bluuebunny/crossref_metadata_2025_split huggingface dataset:
Global and Arctic climate sensitivity enhanced by changes in North Pacific heat flux
Authors: Praetorius Summer , Rugenstein Maria , Persad Geeta , Caldeira Ken 
Published: August 2018

AbstractArctic amplification is a consequence of surface albedo, cloud, and temperature feedbacks, as well as poleward oceanic and atmospheric heat transport. However, the relative impact of changes in sea surface temperature (SST) patterns and ocean heat flux sourced from different regions on Arctic temperatures are not well constrained. We modify ocean-to-atmosphere heat fluxes in the North Pacific and North Atlantic in a climate model to determine the sensitivity of Arctic temperatures to zonal heterogeneities in northern hemisphere SST patterns. Both positive and negative ocean heat flux perturbations from the North Pacific result in greater global and Arctic surface air temperature anomalies than equivalent magnitude perturbations from the North Atlantic; a response we primarily attribute to greater moisture flux from the subpolar extratropics to Arctic. Enhanced poleward latent heat and moisture transport drive sea-ice retreat and low-cloud formation in the Arctic, amplifying Arctic surface warming through the ice-albedo feedback and infrared warming effect of low clouds. Our results imply that global climate sensitivity may be dependent on patterns of ocean heat flux in the northern hemisphere.
Evaluation of chromatin accessibility in prefrontal cortex of individuals with schizophrenia
Authors: Bryois Julien , Garrett Melanie E. , Song Lingyun , Safi Alexias , Giusti-Rodriguez Paola , Johnson Graham D. , Shieh Annie W. , Buil Alfonso , Fullard John F. , Roussos Panos , Sklar Pamela , Akbarian Schahram , Haroutunian Vahram , Stockmeier Craig A. , Wray Gregory A. , White Kevin P. , Liu Chunyu , Reddy Timothy E. , Ashley-Koch Allison , Sullivan Patrick F. , Crawford Gregory E. 
Published: August 2018

AbstractSchizophrenia genome-wide association studies have identified >150 regions of the genome associated with disease risk, yet there is little evidence that coding mutations contribute to this disorder. To explore the mechanism of non-coding regulatory elements in schizophrenia, we performed ATAC-seq on adult prefrontal cortex brain samples from 135 individuals with schizophrenia and 137 controls, and identified 118,152 ATAC-seq peaks. These accessible chromatin regions in the brain are highly enriched for schizophrenia SNP heritability. Accessible chromatin regions that overlap evolutionarily conserved regions exhibit an even higher heritability enrichment, indicating that sequence conservation can further refine functional risk variants. We identify few differences in chromatin accessibility between cases and controls, in contrast to thousands of age-related differential accessible chromatin regions. Altogether, we characterize chromatin accessibility in the human prefrontal cortex, the effect of schizophrenia and age on chromatin accessibility, and provide evidence that our dataset will allow for fine mapping of risk variants.
Dual-template engineering of triple-layered nanoarray electrode of metal chalcogenides sandwiched with hydrogen-substituted graphdiyne
Authors: Zhuo Sifei , Shi Yusuf , Liu Lingmei , Li Renyuan , Shi Le , Anjum Dalaver H. , Han Yu , Wang Peng 
Published: August 2018

AbstractHybrid nanostructures integrating electroactive materials with functional species, such as metal-organic frameworks, covalent organic frameworks, graphdiyne etc., are of significance for both fundamental research and energy conversion/storage applications. Here, hierarchical triple-layered nanotube arrays, which consist of hydrogen-substituted graphdiyne frameworks seamlessly sandwiched between an outer layer of nickel–cobalt co-doped molybdenum disulfide nanosheets and an inner layer of mixed cobalt sulfide and nickel sulfide (Co9S8/Ni3S2), are directly fabricated on conductive carbon paper. The elaborate triple-layered structure emerges as a useful hybrid electrode for energy conversion and storage, in which the organic hydrogen-substituted graphdiyne middle layer, with an extended π-conjugated system between the electroactive nanomaterials, provides built-in electron and ion channels that are crucial for performance enhancement. This dual-template synthetic method, which makes use of microporous organic networks to confine a self-template, is shown to be versatile and thus provides a promising platform for advanced nanostructure-engineering of hierarchical multi-layered nanostructures towards a wide range of electrochemical applications.
Developmental seizures and mortality result from reducing GABAA receptor α2-subunit interaction with collybistin
Authors: Hines Rochelle M. , Maric Hans Michael , Hines Dustin J. , Modgil Amit , Panzanelli Patrizia , Nakamura Yasuko , Nathanson Anna J. , Cross Alan , Deeb Tarek , Brandon Nicholas J. , Davies Paul , Fritschy Jean-Marc , Schindelin Hermann , Moss Stephen J. 
Published: August 2018

AbstractFast inhibitory synaptic transmission is mediated by γ-aminobutyric acid type A receptors (GABAARs) that are enriched at functionally diverse synapses via mechanisms that remain unclear. Using isothermal titration calorimetry and complementary methods we demonstrate an exclusive low micromolar binding of collybistin to the α2-subunit of GABAARs. To explore the biological relevance of collybistin-α2-subunit selectivity, we generate mice with a mutation in the α2-subunit-collybistin binding region (Gabra2-1). The mutation results in loss of a distinct subset of inhibitory synapses and decreased amplitude of inhibitory synaptic currents.Gabra2–1 mice have a striking phenotype characterized by increased susceptibility to seizures and early mortality. SurvivingGabra2-1 mice show anxiety and elevations in electroencephalogramδpower, which are ameliorated by treatment with the α2/α3-selective positive modulator, AZD7325. Taken together, our results demonstrate an α2-subunit selective binding of collybistin, which plays a key role in patterned brain activity, particularly during development.
Statin as a novel pharmacotherapy of pulmonary alveolar proteinosis
Authors: McCarthy Cormac , Lee Elinor , Bridges James P. , Sallese Anthony , Suzuki Takuji , Woods Jason C. , Bartholmai Brian J. , Wang Tisha , Chalk Claudia , Carey Brenna C. , Arumugam Paritha , Shima Kenjiro , Tarling Elizabeth J. , Trapnell Bruce C. 
Published: August 2018

AbstractPulmonary alveolar proteinosis (PAP) is a syndrome of reduced GM-CSF-dependent, macrophage-mediated surfactant clearance, dysfunctional foamy alveolar macrophages, alveolar surfactant accumulation, and hypoxemic respiratory failure for which the pathogenetic mechanism is unknown. Here, we examine the lipids accumulating in alveolar macrophages and surfactant to define the pathogenesis of PAP and evaluate a novel pharmacotherapeutic approach. In PAP patients, alveolar macrophages have a marked increase in cholesterol but only a minor increase in phospholipids, and pulmonary surfactant has an increase in the ratio of cholesterol to phospholipids. Oral statin therapy is associated with clinical, physiological, and radiological improvement in autoimmune PAP patients, and ex vivo statin treatment reduces cholesterol levels in explanted alveolar macrophages. In Csf2rb−/− mice, statin therapy reduces cholesterol accumulation in alveolar macrophages and ameliorates PAP, and ex vivo statin treatment increases cholesterol efflux from macrophages. These results support the feasibility of statin as a novel pathogenesis-based pharmacotherapy of PAP.
A mouse model reproducing the pathophysiology of neonatal group B streptococcal infection
Authors: Andrade Elva Bonifácio , Magalhães Ana , Puga Ana , Costa Madalena , Bravo Joana , Portugal Camila Cabral , Ribeiro Adília , Correia-Neves Margarida , Faustino Augusto , Firon Arnaud , Trieu-Cuot Patrick , Summavielle Teresa , Ferreira Paula 
Published: August 2018

AbstractGroup B streptococcal (GBS) meningitis remains a devastating disease. The absence of an animal model reproducing the natural infectious process has limited our understanding of the disease and, consequently, delayed the development of effective treatments. We describe here a mouse model in which bacteria are transmitted to the offspring from vaginally colonised pregnant females, the natural route of infection. We show that GBS strain BM110, belonging to the CC17 clonal complex, is more virulent in this vertical transmission model than the isogenic mutant BM110∆cylE, which is deprived of hemolysin/cytolysin. Pups exposed to the more virulent strain exhibit higher mortality rates and lung inflammation than those exposed to the attenuated strain. Moreover, pups that survive to BM110 infection present neurological developmental disability, revealed by impaired learning performance and memory in adulthood. The use of this new mouse model, that reproduces key steps of GBS infection in newborns, will promote a better understanding of the physiopathology of GBS-induced meningitis.
Persistent structures in a three-dimensional dynamical system with flowing and non-flowing regions
Authors: Zaman Zafir , Yu Mengqi , Park Paul P. , Ottino Julio M. , Lueptow Richard M. , Umbanhowar Paul B. 
Published: August 2018

AbstractMixing of fluids and mixing of solids are both relatively mature fields. In contrast, mixing in systems where flowing and non-flowing regions coexist remains largely unexplored and little understood. Here we report remarkably persistent mixing and non-mixing regions in a three-dimensional dynamical system where randomness is expected. A spherical shell half-filled with dry non-cohesive particles and periodically rotated about two horizontal axes generates complex structures that vary non-trivially with the rotation angles. They result from the interplay between fluid-like mixing by stretching-and-folding, and solids mixing by cutting-and-shuffling. In the experiments, larger non-mixing regions predicted by a cutting-and-shuffling model alone can persist for a range of protocols despite the presence of stretching-and-folding flows and particle-collision-driven diffusion. By uncovering the synergy of simultaneous fluid and solid mixing, we point the way to a more fundamental understanding of advection driven mixing in materials with coexisting flowing and non-flowing regions.
Critical role of CD4+ T cells and IFNγ signaling in antibody-mediated resistance to Zika virus infection
Authors: Lucas Carolina G. O. , Kitoko Jamil Z. , Ferreira Fabricio M. , Suzart Vinicius G. , Papa Michelle P. , Coelho Sharton V. A. , Cavazzoni Cecilia B. , Paula-Neto Heitor A. , Olsen Priscilla C. , Iwasaki Akiko , Pereira Renata M. , Pimentel-Coelho Pedro M. , Vale Andre M. , de Arruda Luciana B. , Bozza Marcelo T. 
Published: August 2018

AbstractProtective adaptive immunity to Zika virus (ZIKV) has been mainly attributed to cytotoxic CD8+ T cells and neutralizing antibodies, while the participation of CD4+ T cells in resistance has remained largely uncharacterized. Here, we show a neutralizing antibody response, dependent on CD4+ T cells and IFNγ signaling, which we detected during the first week of infection and is associated with reduced viral load in the brain, prevention of rapid disease onset and survival. We demonstrate participation of these components in the resistance to ZIKV during primary infection and in murine adoptive transfer models of heterologous ZIKV infection in a background of IFNR deficiency. The protective effect of adoptively transferred CD4+ T cells requires IFNγ signaling, CD8+ T cells and B lymphocytes in recipient mice. Together, this indicates the importance of CD4+ T cell responses in future vaccine design for ZIKV.
Monitoring the action of redox-directed cancer therapeutics using a human peroxiredoxin-2-based probe
Authors: Langford Troy F. , Huang Beijing K. , Lim Joseph B. , Moon Sun Jin , Sikes Hadley D. 
Published: August 2018

AbstractRedox cancer therapeutics target the increased reliance on intracellular antioxidant systems and enhanced susceptibility to oxidant-induced stress of some cancer cells compared to normal cells. Many of these therapeutics are thought to perturb intracellular levels of the oxidant hydrogen peroxide (H2O2), a signaling molecule that modulates a number of different processes in human cells. However, fluorescent probes for this species remain limited in their ability to detect the small perturbations induced during successful treatments. We report a fluorescent sensor based upon human peroxiredoxin-2, which acts as the natural indicator of small H2O2 fluctuations in human cells. The new probe reveals peroxide-induced oxidation in human cells below the detection limit of current probes, as well as peroxiredoxin-2 oxidation caused by two different redox cancer therapeutics in living cells. This capability will be useful in elucidating the mechanism of current redox-based therapeutics and in developing new ones.
ATP activates bestrophin ion channels through direct interaction
Authors: Zhang Yu , Kittredge Alec , Ward Nancy , Ji Changyi , Chen Shoudeng , Yang Tingting 
Published: August 2018

AbstractHuman Bestrophin1 (hBest1) is a Ca2+-activated Cl− channel in retinal pigment epithelium (RPE) essential for retina physiology, and its mutation results in retinal degenerative diseases that have no available treatments. Here, we discover that hBest1’s channel activity in human RPE is significantly enhanced by adenosine triphosphate (ATP) in a dose-dependent manner. We further demonstrate a direct interaction between ATP and bestrophins, and map the ATP-binding motif on hBest1 to an intracellular loop adjacent to the channel activation gate. Importantly, a disease-causing mutation of hBest1 located within the ATP-binding motif, p.I201T, diminishes ATP-dependent activation of the channel in patient-derived RPE, while the corresponding mutants in bestrophin homologs display defective ATP binding and a conformational change in the ATP-binding motif. Taken together, our results identify ATP as a critical activator of bestrophins, and reveal the molecular mechanism of an hBest1 patient-specific mutation.
Variation in bradyrhizobial NopP effector determines symbiotic incompatibility with Rj2-soybeans via effector-triggered immunity
Authors: Sugawara Masayuki , Takahashi Satoko , Umehara Yosuke , Iwano Hiroya , Tsurumaru Hirohito , Odake Haruka , Suzuki Yuta , Kondo Hitoshi , Konno Yuki , Yamakawa Takeo , Sato Shusei , Mitsui Hisayuki , Minamisawa Kiwamu 
Published: August 2018

AbstractGenotype-specific incompatibility in legume–rhizobium symbiosis has been suggested to be controlled by effector-triggered immunity underlying pathogenic host-bacteria interactions. However, the rhizobial determinant interacting with the host resistance protein (e.g., Rj2) and the molecular mechanism of symbiotic incompatibility remain unclear. Using natural mutants of Bradyrhizobium diazoefficiens USDA 122, we identified a type III-secretory protein NopP as the determinant of symbiotic incompatibility with Rj2-soybean. The analysis of nopP mutations and variants in a culture collection reveal that three amino acid residues (R60, R67, and H173) in NopP are required for Rj2-mediated incompatibility. Complementation of rj2-soybean by the Rj2 allele confers the incompatibility induced by USDA 122-type NopP. In response to incompatible strains, Rj2-soybean plants activate defense marker gene PR-2 and suppress infection thread number at 2 days after inoculation. These results suggest that Rj2-soybeans monitor the specific variants of NopP and reject bradyrhizobial infection via effector-triggered immunity mediated by Rj2 protein.
Chemical genetic-based phenotypic screen reveals novel regulators of gluconeogenesis in human primary hepatocytes
Authors: Zou Haixia , Liu Qian , Meng Li , Zhou Jingye , Da Chenxiao , Wu Xikun , Jiang Lichun , Shou Jianyong , Hua Haiqing 
Published: August 2018

AbstractInsulin resistance is a pathophysiological hallmark of type 2 diabetes and nonalcoholic fatty liver disease. Under the condition of fat accumulation in the liver, suppression of hepatic glucose production by insulin is diminished. In order to gain deeper understanding of dysregulation of glucose production in metabolic diseases, in the present study, we performed an unbiased phenotypic screening in primary human hepatocytes to discover novel mechanisms that regulate gluconeogenesis in the presence of insulin. To optimize phenotypic screening process, we used a chemical genetic screening approach by building a small-molecule library with prior knowledge of activity-based protein profiling. The “positive hits” result from the screen will be small molecules with known protein targets. This makes downstream deconvolution process (i.e., determining the relevant biological targets) less time-consuming. To unbiasedly decipher the molecular targets, we developed a novel statistical method and discovered a set of genes, including DDR3 and CACNA1E that suppressed gluconeogenesis in human hepatocytes. Further investigation, including transcriptional profiling and gene network analysis, was performed to understand the molecular functions of DRD3 and CACNA1E in human hepatocytes.
Radiocarbon analysis of modern olive wood raises doubts concerning a crucial piece of evidence in dating the Santorini eruption
Authors: Ehrlich Yael , Regev Lior , Boaretto Elisabetta 
Published: August 2018

AbstractCharred olive wood is abundant in the archaeological record, especially around the Mediterranean. As the outermost ring closest to the bark is assumed to represent the latest time that the tree was alive, the radiocarbon date obtained from the outermost rings of an olive branch buried during the Santorini volcanic eruption is regarded as crucial evidence for the date of this cataclysmic event. The date of this eruption has far reaching consequences in the archaeology of the Aegean, Egypt and the Levant, and the understanding of their interconnections. We analyzed the radiocarbon concentrations in cross-sections from a modern olive tree trunk as well as from a living branch, and obtained near-annual resolution dates using the radiocarbon “bomb peak”. In both cases we show that radiocarbon dates of the last formed wood along the circumference are not chronologically homogenous, and can differ by up to a few decades. Thus the outermost wood layer does not necessarily represent the date of the last year of growth. These findings challenge the interpretation of the results obtained from dating the olive branch from the Santorini volcanic eruption, as it could predate the eruption by a few decades. In addition, our results are also significant for any future studies based on archaeologically preserved olive wood.
Essential role of MED1 in the transcriptional regulation of ER-dependent oncogenic miRNAs in breast cancer
Authors: Nagpal Neha , Sharma Shivani , Maji Sourobh , Durante Giorgio , Ferracin Manuela , Thakur Jitendra K. , Kulshreshtha Ritu 
Published: August 2018

AbstractMediator complex has been extensively shown to regulate the levels of several protein-coding genes; however, its role in the regulation of miRNAs in humans remains unstudied so far. Here we show that MED1, a Mediator subunit in the Middle module of Mediator complex, is overexpressed in breast cancer and is a negative prognostic factor. The levels of several miRNAs (miR-100-5p, -191-5p, -193b-3p, -205-5p, -326, -422a and -425-5p) were found to be regulated by MED1. MED1 induces miR-191/425 cluster in an estrogen receptor-alpha (ER-α) dependent manner. Occupancy of MED1 on estrogen response elements (EREs) upstream of miR-191/425 cluster is estrogen and ER-α-dependent and ER-α-induced expression of these miRNAs is MED1-dependent. MED1 mediates induction of cell proliferation and migration and the genes associated with it (JUN, FOS, EGFR, VEGF, MMP1, and ERBB4) in breast cancer, which is abrogated when used together with miR-191-inhibition. Additionally, we show that MED1 also regulates the levels of direct miR-191 target genes such as SATB1, CDK6 and BDNF. Overall, the results show that MED1/ER-α/miR-191 axis promotes breast cancer cell proliferation and migration and may serve as a novel target for therapy.
Classification and Regression Tree Approach for Prediction of Potential Hazards of Urban Airborne Bacteria during Asian Dust Events
Authors: Yoo Keunje , Yoo Hyunji , Lee Jae Min , Shukla Sudheer Kumar , Park Joonhong 
Published: August 2018

AbstractDespite progress in monitoring and modeling Asian dust (AD) events, real-time public hazard prediction based on biological evidence during AD events remains a challenge. Herein, both a classification and regression tree (CART) and multiple linear regression (MLR) were applied to assess the applicability of prediction for potential urban airborne bacterial hazards during AD events using metagenomic analysis and real-time qPCR. In the present work, Bacillus cereus was screened as a potential pathogenic candidate and positively correlated with PM10 concentration (p < 0.05). Additionally, detection of the bceT gene with qPCR, which codes for an enterotoxin in B. cereus, was significantly increased during AD events (p < 0.05). The CART approach more successfully predicted potential airborne bacterial hazards with a relatively high coefficient of determination (R2) and small bias, with the smallest root mean square error (RMSE) and mean absolute error (MAE) compared to the MLR approach. Regression tree analyses from the CART model showed that the PM10 concentration, from 78.4 µg/m3 to 92.2 µg/m3, is an important atmospheric parameter that significantly affects the potential airborne bacterial hazard during AD events. The results show that the CART approach may be useful to effectively derive a predictive understanding of potential airborne bacterial hazards during AD events and thus has a possible for improving decision-making tools for environmental policies associated with air pollution and public health.
Following laser induced changes of plant phenylpropanoids by Raman microscopy
Authors: Prats-Mateu Batirtze , Bock Peter , Schroffenegger Martina , Toca-Herrera José Luis , Gierlinger Notburga 
Published: August 2018

AbstractRaman microscopy is a powerful imaging technique for biological materials providing information about chemistry in context with microstructure. A 532 nm laser is often used as excitation source, because high spatial resolution and signal intensity can be achieved. The latter can be controlled by laser power and integration time, whereby high power and long times give good signal to noise ratio. However, most biological materials absorb in the VIS range and fluorescence masking the signal or even sample degradation might be hindering. Here, we show that on lignified plant cell walls even very short integration times and low laser powers induce a change in the ratio of the lignin bands at 1660 and 1600 cm−1. Time series on lignin model compounds revealed this change only in aromatic molecules with two OH-groups, such as coniferyl alcohol. Therefore, we conclude that monolignols are present in the cell wall and responsible for the observed effect. The solvent selectivity of the changes points to a laser induced polymerization process. The results emphasize how crucial careful adjustment of experimental parameters in Raman imaging of biological materials is and show the potential of time series and repeated imaging to get additional insights (e.g. monolignols).