bluuebunny/crossref_metadata_2025_split huggingface dataset:
Organ-specific, multimodal, wireless optoelectronics for high-throughput phenotyping of peripheral neural pathways
Authors: Kim Woo Seok , Hong Sungcheol , Gamero Milenka , Jeevakumar Vivekanand , Smithhart Clay M. , Price Theodore J. , Palmiter Richard D. , Campos Carlos , Park Sung Il 
Published: January 2021

AbstractThe vagus nerve supports diverse autonomic functions and behaviors important for health and survival. To understand how specific components of the vagus contribute to behaviors and long-term physiological effects, it is critical to modulate their activity with anatomical specificity in awake, freely behaving conditions using reliable methods. Here, we introduce an organ-specific scalable, multimodal, wireless optoelectronic device for precise and chronic optogenetic manipulations in vivo. When combined with an advanced, coil-antenna system and a multiplexing strategy for powering 8 individual homecages using a single RF transmitter, the proposed wireless telemetry enables low cost, high-throughput, and precise functional mapping of peripheral neural circuits, including long-term behavioral and physiological measurements. Deployment of these technologies reveals an unexpected role for stomach, non-stretch vagal sensory fibers in suppressing appetite and demonstrates the durability of the miniature wireless device inside harsh gastric conditions.
Gut microbiota impact on the peripheral immune response in non-alcoholic fatty liver disease related hepatocellular carcinoma
Authors: Behary Jason , Amorim Nadia , Jiang Xiao-Tao , Raposo Anita , Gong Lan , McGovern Emily , Ibrahim Ragy , Chu Francis , Stephens Carlie , Jebeili Hazem , Fragomeli Vincenzo , Koay Yen Chin , Jackson Miriam , O’Sullivan John , Weltman Martin , McCaughan Geoffrey , El-Omar Emad , Zekry Amany 
Published: January 2021

AbstractThe gut microbiota is reported to modulate the immune response in hepatocellular carcinoma (HCC). Here, we employ metagenomic and metabolomic studies to characterise gut microbiota in patients with non-alcoholic fatty liver disease (NAFLD) related cirrhosis, with or without HCC, and evaluate its effect on the peripheral immune response in an ex vivo model. We find that dysbiosis characterises the microbiota of patients with NAFLD-cirrhosis, with compositional and functional shifts occurring with HCC development. Gene function of the microbiota in NAFLD-HCC supports short chain fatty acid production, and this is confirmed by metabolomic studies. Ex vivo studies show that bacterial extracts from the NAFLD-HCC microbiota, but not from the control groups, elicit a T cell immunosuppressive phenotype, characterised by expansion of regulatory T cells and attenuation of CD8 + T cells. Our study suggest that the gut microbiota in NAFLD-HCC is characterised by a distinctive microbiome/metabolomic profile, and can modulate the peripheral immune response.
Microbial production of multiple short-chain primary amines via retrobiosynthesis
Authors: Kim Dong In , Chae Tong Un , Kim Hyun Uk , Jang Woo Dae , Lee Sang Yup 
Published: January 2021

AbstractBio-based production of many chemicals is not yet possible due to the unknown biosynthetic pathways. Here, we report a strategy combining retrobiosynthesis and precursor selection step to design biosynthetic pathways for multiple short-chain primary amines (SCPAs) that have a wide range of applications in chemical industries. Using direct precursors of 15 target SCPAs determined by the above strategy,Streptomyces viridifaciens vlmDencoding valine decarboxylase is examined as a proof-of-concept promiscuous enzyme both in vitro and in vivo for generating SCPAs from their precursors.Escherichia coliexpressing the heterologousvlmDproduces 10 SCPAs by feeding their direct precursors. Furthermore, metabolically engineeredE. colistrains are developed to produce representative SCPAs from glucose, including the one producing 10.67 g L−1ofiso-butylamine by fed-batch culture. This study presents the strategy of systematically designing biosynthetic pathways for the production of a group of related chemicals as demonstrated by multiple SCPAs as examples.
Conditional quantum operation of two exchange-coupled single-donor spin qubits in a MOS-compatible silicon device
Authors: Ma̧dzik Mateusz T. , Laucht Arne , Hudson Fay E. , Jakob Alexander M. , Johnson Brett C. , Jamieson David N. , Itoh Kohei M. , Dzurak Andrew S. , Morello Andrea 
Published: January 2021

AbstractSilicon nanoelectronic devices can host single-qubit quantum logic operations with fidelity better than 99.9%. For the spins of an electron bound to a single-donor atom, introduced in the silicon by ion implantation, the quantum information can be stored for nearly 1 second. However, manufacturing a scalable quantum processor with this method is considered challenging, because of the exponential sensitivity of the exchange interaction that mediates the coupling between the qubits. Here we demonstrate the conditional, coherent control of an electron spin qubit in an exchange-coupled pair of 31P donors implanted in silicon. The coupling strength, J = 32.06 ± 0.06 MHz, is measured spectroscopically with high precision. Since the coupling is weaker than the electron-nuclear hyperfine coupling A ≈ 90 MHz which detunes the two electrons, a native two-qubit controlled-rotation gate can be obtained via a simple electron spin resonance pulse. This scheme is insensitive to the precise value of J, which makes it suitable for the scale-up of donor-based quantum computers in silicon that exploit the metal-oxide-semiconductor fabrication protocols commonly used in the classical electronics industry.
Conformational and migrational dynamics of slipped-strand DNA three-way junctions containing trinucleotide repeats
Authors: Hu Tianyu , Morten Michael J. , Magennis Steven W. 
Published: January 2021

AbstractExpansions of CAG/CTG trinucleotide repeats in DNA are the cause of at least 17 degenerative human disorders, including Huntington’s Disease. Repeat instability is thought to occur via the formation of intrastrand hairpins during replication, repair, recombination, and transcription though relatively little is known about their structure and dynamics. We use single-molecule Förster resonance energy transfer to study DNA three-way junctions (3WJs) containing slip-outs composed of CAG or CTG repeats. 3WJs that only have repeats in the slip-out show two-state behavior, which we attribute to conformational flexibility at the 3WJ branchpoint. When the triplet repeats extend into the adjacent duplex, additional dynamics are observed, which we assign to interconversion of positional isomers. We propose a branchpoint migration model that involves conformational rearrangement, strand exchange, and bulge-loop movement. This migration has implications for how repeat slip-outs are processed by the cellular machinery, disease progression, and their development as drug targets.
Predicting postoperative peritoneal metastasis in gastric cancer with serosal invasion using a collagen nomogram
Authors: Chen Dexin , Liu Zhangyuanzhu , Liu Wenju , Fu Meiting , Jiang Wei , Xu Shuoyu , Wang Guangxing , Chen Feng , Lu Jianping , Chen Hao , Dong Xiaoyu , Li Guoxin , Chen Gang , Zhuo Shuangmu , Yan Jun 
Published: January 2021

AbstractAccurate prediction of peritoneal metastasis for gastric cancer (GC) with serosal invasion is crucial in clinic. The presence of collagen in the tumour microenvironment affects the metastasis of cancer cells. Herein, we propose a collagen signature, which is composed of multiple collagen features in the tumour microenvironment of the serosa derived from multiphoton imaging, to describe the extent of collagen alterations. We find that a high collagen signature is significantly associated with a high risk of peritoneal metastasis (P < 0.001). A competing-risk nomogram including the collagen signature, tumour size, tumour differentiation status and lymph node metastasis is constructed. The nomogram demonstrates satisfactory discrimination and calibration. Thus, the collagen signature in the tumour microenvironment of the gastric serosa is associated with peritoneal metastasis in GC with serosal invasion, and the nomogram can be conveniently used to individually predict the risk of peritoneal metastasis in GC with serosal invasion after radical surgery.
Large-area and efficient perovskite light-emitting diodes via low-temperature blade-coating
Authors: Chu Shenglong , Chen Wenjing , Fang Zhibin , Xiao Xun , Liu Yan , Chen Jia , Huang Jinsong , Xiao Zhengguo 
Published: January 2021

AbstractLarge-area light-emitting diodes (LEDs) fabricated by mass-production techniques are needed for low-cost flat-panel lighting. Nevertheless, it is still challenging to fabricate efficient large-area LEDs using organic small molecules (OLEDs), quantum dots (QLEDs), polymers (PLEDs), and recently-developed hybrid perovskites (PeLEDs) due to difficulties controlling film uniformity. To that end, we report sol-gel engineering of low-temperature blade-coated methylammonium lead iodide (MAPbI3) perovskite films. The precipitation, gelation, aging, and phase transformation stages are dramatically shortened by using a diluted, organoammonium-excessed precursor, resulting in ultra-flat large-area films (54 cm2) with roughness reaching 1 nm. The external quantum efficiency of doctor-bladed PeLEDs reaches 16.1%, higher than that of best-performing blade-coated OLEDs, QLEDs, and PLEDs. Furthermore, benefitting from the throughput of the blade-coating process and cheap materials, the expected cost of the emissive layer is projected to be as low as 0.02 cents per cm2, emphasizing its application potential.
HIV-1 diversity considerations in the application of the Intact Proviral DNA Assay (IPDA)
Authors: Kinloch Natalie N. , Ren Yanqin , Conce Alberto Winiffer D. , Dong Winnie , Khadka Pragya , Huang Szu Han , Mota Talia M. , Wilson Andrew , Shahid Aniqa , Kirkby Don , Harris Marianne , Kovacs Colin , Benko Erika , Ostrowski Mario A. , Del Rio Estrada Perla M. , Wimpelberg Avery , Cannon Christopher , Hardy W. David , MacLaren Lynsay , Goldstein Harris , Brumme Chanson J. , Lee Guinevere Q. , Lynch Rebecca M. , Brumme Zabrina L. , Jones R. Brad 
Published: January 2021

AbstractThe Intact Proviral DNA Assay (IPDA) was developed to address the critical need for a scalable method for intact HIV-1 reservoir quantification. This droplet digital PCR-based assay simultaneously targets two HIV-1 regions to distinguish genomically intact proviruses against a large background of defective ones, and its application has yielded insights into HIV-1 persistence. Reports of assay failures however, attributed to HIV-1 polymorphism, have recently emerged. Here, we describe a diverse North American cohort of people with HIV-1 subtype B, where the IPDA yielded a failure rate of 28% due to viral polymorphism. We further demonstrate that within-host HIV-1 diversity can lead the IPDA to underestimate intact reservoir size, and provide examples of how this phenomenon could lead to erroneous interpretation of clinical trial data. While the IPDA represents a major methodological advance, HIV-1 diversity should be addressed before its widespread adoption as a principal readout in HIV-1 remission trials.
Host and viral determinants for efficient SARS-CoV-2 infection of the human lung
Authors: Chu Hin , Hu Bingjie , Huang Xiner , Chai Yue , Zhou Dongyan , Wang Yixin , Shuai Huiping , Yang Dong , Hou Yuxin , Zhang Xi , Yuen Terrence Tsz-Tai , Cai Jian-Piao , Zhang Anna Jinxia , Zhou Jie , Yuan Shuofeng , To Kelvin Kai-Wang , Chan Ivy Hau-Yee , Sit Ko-Yung , Foo Dominic Chi-Chung , Wong Ian Yu-Hong , Ng Ada Tsui-Lin , Cheung Tan To , Law Simon Ying-Kit , Au Wing-Kuk , Brindley Melinda A. , Chen Zhiwei , Kok Kin-Hang , Chan Jasper Fuk-Woo , Yuen Kwok-Yung 
Published: January 2021

AbstractUnderstanding the factors that contribute to efficient SARS-CoV-2 infection of human cells may provide insights on SARS-CoV-2 transmissibility and pathogenesis, and reveal targets of intervention. Here, we analyze host and viral determinants essential for efficient SARS-CoV-2 infection in both human lung epithelial cells and ex vivo human lung tissues. We identify heparan sulfate as an important attachment factor for SARS-CoV-2 infection. Next, we show that sialic acids present on ACE2 prevent efficient spike/ACE2-interaction. While SARS-CoV infection is substantially limited by the sialic acid-mediated restriction in both human lung epithelial cells and ex vivo human lung tissues, infection by SARS-CoV-2 is limited to a lesser extent. We further demonstrate that the furin-like cleavage site in SARS-CoV-2 spike is required for efficient virus replication in human lung but not intestinal tissues. These findings provide insights on the efficient SARS-CoV-2 infection of human lungs.
SLE non-coding genetic risk variant determines the epigenetic dysfunction of an immune cell specific enhancer that controls disease-critical microRNA expression
Authors: Hou Guojun , Harley Isaac T. W. , Lu Xiaoming , Zhou Tian , Xu Ning , Yao Chao , Qin Yuting , Ouyang Ye , Ma Jianyang , Zhu Xinyi , Yu Xiang , Xu Hong , Dai Dai , Ding Huihua , Yin Zhihua , Ye Zhizhong , Deng Jun , Zhou Mi , Tang Yuanjia , Namjou Bahram , Guo Ya , Weirauch Matthew T. , Kottyan Leah C. , Harley John B. , Shen Nan 
Published: January 2021

AbstractSince most variants that impact polygenic disease phenotypes localize to non-coding genomic regions, understanding the consequences of regulatory element variants will advance understanding of human disease mechanisms. Here, we report that the systemic lupus erythematosus (SLE) risk variant rs2431697 as likely causal for SLE through disruption of a regulatory element, modulating miR-146a expression. Using epigenomic analysis, genome-editing and 3D chromatin structure analysis, we show that rs2431697 tags a cell-type dependent distal enhancer specific for miR-146a that physically interacts with the miR-146a promoter. NF-kB binds the disease protective allele in a sequence-specific manner, increasing expression of this immunoregulatory microRNA. Finally, CRISPR activation-based modulation of this enhancer in the PBMCs of SLE patients attenuates type I interferon pathway activation by increasing miR-146a expression. Our work provides a strategy to define non-coding RNA functional regulatory elements using disease-associated variants and provides mechanistic links between autoimmune disease risk genetic variation and disease etiology.
Structures of human dual oxidase 1 complex in low-calcium and high-calcium states
Authors: Wu Jing-Xiang , Liu Rui , Song Kangcheng , Chen Lei 
Published: January 2021

AbstractDual oxidases (DUOXs) produce hydrogen peroxide by transferring electrons from intracellular NADPH to extracellular oxygen. They are involved in many crucial biological processes and human diseases, especially in thyroid diseases. DUOXs are protein complexes co-assembled from the catalytic DUOX subunits and the auxiliary DUOXA subunits and their activities are regulated by intracellular calcium concentrations. Here, we report the cryo-EM structures of human DUOX1-DUOXA1 complex in both high-calcium and low-calcium states. These structures reveal the DUOX1 complex is a symmetric 2:2 hetero-tetramer stabilized by extensive inter-subunit interactions. Substrate NADPH and cofactor FAD are sandwiched between transmembrane domain and the cytosolic dehydrogenase domain of DUOX. In the presence of calcium ions, intracellular EF-hand modules might enhance the catalytic activity of DUOX by stabilizing the dehydrogenase domain in a conformation that allows electron transfer.
Exposure to pesticides in utero impacts the fetal immune system and response to vaccination in infancy
Authors: Prahl Mary , Odorizzi Pamela , Gingrich David , Muhindo Mary , McIntyre Tara , Budker Rachel , Jagannathan Prasanna , Farrington Lila , Nalubega Mayimuna , Nankya Felistas , Sikyomu Esther , Musinguzi Kenneth , Naluwu Kate , Auma Ann , Kakuru Abel , Kamya Moses R. , Dorsey Grant , Aweeka Francesca , Feeney Margaret E. 
Published: January 2021

AbstractThe use of pesticides to reduce mosquito vector populations is a cornerstone of global malaria control efforts, but the biological impact of most pesticides on human populations, including pregnant women and infants, is not known. Some pesticides, including carbamates, have been shown to perturb the human immune system. We measure the systemic absorption and immunologic effects of bendiocarb, a commonly used carbamate pesticide, following household spraying in a cohort of pregnant Ugandan women and their infants. We find that bendiocarb is present at high levels in maternal, umbilical cord, and infant plasma of individuals exposed during pregnancy, indicating that it is systemically absorbed and trans-placentally transferred to the fetus. Moreover, bendiocarb exposure is associated with numerous changes in fetal immune cell homeostasis and function, including a dose-dependent decrease in regulatory CD4 T cells, increased cytokine production, and inhibition of antigen-driven proliferation. Additionally, prenatal bendiocarb exposure is associated with higher post-vaccination measles titers at one year of age, suggesting that its impact on functional immunity may persist for many months after birth. These data indicate that in utero bendiocarb exposure has multiple previously unrecognized biological effects on the fetal immune system.
Selective capture of carbon dioxide from hydrocarbons using a metal-organic framework
Authors: Qazvini Omid T. , Babarao Ravichandar , Telfer Shane G. 
Published: January 2021

AbstractEfficient and sustainable methods for carbon dioxide capture are highly sought after. Mature technologies involve chemical reactions that absorb CO2,but they have many drawbacks. Energy-efficient alternatives may be realised by porous physisorbents with void spaces that are complementary in size and electrostatic potential to molecular CO2. Here, we present a robust, recyclable and inexpensive adsorbent termed MUF-16. This metal-organic framework captures CO2with a high affinity in its one-dimensional channels, as determined by adsorption isotherms, X-ray crystallography and density-functional theory calculations. Its low affinity for other competing gases delivers high selectivity for the adsorption of CO2over methane, acetylene, ethylene, ethane, propylene and propane. For equimolar mixtures of CO2/CH4and CO2/C2H2, the selectivity is 6690 and 510, respectively. Breakthrough gas separations under dynamic conditions benefit from short time lags in the elution of the weakly-adsorbed component to deliver high-purity hydrocarbon products, including pure methane and acetylene.
High-resolution single-cell 3D-models of chromatin ensembles during Drosophila embryogenesis
Authors: Sun Qiu , Perez-Rathke Alan , Czajkowsky Daniel M. , Shao Zhifeng , Liang Jie 
Published: January 2021

AbstractSingle-cell chromatin studies provide insights into how chromatin structure relates to functions of individual cells. However, balancing high-resolution and genome wide-coverage remains challenging. We describe a computational method for the reconstruction of large 3D-ensembles of single-cell (sc) chromatin conformations from population Hi-C that we apply to study embryogenesis in Drosophila. With minimal assumptions of physical properties and without adjustable parameters, our method generates large ensembles of chromatin conformations via deep-sampling. Our method identifies specific interactions, which constitute 5–6% of Hi-C frequencies, but surprisingly are sufficient to drive chromatin folding, giving rise to the observed Hi-C patterns. Modeled sc-chromatins quantify chromatin heterogeneity, revealing significant changes during embryogenesis. Furthermore, >50% of modeled sc-chromatin maintain topologically associating domains (TADs) in early embryos, when no population TADs are perceptible. Domain boundaries become fixated during development, with strong preference at binding-sites of insulator-complexes upon the midblastula transition. Overall, high-resolution 3D-ensembles of sc-chromatin conformations enable further in-depth interpretation of population Hi-C, improving understanding of the structure-function relationship of genome organization.
Plasma ctDNA is a tumor tissue surrogate and enables clinical-genomic stratification of metastatic bladder cancer
Authors: Vandekerkhove Gillian , Lavoie Jean-Michel , Annala Matti , Murtha Andrew J. , Sundahl Nora , Walz Simon , Sano Takeshi , Taavitsainen Sinja , Ritch Elie , Fazli Ladan , Hurtado-Coll Antonio , Wang Gang , Nykter Matti , Black Peter C. , Todenhöfer Tilman , Ost Piet , Gibb Ewan A. , Chi Kim N. , Eigl Bernhard J. , Wyatt Alexander W. 
Published: January 2021

AbstractMolecular stratification can improve the management of advanced cancers, but requires relevant tumor samples. Metastatic urothelial carcinoma (mUC) is poised to benefit given a recent expansion of treatment options and its high genomic heterogeneity. We profile minimally-invasive plasma circulating tumor DNA (ctDNA) samples from 104 mUC patients, and compare to same-patient tumor tissue obtained during invasive surgery. Patient ctDNA abundance is independently prognostic for overall survival in patients initiating first-line systemic therapy. Importantly, ctDNA analysis reproduces the somatic driver genome as described from tissue-based cohorts. Furthermore, mutation concordance between ctDNA and matched tumor tissue is 83.4%, enabling benchmarking of proposed clinical biomarkers. While 90% of mutations are identified across serial ctDNA samples, concordance for serial tumor tissue is significantly lower. Overall, our exploratory analysis demonstrates that genomic profiling of ctDNA in mUC is reliable and practical, and mitigates against disease undersampling inherent to studying archival primary tumor foci. We urge the incorporation of cell-free DNA profiling into molecularly-guided clinical trials for mUC.
High efficiency hierarchical porous composite microfiltration membrane for high-temperature particulate matter capturing
Authors: Gui Wanyuan , Qu Yuhai , Liang Yongfeng , Wang Yanli , Zhang Hui , Luan Benli , Lin Junpin 
Published: January 2021

AbstractPorous intermetallic membrane with extensive interconnected pores are potential candidates as functional materials for high-temperature particulate matter (PM) capturing. However, fabrication of intermetallic membrane with a combined performance of high filtration efficiency and high-temperature oxidation resistance remains a challenge. To tackle this issue, a hierarchical micro-/nano-dual-scale sized pores was constructed on the inner cell walls of a porous support through mutual diffusion and chemical reaction. Benefited from its hierarchical micro/nano-dual-scaled pore structural features, the high Nb containing TiAl-based porous composite microfiltration membrane demonstrates ultrahigh PM>2.5removal efficiency (99.58%) and favorable oxidation/sulfidation performance at high temperature. These features, combined with our experimental design strategy, provide insight into designing high-temperature PM filtration membrane materials with enhanced performance and durability.