bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dual role of Ca2+-activated Cl− channel transmembrane member 16A in lipopolysaccharide-induced intestinal epithelial barrier dysfunction in vitro
Authors: Sui Jingru , Zhang Chi , Fang Xuesheng , Wang Jianwen , Li Yu , Wang Jingyu , Wang Liang , Dong Jianyi , Zhou Zijuan , Li Changyi , Chen Jun , Ma Tonghui , Chen Dapeng 
Published: May 2020

AbstractDysfunction of intestinal epithelial Cl− currents and channels have previously been reported in inflammatory intestinal diseases. However, the expression and function of the newly identified Ca2+-activated Cl− channel transmembrane member 16A (TMEM16A) in the intestinal epithelium is unclear. In this study, we investigated the effects of TMEM16A on intestinal epithelial barrier function in vitro. Intestinal epithelial barrier dysfunction was modeled by lipopolysaccharide (LPS)-induced cell damage in intestinal epithelial IEC-6 cells and the effects of TMEM16A knockdown and overexpression on cell apoptosis and tight junctions were studied. Corresponding mRNA and protein expression levels were measured by quantitative real-time polymerase chain reaction, western blotting, and immunofluorescence analysis, respectively. TMEM16A expression was significantly increased by LPS, possibly via a process involving the transcription factor nuclear factor-κB and both Th1 and Th2 cytokines. Low- and high-dose LPS dysregulated tight junctions (high-myosin light-chain kinase expression) and cell apoptosis-dependent cell barrier dysfunction, respectively. TMEM16A aggravated cell barrier dysfunction in IEC-6 cells pretreated with low-dose LPS by activating ERK1/MLCK signaling pathways, but protected against cell barrier dysfunction by activating ERK/Bcl-2/Bax signaling pathways in IEC-6 cells pretreated with high-dose LPS. We concluded that TMEM16A played a dual role in LPS-induced epithelial dysfunction in vitro. The present results indicated the complex regulatory mechanisms and targeting of TMEM16A may provide potential treatment strategies for intestinal epithelial barrier damage, as well as forming the basis for future studies of the expression and function of TMEM16A in normal and inflammatory intestinal diseases in vivo.
The interaction of interleukin-8 and PTEN inactivation promotes the malignant progression of head and neck squamous cell carcinoma via the STAT3 pathway
Authors: Xu Qiaoshi , Ma Hailong , Chang Hanyue , Feng Zhien , Zhang Chenping , Yang Xi 
Published: May 2020

AbstractInterleukin-8 (IL-8) expression correlates with poor prognosis in many cancers, including head and neck squamous cell carcinoma (HNSCC), but the underlying mechanism is poorly understood. In this study, we found that overexpression of IL-8 correlated with poor outcome in HNSCC patients. IL-8 significantly increased cellular proliferation, migration, and invasion ability both in vitro and in vivo, which could be blocked by a CXCR1/2 inhibitor. IL-8 promoted the expression of MMP2, MMP9, snail, and vimentin in HNSCC cells. Furthermore, IL-8 could inactivate PTEN via phosphorylation, and then inactivated PTEN affected the phosphorylation of STAT3. Recombinant PTEN that internalized in cytoplasm decreased the expression of phosphorylated STAT3, while knockdown of PTEN led to the increased expression of phosphorylated STAT3. A STAT3 inhibitor could reverse the upregulation of invasion-associated proteins mediated by IL-8 stimulation. Furthermore, overexpression of snail and inactivated PTEN jointly promoted the autocrine effect of IL-8 on tumor cells. Last, there were positive correlations between IL-8 and snail, vimentin expression in HNSCC tissues. In summary, our study demonstrates that PTEN acts as a novel “molecular switch” to regulate IL-8/STAT3 signaling, promoting the progression of HNSCC, and indicating that this pathway may be a potential therapeutic target for HNSCC.
Anisotropic ESCRT-III architecture governs helical membrane tube formation
Authors: Moser von Filseck Joachim , Barberi Luca , Talledge Nathaniel , Johnson Isabel E. , Frost Adam , Lenz Martin , Roux Aurélien 
Published: May 2020

AbstractESCRT-III proteins assemble into ubiquitous membrane-remodeling polymers during many cellular processes. Here we describe the structure of helical membrane tubes that are scaffolded by bundled ESCRT-III filaments. Cryo-ET reveals how the shape of the helical membrane tube arises from the assembly of two distinct bundles of helical filaments that have the same helical path but bind the membrane with different interfaces. Higher-resolution cryo-EM of filaments bound to helical bicelles confirms that ESCRT-III filaments can interact with the membrane through a previously undescribed interface. Mathematical modeling demonstrates that the interface described above is key to the mechanical stability of helical membrane tubes and helps infer the rigidity of the described protein filaments. Altogether, our results suggest that the interactions between ESCRT-III filaments and the membrane could proceed through multiple interfaces, to provide assembly on membranes with various shapes, or adapt the orientation of the filaments towards the membrane during membrane remodeling.
Quantum clocks and the temporal localisability of events in the presence of gravitating quantum systems
Authors: Castro-Ruiz Esteban , Giacomini Flaminia , Belenchia Alessio , Brukner Časlav 
Published: May 2020

AbstractThe standard formulation of quantum theory relies on a fixed space-time metric determining the localisation and causal order of events. In general relativity, the metric is influenced by matter, and is expected to become indefinite when matter behaves quantum mechanically. Here, we develop a framework to operationally define events and their localisation with respect to a quantum clock reference frame, also in the presence of gravitating quantum systems. We find that, when clocks interact gravitationally, the time localisability of events becomes relative, depending on the reference frame. This relativity is a signature of an indefinite metric, where events can occur in an indefinite causal order. Even if the metric is indefinite, for any event we can find a reference frame where local quantum operations take their standard unitary dilation form. This form is preserved when changing clock reference frames, yielding physics covariant with respect to quantum reference frame transformations.
ISG15 and ISGylation is required for pancreatic cancer stem cell mitophagy and metabolic plasticity
Authors: Alcalá Sonia , Sancho Patricia , Martinelli Paola , Navarro Diego , Pedrero Coral , Martín-Hijano Laura , Valle Sandra , Earl Julie , Rodríguez-Serrano Macarena , Ruiz-Cañas Laura , Rojas Katerin , Carrato Alfredo , García-Bermejo Laura , Fernández-Moreno Miguel Ángel , Hermann Patrick C. , Sainz Bruno 
Published: May 2020

AbstractPancreatic cancer stem cells (PaCSCs) drive pancreatic cancer tumorigenesis, chemoresistance and metastasis. While eliminating this subpopulation of cells would theoretically result in tumor eradication, PaCSCs are extremely plastic and can successfully adapt to targeted therapies. In this study, we demonstrate that PaCSCs increase expression of interferon-stimulated gene 15 (ISG15) and protein ISGylation, which are essential for maintaining their metabolic plasticity. CRISPR-mediated ISG15 genomic editing reduces overall ISGylation, impairing PaCSCs self-renewal and their in vivo tumorigenic capacity. At the molecular level, ISG15 loss results in decreased mitochondrial ISGylation concomitant with increased accumulation of dysfunctional mitochondria, reduced oxidative phosphorylation (OXPHOS) and impaired mitophagy. Importantly, disruption in mitochondrial metabolism affects PaCSC metabolic plasticity, making them susceptible to prolonged inhibition with metformin in vivo. Thus, ISGylation is critical for optimal and efficient OXPHOS by ensuring the recycling of dysfunctional mitochondria, and when absent, a dysregulation in mitophagy occurs that negatively impacts PaCSC stemness.
TRPV4 disrupts mitochondrial transport and causes axonal degeneration via a CaMKII-dependent elevation of intracellular Ca2+
Authors: Woolums Brian M. , McCray Brett A. , Sung Hyun , Tabuchi Masashi , Sullivan Jeremy M. , Ruppell Kendra Takle , Yang Yunpeng , Mamah Catherine , Aisenberg William H. , Saavedra-Rivera Pamela C. , Larin Bryan S. , Lau Alexander R. , Robinson Douglas N. , Xiang Yang , Wu Mark N. , Sumner Charlotte J. , Lloyd Thomas E. 
Published: May 2020

AbstractThe cation channel transient receptor potential vanilloid 4 (TRPV4) is one of the few identified ion channels that can directly cause inherited neurodegeneration syndromes, but the molecular mechanisms are unknown. Here, we show that in vivo expression of a neuropathy-causing TRPV4 mutant (TRPV4R269C) causes dose-dependent neuronal dysfunction and axonal degeneration, which are rescued by genetic or pharmacological blockade of TRPV4 channel activity. TRPV4R269Ctriggers increased intracellular Ca2+through a Ca2+/calmodulin-dependent protein kinase II (CaMKII)-mediated mechanism, and CaMKII inhibition prevents both increased intracellular Ca2+and neurotoxicity inDrosophilaand cultured primary mouse neurons. Importantly, TRPV4 activity impairs axonal mitochondrial transport, and TRPV4-mediated neurotoxicity is modulated by the Ca2+-binding mitochondrial GTPase Miro. Our data highlight an integral role for CaMKII in neuronal TRPV4-associated Ca2+responses, the importance of tightly regulated Ca2+dynamics for mitochondrial axonal transport, and the therapeutic promise of TRPV4 antagonists for patients with TRPV4-related neurodegenerative diseases.
The netrin receptor UNC-40/DCC assembles a postsynaptic scaffold and sets the synaptic content of GABAA receptors
Authors: Zhou Xin , Gueydan Marine , Jospin Maelle , Ji Tingting , Valfort Aurore , Pinan-Lucarré Bérangère , Bessereau Jean-Louis 
Published: May 2020

AbstractIncreasing evidence indicates that guidance molecules used during development for cellular and axonal navigation also play roles in synapse maturation and homeostasis. In C. elegans the netrin receptor UNC-40/DCC controls the growth of dendritic-like muscle cell extensions towards motoneurons and is required to recruit type A GABA receptors (GABAARs) at inhibitory neuromuscular junctions. Here we show that activation of UNC-40 assembles an intracellular synaptic scaffold by physically interacting with FRM-3, a FERM protein orthologous to FARP1/2. FRM-3 then recruits LIN-2, the ortholog of CASK, that binds the synaptic adhesion molecule NLG-1/Neuroligin and physically connects GABAARs to prepositioned NLG-1 clusters. These processes are orchestrated by the synaptic organizer CePunctin/MADD-4, which controls the localization of GABAARs by positioning NLG-1/neuroligin at synapses and regulates the synaptic content of GABAARs through the UNC-40-dependent intracellular scaffold. Since DCC is detected at GABA synapses in mammals, DCC might also tune inhibitory neurotransmission in the mammalian brain.
Insights into the mechanism of coreactant electrochemiluminescence facilitating enhanced bioanalytical performance
Authors: Zanut Alessandra , Fiorani Andrea , Canola Sofia , Saito Toshiro , Ziebart Nicole , Rapino Stefania , Rebeccani Sara , Barbon Antonio , Irie Takashi , Josel Hans-Peter , Negri Fabrizia , Marcaccio Massimo , Windfuhr Michaela , Imai Kyoko , Valenti Giovanni , Paolucci Francesco 
Published: May 2020

AbstractElectrochemiluminescence (ECL) is a powerful transduction technique with a leading role in the biosensing field due to its high sensitivity and low background signal. Although the intrinsic analytical strength of ECL depends critically on the overall efficiency of the mechanisms of its generation, studies aimed at enhancing the ECL signal have mostly focused on the investigation of materials, either luminophores or coreactants, while fundamental mechanistic studies are relatively scarce. Here, we discover an unexpected but highly efficient mechanistic path for ECL generation close to the electrode surface (signal enhancement, 128%) using an innovative combination of ECL imaging techniques and electrochemical mapping of radical generation. Our findings, which are also supported by quantum chemical calculations and spin trapping methods, led to the identification of a family of alternative branched amine coreactants, which raises the analytical strength of ECL well beyond that of present state-of-the-art immunoassays, thus creating potential ECL applications in ultrasensitive bioanalysis.
Geophysical imaging of ophiolite structure in the United Arab Emirates
Authors: Ali M. Y. , Watts A. B. , Searle M. P. , Keats B. , Pilia S. , Ambrose T. 
Published: May 2020

AbstractThe Oman-United Arab Emirates ophiolite has been used extensively to document the geological processes that form oceanic crust. The geometry of the ophiolite, its extension into the Gulf of Oman, and the nature of the crust that underlies it are, however, unknown. Here, we show the ophiolite forms a high velocity, high density, >15 km thick east-dipping body that during emplacement flexed down a previously rifted continental margin thereby contributing to subsidence of flanking sedimentary basins. The western limit of the ophiolite is defined onshore by the Semail thrust while the eastern limit extends several km offshore, where it is defined seismically by a ~40–45°, east-dipping, normal fault. The fault is interpreted as the southwestern margin of an incipient suture zone that separates the Arabian plate from in situ Gulf of Oman oceanic crust and mantle presently subducting northwards beneath the Eurasian plate along the Makran trench.
Geomorpho90m, empirical evaluation and accuracy assessment of global high-resolution geomorphometric layers
Authors: Amatulli Giuseppe , McInerney Daniel , Sethi Tushar , Strobl Peter , Domisch Sami 
Published: May 2020

AbstractTopographical relief comprises the vertical and horizontal variations of the Earth’s terrain and drives processes in geomorphology, biogeography, climatology, hydrology and ecology. Its characterisation and assessment, through geomorphometry and feature extraction, is fundamental to numerous environmental modelling and simulation analyses. We, therefore, developed the Geomorpho90m global dataset comprising of different geomorphometric features derived from the MERIT-Digital Elevation Model (DEM) - the best global, high-resolution DEM available. The fully-standardised 26 geomorphometric variables consist of layers that describe the (i) rate of change across the elevation gradient, using first and second derivatives, (ii) ruggedness, and (iii) geomorphological forms. The Geomorpho90m variables are available at 3 (~90 m) and 7.5 arc-second (~250 m) resolutions under the WGS84 geodetic datum, and 100 m spatial resolution under the Equi7 projection. They are useful for modelling applications in fields such as geomorphology, geology, hydrology, ecology and biogeography.
Olaparib monotherapy for Asian patients with a germline BRCA mutation and HER2-negative metastatic breast cancer: OlympiAD randomized trial subgroup analysis
Authors: Im Seock-Ah , Xu Binghe , Li Wei , Robson Mark , Ouyang Quchang , Yeh Dah-Cherng , Iwata Hiroji , Park Yeon Hee , Sohn Joo Hyuk , Tseng Ling-Ming , Goessl Carsten , Wu Wenting , Masuda Norikazu 
Published: May 2020

AbstractThe OlympiAD Phase III study (NCT02000622) established the clinical benefits of olaparib tablet monotherapy (300 mg twice daily) over chemotherapy treatment of physician’s choice (TPC) in patients with a germline BRCA1/2 mutation (gBRCAm) and human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer who had received ≤2 chemotherapy lines in the metastatic setting. Here, we report pre-specified analyses of data from Asian (China, Japan, Korea and Taiwan) patients in the study. All patients were randomized 2:1 to olaparib tablets (300 mg twice daily) or single-agent chemotherapy TPC (21-day cycles of either capecitabine, eribulin or vinorelbine). The primary endpoint was progression-free survival assessed by blinded independent central review. The prevalence of gBRCAm in the OlympiAD Asian subgroup screened for study recruitment was 13.5%. Patient demographics and disease characteristics of the Asian subgroup (87/302 patients) were generally well balanced between treatment arms. Asian patients in the olaparib arm achieved longer median progression-free survival, assessed by blinded independent central review, versus the chemotherapy TPC arm (5.7 vs 4.2 months; HR = 0.53 [95% CI: 0.29–0.97]), which was consistent with findings in the global OlympiAD study population. Findings on secondary efficacy and safety/tolerability outcome measures in Asian patients were also similar to those observed in the global OlympiAD study population. The OlympiAD study was not powered to detect race-related differences between treatment groups; however, the consistency of our findings with the global OlympiAD study population suggests that previously reported findings are generalizable to Asian patients.
The use of click beetle pheromone traps to optimize the risk assessment of wireworm (Coleoptera: Elateridae) maize damage
Authors: Furlan Lorenzo , Contiero Barbara , Chiarini Francesca , Benvegnù Isadora , Tóth Miklós 
Published: May 2020

AbstractMaize seeds are routinely coated with insecticide to target Agriotes spp. larvae (wireworms). However, in order to find fields where pest control is actually needed, it might be useful to estimate the adult Agriotes population levels and thus the pressure they exert, with a low-cost risk assessment tool, such as YATLORf (Yf) sex pheromone traps. A database containing 17 consecutive years (1998–2014) of field monitoring was analyzed, with information including both pheromone-trap catches of adults and maize-plant damage by wireworms. Significant associations were discovered between seasonal adult catches in-field, subsequent wireworm populations, and plant damage/yield reduction. When each trap contained over 1,100 A. sordidus adults and over 210 A. brevis adults one year prior (Y-1), the risk of 15%-plus plant damage in Year 0 (Y0) increased by 6 times and 37 times respectively when compared with lower numbers. More than 1,000 A. brevis adults/trap two years prior (Y-2) increased the risk of 15%-plus plant damage in Y0 by 13 times when compared with lower numbers. Cumulative thresholds were also found in Y-1 and Y-2 at the same site. Yf threshold values allowed us to detect fields with a negligible crop-damage risk and thus to reduce the use of insecticides.
Validation of a hybrid approach to standardize immunophenotyping analysis in large population studies: The Health and Retirement Study
Authors: Hunter-Schlichting DeVon , Lane John , Cole Benjamin , Flaten Zachary , Barcelo Helene , Ramasubramanian Ramya , Cassidy Erin , Faul Jessica , Crimmins Eileen , Pankratz Nathan , Thyagarajan Bharat 
Published: May 2020

AbstractTraditional manual gating strategies are often time-intensive, place a high burden on the analyzer, and are susceptible to bias between analyzers. Several automated gating methods have shown to exceed performance of manual gating for a limited number of cell subsets. However, many of the automated algorithms still require significant manual interventions or have yet to demonstrate their utility in large datasets. Therefore, we developed an approach that utilizes a previously published automated algorithm (OpenCyto framework) with a manually created hierarchically cell gating template implemented, along with a custom developed visualization software (FlowAnnotator) to rapidly and efficiently analyze immunophenotyping data in large population studies. This approach allows pre-defining populations that can be analyzed solely by automated analysis and incorporating manual refinement for smaller downstream populations. We validated this method with traditional manual gating strategies for 24 subsets of T cells, B cells, NK cells, monocytes and dendritic cells in 931 participants from the Health and Retirement Study (HRS). Our results show a high degree of correlation (r ≥ 0.80) for 18 (78%) of the 24 cell subsets. For the remaining subsets, the correlation was low (<0.80) primarily because of the low numbers of events recorded in these subsets. The mean difference in the absolute counts between the hybrid method and manual gating strategy of these cell subsets showed results that were very similar to the traditional manual gating method. We describe a practical method for standardization of immunophenotyping methods in large scale population studies that provides a rapid, accurate and reproducible alternative to labor intensive manual gating strategies.
Two nights of recovery sleep restores hippocampal connectivity but not episodic memory after total sleep deprivation
Authors: Chai Ya , Fang Zhuo , Yang Fan Nils , Xu Sihua , Deng Yao , Raine Andrew , Wang Jieqiong , Yu Meichen , Basner Mathias , Goel Namni , Kim Junghoon J. , Wolk David A. , Detre John A. , Dinges David F. , Rao Hengyi 
Published: May 2020

AbstractSleep deprivation significantly impairs a range of cognitive and brain function, particularly episodic memory and the underlying hippocampal function. However, it remains controversial whether one or two nights of recovery sleep following sleep deprivation fully restores brain and cognitive function. In this study, we used functional magnetic resonance imaging (fMRI) and examined the effects of two consecutive nights (20-hour time-in-bed) of recovery sleep on resting-state hippocampal connectivity and episodic memory deficits following one night of total sleep deprivation (TSD) in 39 healthy adults in a controlled in-laboratory protocol. TSD significantly reduced memory performance in a scene recognition task, impaired hippocampal connectivity to multiple prefrontal and default mode network regions, and disrupted the relationships between memory performance and hippocampal connectivity. Following TSD, two nights of recovery sleep restored hippocampal connectivity to baseline levels, but did not fully restore memory performance nor its associations with hippocampal connectivity. These findings suggest that more than two nights of recovery sleep are needed to fully restore memory function and hippocampal-memory associations after one night of total sleep loss.
Lipid Mediator Profiles Predict Response to Therapy with an Oral Frankincense Extract in Relapsing-Remitting Multiple Sclerosis
Authors: Stürner Klarissa Hanja , Werz Oliver , Koeberle Andreas , Otto Markus , Pless Ole , Leypoldt Frank , Paul Friedemann , Heesen Christoph 
Published: May 2020

AbstractLipid mediators (LMs) are a unique class of immunoregulatory signalling molecules and known to be affected by frankincense extracts. We performed LM profiling by metabololipidomics in plasma samples from 28 relapsing-remitting multiple sclerosis (RR-MS) patients who took a standardised frankincense extract (SFE) daily for eight months in a clinical phase IIa trial (NCT01450124) and in 28 age- and gender-matched healthy controls. Magnetic resonance imaging, immunological outcomes and serum neurofilament light chain levels were correlated to changes in the LM profiles of the RR-MS cohort. Eight out of 44 analysed LMs were significantly reduced during an eight-month treatment period by the SFE and seven of these eight significant LM derive from the 5-lipoxygenase (5-LO) pathway. Baseline levels of 12- and 15-LO products were elevated in patients who exhibited disease activity (EDA) during SFE treatment compared to no-evidence-of-disease-activity (NEDA) patients and could predict treatment response to the SFE in a prediction model at baseline. Oral treatment with an SFE significantly reduces 5-LO-derived LMs in RR-MS patients during an eight-month treatment period. Treatment response to an SFE, however, seems to be related to 12-,15-LO and cyclooxygenase product levels before SFE exposure. Further studies should confirm their biomarker potential in RR-MS and SFE treatment.