bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chloroquine modulates inflammatory autoimmune responses through Nurr1 in autoimmune diseases
Authors: Park Tae-Yoon , Jang Yongwoo , Kim Woori , Shin Joon , Toh Hui Ting , Kim Chun-Hyung , Yoon Ho Sup , Leblanc Pierre , Kim Kwang-Soo 
Published: October 2019

AbstractFor over a half-century the anti-malarial drug chloroquine (CQ) has been used as a therapeutic agent, alone or in combination, to treat autoimmune diseases. However, neither the underlying mechanism(s) of action nor their molecular target(s) are well defined. The orphan nuclear receptor Nurr1 (also known as NR4A2) is an essential transcription factor affecting the development and maintenance of midbrain dopaminergic neurons. In this study, using in vitro T cell differentiation models, we demonstrate that CQ activates TREG cell differentiation and induces Foxp3 gene expression in a Nurr1-dependent manner. Remarkably, CQ appears to induce Nurr1 function by two distinct mechanisms: firstly, by direct binding to Nurr1’s ligand-binding domain and promoting its transcriptional activity and secondly by upregulation of Nurr1 expression through the CREB signaling pathway. In contrast, CQ suppressed gene expression and differentiation of pathogenic TH17 cells. Importantly, using a valid animal model of inflammatory bowel disease (IBD), we demonstrated that CQ promotes Foxp3 expression and differentiation of TREG cells in a Nurr1-dependent manner, leading to significant improvement of IBD-related symptoms. Taken together, these data suggest that CQ ameliorates autoimmune diseases via regulating Nurr1 function/expression and that Nurr1 is a promising target for developing effective therapeutics of human inflammatory autoimmune diseases.
Intercomparison of in-situ aircraft and satellite aerosol measurements in the stratosphere
Authors: Sandvik Oscar S. , Friberg Johan , Martinsson Bengt G. , van Velthoven Peter F. J. , Hermann Markus , Zahn Andreas 
Published: October 2019

AbstractAerosol composition and optical scattering from particles in the lowermost stratosphere (LMS) have been studied by comparing in-situ aerosol samples from the IAGOS-CARIBIC passenger aircraft with vertical profiles of aerosol backscattering obtained from the CALIOP lidar aboard the CALIPSO satellite. Concentrations of the dominating fractions of the stratospheric aerosol, being sulphur and carbon, have been obtained from post-flight analysis of IAGOS-CARIBIC aerosol samples. This information together with literature data on black carbon concentrations were used to calculate the aerosol backscattering which subsequently is compared with measurements by CALIOP. Vertical optical profiles were taken in an altitude range of several kilometres from and above the northern hemispheric extratropical tropopause for the years 2006-2014. We find that the two vastly different measurement platforms yield different aerosol backscattering, especially close to the tropopause where the influence from tropospheric aerosol is strong. The best agreement is found when the LMS is affected by volcanism, i.e., at elevated aerosol loadings. At background conditions, best agreement is obtained some distance (>2 km) above the tropopause in winter and spring, i.e., at likewise elevated aerosol loadings from subsiding aerosol-rich stratospheric air. This is to our knowledge the first time the CALIPSO lidar measurements have been compared to in-situ long-term aerosol measurements.
Dynamic size-weight changes after object lifting reduce the size-weight illusion
Authors: van Polanen Vonne , Davare Marco 
Published: October 2019

AbstractIn the size-weight illusion, the smaller object from two equally weighted objects is typically judged as being heavier. One explanation is that the mismatch between the weight expectation based on object size and actual sensory feedback influences heaviness perception. In most studies, the size of an object is perceived before its weight. We investigated whether size changes would influence weight judgement if both would be perceived simultaneously. We used virtual reality to change the size and weight of an object after lifting and asked participants to judge whether the object became lighter or heavier. We found that simultaneous size-weight changes greatly reduced the size-weight illusion to perceptual biases below discrimination thresholds. In a control experiment in which we used a standard size-weight illusion protocol with sequential lifts of small and large objects in the same virtual reality setup, we found a larger, typical perceptual bias. These results show that the size-weight illusion is smaller when size and weight information is perceived simultaneously. This provides support for the prediction mismatch theory explaining the size-weight illusion. The comparison between perceived and expected weight during the lifting phase could be a critical brain mechanism for mediating the size-weight illusion.
Expression level of CEBPA gene in acute lymphoblastic leukemia individuals
Authors: Szmajda Dagmara , Krygier Adrian , Jamroziak Krzysztof , Żebrowska-Nawrocka Marta , Balcerczak Ewa 
Published: October 2019

AbstractCurrently, acute lymphoblastic leukemia (ALL) has an overall survival of nearly 80% when it occurs in children, however cure rates among adults are far reduced. Leukemogenesis can be driven up by a slight change in the expression or function of certain transcription factors. CCAAT Enhancer Binding Protein Alpha (CEBPA) is a transcription factor with role in cell cycle regulation, granulocytic differentiation and more. Some studies suggest its oncogenic function. The potential role of CEBPA as an oncogene in ALL development has not been completely elucidated so far. Therefore, the aim of the present study was to evaluate mRNA level of CEBPA gene in 60 adult patients diagnosed with ALL. Quantitative analysis was performed by qPCR reaction. Analysis revealed that men tended to have higher and more variable CEBPA expression levels (P = 0.032). No associations for other parameters (ALL subtype, age, leukocytosis, blast percentage, Philadelphia chromosome presence, CD10 marker presence) were found. When comparing the results of CEBPA expression with patients suffering from acute myeloid leukemia, ALL cases showed statistically significant lower levels of CEBPA (P < 0.0000). It may seem that CEBPA expression level itself has potentially no effect on arising and progression of acute lymphoblastic leukemia, although it is a matter that needs further investigation.
Novel dihydroartemisinin dimer containing nitrogen atoms inhibits growth of endometrial cancer cells and may correlate with increasing intracellular peroxynitrite
Authors: Zhu Yan , Klausen Christian , Zhou Jieyun , Guo Xiangjie , Zhang Yu , Zhu Hua , Li Zhao , Cheng Jung-Chien , Xie Shuwu , Yang Wenjie , Li Ying , Leung Peter C. K. 
Published: October 2019

AbstractIn the present study, a novel dimer, SM1044, selected from a series of dihydroartemisinin (DHA) derivatives containing nitrogen atoms comprising simple aliphatic amine linkers, showed strong growth inhibition in six types of human endometrial cancer (EC) cells, with half maximal inhibitory concentration (IC50) and 95% confidence interval (CI) < 3.6 (1.16~11.23) μM. SM1044 evoked apoptosis and activated caspase-3, −8 and −9 in a concentration- and time-dependent manner, and these effects were manifested early in RL95-2 compared to KLE cells, possibly correlated with the induction of intracellular ONOO−. Catalase and uric acid attenuated the growth inhibitory effects of SM1044 on EC cells, but sodium pyruvate did not. In vivo, the average xenograft tumour growth inhibition rates ranged from 35.8% to 49.9%, respectively, after 2.5 and 5.0 mg/kg SM1044 intraperitoneal treatment, and no obvious behavioural and histopathological abnormalities were observed in SM1044-treated mice in this context. SM1044 predominantly accumulated in the uteri of mice after a single injection. SM1044 displayed efficacy as a tumour suppressor with distinct mechanism of action and unique tissue distribution, properties that distinguish it from other artemisinin analogues. Our findings provide a new clue for artemisinin analogue against cancer.
Leucine-rich diet induces a shift in tumour metabolism from glycolytic towards oxidative phosphorylation, reducing glucose consumption and metastasis in Walker-256 tumour-bearing rats
Authors: Viana Laís Rosa , Tobar Natália , Busanello Estela Natacha Brandt , Marques Ana Carolina , de Oliveira Andre Gustavo , Lima Tanes I. , Machado Gabrielly , Castelucci Bianca Gazieri , Ramos Celso Dario , Brunetto Sérgio Q , Silveira Leonardo Reis , Vercesi Anibal Eugenio , Consonni Sílvio Roberto , Gomes-Marcondes Maria Cristina Cintra 
Published: October 2019

AbstractLeucine can stimulate protein synthesis in skeletal muscle, and recent studies have shown an increase in leucine-related mitochondrial biogenesis and oxidative phosphorylation capacity in muscle cells. However, leucine-related effects in tumour tissues are still poorly understood. Thus, we described the effects of leucine in both in vivo and in vitro models of a Walker-256 tumour. Tumour-bearing Wistar rats were randomly distributed into a control group (W; normoprotein diet) and leucine group (LW; leucine-rich diet [normoprotein + 3% leucine]). After 20 days of tumour evolution, the animals underwent 18-fludeoxyglucose positron emission computed tomography (18F-FDG PET-CT) imaging, and after euthanasia, fresh tumour biopsy samples were taken for oxygen consumption rate measurements (Oroboros Oxygraph), electron microscopy analysis and RNA and protein extraction. Our main results from the LW group showed no tumour size change, lower tumour glucose (18F-FDG) uptake, and reduced metastatic sites. Furthermore, leucine stimulated a shift in tumour metabolism from glycolytic towards oxidative phosphorylation, higher mRNA and protein expression of oxidative phosphorylation components, and enhanced mitochondrial density/area even though the leucine-treated tumour had a higher number of apoptotic nuclei with increased oxidative stress. In summary, a leucine-rich diet directed Walker-256 tumour metabolism to a less glycolytic phenotype profile in which these metabolic alterations were associated with a decrease in tumour aggressiveness and reduction in the number of metastatic sites in rats fed a diet supplemented with this branched-chain amino acid.
Cavitation-induced traumatic cerebral contusion and intracerebral hemorrhage in the rat brain by using an off-the-shelf clinical shockwave device
Authors: Huang Abel Po-Hao , Lai Dar-Ming , Hsu Yi-Hua , Kung Yi , Lan Chiang , Yeh Chia-Shan , Tsai Hsin-Han , Lin Chih-Feng , Chen Wen-Shiang 
Published: October 2019

AbstractTraumatic cerebral contusion and intracerebral hemorrhages (ICH) commonly result from traumatic brain injury and are associated with high morbidity and mortality rates. Current animal models require craniotomy and provide less control over injury severity. This study proposes a highly reproducible and controllable traumatic contusion and ICH model using non-invasive extracorporeal shockwaves (ESWs). Rat heads were exposed to ESWs generated by an off-the-shelf clinical device plus intravenous injection of microbubbles to enhance the cavitation effect for non-invasive induction of injury. Results indicate that injury severity can be effectively adjusted by using different ESW parameters. Moreover, the location or depth of injury can be purposefully determined by changing the focus of the concave ESW probe. Traumatic contusion and ICH were confirmed by H&E staining. Interestingly, the numbers of TUNEL-positive cells (apoptotic cell death) peaked one day after ESW exposure, while Iba1-positive cells (reactive microglia) and GFAP-positive cells (astrogliosis) respectively peaked seven and fourteen days after exposure. Cytokine assay showed significantly increased expressions of IL-1β, IL-6, and TNF-α. The extent of brain edema was characterized with magnetic resonance imaging. Conclusively, the proposed non-invasive and highly reproducible preclinical model effectively simulates the mechanism of closed head injury and provides focused traumatic contusion and ICH.
Molecular characterization of root-knot nematodes (Meloidogyne spp.) from Arkansas, USA
Authors: Ye Weimin , Robbins Robert Thomas , Kirkpatrick Terry 
Published: October 2019

AbstractRoot-knot nematodes (Meloidogyne spp.) are the most common major pathogens of many crops throughout the world, impacting both the quantity and quality of marketable yields. In this study, a total of 244 root-knot nematode populations from various hosts from 39 counties in Arkansas were tested to determine the species diversity. Molecular characterization was performed on these populations by DNA sequencing of the ribosomal DNA 18S-ITS-5.8S, 28S D2/D3 and a mitochondrial DNA fragment flanking cytochrome oxidase gene subunit II - the intergenic spacer. Five species were identified, including M. incognita (Kofoid & White, 1919) Chitwood, 1949 from soybean, cotton, corn and various vegetables (232 samples); M. hapla Chitwood, 1949 from rose (1 sample); M. haplanaria Eisenback, Bernard, Starr, Lee & Tomaszewski, 2003 from okra, tomato, peanut, Indian hawthorn, ash, willow and elm trees (7 samples); M. marylandi Jepson & Golden in Jepson, 1987 from grasses (3 samples); and M. partityla Kleynhans, 1986 from pecan (1 sample) through a combined analysis of DNA sequencing and PCR by species-specific primers. Meloidogyne incognita is the most abundant species that was identified in 95% samples and was the only species in field crops including soybean and cotton, except for one population of M. haplanaria from soybean in Logan County (TK201). Species-specific primers were used to verify M. incognita through PCR by species-specific primers. Unlike historical data, M. arenaria, M. javanica and M. graminis were not detected from any of the samples collected during this study. This result is essential for effective and sustainable management strategies against root-knot nematodes in Arkansas.
mRhubarb: Engineering of monomeric, red-shifted, and brighter variants of iRFP using structure-guided multi-site mutagenesis
Authors: Rogers Oliver C. , Johnson Dorothy M. , Firnberg Elad 
Published: October 2019

AbstractFar-red and near-infrared fluorescent proteins (FPs) enable in vivo tissue imaging with greater depth and clarity compared to FPs in the visible spectrum due to reduced light absorbance and scatter by tissues. However current tools are limited by low brightness, limited red-shifting, and a non-ideal dimeric oligomerization state. In this study we developed a monomeric variant of iRFP, termed mRhubarb713, and subsequently used a targeted and expansive multi-site mutagenesis approach to screen for variants with red-shifted spectral activity. Two monomeric variants were discovered, deemed mRhubarb719 and mRhubarb720, with red-shifted spectra and increased quantum yield compared to iRFP. These tools build on previously developed near-IR FPs and should enable improved in vivo imaging studies with a genetically encoded reporter.
The interferon stimulated gene viperin, restricts Shigella. flexneri in vitro
Authors: Helbig K. J. , Teh M. Y. , Crosse K. M. , Monson E. A. , Smith M. , Tran E. N. , Standish A. J. , Morona R. , Beard M. R. 
Published: October 2019

AbstractThe role of interferon and interferon stimulated genes (ISG) in limiting bacterial infection is controversial, and the role of individual ISGs in the control of the bacterial life-cycle is limited. Viperin, is a broad acting anti-viral ISGs, which restricts multiple viral pathogens with diverse mechanisms. Viperin is upregulated early in some bacterial infections, and using the intracellular bacterial pathogen, S. flexneri, we have shown for the first time that viperin inhibits the intracellular bacterial life cycle. S. flexneri replication in cultured cells induced a predominantly type I interferon response, with an early increase in viperin expression. Ectopic expression of viperin limited S. flexneri cellular numbers by as much as 80% at 5hrs post invasion, with similar results also obtained for the intracellular pathogen, Listeria monocytogenes. Analysis of viperins functional domains required for anti-bacterial activity revealed the importance of both viperin’s N-terminal, and its radical SAM enzymatic function. Live imaging of S. flexneri revealed impeded entry into viperin expressing cells, which corresponded to a loss of cellular cholesterol. This data further defines viperin’s multi-functional role, to include the ability to limit intracellular bacteria; and highlights the role of ISGs and the type I IFN response in the control of bacterial pathogens.
Interactive Effects of Nitrogen-Fixing Bacteria Inoculation and Nitrogen Fertilization on Soybean Yield in Unfavorable Edaphoclimatic Environments
Authors: Cordeiro Carlos Felipe dos Santos , Echer Fábio Rafael 
Published: October 2019

AbstractThe objective of this work was to evaluate the effect of nitrogen (N) fertilization and the biological nitrogen fixation efficiency in soybean crops grown in unfavorable environments (high temperature, low fertility, and areas with sandy soil). Six field experiments were conducted between 2015 and 2018. Two experiments were performed per year. They were conducted in two separate areas. One was previously covered with degraded pasture (post-pasture area). The other was previously used to plant soybean (post-soybean crop area). The treatments consisted of inoculations with N-fixing bacteria (NFB) (0, 4, 8, and 12 doses ha−1) and N fertilization with rates of 0, 25, 50, and 100 kg ha−1. N fertilization and inoculation with NFB increased soil N, though the levels were still low. Among the tested groups, those with the application of eight doses of inoculant recorded the highest grain yields in post-soybean areas. They showed 10% (237 kg ha−1) and 15% (336 kg ha−1) higher grain yields when compared to crops treated without inoculant and crops with four doses of inoculant, respectively. N fertilization with 25 and 100 kg ha−1 decreased the root nodules of soybean plants grown in the post-soybean and post-pasture areas, respectively. Soybean crops grown on degraded pasture areas also showed good response to N fertilization (50 kg ha−1) when combined with NFB inoculation (12 doses ha−1). These showed grain yields 22% (439 kg ha−1) higher than those of plants treated with just 12 doses of inoculant and no N fertilization.
PdAg Nanoparticles within Core-Shell Structured Zeolitic Imidazolate Framework as a Dual Catalyst for Formic Acid-based Hydrogen Storage/Production
Authors: Wen Meicheng , Mori Kohsuke , Futamura Yuya , Kuwahara Yasutaka , Navlani-García Miriam , An Taicheng , Yamashita Hiromi 
Published: October 2019

AbstractFormic acid (FA; HCOOH) is one of the most promising candidates for the storage of hydrogen (H2). Herein, we report a H2 storage/production system based on the hydrogenation of CO2 and dehydrogenation of FA, using a nanostructured heterogeneous catalyst. Pd1Ag2 nanoparticles with an average size of 2.8 nm were encapsulated within a zeolitic imidazolate framework (ZIF-8) having a core-shell structure (ZIF-8@Pd1Ag2@ZIF-8). This composite displayed high activity and stability during both the hydrogenation of CO2 to produce FA and the dehydrogenation of FA into H2 and CO2. This improved performance is attributed to the use of ultrafine Pd1Ag2 nanoparticles as well as the spatial regulation of the nanoparticles within the reaction field. This study suggests a new strategy for controlling the spatial distribution of metal nanoparticles within MOFs so as to fine-tune the catalytic activity and selectivity of ZIF-8@metal nanoparticles@ZIF-8 catalysts.
Residues of acidic chitinase cause chitinolytic activity degrading chitosan in porcine pepsin preparations
Authors: Tabata Eri , Wakita Satoshi , Kashimura Akinori , Sugahara Yasusato , Matoska Vaclav , Bauer Peter O. , Oyama Fumitaka 
Published: October 2019

AbstractCommercially available porcine pepsin preparations have been used for the production of chitooligosaccharides with various biomedical activities. However, the origin of this activity is not well understood. Here we show that the chitosan-degrading activity is conferred by residues with chitinolytic activity of truncated forms of acidic chitinase (Chia) persisting in the pepsin preparation. Chia is an acid-stable and pepsin-resistant enzyme that degrades chitin to produce N-acetyl-D-glucosamine dimer. We found that Chia can be truncated by pepsin under stomach-like conditions while maintaining its enzymatic activity. Similarly to the full-length protein, truncated Chia as well as the pepsin preparations digested chitosan with different degrees of deacetylation (DD: 69–84%) with comparable degradation products. The efficiency was DD-dependent with a marked decrease with higher DD, indicating that the chitosan-degrading activity in the pepsin preparation is due to the chitinolytic activity rather than chitosanolytic activity. We suggest that natural or recombinant porcine Chia are suitable for producing chitooligosaccharides for biomedical purposes.
The influences of gender and aging on optic nerve head microcirculation in healthy adults
Authors: Kobayashi Tatsuhiko , Shiba Tomoaki , Kinoshita Ayako , Matsumoto Tadashi , Hori Yuichi 
Published: October 2019

AbstractPotential differences in the nature of the influences of aging and gender on the optic nerve head (ONH) microcirculation, using laser speckle flowgraphy (LSFG) were evaluated. We studied 908 healthy subjects (men = 701, age: 50.0 ± 9.1 yrs, women = 208, 49.8 ± 9.5 yrs, p = 0.76). The average, maximum (Max), and minimum (Min) mean blur rate (MBR) in a heartbeat were evaluated. The parameters were analyzed separately for the tissue, vessels, and throughout the ONH (All). We investigated which MBR sections are correlated with gender and age by univariate and multivariate regression analyses. The Max MBR-All (r = −0.31) was most strongly correlated with gender (men = 1, women = 0). The Min MBR-All (r = −0.24) was most strongly correlated with age, followed by Min MBR-All (r = −0.20). The factors contributing independently to the Max MBR-All were gender (β = −0.15), pulse pressure, spherical refraction, ocular perfusion pressure, and red blood cell (RBC) count. The factors contributing independently to the Min MBR-Vessel were gender (β = −0.09), age (β = −0.25), body mass index, heart rate, and spherical refraction. The factors contributing independently to the Min-MBR-All were age (β = −0.22), heart rate, and RBC count. Our results revealed that gender differences influence the Max MBR, and aging influences the Min MBR. These correlations were stronger than that of average MBR.