bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metformin attenuates the effect of Staphylococcus aureus on airway tight junctions by increasing PKCζ‐mediated phosphorylation of occludin
Authors: Kalsi Kameljit K. , Garnett James P. , Patkee Wishwanath , Weekes Alexina , Dockrell Mark E. , Baker Emma H. , Baines Deborah L. 
Published: November 2018

AbstractAirway epithelial tight junction (TJ) proteins form a resistive barrier to the external environment, however, during respiratory bacterial infection TJs become disrupted compromising barrier function. This promotes glucose flux/accumulation into the lumen which acts as a nutrient source for bacterial growth. Metformin used for the treatment of diabetes increases transepithelial resistance (TEER) and partially prevents the effect of bacteria but the mechanisms of action are unclear. We investigated the effect of metformin and Staphylococcus aureus on TJ proteins, zonula occludins (ZO)‐1 and occludin in human airway epithelial cells (H441). We also explored the role of AMP‐activated protein kinase (AMPK) and PKCζ in metformin‐induced effects. Pretreatment with metformin prevented the S. aureus‐induced changes in ZO‐1 and occludin. Metformin also promoted increased abundance of full length over smaller cleaved occludin proteins. The nonspecific PKC inhibitor staurosporine reduced TEER but did not prevent the effect of metformin indicating that the pathway may involve atypical PKC isoforms. Investigation of TJ reassembly after calcium depletion showed that metformin increased TEER more rapidly and promoted the abundance and localization of occludin at the TJ. These effects were inhibited by the AMPK inhibitor, compound C and the PKCζ pseudosubstrate inhibitor (PSI). Metformin increased phosphorylation of occludin and acetyl‐coA‐carboxylase but only the former was prevented by PSI. This study demonstrates that metformin improves TJ barrier function by promoting the abundance and assembly of full length occludin at the TJ and that this process involves phosphorylation of the protein via an AMPK‐PKCζ pathway.
Whole exome sequencing identified a novel DAG1 mutation in a patient with rare, mild and late age of onset muscular dystrophy‐dystroglycanopathy
Authors: Dai Yi , Liang Shengran , Dong Xue , Zhao Yanhuan , Ren Haitao , Guan Yuzhou , Yin Haifang , Li Chen , Chen Lin , Cui Liying , Banerjee Santasree 
Published: November 2018

AbstractMuscular dystrophy‐dystroglycanopathy (limb‐girdle), type C, 9 (MDDGC9) is the rarest type of autosomal recessive muscular dystrophies. MDDGC9 is manifested with an early onset in childhood. Patients with MDDGC9 usually identified with defective glycosylation of DAG1, hence it is known as “dystroglycanopathies”. Here, we report a Chinese pedigree presented with mild MDDGC9. The proband is a 64 years old Chinese man. In this family, both the proband and proband's younger brother have been suffering from mild and late onset MDDGC9. Muscle biopsy showed that the left deltoid muscle with an advanced stage of dystrophic change. Immunohistochemistry staining of dystrophin, α‐sarcoglycan, β‐sarcoglycan and dysferlin are normal. Molecular genetic analysis of the proband has been done with whole exome sequencing. A homozygous novel missense mutation (c.2326C>T; p.R776C) in the exon 3 of the DAG1 gene has been identified in the proband. Sanger sequencing revealed that this missense mutation is co‐segregated well among the affected and unaffected (carrier) family members. This mutation is not detected in 200 normal healthy control individuals. This novel homozygous missense mutation (c.2326C>T) causes substitution of arginine by cystine at the position of 776 (p.R776C) which is evolutionarily highly conserved. Immunoblotting studies revealed that a significant reduction of α‐dystroglycan expression in the muscle tissue. The novelty of our study is that it is a first report of DAG1 associated muscular dystrophy‐dystroglycanopathy (limb‐girdle), type C, 9 (MDDGC9) with mild and late age of onset. In Chinese population this is the first report of DAG1 associated MDDGC9.
Autotaxin/lysophosphatidic acid signaling mediates obesity‐related cardiomyopathy in mice and human subjects
Authors: Weng Jiakan , Jiang Sheng , Ding Lu , Xu Yi , Zhu Xiongfei , Jin Peifeng 
Published: November 2018

AbstractObesity is associated with increased cardiovascular morbidity and mortality, but the direct signals to initiate or exaggerate cardiomyopathy remain largely unknown. Present study aims to explore the pathophysiological role of autotaxin/lysophosphatidic acid (LPA) in the process of cardiomyopathy during obesity. Through utilizing mouse model and clinical samples, present study investigates the therapeutic benefits of autotaxin inhibitor and clinical correlation to obesity‐related cardiomyopathy. The elevated circulating levels of autotaxin are closely associated with cardiac parameters in mice. Administration with autotaxin inhibitor, PF‐8380 effectively attenuates high fat diet‐induced cardiac hypertrophy, dysfunction and inflammatory response. Consistently, autotaxin inhibition also decreases circulating LPA levels in obese mice. In in vitro study, LPA directly initiates cell size enlargement and inflammation in neonatal cardiomyocytes. More importantly, circulating levels of autotaxin are positively correlated with cardiac dysfunction and hypertrophy in 55 patients. In conclusion, present study uncovers the correlation between circulating autotaxin and cardiac parameters in mice and human patient, and provided solid evidence of the therapeutic application of autotaxin inhibitor in combating obesity‐related cardiomyopathy.
Common mycorrhizal networks activate salicylic acid defense responses of trifoliate orange (Poncirus trifoliata)
Authors: Zhang Yi‐Can , Zou Ying‐Ning , Liu Li‐Ping , Wu Qiang‐Sheng 
Published: November 2018

AbstractCitrus canker, caused by Xanthomonas axonopodis pv. citri (‘Xac’), is an important quarantine disease in citrus crops. Arbuscular mycorrhizal fungi (AMF) form symbiotic interactions with host plants and further affect their disease resistance, possibly by modulating the activity of salicylic acid (SA), a key phytohormone in disease resistance. Common mycorrhizal networks (CMNs) can interconnect plants, but it is not yet clear whether CMNs promote resistance to citrus canker and, if so, whether SA signaling is involved in this process. To test this possibility, we used a two‐chambered rootbox to establish CMNs between trifoliate orange (Poncirus trifoliata) seedlings in chambers inoculated (treated) or not (neighboring) with the AMF, Paraglomus occultum. A subset of the AMF‐inoculated seedlings were also inoculated with Xac (+AMF+Xac). At 2 d post‐inoculation (dpi), compared with the +AMF−Xac treatment, neighboring seedlings in +AMF+Xac treatment had lower expression levels of the SA biosynthetic genes, PtPAL, PtEPS1, and PtPBS3, but higher SA levels, which attributed to the upregulation of PtPAL and PtPBS3 in treated seedlings and the transfer of SA, via CMNs, to the neighboring seedlings. At 4 dpi, the pathogenesis‐related (PR) protein genes, PtPR1, PtPR4, and PtPR5, and the transcriptional regulatory factor gene, PtNPR1, were activated in neighboring seedlings of +AMF+Xac treatment. At 9 dpi, root phenylalanine ammonia‐lyase activity and total soluble phenol and lignin concentrations increased in neighboring seedlings of +AMF+Xac treatment, likely due to the linkage and signal transfer, via CMNs. These findings support the hypothesis that CMNs transfer the SA signal from infected to neighboring healthy seedlings, to activate defense responses and affording protection to neighboring plants against citrus canker infection.
GW5‐Like, a homolog of GW5, negatively regulates grain width, weight and salt resistance in rice
Authors: Tian Peng , Liu Jiafan , Mou Changling , Shi Cuilan , Zhang Huan , Zhao Zhichao , Lin Qibing , Wang Jie , Wang Jiulin , Zhang Xin , Guo Xiuping , Cheng Zhijun , Zhu Shanshan , Ren Yulong , Lei Cailin , Wang Haiyang , Wan Jianmin 
Published: November 2018

AbstractGrain size is an important determinant of yield potential in crops. We previously demonstrated that natural mutations in the regulatory sequences of qSW5/GW5 confer grain width diversity in rice. However, the biological function of a GW5 homolog, named GW5‐Like (GW5L), remains unknown. In this study, we report on GW5L knockout mutants in Kitaake, a japonica cultivar (cv.) considered to have a weak gw5 variant allele that confers shorter and wider grains. GW5L is evenly expressed in various tissues, and its protein product is localized to the plasma membrane. Biochemical assays verified that GW5L functions in a similar fashion to GW5. It positively regulates brassinosteroid (BR) signaling through repression of the phosphorylation activity of GSK2. Genetic data show that GW5L overexpression in either Kitaake or a GW5 knockout line, Kasaorf3 (indica cv. Kasalath background), causes more slender, longer grains relative to the wild‐type. We also show that GW5L could confer salt stress resistance through an association with calmodulin protein OsCaM1‐1. These findings identify GW5L as a negative regulator of both grain size and salt stress tolerance, and provide a potential target for breeders to improve grain yield and salt stress resistance in rice.
Regulating for a reason: Emotion regulation goals are linked to spontaneous strategy use
Authors: Eldesouky Lameese , English Tammy 
Published: November 2018

AbstractObjectiveWe investigated how individual differences in emotion regulation goals predict emotion regulation strategy use in daily life.MethodAcross three studies, we assessed two common types of emotion regulation goals (hedonic, social) and strategies spanning the entire process model of emotion regulation. We conducted two studies using global measures with undergraduates (N = 394; 18–25 years; 69% female; 56% European American) and community members (N = 302; 19–74 years; 50% female; 75% European American), and a nine‐day daily diary study with another community sample (N = 272; 23–85 years; 50% female; 84% European American).ResultsGlobally and in daily life, pro‐hedonic goals were positively associated with all antecedent‐focused strategies (situation selection, situation modification, distraction, and reappraisal), pro‐social goals were positively linked to reappraisal, and impression management goals positively predicted suppression. Contra‐hedonic goals were negatively associated with reappraisal and positively associated with suppression in some studies.ConclusionsThe reasons why people regulate their emotions are predictive of the strategies they use in daily life. These links may be functional, such that people typically use strategies that are suitable for their goals. These findings demonstrate the value of an individual difference approach and highlight the motivational component of emotion regulation.
Place‐based policies, firm productivity, and displacement effects: Evidence from Shenzhen, China
Authors: Koster Hans R.A. , Cheng Fang Fang , Gerritse Michiel , van Oort Frank G. 
Published: November 2018

AbstractDeveloping and transitional countries devote considerable funds to selected areas to stimulate local growth and firm productivity. We examine the impact of place‐based interventions due to the opening of science parks in Shenzhen, China, on firm productivity and factor use. Our identification strategy, exploiting spatial and temporal differencing in firm‐level data, addresses the issues that (a) the selection of science park locations is not random and (b) high‐productivity firms sort themselves into science parks. Firm productivity is approximately 15–25% higher due to the science park policy. The policy also increases local wages and leads to distortions due to job displacement.
Vitamin D and cardiometabolic disorders: a review of current evidence, genetic determinants and pathomechanisms
Authors: Marquina C. , Mousa A. , Scragg R. , de Courten B. 
Published: November 2018

SummaryVitamin D deficiency has been implicated in the pathophysiology of cardiometabolic disorders including obesity, type 2 diabetes mellitus, cardiovascular diseases and polycystic ovary syndrome. Despite a large number of experimental and observational studies supporting a role for vitamin D in these pathologies, randomized controlled trials have reported little to no effect of vitamin D supplementation in the prevention or treatment of these disorders, although some results remain ambiguous. Polymorphisms in genes related to vitamin D metabolism, particularly in the vitamin D receptor and binding protein and the metabolizing enzyme 1‐α‐hydroxylase, have emerged as potential contributors to these divergent results. It is now becoming increasingly recognized that the effects and potential benefits of vitamin D supplementation may vary by several factors including vitamin D deficiency status, ethnicity and/or the presence of genetic variants, which affect individual responses to supplementation. However, these factors have seldom been explored in the available literature. Future trials should consider inter‐individual differences and, in particular, should aim to clarify whether certain subgroups of individuals may benefit from vitamin D supplementation in the context of cardiometabolic health.
Mechanisms underlying UCP1 dependent and independent adipocyte thermogenesis
Authors: Chang Seo‐Hyuk , Song No‐Joon , Choi Jin Hee , Yun Ui Jeong , Park Kye Won 
Published: November 2018

SummaryThe growing focus on brown adipocytes has spurred an interest in their potential benefits for metabolic diseases. Brown and beige (or brite) adipocytes express high levels of uncoupling protein 1 (Ucp1) to dissipate heat instead of generating ATP. Ucp1 induction by stimuli including cold, exercise, and diet increases nonshivering thermogenesis, leading to increased energy expenditure and prevention of obesity. Recently, studies in adipocytes have indicated the existence of functional Ucp1‐independent thermogenic regulators. Furthermore, substrate cycling involving creatine metabolites, cold‐induced N‐acyl amino acids, and oxidized lipids in white adipocytes can increase energy expenditure in the absence of Ucp1. These studies emphasize the need for a better understanding of the mechanisms governing energy expenditure in adipocytes and their potential applications in the prevention of human obesity and metabolic diseases.
Systematic review of olfactory shifts related to obesity
Authors: Peng Mei , Coutts Duncan , Wang Ting , Cakmak Yusuf O. 
Published: November 2018

SummaryObjectiveThe modern food environment is a key driver of rising levels of obesity. While olfaction is known to play a major role in food choice; however, its relationship to obesity is yet to be understood. This review assesses current knowledge of the interaction between obesity and olfaction.MethodsThis review is based on observational studies comparing olfactory abilities across weight groups (N = 10) and clinical studies evaluating olfactory changes following bariatric surgery (N = 9). Meta‐analyses were performed on data collected by a standard olfactory assessment tool (Sniffin΄ Sticks), to test whether olfaction has any association with body weight or bariatric surgery.ResultsThis review synthesizes findings derived from 38 datasets, with a total of 1432 individual olfactory assessments. The meta‐analyses suggest that olfactory function is negatively correlated with body weight. In addition, Roux‐en‐Y gastric bypass patients frequently report olfactory changes, yet more pronounced and immediate shifts have been observed among sleeve gastrectomy recipients.ConclusionsOur review finds strong evidence for the link between olfaction and obesity and indicates that bariatric surgery (particularly the sleeve gastrectomy) is effective in reversing olfactory decline associated with obesity. In conclusion, we present mechanistic models to underpin the observed relationship between olfaction and obesity.
Scleral asymmetry as a potential predictor for scleral lens compression
Authors: Consejo Alejandra , Behaegel Joséphine , Van Hoey Maarten , Iskander D Robert , Rozema Jos J 
Published: November 2018

AbstractPurposeTo identify the position and magnitude of lens compression due to short‐term miniscleral contact lens wear, as well as evaluating the usefulness of scleral asymmetry as a predictor for scleral lens decentered compression.MethodsFourteen healthy subjects (mean ± S.D.: 29.2 ± 6.0 years) wore a highly gas‐permeable spherical haptic miniscleral contact lens during a 5‐h period. Corneo‐scleral height Fourier profilometry was captured using an Eye Surface Profiler (www.eaglet-eye.com) before and immediately after lens removal. Scleral asymmetry, lens compression location and magnitude were processed using custom‐made algorithms, both globally and for scleral quadrants.ResultsMiniscleral contact lenses do not set uniformly on the ocular surface, with the largest decentration seen along the horizontal meridian. The greatest flexural stress exerted by the lens on the ocular surface occurs at the point coinciding with the inner diameter landing point of the lens and not with its overall diameter. Scleral asymmetry was significantly correlated with compression location (R = 0.71, p = 0.002) and compression magnitude (R = 0.81, p < 0.001), showing its potential as compression predictor.ConclusionLarger amounts of scleral asymmetry will lead to more decentration of spherical haptic scleral lenses. Objective and accurate methods, like the one presented here, could help the practitioner prevent cases of scleral blanching or discomfort due to an excessive compression by the lens.
Reflection Without Regress
Authors: Davia Cory 
Published: November 2018

AbstractRegress arguments show that to do something for a reason, one does not have to have reflectively endorsed that reason. This might seem to establish that reflection does not play a fundamental role in agency. This paper argues that this conclusion rests on too narrow a conception of agency. If agents are not just creatures who act for reasons but also creatures who can take ownership of the reasons for which they act, then there is a central role for reflection to play in agency even if it's not the role that philosophers of action have typically envisioned for it.
Hart and the Metaphysics and Semantics of Legal Normativity
Authors: Kramer Matthew H. 
Published: November 2018

AbstractA number of philosophers in recent years have maintained that H. L. A. Hart inThe Concept of Lawpropounded an expressivist account of the semantics of the legal statements that are uttered from the internal viewpoint of the people who run the institutions of legal governance in any jurisdiction. Although the primary aim of this article is to attack the attribution of that semantic doctrine to Hart, the article will begin with some metaphysical matters—the matters of reductionism and naturalism—that often lie behind the development of expressivist approaches to the semantics of normative discourse. After briefly exploring those metaphysical concerns (to which I will return later), the article will begin its main discussion by rehearsing the distinction between the semantics and the pragmatics of utterances. It will then delineate the doctrine of expressivism which the aforementioned philosophers have in mind when they ascribe that doctrine to Hart. Although I will make reference to a few such philosophers, I will focus chiefly on an article by Kevin Toh that has been the fountainhead of all the subsequent attributions of expressivism to Hart. As will be argued herein, Toh and like‐minded philosophers have gone astray in imputing to Hart a semantic version of expressivism. Notwithstanding that Hart’s theory of law can aptly be characterized as expressivist, that characterization is appropriate only when expressivism is understood as an account of the pragmatics of legal statements rather than as an account of their semantics.
Why Legal Formalism Is Not a Stupid Thing
Authors: Troop Paul 
Published: November 2018

AbstractLegal formalism is the foil for many theories of law. Yet formalism remains controversial, meaning that its critics focus on claims that are not central. This paper sets out a view of formalism using a methodology that embraces one of formalism’s most distinct claims, that formalism is a scientific theory of law. This naturalistic view of formalism helps to distinguish two distinct types of formalism, “doctrinal formalism,” the view that judicial behaviour can be represented using rules, and “rule formalism,” the view that judges follow external rules when they are deciding cases. Doctrinal formalism, understood in naturalistic terms, overcomes many of the criticisms that have been levelled at formalism and can also be used to rehabilitate the currently out‐of‐favour “declaratory theory of law.” Doctrinal formalism is also a longstanding view of law, reflecting both what the original formalists thought of law, and what many present‐day doctrinal lawyers seem to believe. The naturalistic methodology is used to show that the main dispute between doctrinal formalism and American legal realism can be explained by a difference of assumptions concerning whether the values of judges are relative to society, or relative to other judges.
Group Vulnerability, Asymmetrical Balance, and Multicultural Recognition
Authors: Macioce Fabio 
Published: November 2018

AbstractIn this paper I argue for a cautious multicultural approach, with specific regard to its implementation as a legal strategy. Such an approach is cautious only because, as I will demonstrate, it stems from an awareness that in some cases, and for different reasons (political, social, as well as legal), other multicultural policies based on minority or group rights do not work. In other words, I will argue for a strategy of recognition that is additional to others, and that can be implemented and juxtaposed with others, in order to offer a better defence of those rights and claims, which other policies do not recognise (or recognise insufficiently).
The association between early specialization and performance level with injury and illness risk in youth elite athletes
Authors: Moseid Christine H. , Myklebust Grethe , Fagerland Morten W. , Bahr Roald 
Published: November 2018

A trend is observed towards more specialized training and selection into talent programs at an early age for youth athletes. Little is known how this might influence the risk of illness and injury. The aim of the study was to assess whether, in a group of youth elite athletes, those specializing early or performing best were at increased risk of incurring injury or illness after entering a specialized Sport Academy High School program. We enrolled 259 16‐year‐old elite athletes. They completed a baseline web‐based questionnaire covering their age at specialization, single‐ versus multi‐sport involvement during the previous 2 years and current performance level (rated by themselves and their coach). Subsequently, the Oslo Sports Trauma Research Centre (OSTRC) questionnaire on health problems was used to self‐report injuries and illnesses weekly for 26 weeks from October to May. In this specialized Sport Academy High School program, 39% of the athletes reported early specialization (at 12 years or younger). However, early specialization did not increase the risk of injury or illness during the 26 weeks, nor did being a single‐sport athlete the previous two years increase this risk. The best performing athletes at the time of enrollment were not at greater risk of becoming injured or ill during the 26 weeks. In conclusion, in a group of youth elite athletes entering a specialized Sport Academy High School program neither early single‐sport specialization nor performance level appears to represent risk factors for injury or illness after enrollment.