bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibitory activity of FOXP3+ regulatory T cells reveals high specificity for displaying immune tolerance in remission state rheumatoid arthritis
Authors: Kanjana Korawit , Chevaisrakul Parawee , Matangkasombut Ponpan , Paisooksantivatana Karan , Lumjiaktase Putthapoom 
Published: November 2020

AbstractImmune regulation status may indicate immunological remission in rheumatoid arthritis (RA). This cross-sectional study aimed to determine the Regulatory T cell (Treg) properties, together with 14 plasma cytokines levels between active RA and clinical remission patients. Peripheral blood (PB) Foxp3+ Treg was collected from RA patients for determination of Treg inhibitory activity using a co-culture system. Other PB T cell types and plasma cytokines were determined by flow-cytometry. The Treg results were analyzed according to the disease activity score-28 (DAS28). Then sensitivity and specificity were calculated for the indication of the remission status. The number and inhibitory activity of Treg are higher in the clinical remission as compared to the active RA (p value < 0.0001). Also, Treg: CD4+CD25+CD127+ cell ratio demonstrates the similar result (p value < 0.05). Treg inhibitory activity is inversely correlated with the DAS28. Specificity and positive likelihood ratio of inhibitory activity for indicating remission status are 92.31% (95% CI 63.97–99.81) and 11.14 (95% CI 1.67–74.14), respectively. Treg inhibitory activity is a promising prognostic marker and probably represents the immunological remission status in RA.
European landrace diversity for common bean biofortification: a genome-wide association study
Authors: Caproni Leonardo , Raggi Lorenzo , Talsma Elise F. , Wenzl Peter , Negri Valeria 
Published: November 2020

AbstractMineral deficiencies represent a global challenge that needs to be urgently addressed. An adequate intake of iron and zinc results in a balanced diet that reduces chances of impairment of many metabolic processes that can lead to clinical consequences. In plants, bioavailability of such nutrients is reduced by presence of compounds such as phytic acid, that can chelate minerals and reduce their absorption. Biofortification of common bean (Phaseolus vulgaris L.) represents an important strategy to reduce mineral deficiencies, especially in areas of the world where this crop plays a key role in the diet. In this study, a panel of diversity encompassing 192 homozygous genotypes, was screened for iron, zinc and phytate seed content. Results indicate a broad variation of these traits and allowed the identification of accessions reasonably carrying favourable trait combinations. A significant association between zinc seed content and some molecular SNP markers co-located on the common bean Pv01 chromosome was detected by means of genome-wide association analysis. The gene Phvul001G233500, encoding for an E3 ubiquitin-protein ligase, is proposed to explain detected associations. This result represents a preliminary evidence that can foster future research aiming at understanding the genetic mechanisms behind zinc accumulation in beans.
Preparation of highly wettable coatings on Ti–6Al–4V ELI alloy for traumatological implants using micro-arc oxidation in an alkaline electrolyte
Authors: Gabor Roman , Doubkova Martina , Gorosova Simona , Malanik Karel , Vandrovcova Marta , Cvrcek Ladislav , Drobikova Klara , Mamulova Kutlakova Katerina , Bacakova Lucie 
Published: November 2020

AbstractPulsed micro-arc oxidation (MAO) in a strongly alkaline electrolyte (pH > 13), consisting of Na2SiO3⋅9H2O and NaOH, was used to form a thin porous oxide coating consisting of two layers differing in chemical and phase composition. The unique procedure, combining MAO and removal of the outer layer by blasting, enables to prepare a coating suitable for application in temporary traumatological implants. A bilayer formed in an alkaline electrolyte environment during the application of MAO enables the formation of a wear-resistant layer with silicon incorporated in the oxide phase. Following the removal of the outer rutile-containing porous layer, the required coating properties for traumatological applications were determined. The prepared surfaces were characterized by scanning electron microscopy, X-ray diffraction patterns, X-ray photoelectron spectroscopy, atomic force microscopy and contact angle measurements. Cytocompatibility was evaluated using human osteoblast-like Saos-2 cells. The newly-developed surface modifications of Ti–6Al–4V ELI alloy performed satisfactorily in all cellular tests in comparison with MAO-untreated alloy and standard tissue culture plastic. High cell viability was supported, but the modifications allowed only relatively slow cell proliferation, and showed only moderate osseointegration potential without significant support for matrix mineralization. Materials with these properties are promising for utilization in temporary traumatological implants.
Probing local distortion around structural defects in half-Heusler thermoelectric NiZrSn alloy
Authors: Miyazaki Hidetoshi , Ozkendir Osman Murat , Gunaydin Selen , Watanabe Kosuke , Soda Kazuo , Nishino Yoichi 
Published: November 2020

AbstractThe half-Heusler NiZrSn (NZS) alloy is particularly interesting owing to its excellent thermoelectric properties, mechanical strength, and oxidation resistance. However, the experimentally investigated thermal conductivity of half-Heusler NZS alloys shows discrepancies when compared to the theoretical predictions. This study investigates the crystal structure around atomic defects by comparing experimental and theoretical X-ray absorption fine structure (XAFS) spectra of the crystal structure of a half-Heusler NZS alloy. The results of both Zr and Ni K-edge XAFS spectra verified the existence of atomic defects at the vacancy sites distorting the C1b-type crystal structure. We concluded that the distortion of the atoms around the interstitial Ni disorder could be the probable reason for the observed lower thermal conductivity values compared to that predicted theoretically in half-Heusler alloys. Our study makes a significant contribution to the literature because the detailed investigation of the lattice distortion around atomic defects will pave the way to further reduce the thermal conductivity by controlling this distortion.
Beneficial effects of daytime high-intensity light exposure on daily rhythms, metabolic state and affect
Authors: Bilu Carmel , Einat Haim , Zimmet Paul , Vishnevskia-Dai Vicktoria , Kronfeld-Schor Noga 
Published: November 2020

AbstractWhile the importance of the circadian system to health and well-being is extensively studied, the role of daylight exposure in these interactions is relatively poorly understood. Here we show, using a diurnal animal model naturally exposed to daylight, that daily morning exposure to 3000 lux, full spectrum electric light has beneficial health effects. Compared with controls, sand rats (Psammomys obesus) subjected to morning light treatment demonstrate daily rhythms with high peak to trough difference in activity, blood glucose levels and per2 gene expression in the suprachiasmatic nucleus, pre-frontal cortex, kidney and liver. The treated animals were also healthier, being normoglycemic, having higher glucose tolerance, lower body and heart weight and lower anxiety- and depression-like behavior. Our results suggest that exposure to high intensity light is important for the proper function of the circadian system and well-being, and are important in face of human's low exposure to daylight and extensive use of artificial light at night.
Chloroplast genomes elucidate diversity, phylogeny, and taxonomy of Pulsatilla (Ranunculaceae)
Authors: Li Qiu-jie , Su Na , Zhang Ling , Tong Ru-chang , Zhang Xiao-hui , Wang Jun-ru , Chang Zhao-yang , Zhao Liang , Potter Daniel 
Published: November 2020

AbstractPulsatilla (Ranunculaceae) consists of about 40 species, and many of them have horticultural and/or medicinal value. However, it is difficult to recognize and identify wild Pulsatilla species. Universal molecular markers have been used to identify these species, but insufficient phylogenetic signal was available. Here, we compared the complete chloroplast genomes of seven Pulsatilla species. The chloroplast genomes of Pulsatilla were very similar and their length ranges from 161,501 to 162,669 bp. Eight highly variable regions and potential sources of molecular markers such as simple sequence repeats, large repeat sequences, and single nucleotide polymorphisms were identified, which are valuable for studies of infra- and inter-specific genetic diversity. The SNP number differentiating any two Pulsatilla chloroplast genomes ranged from 112 to 1214, and provided sufficient data for species delimitation. Phylogenetic trees based on different data sets were consistent with one another, with the IR, SSC regions and the barcode combination rbcL + matK + trnH-psbA produced slightly different results. Phylogenetic relationships within Pulsatilla were certainly resolved using the complete cp genome sequences. Overall, this study provides plentiful chloroplast genomic resources, which will be helpful to identify members of this taxonomically challenging group in further investigation.
Stress-induced sleep-like inactivity modulates stress susceptibility in mice
Authors: Nagai Midori , Nagai Hirotaka , Numa Chisato , Furuyashiki Tomoyuki 
Published: November 2020

AbstractSevere environmental and social stress induces dysregulation of sleep along with mood and cognitive disturbances. However, the role and mechanism of this sleep dysregulation remain elusive. Here we evaluated sleep-like inactivity measured by voluntary movements and its relationship to social behaviors in mice without or with social defeat stress as well as the stressed mice with subsequent sleep deprivation. Social defeat stress immediately induced sleep-like inactivity with decreased body temperature. In the social interaction test, the control mice showed high social interest and its correlation with social sniffing intensity, the latter of which indicates positive valence of social sniffing. After the stress, these social characteristics were maintained in stress-resilient mice, but disrupted in stress-susceptible mice, leading to social avoidance. Sleep deprivation after the stress decreased social sniffing intensity along with reduced social interest, but enhanced the exploratory activity with the positive valence of social sniffing. We also found by c-Fos immunohistochemistry that the stress activated sleep-related brain regions, the dorsomedial hypothalamus and ventrolateral periaqueductal gray. Collectively, these findings show that stress activates sleep-related brain regions and induces sleep-like inactivity, contributing to multiple roles of stress-induced sleep for social behaviors.
Discovery of carbon nanotubes in sixth century BC potteries from Keeladi, India
Authors: Kokarneswaran Manivannan , Selvaraj Prakash , Ashokan Thennarasan , Perumal Suresh , Sellappan Pathikumar , Murugan Kandhasamy Durai , Ramalingam Sivanantham , Mohan Nagaboopathy , Chandrasekaran Vijayanand 
Published: November 2020

AbstractUnique black coatings were observed in the inner wall of pottery shreds excavated from Keeladi, Tamilnadu, India. Raman spectroscopy, transmission electron microscopy, and X-ray photoelectron spectroscopy were used to understand the nature of the coating. The analysis revealed the presence of single, multi-walled carbon nanotubes and layered sheets in the coating. The average diameter of single-walled carbon nanotube found to be about 0.6 ± 0.05 nm. This is the lowest among the single-walled carbon nanotubes reported from artefacts so far and close to the theoretically predicted value (0.4 nm). These nanomaterials were coated in the pottery’s that date backs to sixth century BC, and still retain its stability and adhesion. The findings of nano materials in the pre-historic artifacts, its significance and impact are discussed in this article.
Mutational analysis in familial Alzheimer’s disease of Han Chinese in Taiwan with a predominant mutation PSEN1 p.Met146Ile
Authors: Lin Yung-Shuan , Cheng Chih-Ya , Liao Yi-Chu , Hong Chen-Jee , Fuh Jong-Ling 
Published: November 2020

AbstractMutations in PSEN1, PSEN2, or APP genes are known to be causative for autosomal dominant Alzheimer’s disease (ADAD). While more than 400 mutations were reported worldwide, predominantly PSEN1, over 40 mutations have been reported in Han Chinese and were associated with earlier onset and more affected family members. Between 2002 and 2018, 77 patients in the neurological clinic of Taipei Veterans General Hospital with a history suggestive of ADAD were referred for mutational analysis. We retrospectively collected demographics, initial symptoms, neurological features and inheritance. We identified 16 patients with PSEN1 and 1 with APP mutation. Among the mutations identified, PSEN1 p.Pro117Leu, p.Met146Ile, p.Gly206Asp, p.Gly209Glu, p.Glu280Lys and p.Leu286Val and APP p.Asp678His were known pathogenic mutations; PSEN1 p.His131Arg and p.Arg157Ser were classified as likely pathogenic and variance of unknown significance respectively. The mean age at onset was 46.2 ± 6.2 years in patients with mutation found. PSEN1 p.Met146Ile, occurred in 56.2% (9/16) of patients with PSEN1 mutations, was the most frequent mutation in the cohort. The additional neurological features occurring in 9 PSEN1 p.Met146Ile index patients were similar with the literature. We found patients with genetic diagnoses were more likely to have positive family history, younger age at onset and less brain white matter hyperintensity.
Dynamics and within-host interaction of Theileria lestoquardi and T. ovis among naive sheep in Oman
Authors: Awad Hoyam , Gadalla Amal A. H. , Postigo Milagros , Al-Hamidhi Salama , Tageldin Mohammed H. , Skariah Sini , Sultan Ali A. , Johnson Eugene H. , Shiels Brian , Pain Arnab , Thompson Joanne , Babiker Hamza A. 
Published: November 2020

AbstractMixed species infections of Theileria spp. are common in nature. Experimental and epidemiological data suggest that mixed species infections elicit cross-immunity that can modulate pathogenicity and disease burden at the population level. The present study examined within-host interactions, over a period of 13 months during natural infections with two Theileria spp., pathogenic (T. lestoquardi) and non-pathogenic (T. ovis), amongst a cohort of naive sheep in Oman. In the first two months after exposure to infection, a high rate of mortality was seen among sheep infected with T. lestoquardi alone. However, subsequently mixed-infections of T. lestoquardi and T. ovis prevailed, and no further death occurred. The overall densities of both parasite species were significantly higher as single infection vs mixed infection and the higher relative density of pathogenic T. lestoquardi indicated a competitive advantage over T. ovis in mixed infection. The density of both species fluctuated significantly over time, with no difference in density between the very hot (May to August) and warm season (September to April). A high degree of genotype multiplicity was seen among T. lestoquardi infections, which increased with rising parasite density. Our results illustrate a potential competitive interaction between the two ovine Theileria spp., and a substantial reduction in the risk of mortality in mixed parasite infections, indicating that T. ovis confers heterologous protection against lethal T. lestoquardi infection.
Novel immunotherapeutic effects of topically administered ripasudil (K-115) on corneal allograft survival
Authors: Inomata Takenori , Fujimoto Keiichi , Okumura Yuichi , Zhu Jun , Fujio Kenta , Shokirova Hurramhon , Miura Maria , Okano Mikiko , Funaki Toshinari , Sung Jaemyoung , Negishi Naoko , Murakami Akira 
Published: November 2020

AbstractCorneal allograft survival is mediated by the variety of immunological reactions and wound healing process. Our aim was to explore the effects of topical administration of ripasudil, a selective Rho-associated coiled-coil protein kinase inhibitor, on corneal allograft survival. Ripasudil was administered to mice thrice a day after allogeneic corneal transplantation. Corneal graft survival, opacity, neovascularization, re-epithelization, immune cell infiltration, and mRNA levels of angiogenic and pro-inflammatory factors in the grafted cornea and draining lymph nodes (dLNs) were evaluated with slit-lamp microscopy, immunohistochemistry, flow cytometry, and polymerase chain reaction. Graft survival was significantly prolonged with lower graft opacity and neovascularization scores in 0.4% and 2.0% ripasudil-treated groups, and mRNA levels of angiogenic and pro-inflammatory factors in ripasudil-treated grafted corneas were reduced. Moreover, 0.4% and 2.0% ripasudil reduced CD45+-infiltrated leukocyte frequency, Cd11b and Cd11c mRNA levels, and the frequencies of mature dendritic cells, IFNγ-, and IL-17- producing CD4+T cells in the dLNs of recipients. Re-epithelization rate of the grafted cornea was significantly higher in the 0.4% and 2.0% ripasudil groups than in the control. Topically applied ripasudil prolonged graft survival by downregulating neovascularization and inflammation factors, while promoting corneal re-epithelization, suggesting that ripasudil may be useful for suppressing immunological rejection in corneal transplantation.
Complex network dynamics of the topological structure in a geochemical field from the Nanling area in South China
Authors: Peng Nian , Zhu Xiaoyan , Liu Yongshun , Nie Baofeng , Cui Ying , Geng Qianqian , Yu Chongwen 
Published: November 2020

AbstractThe topological classification of geochemical elements is widely used as a reference for regional prospecting prediction. In this study, we analyze the topological correlation structures of 39 representative geochemical elements from the Nanling area of South China by implementing the complex networks theory. The topological correlation structures of geochemical elements have a high clustering coefficient (0.8120–0.8880), but the magnitude of the shortest path (1.2950–2.3600) is small. In combination with the analysis of complex networks characteristics, we report that the topological correlation structures of the geochemical elements in this area have small-world characteristics, which reveals the self-organized criticality. As shown in the topological network, two random elements have some level of associations, which present a specific community feature. Our preliminary result shows that with changing the control parameter (k) of “coarse-graining”, the topological correlation structures undergo two critical phase transitions. As the control parameter (k) reaches 0.44, the entire element system evolves into two parts. When the control parameter (k) reaches 0.63, the system forms three “communities”. It is worth noting that the three “communities” are basically consistent with the Goldschmidt’s geochemical classification of the elements, which are lithophile, siderophile, and chalcophile groups, respectively. In these “communities”, we also found that a small level of component units is nested.
Formation of intramolecular dimer radical ions of diphenyl sulfones
Authors: Okamoto Kazumasa , Kawai Shunpei , Kozawa Takahiro 
Published: November 2020

AbstractDimer radical ions of aromatic molecules in which excess charge is localized in a pair of rings have been extensively investigated. While dimer radical cations of aromatics have been previously produced in the condensed phase, the number of molecules that form dimer anions is very limited. In this study, we report the formation of intramolecular dimer radical ions (cations and anions) of diphenyl sulfone derivatives (DPs) by electron beam pulse radiolysis in the liquid phase at room temperature. The density functional theory (DFT) calculations also showed the formation of the dimer radical ions. The torsion barrier of the phenyl ring of DPs was also calculated. It was found that the dimer radical ions show the larger barrier than the neutral state. Finally, stability of the dimer radical anion is dependent on not only the inductive effect of the sulfonyl group but the conjugation involving the d-orbital of the S atom and the phenyl rings.
Image-based phenotyping of disaggregated cells using deep learning
Authors: Berryman Samuel , Matthews Kerryn , Lee Jeong Hyun , Duffy Simon P. , Ma Hongshen 
Published: November 2020

AbstractThe ability to phenotype cells is fundamentally important in biological research and medicine. Current methods rely primarily on fluorescence labeling of specific markers. However, there are many situations where this approach is unavailable or undesirable. Machine learning has been used for image cytometry but has been limited by cell agglomeration and it is currently unclear if this approach can reliably phenotype cells that are difficult to distinguish by the human eye. Here, we show disaggregated single cells can be phenotyped with a high degree of accuracy using low-resolution bright-field and non-specific fluorescence images of the nucleus, cytoplasm, and cytoskeleton. Specifically, we trained a convolutional neural network using automatically segmented images of cells from eight standard cancer cell-lines. These cells could be identified with an average F1-score of 95.3%, tested using separately acquired images. Our results demonstrate the potential to develop an “electronic eye” to phenotype cells directly from microscopy images.
Targeting endothelin 1 receptor-miR-200b/c-ZEB1 circuitry blunts metastatic progression in ovarian cancer
Authors: Sestito Rosanna , Cianfrocca Roberta , Tocci Piera , Rosanò Laura , Sacconi Andrea , Blandino Giovanni , Bagnato Anna 
Published: November 2020

AbstractIdentification of regulatory mechanisms underlying the poor prognosis of ovarian cancer is necessary for diagnostic and therapeutic implications. Here we show that endothelin A receptor (ETAR) and ZEB1 expression is upregulated in mesenchymal ovarian cancer and correlates with poor prognosis. Notably, the expression of ETAR and ZEB1 negatively correlates with miR-200b/c. These miRNAs, besides targeting ZEB1, impair ETAR expression through the 3’UTR binding. ZEB1, in turn, restores ETAR levels by transcriptionally repressing miR-200b/c. Activation of ETAR drives the expression of ZEB1 integrating the miR-200/ZEB1 double negative feedback loop. The ETAR-miR-200b/c-ZEB1 circuit promotes epithelial-mesenchymal transition, cell plasticity, invasiveness and metastasis. Of therapeutic interest, ETAR blockade with macitentan, a dual ETAR and ETBR antagonist, increases miR-200b/c and reduces ZEB1 expression with the concomitant inhibition of metastatic dissemination. Collectively, these findings highlight the reciprocal network that integrates ETAR and ZEB1 axes with the miR-200b/c regulatory circuit to favour metastatic progression in ovarian cancer.
A triple farnesoid X receptor and peroxisome proliferator-activated receptor α/δ activator reverses hepatic fibrosis in diet-induced NASH in mice
Authors: Heitel Pascal , Faudone Giuseppe , Helmstädter Moritz , Schmidt Jurema , Kaiser Astrid , Tjaden Amelie , Schröder Martin , Müller Susanne , Schierle Simone , Pollinger Julius , Merk Daniel 
Published: November 2020

AbstractNon-alcoholic steatohepatitis (NASH) - a hepatic manifestation of the metabolic syndrome - is a multifactorial disease with alarming global prevalence. It involves steatosis, inflammation and fibrosis in the liver, thus demanding multiple modes of action for robust therapeutic efficacy. Aiming to fuse complementary validated anti-NASH strategies in a single molecule, we have designed and systematically optimized a scaffold for triple activation of farnesoid X receptor (FXR), peroxisome proliferator-activated receptor (PPAR) α and PPARδ. Pilot profiling of the resulting triple modulator demonstrated target engagement in native cellular settings and in mice, rendering it a suitable tool to probe the triple modulator concept in vivo. In DIO NASH in mice, the triple agonist counteracted hepatic inflammation and reversed hepatic fibrosis highlighting the potential of designed polypharmacology in NASH.