bluuebunny/crossref_metadata_2025_split huggingface dataset:
Methylglyoxal-derived posttranslational arginine modifications are abundant histone marks
Authors: Galligan James J. , Wepy James A. , Streeter Matthew D. , Kingsley Philip J. , Mitchener Michelle M. , Wauchope Orrette R. , Beavers William N. , Rose Kristie L. , Wang Tina , Spiegel David A. , Marnett Lawrence J. 
Published: August 2018

Significance
Chromatin comprises the approximately 3 billion bases in the human genome and histone proteins. Histone posttranslational modifications (PTMs) regulate chromatin dynamics and protein transcription to expand the genetic code. Herein we describe the existence of Lys and Arg modifications on histones derived from a glycolytic by-product, methylglyoxal (MGO). These PTMs are abundant modifications, present at similar levels as those of modifications known to modulate chromatin function and leading to altered gene transcription. Using CRISPR-Cas9, we show that the deglycase DJ-1 protects histones from adduction by MGO. These findings demonstrate the existence of a previously undetected histone modification and provide a link between cellular metabolism and the histone code.
Multiproxy evidence for leaf-browsing and closed habitats in extinct proboscideans (Mammalia, Proboscidea) from Central Chile
Authors: González-Guarda Erwin , Petermann-Pichincura Alia , Tornero Carlos , Domingo Laura , Agustí Jordi , Pino Mario , Abarzúa Ana M. , Capriles José M. , Villavicencio Natalia A. , Labarca Rafael , Tolorza Violeta , Sevilla Paloma , Rivals Florent 
Published: August 2018

Significance
The multiproxy approach represents a novel methodology and a unique opportunity to obtain a more detailed view of ancient resource use. Our multiproxy study, carried out on gomphotheres from Chile, widens potential occupied habitats to closed-canopy forests. This habitat variability supports the hypothesis that the diet of gomphotheres appears to be more constrained by resource availability than by the potential dietary range. We strongly recommend the use of a multiproxy approach, where morphology analyses are complemented by other sources of information. This approach prevents misleading conclusions about the origin of the proxy’s signal from arising, such as a leaf-browsing diet inferred from the dental calculus and microwear not necessarily being indicative of humidity.
Screening for genes that regulate the differentiation of human megakaryocytic lineage cells
Authors: Zhu Fangfang , Feng Mingye , Sinha Rahul , Seita Jun , Mori Yasuo , Weissman Irving L. 
Published: August 2018

Significance
Megakaryocyte progenitors (MkPs), derived from hematopoietic stem cells (HSCs), play major roles in hemostasis, thrombosis, inflammation, and vascular biology through generating platelets. However, the regulatory factors involved in MkP differentiation from HSCs are largely unknown. Here, we utilized a unique genomic approach, including the microarray gene expression commons platform, CRISPR/Cas9-mediated gene deletion, lentivirus-mediated gene overexpression, as well as multicolor flow cytometry and functional assays, and identified 10 genes that are highly expressed in MkPs and required for and can promote MkP generation from HSCs. In addition, we found inhibition of histone deacetylase activity increased MkP differentiation. Our results will not only shed light on the regulations of MkPs, but also facilitate efficient generation of MkPs and platelets for clinical applications.
Entropic forces drive clustering and spatial localization of influenza A M2 during viral budding
Authors: Madsen Jesper J. , Grime John M. A. , Rossman Jeremy S. , Voth Gregory A. 
Published: August 2018

Significance
For influenza virus to release from the infected host cell, controlled viral budding must finalize with membrane scission of the viral envelope. Curiously, influenza carries its own protein, M2, which can sever the membrane of the constricted budding neck. Here we elucidate the physical mechanism of clustering and spatial localization of the M2 scission proteins through a combined computational and experimental approach. Our results provide fundamental insights into how M2 clustering and localization interplay with membrane curvature, membrane lateral stresses, and lipid bilayer phase behavior during viral budding to contribute to virion release.
Structure of a patient-derived antibody in complex with allergen reveals simultaneous conventional and superantigen-like recognition
Authors: Mitropoulou Alkistis N. , Bowen Holly , Dodev Tihomir S. , Davies Anna M. , Bax Heather J. , Beavil Rebecca L. , Beavil Andrew J. , Gould Hannah J. , James Louisa K. , Sutton Brian J. 
Published: August 2018

SignificanceWe have discovered that a human antibody can simultaneously bind two molecules of antigen, in this case a grass pollen allergen, one in a conventional manner and the other unconventionally. The two allergen molecules also bridge two identical antibodies. These observations challenge the dogma that one antibody recognizes only a single antigen/allergen epitope. The mechanism of antibody cross-linking seen here may explain the potency of certain allergens in triggering an allergic reaction, extending our understanding of the nature of allergenicity and informing the design of hypoallergenic molecules for allergen immunotherapy. This dual reactivity and potential for cross-linking surface immunoglobulin on B cells suggests mechanisms by which human autoimmune and other diseases might be initiated.
Palmitoylation enables MAPK-dependent proteostasis of axon survival factors
Authors: Summers Daniel W. , Milbrandt Jeffrey , DiAntonio Aaron 
Published: August 2018

Significance
Neurons extend long structures called axons that are highly susceptible to damage and undergo degeneration in many neurological disorders. One strategy for treating these diseases is by elevating the abundance of axon survival factors that suppress axon death. Herein, we describe a protein homeostasis network that regulates axon degeneration by tuning the local levels of axon survival factors. In particular, we find that small-molecule inhibitors targeting a MAPK stress pathway protect axons from pathological degeneration by elevating the local abundance of axon survival factors NMNAT2 and SCG10. Furthermore, we discover that intracellular location imparts sensitivity to distinct protein homeostasis networks. Inactivating multiple nodes in this protein homeostasis network confers maximal therapeutic potential in diseases of axon degeneration.
Mechanisms of enhanced drug delivery in brain metastases with focused ultrasound-induced blood–tumor barrier disruption
Authors: Arvanitis Costas D. , Askoxylakis Vasileios , Guo Yutong , Datta Meenal , Kloepper Jonas , Ferraro Gino B. , Bernabeu Miguel O. , Fukumura Dai , McDannold Nathan , Jain Rakesh K. 
Published: August 2018

Significance
Improved penetration along with accurate prediction and mechanistic understanding of anticancer agent delivery across the blood–brain/blood–tumor barrier (BBB/BTB) are essential for the rational development of effective therapeutic strategies in intracranial malignancies. In this study, we provide insights in drug pharmacokinetics in brain metastases after focused ultrasound-induced BBB/BTB disruption by integrating quantitative microscopy with mathematical modeling. We demonstrate that focused ultrasound-induced BBB/BTB disruption contributes to enhanced interstitial convective transport in solid tumors, in addition to alleviating vascular barriers, and provide evidence of improved penetration of nontargeted and antibody-targeted chemotherapies. Together, our work provides a unified framework for prospective, quantitative, and mechanistic investigation of the penetration of anticancer drugs across the BBB/BTB in brain tumors.
Cyclin E1 and cyclin-dependent kinase 2 are critical for initiation, but not for progression of hepatocellular carcinoma
Authors: Sonntag Roland , Giebeler Nives , Nevzorova Yulia A. , Bangen Jörg-Martin , Fahrenkamp Dirk , Lambertz Daniela , Haas Ute , Hu Wei , Gassler Nikolaus , Cubero Francisco Javier , Müller-Newen Gerhard , Abdallah Ali T. , Weiskirchen Ralf , Ticconi Fabio , Costa Ivan G. , Barbacid Mariano , Trautwein Christian , Liedtke Christian 
Published: August 2018

Significance
The two E-type cyclins E1 and E2 are known to interact with Cdk2 and are thought to trigger cell cycle activity in carcinogenesis. However, the individual contributions of cyclin E1, cyclin E2, and Cdk2 for initiation and progression of hepatocellular carcinoma (HCC) are unknown. In the present study, we discovered that only cyclin E1—but not cyclin E2—is essential for initiation of liver cancer and requires Cdk2. Unexpectedly, advanced liver cancer progression can be mediated in presence of any E-cyclin, but in a Cdk2-independent manner. We identified the specific expression profiles of cyclin E1-dependent and cyclin E1-independent hepatoma cells. These signatures are useful for predicting patient prognosis and for developing novel cyclin E-based HCC therapies.
Adjuvant effect of the novel TLR1/TLR2 agonist Diprovocim synergizes with anti–PD-L1 to eliminate melanoma in mice
Authors: Wang Ying , Su Lijing , Morin Matthew D. , Jones Brian T. , Mifune Yuto , Shi Hexin , Wang Kuan-wen , Zhan Xiaoming , Liu Aijie , Wang Jianhui , Li Xiaohong , Tang Miao , Ludwig Sara , Hildebrand Sara , Zhou Kejin , Siegwart Daniel J. , Moresco Eva Marie Y. , Zhang Hong , Boger Dale L. , Beutler Bruce 
Published: August 2018

Significance
Adjuvants enhance adaptive immune responses, sometimes through unknown mechanisms, and can be used to augment both humoral and cellular responses to cancer antigens. We report the immunological effects of the synthetic chemical adjuvant Diprovocim, which targets the innate immune receptor TLR1/TLR2 in mice and humans. Diprovocim displayed strong adjuvant activity in mice, particularly abetting cellular immune responses. Immunization against a genetically engineered tumor-specific antigen, ovalbumin, when adjuvanted with Diprovocim, inhibited growth of B16 melanoma and prolonged survival in the presence of immune checkpoint blockade by anti–PD-L1; 100% of mice responded to treatment. Our data suggest Diprovocim boosts the success of anti–PD-L1 treatment by increasing the number and activation of tumor-specific CTLs capable of responding to this checkpoint inhibitor.
Protein evolution speed depends on its stability and abundance and on chaperone concentrations
Authors: Agozzino Luca , Dill Ken A. 
Published: August 2018

Significance
Some biological evolution is slow (millions of years), and some is fast (months to years). The speed at which a protein evolves depends on how stable a protein’s folded structure is, how well it avoids aggregation, and how well-chaperoned it is. What are the mechanisms? We compute fitness landscapes by combining a model of protein-folding equilibria with sequence-change dynamics. We find that adapting to a new environment is fastest for proteins that are least stably folded, because those sit on steep downhill parts of fitness potentials. The modeling shows that cells should adapt to warmer environments faster than to colder ones, explains why increasing a protein’s abundance slows cell evolution, and explains how chaperones accelerate evolution by mitigating this effect.
医患互动研究
Authors: Li Fang 
Published: August 2018

抽象
医患互动历来被认为是医疗保健与健康传播的核心，近年来逐渐成为人文社科跨学科研究热点。目前国际范围内医患互动研究已经取得了一定的成果，但同时也展现出新的问题和挑战。本文对过去50年间的海内外医患互动研究进行了梳理和回顾，旨在呈现主要研究方法与视角、发展阶段、以及重要发现与成果。文章分别回顾了国外和国内医患互动研究，分析了国内研究尚存在的不足，并基于此对未来研究提出了建议和展望。主要发现有：（1）国外医患互动研究从1960年代起步，研究视角和方法呈现多元化趋势，相关研究可以被细化分类为：宏观“行为”研究、微观“话语”研究和会话分析研究。（2）国内相关研究始于1980年代后期，经历了萌芽、起步和成熟等三个发展阶段；语言学视角下的相关研究独树一帜，做出独特的贡献。（3）对比发现，国内研究在研究范式、内容和方法等方面有待进一步完善。本文希望能够为相关领域的研究者提供参考，助力学界围绕医患互动展开更深入、系统、具体的理论和实践探讨。
‘Come what come may, Time, and the Houre, runs through the roughest Day’
Authors: Bondi Marina , Sezzi Annalisa 
Published: August 2018

AbstractThe paper maps the lexico-grammatical resources of the representation of time inMacbeth,looking in particular at the way futurity is portrayed. The study is based on concordance analysis of the top full lexical items in frequency lists and of time-related keywords (generated using the other Shakespearian tragedies as a reference corpus). Paying particular attention to the occurrences in Macbeth and his wife’s speeches, the analysis centres on the collocations and semantic preferences of the items identified. The top full lexical items in the wordlist are shown to be related to the notion of time, especially contrasting the present and the future, hence contributing to the pace of the plot in the play. Keywords highlight the connection of the notion of time with the notion of fear and with the impossibility of predicting the future. In general, the analysis depicts a conceptual space in which time and futurity are not connected to hope but to fear, thus creating a menacing universe that has its origins in the protagonist himself, in the tension between deceitful prediction and frustrated volition.
Progressive or not progressive?
Authors: Rautionaho Paula , Deshors Sandra C. 
Published: August 2018

AbstractThis multifactorial analysis of progressive marking contrasts native English to two Asian Englishes and Dutch English. Specifically, we (i) model writers’ constructional choices (progressive vs. non-progressive) across Englishes based on several linguistic predictors simultaneously, (ii) assess how those factors impact the progressive vs. non-progressive alternation, (iii) how several linguistic factors determine, simultaneously, writers’ constructional choices and (iv) how those choices differ across varieties and genres. Based on 4,661 verb constructions from five comparable multi-genre corpora, we ran a logistic regression analysis to determine which factors cause English-speaking populations to differ in their constructional choices and in which specific contexts. While the model strongly predicts speakers’ choices, within individual genres, tense and modality are found to influence speakers’ choices differently. Overall, our results yield nuanced insights into the (dis)similarities among and within ESL/EFL varieties and contribute to the broader issue of the native-foreign-second language continuum across genres.
The progressive form and its functions in spoken learner English
Authors: Meriläinen Lea 
Published: August 2018

Abstract
Present-day English manifests ongoing changes in the frequency and semantic range of the progressive form, which presents a
challenge for foreign language learners. This study examines the frequencies and semantic functions of the progressive in the
Louvain International Database of Spoken English Interlanguage with the aim of finding out to what extent
learners are adopting the ongoing changes. This study analyses the effects of an exposure-rich learning environment by comparing
learners from countries where English is used in varying degrees outside formal educational contexts and by examining intra-corpus
variation between learners who have vs. have not spent time in English-speaking countries. The results reveal that exposure to
English in the home country explains some of the variation in the progressive frequencies, but most of all it shows in the extent
to which the learners have adopted its new semantic uses. By contrast, stay in English-speaking countries was not found to be an
influential variable for all learner groups.
The use of stative progressives by school-age learners of English and the importance of the variable context
Authors: Fuchs Robert , Werner Valentin 
Published: August 2018

AbstractPrevious studies indicate that even advanced learners of English as a Foreign Language and speakers of English as a Second Language extend the progressive to stative verbs, contrary to the predictions of the Aspect Hypothesis (AH). We test this claim based on a corpus of beginning and lower intermediate learner writing produced by speakers of three languages with and three without a progressive. In contrast to previous studies, we measure the frequency of stative progressives using the variable context method, which is frequently used in research on dialectal variation. Results reveal that stative progressives are very rare at the beginning/lower intermediate level, regardless of the presence of a progressive in the learners’ L1, confirming the claim of the AH for beginning and lower intermediate learners. Moreover, stative progressives mostly occur in contexts that are grammatical in native usage, especially in the interlanguage of learners with a progressive in their L1.
“I wanna be a toy”
Authors: Webster Lexi 
Published: August 2018

Abstract
The paradigmatic transgender woman is often negatively oversexualised, pornographised and fetishised in mainstream
conceptualisations and discourses. However, self-sexualisation by transgender individuals is often portrayed as a (sex-)positive
social phenomenon. Little research has been conducted that analyses the self-sexualisation strategies of the multiple
instantiations of gender-variant identity, including transmasculine and non-binary social actors. This paper uses a corpus-informed
socio-cognitive approach to critical discourse studies to identify differences between the self-sexualisation strategies and
underpinning cognitive models of different gender-variant user-groups on Twitter. 2,565 users are coded into five categories: (1)
transfeminine; (2) transmasculine; (3) transsexual; (4) transvestite; (5) non-binary. Findings show that transvestite- and
transsexual-identifying users most closely fit the pornographised and fetishised conceptualisation, whilst non-binary users are the
least self-sexualising user-group.
Corpus linguistics in language and sexuality studies
Authors: Motschenbacher Heiko 
Published: August 2018

AbstractAs an introduction to the special issue, this paper presents an overview of previous corpus linguistic work in the field of language and sexuality and discusses the compatibility of corpus linguistic methodology with queer linguistics as a central theoretical approach in language and sexuality studies. The discussion is structured around five prototypical aspects of corpus linguistics that may be deemed problematic from a poststructuralist, queer linguistic perspective: quantification and associated notions of objectivity, reliance on linguistic forms and formal presence, concentration on highly frequent features, reliance on categories, and highlighting of differences. It is argued that none of these aspects rules out an application of corpus linguistic techniques within queer theoretically informed linguistic work per se and that it is rather the way these techniques are employed that can be seen as more or less compatible with queer linguistics. To complement the theoretical discussion, a collocation analysis of sexual descriptive adjectives in the Corpus of Contemporary American English (COCA) is conducted in an attempt to address some of the issues raised. The concluding section makes suggestions for future research.
Discourses of marriage in same-sex marriage debates in the UK press 2011–2014
Authors: Paterson Laura L. , Coffey-Glover Laura 
Published: August 2018

Abstract
This paper interrogates media representations of same-sex marriage debates in the UK using a combination of corpus linguistics
tools and close reading, and drawing on Queer Linguistics. Following related work by Bachmann
(2011), Baker (2004), and Love and Baker
(2015), we analyse a 1.3 million-word corpus of UK national newspaper texts compiled for the Discourses of Marriage
Research Group. Our corpus stretches from September 2011 and the announcement of a government consultation on same-sex marriage,
to April 2014 when the first same-sex marriages took place. Using a top-down approach we investigate the discourses drawn upon in
same-sex marriage debates (as indexed by keywords and key semantic fields) and uncover the binary social categories used to
normalise social structures and hold the same-sex marriage debate in place. We also consider which social actors are (not) given a
voice and/or agency and discuss how (same-sex) marriage is constituted.
Nonnative accent and the perceived grammaticality of spoken grammar forms
Authors: Ruivivar June , Collins Laura 
Published: August 2018

Abstract
Scholars advocate for more classroom attention to be paid to spoken grammar which deviates from commonly taught rules of writing.
However, these recommendations have not considered potential barriers that learners may encounter when using spoken grammar with
L1 speakers. We investigate one such challenge: the effect of learners’ accents and degree of accentedness on how their use of
these forms is subjectively perceived by L1 speakers. Ten non-expert raters rated the grammatical acceptability of four frequent
spoken grammar forms, read out by 15 speakers (10 L1 Tagalog, 5 L1 English) rated as having heavy, moderate, or no accents. A
one-way ANOVA revealed a significant effect of accent on grammaticality scores. Post-hoc tests showed a strong correlation between
accent and perceived grammaticality, with more accented speakers scoring significantly lower on grammaticality. The discussion
considers implications for spoken grammar teaching, and future research on the relationship between accent and perceived
grammaticality.
Meta-analysis in second language acquisition research
Authors: Ellis Rod 
Published: August 2018

Abstract
Meta-analysis has become increasingly popular in second language acquisition research (SLA) and has provided valuable summative
information about a number of key areas. There are, however, dangers. This article examines a number of key issues that need to be
considered in conducting a meta-analysis – inclusiveness, the heterogeneity of language learners, the definition of the
independent and dependent variables, the need to consider alternative explanations of observed effects, the importance of
examining the quality of the studies included in the analysis, and the apples and oranges problem. These issues are illustrated in
a discussion of number of SLA meta-analyses (e.g. Norris and Ortega, 2000; Plonsky, 2011; Qureshi, 2016; Spada and Tomita, 2010). The article concludes by suggesting a number of factors that
need to be considered in deciding whether to conduct a meta-analysis and when carrying one out. I argue the need for systematic
reviews but suggest that these can often best present their findings in narrative form rather than statistically. I also suggest
that a preliminary narrative account of the findings of s systematic review can indicate whether a meta-analysis is
appropriate.
On over- and underuse in learner corpus research and multifactoriality in corpus linguistics more generally
Authors: Gries Stefan Th. 
Published: August 2018

AbstractThis paper critically discusses how corpus linguistics in general, but learner corpus research in particular, has been dealing with all sorts of frequency data in general, but over- and underuse frequencies in particular. I demonstrate on the basis of learner corpus data the pitfalls of using aggregate data and lacking statistical control that much work is unfortunately characterized by. In fact, I will demonstrate that monofactorial methods have very little to offer at all to research on observational data. While this paper is admittedly very didactic and methodological, I think the discussion of the empirical data offered here – a reanalysis of previously published work – shows how misleading many studies potentially and provides far-reaching implications for much of corpus linguistics and learner corpus research. Ideally/maximally, this paper together with Paquot & Plonsky (2017,Intntl. J. of Learner Corpus Research) would lead to a complete revision of how learner corpus linguists use quantitative methods and study over-/underuse; minimally, this paper would stimulate a much-needed discussion of currently lacking methodological sophistication.