bluuebunny/crossref_metadata_2025_split huggingface dataset:
Redox-triggered switching in three-dimensional covalent organic frameworks
Authors: Gao Chao , Li Jian , Yin Sheng , Sun Junliang , Wang Cheng 
Published: October 2020

AbstractThe tuning of molecular switches in solid state toward stimuli-responsive materials has attracted more and more attention in recent years. Herein, we report a switchable three-dimensional covalent organic framework (3D COF), which can undergo a reversible transformation through a hydroquinone/quinone redox reaction while retaining the crystallinity and porosity. Our results clearly show that the switching process gradually happened through the COF framework, with an almost quantitative conversion yield. In addition, the redox-triggered transformation will form different functional groups on the pore surface and modify the shape of pore channel, which can result in tunable gas separation property. This study strongly demonstrates 3D COFs can provide robust platforms for efficient tuning of molecular switches in solid state. More importantly, switching of these moieties in 3D COFs can remarkably modify the internal pore environment, which will thus enable the resulting materials with interesting stimuli-responsive properties.
Mendelian randomization while jointly modeling cis genetics identifies causal relationships between gene expression and lipids
Authors: van der Graaf Adriaan , Claringbould Annique , Rimbert Antoine ,   BIOS Consortium, Heijmans Bastiaan T. , Hoen Peter A. C.’t , van Meurs Joyce B. J. , Jansen Rick , Franke Lude , Westra Harm-Jan , Li Yang , Wijmenga Cisca , Sanna Serena 
Published: October 2020

AbstractInference of causality between gene expression and complex traits using Mendelian randomization (MR) is confounded by pleiotropy and linkage disequilibrium (LD) of gene-expression quantitative trait loci (eQTL). Here, we propose an MR method, MR-link, that accounts for unobserved pleiotropy and LD by leveraging information from individual-level data, even when only one eQTL variant is present. In simulations, MR-link shows false-positive rates close to expectation (median 0.05) and high power (up to 0.89), outperforming all other tested MR methods and coloc. Application of MR-link to low-density lipoprotein cholesterol (LDL-C) measurements in 12,449 individuals with expression and protein QTL summary statistics from blood and liver identifies 25 genes causally linked to LDL-C. These include the known SORT1 and ApoE genes as well as PVRL2, located in the APOE locus, for which a causal role in liver was not known. Our results showcase the strength of MR-link for transcriptome-wide causal inferences.
Local-scale Arctic tundra heterogeneity affects regional-scale carbon dynamics
Authors: Lara M. J. , McGuire A. D. , Euskirchen E. S. , Genet H. , Yi S. , Rutter R. , Iversen C. , Sloan V. , Wullschleger S. D. 
Published: October 2020

AbstractIn northern Alaska nearly 65% of the terrestrial surface is composed of polygonal ground, where geomorphic tundra landforms disproportionately influence carbon and nutrient cycling over fine spatial scales. Process-based biogeochemical models used for local to Pan-Arctic projections of ecological responses to climate change typically operate at coarse-scales (1km2–0.5°) at which fine-scale (<1km2) tundra heterogeneity is often aggregated to the dominant land cover unit. Here, we evaluate the importance of tundra heterogeneity for representing soil carbon dynamics at fine to coarse spatial scales. We leveraged the legacy of data collected near Utqiaġvik, Alaska between 1973 and 2016 for model initiation, parameterization, and validation. Simulation uncertainty increased with a reduced representation of tundra heterogeneity and coarsening of spatial scale. Hierarchical cluster analysis of an ensemble of 21st-century simulations reveals that a minimum of two tundra landforms (dry and wet) and a maximum of 4km2 spatial scale is necessary for minimizing uncertainties (<10%) in regional to Pan-Arctic modeling applications.
Nano polarimetry: enhanced AFM-NSOM triple-mode polarimeter tip
Authors: Karelits Matityahu , Zalevsky Zeev , Karsenty Avi 
Published: October 2020

AbstractA novel application of a combined and enhanced NSOM-AFM tip-photodetector system resulted in a nanoscale Polarimeter, generated by four different holes, each sharing a different shape, and enabling that the four photonic readouts forming the tip will be the four Stokes coefficients, this in order to place the polarization state in the Poincare sphere. The new system has been built on standard Atomic Force Microscope (AFM) cantilever, in order to serve as a triple-mode scanning system, sharing complementary scanning topography, optical data analysis and polarization states. This new device, which has been designed and simulated using Comsol Multi-Physics software package, consists in a Platinum-Silicon drilled conical photodetector, sharing subwavelength apertures, and has been processed using advanced nanotechnology tools on a commercial silicon cantilever. After a comparison study of drilled versus filled tips advantages, and of several optics phenomena such as interferences, the article presents the added value of multiple-apertures scanning tip for nano-polarimetry.
Antiviral activity of digoxin and ouabain against SARS-CoV-2 infection and its implication for COVID-19
Authors: Cho Junhyung , Lee Young Jae , Kim Je Hyoung , Kim Sang il , Kim Sung Soon , Choi Byeong-Sun , Choi Jang-Hoon 
Published: October 2020

AbstractThe current coronavirus (COVID-19) pandemic is exacerbated by the absence of effective therapeutic agents. Notably, patients with COVID-19 and comorbidities such as hypertension and cardiac diseases have a higher mortality rate. An efficient strategy in response to this issue is repurposing drugs with antiviral activity for therapeutic effect. Digoxin (DIG) and ouabain (OUA) are FDA drugs for heart diseases that have antiviral activity against several coronaviruses. Thus, we aimed to assess antiviral activity of DIG and OUA against SARS-CoV-2 infection. The half-maximal inhibitory concentrations (IC50) of DIG and OUA were determined at a nanomolar concentration. Progeny virus titers of single-dose treatment of DIG, OUA and remdesivir were approximately 103-, 104- and 103-fold lower (> 99% inhibition), respectively, than that of non-treated control or chloroquine at 48 h post-infection (hpi). Furthermore, therapeutic treatment with DIG and OUA inhibited over 99% of SARS-CoV-2 replication, leading to viral inhibition at the post entry stage of the viral life cycle. Collectively, these results suggest that DIG and OUA may be an alternative treatment for COVID-19, with potential additional therapeutic effects for patients with cardiovascular disease.
Differential expression of miRNAs in skeletal muscles of Indian sheep with diverse carcass and muscle traits
Authors: Kaur Mandeep , Kumar Ashish , Siddaraju Naveen Kumar , Fairoze Mohamed Nadeem , Chhabra Pooja , Ahlawat Sonika , Vijh Ramesh Kumar , Yadav Anita , Arora Reena 
Published: October 2020

AbstractThe study presents the miRNA profiles of two Indian sheep populations with divergent carcass and muscle traits. The RNA sequencing of longissimus thoracis muscles from the two populations revealed a total of 400 known miRNAs. Myomirs or miRNAs specific to skeletal muscles identified in our data included oar-miR-1, oar-miR-133b, oar-miR-206 and oar-miR-486. Comparison of the two populations led to identification of 100 differentially expressed miRNAs (p < 0.05). A total of 45 miRNAs exhibited a log2 fold change of ≥ ( ±) 3.0. Gene Ontology analysis revealed cell proliferation, epithelial to mesenchymal transition, apoptosis, immune response and cell differentiation as the most significant functions of the differentially expressed miRNAs. The differential expression of some miRNAs was validated by qRT-PCR analysis. Enriched pathways included metabolism of proteins and lipids, PI3K-Akt, EGFR and cellular response to stress. The microRNA-gene interaction network revealed miR-21, miR-155, miR-143, miR-221 and miR-23a as the nodal miRNAs, with multiple targets. MicroRNA-21 formed the focal point of the network with 42 interactions. The hub miRNAs identified in our study form putative regulatory candidates for future research on meat quality traits in Indian sheep. Our results provide insight into the biological pathways and regulatory molecules implicated in muscling traits of sheep.
STAT3 deficiency in B cells exacerbates uveitis by promoting expansion of pathogenic lymphocytes and suppressing regulatory B cells (Bregs) and Tregs
Authors: Oladipupo Favour O. , Yu Cheng-Rong , Olumuyide Ezekiel , Jittaysothorn Yingyos , Choi Jin Kyeong , Egwuagu Charles E. 
Published: October 2020

AbstractSTAT3 transcription factor induces differentiation of naïve T cells into Th17 cells and loss of STAT3 in T cell prevents development of CNS autoimmune diseases. However, function of STAT3 in the B lymphocyte subset is not well understood. In this study, we have generated mice lacking STAT3 in CD19+B cells (CD19-STAT3KO) and investigated intrinsic and extrinsic functions of STAT3 in B cells and its potential role in resistance or pathogenesis of organ-specific autoimmune diseases. We show that STAT3 regulates metabolic mechanisms in B cells with implications for bioenergetic and metabolic pathways that control cellular homeostasis in B cells. Thus, loss of STAT3 in CD19-STAT3KO cells perturbed growth and apoptosis by inducing rapid entry of B cells into the S-phase of the cell cycle, decreasing expression of cyclin-dependent kinase inhibitors and upregulating pro-apoptotic proteins. We further show that the CD19-STAT3KO mice develop severe experimental autoimmune uveitis (EAU), an animal model of human uveitis. Exacerbated uveitis in CD19-STAT3KO mice derived in part from enhanced expression of costimulatory molecules on B cells, marked increase of Th17 responses and increased recruitment of granulocytes into the neuroretina. The enhanced autoimmunity upon deletion of STAT3 in B cells is also recapitulated in experimental autoimmune encephalitis, a mouse model of multiple sclerosis and thus support our conclusion that STAT3 deletion in B cells enhanced inflammation and the effects observed are not model specific. Our data further indicate that STAT3 pathway modulates interactions between B and T cells during EAU resulting in alteration of lymphocyte repertoire by increasing levels of autoreactive pathogenic T cells while suppressing development and/or expansion of immune-suppressive lymphocytes (Bregs and Tregs). Taken together, STAT3 exerts diametrically opposite effects in lymphocytes, with loss of STAT3 in B cells exacerbating uveitis whereasStat3deletion in T cells confers protection.
Accuracy of endobronchial ultrasound-guided transbronchial needle aspiration in HIV-infected patients with thoracic lymphadenopathy in a tuberculosis low-burden area
Authors: Tetart Macha , Betraoui Farid , Huleux Thomas , Wallyn Frédéric , Brichet Anne , Thill Pauline , Robineau Olivier , Meybeck Agnès 
Published: October 2020

AbstractEndobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is an innovative technique to explore hilar and mediastinal lymphadenopathy. We aimed to assess its diagnostic accuracy in HIV-infected patients in a tuberculosis low-burden area. A retrospective review was performed of all HIV-infected patients with thoracic lymphadenopathy referred for EBUS-TBNA between January 2012 and January 2019 in 3 Northern French Hospitals. A total of 15 patients was included during the study period. Our patients were predominantly male (80%), with a mean age of 50 ± 11 years. Six patients (43%) had a CD4 cells count of less than 200/mm3. Eleven patients (73%) were receiving antiretroviral therapy, and 7 (47%) reached undetectable viral load. Adequate lymphnode sampling was accomplished in all patients. No serious complications were reported. EBUS-TBNA led to a definitive diagnosis in 12 out of 15 patients (80%). It identified 4 neoplasia, 3 atypical mycobacterial diseases, 2 tuberculosis, 1 Castleman disease, 1 sarcoidosis, and 1 professional dustiness. In 3 cases, sampling revealed normal lymphoid tissue. Active surveillance confirmed the suspected diagnosis of HIV adenitis with regression of lymphadenopathy on antiretroviral therapy in 2 cases. In one case of negative sampling, thoracoscopy led to the diagnosis of tuberculosis. In our cohort, accuracy of EBUS-TBNA was 92%. EBUS-TBNA appeared to be a safe and accurate tool in the investigation of mediastinal lymphadenopathy in HIV-infected patients in settings of tuberculosis low-prevalence. It can avoid more invasive procedures such as mediastinoscopy.
The application of single-port laparoscopic percutaneous internal ring suture for the management of indirect inguinal hernia in female adults
Authors: Wang Shih-Hsien , Yen Ju-Bei , Hsu Sheng-Lung 
Published: October 2020

AbstractAs most of the female inguinal hernias are of indirect type, we conducted this retrospective study to evaluate whether the single port laparoscopic percutaneous internal ring suture is feasible for the management of indirect inguinal hernia in female adults. From April 2016 to August 2019, there were 31 female adults who were diagnosed with inguinal hernias and received laparoscopic inspection at our surgical department. One patient who was finally diagnosed as an encysted hydrocele was excluded from the statistic study. All the 30 cases were of indirect type with a total of 35 single port laparoscopic percutaneous internal ring sutures performed. The median age was 38 years (range 20–88 years). The number and percentage of patients with right, left and bilateral hernias were 17 (56%), 11 (37%) and 2 (7%) respectively. Three contralateral patent processi vaginalium and 1 occult femoral hernia were found during operation. The percentages of the respective classifications according to the European Hernia Society system for the 35 PIRSs were L1: 40%, L2: 49%, and L3: 11%. The average operation time was 18 min for unilateral and 30 min for bilateral hernias. There were 1 recurrence and 1 chronic postoperative inguinal pain. Both had their symptoms and signs resolved after reoperation. The mean follow-up period was 13.6 months. We concluded that the single-port laparoscopic percutaneous internal ring suture is feasible for the management of indirect inguinal hernia in female adults.
Reproductive characteristics of American bullfrogs (Lithobates catesbeianus) in their invasive range of the Pacific Northwest, USA
Authors: Urbina Jenny , Bredeweg Evan M. , Cousins Christopher , Blaustein Andrew R. , Garcia Tiffany S. 
Published: October 2020

AbstractInvasive species pose a major threat to global biodiversity. The effects of invasive species can be strongly influenced and potentially mediated by their reproductive characteristics, such as fecundity, egg production, and duration and number of reproductive events. Selection for smaller body size at first reproduction can also play a role in their establishment, facilitating colonization and spread. The American bullfrog, native to the eastern U.S. (Lithobates catesbeianus), is a species that has invaded more than 40 countries across 4 continents. This species has become especially prevalent in the western United States since its introduction in the early 1900s. This study characterized reproductive characteristics of bullfrogs with emphasis on the minimum size at which males and females reach sexual maturity in the Willamette Valley, Oregon, USA invasion range. We collected and dissected 121 individuals in 2013 and 2017, quantifying characteristics of sexual maturity including snout-vent length, total length, sex, tympanum diameter, presence of distended oviducts or eggs for females, and testes length and sperm activity in males. Our results showed that the minimum reproductive size of both males and females was smaller relative to bullfrogs in their native range as well as in populations across their invasive range. Reduction in size at reproductive maturity is likely impacting the invasive success of American bullfrogs and this study gives us insight on management actions to control the invasion. Applying this insight, managers can adjust their definition of reproductively active adults, increasing the target population of culling and other control methods.
Metal ions shape α-synuclein
Authors: Moons Rani , Konijnenberg Albert , Mensch Carl , Van Elzen Roos , Johannessen Christian , Maudsley Stuart , Lambeir Anne-Marie , Sobott Frank 
Published: October 2020

Abstractα-Synuclein is an intrinsically disordered protein that can self-aggregate and plays a major role in Parkinson’s disease (PD). Elevated levels of certain metal ions are found in protein aggregates in neurons of people suffering from PD, and environmental exposure has also been linked with neurodegeneration. Importantly, cellular interactions with metal ions, particularly Ca2+, have recently been reported as key for α-synuclein’s physiological function at the pre-synapse. Here we study effects of metal ion interaction with α-synuclein at the molecular level, observing changes in the conformational behaviour of monomers, with a possible link to aggregation pathways and toxicity. Using native nano-electrospray ionisation ion mobility-mass spectrometry (nESI-IM-MS), we characterize the heterogeneous interactions of alkali, alkaline earth, transition and other metal ions and their global structural effects on α-synuclein. Different binding stoichiometries found upon titration with metal ions correlate with their specific binding affinity and capacity. Subtle conformational effects seen for singly charged metals differ profoundly from binding of multiply charged ions, often leading to overall compaction of the protein depending on the preferred binding sites. This study illustrates specific effects of metal coordination, and the associated electrostatic charge patterns, on the complex structural space of the intrinsically disordered protein α-synuclein.
Reconstruction and analysis of genome-scale metabolic model of weak Crabtree positive yeast Lachancea kluyveri
Authors: Nanda Piyush , Patra Pradipta , Das Manali , Ghosh Amit 
Published: October 2020

AbstractLachancea kluyveri, a weak Crabtree positive yeast, has been extensively studied for its unique URC pyrimidine catabolism pathway. It produces more biomass than Saccharomyces cerevisiae due to the underlying weak Crabtree effect and resorts to fermentation only in oxygen limiting conditions that renders it as a suitable industrial host. The yeast also produces ethyl acetate as a major overflow metabolite in aerobic conditions. Here, we report the first genome-scale metabolic model, iPN730, of L. kluyveri comprising of 1235 reactions, 1179 metabolites, and 730 genes distributed in 8 compartments. The in silico viability in different media conditions and the growth characteristics in various carbon sources show good agreement with experimental data. Dynamic flux balance analysis describes the growth dynamics, substrate utilization and product formation kinetics in various oxygen-limited conditions. We have also demonstrated the effect of switching carbon sources on the production of ethyl acetate under varying oxygen uptake rates. A phenotypic phase plane analysis described the energetic cost penalty of ethyl acetate and ethanol production on the specific growth rate of L. kluyveri. We generated the context specific models of L. kluyveri growing on uracil or ammonium salts as the sole nitrogen source. Differential flux calculated using flux variability analysis helped us in highlighting pathways like purine, histidine, riboflavin and pyrimidine metabolism associated with uracil degradation. The genome-scale metabolic construction of L. kluyveri will provide a better understanding of metabolism behind ethyl acetate production as well as uracil catabolism (pyrimidine degradation) pathway. iPN730 is an addition to genome-scale metabolic models of non-conventional yeasts that will facilitate system-wide omics analysis to understand fungal metabolic diversity.
Pharmacokinetic prediction of an antibody in mice based on an in vitro cell-based approach using target receptor-expressing cells
Authors: Noguchi Yuki , Ozeki Kazuhisa , Akita Hidetaka 
Published: October 2020

AbstractIn vivo pharmacokinetics (PK) studies using mice and monkeys are the main approaches for evaluating and predicting the PK of antibodies, and there is a strong demand for methods that do not require animal experiments. In this work, we focused on quantitatively predicting the nonlinear PK of an antibody based on cell-based assays. An anti-mouse Fc gamma receptor IIB antibody was used as a model antibody. To determine the PK parameters related to nonspecific elimination in vivo, the plasma concentration profile at 100 mg/kg, at which target-specific clearance is saturated, was analyzed by a 2-compartment model. To estimate the parameters related to target-specific elimination, the Michaelis–Menten constant (Km) and the maximum elimination rate (Vmax) were determined by an uptake assay using Chinese hamster ovary (CHO) cells expressing the target receptor. Finally, the integration of all of these parameters permitted the PK to be predicted at doses ranging from 1 to 100 mg/kg regardless of whether target-specific clearance was saturated or nonsaturated. The findings presented herein show that in vitro assays using target-expressing cells are useful tools for obtaining PK parameters and predicting PK profiles and, in some cases, eliminate the need for in vivo PK studies using experimental animals.
Integrated transcriptomic and metabolomic data reveal the flavonoid biosynthesis metabolic pathway in Perilla frutescens (L.) leaves
Authors: Jiang Tao , Guo Kunyuan , Liu Lingdi , Tian Wei , Xie Xiaoliang , Wen Saiqun , Wen Chunxiu 
Published: October 2020

AbstractPerilla frutescens (L.) is an important medicinal and edible plant in China with nutritional and medical uses. The extract from leaves of Perilla frutescens contains flavonoids and volatile oils, which are mainly used in traditional Chinese medicine. In this study, we analyzed the transcriptomic and metabolomic data of the leaves of two Perilla frutescens varieties: JIZI 1 and JIZI 2. A total of 9277 differentially expressed genes and 223 flavonoid metabolites were identified in these varieties. Chrysoeriol, apigenin, malvidin, cyanidin, kaempferol, and their derivatives were abundant in the leaves of Perilla frutescens, which were more than 70% of total flavonoid contents. A total of 77 unigenes encoding 15 enzymes were identified as candidate genes involved in flavonoid biosynthesis in the leaves of Perilla frutescens. High expression of the CHS gene enhances the accumulation of flavonoids in the leaves of Perilla frutescens. Our results provide valuable information on the flavonoid metabolites and candidate genes involved in the flavonoid biosynthesis pathways in the leaves of Perilla frutescens.