bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of two fnr genes and characterisation of their role in the anaerobic switch in Sphingopyxis granuli strain TFA
Authors: González-Flores Yolanda Elisabet , de Dios Rubén , Reyes-Ramírez Francisca , Santero Eduardo 
Published: December 2020

AbstractSphingopyxis granuli strain TFA is able to grow on the organic solvent tetralin as the only carbon and energy source. The aerobic catabolic pathway for tetralin, the genes involved and their regulation have been fully characterised. Unlike most of the bacteria belonging to the sphingomonads group, this strain is able to grow in anoxic conditions by respiring nitrate, though not nitrite, as the alternative electron acceptor. In this work, two fnr-like genes, fnrN and fixK, have been identified in strain TFA. Both genes are functional in E. coli and Sphingopyxis granuli although fixK, whose expression is apparently activated by FnrN, seems to be much less effective than fnrN in supporting anaerobic growth. Global transcriptomic analysis of a ΔfnrN ΔfixK double mutant and identification of Fnr boxes have defined a minimal Fnr regulon in this bacterium. However, expression of a substantial number of anaerobically regulated genes was not affected in the double mutant. Additional regulators such regBA, whose expression is also activated by Fnr, might also be involved in the anaerobic response. Anaerobically induced stress response genes were not regulated by Fnr but apparently induced by stress conditions inherent to anaerobic growth, probably due to accumulation of nitrite and nitric oxide.
Topological image modification for object detection and topological image processing of skin lesions
Authors: Vandaele Robin , Nervo Guillaume Adrien , Gevaert Olivier 
Published: December 2020

AbstractWe propose a new method based on Topological Data Analysis (TDA) consisting of Topological Image Modification (TIM) and Topological Image Processing (TIP) for object detection. Through this newly introduced method, we artificially destruct irrelevant objects, and construct new objects with known topological properties in irrelevant regions of an image. This ensures that we are able to identify the important objects in relevant regions of the image. We do this by means of persistent homology, which allows us to simultaneously select appropriate thresholds, as well as the objects corresponding to these thresholds, and separate them from the noisy background of an image. This leads to a new image, processed in a completely unsupervised manner, from which one may more efficiently extract important objects. We demonstrate the usefulness of this proposed method for topological image processing through a case-study of unsupervised segmentation of the ISIC 2018 skin lesion images. Code for this project is available on https://bitbucket.org/ghentdatascience/topimgprocess.
Fluoroindate glasses co-doped with Pr3+/Er3+ for near-infrared luminescence applications
Authors: Pisarski Wojciech A. , Pisarska Joanna , Kuwik Marta , Kochanowicz Marcin , Żmojda Jacek , Miluski Piotr , Baranowska Agata , Dorosz Jan , Leśniak Magdalena , Dorosz Dominik 
Published: December 2020

AbstractFluoroindate glasses co-doped with Pr3+/Er3+ ions were synthesized and their near-infrared luminescence properties have been examined under selective excitation wavelengths. For the Pr3+/Er3+ co-doped glass samples several radiative and nonradiative relaxation channels and their mechanisms are proposed under direct excitation of Pr3+ and/or Er3+. The energy transfer processes between Pr3+ and Er3+ ions in fluoroindate glasses were identified. In particular, broadband near-infrared luminescence (FWHM = 278 nm) associated to the 1G4 → 3H5 (Pr3+), 1D2 → 1G4 (Pr3+) and 4I13/2 → 4I15/2 (Er3+) transitions of rare earth ions in fluoroindate glass is successfully observed under direct excitation at 483 nm. Near-infrared luminescence spectra and their decays for glass samples co-doped with Pr3+/Er3+ are compared to the experimental results obtained for fluoroindate glasses singly doped with rare earth ions.
CCDC66 frameshift variant associated with a new form of early-onset progressive retinal atrophy in Portuguese Water Dogs
Authors: Murgiano Leonardo , Becker Doreen , Spector Courtney , Carlin Kendall , Santana Evelyn , Niggel Jessica K. , Jagannathan Vidhya , Leeb Tosso , Pearce-Kelling Sue , Aguirre Gustavo D. , Miyadera Keiko 
Published: December 2020

AbstractAberrant photoreceptor function or morphogenesis leads to blinding retinal degenerative diseases, the majority of which have a genetic aetiology. A variant in PRCD previously identified in Portuguese Water Dogs (PWDs) underlies prcd (progressive rod-cone degeneration), an autosomal recessive progressive retinal atrophy (PRA) with a late onset at 3–6 years of age or older. Herein, we have identified a new form of early-onset PRA (EOPRA) in the same breed. Pedigree analysis suggested an autosomal recessive inheritance. Four PWD full-siblings affected with EOPRA diagnosed at 2–3 years of age were genotyped (173,661 SNPs) along with 2 unaffected siblings, 2 unaffected parents, and 15 unrelated control PWDs. GWAS, linkage analysis and homozygosity mapping defined a 26-Mb candidate region in canine chromosome 20. Whole-genome sequencing in one affected dog and its obligatory carrier parents identified a 1 bp insertion (CFA20:g.33,717,704_33,717,705insT (CanFam3.1); c.2262_c.2263insA) in CCDC66 predicted to cause a frameshift and truncation (p.Val747SerfsTer8). Screening of an extended PWD population confirmed perfect co-segregation of this genetic variant with the disease. Western blot analysis of COS-1 cells transfected with recombinant mutant CCDC66 expression constructs showed the mutant transcript translated into a truncated protein. Furthermore, in vitro studies suggest that the mutant CCDC66 is mislocalized to the nucleus relative to wild type CCDC66. CCDC66 variants have been associated with inherited retinal degenerations (RDs) including canine and murine ciliopathies. As genetic variants affecting the primary cilium can cause ciliopathies in which RD may be either the sole clinical manifestation or part of a syndrome, our findings further support a role for CCDC66 in retinal function and viability, potentially through its ciliary function.
PorA, a conserved C-terminal domain-containing protein, impacts the PorXY-SigP signaling of the type IX secretion system
Authors: Yukitake Hideharu , Shoji Mikio , Sato Keiko , Handa Yusuke , Naito Mariko , Imada Katsumi , Nakayama Koji 
Published: December 2020

AbstractPorphyromonas gingivalis, a periodontal pathogen, translocates many virulence factors including the cysteine proteases referred to as gingipains to the cell surface via the type IX secretion system (T9SS). Expression of the T9SS component proteins is regulated by the tandem signaling of the PorXY two-component system and the ECF sigma factor SigP. However, the details of this regulatory pathway are still unknown. We found that one of the T9SS conserved C-terminal domain-containing proteins, PGN_0123, which we have designated PorA, is involved in regulating expression of genes encoding T9SS structural proteins and that PorA can be translocated onto the cell surface without the T9SS translocation machinery. X-ray crystallography revealed that PorA has a domain similar to the mannose-binding domain of Escherichia coli FimH, the tip protein of Type 1 pilus. Mutations in the cytoplasmic domain of the sensor kinase PorY conferred phenotypic recovery on the ΔporA mutant. The SigP sigma factor, which is activated by the PorXY two-component system, markedly decreased in the ΔporA mutant. These results strongly support a potential role for PorA in relaying a signal from the cell surface to the PorXY-SigP signaling pathway.
Stability enhancement in a mAb and Fab coformulation
Authors: Zhang Hongyu , Dalby Paul A. 
Published: December 2020

AbstractMultiple therapeutic proteins can be combined into a single dose for synergistic targeting to multiple sites of action. Such proteins would be mixed in dose-specific ratios to provide the correct potency for each component, and yet the formulations must also preserve their activity and keep degradation to a minimum. Mixing different therapeutic proteins could adversely affect their stability, and reduce the shelf life of each individual component, making the control of such products very challenging. In this study, a therapeutic monoclonal antibody and a related Fab fragment, were combined to investigate the impact of coformulation on their degradation kinetics. Under mildly destabilizing conditions, these proteins were found to protect each other from degradation. The protective effect appeared to originate from the interaction of Fab and IgG1 in small soluble oligomers, or through the rapid coalescence of pre-existing monomeric IgG1 nuclei into a dead-end aggregate, rather than through macromolecular crowding or diffusion-limitations.
Infectious RNA vaccine protects mice against chikungunya virus infection
Authors: Szurgot Inga , Ljungberg Karl , Kümmerer Beate M. , Liljeström Peter 
Published: December 2020

AbstractWe describe a novel vaccine platform that can generate protective immunity to chikungunya virus (CHIKV) in C57BL/6J mice after a single immunization by employing an infectious RNA (iRNA), which upon introduction into a host cell launches an infectious attenuated virus. We and others have previously reported that an engineered deletion of 183 nucleotides in the nsP3 gene attenuates chikungunya virus (CHIKV) and reduces in vivo viral replication and viremia after challenge in mice, macaques and man. Here, we demonstrated that in vitro transfection of iRNA carrying the nsP3 deletion generated infectious viruses, and after intramuscular injection, the iRNA induced robust antibody responses in mice. The iRNA was superior at eliciting binding and neutralizing antibody responses as compared to a DNA vaccine encoding the same RNA (iDNA) or a non-propagating RNA replicon (RREP) lacking the capsid encoding gene. Subsequent challenge with a high dose of CHIKV demonstrated that the antibody responses induced by this vaccine candidate protected animals from viremia. The iRNA approach constitutes a novel vaccine platform with the potential to impact the spread of CHIKV. Moreover, we believe that this approach is likely applicable also to other positive-strand viruses.
Subcritical dimethyl ether extraction as a simple method to extract nutraceuticals from byproducts from rice bran oil manufacture
Authors: Wongwaiwech Donporn , Weerawatanakorn Monthana , Boonnoun Panatpong 
Published: December 2020

AbstractThe byproducts of rice bran oil processes are a good source of fat-soluble nutraceuticals, including γ-oryzanol, phytosterol, and policosanols. This study aimed to investigate the effects of green technology with low pressure as the subcritical fluid extraction with dimethyl ether (SUBFDME) on the amount of γ-oryzanol, phytosterol, and policosanol extracted from the byproducts and to increase the purity of policosanols. The SUBFDME extraction apparatus was operated under pressures below 1 MPa. Compared to the chemical extraction method, SUBFDME gave the highest content of γ-oryzanol at 924.51 mg/100 g from defatted rice bran, followed by 829.88 mg/100 g from the filter cake, while the highest phytosterol content was 367.54 mg/100 g. Transesterification gave the highest extraction yield of 43.71% with the highest policosanol content (30,787 mg/100 g), and the SUBFDME method increased the policosanol level from transesterified rice bran wax to 84,913.14 mg/100 g. The results indicate that the SUBFDME method is a promising tool to extract γ-oryzanol and phytosterol and a simple and effective technique to increase the purity of policosanol. The study presented a novel technique for the potential use of SUBSFDME as an alternative low-pressure and low-temperature technique to extract γ-oryzanol and phytosterol. The combination of transesterification and the SUBFDME technique is a potential simple two-step method to extract and purify policosanol, which is beneficial for the manufacture of dietary supplements, functional foods and pharmaceutical products.
Generation of immune cell containing adipose organoids for in vitro analysis of immune metabolism
Authors: Taylor Jacqueline , Sellin Julia , Kuerschner Lars , Krähl Lennart , Majlesain Yasmin , Förster Irmgard , Thiele Christoph , Weighardt Heike , Weber Elvira 
Published: December 2020

AbstractAdipose tissue is an organized endocrine organ with important metabolic and immunological functions and immune cell-adipocyte crosstalk is known to drive various disease pathologies. Suitable 3D adipose tissue organoid models often lack resident immune cell populations and therefore require the addition of immune cells isolated from other organs. We have created the first 3D adipose tissue organoid model which could contain and maintain resident immune cell populations of the stromal vascular fraction (SVF) and proved to be effective in studying adipose tissue biology in a convenient manner. Macrophage and mast cell populations were successfully confirmed within our organoid model and were maintained in culture without the addition of growth factors. We demonstrated the suitability of our model for monitoring the lipidome during adipocyte differentiation in vitro and confirmed that this model reflects the physiological lipidome better than standard 2D cultures. In addition, we applied mass spectrometry-based lipidomics to track lipidomic changes in the lipidome upon dietary and immunomodulatory interventions. We conclude that this model represents a valuable tool for immune-metabolic research.
Silk fibroin vascular graft: a promising tissue-engineered scaffold material for abdominal venous system replacement
Authors: Kiritani Sho , Kaneko Junichi , Ito Daisuke , Morito Masaaki , Ishizawa Takeaki , Akamatsu Nobuhisa , Tanaka Mariko , Iida Takuya , Tanaka Takashi , Tanaka Ryo , Asakura Tetsuo , Arita Junichi , Hasegawa Kiyoshi 
Published: December 2020

AbstractNo alternative tissue-engineered vascular grafts for the abdominal venous system are reported. The present study focused on the development of new tissue-engineered vascular graft using a silk-based scaffold material for abdominal venous system replacement. A rat vein, the inferior vena cava, was replaced by a silk fibroin (SF, a biocompatible natural insoluble protein present in silk thread), tissue-engineered vascular graft (10 mm long, 3 mm diameter, n = 19, SF group). The 1 and 4 -week patency rates and histologic reactions were compared with those of expanded polytetrafluoroethylene vascular grafts (n = 10, ePTFE group). The patency rate at 1 and 4 weeks after replacement in the SF group was 100.0% and 94.7%, and that in the ePTFE group was 100.0% and 80.0%, respectively. There was no significant difference between groups (p = 0.36). Unlike the ePTFE graft, CD31-positive endothelial cells covered the whole luminal surface of the SF vascular graft at 4 weeks, indicating better endothelialization. SF vascular grafts may be a promising tissue-engineered scaffold material for abdominal venous system replacement.
Urinary charged metabolite profiling of colorectal cancer using capillary electrophoresis-mass spectrometry
Authors: Udo Ryutaro , Katsumata Kenji , Kuwabara Hiroshi , Enomoto Masanobu , Ishizaki Tetsuo , Sunamura Makoto , Nagakawa Yuichi , Soya Ryoko , Sugimoto Masahiro , Tsuchida Akihiko 
Published: December 2020

AbstractColorectal cancer (CRC) has increasing global prevalence and poor prognostic outcomes, and the development of low- or less invasive screening tests is urgently required. Urine is an ideal biofluid that can be collected non-invasively and contains various metabolite biomarkers. To understand the metabolomic profiles of different stages of CRC, we conducted metabolomic profiling of urinary samples. Capillary electrophoresis-time-of-flight mass spectrometry was used to quantify hydrophilic metabolites in 247 subjects with stage 0 to IV CRC or polyps, and healthy controls. The 154 identified and quantified metabolites included metabolites of glycolysis, TCA cycle, amino acids, urea cycle, and polyamine pathways. The concentrations of these metabolites gradually increased with the stage, and samples of CRC stage IV especially showed a large difference compared to other stages. Polyps and CRC also showed different concentration patterns. We also assessed the differentiation ability of these metabolites. A multiple logistic regression model using three metabolites was developed with a randomly designated training dataset and validated using the remaining data to differentiate CRC and polys from healthy controls based on a panel of urinary metabolites. These data highlight the changes in metabolites from early to late stage of CRC and also the differences between CRC and polyps.
Threshold-based evolutionary magnitude estimation for an earthquake early warning system in the Sichuan–Yunnan region, China
Authors: Wang Yuan , Li Shanyou , Song Jindong 
Published: December 2020

AbstractThe Sichuan–Yunnan region is one of the most seismically vulnerable areas in China. Accordingly, an earthquake early warning (EEW) system for the region is essential to reduce future earthquake hazards. This research analyses the utility of two early warning parameters (τc and Pd) for magnitude estimation using 273 events that occurred in the Sichuan–Yunnan region during 2007–2015. We find that τc can more reliably predict high-magnitude events during a short P-wave time window (PTW) but produces greater uncertainty in the low-magnitude range, whereas Pd is highly correlated with the event magnitude depending on the selection of an appropriate PTW. Here, we propose a threshold-based evolutionary magnitude estimation method based on a specific combination of τc and Pd that both offers more robust advance magnitude estimates for large earthquakes and ensures the estimation accuracy for low-magnitude events. The advantages of the proposed approach are validated using data from 2016–2017 and the Ms 8.0 Wenchuan earthquake in an offline simulation. The proposed concept provides a useful basis for the future implementation of an EEW system in the Sichuan–Yunnan region.
Polymorphisms in the BER and NER pathways and their influence on survival and toxicity in never-smokers with lung cancer
Authors: Casal-Mouriño Ana , Ruano-Ravina Alberto , Torres-Durán María , Parente-Lamelas Isaura , Provencio-Pulla Mariano , Castro-Añón Olalla , Vidal-García Iria , Abal-Arca José , Piñeiro-Lamas María , Fernández-Villar Alberto , Valdés-Cuadrado Luis , Barros-Dios Juan Miguel , Pérez-Ríos Mónica 
Published: December 2020

AbstractPolymorphisms in DNA repair pathways may play a relevant role in lung cancer survival in never-smokers. Furthermore, they could be implicated in the response to chemotherapy and toxicity of platinum agents. The aim of this study was to evaluate the influence of various genetic polymorphisms in the BER and NER DNA repair pathways on survival and toxicity in never-smoker LC patients. The study included never-smokers LC cases diagnosed from 2011 through 2019, belonging to the Lung Cancer Research In Never Smokers study. A total of 356 never-smokers cases participated (79% women; 83% adenocarcinoma and 65% stage IV). Survival at 3 and 5 years from diagnosis was not associated with genetic polymorphisms, except in the subgroup of patients who received radiotherapy or chemo-radiotherapy, and presented with ERCC1 rs3212986 polymorphism. There was greater toxicity in those presenting OGG1 rs1052133 (CG) and ERCC1 rs11615 polymorphisms among patients treated with radiotherapy or chemo-radiotherapy, respectively. In general, polymorphisms in the BER and NER pathways do not seem to play a relevant role in survival and response to treatment among never-smoker LC patients.
Non-epigenetic induction of HEXIM1 by DNMT1 inhibitors and functional relevance
Authors: Sharma Vikas , Montano Monica M. 
Published: December 2020

AbstractWe have been studying the role of Hexamethylene bisacetamide (HMBA) Induced Protein 1 (HEXIM1) as a tumor suppressor whose expression is decreased in breast and prostate cancer. The anti-cancer actions of HEXIM1 in melanomas and AML have been reported by other groups. Previous studies have shown that 5-Aza-2′deoxycytidine (5-AzadC), a DNMT1 inhibitor, induces re-expression of tumor suppressor genes by removing/erasing methylation marks from their promoters. Our studies highlighted another mechanism wherein 5-AzadC induced DNA damage, which then resulted in enhanced occupancy of NF-ĸB, P-TEFb, and serine 2 phosphorylated RNA Polymerase II on the HEXIM1 gene. As a consequence, 5-AzadC induced HEXIM1 expression in prostate cancer cell lines and triple negative breast cancers. 5-AzadC-induced DNA damage enhanced P-TEFb occupancy via a mechanism that involved activation of ATR and ATM and induction of NF-ĸB recruitment to the HEXIM1 promoter. Downregulation of NF-ĸB attenuated 5-AzadC-induced HEXIM1 expression in prostate and breast cancer cells. The functional relevance of 5-AzadC-induced HEXIM1 expression is revealed by studies showing the HEXIM1 is required for the induction of apoptosis. Collectively, our findings support a non-epigenetic mechanism for 5-AzadC-induced re-expression of HEXIM1 protein, and may contribute to the clinical efficacy of 5-AzadC.
Macular retinal thickness differs markedly in age-related macular degeneration driven by risk polymorphisms on chromosomes 1 and 10
Authors: Zouache Moussa A. , Bennion Alex , Hageman Jill L. , Pappas Christian , Richards Burt T. , Hageman Gregory S. 
Published: December 2020

AbstractThe two most common genetic contributors to age-related macular degeneration (AMD), a leading cause of irreversible vision loss worldwide, are variants associated with CFH-CFHR5 on chromosome 1 (Chr1) and ARMS2/HTRA1 on chromosome 10 (Chr10). We sought to determine if risk and protective variants associated with these two loci drive differences in macular retinal thickness prior and subsequent to the onset of clinically observable signs of AMD. We considered 299 individuals (547 eyes) homozygous for risk variants or haplotypes on Chr1 or Chr10 exclusively (Chr1-risk and Chr10-risk, respectively) or homozygous for a neutral haplotype (Chr1-neu), for the protective I62 tagged haplotype (Chr1-prot-I62) or for the protection conferring CFHR3/1 deletion haplotype (Chr1-prot-del) on Chr1 without any risk alleles on Chr10. Among eyes with no clinically observable signs of AMD, the deletion of CFHR3/1, which is strongly protective against this disease, is associated with significantly thicker retinas in the perifovea. When controlling for age, Chr10-risk eyes with early or intermediate AMD have thinner retinas as compared to eyes from the Chr1-risk group with similar disease severity. Our analysis indicates that this difference likely results from distinct biological and disease initiation and progression events associated with Chr1- and Chr10-directed AMD.