bluuebunny/crossref_metadata_2025_split huggingface dataset:
FACELESS HIERARCHY AT NIXTUN-CH'ICH’, PETEN, GUATEMALA
Authors: Pugh Timothy W. , Chan Nieto Evelyn M. , Zygadło Gabriela W. 
Published: September 2019

AbstractSocieties vary in how they approach the challenges of increased population, inequality, and occupational specialization. The city of Nixtun-Ch'ich’ and its satellite, T'up, in Peten, Guatemala exhibit orthogonal urban grids—a trait absent from all other known Maya cities. Such grids require extensive planning and the ability to mobilize the population. The present data suggests that Nixtun-Ch'ich’ was substantially larger than any of the surrounding settlements and was, therefore, a primate center during the Middle Preclassic period. The extensive urban planning of the site, as well as that of T'up suggests centralized planning. Yet, we have not encountered evidence of a central ruler propagated as a unifying symbol of the polity. The gridded public streets and lack of a rulership cult suggest that Nixtun-Ch'ich’ had a more collaborative social system.
Propositions First: Biting Geach's Bullet
Authors: Frápolli M. J. 
Published: September 2019

AbstractTo be a proposition is to possess propositional properties and to stand in inferential relations. This is the organic intuition, [OI], concerning propositional recognition. [OI] is not a circular characterization as long as those properties and relations that signal the presence of propositions are independently identified. My take on propositions does not depart from the standard approach widely accepted among philosophers of language. Propositions are truth-bearers, the arguments of truth-functions (‘not’, ‘or’, ‘and’, ‘if’), the arguments of propositional-attitude verbs (‘know’, ‘believe’, ‘doubt’, ‘assume’, ‘reject’) and the kind of entity capable of standing in inferential relations (which are basically implication and incompatibility). The aim of this paper is to argue for [OI]. In doing so, I will show that even what is probably the most repeated argument against non-descriptivism, the so-called Frege-Geach Argument (FGA), presupposes something like [OI], a presupposition that Geach shares with his critics. Despite the huge success of FGA, a thorough analysis of the actual scope of this argument has yet to be given. I will provide such an analysis in section 3 below. In this paper, I argue that [OI] is a meta-theoretical principle which is neutral with respect to specific metaphysical debates about the nature of propositions, as well as specific proposals about the semantics of declarative sentences.
Global Expressivism by the Method of Differences
Authors: Price Huw 
Published: September 2019

AbstractIn this piece I characterise global expressivism, as I understand it, by contrasting it with five other views: the so-called Canberra Plan; Moorean non-naturalism and platonism; ‘relaxed realism’ and quietism; local expressivism; and response-dependent realism. Some other familiar positions, including fictionalism, error theories, and idealism, are also mentioned, but as sub-cases to one of these five.
The autism-mutated ADNP plays a key role in stress response
Authors: Sragovich Shlomo , Ziv Yarden , Vaisvaser Sharon , Shomron Noam , Hendler Talma , Gozes Illana 
Published: September 2019

AbstractActivity-dependent neuroprotective protein (ADNP), discovered and first characterized in our laboratory (IG), is vital for mammalian brain formation and presents one of the leading genes mutated de novo causing an autistic syndrome, namely the ADNP syndrome. Furthermore, a unique mouse model of Adnp-haploinsufficiency was developed in the laboratory (IG), with mice exhibiting cognitive and social deficiencies. ADNP is regulated by vasoactive intestinal peptide (VIP), and pituitary adenylate cyclase-activating peptide (PACAP). In this respect, PACAP was independently identified as a sexual divergent master regulator of the stress response. Here, we sought to determine the impact of the Adnp genotype and the efficacy of PACAP pre-treatment when subjecting Adnp+/− mice to stressful conditions. Significant sex differences were observed with Adnp+/− males being more susceptible to stress in the object and social recognition tests, and the females more susceptible in the open field and elevated plus maze tests. Splenic Adnp expression and plasma cortisol levels in mice were correlated with cognition (male mice) and anxiety-related behavior. These findings were further translated to humans, with observed correlations between ADNP expression and stress/cortisol content in a young men cohort. Altogether, our current results may establish ADNP as a marker of stress response.
RNA-binding protein CELF6 is cell cycle regulated and controls cancer cell proliferation by stabilizing p21
Authors: Liu Gang , Zhang Qianwen , Xia Li , Shi Mengjuan , Cai Jin , Zhang Haowei , Li Jia , Lin Guanglan , Xie Weidong , Zhang Yaou , Xu Naihan 
Published: September 2019

AbstractCELF6, a member of the CELF family of RNA-binding proteins, regulates muscle-specific alternative splicing and contributes to the pathogenesis of myotonic dystrophy (DM), however the role of CELF6 in cancer cell proliferation is less appreciated. Here, we show that the expression of CELF6 is cell cycle regulated. The cell cycle-dependent expression of CELF6 is mediated through the ubiquitin-proteasome pathway, SCF-β-TrCP recognizes a nonphospho motif in CELF6 and regulates its proteasomal degradation. Overexpression or depletion of CELF6 modulates p21 gene expression. CELF6 binds to the 3′UTR of p21 transcript and increases its mRNA stability. Depletion of CELF6 promotes cell cycle progression, cell proliferation and colony formation whereas overexpression of CELF6 induces G1 phase arrest. The effect of CELF6 on cell proliferation is p53 and/or p21 dependent. Collectively, these data demonstrate that CELF6 might be a potential tumor suppressor, CELF6 regulates cell proliferation and cell cycle progression via modulating p21 stability.
MNS1 variant associated with situs inversus and male infertility
Authors: Leslie Joseph S. , Rawlins Lettie E. , Chioza Barry A. , Olubodun Oluwaseun R. , Salter Claire G. , Fasham James , Jones Hannah F. , Cross Harold E. , Lam Simon , Harlalka Gaurav V. , Muggenthaler Martina M. A. , Crosby Andrew H. , Baple Emma L. 
Published: September 2019

Abstract
Ciliopathy disorders due to abnormalities of motile cilia encompass a range of autosomal recessive conditions typified by chronic otosinopulmonary disease, infertility, situs abnormalities and hydrocephalus. Using a combination of genome-wide SNP mapping and whole exome sequencing (WES), we investigated the genetic cause of a form of situs inversus (SI) and male infertility present in multiple individuals in an extended Amish family, assuming that an autosomal recessive founder variant was responsible. This identified a single shared (2.34 Mb) region of autozygosity on chromosome 15q21.3 as the likely disease locus, in which we identified a single candidate biallelic frameshift variant in MNS1 [NM_018365.2: c.407_410del; p.(Glu136Glyfs*16)]. Genotyping of multiple family members identified randomisation of the laterality defects in other homozygous individuals, with all wild type or MNS1 c.407_410del heterozygous carriers being unaffected, consistent with an autosomal recessive mode of inheritance. This study identifies an MNS1 variant as a cause of laterality defects and male infertility in humans, mirroring findings in Mns1-deficient mice which also display male infertility and randomisation of left–right asymmetry of internal organs, confirming a crucial role for MNS1 in nodal cilia and sperm flagella formation and function.
Dynamic regulation of interregional cortical communication by slow brain oscillations during working memory
Authors: Berger B. , Griesmayr B. , Minarik T. , Biel A. L. , Pinal D. , Sterr A. , Sauseng P. 
Published: September 2019

AbstractTransiently storing information and mentally manipulating it is known as working memory. These operations are implemented by a distributed, fronto-parietal cognitive control network in the brain. The neural mechanisms controlling interactions within this network are yet to be determined. Here, we show that during a working memory task the brain uses an oscillatory mechanism for regulating access to prefrontal cognitive resources, dynamically controlling interactions between prefrontal cortex and remote neocortical areas. Combining EEG with non-invasive brain stimulation we show that fast rhythmical brain activity at posterior sites are nested into prefrontal slow brain waves. Depending on cognitive demand this high frequency activity is nested into different phases of the slow wave enabling dynamic coupling or de-coupling of the fronto-parietal control network adjusted to cognitive effort. This mechanism constitutes a basic principle of coordinating higher cognitive functions in the human brain.
A Bayesian psychophysics model of sense of agency
Authors: Legaspi Roberto , Toyoizumi Taro 
Published: September 2019

AbstractSense of agency (SoA) refers to the experience or belief that one’s own actions caused an external event. Here we present a model of SoA in the framework of optimal Bayesian cue integration with mutually involved principles, namely reliability of action and outcome sensory signals, their consistency with the causation of the outcome by the action, and the prior belief in causation. We used our Bayesian model to explain the intentional binding effect, which is regarded as a reliable indicator of SoA. Our model explains temporal binding in both self-intended and unintentional actions, suggesting that intentionality is not strictly necessary given high confidence in the action causing the outcome. Our Bayesian model also explains that if the sensory cues are reliable, SoA can emerge even for unintended actions. Our formal model therefore posits a precision-dependent causal agency.
Modular enzyme assembly for enhanced cascade biocatalysis and metabolic flux
Authors: Kang Wei , Ma Tian , Liu Min , Qu Jiale , Liu Zhenjun , Zhang Huawei , Shi Bin , Fu Shuai , Ma Juncai , Lai Louis Tung Faat , He Sicong , Qu Jianan , Wing-Ngor Au Shannon , Ho Kang Byung , Yu Lau Wilson Chun , Deng Zixin , Xia Jiang , Liu Tiangang 
Published: September 2019

AbstractEnzymatic reactions in living cells are highly dynamic but simultaneously tightly regulated. Enzyme engineers seek to construct multienzyme complexes to prevent intermediate diffusion, to improve product yield, and to control the flux of metabolites. Here we choose a pair of short peptide tags (RIAD and RIDD) to create scaffold-free enzyme assemblies to achieve these goals. In vitro, assembling enzymes in the menaquinone biosynthetic pathway through RIAD–RIDD interaction yields protein nanoparticles with varying stoichiometries, sizes, geometries, and catalytic efficiency. In Escherichia coli, assembling the last enzyme of the upstream mevalonate pathway with the first enzyme of the downstream carotenoid pathway leads to the formation of a pathway node, which increases carotenoid production by 5.7 folds. The same strategy results in a 58% increase in lycopene production in engineered Saccharomyces cerevisiae. This work presents a simple strategy to impose metabolic control in biosynthetic microbe factories.
High correlation between Zika virus NS1 antibodies and neutralizing antibodies in selected serum samples from normal healthy Thais
Authors: Sornjai Wannapa , Ramphan Suwipa , Wikan Nitwara , Auewarakul Prasert , Smith Duncan R. 
Published: September 2019

AbstractDespite the widespread presence of the mosquito transmitted Zika virus (ZIKV) over much of Southeast Asia, the number of reported cases remains low. One possibility is that residents in Southeast Asia are immunologically protected, although the nature of any such protection remains unclear. This study sought to investigate the presence of antibodies directed to ZIKV NS1 protein in a selected sub-set of samples from a well characterized cohort of serum samples from normal, healthy Thais that had been previously characterized for the presence of neutralizing antibodies to ZIKV, DENV 1-4, and JEV. Because of similarities in molecular weight between the flavivirus E and NS1 proteins, an immunoblot system was established in which the NS1 antigen was not denatured, allowing detection of the dimer form of NS1, distinctly clear from the migration position of the E and NS1 monomer proteins. The results showed that antibodies to ZIKV NS1 protein were only detected in samples with ZIKV neutralizing antibodies (27/30 samples), and no sample (0/30) with a ZIKV plaque reduction neutralization test (PRNT)90 < 20 showed evidence of anti-ZIKV NS1 antibodies. The high correlation between the presence of ZIKV NS1 antibodies and ZIKV PRNT suggests that immunological protection against ZIKV infection in Thailand arises from prior exposure to ZIKV, and not through cross neutralization.
Non-thermal plasma inhibits mast cell activation and ameliorates allergic skin inflammatory diseases in NC/Nga mice
Authors: Lee Myung-Hoon , Lee Yun Sang , Kim Haeng Jun , Han Chang Hak , Kang Sung Un , Kim Chul-Ho 
Published: September 2019

AbstractNon-thermal plasma (NTP) has many functional activities such as, sterilization, wound healing and anti-cancer activity. Despite of its wide spread biomedical application, the effect of NTP on immune cells and allergic response has not been well studied. In this study, we determined whether NTP suppresses mast cell activation, which is important for allergic response, and ameliorates an atopic dermatitis (AD)-like skin inflammatory disease in mice. Exposure to NTP-treated medium during mast cell activation inhibited the expression and production of IL-6, TNF-α and suppressed NF-κB activation. We also investigated whether NTP treatment ameliorates house dust mite (HDM)-induced AD-like skin inflammation in mice. NTP treatment inhibited increases in epidermal thickness and recruitment of mast cells and eosinophils, which are important cell types in AD pathogenesis. In addition, Th2 cell differentiation was induced by application of HDM and the differentiation was also inhibited in the draining lymph node of NTP-treated mice. Finally, the expression of AD-related cytokines and chemokines was also decreased in NTP-treated mice. Taken together, these results suggest that NTP might be useful in the treatment of allergic skin diseases, such as AD.
MR g-ratio-weighted connectome analysis in patients with multiple sclerosis
Authors: Kamagata Koji , Zalesky Andrew , Yokoyama Kazumasa , Andica Christina , Hagiwara Akifumi , Shimoji Keigo , Kumamaru Kanako K. , Takemura Mariko Y. , Hoshino Yasunobu , Kamiya Kouhei , Hori Masaaki , Pantelis Christos , Hattori Nobutaka , Aoki Shigeki 
Published: September 2019

AbstractMultiple sclerosis (MS) is a brain network disconnection syndrome. Although the brain network topology in MS has been evaluated using diffusion MRI tractography, the mechanism underlying disconnection in the disorder remains unclear. In this study, we evaluated the brain network topology in MS using connectomes with connectivity strengths based on the ratio of the inner to outer myelinated axon diameter (i.e., g-ratio), thereby providing enhanced sensitivity to demyelination compared with the conventional measures of connectivity. We mapped g-ratio-based connectomes in 14 patients with MS and compared them with those of 14 age- and sex-matched healthy controls. For comparison, probabilistic tractography was also used to map connectomes based on the number of streamlines (NOS). We found that g-ratio- and NOS-based connectomes comprised significant connectivity reductions in patients with MS, predominantly in the motor, somatosensory, visual, and limbic regions. However, only the g-ratio-based connectome enabled detection of significant increases in nodal strength in patients with MS. Finally, we found that the g-ratio-weighted nodal strength in motor, visual, and limbic regions significantly correlated with inter-individual variation in measures of disease severity. The g-ratio-based connectome can serve as a sensitive biomarker for diagnosing and monitoring disease progression.
Oxidative stress-responsive apoptosis inducing protein (ORAIP) plays a critical role in cerebral ischemia/reperfusion injury
Authors: Kishimoto Masao , Suenaga Jun , Takase Hajime , Araki Kota , Yao Takako , Fujimura Tsutomu , Murayama Kimie , Okumura Ko , Ueno Ryu , Shimizu Nobuyuki , Kawahara Nobutaka , Yamamoto Tetsuya , Seko Yoshinori 
Published: September 2019

AbstractOxidative stress is known to play a critical role in the pathogenesis of various disorders, especially in ischemia/reperfusion (I/R) injury. We identified an apoptosis-inducing humoral factor and named this novel post translationally modified secreted form of eukaryotic translation initiation factor 5A (eIF5A) “oxidative stress-responsive apoptosis inducing protein” (ORAIP). The purpose of this study was to investigate the role of ORAIP in the mechanisms of cerebral I/R injury. Hypoxia/reoxygenation induced expression of ORAIP in cultured rat cerebral neurons, resulting in extensive apoptosis of these cells, which was largely suppressed by neutralizing anti-ORAIP monoclonal antibody (mAb) in vitro. Recombinant-ORAIP induced extensive apoptosis of cerebral neurons. Cerebral I/R induced expression of ORAIP in many neurons in a rat tandem occlusion model in vivo. In addition, we analyzed the effects of intracerebroventricular administration of neutralizing anti-ORAIP mAb on the development of cerebral infarction. Cerebral I/R significantly increased ORAIP levels in cerebrospinal fluid. Treatment with intracerebroventricular administration of neutralizing anti-ORAIP mAb reduced infarct volume by 72%, and by 55% even when started after reperfusion. These data strongly suggest that ORAIP plays a pivotal role and will offer a critical therapeutic target for cerebral I/R injury induced by thrombolysis and thrombectomy for acute ischemic stroke.
Revisiting the use of web search data for stock market movements
Authors: Zhong Xu , Raghib Michael 
Published: September 2019

AbstractAdvances in Big Data make it possible to make short-term forecasts for market trends from previously unexplored sources. Trading strategies were recently developed by exploiting a link between the online search activity of certain terms semantically related to finance and market movements. Here we build on these earlier results by exploring a data-driven strategy which adaptively leverages the Google Correlate service and automatically chooses a new set of search terms for every trading decision. In a backtesting experiment run from 2008 to 2017 we obtained a 499% cumulative return which compares favourably with benchmark strategies. A crowdsourcing exercise reveals that the term selection process preferentially selects highly specific terms semantically related to finance (e.g. Wells Fargo Bank), which may capture the transient interests of investors, but at the cost of a shorter span of validity. The adaptive strategy quickly updates the set of search terms when a better combination is found, leading to more consistent predictability. We anticipate that this adaptive decision framework can be of value not only for financial applications, but also in other areas of computational social science, where linkages between facets of collective human behavior and online searches can be inferred from digital footprint data.
Le placebo à l’hôpital
Authors: Héron Anne , Leroux Christophe , Dubayle David 
Published: September 2019

Un placebo est défini comme un traitement sans efficacité pharmacologique propre qui agit, lorsque le patient pense recevoir un traitement actif, par des mécanismes psychologiques et physiologiques. Notre étude avait pour but d’évaluer l’utilisation du placebo dans les unités de médecine polyvalente des hôpitaux français. Pour cela, un questionnaire comprenant 15 items a été transmis à plusieurs unités. L’analyse des réponses reçues confirme que l’utilisation de placebos à l’hôpital est fréquente, près des deux tiers des professionnels ayant répondu déclarent en faire usage. L’administration du placebo en gélule par voie orale est la forme la plus couramment utilisée. À l’hôpital, il est administré principalement la nuit, le plus souvent sans prescription médicale, en cas de douleur, d’insomnie ou d’anxiété, à des patients dits « difficiles » (solliciteurs d’attention et de soin). Dans la plupart des cas, les patients ne sont pas informés qu’il s’agit d’un placebo. La majorité des professionnels « croit » en l’effet placebo, mais se considèrent cependant insuffisamment informés et formés à son utilisation. Fréquemment utilisé à l’hôpital, son efficacité thérapeutique étant largement admise, des considérations éthiques et juridiques imposent de recommander que sa nature soit précisée au patient lors de sa prescription (au même titre que les autres préparations hospitalières). On parlera alors de « placebo ouvert », c’est-à-dire que des explications sur les effets et les mécanismes d’action du placebo seront données au patient. Des études récentes montrent que dire au patient qu’il reçoit un placebo ouvert n’affecte en rien son effet.
Syndrome néphrotique idiopathique et facteurs circulants
Authors: Lorenzo Hans-Kristian , Candelier Jean-Jacques 
Published: September 2019

La fonction d’excrétion du rein fait intervenir des glomérules chargés de filtrer sélectivement le sang. L’acteur principal du filtre glomérulaire est le podocyte dont les pédicelles entrelacés portent des complexes moléculaires (néphrine, podocine, etc.) qui sont responsables du fonctionnement de la barrière de filtration (diaphragme de fente). Des altérations de ces podocytes entraînent une protéinurie massive qui caractérise le syndrome néphrotique. Parmi les formes les plus malignes de cette pathologie, se trouve le syndrome néphrotique idiopathique dont la physiopathologie reste inconnue. Ce syndrome regroupe essentiellement deux entités : les lésions glomérulaires minimes et la hyalinose segmentaire et focale. Ces pathologies impliqueraient les cellules du système immunitaire et plusieurs facteurs de perméabilité circulants qui agiraient sur la morphologie et le fonctionnement des podocytes.
Les fonctions de l’innervation sympathique artérielle
Authors: Simonnet Émilie , Brunet Isabelle 
Published: September 2019

L’innervation sympathique artérielle (ISA) est un processus biologique complexe nécessitant un guidage fin des axones des neurones sympathiques par les artères. L’ISA est un élément clé de l’adaptation du système cardiovasculaire aux différentes contraintes (exposition au froid, exercice, etc.) : elle contrôle le diamètre des artères de résistance, donc le flux sanguin parvenant aux organes et la pression artérielle systémiqueviala modulation du tonus artériel. Son importance lors du vieillissement et dans de nombreux contextes pathologiques est de mieux en mieux reconnue et comprise. Son intégration à la prise en charge de nombreuses maladies (hypertension, cancer, etc.) permettrait d’en améliorer traitements et pronostic.