bluuebunny/crossref_metadata_2025 huggingface dataset:
Martian Infrasound: Numerical Modeling and Analysis of InSight's Data
Authors: Martire Léo , Garcia R. F. , Rolland Lucie , Spiga Aymeric , Lognonné Philippe Henri , Banfield Don , Banerdt William Bruce , Martin Roland
Published: May 2020

Acoustic waves in planetary atmospheres couple into the solid surface, producing ground displacements that can be measured using seismometers. On 26 November 2018, the InSight mission successfully landed on Mars. Its objectives include studying Mars' interior using the seismometer SEIS (Seismic Experiment for Interior Structures) and the atmosphere through the weather station APSS (Auxiliary Payload Sensor Suite). Because InSight is the first mission capable of studying infrasound on Mars, we investigate the signature of infrasound both in terms of air pressure and ground velocities. Using numerical simulations, we characterize (1) the acoustic propagation pattern in Martian dusk and (2) the mechanical atmosphere‐to‐ground coupling under acoustic waves. Then, using SEIS data, we demonstrate that two low‐frequency monotone events (S0133a and S0189a) are in fact infrasound trapped in the atmospheric nocturnal surface waveguide. We base our demonstration on the following facts. (1) Seismic signals rarely produce, at a given station, a single frequency varying from one event to the other. (2) No clear seismic phases have been identified for such events. (3) The observed SEIS signals present the characteristics expected for trapped infrasound observed through their compliance effects (specific frequency response, more energy on the vertical component, ±90° phase shift between vertical and horizontal components, and no detection on pressure sensor at these low amplitude levels). Our simulations of the nocturnal waveguide's response are however subject to uncertainties because (1) it relies on the sol‐to‐sol variability of the atmosphere, and (2) subsurface properties are not properly known at this  time.
Targeting STAT3 signaling using stabilised sulforaphane (SFX-01) inhibits endocrine resistant stem-like cells in ER-positive breast cancer
Authors: Simões Bruno M. , Santiago-Gómez Angélica , Chiodo Chiara , Moreira Tiago , Conole Daniel , Lovell Scott , Alferez Denis , Eyre Rachel , Spence Katherine , Sarmiento-Castro Aida , Kohler Bertram , Morisset Ludivine , Lanzino Marilena , Andò Sebastiano , Marangoni Elisabetta , Sims Andrew H. , Tate Edward W. , Howell Sacha J. , Clarke Robert B.
Published: May 2020

Estrogen receptor (ER) positive breast cancer is frequently sensitive to endocrine therapy. Multiple mechanisms of endocrine therapy resistance have been identified, including cancer stem-like cell (CSC) activity. Here we investigate SFX-01, a stabilised formulation of sulforaphane (SFN), for its effects on breast CSC activity in ER+ preclinical models. SFX‐01 reduced mammosphere formation efficiency (MFE) of ER+ primary and metastatic patient samples. Both tamoxifen and fulvestrant increased MFE and aldehyde dehydrogenase (ALDH) activity of patient-derived xenograft (PDX) tumors, which was reversed by combination with SFX‐01. SFX-01 significantly reduced tumor-initiating cell frequency in secondary transplants and reduced the formation of spontaneous lung micrometastases by PDX tumors in mice. Mechanistically, we establish that both tamoxifen and fulvestrant induce STAT3 phosphorylation. SFX-01 suppressed phospho‐STAT3 and SFN directly bound STAT3 in patient and PDX samples. Analysis of ALDH+ cells from endocrine-resistant patient samples revealed activation of STAT3 target genesMUC1andOSMR, which were inhibited by SFX-01 in patient samples. Increased expression of these genes after 3 months’ endocrine treatment of ER+ patients (n = 68) predicted poor prognosis. Our data establish the importance of STAT3 signaling in CSC-mediated resistance to endocrine therapy and the potential of SFX-01 for improving clinical outcomes in ER+ breast cancer.
Acetylation promotes BCAT2 degradation to suppress BCAA catabolism and pancreatic cancer growth
Authors: Lei Ming-Zhu , Li Xu-Xu , Zhang Ye , Li Jin-Tao , Zhang Fan , Wang Yi-Ping , Yin Miao , Qu Jia , Lei Qun-Ying
Published: May 2020

Pancreatic ductal adenocarcinoma (PDAC) is well-known for inefficient early diagnosis, with most patients diagnosed at advanced stages. Increasing evidence indicates that elevated plasma levels of branched-chain amino acids (BCAAs) are associated with an increased risk of pancreatic cancer. Branched-chain amino acid transaminase 2 (BCAT2) is an important enzyme in BCAA catabolism that reversibly catalyzes the initial step of BCAA degradation to branched-chain acyl-CoA. Here, we show that BCAT2 is acetylated at lysine 44 (K44), an evolutionarily conserved residue. BCAT2 acetylation leads to its degradation through the ubiquitin–proteasome pathway and is stimulated in response to BCAA deprivation. cAMP-responsive element-binding (CREB)-binding protein (CBP) and SIRT4 are the acetyltransferase and deacetylase for BCAT2, respectively. CBP and SIRT4 bind to BCAT2 and control the K44 acetylation level in response to BCAA availability. More importantly, the K44R mutant promotes BCAA catabolism, cell proliferation, and pancreatic tumor growth. Collectively, the data from our study reveal a previously unknown regulatory mechanism of BCAT2 in PDAC and provide a potential therapeutic target for PDAC treatment.
Correction: Treatment patterns and survival in HER2-positive early breast cancer: a whole-of-population Australian cohort study (2007–2016)
Authors: Tang Monica , Schaffer Andrea , Kiely Belinda E. , Daniels Benjamin , Simes Robert J. , Lee Chee K. , Pearson Sallie-Anne
Published: May 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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

Dysfunction 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

Interleukin-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

ESCRT-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

The 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

Pancreatic 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

The 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

Increasing 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

Electrochemiluminescence (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

The 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

Topographical 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

The 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

Maize 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

Traditional 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

Sleep 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

Lipid 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.
Energy-Dispersive X-ray Absorption Spectroscopy with an Inverse Compton Source
Authors: Huang Juanjuan , Günther Benedikt , Achterhold Klaus , Cui Yi-tao , Gleich Bernhard , Dierolf Martin , Pfeiffer Franz
Published: May 2020

Novel compact x-ray sources based on inverse Compton scattering can generate brilliant hard x-rays in a laboratory setting. Their collimated intense beams with tunable well-defined x-ray energies make them well suited for x-ray spectroscopy techniques, which are typically carried out at large facilities. Here, we demonstrate a first x-ray absorption spectroscopy proof-of-principle experiment using an inverse Compton x-ray source with a flux of >1010 photons/s in <5% bandwidth. We measured x-ray absorption near edge structure and extended x-ray absorption fine structure at the silver K-edge (~25.5 keV) for a series of silver samples. We propose an energy-dispersive geometry specifically adapted to the x-ray beam properties of inverse Compton x-ray sources together with a fast concentration correction method that corrects sample inhomogeneities very effectively. The combination of our setup with the inverse Compton source generates x-ray absorption spectra with high energy resolution in exposure times down to one minute. Our results unravel the great benefit of inverse Compton scattering sources for x-ray absorption techniques in a laboratory environment, especially in the hard x-ray regime, which allows to probe absorption edges of high Z materials.
Reservoir characteristics and logging evaluation of gas−bearing mudstone in the south of North China Plain
Authors: Liu Liang , Pan Heping , Lin Zhenzhou , Zhang Shihui , Qin Zhen , Li Jianwei , Huang Guoshu , Wang Lei , Li Dong
Published: May 2020

Mudstone is very similar to shale except it lacks sheet bedding. Shale gas is widely concerned and successfully exploited commercially in the world, while gas-bearing mudstone is rarely paid attention. To evaluate the reservoir characteristics and exploitation potential of gas-bearing mudstone, a total of 127 mudstone samples from the Shanxi formation were tested by X-ray diffraction (XRD), scanning electron microscope (SEM), gas content, etc., and the qualitative identification and quantitative evaluation of gas-bearing mudstone reservoirs were performed on four wells using the logging curve overlay method and reservoir parameter calculation equations. The results showed that: (1) the average total gas content of core measurement is 1.81 m3/t, and the total content of brittle minerals is 44.2%, which confirms that mudstones can also have good gas content and fracturing performance; (2) logging evaluation the average thickness of gas-bearing mudstone is 55.7 m, the average total gas content is 1.6 m3/t, and the average brittleness index is 38.1%, which indicates that the mudstone of Shanxi formation in the study area is generally gas-bearing and widely distributed. All the results reveal that gas-bearing mudstone with block bedding has the same exploitation potential as shale with sheet bedding,which deserves more attention.
Evaluating and forecasting movement patterns of magnetically driven microbeads in complex geometries
Authors: Klingbeil Finn , Block Findan , Sajjad Umer , Holländer Rasmus B. , Deshpande Sughosh , McCord Jeffrey
Published: May 2020

The manipulation of superparamagnetic microbeads for lab-on-a-chip applications relies on the steering of microbeads across an altering stray field landscape on top of soft magnetic parent structures. Using ab initio principles, we show three-dimensional simulations forecasting the controlled movement of microbeads. Simulated aspects of microbead behaviour include the looping and lifting of microbeads around a magnetic circular structure, the flexible bead movement along symmetrically distributed triangular structures, and the dragging of magnetic beads across an array of exchange biased magnetic microstripes. The unidirectional motion of microbeads across a string of oval elements is predicted by simulations and validated experimentally. Each of the simulations matches the experimental results, proving the robustness and accuracy of the applied numerical method. The computer experiments provide details on the particle motion not accessible by experiments. The simulation capabilities prove to be an essential part for the estimation of future lab-on-chip designs.
Oriented immobilization of basic fibroblast growth factor: Bioengineered surface design for the expansion of human mesenchymal stromal cells
Authors: Shakya Ajay , Imado Eiji , Nguyen Phuong Kim , Matsuyama Tamamo , Horimoto Kotaro , Hirata Isao , Kato Koichi
Published: May 2020

E. coli expressed recombinant basic fibroblast growth factor (bFGF) with histidine-tag (bFGF-His) was immobilized onto the surface of a glass plate modified with a Ni(II)-chelated alkanethiol monolayer. The immobilization is expected to take place through the coordination between Ni(II) and His-tag. The bFGF-immobilized surface was exposed to citrate buffer solution to refold in situ the surface-immobilized bFGF. The secondary structure of immobilized bFGF-His was analyzed by solid-phase circular dichroism (CD) spectroscopy. Immortalized human mesenchymal stromal cells (hMSCs) were cultured on the bFGF-His-immobilized surface to examine their proliferation. CD spectroscopy revealed that the immobilized bFGF initially exhibited secondary structure rich in α-helix and that the spectrum was gradually transformed to exhibit the formation of β-strands upon exposure to citrate buffer solution, approaching to the spectrum of native bFGF. The rate of hMSC proliferation was 1.2-fold higher on the bFGF-immobilized surface treated with in situ citrate buffer, compared to the polystyrene surface. The immobilized bFGF-His treated in situ with citrate buffer solution seemed to be biologically active because its secondary structure approached its native state. This was well demonstrated by the cell culture experiments. From these results we conclude that immobilization of bFGF on the culture substrate serves to enhance proliferation of hMSCs.
Development and selection of low-level multi-drug resistance over an extended range of sub-inhibitory ciprofloxacin concentrations in Escherichia coli
Authors: Ching Carly , Zaman Muhammad H.
Published: May 2020

To better combat bacterial antibiotic resistance, a growing global health threat, it is imperative to understand its drivers and underlying biological mechanisms. One potential driver of antibiotic resistance is exposure to sub-inhibitory concentrations of antibiotics. This occurs in both the environment and clinic, from agricultural contamination to incorrect dosing and usage of poor-quality medicines. To better understand this driver, we tested the effect of a broad range of ciprofloxacin concentrations on antibiotic resistance development in Escherichia coli. We observed the emergence of stable, low-level multi-drug resistance that was both time and concentration dependent. Furthermore, we identified a spectrum of single mutations in strains with resistant phenotypes, both previously described and novel. Low-level class-wide resistance, which often goes undetected in the clinic, may allow for bacterial survival and establishment of a reservoir for outbreaks of high-level antibiotic resistant infections.
Temporal Context affects interval timing at the perceptual level
Authors: Zimmermann Eckart , Cicchini Guido Marco
Published: May 2020

There is now ample evidence that when observers are asked to estimate features of an object they take into account recent stimulation history and blend the current sensory evidence with the recent stimulus intensity according to their reliability. Most of this evidence has been obtained via estimation or production paradigms both of which entail a conspicuous post-perceptual decision stage. So it is an unsolved question, as to whether the trace of previous stimulation contributes at the decision stage or as early as the perceptual stage. To this aim we focused on duration judgments, which typically exhibit strong central tendency effects and asked a duration comparison between two intervals, one of which characterized by high uncertainty. We found that the perceived duration of this interval regressed toward the average duration, demonstrating a genuine perceptual bias. Regression did not transfer between the visual and the auditory modality, indicating it is modality specific, but generalized across passively observed and actively produced intervals. These findings suggest that temporal central tendency effects modulate how long an interval appears to us and that integration of current sensory evidence can occur as early as in the sensory systems.
Signal profiling of the β1AR reveals coupling to novel signalling pathways and distinct phenotypic responses mediated by β1AR and β2AR
Authors: Lukasheva Viktoriya , Devost Dominic , Le Gouill Christian , Namkung Yoon , Martin Ryan D. , Longpré Jean-Michel , Amraei Mohammad , Shinjo Yuji , Hogue Mireille , Lagacé Monique , Breton Billy , Aoki Junken , Tanny Jason C. , Laporte Stéphane A. , Pineyro Graciela , Inoue Asuka , Bouvier Michel , Hébert Terence E.
Published: May 2020

A comprehensive understanding of signalling downstream of GPCRs requires a broad approach to capture novel signalling modalities in addition to established pathways. Here, using an array of sixteen validated BRET-based biosensors, we analyzed the ability of seven different β-adrenergic ligands to engage five distinct signalling pathways downstream of the β1-adrenergic receptor (β1AR). In addition to generating signalling signatures and capturing functional selectivity for the different ligands toward these pathways, we also revealed coupling to signalling pathways that have not previously been ascribed to the βAR. These include coupling to Gzand G12pathways. The signalling cascade linking the β1AR to calcium mobilization was also characterized using a combination of BRET-based biosensors and CRISPR-engineered HEK 293 cells lacking the Gαs subunit or with pharmacological or genetically engineered pathway inhibitors. We show that both Gsand G12are required for the full calcium response. Our work highlights the power of combining signal profiling with genome editing approaches to capture the full complement of GPCR signalling activities in a given cell type and to probe their underlying mechanisms.
Oxygen-evolution reaction by nickel/nickel oxide interface in the presence of ferrate(VI)
Authors: Ali Akbari Mohammad Saleh , Bagheri Robabeh , Song Zhenlun , Najafpour Mohammad Mahdi
Published: May 2020

In this study, we investigate the effect of K2FeO4, as a new and soluble Fe salt at alkaline conditions, on oxygen-evolution reaction (OER) of Ni oxide. Both oxidation and reduction peaks for Ni in the presence and absence of Fe are linearly changed by (scan rate)1/2. Immediately after the interaction of [FeO4]2- with the surface of the electrode, a significant increase in OER is observed. This could be indicative of the fact that either the [FeO4]2- on the surface of Ni oxide is directly involved in OER, or, it is important to activate Ni oxide toward OER. Due to the change in the Ni(II)/(III) peak, it is hypothesized that Fe impurity in KOH or electrochemical cell has different effects at the potential range. At low potential, [FeO4]2− is reduced on the surface of the electrode, and thus, is significantly adsorbed on the electrode. Finally, oxygen-evolution measurements of K2FeO4 and Ni2O3 are investigated under chemical conditions. K2FeO4 is not stable in the presence of Ni(II) oxide, and OER is observed in a KOH solution (pH ≈ 13).
Recombinant spider silk protein eADF4(C16)-RGD coatings are suitable for cardiac tissue engineering
Authors: Kramer Johannes P. M. , Aigner Tamara B. , Petzold Jana , Roshanbinfar Kaveh , Scheibel Thomas , Engel Felix B.
Published: May 2020

Cardiac tissue engineering is a promising approach to treat cardiovascular diseases, which are a major socio-economic burden worldwide. An optimal material for cardiac tissue engineering, allowing cardiomyocyte attachment and exhibiting proper immunocompatibility, biocompatibility and mechanical characteristics, has not yet emerged. An additional challenge is to develop a fabrication method that enables the generation of proper hierarchical structures and constructs with a high density of cardiomyocytes for optimal contractility. Thus, there is a focus on identifying suitable materials for cardiac tissue engineering. Here, we investigated the interaction of neonatal rat heart cells with engineered spider silk protein (eADF4(C16)) tagged with the tripeptide arginyl-glycyl-aspartic acid cell adhesion motif RGD, which can be used as coating, but can also be 3D printed. Cardiomyocytes, fibroblasts, and endothelial cells attached well to eADF4(C16)-RGD coatings, which did not induce hypertrophy in cardiomyocytes, but allowed response to hypertrophic as well as proliferative stimuli. Furthermore, Kymograph and MUSCLEMOTION analyses showed proper cardiomyocyte beating characteristics on spider silk coatings, and cardiomyocytes formed compact cell aggregates, exhibiting markedly higher speed of contraction than cardiomyocyte mono-layers on fibronectin. The results suggest that eADF4(C16)-RGD is a promising material for cardiac tissue engineering.
Author Correction: Evidence for Human Streptococcus pneumoniae in wild and captive chimpanzees: A potential threat to wild populations
Authors: Köndgen Sophie , Calvignac-Spencer Sebastien , Grützmacher Kim , Keil Verena , Mätz-Rensing Kerstin , Nowak Kathrin , Metzger Sonja , Kiyang John , Lübke-Becker Antina , Deschner Tobias , Wittig Roman M. , Lankester Felix , Leendertz Fabian H.
Published: May 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: Ultra-high throughput single-cell analysis of proteins and RNAs by split-pool synthesis
Authors: O’Huallachain Maeve , Bava Felice-Alessio , Shen Mary , Dallett Carolina , Paladugu Sri , Samusik Nikolay , Yu Simon , Hussein Razika , Hillman Grantland R. , Higgins Samuel , Lou Melanie , Trejo Angelica , Qin Laura , Tai Yu Chuan , Kinoshita Shigemi M. , Jager Astraea , Lashkari Deval , Goltsev Yury , Ozturk Sedide , Nolan Garry P.
Published: May 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Phenolic content, anti-inflammatory properties, and dermal wound repair properties of industrially processed and non-processed acai from the Brazilian Amazon
Authors: Xiong Jia , Matta Fernanda V. , Grace Mary , Lila Mary Ann , Ward Neil I. , Felipe-Sotelo Monica , Esposito Debora
Published: May 2020

Industrial processing affected polyphenol content, anti-inflammatory properties, and dermal wound repair properties of Brazilian Amazon Acai extracts.
Combo-targeted nanoassemblies as a chemotherapy delivery system against peritoneal carcinomatosis colorectal cancer
Authors: Shen Ming-Yin , Chang Siou-Han , Liu Te-I. , Lu Ting-Yu , Sabu Arjun , Chen Hsin-Hung , Chiu Hsin-Cheng
Published: May 2020

Dual tumor-targeted therapeutic NPs enable chemotherapy to effectively suppress the growth of peritoneal carcinomatosis colorectal cancer.
Epoxycyclopentane hydrate for sustainable hydrate-based energy storage: notable improvements in thermodynamic condition and storage capacity
Authors: Seol Jiwoong , Park Juwoon , Shin Woongchul
Published: May 2020

The thermodynamic stability and storage capacity of the novel epoxycyclopentane hydrate are superior to those of THF or cyclopentane hydrate.
Designing novel morphologies of l-cysteine surface capped 2D covellite (CuS) nanoplates to study the effect of CuS morphologies on dye degradation rate under visible light
Authors: Iqbal Shahid , Bahadur Ali , Anwer Shoaib , Shoaib Muhammad , Liu Guocong , Li Hao , Raheel Muhammad , Javed Mohsin , Khalid Bilal
Published: May 2020

Novel CuS@l-Cys NPs are designed by a hydrothermal route. The effects of synthetic parameters on the morphologies of CuS@l-Cys NPs were investigated. CuS@l-Cys NPs exhibit an enhanced dye degradation rate under visible light.
Photophysical properties of Ag, Zn and Cd - N-(4-pyridylmethyl)-1,8-naphthalimide complexes: influences of π-stacking and C–H⋯O interactions
Authors: Singh Munendra Pal , Baruah Jubaraj B.
Published: May 2020

In solution ligand and complexes show similiar fluorescence emission whereas emission in solid samples are distinguishable.
Benzothiadiazole bridged EDOT based donor–acceptor polymers with tunable optical, electrochemical, morphological and electrochromic performance: effects of solvents and electrolytes
Authors: Singhal Sanchita , Patra Asit
Published: May 2020

We present systematic opto-electrochemical studies of D–A polymer films prepared using different electrolytes and solvents. Significant effects of both the factors on the optical, electrochemical, morphology and electrochromic properties were found.
Performance enhancement of oxygen evolution reaction through incorporating bimetallic electrocatalysts in two-dimensional metal–organic frameworks
Authors: Yang Chun , Cai Wen-Jing , Yu Bin-Bin , Qiu Hong , Li Meng-Li , Zhu Lian-Wen , Yan Zheng , Hou Lei , Wang Yao-Yu
Published: May 2020

We designed and synthesized a series of bimetallic and monometallic 2D metal–organic framework electrocatalysts with excellent stability, discussing their different electrochemical catalysts for oxygen evolution reaction (OER).
Leaching potential of heavy metals from road-deposited sediment and sorptive media during dry periods in storm water quality improvement devices
Authors: Rommel Steffen H. , Noceti Luca , Stinshoff Philipp , Helmreich Brigitte
Published: May 2020

This study evaluated if retained heavy metals leach from trapped sediment or sorptive media in storm water quality improvement devices during dry periods.
Lactobacillus plantarum KFY04 prevents obesity in mice through the PPAR pathway and alleviates oxidative damage and inflammation
Authors: Long Xingyao , Zeng Xiaofei , Tan Fang , Yi Ruokun , Pan Yanni , Zhou Xianrong , Mu Jianfei , Zhao Xin
Published: May 2020

Lactobacillus plantarum KFY04 can significantly inhibited the increase of adipocytes and decrease the adipocyte size in adipose tissue. LP-KFY04 can be used to mitigate high-fat-diet-induced obesity in mice.
Comparison of three reconstruction methods based on deconvolution, iterative algorithm and neural network for X-ray fluorescence imaging with coded aperture optics
Authors: Kulow Anico , Guilherme Buzanich Ana , Reinholz Uwe , Emmerling Franziska , Hampel Sven , Fittschen Ursula Elisabeth Adriane , Streli Christina , Radtke Martin
Published: May 2020

Superimposed images acquired by XRF with coded aperture optics can be recovered successfully iteratively.