bluuebunny/crossref_metadata_2025_split huggingface dataset:
BAP1 complex promotes transcription by opposing PRC1-mediated H2A ubiquitylation
Authors: Campagne Antoine , Lee Ming-Kang , Zielinski Dina , Michaud Audrey , Le Corre Stéphanie , Dingli Florent , Chen Hong , Shahidian Lara Z. , Vassilev Ivaylo , Servant Nicolas , Loew Damarys , Pasmant Eric , Postel-Vinay Sophie , Wassef Michel , Margueron Raphaël 
Published: January 2019

AbstractIn Drosophila, a complex consisting of Calypso and ASX catalyzes H2A deubiquitination and has been reported to act as part of the Polycomb machinery in transcriptional silencing. The mammalian homologs of these proteins (BAP1 and ASXL1/2/3, respectively), are frequently mutated in various cancer types, yet their precise functions remain unclear. Using an integrative approach based on isogenic cell lines generated with CRISPR/Cas9, we uncover an unanticipated role for BAP1 in gene activation. This function requires the assembly of an enzymatically active BAP1-associated core complex (BAP1.com) containing one of the redundant ASXL proteins. We investigate the mechanism underlying BAP1.com-mediated transcriptional regulation and show that it does not participate in Polycomb-mediated silencing. Instead, our results establish that the function of BAP1.com is to safeguard transcriptionally active genes against silencing by the Polycomb Repressive Complex 1.
A brain-wide functional map of the serotonergic responses to
acute stress and fluoxetine
Authors: Grandjean Joanes , Corcoba Alberto , Kahn Martin C. , Upton A. Louise , Deneris Evan S. , Seifritz Erich , Helmchen Fritjof , Mansuy Isabelle M. , Mann Edward O. , Rudin Markus , Saab Bechara J. 
Published: January 2019

AbstractCentral serotonin (5-HT) orchestrates myriad cognitive processes and
lies at the core of many stress-related psychiatric illnesses. However, the basic
relationship between its brain-wide axonal projections and functional dynamics is
not known. Here we combine optogenetics and fMRI to produce a brain-wide 5-HT evoked
functional map. We find that DRN photostimulation leads to an increase in the
hemodynamic response in the DRN itself, while projection areas predominately exhibit
a reduction of cerebral blood volume mirrored by suppression of cortical delta
oscillations. We find that the regional distribution of post-synaptically expressed
5-HT receptors better correlates with DRN 5-HT functional connectivity than
anatomical projections. Our work suggests that neuroarchitecture is not the primary
determinant of function for the DRN 5-HT. With respect to two 5-HT elevating
stimuli, we find that acute stress leads to circuit-wide blunting of the DRN output,
while the SSRI fluoxetine noticeably enhances DRN functional connectivity. These
data provide fundamental insight into the brain-wide functional dynamics of the 5-HT
projection system.
Efficient oral vaccination by bioengineering virus-like particles with protozoan surface proteins
Authors: Serradell Marianela C. , Rupil Lucía L. , Martino Román A. , Prucca César G. , Carranza Pedro G. , Saura Alicia , Fernández Elmer A. , Gargantini Pablo R. , Tenaglia Albano H. , Petiti Juan P. , Tonelli Renata R. , Reinoso-Vizcaino Nicolás , Echenique José , Berod Luciana , Piaggio Eliane , Bellier Bertrand , Sparwasser Tim , Klatzmann David , Luján Hugo D. 
Published: January 2019

AbstractIntestinal and free-living protozoa, such as Giardia lamblia, express a dense coat of variant-specific surface proteins (VSPs) on trophozoites that protects the parasite inside the host’s intestine. Here we show that VSPs not only are resistant to proteolytic digestion and extreme pH and temperatures but also stimulate host innate immune responses in a TLR-4 dependent manner. We show that these properties can be exploited to both protect and adjuvant vaccine antigens for oral administration. Chimeric Virus-like Particles (VLPs) decorated with VSPs and expressing model surface antigens, such as influenza virus hemagglutinin (HA) and neuraminidase (NA), are protected from degradation and activate antigen presenting cells in vitro. Orally administered VSP-pseudotyped VLPs, but not plain VLPs, generate robust immune responses that protect mice from influenza infection and HA-expressing tumors. This versatile vaccine platform has the attributes to meet the ultimate challenge of generating safe, stable and efficient oral vaccines.
Suppression of magnetic ordering in XXZ-type antiferromagnetic monolayer NiPS3
Authors: Kim Kangwon , Lim Soo Yeon , Lee Jae-Ung , Lee Sungmin , Kim Tae Yun , Park Kisoo , Jeon Gun Sang , Park Cheol-Hwan , Park Je-Geun , Cheong Hyeonsik 
Published: January 2019

AbstractHow a certain ground state of complex physical systems emerges, especially in two-dimensional materials, is a fundamental question in condensed-matter physics. A particularly interesting case is systems belonging to the class of XY Hamiltonian where the magnetic order parameter of conventional nature is unstable in two-dimensional materials leading to a Berezinskii−Kosterlitz−Thouless transition. Here, we report how the XXZ-type antiferromagnetic order of a magnetic van der Waals material, NiPS3, behaves upon reducing the thickness and ultimately becomes unstable in the monolayer limit. Our experimental data are consistent with the findings based on renormalization-group theory that at low temperatures a two-dimensional XXZ system behaves like a two-dimensional XY one, which cannot have a long-range order at finite temperatures. This work provides the experimental examination of the XY magnetism in the atomically thin limit and opens opportunities of exploiting these fundamental theorems of magnetism using magnetic van der Waals materials.
Control of structural flexibility of layered-pillared metal-organic frameworks anchored at surfaces
Authors: Wannapaiboon Suttipong , Schneemann Andreas , Hante Inke , Tu Min , Epp Konstantin , Semrau Anna Lisa , Sternemann Christian , Paulus Michael , Baxter Samuel J. , Kieslich Gregor , Fischer Roland A. 
Published: January 2019

AbstractFlexible metal-organic frameworks (MOFs) are structurally flexible, porous, crystalline solids that show a structural transition in response to a stimulus. If MOF-based solid-state and microelectronic devices are to be capable of leveraging such structural flexibility, then the integration of MOF thin films into a device configuration is crucial. Here we report the targeted and precise anchoring of Cu-based alkylether-functionalised layered-pillared MOF crystallites onto substrates via stepwise liquid-phase epitaxy. The structural transformation during methanol sorption is monitored by in-situ grazing incidence X-ray diffraction. Interestingly, spatially-controlled anchoring of the flexible MOFs on the surface induces a distinct structural responsiveness which is different from the bulk powder and can be systematically controlled by varying the crystallite characteristics, for instance dimensions and orientation. This fundamental understanding of thin-film flexibility is of paramount importance for the rational design of MOF-based devices utilising the structural flexibility in specific applications such as selective sensors.
Both rare and common genetic variants contribute to autism in the Faroe Islands
Authors: Leblond Claire S , Cliquet Freddy , Carton Coralie , Huguet Guillaume , Mathieu Alexandre , Kergrohen Thomas , Buratti Julien , Lemière Nathalie , Cuisset Laurence , Bienvenu Thierry , Boland Anne , Deleuze Jean-François , Stora Tormodur , Biskupstoe Rannva , Halling Jónrit , Andorsdóttir Guðrið , Billstedt Eva , Gillberg Christopher , Bourgeron Thomas 
Published: January 2019

AbstractThe number of genes associated with autism is increasing, but few studies have been performed on epidemiological cohorts and in isolated populations. Here, we investigated 357 individuals from the Faroe Islands including 36 individuals with autism, 136 of their relatives and 185 non-autism controls. Data from SNP array and whole exome sequencing revealed that individuals with autism had a higher burden of rare exonic copy-number variants altering autism associated genes (deletions (p = 0.0352) or duplications (p = 0.0352)), higher inbreeding status (p = 0.023) and a higher load of rare homozygous deleterious variants (p = 0.011) compared to controls. Our analysis supports the role of several genes/loci associated with autism (e.g., NRXN1, ADNP, 22q11 deletion) and identified new truncating (e.g., GRIK2, ROBO1, NINL, and IMMP2L) or recessive deleterious variants (e.g., KIRREL3 and CNTNAP2) affecting autism-associated genes. It also revealed three genes involved in synaptic plasticity, RIMS4, KALRN, and PLA2G4A, carrying de novo deleterious variants in individuals with autism without intellectual disability. In summary, our analysis provides a better understanding of the genetic architecture of autism in isolated populations by highlighting the role of both common and rare gene variants and pointing at new autism-risk genes. It also indicates that more knowledge about how multiple genetic hits affect neuronal function will be necessary to fully understand the genetic architecture of autism.
Cytostatic and Anti-tumor Potential of Ajwa Date Pulp against Human Hepatocellular Carcinoma HepG2 Cells
Authors: Siddiqui Sahabjada , Ahmad Rumana , Khan Mohsin Ali , Upadhyay Shivbrat , Husain Ishrat , Srivastava Anand Narain 
Published: January 2019

AbstractAjwa dates (Phoenix dactylifera L.) are used by traditional therapeutic practitioners for several health benefits but most remain to be scientifically validated. In this study, we evaluated the apoptosis-inducing effect of ethanolic extract of Ajwa date pulp (ADP) on human hepatocellular carcinoma (HCC) HepG2 cells. High performance liquid chromatography analysis revealed the presence of polysaccharide β-D-glucan in ADP extract. Treated HCC cells revealed morphological characteristics of apoptosis under phase contrast microscopy. MTT assay demonstrated significant (p < 0.05) dose- and time-dependent inhibition of HCC cell growth. HCC cells were found to be in late apoptotic stage on treatment with higher doses of ADP extract as depicted by acridine orange/ethidium bromide and Annexin V-FITC/PI double stain. Importantly, ADP extract increased the reactive oxygen species level and decreased the mitochondrial membrane potential in treated HCC cells. Flow cytometry analysis demonstrated that ADP extract induced elevation of S and G2/M phases of cell cycle. Moreover, ADP extract induced apoptosis in HCC cells independent of tumor suppressor genes viz. CHEK2, ATM and TP53. Interestingly, ADP extract did not display any significant effect on normal cell line Vero. This study provides validation that ADP extract can be considered as a safe and natural potential drug candidate against human liver cancer.
Computational insight into the interaction of oxaliplatin with insulin
Authors: Sciortino Giuseppe , Sánchez-Aparicio José-Emilio , Rodríguez-Guerra Pedregal Jaime , Garribba Eugenio , Maréchal Jean-Didier 
Published: January 2019

AbstractIn an organism, cisplatin and its derivatives are known to interact with proteins besides their principal DNA target. These off-target interactions have major therapeutic consequences including undesired side effects, loss of bioavailability and emergence of resistance. Insulin is one of the prototypical protein targets of platinum drugs as it has been seen to be involved in bioavailability reduction and might also determine resistance in certain cancer lines. However, despite the interest in understanding the nature of the oxaliplatin–insulin adducts, no 3D models have been achieved so far. In this study, we apply our recent computational multiscale protocol optimized for bioinorganic interactions to provide structural insights into these systems. To do so, the initial structures are predicted by blind protein–metalloligand docking calculations optimized to account for a metal-containing species, and then refined using a Molecular Dynamics (MD) and Quantum Mechanics/Molecular Mechanics (QM/MM) integrated protocol. The results are consistent with experimental information obtained from fragment analysis, and also provide novel structural information like conformational changes occurring upon binding and potential effects on the biological functions of the protein. This study opens an avenue towards applying similar strategies to a wide ensemble of metallodrug–protein/peptide systems for which no structural data are available.
Noninvasive Collateral Flow Velocity Imaging in Acute Ischemic Stroke: Intraindividual Comparison of 4D-CT Angiography with Digital Subtraction Angiography
Authors: Muehlen Iris , Kloska Stephan P. , Gölitz Philipp , Hölter Philip , Breuer Lorenz , Ditt Hendrik , Doerfler Arnd 
Published: January 2019

Purpose The collateral status can be defined not only by its morphological extent but also by the velocity of collateral filling characterized by the relative filling time delay (rFTD). The aim of our study was to compare different methods of noninvasive visualization of rFTD derived from 4D-CT angiography (4D-CTA) with digital substraction angiography (DSA) and to investigate the correlation between functional and morphological collateral status on timing-invariant CTA.
Materials and Methods 50 consecutive patients with acute occlusion in the M1 segment who underwent DSA for subsequent mechanical recanalization after multimodal CT were retrospectively analyzed. 4D-CTA data were used to assess the relative filling time delay between the A1 segment of the affected hemisphere and the sylvian branches distal to the occluded M1 segment using source images (4D-CTA-SI) and color-coded flow velocity visualization with prototype software (fv-CTA) in comparison to DSA. The morphological extent of collaterals was assessed on the basis of the Collateral Score (CS) on temporal maximum intensity projections (tMIP) derived from CT perfusion data.
Results There was very good correlation of rFTD between fv-CTA and DSA (n = 50, r = 0.9, p < 0.05). Differences of absolute rFTD values were not significant. 4D-CTA-SI and DSA also showed good correlation (n = 50, r = 0.6, p < 0.05), but mean values of rFTD were significantly different (p < 0.05). rFTD derived from fvCTA and CS derived from timing-invariant CTA showed a negative association (R = – 0.5; P = 0.000). In patients with a favorable radiological outcome defined by a TICI score of 2b or 3, there was a significant negative correlation of CS and mRS at 3 months (R = – 0.4, P = 0.006).
Conclusion Collateral status plays an important role in the outcome in stroke patients. rFTD derived from 4D-CTA is a suitable parameter for noninvasive imaging of collateral velocity, which correlates with the morphological extent of collaterals. Further studies are needed to define valid thresholds for rFTD and to evaluate the diagnostic and prognostic value.
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Simulation to Improve Trainee Skill and Comfort with Forceps-Assisted Vaginal Deliveries
Authors: Rose Kelsey , Jensen Kirsten , Guo Rong , Afshar Yalda 
Published: January 2019

Objective Simulation training is a powerful learning tool for low frequency events. Forceps-assisted vaginal deliveries (FAVD) are an important tool in reducing cesarean deliveries. The aim of this study is to create a high-fidelity simulation-based curriculum for residency education and investigate pre- and posttest skill and confidence.
Methods A prospective cohort study was conducted involving obstetrics and gynecology residents over 2 academic years. Residents participated in one to three FAVD simulation trainings. All sessions involved video, didactic, and hands-on practice. Pre- and postsurvey and skills assessment were conducted to assess confidence, ability to consent, and perform a FAVD. Wilcoxon's signed-rank tests and Kruskal–Wallis tests were used.
Results Thirty residents (73%) completed at least one forceps simulation training session. Participants demonstrated significant improvement in confidence (p < 0.005) following training. Before the intervention, there was a disparity in confidence by postgraduate level (p < 0.005); however, this difference was not seen postsimulation (p = 0.24). Residents demonstrated significant improvement in their FAVD skills (p < 0.05), as well as their ability to consent (p < 0.01).
Conclusion Simulation training improves residents' perceived confidence in FAVD. Simulation helped to better equalize confidence across classes. FAVD simulations improves resident confidence, skill, and more broadly broadened the armamentarium to decrease the cesarean delivery rate.
Non-prototypical clefts
Authors: Karssenberg Lena , Lahousse Karen , Lamiroy Béatrice , Marzo Stefania , Drobnjakovic Ana 
Published: January 2019

AbstractIn this article we present an overview of current debates in the analysis of cleft sentences. The types of sentences that are often seen as prototypical examples of the cleft category are introduced byit isor a cross-linguistic equivalent; in addition, they have specificational semantics and a focus-background information structure articulation. We argue here that other, less prototypical types of constructions, which have received less attention, also belong to the cleft category: sentences that are introduced by expressions such asthere isandyou’ve got(and their cross-linguistic equivalents), as well as sentences introduced byit iswhich do not have specificational semantics and which express other types of information structure articulations (e.g. all-focus or topic-comment). We argue that it is fruitful to analyse these ‘non-prototypical’ clefts in more depth, not only to come to a better understanding about these sentence types in their own right, but also to arrive at insights in the phenomenon of ‘clefts’ in general.
Setting the boundaries
Authors: Cruschina Silvio 
Published: January 2019

AbstractConstructions that are typically used to introduce a new referent into the discourse may extend this function so as to introduce a new event or situation. In this paper, I examine the case of presentationalci-sentences in Italian, which have developed exactly this new function out of existential sentences. Despite being superficially similar to existential sentences, as well as to clefts, presentationalci-sentences must be kept separate from both sentence types, and must be treated as an independent construction with distinct structural and functional properties. Unlike existentials, presentationalci-sentences assert the existence of an event or situation and involve a predicational structure characterized by a CP (the relative clause) that functions as the predicate of the DP. Unlike clefts, which are typically used to mark narrow focus, presentationalci-sentences display a sentence-focus structure whereby the event is presented as all new. A contrastive analysis of presentationalci-sentences against existentials and clefts will thus allow us not only to understand the exact boundaries between these constructions, but also to identify more precisely the distinctive characteristic properties of each sentence type.
The semantics of the simple tenses and full-verb inversion in English
Authors: De Wit Astrid 
Published: January 2019

AbstractThis paper offers a fresh perspective on (restrictions on) aspectual coercion, thereby focusing on the essentially epistemic import of aspectual constructions. The case study that I will discuss is the unexpected use of the simple tenses for ongoing event reports in sentences involving full-verb inversion. I will argue that this attestation of the simple present/past in inverted sentences can be analyzed as a kind of aspectual mismatch between the higher-order construction and the embedded tenses. Yet at a more basic, epistemic level of analysis, there is no mismatch: the full-verb inversion construction and the embedded tenses are similar in the sense that both report events that are conceived of as fully and instantly identifiable.
Constructional contamination in morphology and syntax
Authors: Pijpops Dirk , De Smet Isabeau , Van de Velde Freek 
Published: January 2019

AbstractIn every-day language use, two or more structurally unrelated constructions may occasionally give rise to strings that look very similar on the surface. As a result of this superficial resemblance, a subset of instances of one of these constructions may deviate in the probabilistic preference for either of several possible formal variants. This effect is called ‘constructional contamination’, and was introduced inPijpops & Van de Velde (2016). Constructional contamination bears testimony to the hypothesis that language users do not always execute a full parse of the utterances they interpret, but instead often rely on ‘shallow parsing’ and the storage of large, unanalyzed chunks of language in memory, as proposed inFerreira, Bailey, & Ferraro (2002),Ferreira & Patson (2007), andDąbrowska (2014).Pijpops & Van de Velde (2016)investigated a single case study in depth, namely the Dutch partitive genitive. This case study is reviewed, and three new case studies are added, namely the competition between long and bare infinitives, word order variation in verbal clusters, and preterite formation. We find evidence of constructional contamination in all case studies, albeit in varying degrees. This indicates that constructional contamination is not a particularity of the Dutch partitive genitive but appears to be more wide-spread, affecting both morphology and syntax. Furthermore, we distinguish between two forms of constructional contamination, viz. first degree and second degree contamination, with first degree contamination producing greater effects than second degree contamination.
A qualitative case study of CSL learners’ reading strategies
Authors: Huang Sha 
Published: January 2019

Abstract
Reading is a challenging task for Chinese as a second language (CSL) learners. Research has shown that effective use of strategies
helps to enhance reading comprehension. However, studies about the reading strategies of CSL learners are extremely limited, and
even fewer studies focus on how CSL readers use reading strategies to facilitate comprehension when reading a Chinese text. This
case study addressed this gap by conducting an in-depth analysis of how three CSL readers used strategies to enhance their
comprehension. Through think-aloud and recall protocols, close observations, and interviews, this study identified 26
comprehension strategies used by these readers during the reading process. It also reported the strategies commonly used by these
readers to enhance reading comprehension effectively, such as using context to decode words, monitoring, identifying important
information, and skipping unimportant parts. This article presents the study’s findings and their implications.
Intelligibility of an L2 variety in ELF interactions
Authors: Gardiner Ishamina Athirah 
Published: January 2019

AbstractThis paper investigates the occurrence of misunderstandings in ELF (English as a Lingua Franca) interactions caused by vowel pronunciation in Brunei English. The study is based on ten audio recordings, each consisting of conversations between two participants: a Bruneian (L2 speaker) and a non-Bruneian speaker. Out of a total of 152 tokens (occurrences) of misunderstandings identified, 36 of them (23.7%) are found to involve vowel pronunciation. Data analysis includes examining vowel length, the vowels offace, goat, price, mouth, monosyllabic triphthongs,trap, vowel reduction, spelling pronunciation and American pronunciation in causing misunderstandings. The findings indicate that misunderstandings may be caused by a change in vowel length and quality in 28 tokens. The study concludes that vowel pronunciation in Brunei English conversational speech, particularly in the lack of vowel length distinction and absence of diphthongs in closed syllables may occasionally lead to a loss of intelligibility in ELF settings.