bluuebunny/crossref_metadata_2025 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

The 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

Nutrient 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

Shales 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.
Correction: Age-specific reference values for carotid arterial stiffness estimated by ultrasonic wall tracking
Authors:   for the E-Tracking International Collaboration Group (ETIC), Uejima Tokuhisa , Dunstan Frank D. , Arbustini Eloisa , Łoboz-Grudzień Krystyna , Hughes Alun D. , Carerj Scipione , Favalli Valentina , Antonini-Canterin Francesco , Vriz Olga , Vinereanu Dragos , Zamorano Jose L. , Popescu Bogdan A. , Evangelista Arturo , Lancellotti Patrizio , Lefthériotis Georges , Kozakova Michaela , Palombo Carlo , Fraser Alan G.
Published: January 2020

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

Apoptosis 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

PD-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

Developmental 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

Metronidazole 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

Physical 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

The 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.
Author Correction: Blood–brain barrier permeable nano immunoconjugates induce local immune responses for glioma therapy
Authors: Galstyan Anna , Markman Janet L. , Shatalova Ekaterina S. , Chiechi Antonella , Korman Alan J. , Patil Rameshwar , Klymyshyn Dmytro , Tourtellotte Warren G. , Israel Liron L. , Braubach Oliver , Ljubimov Vladimir A. , Mashouf Leila A. , Ramesh Arshia , Grodzinski Zachary B. , Penichet Manuel L. , Black Keith L. , Holler Eggehard , Sun Tao , Ding Hui , Ljubimov Alexander V. , Ljubimova Julia Y.
Published: January 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: Membrane protein megahertz crystallography at the European XFEL
Authors: Gisriel Chris , Coe Jesse , Letrun Romain , Yefanov Oleksandr M. , Luna-Chavez Cesar , Stander Natasha E. , Lisova Stella , Mariani Valerio , Kuhn Manuela , Aplin Steve , Grant Thomas D. , Dörner Katerina , Sato Tokushi , Echelmeier Austin , Villarreal Jorvani Cruz , Hunter Mark S. , Wiedorn Max O. , Knoska Juraj , Mazalova Victoria , Roy-Chowdhury Shatabdi , Yang Jay-How , Jones Alex , Bean Richard , Bielecki Johan , Kim Yoonhee , Mills Grant , Weinhausen Britta , Meza Jose D. , Al-Qudami Nasser , Bajt Saša , Brehm Gerrit , Botha Sabine , Boukhelef Djelloul , Brockhauser Sandor , Bruce Barry D. , Coleman Matthew A. , Danilevski Cyril , Discianno Erin , Dobson Zachary , Fangohr Hans , Martin-Garcia Jose M. , Gevorkov Yaroslav , Hauf Steffen , Hosseinizadeh Ahmad , Januschek Friederike , Ketawala Gihan K. , Kupitz Christopher , Maia Luis , Manetti Maurizio , Messerschmidt Marc , Michelat Thomas , Mondal Jyotirmoy , Ourmazd Abbas , Previtali Gianpietro , Sarrou Iosifina , Schön Silvan , Schwander Peter , Shelby Megan L. , Silenzi Alessandro , Sztuk-Dambietz Jolanta , Szuba Janusz , Turcato Monica , White Thomas A. , Wrona Krzysztof , Xu Chen , Abdellatif Mohamed H. , Zook James D. , Spence John C. H. , Chapman Henry N. , Barty Anton , Kirian Richard A. , Frank Matthias , Ros Alexandra , Schmidt Marius , Fromme Raimund , Mancuso Adrian P. , Fromme Petra , Zatsepin Nadia A.
Published: January 2020

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

Manipulating 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.
Author Correction: Recurrent PTPRT/JAK2 mutations in lung adenocarcinoma among African Americans
Authors: Mitchell Khadijah A. , Nichols Noah , Tang Wei , Walling Jennifer , Stevenson Holly , Pineda Marbin , Stefanescu Roxana , Edelman Daniel C. , Girvin Andrew T. , Zingone Adriana , Sinha Sanju , Bowman Elise , Rossi Emily L. , Arauz Rony F. , Zhu Yuelin Jack , Lack Justin , Weingartner Elizabeth , Waterfall Joshua J. , Pine Sharon R. , Simmons John , Meltzer Paul , Ryan Bríd M.
Published: January 2020

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

NAD(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

Asymmetric 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

Angiogenesis 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

No 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.
Author Correction: iTRAQ-based quantitative analysis reveals proteomic changes in Chinese cabbage (Brassica rapa L.) in response to Plasmodiophora brassicae infection
Authors: Lan Mei , Li Guoliang , Hu Jingfeng , Yang Hongli , Zhang Liqin , Xu Xuezhong , Liu Jiajia , He Jiangming , Sun Rifei
Published: January 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
The risk of urinary tract infection in vegetarians and non-vegetarians: a prospective study
Authors: Chen Yen-Chang , Chang Chia-Chen , Chiu Tina H. T. , Lin Ming-Nan , Lin Chin-Lon
Published: January 2020

Urinary tract infection (UTI) is caused principally by ascending Escherichia coli infection via an intestine-stool-urethra route. Recent studies found that the strains of E. coli causing UTIs, called extra-intestinal pathogenic E. coli (ExPEC), were distinct from the intestinal pathogenic strains and normal commensal strains. Further analysis found the meat including poultry and pork is the major reservoir for ExPECs. Vegetarians avoid meat and should theoretically have less exposure to ExPEC. However, no study thus far has examined whether vegetarian diets reduce the risk of UTI. Our aim was to examine the association between vegetarian diet and UTI risk in a Taiwanese Buddhist population. We prospectively followed 9724 Buddhists free of UTI from 2005 to 2014. During the 10-year follow-up, 661 incident UTI cases were confirmed. Diet was assessed through a food frequency questionnaire. Cox regression was used to evaluate the prospective association between a vegetarian diet on risk of UTI while adjusting for age, sex, educational level, alcohol-drinking, smoking, hypertension, diabetes mellitus, hyperlipidemia, and disease conditions predisposing to UTIs. Overall, vegetarian diet was associated with 16% lower hazards (hazard ratio [HR]: 0.84, 95% confidence interval [CI]: 0.71–0.99). In subgroup analysis, the protective association between vegetarian diet and UTI is observed mainly in the female (HR: 0.82, 95% CI: 0.69–0.99), never smokers (HR: 0.80, 95% CI: 0.67–0.95), and for uncomplicated UTI (HR: 0.81, 95% CI: 0.68–0.98).
Micronutrients in critically ill patients with severe acute kidney injury – a prospective study
Authors: Ostermann Marlies , Summers Jennifer , Lei Katie , Card David , Harrington Dominic J. , Sherwood Roy , Turner Charles , Dalton Neil , Peacock Janet , Bear Danielle E.
Published: January 2020

Malnutrition is common in patients with acute kidney injury (AKI) and the risk of mortality is high, especially if renal replacement therapy is needed. Between April 2013 through April 2014, we recruited critically ill adult patients (≥18 years) with severe AKI in two University hospitals in London, UK, and measured serial plasma concentrations of vitamin B1, B6, B12, C and D, folate, selenium, zinc, copper, iron, carnitine and 22 amino acids for six consecutive days. In patients receiving continuous renal replacement therapy (CRRT), the concentrations of the same nutrients in the effluent were also determined. CRRT patients (n = 31) had lower plasma concentrations of citrulline, glutamic acid and carnitine at 24 hrs after enrolment and significantly lower plasma glutamic acid concentrations (74.4 versus 98.2 μmol/L) at day 6 compared to non-CRRT patients (n = 24). All amino acids, trace elements, vitamin C and folate were detectable in effluent fluid. In >30% of CRRT and non-CRRT patients, the plasma nutrient concentrations of zinc, iron, selenium, vitamin D3, vitamin C, trytophan, taurine, histidine and hydroxyproline were below the reference range throughout the 6-day period. In conclusion, altered micronutrient status is common in patients with severe AKI regardless of treatment with CRRT.
p53 dynamics in single cells are temperature-sensitive
Authors: Jentsch Marcel , Snyder Petra , Sheng Caibin , Cristiano Elena , Loewer Alexander
Published: January 2020

Cells need to preserve genome integrity despite varying cellular and physical states. p53, the guardian of the genome, plays a crucial role in the cellular response to DNA damage by triggering cell cycle arrest, apoptosis or senescence. Mutations in p53 or alterations in its regulatory network are major driving forces in tumorigenesis. As multiple studies indicate beneficial effects for hyperthermic treatments during radiation- or chemotherapy of human cancers, we aimed to understand how p53 dynamics after genotoxic stress are modulated by changes in temperature across a physiological relevant range. To this end, we employed a combination of time-resolved live-cell microscopy and computational analysis techniques to characterise the p53 response in thousands of individual cells. Our results demonstrate that p53 dynamics upon ionizing radiation are temperature dependent. In the range of 33 °C to 39 °C, pulsatile p53 dynamics are modulated in their frequency. Above 40 °C, which corresponds to mild hyperthermia in a clinical setting, we observed a reversible phase transition towards sustained hyperaccumulation of p53 disrupting its canonical response to DNA double strand breaks. Moreover, we provide evidence that mild hyperthermia alone is sufficient to induce a p53 response in the absence of genotoxic stress. These insights highlight how the p53-mediated DNA damage response is affected by alterations in the physical state of a cell and how this can be exploited by appropriate timing of combination therapies to increase the efficiency of cancer treatments.
Analysis of Plasmodium falciparum Rh2b deletion polymorphism across different transmission areas
Authors: Aniweh Yaw , Suurbaar Jonathan , Morang’a Collins M. , Nyarko Prince B. , Wright Katherine E. , Kusi Kwadwo A. , Ansah Felix , Kyei-Baafour Eric , Quansah Evelyn , Asante Jessica , Thiam Laty G. , Higgins Matthew K. , Awandare Gordon A.
Published: January 2020

Despite significant progress in controlling malaria, the disease remains a global health burden. The intricate interactions the parasite Plasmodium falciparum has with its host allows it to grow and multiply in human erythrocytes. The mechanism by which P. falciparum merozoites invade human erythrocytes is complex, involving merozoite proteins as well as erythrocyte surface proteins. Members of the P. falciparum reticulocyte binding-like protein homolog (PfRh) family of proteins play a pivotal role in merozoite invasion and hence are important targets of immune responses. Domains within the PfRh2b protein have been implicated in its ability to stimulate natural protective antibodies in patients. More specifically, a 0.58 kbp deletion, at the C-terminus has been reported in high frequencies in Senegalese and Southeast Asian parasite populations, suggesting a possible role in immune evasion. We analysed 1218 P. falciparum clinical isolates, and the results show that this deletion is present in Ghanaian parasite populations (48.5% of all isolates), with Kintampo (hyper-endemic, 53.2%), followed by Accra (Hypo-endemic, 50.3%), Cape Coast (meso-endemic, 47.9%) and Sogakope (meso-endemic, 43.15%). Further analysis of parasite genomes stored in the MalariaGEN database revealed that the deletion variant was common across transmission areas globally, with an overall frequency of about 27.1%. Interestingly, some parasite isolates possessed mixed PfRh2b deletion and full-length alleles. We further showed that levels of antibodies to the domain of PfRh2 protein were similar to antibody levels of PfRh5, indicating it is less recognized by the immune system.
RETRACTED ARTICLE: Topological analysis of carbon and boron nitride nanotubes
Authors: Yousaf Awais , Alolaiyan Hanan , Nadeem Muhammad , Razaq Abdul
Published: January 2020

Graph theoretical concepts are broadly used in several fields to examine and model various applications. In computational chemistry, the characteristics of a molecular compound can be assessed with the help of a numerical value, known as a topological index. Topological indices are extensively used to study the molecular mechanics in QSAR and QSPR modeling. In this study, we have developed the closed formulae to estimate ABC, ABC4, GA, and GA5 topological indices for the graphical structures of boron nitride and carbon nanotube.
Innervation of papillary thyroid cancer and its association with extra-thyroidal invasion
Authors: Rowe Christopher W. , Dill Tony , Griffin Nathan , Jobling Phil , Faulkner Sam , Paul Jonathan W. , King Simon , Smith Roger , Hondermarck Hubert
Published: January 2020

Nerves are emerging regulators of cancer progression and in several malignancies innervation of the tumour microenvironment is associated with tumour aggressiveness. However, the innervation of thyroid cancer is unclear. Here, we investigated the presence of nerves in thyroid cancers and the potential associations with clinicopathological parameters. Nerves were detected by immunohistochemistry using the pan-neuronal marker PGP9.5 in whole-slide sections of papillary thyroid cancer (PTC) (n = 75), compared to follicular thyroid cancer (FTC) (n = 13), and benign thyroid tissues (n = 26). Nerves were detected in most normal thyroid tissues and thyroid cancers, but nerve density was increased in PTC (12 nerves/cm2 [IQR 7–21]) compared to benign thyroid (6 nerves/cm2 [IQR: 3–10]) (p = 0.001). In contrast, no increase in nerve density was observed in FTC. In multivariate analysis, nerve density correlated positively with extrathyroidal invasion (p < 0.001), and inversely with tumour size (p < 0.001). The majority of nerves were adrenergic, although cholinergic and peptidergic innervation was detected. Perineural invasion was present in 35% of PTC, and was independently associated with extrathyroidal invasion (p = 0.008). This is the first report of infiltration of nerves into the tumour microenvironment of thyroid cancer and its association with tumour aggressiveness. The role of nerves in thyroid cancer pathogenesis should be further investigated.
Deep Learning Models for Histopathological Classification of Gastric and Colonic Epithelial Tumours
Authors: Iizuka Osamu , Kanavati Fahdi , Kato Kei , Rambeau Michael , Arihiro Koji , Tsuneki Masayuki
Published: January 2020

Histopathological classification of gastric and colonic epithelial tumours is one of the routine pathological diagnosis tasks for pathologists. Computational pathology techniques based on Artificial intelligence (AI) would be of high benefit in easing the ever increasing workloads on pathologists, especially in regions that have shortages in access to pathological diagnosis services. In this study, we trained convolutional neural networks (CNNs) and recurrent neural networks (RNNs) on biopsy histopathology whole-slide images (WSIs) of stomach and colon. The models were trained to classify WSI into adenocarcinoma, adenoma, and non-neoplastic. We evaluated our models on three independent test sets each, achieving area under the curves (AUCs) up to 0.97 and 0.99 for gastric adenocarcinoma and adenoma, respectively, and 0.96 and 0.99 for colonic adenocarcinoma and adenoma respectively. The results demonstrate the generalisation ability of our models and the high promising potential of deployment in a practical histopathological diagnostic workflow system.
Efficient Luminescence of Sr2Si5N8:Eu2+ nanophosphor and its film applications to LED and Solar cell as a downconverter
Authors: Kang Taewook , Lee Sunghoon , Kim Taehoon , Kim Jongsu
Published: January 2020

Here we present the synthesis of the efficient nanophosphor Sr2Si5N8:Eu2+ (D50 = 144 nm) by a simple milling approach, its strong Rayleigh scattering, and its film applications to white LED and silicon solar cell as a downshifting medium. The final nanophosphor product showed the quantum efficiency comparable to the bulk phosphor which is, to our knowledge, the highest record of nitride nanophosphors. Especially the nanophosphor showed the more tail emission at the shorter-wavelength side of the emission spectrum and the faster thermal quenching with the more spectral broadening along with the temperature due to Rayleigh scattering. Also the lowering in the excitation spectrum was observed due to lower absorbance. Finally, the nanophosphor-dispersed polyvinyl alcohol (PVA) film was made, and its applications to white LED and silicon solar cell as a downshifting medium demonstrated that it gave the high color rendering property in white LED in spite of still lower luminous efficiency, and it caused the increase in efficiency of silicon solar cell.
A resonant single frequency molecular detector with high sensitivity and selectivity for gas mixtures
Authors: Branković Zorica , Rostovtsev Yuri
Published: January 2020

Air quality control is an important task in prevention of human exposure to toxic and harmful gases and requires reliable gas sensors. During last decades many gas sensing mechanisms, based on different physical or chemical interactions with sensitive materials, have been developed, but the problem of precise analysis of gas mixtures still remains. The problem can be solved by introducing new sensing mechanism based on an adiabatically changing electric field interacting with the rotational structure of the molecules with dipole moments. We have theoretically demonstrated a single low frequency gas detector that can be used for sensing of gas mixtures with high selectivity, accuracy, and sensitivity. The enhancement of the population difference between corresponding molecular levels and reached the theoretical maximum of absorption have been shown.
Evaluation of intraocular gas using magnetic resonance imaging after pars plana vitrectomy with gas tamponade for rhegmatogenous retinal detachment
Authors: Gozawa Makoto , Kanamoto Masayuki , Ishida Shota , Takamura Yoshihiro , Iwasaki Kentaro , Kimura Hirohiko , Inatani Masaru
Published: January 2020

We used magnetic resonance imaging (MRI) to assess how a patient’s posture affects intraocular gas changes and whether the postoperative prone position is required after pars plana vitrectomy (PPV) with gas tamponade for rhegmatogenous retinal detachments (RRDs). Eight patients with RRDs who underwent PPV combined with cataract surgery with gas tamponade were prospectively included. They underwent MRI examination both in the prone and supine positions. We separated the retina into four parts: superior–posterior, superior–anterior, inferior–posterior, and inferior–anterior. We then calculated the gas contact rate as (the length of the retina contacting the gas in each retinal part) divided by (the length of each retinal part) × 100% in both the prone and supine positions. The mean gas contact rate of the superior–anterior part of the retina was significantly higher (P = 0.006) in the supine position than in the prone position. The mean gas contact rate of the inferior–anterior part of the retina was also significantly higher (P = 0.0004) in the supine position than in the prone position. We believe that if all retinal breaks were located anterior to the equator, the supine position may provide better tamponade gas coverage for the breaks than the prone position. Although potential postoperative complications caused by the supine position require careful attention, our result may shorten the duration of postoperative prone position and may decrease the patients’ discomfort after PPV with gas tamponade for RRDs.
Author Correction: Efficient derivation of knock-out and knock-in rats using embryos obtained by in vitro fertilization
Authors: Honda Arata , Tachibana Ryoma , Hamada Kazuya , Morita Kohtaro , Mizuno Naoaki , Morita Kento , Asano Masahide
Published: January 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: Notch signaling pathway is a potential therapeutic target for extracranial vascular malformations
Authors: Davis Reema B. , Pahl Kristy , Datto Nicholas C. , Smith Scott V. , Shawber Carrie , Caron Kathleen M. , Blatt Julie
Published: January 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Publisher Correction: High Entropy Alloys Mined From Binary Phase Diagrams
Authors: Qi Jie , Cheung Andrew M. , Poon S. Joseph
Published: January 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Tunable one-step double functionalization of graphene based on fluorographene chemistry
Authors: Chronopoulos Demetrios D. , Medveď Miroslav , Potsi Georgia , Tomanec Ondřej , Scheibe Magdalena , Otyepka Michal
Published: January 2020

Double functionalized graphene derivatives were synthetized by a one-pot reaction of fluorographene with organometallic nucleophiles.
Salen-based hypercrosslinked polymer-supported Pd as an efficient and recyclable catalyst for C–H halogenation
Authors: Meng Di , Bi Jiajun , Dong Yahao , Hao Bo , Qin Kaiwei , Li Tao , Zhu Dajian
Published: January 2020

In this work, we report the first use of a salen-based hypercrosslinked polymer-supported Pd catalyst to carry out C–H halogenation.
Enhanced propane dehydrogenation to propylene over zinc-promoted chromium catalysts
Authors: Liu Jie , Liu Yong , Ni Youming , Liu Hongchao , Zhu Wenliang , Liu Zhongmin
Published: January 2020

A small-size Zn–Cr spinel with defect sites formed by adding Zn to Cr2O3 is favorable for the PDH reaction.
DFT study on the mechanism of bimetallic Pd–Zn-catalyzed cycloaddition of alkynyl aryl ethers with internal alkynes
Authors: Wang Mei-yan , Chen Li , Li Bing-wen , Liu Jing-yao
Published: January 2020

C6H5OCCSiiPr3 is the most reactive substrate, due to strong electron-withdrawing inductive effect of the O atom and relatively large steric repulsion of the SiiPr3 group.
TiO2/Cu2O nanoparticle-catalyzed direct C(sp)–P bond formation via aerobic oxidative coupling in air and visible light
Authors: Hosseini-Sarvari Mona , Jafari Fattaneh
Published: January 2020

Visible light organophosphorus synthesis using TiO2/Cu2O nanoparticles.
The holistico-reductionist Siga classification according to the degree of food processing: an evaluation of ultra-processed foods in French supermarkets
Authors: Davidou Sylvie , Christodoulou Aris , Fardet Anthony , Frank Kelly
Published: January 2020

The Siga classification of foods according to degree of processing showed that two-thirds of 24 932 packaged foods collected in French supermarkets are ultra-processed at various degrees.
Synchrotron hard X-ray chemical imaging of trace element speciation in heterogeneous samples: development of criteria for uncertainty analysis
Authors: Wielinski Jonas , Marafatto Francesco Femi , Gogos Alexander , Scheidegger Andreas , Voegelin Andreas , Müller Christoph R. , Morgenroth Eberhard , Kaegi Ralf
Published: January 2020

Synthetic datasets with known uncertainty are used to quantify the interpretability of experimental hard X-ray derived chemical images.
Unprecedented capacitive deionization performance of interconnected iron–nitrogen-doped carbon tubes in oxygenated saline water
Authors: Xu Xingtao , Tang Jing , Kaneti Yusuf Valentino , Tan Haibo , Chen Tao , Pan Likun , Yang Tao , Bando Yoshio , Yamauchi Yusuke
Published: January 2020

This work reports the layer-by-layer motif synthesis of 3D interconnected nitrogen–iron-doped carbon tubes (3D-FeNC tubes) by using continuous polymeric fibers as templates with high capacitive deionization performance in oxygenated saline water.
pH dependence of the non-cooperative binding of Bi3+ to human apo-metallothionein 1A: kinetics, speciation, and stoichiometry
Authors: Korkola Natalie C , Scarrow Patti M , Stillman Martin J
Published: January 2020

Bismuth is a well-known therapeutic agent that is used primarily for treatment against peptic ulcers. It has also had success in protecting against nephrotoxicity caused by the anticancer compound cisplatin by inducing the liver and kidney metalloprotein, metallothionein (MT) that then binds to the cisplatin. MT is a small, ubiquitous protein that binds monovalent, divalent, and trivalent metals using its abundant cysteine thiols (20 cysteines in the mammalian protein). It is important in the understanding of both these therapeutic applications to explore in detail the earliest stages of MT binding to bismuth salts. In this paper, we explored the binding of [Bi(cit)]− and [Bi(EDTA)]− to apo-MT 1a as the most basic of binding motifs. It was found that both Bi3+ salts bound in a non-cooperative stepwise manner to terminal cysteinal thiolates at pH 2.6, 5.0, and 7.4. We report that [Bi(EDTA)]− only binds stepwise up to Bi6MT, whereas [Bi(cit)]− forms up to Bi8MT, where the 7th and 8th Bi3+ appear to be adducts. Stepwise speciation analysis provided the 7 binding constants that decreased systematically from K1 to K7 indicating a non-cooperative binding profile. They are reported as log K1 = 27.89, log K2 = 27.78, log K3 = 27.77, log K4 = 27.62, log K5 = 27.32, log K6 = 26.75, and log K7 = 26.12, with log K[Bi(cit)]− determined to be 24.17. Cysteine modifications with benzoquinone and iodoacetamide revealed that when apoMT is fully metallated with Bi3+ there are two free cysteines, meaning 18 cysteines are used in binding the 6 Bi3+. Kinetic studies showed that [Bi(EDTA)]− binds very slowly at pH 2.6 (k = 0.0290 × 106 M−1 s−1) and approximately 2000 times faster at pH 7.4 (k = 66.5 × 106 M−1 s−1). [Bi(cit)]− binding at pH 2.6 was faster than [Bi(EDTA)]− (k = 672 × 106 M−1 s−1) at either pH level. The data strongly support a non-clustered binding motif, emphasizing the non-traditional pathway reported previously for As3+.