bluuebunny/crossref_metadata_2025_split huggingface dataset:
Southern Hemisphere forcing of South Asian monsoon precipitation over the past ~1 million years
Authors: Gebregiorgis D. , Hathorne E. C. , Giosan L. , Clemens S. , Nürnberg D. , Frank M. 
Published: November 2018

AbstractThe orbital-scale timing of South Asian monsoon (SAM) precipitation is poorly understood. Here we present new SST and seawater δ18O (δ18Osw) records from the Bay of Bengal, the core convective region of the South Asian monsoon, over the past 1 million years. Our records reveal that SAM precipitation peaked in the precession band ~9 kyrs after Northern Hemisphere summer insolation maxima, in phase with records of SAM winds in the Arabian Sea and eastern Indian Ocean. Precession-band variance, however, accounts for ~30% of the total variance of SAM precipitation while it was either absent or dominant in records of the East Asian monsoon (EAM). This and the observation that SAM precipitation was phase locked with obliquity minima and was sensitive to Southern Hemisphere warming provides clear evidence that SAM and EAM precipitation responded differently to orbital forcing and highlights the importance of internal processes forcing monsoon variability.
Electrically induced and detected Néel vector reversal in a collinear antiferromagnet
Authors: Godinho J. , Reichlová H. , Kriegner D. , Novák V. , Olejník K. , Kašpar Z. , Šobáň Z. , Wadley P. , Campion R. P. , Otxoa R. M. , Roy P. E. , Železný J. , Jungwirth T. , Wunderlich J. 
Published: November 2018

AbstractAntiferromagnets are enriching spintronics research by many favorable properties that include insensitivity to magnetic fields, neuromorphic memory characteristics, and ultra-fast spin dynamics. Designing memory devices with electrical writing and reading is one of the central topics of antiferromagnetic spintronics. So far, such a combined functionality has been demonstrated via 90° reorientations of the Néel vector generated by the current-induced spin orbit torque and sensed by the linear-response anisotropic magnetoresistance. Here we show that in the same antiferromagnetic CuMnAs films as used in these earlier experiments we can also control 180° Néel vector reversals by switching the polarity of the writing current. Moreover, the two stable states with opposite Néel vector orientations in this collinear antiferromagnet can be electrically distinguished by measuring a second-order magnetoresistance effect. We discuss the general magnetic point group symmetries allowing for this electrical readout effect and its specific microscopic origin in CuMnAs.
Structural basis for the recognition of sulfur in phosphorothioated DNA
Authors: Liu Guang , Fu Wencheng , Zhang Zhenyi , He Yao , Yu Hao , Wang Yuli , Wang Xiaolei , Zhao Yi-Lei , Deng Zixin , Wu Geng , He Xinyi 
Published: November 2018

AbstractThere have been very few reports on protein domains that specifically recognize sulfur. Here we present the crystal structure of the sulfur-binding domain (SBD) from the DNA phosphorothioation (PT)-dependent restriction endonuclease ScoMcrA. SBD contains a hydrophobic surface cavity that is formed by the aromatic ring of Y164, the pyrolidine ring of P165, and the non-polar side chains of four other residues that serve as lid, base, and wall of the cavity. The SBD and PT-DNA undergo conformational changes upon binding. The S187RGRR191 loop inserts into the DNA major groove to make contacts with the bases of the GPSGCC core sequence. Mutating key residues of SBD impairs PT-DNA association. More than 1000 sequenced microbial species from fourteen phyla contain SBD homologs. We show that three of these homologs bind PT-DNA in vitro and restrict PT-DNA gene transfer in vivo. These results show that SBD-like PT-DNA readers exist widely in prokaryotes.
Probing molecule-like isolated octahedra via phase stabilization of zero-dimensional cesium lead halide nanocrystals
Authors: Arunkumar Paulraj , Cho Han Bin , Gil Kyeong Hun , Unithrattil Sanjith , Kim Yoon Hwa , Bin Im Won 
Published: November 2018

AbstractZero-dimensional (0D) inorganic perovskites have recently emerged as an interesting class of material owing to their intrinsic Pb2+ emission, polaron formation, and large exciton binding energy. They have a unique quantum-confined structure, originating from the complete isolation of octahedra exhibiting single-molecule behavior. Herein, we probe the optical behavior of single-molecule-like isolated octahedra in 0D Cesium lead halide (Cs4PbX6, X = Cl, Br/Cl, Br) nanocrystals through isovalent manganese doping at lead sites. The incorporation of manganese induced phase stabilization of 0D Cs4PbX6 over CsPbX3 by lowering the symmetry of PbX6 via enhanced octahedral distortion. This approach enables the synthesis of CsPbX3 free Cs4PbX6 nanocrystals. A high photoluminescence quantum yield for manganese emission was obtained in colloidal (29%) and solid (21%, powder) forms. These performances can be attributed to structure-induced confinement effects, which enhance the energy transfer from localized host exciton states to Mn2+ dopant within the isolated octahedra.
Divergent trends in functional and phylogenetic structure in reptile communities across Africa
Authors: Ramm Till , Cantalapiedra Juan L. , Wagner Philipp , Penner Johannes , Rödel Mark-Oliver , Müller Johannes 
Published: November 2018

AbstractDespite extensive research on ecological community compositions, general patterns across large-scale environmental gradients have remained unclear. A widely used explanatory model is the stress dominance hypothesis (SDH), predicting that the relative influence of environmental filtering is greater in stressful habitats while competition is more important in benign environments. Here, we test the SDH using African squamates as a model system to facilitate general predictions on community structures amidst changing global environments. For the first time we investigate changes in functional, phylogenetic and species diversity across continental, environmental gradients within a multidimensional, phylogenetically informed approach. Results suggest that phylogenetic patterns of African squamates were likely shaped by clade-specific biogeographic histories, whereas functional structure reflects SDH predictions. We further detected significant structuring at both local and regional spatial scales, emphasizing the impact of regional-historical processes on local assemblages, and the need for broad conceptual frameworks to detect general patterns of community composition.
Structure of the 4-1BB/4-1BBL complex and distinct binding and functional properties of utomilumab and urelumab
Authors: Chin S. Michael , Kimberlin Christopher R. , Roe-Zurz Zygy , Zhang Pamela , Xu Allison , Liao-Chan Sindy , Sen Debasish , Nager Andrew R. , Oakdale Nicole Schirle , Brown Colleen , Wang Feng , Yang Yuting , Lindquist Kevin , Yeung Yik Andy , Salek-Ardakani Shahram , Chaparro-Riggers Javier 
Published: November 2018

Abstract4-1BB (CD137,TNFRSF9) is an inducible costimulatory receptor expressed on activated T cells. Clinical trials of two agonist antibodies, utomilumab (PF-05082566) and urelumab (BMS-663513), are ongoing in multiple cancer indications, and both antibodies demonstrate distinct activities in the clinic. To understand these differences, we solved structures of the human 4-1BB/4-1BBL complex, the 4-1BBL trimer alone, and 4-1BB bound to utomilumab or urelumab. The 4-1BB/4-1BBL complex displays a unique interaction between receptor and ligand when compared with other TNF family members. Furthermore, our ligand-only structure differs from previously published data. Utomilumab, a ligand-blocking antibody, binds 4-1BB between CRDs 3 and 4. In contrast, urelumab binds 4-1BB CRD-1, away from the ligand binding site. Finally, cell-based assays demonstrate utomilumab is a milder agonist than urelumab. Collectively, our data provide a deeper understanding of the 4-1BB signaling complex, providing a template for future development of next generation 4-1BB targeted biologics.
Long term but not short term exposure to obesity related microbiota promotes host insulin resistance
Authors: Foley Kevin P. , Zlitni Soumaya , Denou Emmanuel , Duggan Brittany M. , Chan Rebecca W. , Stearns Jennifer C. , Schertzer Jonathan D. 
Published: November 2018

AbstractThe intestinal microbiota and insulin sensitivity are rapidly altered after ingestion of obesogenic diets. We find that changes in the composition of the fecal microbiota precede changes in glucose tolerance when mice are fed obesogenic, low fiber, high fat diets (HFDs). Antibiotics alter glycemia during the first week of certain HFDs, but antibiotics show a more robust improvement in glycemic control in mice with protracted obesity caused by long-term feeding of multiple HFDs. Microbiota transmissible dysglycemia and glucose intolerance only occur when germ-free mice are exposed to obesity-related microbes for more than 45 days. We find that sufficient host exposure time to microbiota derived from HFD-fed mice allows microbial factors to contribute to insulin resistance, independently from increased adiposity in mice. Our results are consistent with intestinal microbiota contributing to chronic insulin resistance and dysglycemia during prolonged obesity, despite rapid diet-induced changes in the taxonomic composition of the fecal microbiota.
Src-transformed cells hijack mitosis to extrude from the epithelium
Authors: Anton Katarzyna A. , Kajita Mihoko , Narumi Rika , Fujita Yasuyuki , Tada Masazumi 
Published: November 2018

AbstractAt the initial stage of carcinogenesis single mutated cells appear within an epithelium. Mammalian in vitro experiments show that potentially cancerous cells undergo live apical extrusion from normal monolayers. However, the mechanism underlying this process in vivo remains poorly understood. Mosaic expression of the oncogene vSrc in a simple epithelium of the early zebrafish embryo results in extrusion of transformed cells. Here we find that during extrusion components of the cytokinetic ring are recruited to adherens junctions of transformed cells, forming a misoriented pseudo-cytokinetic ring. As the ring constricts, it separates the basal from the apical part of the cell releasing both from the epithelium. This process requires cell cycle progression and occurs immediately after vSrc-transformed cell enters mitosis. To achieve extrusion, vSrc coordinates cell cycle progression, junctional integrity, cell survival and apicobasal polarity. Without vSrc, modulating these cellular processes reconstitutes vSrc-like extrusion, confirming their sufficiency for this process.
Adaptation to sub-optimal hosts is a driver of viral diversification in the ocean
Authors: Enav Hagay , Kirzner Shay , Lindell Debbie , Mandel-Gutfreund Yael , Béjà Oded 
Published: November 2018

AbstractCyanophages of theMyoviridaefamily include generalist viruses capable of infecting a wide range of hosts including those from different cyanobacterial genera. While the influence of phages on host evolution has been studied previously, it is not known how the infection of distinct hosts influences the evolution of cyanophage populations. Here, using an experimental evolution approach, we investigated the adaptation of multiple cyanophage populations to distinct cyanobacterial hosts. We show that when infecting an “optimal” host, whose infection is the most efficient, phage populations accumulated only a few mutations. However, when infecting “sub-optimal” hosts, different mutations spread in the phage populations, leading to rapid diversification into distinct subpopulations. Based on our results, we propose a model demonstrating how shifts in microbial abundance, which lead to infection of “sub-optimal” hosts, act as a driver for rapid diversification of viral populations.
Vibrational fingerprint of localized excitons in a two-dimensional metal-organic crystal
Authors: Corva M. , Ferrari A. , Rinaldi M. , Feng Z. , Roiaz M. , Rameshan C. , Rupprechter G. , Costantini R. , Dell’Angela M. , Pastore G. , Comelli G. , Seriani N. , Vesselli E. 
Published: November 2018

AbstractLong-lived excitons formed upon visible light absorption play an essential role in photovoltaics, photocatalysis, and even in high-density information storage. Here, we describe a self-assembled two-dimensional metal-organic crystal, composed of graphene-supported macrocycles, each hosting a single FeN4center, where a single carbon monoxide molecule can adsorb. In this heme-like biomimetic model system, excitons are generated by visible laser light upon a spin transition associated with the layer 2D crystallinity, and are simultaneously detected via the carbon monoxide ligand stretching mode at room temperature and near-ambient pressure. The proposed mechanism is supported by the results of infrared and time-resolved pump-probe spectroscopies, and by ab initio theoretical methods, opening a path towards the handling of exciton dynamics on 2D biomimetic crystals.
Systemic neurotransmitter responses to clinically approved and experimental neuropsychiatric drugs
Authors: Noori Hamid R. , Mervin Lewis H. , Bokharaie Vahid , Durmus Özlem , Egenrieder Lisamon , Fritze Stefan , Gruhlke Britta , Reinhardt Giulia , Schabel Hans-Hendrik , Staudenmaier Sabine , Logothetis Nikos K. , Bender Andreas , Spanagel Rainer 
Published: November 2018

AbstractNeuropsychiatric disorders are the third leading cause of global disease burden. Current pharmacological treatment for these disorders is inadequate, with often insufficient efficacy and undesirable side effects. One reason for this is that the links between molecular drug action and neurobehavioral drug effects are elusive. We use a big data approach from the neurotransmitter response patterns of 258 different neuropsychiatric drugs in rats to address this question. Data from experiments comprising 110,674 rats are presented in the Syphad database [www.syphad.org]. Chemoinformatics analyses of the neurotransmitter responses suggest a mismatch between the current classification of neuropsychiatric drugs and spatiotemporal neurostransmitter response patterns at the systems level. In contrast, predicted drug–target interactions reflect more appropriately brain region related neurotransmitter response. In conclusion the neurobiological mechanism of neuropsychiatric drugs are not well reflected by their current classification or their chemical similarity, but can be better captured by molecular drug–target interactions.
Predicting accurate cathode properties of layered oxide materials using the SCAN meta-GGA density functional
Authors: Chakraborty Arup , Dixit Mudit , Aurbach Doron , Major Dan T. 
Published: November 2018

AbstractLayered lithium intercalating transition metal oxides are promising cathode materials for Li-ion batteries. Here, we scrutinize the recently developed strongly constrained and appropriately normed (SCAN) density functional method to study structural, magnetic, and electrochemical properties of prototype cathode materials LiNiO2, LiCoO2, and LiMnO2 at different Li-intercalation limits. We show that SCAN outperforms earlier popular functional combinations, providing results in considerably better agreement with experiment without the use of Hubbard parameters, and dispersion corrections are found to have a small effect. In particular, SCAN fares better than Perdew–Burke–Ernzerhof (PBE) functional for the prediction of band-gaps and absolute voltages, better than PBE+U for the electronic density of states and voltage profiles, and better than both PBE and PBE+U for electron densities and in operando lattice parameters. This overall better performance of SCAN may be ascribed to improved treatment of localized states and a better description of short-range dispersion interactions.
FXR agonist obeticholic acid induces liver growth but exacerbates biliary injury in rats with obstructive cholestasis
Authors: van Golen Rowan F. , Olthof Pim B. , Lionarons Daniël A. , Reiniers Megan J. , Alles Lindy K. , Uz Zehra , de Haan Lianne , Ergin Bulent , de Waart Dirk R. , Maas Adrie , Verheij Joanne , Jansen Peter L. , Damink Steven W. Olde , Schaap Frank G. , van Gulik Thomas M. , Heger Michal 
Published: November 2018

AbstractCholestasis impairs liver regeneration following partial liver resection (PHx). Bile acid receptor farnesoid X-receptor (FXR) is a key mediator of liver regeneration. The effects of FXR agonist obeticholic acid (OCA) on liver (re)growth were therefore studied in cholestatic rats. Animals underwent sham surgery or reversible bile duct ligation (rBDL). PHx with concurrent internal biliary drainage was performed 7 days after rBDL. Animals were untreated or received OCA (10 mg/kg/day) per oral gavage from rBDL until sacrifice. After 7 days of OCA treatment, dry liver weight increased in the rBDL + OCA group, indicating OCA-mediated liver growth. Enhanced proliferation in the rBDL + OCA group prior to PHx concurred with a rise in Ki67-positive hepatocytes, elevated hepatic Ccnd1 and Cdc25b expression, and an induction of intestinal fibroblast growth factor 15 expression. Liver regrowth after PHx was initially stagnant in the rBDL + OCA group, possibly due to hepatomegaly prior to PHx. OCA increased hepatobiliary injury markers during BDL, which was accompanied by upregulation of the bile salt export pump. There were no differences in histological liver injury. In conclusion, OCA induces liver growth in cholestatic rats prior to PHx but exacerbates biliary injury during cholestasis, likely by forced pumping of bile acids into an obstructed biliary tree.
Proportion of neuropathic pain in the back region in chronic low back pain patients -a multicenter investigation
Authors: Li Jun , He Jing , Li Hu , Fan Bi-Fa , Liu Bo-Tao , Mao Peng , Jin Yi , Cheng Zhu-Qiang , Zhang Ting-Jie , Zhong Zhi-Fang , Li Si-Ji , Zhu Sai-Nan , Feng Yi 
Published: November 2018

AbstractNeuropathy can contribute to low back pain (LBP) in the region of the back. Our study investigated the proportion of neuropathic pain (NP) in low back region in chronic LBP patients from multicenter and clinics in China and identified associated factors. Assessment was made using a questionnaire and the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS, only tested in low back region), as well as Quantitative Sensory Testing (QST, merely applied to the low back region), the Hospital Anxiety and Depression Scale (HADS) and the Oswestry Disability Index (ODI). Our questionnaire collected demographic information, behavioral habits and medical records. 2116 outpatients over 18 years old complaining of LBP lasting more than 3 months were enrolled in this study. The NP proportion in low back region in chronic LBP patients was 2.8%. Multivariable logistic regression analysis showed that histories of lumbar surgery, abdominal or pelvic surgery, and drinking alcohol were independent positive predictors for LBP of predominantly neuropathic origin (LBNPO), while history of low back sprain and frequently carrying weight as independent negative predictor. Using these parameters may help the identification of patients with chronic LBP likely to develop NP leading to improved treatment outcomes.
LIP formation and protracted lower mantle upwelling induced by rifting and delamination
Authors: Petersen Kenni Dinesen , Schiffer Christian , Nagel Thorsten 
Published: November 2018

AbstractLarge Igneous Provinces (LIPs) are commonly attributed to mantle plumes, hot upwellings from the deep lower mantle, apparently unrelated to plate motions. However, LIPs often form in association with rifting and breakup. Using numerical modelling, we introduce a novel idea that explains plume-like mantle upwelling by plate tectonic processes. Our model indicates that rifting-induced delamination of orogenic lithosphere can perturb the thermochemical mantle stratification and induce lower mantle upwelling which causes syn-rift LIP formation followed by protracted and enhanced mid ocean ridge basalt (MORB) generation. Our model provides an explanation for the geographical correlation between the Caledonian suture, the North Atlantic Igneous Province (NAIP) and present-day Icelandic magmatism.
The Antiarrhythmic Drug, Dronedarone, Demonstrates Cytotoxic Effects in Breast Cancer Independent of Thyroid Hormone Receptor Alpha 1 (THRα1) Antagonism
Authors: Elliott Mitchell J. , Jerzak Katarzyna J. , Cockburn Jessica G. , Safikhani Zhaleh , Gwynne William D. , Hassell John A. , Bane Anita , Silvester Jennifer , Thu Kelsie L. , Haibe-Kains Benjamin , Mak Tak W. , Cescon David W. 
Published: November 2018

AbstractPrevious research has suggested that thyroid hormone receptor alpha 1 (THRα1), a hormone responsive splice variant, may play a role in breast cancer progression. Whether THRα1 can be exploited for anti-cancer therapy is unknown. The antiproliferative and antitumor effects of dronedarone, an FDA-approved anti-arrhythmic drug which has been shown to antagonize THRα1, was evaluated in breast cancer cell lines in vitro and in vivo. The THRα1 splice variant and the entire receptor, THRα, were also independently targeted using siRNA to determine the effect of target knockdown in vitro. In our study, dronedarone demonstrates cytotoxic effects in vitro and in vivo in breast cancer cell lines at doses and concentrations that may be clinically relevant. However, knockdown of either THRα1 or THRα did not cause substantial anti-proliferative or cytotoxic effects in vitro, nor did it alter the sensitivity to dronedarone. Thus, we conclude that dronedarone’s cytotoxic effect in breast cancer cell lines are independent of THRα or THRα1 antagonism. Further, the depletion of THRα or THRα1 does not affect cell viability or proliferation. Characterizing the mechanism of dronedarone’s anti-tumor action may facilitate drug repurposing or the development of new anti-cancer agents.
Gradient Relationship between Increased Mean Corpuscular Volume and Mortality Associated with Cerebral Ischemic Stroke and Ischemic Heart Disease: A Longitudinal Study on 66,294 Taiwanese
Authors: Wu Tzy-Haw , Fann Jean Ching-Yuan , Chen Sam Li-Sheng , Yen Amy Ming-Fang , Wen Chiung-Jung , Lu Yun-Ru , Chen Hsiu-Hsi , Chiu Sherry Yueh-Hsia , Liou Horng-Huei 
Published: November 2018

AbstractThe gradient relationship between mean corpuscular volume (MCV) and mortality due to ischemic vascular disease has not been researched using a large-scale population-based study. This study evaluated the association between MCV and death attributable to cerebrovascular disease (CVD) and cardiovascular disease (CAD) in a large population- and community-based Taiwanese cohort. A longitudinal study with a 9-year follow-up was conducted to evaluate individuals aged 20 years or older who had participated in the Keelung (the northernmost city in Taiwan) community-based integrated screening (abbreviated as KCIS) program since September 1999. The mortality rates associated with CVD and CAD were classified across a range of different MCV levels. Increased MCV levels were associated with an increased risk of CVD/CAD-related death (adjusted hazard ratio [aHR] = 1.42, trend test P = 0.0119). Marginally statistically significant associations were noted for specific deaths from ischemic heart disease (aHR = 1.44, trend test P = 0.0992) and cerebral ischemic stroke (aHR = 1.66, trend test P = 0.0667), respectively, but no significant gradient relationship was noted for death from cerebral hemorrhage stroke (aHR = 1.23, trend test, P = 0.6278). A gradient relationship between baseline MCV level and CVD/CAD-related death was noted, but whether such gradient relationships existed for two specific deaths and how these relationships may be confounded by extraneous factors that were not considered here should be investigated in the future.