated C12–C15 chain‐length fatty acids. Despite the fact that residues, Arg47 and Tyr52, exert significant controls for the sub‐terminal hydroxylation via hydrogen bonding interactions at carboxylate ends of these fatty acids, in any case, the fluorine substituent(s) at omega position plays an essential role in the regio‐selective hydroxylation occurred at omega‐3 position through unique van der Waals interactions. For instance, the catalytic turnover of fluorinated lauric acid substrates by recombinant cytochrome P450 BM3 exhibit higher activities than that of their parent substrate. In conclusion, our data suggest that hydrophobic residues in the heme pocket of P450 enzymes are involved in tuning the orientation of substrates and this further leads to the controlled oxidation of aliphatics mediated by high valent iron‐oxo species.This work was supported by Academia Sinica and grants from the National Science Council, R.O.C. (NSC 97–2113‐M‐001–006‐MY3 and 101–2113‐M‐001–007‐MY3).
Deficiency of sphingosine kinase 1 ameliorates hepatic steatosis and inflammation in diet‐induced obesity
Authors: Geng Tuoyu , Sutter Alton , Lewin David , Ross Jessica , Chavin Kenneth D. , Cowart L. Ashley 
Published: June 2021

Obesity‐associated nonalcoholic fatty liver disease (NAFLD) is characterized by a continuum of pathological changes in the liver. Although progression from simple steatosis to the inflammatory stage of NAFLD (i.e. nonalcoholic steatohepatitis/NASH) represents a critical switch from a benign to a harmful status in the progression of NAFLD, the mechanism underlying this switch is little understood. As sphingosine kinase 1 (SK1) catalyzes the biosynthesis of sphingosine‐1‐phosphate, a lipid implicated in inflammation, we hypothesized that deficiency of SK1 might prevent the progression from simple steatosis to NASH in diet‐induced obesity. We thus administrated SK1‐deficient and wild type mice with both high fat diet (HFD) and isocaloric low fat control diet.ResultsSK1 deficiency diminished HFD‐induced pathological changes, including severe lipid accumulation and macrosteatosis, increases in serum alanine aminotransferase activity, immune cell infiltration into liver parenchyma, and induction of inflammatory cytokines. Moreover, SK1 deficiency also attenuated HFD induction of prosteatotic and proinflammatory genes in the liver.ConclusionSK1 is essential to progression from simple steatosis into NASH in diet‐induced obesity. Funding: a VA Merit award and the NIH COBRE in Lipidomics and Pathobiology (P20RR017677), both to LAC, and NIH Grant 1R01DK069369 to KDC.
Mesenchymal stem cell therapy to promote peripheral tissue insulin sensitivity in the high‐fat fed, myocardial infarcted mouse
Authors: Hughey Curtis , Ma Lianli , James Freyja D , Bracy Deanna P , Wasserman David H , Rottman Jeffrey N , Shearer Jane 
Published: June 2021

OBJECTIVEIdentify the influence of mesenchymal stem cell (MSC) therapy on peripheral tissue glucose utilization following a myocardial infarction (MI) and dietary‐induced insulin resistance (IR).METHODSC57BL6 mice were high‐fat fed (HFF) for eight weeks. Mice were then segregated into three groups: HFF‐SHAM mice, HFF‐MI+PBS mice undergoing coronary artery ligation to induce a MI followed by intramyocardial injection of phospho‐buffered saline and the HFF‐MI+MSC group receiving MSCs. HFF groups were age‐matched with chow‐fed mice.RESULTSFive weeks post‐MI, glucose utilization was assessed in the conscious, unrestrained mouse by employing a hyperinsulinemic‐euglycemic (insulin) clamp combined with administration of [14C]‐2‐deoxyglucose. The MSC‐treated, chow‐fed mice displayed elevated glucose uptake in the soleus muscle. High‐fat feeding enhanced the MSC‐effect on insulin sensitivity. Whole body insulin responsiveness was higher in the HFF‐MI+MSC, as indicated by a 1.6‐fold increase in glucose infusion rate compared to HFF‐SHAM mice (n=8–12). Also, tissue‐specific glucose uptake (μg/mg/min) was elevated in the soleus (0.95 vs 1.46; HFF‐SHAM vs. HFF‐MI+MSC), gastrocnemius (0.19 vs 0.27), vastus lateralis (0.11 vs 0.23) and adipose tissue (0.03 vs 0.05).CONCLUSIONSMSC transplantation represents a novel therapy for IR induced by diet and a MI. Funded by CIHR and Killam Trusts.
C3′/C4′‐Stereochemical Effects of Digitoxigenin a‐L‐/a‐D‐Glycoside in Cancer Cytotoxicity
Authors: McKenna Sean , Hinds John 
Published: June 2021

Digitoxin, used for the treatment of congestive heart failure, has more recently been recognized for its potential application in oncology. The mechanism of action occurs via an increase of Ca2+ influx as a result of inhibition of the extracellular Na+/K+‐ATPase pump. In contrast to the cardiotonic effects, less detail is known for the mechanism of antitumor activity. Several studies suggest that in cancer cells, a cardiac glycoside‐bound Na+/K+‐ATPase complex signals via Src‐tyrosine kinase and 1,4,5‐ triphosphoinositol (IP3), ultimately leading to apoptosis. This signaling pathway is believed to occur through specific isoforms of the Na+/K+‐ATPase pump.Using our lead digitoxin analogue (a‐L‐rhamno 1), we conducted a systematic SAR study, focusing on the stereochemistry and functionality of the C3′‐ and C4′‐stereocenters. We examined the cytotoxicity of digitoxin analouges against four different cancer cell lines: NCI‐H460, A549, MCF‐7, and MDA‐MB‐231. MTT assays were performed from nM to M concentrations. This study helps define limits of digitoxin monosaccharide carbohydrate substitution on cytotoxicity and points towards further analogue design. In contrast to substitution at the C‐2,4 and 5‐positions of the carbohydrate, this study shows the potential for C‐3 substitution for Na/K‐ATP‐ase isoform selectivity without loss of activity.
Endosomal sorting of VAMP3 is regulated by Phosphatidylinositol 4‐kinase IIa
Authors: Jovic Marko , Kean Michelle , Gingras Anne‐Claude , Brill Julie , Balla Tamas 
Published: June 2021

Membrane fusion along endocytic pathways is directly dependent on proper distribution of Soluble NSF‐attachment receptors (SNAREs). Although SNAREs are fairly promiscuous in vitro, significant specificity is achieved in vivo through spatial segregation and shielding of SNAREs prior to cognate Q‐SNARE binding. In particular, long R‐SNAREs are capable of autoinhibition, while short R‐SNAREs were shown to associate with phospholipids on vesicular membranes in vitro. However the exact regulation of this process and the potential lipid binding preference in vivo remains elusive.Here we have identified PtdIns4P kinase PI4KIIa as a binding partner of VAMP3, a small recycling R‐SNARE. PI4KIIa depletion resulted in accumulation of VAMP3 on endosomal compartments, inhibited VAMP3 trafficking to perinuclear membranes and reduced the rate of VAMP3‐mediated transferrin recycling. Similarly, acute depletion of PtdIns4P on endosomes significantly impaired VAMP3 sorting. In addition, VAMP3 association with its cognate Q‐SNARE Vti1a decreased upon PI4KIIa depletion.Taken together, these findings reveal a role for phospholipids in small R‐SNARE sorting, corroborating previous in vitro findings. Direct interaction with the lipid kinase PI4KIIa can, therefore, guarantee a localized supply of PtdIns4P to support the lipid requirement of endosomal SNARE function.Supported by the NICHD Intramural program
Biochemical analysis unveils the mechanism of the interaction between Hsp70s and lipids
Authors: McCallister Chelsea , Nikolaidis Nikolas 
Published: June 2021

Hsp70s are molecular chaperones essential for cellular homeostasis and survival. Several Hsp70s associate with cellular membranes, where they bind to specific lipids. The association of Hsp70s with lipids anchors them to the plasma membrane, where they regulate cell signaling, stabilizes the lysosomal membrane, and is required for microautophagy. Despite these essential functions the Hsp70‐ lipid interactions remain largely uncharacterized. To understand the molecular mechanism of these interactions we characterized the binding of HSPA1A, a cytosolic hsp70, to lipids. We determined the binding affinities of recombinant HSPA1A to several negatively charged phospholipids and established that although lipid‐binding is mediated largely by the nucleotide‐binding domain, allosteric communication between the two protein domains is crucial for lipid‐binding. We also determined that a conformational change caused by nucleotide‐binding reduces lipid‐binding, while binding of protein substrates has no effect on the lipid‐binding. Next, we determined that the HSPA1A‐lipid interaction is not purely electrostatic and the protein is most probably embedded in the lipid‐bilayer. Finally, we observed that binding of HSPA1A to lipids alters the refolding activity of the chaperone, which suggests that lipid‐binding could represent a new regulatory mechanism of chaperone function.This project was supported by funds from CSUPERB and CSUF to NN
Spice Synthetic Cannabinoid Drugs: Lung and Adrenal Cell Models
Authors: Vanderpuye Oluseyi Adewale , Smith Toni , Walker Brandon , Gilbert Myrone , Okediji Olatunde 
Published: June 2021

‘Spice’ refers to designer drugs consisting of plant materials spiked with different synthetic mimetics of delta tetrahydrocannabinol, a psychoactive compound in marijuana. The toxicology and bioactivity of many synthetic cannabinoids are unknown including Spice brands: Barely Legal, Brain Storm and Voodoo.It was hypothesized that the ‘Spice’ brands Barely Legal, Brain Storm and Voodoo Child contain different compounds, overlap in biological activities with delta THC and affect cell physiology and morphology. This study sought possible biomarkers for the effects of ‘Spice’. Fluorescence microscopy detected cannabinoid receptor type 2 proteins but not type 1 receptors on A549 and SW‐13 cells. The complement system regulatory proteins CD46 and CD59 but not CD55 were detected on A549 and SW‐13 cells. Glycoconjugate profiles on these cells were characterized by lectin binding. Exposure to delta THC and Barely Legal Spice caused stronger Con A lectin binding to A549 lung cells than did exposure to Brainstorm Spice or control media. This study is the first description of the complement regulatory protein profile of adrenal gland cells and provided carbohydrate structure profiles of A549 and SW‐13 cells as detected by lectin binding. The results will facilitate more detailed analysis of the toxicology and bioactivities of spice.
Production of transgenic mice expressing human protein C
Authors: MIN Kwan‐Sik , NANJIDSUREN TSEVELMAA , Park Chae‐Won , Yun Sung‐Jo 
Published: June 2021

Human protein C (hPC) is a regulator of homeostasis, suggesting its potential use as a therapy for many disease states. Protein C is a zymogen of a serine protease that is activated by thrombin. Protein C, also known as autoprothrombin ¢òA and blood coagulation factor ¢û¢õ, is a zymogenic (inactive) protein, the activated form of which plays an important role in regulating blood clotting, inflammation, cell death and maintaining the permeability of blood vessel walls in humans and other animals. hPC is a 62 KD disulfide‐linked heterodimer consisting of a 21 KD light chain and a 41 KD heavy chain which circulates as an inactive zymogen in plasma.In this study, we focus on generation of hPC transgenic mice. hPC transgenic mice were produced by using micro‐injection method. The hPC cDNA was cloned into pBC1 vector under goat beta‐casein promoter. One‐cell stage embryos microinjected were transferred to 24 recipient mice on day 1 of the estrus cycle. We screened 61 mice by the PCR. Four line transgenic mice were identified and confirmed expression of protein C gene in mammary gland and several organ. We also analyzed the expression of mRNA and protein through the northern blot and western blot in mammary gland of hPC transgenic mice. hPC was localized in the alveolar epithelial cell by immunohistochemistry. Now, we are collecting the milk from the 2 found lines.