bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mapping the functional anatomy of Orai1 transmembrane domains for CRAC channel gating
Authors: Yeung Priscilla S.-W. , Yamashita Megumi , Ing Christopher E. , Pomès Régis , Freymann Douglas M. , Prakriya Murali 
Published: May 2018

Significance
Store-operated Orai1 channels mediate transcriptional, proliferative, and effector-cell programs in many cells. Mutations in Orai1 that block channel activation or evoke constitutive channel activity are known to cause debilitating diseases in humans such as immunodeficiency, autoimmunity, myopathy, and thrombocytopenia. However, our understanding of the underlying molecular mechanisms of these diseases is limited by fundamental gaps in how Orai1 channels are gated. Here, we map key functional interactions between the transmembrane domains of Orai1 and identify several contacts that are critical for conveying the STIM1 gating signal to the pore. Our findings illuminate important allosteric interactions between topologically distinct domains of Orai1 and help elucidate the molecular underpinnings of disease-causing mutations.
A cytokine network involving IL-36γ, IL-23, and IL-22 promotes antimicrobial defense and recovery from intestinal barrier damage
Authors: Ngo Vu L. , Abo Hirohito , Maxim Estera , Harusato Akihito , Geem Duke , Medina-Contreras Oscar , Merlin Didier , Gewirtz Andrew T. , Nusrat Asma , Denning Timothy L. 
Published: May 2018

Significance
Cytokines are produced in response to microbial threat and aid in the recruitment and activation of immune cells to protect the host. Using complementary in vitro and in vivo approaches, we have defined a cytokine network involving IL-36γ, IL-23, and IL-22 that is induced following intestinal damage and is critical for antimicrobial activity, tissue repair, and host survival. Our data identify IL-36γ/IL-36 receptor signaling as a central upstream driver of the IL-23/IL-22/antimicrobial peptide (AMP) pathway during intestinal injury and advance the concept that IL-36γ and IL-23 are fundamentally linked to repair of acute barrier damage. These findings provide new mechanistic insight into how the host commandeers proinflammatory cytokines for tissue repair and highlight the potential for manipulating the IL-36/IL-23/IL-22/AMP network in treating acute intestinal damage.
Comprehensive phylogeny of ray-finned fishes (Actinopterygii) based on transcriptomic and genomic data
Authors: Hughes Lily C. , Ortí Guillermo , Huang Yu , Sun Ying , Baldwin Carole C. , Thompson Andrew W. , Arcila Dahiana , Betancur-R. Ricardo , Li Chenhong , Becker Leandro , Bellora Nicolás , Zhao Xiaomeng , Li Xiaofeng , Wang Min , Fang Chao , Xie Bing , Zhou Zhuocheng , Huang Hai , Chen Songlin , Venkatesh Byrappa , Shi Qiong 
Published: May 2018

Significance
Ray-finned fishes form the largest and most diverse group of vertebrates. Establishing their phylogenetic relationships is a critical step to explaining their diversity. We compiled the largest comparative genomic database of fishes that provides genome-scale support for previous phylogenetic results and used it to resolve further some contentious relationships in fish phylogeny. A vetted set of exon markers identified in this study is a promising resource for current sequencing approaches to significantly increase genetic and taxonomic coverage to resolve the tree of life for all fishes. Our time-calibrated analysis suggests that most lineages of living fishes were already established in the Mesozoic Period, more than 65 million years ago.
Cochlear amplification and tuning depend on the cellular arrangement within the organ of Corti
Authors: Motallebzadeh Hamid , Soons Joris A. M. , Puria Sunil 
Published: May 2018

Significance
While the near-crystalline structure of the organ-of-Corti cytoarchitecture in the mammalian cochlea has been known for some time, its functional consequences on hearing remain to be established. The present computational-modeling studies show that individual outer hair cells (OHCs) can work together to produce high hearing sensitivity and frequency selectivity because of the overlapping asymmetrical Y-shaped structures that they form with the Deiters’ cells (DCs) and phalangeal processes (PhPs). Altering the geometry and material properties of these structures reveals that all three components have a profound effect on basilar-membrane and reticular-lamina amplification and tuning. One implication is that the DCs and PhPs are not just supporting structures, but that they must also be properly restored in emerging therapies to regenerate OHCs.
Lead pollution recorded in Greenland ice indicates European emissions tracked plagues, wars, and imperial expansion during antiquity
Authors: McConnell Joseph R. , Wilson Andrew I. , Stohl Andreas , Arienzo Monica M. , Chellman Nathan J. , Eckhardt Sabine , Thompson Elisabeth M. , Pollard A. Mark , Steffensen Jørgen Peder 
Published: May 2018

SignificanceAn 1100 BCE to 800 CE record of estimated lead emissions based on continuous, subannually resolved, and precisely dated measurements of lead pollution in deep Greenland ice and atmospheric modeling shows that European emissions closely varied with historical events, including imperial expansion, wars, and major plagues. Emissions rose coeval with Phoenician expansion and accelerated during expanded Carthaginian and Roman lead–silver mining primarily in the Iberian Peninsula. Emissions fluctuated synchronously with wars and political instability, particularly during the Roman Republic, reaching a sustained maximum during the Roman Empire before plunging in the second century coincident with the Antonine plague, and remaining low for >500 years. Bullion in silver coinage declined in parallel, reflecting the importance of lead–silver mining in ancient economies.
The glycolipid GM1 reshapes asymmetric biomembranes and giant vesicles by curvature generation
Authors: Dasgupta Raktim , Miettinen Markus S. , Fricke Nico , Lipowsky Reinhard , Dimova Rumiana 
Published: May 2018

Significance
The multifaceted involvement of GM1 as a ligand in many cellular functions has been well recognized. We find that GM1 readily desorbs from the membrane of cell-sized model biomimetic systems (giant unilamellar vesicles). The desorption is unbalanced, creating an asymmetry between the bilayer leaflets. This results in reshaping weakly curved membranes into nanotubular invaginations stabilized by the membrane spontaneous curvature, which we quantify experimentally. Computer simulations confirm the experimental results. Uncovering the role of GM1 as a fine regulator of membrane curvature broadens our perspective on its important function in reshaping neuronal membranes and emphasizes that GM1 desorption can strongly affect the cell membrane morphology.
Additive-free carbon nanotube dispersions, pastes, gels, and doughs in cresols
Authors: Chiou Kevin , Byun Segi , Kim Jaemyung , Huang Jiaxing 
Published: May 2018

SignificanceCarbon nanotubes can now be produced in the ton scale in the form of powders, but they need to be further processed, usually by solution-based routes, into disaggregated and more usable forms for applications. There has been extensive effort to search and design solvents that can disperse nanotubes, which can also be easily removed afterward. Here, we report thatm-cresol and its liquid mixtures with other isomers, which are already manufactured for other industrial purposes, are such solvents. They can disperse carbon nanotube powders of many types at unprecedentedly high concentrations, rendering them polymer-like rheological and viscoelastic properties, and high processability. This makes carbon nanotube powders immediately usable by current materials-processing techniques for creating desirable structures or composites.
Corticoinsular circuits encode subjective value expectation and violation for effortful goal-directed behavior
Authors: Arulpragasam Amanda R. , Cooper Jessica A. , Nuutinen Makiah R. , Treadway Michael T. 
Published: May 2018

Significance
The ability to form value estimates is crucial for optimal decision making, especially when not all features of a choice option are known. To date, however, the neural mechanisms for expectation processes under conditions of incomplete information are unknown. Using computational fMRI, we show that ventromedial prefrontal cortex encodes the expected value of a trial. We also observe a distinct network composed of dorsal anterior cingulate, anterior insula, and dorsomedial caudate that encodes an expectation violation or prediction error signal, based on previous trial history. These findings highlight how the brain computes and monitors value-based predictions during effortful goal-directed behavior when choice-relevant information is not fully available.
Hydrogel delivery of lysostaphin eliminates orthopedic implant infection by
Staphylococcus aureus
and supports fracture healing
Authors: Johnson Christopher T. , Wroe James A. , Agarwal Rachit , Martin Karen E. , Guldberg Robert E. , Donlan Rodney M. , Westblade Lars F. , García Andrés J. 
Published: May 2018

Significance
Orthopedic implant infections require long-term antibiotic therapy and surgical debridement to successfully retain the implant; however, therapeutic failure can lead to implant removal. Here an injectable PEG-based hydrogel that adheres to exposed tissue and fracture surfaces is engineered to deliver the antimicrobial enzyme lysostaphin to infected, implant-fixed, mouse femoral fractures. Lysostaphin encapsulation within the hydrogel enhances enzyme stability while providing enhanced antibiofilm activity and serving as a controlled delivery platform. In a preclinical animal model of orthopedic-implant infection, we show that lysostaphin-delivering hydrogels outperform prophylactic antibiotic therapy and soluble lysostaphin, by eradicating infection while promoting bone repair. Importantly, lysostaphin-delivering hydrogels are effective against antibiotic-resistant infections. This lysostaphin delivery platform could be highly effective at treating and preventing implant infections.
Heterometallic Ru–Pt metallacycle for two-photon photodynamic therapy
Authors: Zhou Zhixuan , Liu Jiangping , Rees Thomas W. , Wang Heng , Li Xiaopeng , Chao Hui , Stang Peter J. 
Published: May 2018

Significance
Photodynamic therapy is a noninvasive medical procedure in which malignant tissue is damaged by reactive oxygen species generated from targeted light irradiation on a photosensitizer. Herein, we incorporate an Ru(II)-based two-photon photosensitizer into a macrocyclic structure via coordination-driven self-assembly. Properties favorable for photodynamic therapy arise upon formation of the metallacycle, including near-infrared luminescence, strong two-photon absorption, high reactive oxygen species generation efficiency, and selective accumulation in mitochondria and nucleus that are hypersensitive to reactive oxygen species, resulting in good photodynamic therapy efficacy in both in vitro and in vivo investigations. This study shows that supramolecular coordination complexes provide a platform for efficient tuning on the photophysical and biological properties of molecules with biomedical interest.
Broad receptor engagement of an emerging global coronavirus may potentiate its diverse cross-species transmissibility
Authors: Li Wentao , Hulswit Ruben J. G. , Kenney Scott P. , Widjaja Ivy , Jung Kwonil , Alhamo Moyasar A. , van Dieren Brenda , van Kuppeveld Frank J. M. , Saif Linda J. , Bosch Berend-Jan 
Published: May 2018

SignificanceCoronaviruses exhibit a propensity for interspecies transmission, with SARS- and MERS-coronaviruses as notable examples. Cross-species transmission by coronaviruses is foremost determined by the virus’ ability to bind receptors of new hosts. We here report that the recently identified, yet globally distributed porcine deltacoronavirus employs host aminopeptidase N (APN) as an entry receptor via S protein-mediated interaction with an interspecies conserved domain that allows for APN orthologue-mediated entry. Identification of APN as a deltacoronavirus receptor emphasizes the remarkable preferential employment of cell surface host peptidases as receptors by coronaviruses. Our findings provide important insight into how receptor usage of coronaviruses may fuel cross-host transmission between distantly related species and necessitate surveillance studies of deltacoronaviruses in thus far unappreciated potential reservoirs, including humans.
PRDM1 silences stem cell-related genes and inhibits proliferation of human colon tumor organoids
Authors: Liu Changlong , Banister Carolyn E. , Weige Charles C. , Altomare Diego , Richardson Joseph H. , Contreras Carlo M. , Buckhaults Phillip J. 
Published: May 2018

Significance
Our previous studies demonstrated that PRDM1β is activated by p53 accumulation in human colorectal cancer cells. However, the function of PRDM1β in colorectal cancer cells and colon tumor organoids is not clear. Here we show that PRDM1β is a p53-response gene in human colon organoids and that low PRDM1 expression predicts poor survival in colon cancer patients. Also, PRDM1α and PRDM1β proteins repress a largely overlapping suite of genes, many of which are stem cell-related genes. Moreover, we show that forced expression of PRDM1β prevents the proliferation of colon tumor organoids. This work provides support for a role of PRDM1β in regulating normal colon stem cell proliferation.
Temperature regulates NF-κB dynamics and function through timing of A20 transcription
Authors: Harper C. V. , Woodcock D. J. , Lam C. , Garcia-Albornoz M. , Adamson A. , Ashall L. , Rowe W. , Downton P. , Schmidt L. , West S. , Spiller D. G. , Rand D. A. , White M. R. H. 
Published: May 2018

Significance
Inflammation is often accompanied by temperature change, but little is known about the role of temperature in the inflammatory response. We show that physiologically relevant temperature changes significantly perturb NF-κB dynamics following TNFα stimulation in single cells. Using experimentation informed by mathematical modeling, we found that these changes were mediated, at least in part, through the key feedback gene TNFAIP3/A20. Curtailing A20 expression removed temperature sensitivity across the fever range (37 °C to 40 °C). Gene expression was generally unaffected between these temperatures, although a select set of NF-κB−regulated genes was up-regulated at early time points. These genes were predominantly involved in inflammation, signaling, and cell fate. The cellular response to inflammation may therefore be mechanistically and functionally regulated by temperature.
Adjective stacking in Early Modern English
Authors: González-Díaz Victorina 
Published: May 2018

Abstract
Previous scholarship dates the development of stacked modification in English to the late Middle English period and the operationalisation of the modern NP functional structure to the end of the seventeenth century (Fischer 2006; Feist 2012). These studies have mainly focused on linguistic factors playing a role in the change, although observing briefly that socio-stylistic considerations also play a role in the development of stacked strings. Through a descriptive, corpus-based study of two-adjective strings in early Modern English, this paper begins to explore the influence of socio-stylistic matters on the change. The results suggest that the functional-stylistic demands of written genres may have favoured the establishment of particular stacked strings in English and this paper argues for a careful consideration of ‘developing’ genres in early Modern English (especially travelogues) as an important locus of change in the evolution of the English premodifying string.
That-complementiser omission in N + be + that-clauses
Authors: Mantlik Annette , Schmid Hans-Jörg 
Published: May 2018

Abstract
The omission of the complementiser that after lexical verbs, as in I think she went home or I guess she did not enjoy herself, has been studied intensively from a diachronic and synchronic perspective. In contrast, that-complementiser omission in other contexts (e.g. the truth is she never wanted to come anyway or the problem is she does not like these people) has not received much attention. We report the results of a multi-level corpus-based study investigating the diachronic development of the omission of that in the N + BE + that construction. The study is framed in the light of two competing hypotheses suggested by research on that-omission in verb complementation: the assumption that the omission is mainly a matter of stylistic choice and the assumption that it represents a case of diachronic change that can be described as constructional change or even constructionalisation. In order to test these hypotheses, we carry out a quantitative and qualitative analysis of a large dataset extracted from the Corpus of Historical American English. The results suggest that both factors are involved but shift in importance over time. While stylistic choice may have been the original motivation for the omission of that, the later development shows evidence for constructional change and signs indicating the beginning of further changes that could eventually lead to the emergence of a new construction by means of constructional split.
The association between discrimination and health: findings on Russian, Somali and Kurdish origin populations in Finland
Authors: Rask Shadia , Elo Irma T , Koskinen Seppo , Lilja Eero , Koponen Päivikki , Castaneda Anu E 
Published: May 2018

Abstract

Background
The Second European Union Minorities and Discrimination Survey recently demonstrated widespread discrimination across EU countries, with high discrimination rates observed in countries like Finland. Discrimination is known to negatively impact health, but fewer studies have examined how different types of perceived discrimination are related to health.

Methods
This study examines (i) the prevalence of different types of perceived discrimination among Russian, Somali and Kurdish origin populations in Finland, and (ii) the association between different types of perceived discrimination (no experiences; subtle discrimination only; overt or subtle and overt discrimination) and health (self-rated health; limiting long-term illness (LLTI) or disability; mental health symptoms). Data are from the Finnish Migrant Health and Wellbeing Study (n = 1795). Subtle discrimination implies reporting being treated with less courtesy and/or treated with less respect than others, and overt discrimination being called names or insulted and/or threatened or harassed. The prevalence of discrimination and the associations between discrimination and health were calculated with predicted margins and logistic regression.

Results
Experiences of subtle discrimination were more common than overt discrimination in all the studied groups. Subtle discrimination was reported by 29% of Somali origin persons and 35% Russian and Kurdish origin persons. The prevalence of overt discrimination ranged between 22% and 24%. Experiences of discrimination increased the odds for poor self-reported health, LLTI and mental health symptoms, particularly among those reporting subtle discrimination only.

Conclusions
To promote the health of diverse populations, actions against racism and discrimination are highly needed, including initiatives that promote shared belonging.
Physical activity promotion in primary care: a Utopian quest?
Authors: Lion Alexis , Vuillemin Anne , Thornton Jane S , Theisen Daniel , Stranges Saverio , Ward Malcolm 
Published: May 2018

Abstract
The health benefits of physical activity (PA) are acknowledged and promoted by the scientific community, especially within primary care. However, there is little evidence that such promotion is provided in any consistent or comprehensive format. Brief interventions (i.e. discussion, negotiation or encouragement) and exercise referral schemes (i.e. patients being formally referred to a PA professional) are the two dominant approaches within primary care. These cost-effective interventions can generate positive changes in health outcomes and PA levels in inactive patients who are at increased risk for non-communicable diseases. Their success relies on the acceptability and efficiency of primary care professionals to deliver PA counselling. To this end, appropriate training and financial support are crucial. Similarly, human resourcing and synergy between the different stakeholders must be addressed. To obtain maximum adherence, specific populations should be targeted and interventions adapted to their needs. Key enablers include motivational interviewing, social support and multi-disciplinary approaches. Leadership and lines of accountability must be clearly delineated to ensure the success of the initiatives promoting PA in primary care. The synergic and multisectoral action of several stakeholders, especially healthcare professionals, will help overcome physical inactivity in a sustainable way.
The adoption, implementation and maintenance of a school food policy in the Canadian Arctic: a retrospective case study
Authors: Fournier Bonnie , Illasiak Velma , Kushner Kaysi Eastlick , Raine Kim 
Published: May 2018

Summary
With increasing childhood obesity rates and type 2 diabetes developing in younger age groups, many schools have initiated policies to support healthy eating and active living. Policy interventions can influence not only health behaviours in students but can also impact these behaviours beyond the school walls into the community. We articulate a policy story that emerged during the data collection phase of a study focused on building knowledge and capacity to support healthy eating and active living policy options in a small hamlet located in the Canadian Arctic. The policy processes of a local school food policy to address unhealthy eating are discussed. Through 14 interviews, decision makers, policy influencers and health practitioners described a policy process, retrospectively, including facilitators and barriers to adopting and implementing policy. A number of key activities facilitated the successful policy implementation process and the building of a critical mass to support healthy eating and active living in the community. A key contextual factor in school food policies in the Arctic is the influence of traditional (country) foods. This study is the first to provide an in-depth examination of the implementation of a food policy in a Canadian Arctic school. Recommendations are offered to inform intervention research and guide a food policy implementation process in a school environment facing similar issues.
Introduction to Methodology: Virtual Special Issue for the Journal of Design History 2018
Authors: Huppatz D J 
Published: May 2018

Abstract
Design historians generally avoid extended self-reflection or discussion of how they conduct research. Typically, they use historical research methods, yet design historians have also used methods borrowed from art history, cultural and literary studies, anthropology, sociology or other social sciences. This Virtual Special Issue, comprising articles drawn from past issues of the Journal of Design History, addresses the state of design history’s methodology. While few authors in the Journal have focused specifically on the topic of methodology, their implicit adoption of an eclectic variety of research methods over the past thirty years is revealing. This Introduction seeks to contextualize a collection of twelve articles within a brief overview of methodologies in history, art history and design history. The articles are then linked to scholarship beyond the Journal of Design History, and the final section presents additional methodological possibilities for design historians.