bluuebunny/crossref_metadata_2025_split huggingface dataset:
Grain Size Variations in the Murray Formation: Stratigraphic Evidence for Changing Depositional Environments in Gale Crater, Mars
Authors: Rivera‐Hernández Frances , Sumner Dawn Y. , Mangold Nicolas , Banham Steven G. , Edgett Kenneth S. , Fedo Christopher M. , Gupta Sanjeev , Gwizd Samantha , Heydari Ezat , Maurice Sylvestre , Nachon Marion , Newsom Horton , Schieber Juergen , Stack‐Morgan Katie , Stein Nathan , Wiens Roger C. 
Published: January 2020

AbstractThe lowermost exposure of the Murray formation in Gale crater, Mars, was interpreted as sediment deposited in an ancient lake based on data collected by the Curiosity rover. Constraining the stratigraphic extent and duration of this environment has important implications for the paleohydrology of Gale. Insights into early Martian environments and paleofluid flow velocity can be obtained from grain size in rocks. Visual inspection of grain size is not always available for rocks investigated at field sites on Mars due to limited image coverage. But grain sizes can also be estimated from the Gini Index Mean Score, a grain‐size proxy that uses point‐to‐point chemical variations in ChemCam Laser Induced Breakdown Spectroscopy data. New Gini Index Mean Score results indicate that the Murray formation is dominated by mudstones with grains smaller than the spatial resolution of all rover cameras. Intervals of fine to coarse sandstone also are present, some of which are verified using observations of grain size and sedimentary structures in associated images. Overall, results demonstrate that most of the Murray consists of mudstone, suggesting settling of grains from suspension in low energy depositional environments such as lakes. Some of the mudstones contain desiccation cracks indicating periods of drying with a lowering of lake water level. However, beds and lenses of cross‐bedded sandstones are common at specific intervals, suggesting episodes of fluvial and possibly eolian deposition. The persistence of lacustrine deposits interspersed with fluvial deposits suggests that liquid water was sustained on the Martian surface for tens of thousands to millions of years.
Quantifying Landscape Nutrient Inputs With Spatially Explicit Nutrient Source Estimate Maps
Authors: Hamlin Q. F. , Kendall A. D. , Martin S. L. , Whitenack H. D. , Roush J. A. , Hannah B. A. , Hyndman D. W. 
Published: January 2020

AbstractNutrient management is an essential part of watershed planning worldwide to protect water resources from both widespread landscape inputs of nutrients (N and P) and point source emissions. To provide information to regional watershed planners and better understand nutrient sources, we developed the Spatially Explicit Nutrient Source Estimate Map (SENSEmap) to quantify individual sources of N and P at their entry points in the landscape. We modeled seven sources of N and six sources of P across the U.S. Great Lakes Basin at 30‐m resolution: atmospheric deposition, septic systems, chemical nonagricultural fertilizer, chemical agricultural fertilizer, manure, nitrogen fixation, and point sources. By modeling these sources, we provide a more detailed view of nutrient inputs to the landscape beyond what would be possible from land use alone. We found that 71% and 88% of N and P, respectively, came from agricultural sources. The nature of agricultural nutrient inputs varied significantly across the basin, as relative contributions of chemical agricultural fertilizers, manure, and N fixation changed according to diverse land use practices regionally. We then applied k‐means cluster analysis and identified nine Nutrient Input Landscapes (NILs) with N and P source characteristics, grouped into intensive agricultural, urban, and rural landscapes. These NILs can offer insights into landscape variability that land use data alone cannot; within agricultural NILs, application of chemical fertilizer and manure varied greatly, but land uses were similar. These NILs can provide a framework for broadly categorizing watersheds that may prove useful to both ecological and management practices.
Shale as a Source of Organic Carbon in Floodplain Sediments of a Mountainous Watershed
Authors: Fox Patricia M. , Bill Markus , Heckman Katherine , Conrad Mark , Anderson Carolyn , Keiluweit Marco , Nico Peter S. 
Published: January 2020

AbstractShales contain high levels of organic carbon (OC) and represent a large fraction of the Earth's reduced carbon stocks. While recent evidence suggests that shale‐derived OC may be actively cycled in riverine systems, this process is poorly understood and not currently considered in global C models. Through the use of sediment density fractionations, extractions, radiocarbon measurements, and chemical characterization, we provide information on the abundance, chemistry, and mobility of shale‐derived OC in floodplain sediments of a shale‐rich mountainous watershed. The heavy fraction of the sediment, representing mineral‐associated OC, is the largest (84 ± 6% of TOC) and oldest (Δ14C values −224 to −853‰) OC pool. Evidence of shale‐derived OC is observed in all sediment C pools (i.e., occluded light fraction, water‐soluble, and pyrophosphate‐extractable) except the free light fraction, which is entirely modern. Relatively consistent chemistry was observed across samples for extracted and density‐separated OC, despite wide ranges of Δ14C values. Carbon spectroscopy revealed that floodplain sediments had a higher degree of functionalized aromatic groups and lower carbonate content compared to shale collected nearby, consistent with chemical alteration and mixing with other C sources in the floodplain. We estimate that approximately 23–34% of sediment OC is derived from shale, with implications for other shale‐derived elements (e.g., N). This study demonstrates the important contribution of shale‐OC, particularly in environments with low litter inputs. The large impact of radiocarbon‐dead shale‐OC, which has a thermally altered chemical structure distinct from plant litter, on Δ14C values and reactivity of sediment‐OC must be considered.
Overexpression of apoptosis inducing factor aggravates hypoxic-ischemic brain injury in neonatal mice
Authors: Li Tao , Li Kenan , Zhang Shan , Wang Yafeng , Xu Yiran , Cronin Shane J. F. , Sun Yanyan , Zhang Yaodong , Xie Cuicui , Rodriguez Juan , Zhou Kai , Hagberg Henrik , Mallard Carina , Wang Xiaoyang , Penninger Josef M. , Kroemer Guido , Blomgren Klas , Zhu Changlian 
Published: January 2020

AbstractApoptosis inducing factor (AIF) has been shown to be a major contributor to neuron loss in the immature brain after hypoxia-ischemia (HI). Indeed, mice bearing a hypomorphic mutation causing reduced AIF expression are protected against neonatal HI. To further investigate the possible molecular mechanisms of this neuroprotection, we generated an AIF knock-in mouse by introduction of a latent transgene coding for flagged AIF protein into the Rosa26 locus, followed by its conditional activation by a ubiquitously expressed Cre recombinase. Such AIF transgenic mice overexpress the pro-apoptotic splice variant of AIF (AIF1) at both the mRNA (5.9 times higher) and protein level (2.4 times higher), but not the brain-specific AIF splice-isoform (AIF2). Excessive AIF did not have any apparent effects on the phenotype or physiological functions of the mice. However, brain injury (both gray and white matter) after neonatal HI was exacerbated in mice overexpressing AIF, coupled to enhanced translocation of mitochondrial AIF to the nucleus as well as enhanced caspase-3 activation in some brain regions, as indicated by immunohistochemistry. Altogether, these findings corroborate earlier studies demonstrating that AIF plays a causal role in neonatal HI brain injury.
Tumor heterogeneity and clonal cooperation influence the immune selection of IFN-γ-signaling mutant cancer cells
Authors: Williams Jason B. , Li Shuyin , Higgs Emily F. , Cabanov Alexandra , Wang Xiaozhong , Huang Haochu , Gajewski Thomas F. 
Published: January 2020

AbstractPD-1/PD-L1 blockade can promote robust tumor regression yet secondary resistance often occurs as immune selective pressure drives outgrowth of resistant tumor clones. Here using a genome-wide CRISPR screen in B16.SIY melanoma cells, we confirm Ifngr2 and Jak1 as important genes conferring sensitivity to T cell-mediated killing in vitro. However, when implanted into mice, these Ifngr2- and Jak1-deficient tumors paradoxically are better controlled immunologically. This phenotype maps to defective PD-L1 upregulation on mutant tumor cells, which improves anti-tumor efficacy of CD8+ T cells. To reconcile these observations with clinical reports of anti-PD-1 resistance linked to emergence of IFN-γ signaling mutants, we show that when mixed with wild-type tumor cells, IFN-γ-insensitive tumor cells indeed grow out, which depends upon PD-L1 expression by wild-type cells. Our results illustrate the complexity of functions for IFN-γ in anti-tumor immunity and demonstrate that intratumor heterogeneity and clonal cooperation can contribute to immunotherapy resistance.
Loss-of-function mutations in UDP-Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy
Authors: Hengel Holger , Bosso-Lefèvre Célia , Grady George , Szenker-Ravi Emmanuelle , Li Hankun , Pierce Sarah , Lebigot Élise , Tan Thong-Teck , Eio Michelle Y. , Narayanan Gunaseelan , Utami Kagistia Hana , Yau Monica , Handal Nader , Deigendesch Werner , Keimer Reinhard , Marzouqa Hiyam M. , Gunay-Aygun Meral , Muriello Michael J. , Verhelst Helene , Weckhuysen Sarah , Mahida Sonal , Naidu Sakkubai , Thomas Terrence G. , Lim Jiin Ying , Tan Ee Shien , Haye Damien , Willemsen Michèl A. A. P. , Oegema Renske , Mitchell Wendy G. , Pierson Tyler Mark , Andrews Marisa V. , Willing Marcia C. , Rodan Lance H. , Barakat Tahsin Stefan , van Slegtenhorst Marjon , Gavrilova Ralitza H. , Martinelli Diego , Gilboa Tal , Tamim Abdullah M. , Hashem Mais O. , AlSayed Moeenaldeen D. , Abdulrahim Maha M. , Al-Owain Mohammed , Awaji Ali , Mahmoud Adel A. H. , Faqeih Eissa A. , Asmari Ali Al , Algain Sulwan M. , Jad Lamyaa A. , Aldhalaan Hesham M. , Helbig Ingo , Koolen David A. , Riess Angelika , Kraegeloh-Mann Ingeborg , Bauer Peter , Gulsuner Suleyman , Stamberger Hannah , Ng Alvin Yu Jin , Tang Sha , Tohari Sumanty , Keren Boris , Schultz-Rogers Laura E. , Klee Eric W. , Barresi Sabina , Tartaglia Marco , Mor-Shaked Hagar , Maddirevula Sateesh , Begtrup Amber , Telegrafi Aida , Pfundt Rolph , Schüle Rebecca , Ciruna Brian , Bonnard Carine , Pouladi Mahmoud A. , Stewart James C. , Claridge-Chang Adam , Lefeber Dirk J. , Alkuraya Fowzan S. , Mathuru Ajay S. , Venkatesh Byrappa , Barycki Joseph J. , Simpson Melanie A. , Jamuar Saumya S. , Schöls Ludger , Reversade Bruno 
Published: January 2020

AbstractDevelopmental epileptic encephalopathies are devastating disorders characterized by intractable epileptic seizures and developmental delay. Here, we report an allelic series of germline recessive mutations in UGDH in 36 cases from 25 families presenting with epileptic encephalopathy with developmental delay and hypotonia. UGDH encodes an oxidoreductase that converts UDP-glucose to UDP-glucuronic acid, a key component of specific proteoglycans and glycolipids. Consistent with being loss-of-function alleles, we show using patients’ primary fibroblasts and biochemical assays, that these mutations either impair UGDH stability, oligomerization, or enzymatic activity. In vitro, patient-derived cerebral organoids are smaller with a reduced number of proliferating neuronal progenitors while mutant ugdh zebrafish do not phenocopy the human disease. Our study defines UGDH as a key player for the production of extracellular matrix components that are essential for human brain development. Based on the incidence of variants observed, UGDH mutations are likely to be a frequent cause of recessive epileptic encephalopathy.
Plasmid-mediated metronidazole resistance in Clostridioides difficile
Authors: Boekhoud Ilse M. , Hornung Bastian V. H. , Sevilla Eloisa , Harmanus Céline , Bos-Sanders Ingrid M. J. G. , Terveer Elisabeth M. , Bolea Rosa , Corver Jeroen , Kuijper Ed J. , Smits Wiep Klaas 
Published: January 2020

AbstractMetronidazole was until recently used as a first-line treatment for potentially life-threatening Clostridioides difficile (CD) infection. Although cases of metronidazole resistance have been documented, no clear mechanism for metronidazole resistance or a role for plasmids in antimicrobial resistance has been described for CD. Here, we report genome sequences of seven susceptible and sixteen resistant CD isolates from human and animal sources, including isolates from a patient with recurrent CD infection by a PCR ribotype (RT) 020 strain, which developed resistance to metronidazole over the course of treatment (minimal inhibitory concentration [MIC] = 8 mg L−1). Metronidazole resistance correlates with the presence of a 7-kb plasmid, pCD-METRO. pCD-METRO is present in toxigenic and non-toxigenic resistant (n = 23), but not susceptible (n = 563), isolates from multiple countries. Introduction of a pCD-METRO-derived vector into a susceptible strain increases the MIC 25-fold. Our finding of plasmid-mediated resistance can impact diagnostics and treatment of CD infections.
Physical activity and risks of breast and colorectal cancer: a Mendelian randomisation analysis
Authors: Papadimitriou Nikos , Dimou Niki , Tsilidis Konstantinos K. , Banbury Barbara , Martin Richard M. , Lewis Sarah J. , Kazmi Nabila , Robinson Timothy M. , Albanes Demetrius , Aleksandrova Krasimira , Berndt Sonja I. , Timothy Bishop D. , Brenner Hermann , Buchanan Daniel D. , Bueno-de-Mesquita Bas , Campbell Peter T. , Castellví-Bel Sergi , Chan Andrew T. , Chang-Claude Jenny , Ellingjord-Dale Merete , Figueiredo Jane C. , Gallinger Steven J. , Giles Graham G. , Giovannucci Edward , Gruber Stephen B. , Gsur Andrea , Hampe Jochen , Hampel Heather , Harlid Sophia , Harrison Tabitha A. , Hoffmeister Michael , Hopper John L. , Hsu Li , María Huerta José , Huyghe Jeroen R. , Jenkins Mark A. , Keku Temitope O. , Kühn Tilman , La Vecchia Carlo , Le Marchand Loic , Li Christopher I. , Li Li , Lindblom Annika , Lindor Noralane M. , Lynch Brigid , Markowitz Sanford D. , Masala Giovanna , May Anne M. , Milne Roger , Monninkhof Evelyn , Moreno Lorena , Moreno Victor , Newcomb Polly A. , Offit Kenneth , Perduca Vittorio , Pharoah Paul D. P. , Platz Elizabeth A. , Potter John D. , Rennert Gad , Riboli Elio , Sánchez Maria-Jose , Schmit Stephanie L. , Schoen Robert E. , Severi Gianluca , Sieri Sabina , Slattery Martha L. , Song Mingyang , Tangen Catherine M. , Thibodeau Stephen N. , Travis Ruth C. , Trichopoulou Antonia , Ulrich Cornelia M. , van Duijnhoven Franzel J. B. , Van Guelpen Bethany , Vodicka Pavel , White Emily , Wolk Alicja , Woods Michael O. , Wu Anna H. , Peters Ulrike , Gunter Marc J. , Murphy Neil 
Published: January 2020

AbstractPhysical activity has been associated with lower risks of breast and colorectal cancer in epidemiological studies; however, it is unknown if these associations are causal or confounded. In two-sample Mendelian randomisation analyses, using summary genetic data from the UK Biobank and GWA consortia, we found that a one standard deviation increment in average acceleration was associated with lower risks of breast cancer (odds ratio [OR]: 0.51, 95% confidence interval [CI]: 0.27 to 0.98, P-value = 0.04) and colorectal cancer (OR: 0.66, 95% CI: 0.48 to 0.90, P-value = 0.01). We found similar magnitude inverse associations for estrogen positive (ER+ve) breast cancer and for colon cancer. Our results support a potentially causal relationship between higher physical activity levels and lower risks of breast cancer and colorectal cancer. Based on these data, the promotion of physical activity is probably an effective strategy in the primary prevention of these commonly diagnosed cancers.
Dual-mechanism based CTLs infiltration enhancement initiated by Nano-sapper potentiates immunotherapy against immune-excluded tumors
Authors: Huang Yukun , Chen Yu , Zhou Songlei , Chen Liang , Wang Jiahao , Pei Yuanyuan , Xu Minjun , Feng Jingxian , Jiang Tianze , Liang Kaifan , Liu Shanshan , Song Qingxiang , Jiang Gan , Gu Xiao , Zhang Qian , Gao Xiaoling , Chen Jun 
Published: January 2020

AbstractThe failure of immunotherapies in immune-excluded tumor (IET) is largely ascribed to the void of intratumoral cytotoxic T cells (CTLs). The major obstacles are the excessive stroma, defective vasculatures and the deficiency of signals recruiting CTLs. Here we report a dual-mechanism based CTLs infiltration enhancer, Nano-sapper, which can simultaneously reduce the physical obstacles in tumor microenvironment and recruiting CTLs to potentiate immunotherapy in IET. Nano-sapper consists a core that co-loaded with antifibrotic phosphates-modified α-mangostin and plasmid encoding immune-enhanced cytokine LIGHT. Through reversing the abnormal activated fibroblasts, decreasing collagen deposition, normalizing the intratumoral vasculatures, and in situ stimulating the lymphocyte-recruiting chemoattractants expression, Nano-sapper paves the road for the CTLs infiltration, induces the intratumoral tertiary lymphoid structures, thus reshapes tumor microenvironment and potentiates checkpoint inhibitor against IET. This study demonstrates that the combination of antifibrotic agent and immune-enhanced cytokine might represent a modality in promoting immunotherapy against IET.
Electrotunable liquid sulfur microdroplets
Authors: Zhou Guangmin , Yang Ankun , Wang Yifei , Gao Guoping , Pei Allen , Yu Xiaoyun , Zhu Yangying , Zong Linqi , Liu Bofei , Xu Jinwei , Liu Nian , Zhang Jinsong , Li Yanxi , Wang Lin-Wang , Hwang Harold Y. , Brongersma Mark L. , Chu Steven , Cui Yi 
Published: January 2020

AbstractManipulating liquids with tunable shape and optical functionalities in real time is important for electroactive flow devices and optoelectronic devices, but remains a great challenge. Here, we demonstrate electrotunable liquid sulfur microdroplets in an electrochemical cell. We observe electrowetting and merging of sulfur droplets under different potentiostatic conditions, and successfully control these processes via selective design of sulfiphilic/sulfiphobic substrates. Moreover, we employ the electrowetting phenomena to create a microlens based on the liquid sulfur microdroplets and tune its characteristics in real time through changing the shape of the liquid microdroplets in a fast, repeatable, and controlled manner. These studies demonstrate a powerful in situ optical battery platform for unraveling the complex reaction mechanism of sulfur chemistries and for exploring the rich material properties of the liquid sulfur, which shed light on the applications of liquid sulfur droplets in devices such as microlenses, and potentially other electrotunable and optoelectronic devices.
Structural basis for electron transport mechanism of complex I-like photosynthetic NAD(P)H dehydrogenase
Authors: Pan Xiaowei , Cao Duanfang , Xie Fen , Xu Fang , Su Xiaodong , Mi Hualing , Zhang Xinzheng , Li Mei 
Published: January 2020

AbstractNAD(P)H dehydrogenase-like (NDH) complex NDH-1L of cyanobacteria plays a crucial role in cyclic electron flow (CEF) around photosystem I and respiration processes. NDH-1L couples the electron transport from ferredoxin (Fd) to plastoquinone (PQ) and proton pumping from cytoplasm to the lumen that drives the ATP production. NDH-1L-dependent CEF increases the ATP/NADPH ratio, and is therefore pivotal for oxygenic phototrophs to function under stress. Here we report two structures of NDH-1L from Thermosynechococcus elongatus BP-1, in complex with one Fd and an endogenous PQ, respectively. Our structures represent the complete model of cyanobacterial NDH-1L, revealing the binding manner of NDH-1L with Fd and PQ, as well as the structural elements crucial for proper functioning of the NDH-1L complex. Together, our data provides deep insights into the electron transport from Fd to PQ, and its coupling with proton translocation in NDH-1L.
The combination of asymmetric hydrogenation of olefins and direct reductive amination
Authors: Yuan Shuai , Gao Guorui , Wang Lili , Liu Cungang , Wan Lei , Huang Haizhou , Geng Huiling , Chang Mingxin 
Published: January 2020

AbstractAsymmetric hydrogenation (AH) and direct reductive amination (DRA) are both efficient transformations frequently utilized in industry. Here we combine the asymmetric hydrogenation of prochiral olefins and direct reductive amination of aldehydes in one step using hydrogen gas as the common reductant and a rhodium-Segphos complex as the catalyst. With this strategy, the efficiency for the synthesis of the corresponding chiral amino compounds is significantly improved. The practical application of this synthetic approach is demonstrated by the facile synthesis of chiral 3-phenyltetrahydroquinoline and 3-benzylindoline compounds.
Microchannel network hydrogel induced ischemic blood perfusion connection
Authors: Lee Jung Bok , Kim Dae-Hyun , Yoon Jeong-Kee , Park Dan Bi , Kim Hye-Seon , Shin Young Min , Baek Wooyeol , Kang Mi-Lan , Kim Hyun Jung , Sung Hak-Joon 
Published: January 2020

AbstractAngiogenesis induction into damaged sites has long been an unresolved issue. Local treatment with pro-angiogenic molecules has been the most common approach. However, this approach has critical side effects including inflammatory coupling, tumorous vascular activation, and off-target circulation. Here, the concept that a structure can guide desirable biological function is applied to physically engineer three-dimensional channel networks in implant sites, without any therapeutic treatment. Microchannel networks are generated in a gelatin hydrogel to overcome the diffusion limit of nutrients and oxygen three-dimensionally. Hydrogel implantation in mouse and porcine models of hindlimb ischemia rescues severely damaged tissues by the ingrowth of neighboring host vessels with microchannel perfusion. This effect is guided by microchannel size-specific regenerative macrophage polarization with the consequent functional recovery of endothelial cells. Multiple-site implantation reveals hypoxia and neighboring vessels as major causative factors of the beneficial function. This technique may contribute to the development of therapeutics for hypoxia/inflammatory-related diseases.
Observable quantum entanglement due to gravity
Authors: Krisnanda Tanjung , Tham Guo Yao , Paternostro Mauro , Paterek Tomasz 
Published: January 2020

AbstractNo experiment to date has provided evidence for quantum features of the gravitational interaction. Recently proposed tests suggest looking for the generation of quantum entanglement between massive objects as a possible route towards the observation of such features. Motivated by advances in optical cooling of mirrors, here we provide a systematic study of entanglement between two masses that are coupled gravitationally. We first consider the masses trapped at all times in harmonic potentials (optomechanics) and then the masses released from the traps. This leads to the estimate of the experimental parameters required for the observation of gravitationally induced entanglement. The optomechanical setup demands LIGO-like mirrors and squeezing or long coherence times, but the released masses can be light and accumulate detectable entanglement in a timescale shorter than their coherence times. No macroscopic quantum superposition develops during the evolution. We discuss the implications from such thought experiments regarding the nature of the gravitational coupling.