bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nerve growth factor (NGF) with hypoxia response elements loaded by adeno-associated virus (AAV) combined with neural stem cells improve the spinal cord injury recovery
Authors: Wu Qiuji , Xiang Ziyue , Ying Yibo , Huang Zhiyang , Tu Yurong , Chen Min , Ye Jiahui , Dou Haicheng , Sheng Sunren , Li Xiaoyang , Ying Weiyang , Zhu Sipin 
Published: October 2021

AbstractThe ischemia and hypoxia microenvironment after spinal cord injury (SCI) makes SCI repair a challenging problem. With various stimulus, chances for neural stem cells (NSCs) to differentiate into neurons, astrocytes, oligodendrocytes are great and is considered as a potential source of the stem cell therapy to SCI. Our research used adeno-associated virus (AAV) to carry the target gene to transfect neural stem cells. Transfected NSCs can express nerve growth factor (NGF) navigated by five hypoxia-responsive elements (5HRE). Therefore, the 5HRE-NGF-NSCs could express NGF specifically in hypoxia sites to promote the tissue repair and function recovery. Based on the regeneration of neurocytes and promotion of the recovery found in SCI models, via locomotor assessment, histochemical staining and molecular examinations, our results demonstrated that 5HRE-NGF-NSCs could improve the motor function, neurons survival and molecules expression of SCI rats. Meanwhile, the downregulated expression of autophagy-related proteins indicated the inhibitive effect of 5HRE-NGF-NSCs on autophagy. Our research showed that 5HRE-NGF-NSCs contribute to SCI repair which might via inhibiting autophagy and improving the survival rate of neuronal cells. The new therapy also hampered the hyperplasia of neural glial scars and induced axon regeneration. These positive functions of 5HRE-NGF-NSCs all indicate a promising SCI treatment.
Validation of lipid-related therapeutic targets for coronary heart disease prevention using human genetics
Authors: Gordillo-Marañón María , Zwierzyna Magdalena , Charoen Pimphen , Drenos Fotios , Chopade Sandesh , Shah Tina , Engmann Jorgen , Chaturvedi Nishi , Papacosta Olia , Wannamethee Goya , Wong Andrew , Sofat Reecha , Kivimaki Mika , Price Jackie F. , Hughes Alun D. , Gaunt Tom R. , Lawlor Deborah A. , Gaulton Anna , Hingorani Aroon D. , Schmidt Amand F. , Finan Chris 
Published: October 2021

AbstractDrug target Mendelian randomization (MR) studies use DNA sequence variants in or near a gene encoding a drug target, that alter the target’s expression or function, as a tool to anticipate the effect of drug action on the same target. Here we apply MR to prioritize drug targets for their causal relevance for coronary heart disease (CHD). The targets are further prioritized using independent replication, co-localization, protein expression profiles and data from the British National Formulary and clinicaltrials.gov. Out of the 341 drug targets identified through their association with blood lipids (HDL-C, LDL-C and triglycerides), we robustly prioritize 30 targets that might elicit beneficial effects in the prevention or treatment of CHD, including NPC1L1 and PCSK9, the targets of drugs used in CHD prevention. We discuss how this approach can be generalized to other targets, disease biomarkers and endpoints to help prioritize and validate targets during the drug development process.
Light-triggered and phosphorylation-dependent 14-3-3 association with NON-PHOTOTROPIC HYPOCOTYL 3 is required for hypocotyl phototropism
Authors: Reuter Lea , Schmidt Tanja , Manishankar Prabha , Throm Christian , Keicher Jutta , Bock Andrea , Droste-Borel Irina , Oecking Claudia 
Published: October 2021

AbstractNON-PHOTOTROPIC HYPOCOTYL 3 (NPH3) is a key component of the auxin-dependent plant phototropic growth response. We report that NPH3 directly binds polyacidic phospholipids, required for plasma membrane association in darkness. We further demonstrate that blue light induces an immediate phosphorylation of a C-terminal 14-3-3 binding motif in NPH3. Subsequent association of 14-3-3 proteins is causal for the light-induced release of NPH3 from the membrane and accompanied by NPH3 dephosphorylation. In the cytosol, NPH3 dynamically transitions into membraneless condensate-like structures. The dephosphorylated state of the 14-3-3 binding site and NPH3 membrane recruitment are recoverable in darkness. NPH3 variants that constitutively localize either to the membrane or to condensates are non-functional, revealing a fundamental role of the 14-3-3 mediated dynamic change in NPH3 localization for auxin-dependent phototropism. This regulatory mechanism might be of general nature, given that several members of the NPH3-like family interact with 14-3-3 via a C-terminal motif.
Neuronal ribosomes exhibit dynamic and context-dependent exchange of ribosomal proteins
Authors: Fusco Claudia M. , Desch Kristina , Dörrbaum Aline R. , Wang Mantian , Staab Anja , Chan Ivy C. W. , Vail Eleanor , Villeri Veronica , Langer Julian D. , Schuman Erin M. 
Published: October 2021

AbstractOwing to their morphological complexity and dense network connections, neurons modify their proteomes locally, using mRNAs and ribosomes present in the neuropil (tissue enriched for dendrites and axons). Although ribosome biogenesis largely takes place in the nucleus and perinuclear region, neuronal ribosomal protein (RP) mRNAs have been frequently detected remotely, in dendrites and axons. Here, using imaging and ribosome profiling, we directly detected the RP mRNAs and their translation in the neuropil. Combining brief metabolic labeling with mass spectrometry, we found that a group of RPs rapidly associated with translating ribosomes in the cytoplasm and that this incorporation was independent of canonical ribosome biogenesis. Moreover, the incorporation probability of some RPs was regulated by location (neurites vs. cell bodies) and changes in the cellular environment (following oxidative stress). Our results suggest new mechanisms for the local activation, repair and/or specialization of the translational machinery within neuronal processes, potentially allowing neuronal synapses a rapid means to regulate local protein synthesis.
Intracellular delivery of protein drugs with an autonomously lysing bacterial system reduces tumor growth and metastases
Authors: Raman Vishnu , Van Dessel Nele , Hall Christopher L. , Wetherby Victoria E. , Whitney Samantha A. , Kolewe Emily L. , Bloom Shoshana M. K. , Sharma Abhinav , Hardy Jeanne A. , Bollen Mathieu , Van Eynde Aleyde , Forbes Neil S. 
Published: October 2021

AbstractCritical cancer pathways often cannot be targeted because of limited efficiency crossing cell membranes. Here we report the development of a Salmonella-based intracellular delivery system to address this challenge. We engineer genetic circuits that (1) activate the regulator flhDC to drive invasion and (2) induce lysis to release proteins into tumor cells. Released protein drugs diffuse from Salmonella containing vacuoles into the cellular cytoplasm where they interact with their therapeutic targets. Control of invasion with flhDC increases delivery over 500 times. The autonomous triggering of lysis after invasion makes the platform self-limiting and prevents drug release in healthy organs. Bacterial delivery of constitutively active caspase-3 blocks the growth of hepatocellular carcinoma and lung metastases, and increases survival in mice. This success in targeted killing of cancer cells provides critical evidence that this approach will be applicable to a wide range of protein drugs for the treatment of solid tumors.
Stroboscopic operando spectroscopy of the dynamics in heterogeneous catalysis by event-averaging
Authors: Knudsen Jan , Gallo Tamires , Boix Virgínia , Strømsheim Marie Døvre , D’Acunto Giulio , Goodwin Christopher , Wallander Harald , Zhu Suyun , Soldemo Markus , Lömker Patrick , Cavalca Filippo , Scardamaglia Mattia , Degerman David , Nilsson Anders , Amann Peter , Shavorskiy Andrey , Schnadt Joachim 
Published: October 2021

AbstractHeterogeneous catalyst surfaces are dynamic entities that respond rapidly to changes in their local gas environment, and the dynamics of the response is a decisive factor for the catalysts’ action and activity. Few probes are able to map catalyst structure and local gas environment simultaneously under reaction conditions at the timescales of the dynamic changes. Here we use the CO oxidation reaction and a Pd(100) model catalyst to demonstrate how such studies can be performed by time-resolved ambient pressure photoelectron spectroscopy. Central elements of the method are cyclic gas pulsing and software-based event-averaging by image recognition of spectral features. A key finding is that at 3.2 mbar total pressure a metallic, predominantly CO-covered metallic surface turns highly active for a few seconds once the O2:CO ratio becomes high enough to lift the CO poisoning effect before mass transport limitations triggers formation of a √5 oxide.
A class of organic cages featuring twin cavities
Authors: Yang Zhenyu , Yu Chunyang , Ding Junjie , Chen Lihua , Liu Huiyu , Ye Yangzhi , Li Pan , Chen Jiaolong , Wu Kim Jiayi , Zhu Qiang-Yu , Zhao Yu-Quan , Liu Xiaoning , Zhuang Xiaodong , Zhang Shaodong 
Published: October 2021

AbstractA variety of organic cages with different geometries have been developed during the last decade, most of them exhibiting a single cavity. In contrast, the number of organic cages featuring a pair of cavities remains scarce. These structures may pave the way towards novel porous materials with emergent properties and functions.We herein report on rational design of a three-dimensional hexaformyl precursor 1, which exhibits two types of conformers, i.e. Conformer-1 and -2, with different cleft positions and sizes. Aided by molecular dynamics simulations, we select two triamino conformation capturers (denoted CC). Small-sized CC-1 selectively capture Conformer-1 by matching its cleft size, while the large-sized CC-2 is able to match and capture both conformers. This strategy allows the formation of three compounds with twin cavities, which we coin diphane. The self-assembly of diphane units results in superstructures with tunable proton conductivity, which reaches up to 1.37×10-5 S cm-1.
Macrophage deletion of Noc4l triggers endosomal TLR4/TRIF signal and leads to insulin resistance
Authors: Qin Yongli , Jia Lina , Liu Huijiao , Ma Wenqiang , Ren Xinmin , Li Haifeng , Liu Yuanwu , Li Haiwen , Ma Shuoqian , Liu Mei , Li Pingping , Yan Jinghua , Zhang Jiyan , Guo Yangdong , You Hua , Guo Yan , Rahman Nafis A. , Wołczyński Sławomir , Kretowski Adam , Li Dangsheng , Li Xiru , Ren Fazheng , Li Xiangdong 
Published: October 2021

AbstractIn obesity, macrophages drive a low-grade systemic inflammation (LSI) and insulin resistance (IR). The ribosome biosynthesis protein NOC4 (NOC4) mediates 40 S ribosomal subunits synthesis in yeast. Hereby, we reported an unexpected location and function of NOC4L, which was preferentially expressed in human and mouse macrophages. NOC4L was decreased in both obese human and mice. The macrophage-specific deletion of Noc4l in mice displayed IR and LSI. Conversely, Noc4l overexpression by lentivirus treatment and transgenic mouse model improved glucose metabolism in mice. Importantly, we found that Noc4l can interact with TLR4 to inhibit its endocytosis and block the TRIF pathway, thereafter ameliorated LSI and IR in mice.
Optimal value of CA19-9 determined by KRAS-mutated circulating tumor DNA contributes to the prediction of prognosis in pancreatic cancer patients
Authors: Watanabe Fumiaki , Suzuki Koichi , Tamaki Sawako , Abe Iku , Endo Yuhei , Takayama Yuji , Ishikawa Hideki , Kakizawa Nao , Saito Masaaki , Futsuhara Kazushige , Noda Hiroshi , Konishi Fumio , Rikiyama Toshiki 
Published: October 2021

AbstractDespite the acceptance of carbohydrate antigen 19-9 (CA19-9) as a valuable predictor for the prognosis of pancreatic ductal adenocarcinoma (PDAC), its cutoff value remains controversial. Our previous study showed a significant correlation between CA19-9 levels and the presence of KRAS-mutated ctDNA in the blood of patients with PDAC. Based on this correlation, we investigated the optimal cutoff value of CA19-9 before surgery. Continuous CA19-9 values and KRAS-mutated ctDNAs were monitored in 22 patients with unresectable PDAC who underwent chemotherapy between 2015 and 2017. Receiver operating characteristic curve analysis identified 949.7 U/mL of CA19-9 as the cutoff value corresponding to the presence of KRAS-mutated ctDNA. The median value of CA19-9 was 221.1 U/mL. Subsequently, these values were verified for their prognostic values of recurrence-free survival (RFS) and overall survival (OS) in 60 patients who underwent surgery between 2005 and 2013. Multivariate analysis revealed that 949.7 U/mL of CA19-9 was an independent risk factor for OS and RFS in these patients (P = 0.001 and P = 0.010, respectively), along with lymph node metastasis (P = 0.008 and P = 0.017), unlike the median CA19-9 level (P = 0.150 and P = 0.210). The optimal CA19-9 level contributes to the prediction of prognosis in patients with PDAC before surgery.
Bayesian inference of ion velocity distribution function from laser-induced fluorescence spectra
Authors: Tokuda S. , Kawachi Y. , Sasaki M. , Arakawa H. , Yamasaki K. , Terasaka K. , Inagaki S. 
Published: October 2021

AbstractThe velocity distribution function is a statistical description that connects particle kinetics and macroscopic parameters in many-body systems. Laser-induced fluorescence (LIF) spectroscopy is utilized to measure the local velocity distribution function in spatially inhomogeneous plasmas. However, the analytic form of such a function for the system of interest is not always clear under the intricate factors in non-equilibrium states. Here, we propose a novel approach to select the valid form of the velocity distribution function based on Bayesian statistics. We formulate the Bayesian inference of ion velocity distribution function and apply it to LIF spectra locally observed at several positions in a linear magnetized plasma. We demonstrate evaluating the spatial inhomogeneity by verifying each analytic form of the local velocity distribution function. Our approach is widely applicable to experimentally establish the velocity distribution function in plasmas and fluids, including gases and liquids.
Enhanced hyperspectral tomography for bioimaging by spatiospectral reconstruction
Authors: Warr Ryan , Ametova Evelina , Cernik Robert J. , Fardell Gemma , Handschuh Stephan , Jørgensen Jakob S. , Papoutsellis Evangelos , Pasca Edoardo , Withers Philip J. 
Published: October 2021

AbstractHere we apply hyperspectral bright field imaging to collect computed tomographic images with excellent energy resolution (~ 1 keV), applying it for the first time to map the distribution of stain in a fixed biological sample through its characteristic K-edge. Conventionally, because the photons detected at each pixel are distributed across as many as 200 energy channels, energy-selective images are characterised by low count-rates and poor signal-to-noise ratio. This means high X-ray exposures, long scan times and high doses are required to image unique spectral markers. Here, we achieve high quality energy-dispersive tomograms from low dose, noisy datasets using a dedicated iterative reconstruction algorithm. This exploits the spatial smoothness and inter-channel structural correlation in the spectral domain using two carefully chosen regularisation terms. For a multi-phase phantom, a reduction in scan time of 36 times is demonstrated. Spectral analysis methods including K-edge subtraction and absorption step-size fitting are evaluated for an ex vivo, single (iodine)-stained biological sample, where low chemical concentration and inhomogeneous distribution can affect soft tissue segmentation and visualisation. The reconstruction algorithms are available through the open-source Core Imaging Library. Taken together, these tools offer new capabilities for visualisation and elemental mapping, with promising applications for multiply-stained biological specimens.
Multi-drug resistance and high mortality associated with community-acquired bloodstream infections in children in conflict-affected northwest Nigeria
Authors: Chukwumeze Frederick , Lenglet Annick , Olubiyo Ruth , Lawal Abdulhakeem Mohammed , Oluyide Bukola , Oloruntuyi Gbemisola , Ariti Cono , Gomez Diana , Roggeveen Harriet , Nwankwo Chijioke , Augustine Nwogu Ahamba , Egwuenu Abiodun , Maloba Guy , Sherlock Mark , Muhammad Shoaib , Wertheim Heiman , Hopman Joost , Clezy Kate 
Published: October 2021

AbstractPediatric community-acquired bloodstream infections (CA-BSIs) in sub Saharan African humanitarian contexts are rarely documented. Effective treatment of these infections is additionally complicated by increasing rates of antimicrobial resistance. We describe the findings from epidemiological and microbiological surveillance implemented in pediatric patients with suspected CA-BSIs presenting for care at a secondary hospital in the conflict affected area of Zamfara state, Nigeria. Any child (> 2 months of age) presenting to Anka General Hospital from November 2018 to August 2020 with clinical severe sepsis at admission had clinical and epidemiological information and a blood culture collected at admission. Bacterial isolates were tested for antibiotic susceptibility. We calculated frequencies of epidemiological, microbiological and clinical parameters. We explored risk factors for death amongst severe sepsis cases using univariable and multivariable Poisson regression, adjusting for time between admission and hospital exit. We included 234 severe sepsis patients with 195 blood culture results. There were 39 positive blood cultures. Of the bacterial isolates, 14 were Gram positive and 18 were Gram negative; 5 were resistant to empiric antibiotics: methicillin-resistantStaphylococcus aureus(MRSA; n = 2) and Extended Spectrum Beta-Lactamase positive enterobacterales (n = 3). We identified no significant association between sex, age-group, ward, CA-BSI, appropriate intravenous antibiotic, malaria positivity at admission, suspected focus of sepsis, clinical severity and death in the multivariable regression. There is an urgent need for access to good clinical microbiological services, including point of care methods, and awareness and practice around rational antibiotic in healthcare staff in humanitarian settings to reduce morbidity and mortality from sepsis in children.
Enhancement of Campylobacter hepaticus culturing to facilitate downstream applications
Authors: Phung Canh , Wilson Timothy B. , Quinteros José A. , Scott Peter C. , Moore Robert J. , Van Thi Thu Hao 
Published: October 2021

AbstractCampylobacter hepaticus causes Spotty Liver Disease (SLD) in chickens. C. hepaticus is fastidious and slow-growing, presenting difficulties when growing this bacterium for the preparation of bacterin vaccines and experimental disease challenge trials. This study applied genomic analysis and in vitro experiments to develop an enhanced C. hepaticus liquid culture method. In silico analysis of the anabolic pathways encoded by C. hepaticus revealed that the bacterium is unable to biosynthesise l-cysteine, l-lysine and l-arginine. It was found that l-cysteine added to Brucella broth, significantly enhanced the growth of C. hepaticus, but l-lysine or l-arginine addition did not enhance growth. Brucella broth supplemented with l-cysteine (0.4 mM), l-glutamine (4 mM), and sodium pyruvate (10 mM) gave high-density growth of C. hepaticus and resulted in an almost tenfold increase in culture density compared to the growth in Brucella broth alone (log10 = 9.3 vs 8.4 CFU/mL). The type of culture flask used also significantly affected C. hepaticus culture density. An SLD challenge trial demonstrated that C. hepaticus grown in the enhanced culture conditions retained full virulence. The enhanced liquid culture method developed in this study enables the efficient production of bacterial biomass and therefore facilitates further studies of SLD biology and vaccine development.
Changes in the profile properties and chemical weathering characteristics of cultivated soils affected by anthropic activities
Authors: Li Jiangwen , Du Jing , Zhong Shouqin , Ci En , Wei Chaofu 
Published: October 2021

AbstractThe study of the pedogenic process in response to natural evolution, gradual anthropogenic shifts and engineering upheavals is of great significance for understanding, utilizing and transforming nature in the future. Although scholars have considered anthropic activities to be an important factor affecting pedogenesis, research on how and how much anthropic activities influence the soil-forming process is scant. This paper was conducted to analyse pedogenic characteristics dominated by anthropic activities. In this study, the parent materials and soils undergoing natural evolution (NE), tillage perturbation (TP) and engineering perturbation (EP) were selected as research objects. The genetic characteristics of soils undergoing NE, TP and EP are investigated mainly from three aspects: soil profile macromorphological characteristics, soil physical and chemical properties and chemical weathering characteristics. The results indicated that the influence of anthropic activities (TP and EP) on the process of pedogenesis is complicated. First, compared with NE, TP decreases the thickness of topsoil from 22.2 to 21.2 cm, while EP increases the thickness of topsoil from 22.2 to 23.2 cm, and EP causes the soil to have a high profile development index. Second, compared with TP, EP can improve bulk density (BD), soil organic carbon (SOC), total nitrogen (TN) and cation exchange capacity (CEC), Finally, the chemical weathering intensity differed among NE, TP and EP and followed the order of TP > NE > EP. Therefore, in the future, the genetic characteristics of soils dominated by anthropic activities should be considered. This will help us systematically understand the genesis and evolutionary characteristics of soil and lay a foundation for further perfecting the diagnostic horizon and diagnostic characteristics of the Soil Taxonomy and World Reference Base.
Characteristics of serum metabolites in sporadic amyotrophic lateral sclerosis patients based on gas chromatography-mass spectrometry
Authors: Jia Rui , Chen Qiaoyi , Zhou Qingqing , Zhang Ronghua , Jin Jiaoting , Hu Fangfang , Liu Xiao , Qin Xing , Kang Li , Zhao Songzhen , Dang Yonghui , Dang Jingxia 
Published: October 2021

AbstractTo identify differential metabolites and metabolic pathways and provide guidance for the novel biomarkers for diagnosis and prognosis of amyotrophic lateral sclerosis (ALS). ALS patients and people without nervous diseases were recruited. Metabolomic analysis was performed using gas chromatography-mass spectrometry (GC/MS). The orthogonal projections to latent structures discriminant analysis (OPLS-DA) were used to identify differential metabolites. Kyoto Encyclopedia of Genes and Genomes and MetaboAnalyst were used to identify metabolic pathways. 75 metabolites were detected and aligned. The OPLS-DA showed the metabolomic profile of ALS patients and those in the fast-progression and slow-progression ALS groups differed from that of CTRL (p < 0.05). The levels of maltose, glyceric acid, lactic acid, beta-alanine, phosphoric acid, glutamic acid, ethanolamine and glycine in ALS were significantly higher, while 2,4,6-tri-tert-butylbenzenethiol was lower. Glycine, serine and threonine metabolism, D-glutamine and D-glutamate metabolism, alanine, aspartate, and glutamate metabolism, beta-alanine metabolism, and pyruvate metabolism were significantly altered metabolic pathways in ALS. ROC was used to discriminate ALS from CTRL with an AUC of 0.898 (p < 0.001) using 2,4,6-tri-tert-butylbenzenethiol, beta-alanine, glycine, and ethanolamine. The serum metabolites and metabolic pathways in ALS patients are significantly altered compared with CTRL. These findings may contribute to the early diagnosis of ALS.