bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of a dried blood spot C-reactive protein method to identify disease flares in rheumatoid arthritis patients
Authors: D’Cruz Leon G. , McEleney Kevin G. , Cochrane Chris , Tan Kyle B. C. , Shukla Priyank , Gardiner Philip V. , Small Dawn , Zhang Shu-Dong , Gibson David S.
Published: December 2020

Rheumatoid arthritis (RA) is characterised by painful, stiff and swollen joints. RA features sporadic ‘flares’ or inflammatory episodes—mostly occurring outside clinics—where symptoms worsen and plasma C-reactive protein (CRP) becomes elevated. Poor control of inflammation results in higher rates of irreversible joint damage, increased disability, and poorer quality of life. Flares need to be accurately identified and managed. A method comparison study was designed to assess agreement between CRP values obtained by dried blood spot (DBS) versus conventional venepuncture sampling. The ability of a weekly DBS sampling and CRP test regime to detect flare outside the clinic was also assessed. Matched venepuncture and finger lancet DBS samples were collected from n = 100 RA patients with active disease at baseline and 6 weeks (NCT02809547). A subset of n = 30 RA patients submitted weekly DBS samples over the study period. Patient demographics, including self-reported flares were recorded. DBS sample CRP measurements were made by enzyme-linked immunosorbent assay, and venepuncture samples by a reference immunoturbometric assay. Data was compared between sample types by Bland–Altman and weighted Deming regression analyses. Flare detection sensitivity and specificity were compared between ‘minimal’ baseline and 6 week sample CRP data and the ‘continuous’ weekly CRP data. Baseline DBS ELISA assay CRP measures yielded a mean positive bias of 2.693 ± 8.640 (95% limits of agreement − 14.24 to 19.63%), when compared to reference assay data. Deming regression revealed good agreement between the DBS ELISA method and reference assay data, with baseline data slope of 0.978 and intercept -0.153. The specificity of ‘continuous’ area under the curve (AUC) CRP data (72.7%) to identify flares, was greater than ‘minimal’ AUC CRP data (54.5%). This study indicates reasonable agreement between DBS and the reference method, especially at low to mid-range CRP values. Importantly, longitudinal CRP measurement in RA patients helps to clearly identify flare and thus could assist in remote monitoring strategies and may facilitate timely therapeutic intervention.

Trial registration: The Remote Arthritis Disease Activity MonitoR (RADAR) study was registered on 22/06/2016 at ClinicalTrials.gov Identifier: NCT02809547. https://clinicaltrials.gov/ct2/show/NCT02809547.
Fermi surface and kink structures in $$\hbox {Sr}_{{4}}\hbox {Ru}_{{3}}\hbox {O}_{{10}}$$ revealed by synchrotron-based ARPES
Authors: Ngabonziza Prosper , Carleschi Emanuela , Zabolotnyy Volodymyr , Taleb-Ibrahimi Amina , Bertran François , Fittipaldi Rosalba , Granata Veronica , Cuoco Mario , Vecchione Antonio , Doyle Bryan Patrick
Published: December 2020

The low-energy electronic structure, including the Fermi surface topology, of the itinerant metamagnet $$\hbox {Sr}_{{4}}\hbox {Ru}_{{3}}\hbox {O}_{{10}}$$

Sr
4

Ru
3

O
10

is investigated for the first time by synchrotron-based angle-resolved photoemission. Well-defined quasiparticle band dispersions with matrix element dependencies on photon energy or photon polarization are presented. Four bands crossing the Fermi-level, giving rise to four Fermi surface sheets are resolved; and their complete topography, effective mass as well as their electron and hole character are determined. These data reveal the presence of kink structures in the near-Fermi-level band dispersion, with energies ranging from 30 to 69 meV. Together with previously reported Raman spectroscopy and lattice dynamic calculation studies, the data suggest that these kinks originate from strong electron–phonon coupling present in $$\hbox {Sr}_{{4}}\hbox {Ru}_{{3}}\hbox {O}_{{10}}$$

Sr
4

Ru
3

O
10

. Considering that the kink structures of $$\hbox {Sr}_{{4}}\hbox {Ru}_{{3}}\hbox {O}_{{10}}$$

Sr
4

Ru
3

O
10

are similar to those of the other three members of the Ruddlesden Popper structured ruthenates, the possible universality of strong coupling of electrons to oxygen-related phonons in $$\hbox {Sr}_{n+1}\hbox {Ru}_{{n}}\hbox {O}_{3n+1}$$

Sr

n
+
1

Ru
n

O

3
n
+
1

compounds is proposed.
Deletion of the nuclear receptor RORα in macrophages does not modify the development of obesity, insulin resistance and NASH
Authors: L’homme Laurent , Sermikli Benan Pelin , Molendi-Coste Olivier , Fleury Sébastien , Quemener Sandrine , Le Maître Mathilde , Joseph Marie-Laure , Pineau Laurent , Duhem Christian , Gross Barbara , Vallez Emmanuelle , Tailleux Anne , Staels Bart , Dombrowicz David
Published: December 2020

Retinoic acid receptor-related orphan receptor-alpha (RORα) is a transcription factor from the nuclear receptor family expressed by immune cells and involved in the development of obesity, insulin resistance (IR) and non-alcoholic steatohepatitis (NASH). It was recently reported that mice deficient for RORα in macrophages develop more severe NASH upon high fat diet (HFD) feeding due to altered Kupffer cell function. To better understand the role of RORα in obesity and IR, we independently generated a macrophage RORα-deficient mouse line. We report that RORα deletion in macrophages does not impact on HFD-induced obesity and IR. Surprisingly, we did not confirm an effect on NASH development upon HFD feeding nor in the more severe and obesity-independent choline-deficient, L-amino acid-defined diet model. Our results therefore show that RORα deletion in macrophages does not alter the development of obesity and IR and question its role in NASH.
Synergistic anti-biofilm effects of Brassicaceae plant extracts in combination with proteinase K against Escherichia coli O157:H7
Authors: Hu Wen Si , Min Nam Da , Kim Joo-Sung , Koo Ok Kyung
Published: December 2020

Bacteria can form biofilms, complex microbial communities protected from environmental stress, on food contact surfaces. Brassicaceae plant has been shown to contain bioactive compounds with antimicrobial activities. The objective of this study was to evaluate the synergistic effects of Brassicaceae species and proteinase K against E. coli O157:H7 biofilm. We determined the minimum biofilm inhibitory concentration, the fractional inhibitory concentration indexes, and the synergistic inhibitory effect of Raphanus sativus var. longipinnatus, R. sativus, and Brassica oleracea var. acephala extracts with proteinase K on E. coli O157:H7. The biofilm showed a 49% reduction with 2 mg/mL R. sativus. The combination of proteinase K 25 µg/mL significantly increased the effect of 2 mg/mL R. sativus var. longipinnatus and the combined treatment yielded up to 2.68 log reduction on stainless steel coupons. The results showed that the combination of R. sativus var. longipinnatus extract and proteinase K could serve as an anti-biofilm agent with synergistic effects for inhibiting E. coli O157:H7 biofilm on stainless steel surfaces.
Recent land use and management changes decouple the adaptation of livestock diversity to the environment
Authors: Velado-Alonso Elena , Morales-Castilla Ignacio , Gómez-Sal Antonio
Published: December 2020

Native livestock breeds, i.e. those autochthonous to a specific region, are locally adapted domesticated animals that conserve genetic resources, guaranty food security and provide agroecosystem services. Native breeds are largely threatened worldwide by agricultural intensification and rural areas abandonment processes related to recent changes in production schemes and planning. Yet, our gap of knowledge regarding livestock breed-environment relationships may prevent the design of successful conservation measures. In this work, we analyse the links between livestock diversity -i.e. richness of native breeds- and a selection of environmental factors that express at broad scales, with a temporal perspective. We compare native breeds distributional patterns before and after the agricultural intensification, in the context of land-use change in mainland Spain. Our results confirm the existence of strong associations between the distribution of native livestock breeds and environmental factors. These links, however, weaken for contemporary distributions. In fact, changes in breed distribution reflect a shift towards more productive environments. Finally, we found that the areas having higher breed richness are undergoing land abandonment processes. Succeeding in the conservation of threatened native breeds will require going beyond merely genetic and production-oriented views. Ecological and sociocultural perspectives should also be accounted for as global change processes are determinant for livestock agrobiodiversity.
A minimalist model to measure interactions between proteins and synaptic vesicles
Authors: Perego Eleonora , Reshetniak Sofiia , Lorenz Charlotta , Hoffmann Christian , Milovanović Dragomir , Rizzoli Silvio O. , Köster Sarah
Published: December 2020

Protein dynamics in the synaptic bouton are still not well understood, despite many quantitative studies of synaptic structure and function. The complexity of the synaptic environment makes investigations of presynaptic protein mobility challenging. Here, we present an in vitro approach to create a minimalist model of the synaptic environment by patterning synaptic vesicles (SVs) on glass coverslips. We employed fluorescence correlation spectroscopy (FCS) to measure the mobility of monomeric enhanced green fluorescent protein (mEGFP)-tagged proteins in the presence of the vesicle patterns. We observed that the mobility of all eleven measured proteins is strongly reduced in the presence of the SVs, suggesting that they all bind to the SVs. The mobility observed in these conditions is within the range of corresponding measurements in synapses of living cells. Overall, our simple, but robust, approach should enable numerous future studies of organelle-protein interactions in general.
Glioma and temozolomide induced alterations in gut microbiome
Authors: Patrizz Anthony , Dono Antonio , Zorofchian Soheil , Hines Gabriella , Takayasu Takeshi , Husein Nuruddin , Otani Yoshihiro , Arevalo Octavio , Choi H. Alex , Savarraj Jude , Tandon Nitin , Ganesh Bhanu P. , Kaur Balveen , McCullough Louise D. , Ballester Leomar Y. , Esquenazi Yoshua
Published: December 2020

The gut microbiome is fundamental in neurogenesis processes. Alterations in microbial constituents promote inflammation and immunosuppression. Recently, in immune-oncology, specific microbial taxa have been described to enhance the effects of therapeutic modalities. However, the effects of microbial dysbiosis on glioma are still unknown. The aim of this study was to explore the effects of glioma development and Temozolomide (TMZ) on fecal microbiome in mice and humans. C57BL/6 mice were implanted with GL261/Sham and given TMZ/Saline. Fecal samples were collected longitudinally and analyzed by 16S rRNA sequencing. Fecal samples were collected from healthy controls as well as glioma patients at diagnosis, before and after chemoradiation. Compared to healthy controls, mice and glioma patients demonstrated significant differences in beta diversity, Firmicutes/Bacteroides (F/B) ratio, and increase of Verrucomicrobia phylum and Akkermansia genus. These changes were not observed following TMZ in mice. TMZ treatment in the non-tumor bearing mouse-model diminished the F/B ratio, increase Muribaculaceae family and decrease Ruminococcaceae family. Nevertheless, there were no changes in Verrucomicrobia/Akkermansia. Glioma development leads to gut dysbiosis in a mouse-model, which was not observed in the setting of TMZ. These findings seem translational to humans and warrant further study.
A residual dense network assisted sparse view reconstruction for breast computed tomography
Authors: Fu Zhiyang , Tseng Hsin Wu , Vedantham Srinivasan , Karellas Andrew , Bilgin Ali
Published: December 2020

To develop and investigate a deep learning approach that uses sparse-view acquisition in dedicated breast computed tomography for radiation dose reduction, we propose a framework that combines 3D sparse-view cone-beam acquisition with a multi-slice residual dense network (MS-RDN) reconstruction. Projection datasets (300 views, full-scan) from 34 women were reconstructed using the FDK algorithm and served as reference. Sparse-view (100 views, full-scan) projection data were reconstructed using the FDK algorithm. The proposed MS-RDN uses the sparse-view and reference FDK reconstructions as input and label, respectively. Our MS-RDN evaluated with respect to fully sampled FDK reference yields superior performance, quantitatively and visually, compared to conventional compressed sensing methods and state-of-the-art deep learning based methods. The proposed deep learning driven framework can potentially enable low dose breast CT imaging.
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

Sphingopyxis 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

We 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

Fluoroindate 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

Aberrant 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

Porphyromonas 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

Multiple 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

We 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

The 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

Adipose 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

No 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

Colorectal 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

The 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

Polymorphisms 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

We 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

The 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.
Advanced superhard composite materials with extremely improved mechanical strength by interfacial segregation of dilute dopants
Authors: Nishi Tomohiro , Matsunaga Katsuyuki , Mitsuoka Takeshi , Okimura Yasuyuki , Katsu Yusuke
Published: December 2020

Control of heterointerfaces in advanced composite materials is of scientific and industrial importance, because their interfacial structures and properties often determine overall performance and reliability of the materials. Here distinct improvement of mechanical properties of alumina-matrix tungsten-carbide composites, which is expected for cutting-tool application for aerospace industries, is achieved via interfacial atomic segregation. It is found that only a small amount of Zr addition is unexpectedly effective to significantly increase their mechanical properties, and especially their bending strength reaches values far beyond those of conventional superhard composite materials. Atomic-resolution STEM observations show that doped Zr atoms are preferentially located only at interfaces between Al2O3 and WC grains, forming atomic segregation layers. DFT calculations indicate favorable thermodynamic stability of the interfacial Zr segregation due to structural transition at the interface. Moreover, theoretical works of separation demonstrate remarkable increase in interfacial strength through the interfacial structural transition, which strongly supports reinforcement of the interfaces by single-layer Zr segregation.
Biomimicking properties of cellulose nanofiber under ethanol/water mixture
Authors: Halim Abdul , Lin Kuan-Hsuan , Enomae Toshiharu
Published: December 2020

The two types of cellulose nanofiber (CNF) surface characteristics were evaluated by oil contact angle under ethanol–water solution at several concentrations as well as in air. Wood pulp-based 2,2,6,6-tetramethylpiperidine-1-oxylradical (TEMPO)-oxidized cellulose nanofiber (TOCNF) sheets and bamboo-derived mechanical counter collision cellulose nanofiber (ACC-CNF) sheets were fabricated by casting followed by drying. The CNF shows underwater superoleophobic mimicking fish skin properties and slippery surface mimicking Nepenthes pitcher. The underwater superoleophobic properties of CNF was evaluated theoretically and experimentally. The theoretical calculation and experimental results of contact angle showed a large deviation. The roughness, zeta potential, and water absorption at different concentrations were key factors that determine the deviation. Antifouling investigation revealed that CNF was a good candidate for antifouling material.
Strong electric field tuning of magnetism in self-biased multiferroic structures
Authors: Li Xu , Lynch Christopher S.
Published: December 2020

A new type of multiferroic heterostructure has been proposed in this work with strong electric field tuning of magnetism. It is composed of a self-biased magnetic layered structure with perpendicular magnetic anisotropy (PMA) and one piezoelectric substrate. Two configurations were investigated by a modeling approach, Ni/Ni/Ni/PMN-PT with Cu as spacer and Terfenol-D/CoFeB/Ni/PMN-PT. Magnetic multilayers at their resonance exhibit multiple absorption peaks from acoustic and optical modes of spin interaction between adjacent magnetic layers. A piezoelectric substrate transfers electric field induced strain to adjacent magnetic layer and thus shifts resonance frequencies of the multiferroic structure by tuning magnetic effective fields through magnetoelastic coupling. It has been demonstrated computationally that the resonance frequencies for the simulated structures could be up to 76 GHz under zero magnetic bias field. A larger tunability (> 100%) is achieved with applied electric field to the PMN-PT [011] substrate. Resonance mode selectivity is present in the configuration Terfenol-D/CoFeB/Ni/PMN-PT wherein one desired mode exhibits a much higher tunability compared to other modes. This enables the total mode number to be tuned by merging or diverging different modes under E-field.
NADPH diaphorase detects S-nitrosylated proteins in aldehyde-treated biological tissues
Authors: Seckler James M. , Shen Jinshan , Lewis Tristan H. J. , Abdulameer Mohammed A. , Zaman Khalequz , Palmer Lisa A. , Bates James N. , Jenkins Michael W. , Lewis Stephen J.
Published: December 2020

NADPH diaphorase is used as a histochemical marker of nitric oxide synthase (NOS) in aldehyde-treated tissues. It is thought that the catalytic activity of NOS promotes NADPH-dependent reduction of nitro-blue tetrazolium (NBT) to diformazan. However, it has been argued that a proteinaceous factor other than NOS is responsible for producing diformazan in aldehyde-treated tissues. We propose this is a NO-containing factor such as an S-nitrosothiol and/or a dinitrosyl-iron (II) cysteine complex or nitrosated proteins including NOS. We now report that (1) S-nitrosothiols covalently modify both NBT and TNBT, but only change the reduction potential of NBT after modification, (2) addition of S-nitrosothiols or β- or α-NADPH to solutions of NBT did not elicit diformazan, (3) addition of S-nitrosothiols to solutions of NBT plus β- or α-NADPH elicited rapid formation of diformazan in the absence or presence of paraformaldehyde, (4) addition of S-nitrosothiols to solutions of NBT plus β- or α-NADP did not produce diformazan, (5) S-nitrosothiols did not promote NADPH-dependent reduction of tetra-nitro-blue tetrazolium (TNBT) in which all four phenolic rings are nitrated, (6) cytoplasmic vesicles in vascular endothelial cells known to stain for NADPH diaphorase were rich in S-nitrosothiols, and (7) procedures that accelerate decomposition of S-nitrosothiols, markedly reduced NADPH diaphorase staining in tissue sections subsequently subjected to paraformaldehyde fixation. Our results suggest that NADPH diaphorase in aldehyde-fixed tissues is not enzymatic but is due to the presence of NO-containing factors (free SNOs or nitrosated proteins such as NOS), which promote NADPH-dependent reduction of NBT to diformazan.
Epithelial processed Mycobacterium avium subsp. paratuberculosis induced prolonged Th17 response and suppression of phagocytic maturation in bovine peripheral blood mononuclear cells
Authors: Park Hong-Tae , Park Hyun-Eui , Shim Soojin , Kim Suji , Shin Min-Kyoung , Yoo Han Sang
Published: December 2020

Johne’s disease (JD) caused byMycobacterium aviumsubsp.paratuberculosis(MAP) is a chronic, wasting infectious disease in ruminants that causes enormous economic losses to the dairy and beef cattle industries. Understanding the mechanism of persistency of MAP is key to produce novel ideas for the development of new diagnostic methods or prevention techniques. We sought interactions between the host and MAP using epithelial passage model, which mimic initial stage of infection. From the transcriptomic analysis of bovine immune cells (PBMCs), it was suggested that infection through the epithelial cells elicited prolonged Th17-derived immune response, as indicated by upregulation of IL-17A, IL-17F and RORC until 120 h p.i., compared to directly infected PBMCs. Global downregulation of gene expression was observed after 72 h p.i., especially for genes encoding cell surface receptors of phagocytic cells, such as Toll-like receptors and MHC class II molecules. In addition, the cholesterol efflux transporters ABCA1, ABCG1, and APOE, which are regulated by the LXR/RXR pathway, were downregulated. In summary, it would be suggested that the host initiate immune response to activate Th17-derived cytokines, and MAP survives persistently by altering the host adaptive immune response by suppressing surface receptors and manipulating lipid metabolism in phagocytic cells.
Predictors of intensive care unit admission in patients with hematologic malignancy
Authors: Vijenthira Abi , Chiu Nicholas , Jacobson Daniel , Freedman Zoey , Cheung Matthew C. , Goddard Shannon , Fowler Robert , Buckstein Rena
Published: December 2020

Limited data exist on predictors of intensive care unit (ICU) admission in patients with hematologic malignancy. The objective of this study was to identify predictors of ICU admission in hospitalized patients with hematologic malignancies. A retrospective cohort study was conducted on 820 consecutive admissions of patients with a malignant hematology diagnosis at our institution between March 2009 and December 2015. Backward stepwise selection procedure was conducted for multivariable logistic regression analyses. 820 patients were included, of whom 179 (22%) were admitted to the ICU. Types of hematologic cancers included 71% (N = 578) lymphoid cancer, 18% (N = 151) myeloid cancer, and 10% (N = 80) plasma cell neoplasms. 14% (N = 111) of patients had acute leukemia. Six predictors of admission to ICU were found in multivariable analysis, including disease-related (acute leukemia, curative intent chemotherapy), laboratory-related (platelet count < 50 × 109/L, albumin below normal, LDH above normal at time of admission), and physician-related factors (having advanced directives discussion) (p < 0.0001). A significant proportion of patients with hematologic malignancies admitted to hospital are admitted to ICU. Utilizing the identified predictors of ICU admission may help guide timely informed goals of care discussions with patients before clinical deterioration occurs.
Poly(ADP-ribose) polymerase 1 in genome-wide expression control in Drosophila
Authors: Bordet Guillaume , Lodhi Niraj , Guo Danping , Kossenkov Andrew , Tulin Alexei V.
Published: December 2020

Poly(ADP-ribose) polymerase 1 (PARP-1) is a nuclear enzyme involved in DNA repair and transcription regulation, among other processes. Malignant transformations, tumor progression, the onset of some neuropathies and other disorders have been linked to misregulation of PARP-1 activity. Despite intensive studies during the last few decades, the role of PARP-1 in transcription regulation is still not well understood. In this study, a transcriptomic analysis in Drosophila melanogaster third instar larvae was carried out. A total of 602 genes were identified, showing large-scale changes in their expression levels in the absence of PARP-1 in vivo. Among these genes, several functional gene groups were present, including transcription factors and cytochrome family members. The transcription levels of genes from the same functional group were affected by the absence of PARP-1 in a similar manner. In the absence of PARP-1, all misregulated genes coding for transcription factors were downregulated, whereas all genes coding for members of the cytochrome P450 family were upregulated. The cytochrome P450 proteins contain heme as a cofactor and are involved in oxidoreduction. Significant changes were also observed in the expression of several mobile elements in the absence of PARP-1, suggesting that PARP-1 may be involved in regulating the expression of mobile elements.
Significant increase in the secretion of extracellular vesicles and antibiotics resistance from methicillin-resistant Staphylococcus aureus induced by ampicillin stress
Authors: Kim Si Won , Seo Jong-Su , Park Seong Bin , Lee Ae Rin , Lee Jung Seok , Jung Jae Wook , Chun Jin Hong , Lazarte Jassy Mary S. , Kim Jaesung , Kim Jong-Hwan , Song Jong-Wook , Franco Chris , Zhang Wei , Ha Min Woo , Paek Seung-Mann , Jung Myunghwan , Jung Tae Sung
Published: December 2020

Extracellular vesicles (EVs) containing specific cargo molecules from the cell of origin are naturally secreted from bacteria. EVs play significant roles in protecting the bacterium, which can contribute to their survival in the presence of antibiotics. Herein, we isolated EVs from methicillin-resistant Staphylococcus aureus (MRSA) in an environment with or without stressor by adding ampicillin at a lower concentration than the minimum inhibitory concentration (MIC). We investigated whether EVs from MRSA under stress condition or normal condition could defend susceptible bacteria in the presence of several β-lactam antibiotics, and directly degrade the antibiotics. A comparative proteomic approach was carried out in both types of EVs to investigate β-lactam resistant determinants. The secretion of EVs from MRSA under antibiotic stressed conditions was increased by 22.4-fold compared with that of EVs without stress. Proteins related to the degradation of β-lactam antibiotics were abundant in EVs released from the stressed condition. Taken together, the present data reveal that EVs from MRSA play a crucial role in the survival of β-lactam susceptible bacteria by acting as the first line of defense against β-lactam antibiotics, and antibiotic stress leads to release EVs with high defense activity.