bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cross-talk between primary osteocytes and bone marrow macrophages for osteoclastogenesis upon collagen treatment
Authors: Elango Jeevithan , Sanchez Christelle , de Val José Eduardo Maté Sánchez , Henrotin Yves , Wang Shujun , Motaung Keolebogile Shirley Caroline Mamots , Guo Ruihua , Wang Chunxiao , Robinson Jeyashakila , Regenstein Joe M. , Bao Bin , Wu Wenhui 
Published: March 2018

AbstractHomeostasis of osteoclast formation from bone marrow macrophages (BMM) is regulated by paracrine signals of the neighbourhood bone cells particularly mesenchymal stem cells (MSC), osteoblasts and osteocytes (OC). Besides paracrine cues, collagen and glycosaminoglycan are involved in controlling bone homeostasis. Towards this approach, different molecular weight collagens were reacted with MSC, OC and BMM to understand the bone homeostasis activity of collagen. The up-regulating effect of collagens on osteogenic cell growth was confirmed by the presence of mineralized nodules in the osteoblastogenic lineage cells and increased osteogenic stimulatory gene expression. The decreased BMM-derived TRAP+ osteoclasts number and osteoclastogenic regulatory gene expression of OC could demonstrate the exploitive osteoclastogenic activity of collagens. Osteoclastogenesis from BMM was triggered by paracrine cues of OC in some extend, but it was down-regulated by collagen. Overall, the effect of collagen on osteoclastogenesis and osteoblastogenesis may depend on the molecular weight of collagens, and collagen suppresses osteoclastogenesis, at least in part by downregulating the secretion of cytokines in OC.
Dnmt3a in the dorsal dentate gyrus is a key regulator of fear renewal
Authors: Gong Zhiting , Zhou Qiang 
Published: March 2018

AbstractRenewal of extinguished fear memory in an altered context is widely believed to be a major limiting issue for exposure therapy in treating various psychiatric diseases. Effective prevention of fear renewal will significantly improve the efficacy of exposure therapy. DNA methyltransferase (DNMTs) mediated epigenetic processes play critical roles in long term memory, but little is known about their functions in fear memory extinction or renewal. Here we investigated whether DNMTs regulate fear renewal after extinction. We found that elevated Dnmt3a level in the dorsal dentate gyrus (dDG) of hippocampus was associated with the absence of fear renewal in an altered context after extinction training. Overexpression and knockdown of Dnmt3a in the dDG regulated the occurrence of fear renewal in a bi-directional manner. In addition, Dnmt3a overexpression was associated with elevated expression of c-Fos in the dDG during extinction training. Furthermore, we found that renewal of remote fear memory can be prevented, and the absence of renewal was concurrent with an elevated Dnmt3a level. Our results indicate that Dnmt3a in the dDG is a key regulator of fear renewal after extinction, and Dnmt3a may play a critical role in controlling fear memory return and thus has therapeutic values.
Extracting biological age from biomedical data via deep learning: too much of a good thing?
Authors: Pyrkov Timothy V. , Slipensky Konstantin , Barg Mikhail , Kondrashin Alexey , Zhurov Boris , Zenin Alexander , Pyatnitskiy Mikhail , Menshikov Leonid , Markov Sergei , Fedichev Peter O. 
Published: March 2018

AbstractAge-related physiological changes in humans are linearly associated with age. Naturally, linear combinations of physiological measures trained to estimate chronological age have recently emerged as a practical way to quantify aging in the form of biological age. In this work, we used one-week long physical activity records from a 2003–2006 National Health and Nutrition Examination Survey (NHANES) to compare three increasingly accurate biological age models: the unsupervised Principal Components Analysis (PCA) score, a multivariate linear regression, and a state-of-the-art deep convolutional neural network (CNN). We found that the supervised approaches produce better chronological age estimations at the expense of a loss of the association between the aging acceleration and all-cause mortality. Consequently, we turned to the NHANES death register directly and introduced a novel way to train parametric proportional hazards models suitable for out-of-the-box implementation with any modern machine learning software. As a demonstration, we produced a separate deep CNN for mortality risks prediction that outperformed any of the biological age or a simple linear proportional hazards model. Altogether, our findings demonstrate the emerging potential of combined wearable sensors and deep learning technologies for applications involving continuous health risk monitoring and real-time feedback to patients and care providers.
Interleukin-23 as a therapeutic target for inflammatory myopathy
Authors: Umezawa Natsuka , Kawahata Kimito , Mizoguchi Fumitaka , Kimura Naoki , Yoshihashi-Nakazato Yoko , Miyasaka Nobuyuki , Kohsaka Hitoshi 
Published: March 2018

AbstractCurrent treatments of polymyositis and dermatomyositis (PM/DM) depend on non-specific immunosuppressants. This study was performed to elucidate the role of interleukin (IL)-23, as their possible therapeutic target. As was reported earlier in PM/DM patients, serum IL-23 levels were elevated in mice with C protein induced-myositis (CIM), a murine model of PM. IL-23 was expressed by macrophages in the PM/DM and CIM muscles and by dendritic cells and macrophages in the lymph nodes from the CIM mice. It was also expressed by macrophages in the chemically injured muscles, but not those recruited into the muscles by footpad injection of Freund’s complete adjuvant, demonstrating that IL-23 production should be associated with muscle damage. Genetic deletion of IL-23 as well as preventive and therapeutic administration of blocking antibodies against IL-23p19 subunit suppressed CIM. When lymph node cells from the CIM mice were transferred adoptively into naive wild type or IL-23p19 deficient recipient mice, both recipients developed myositis equally. Thus, elevated IL-23 should promote dendritic cells and macrophages to activate the autoaggressive T cells. Our findings suggest that IL-23 should mediate positive feedback loop from the muscle damage to the T cell activation and be a promising therapeutic target for autoimmune myositis.
A prominent air pollutant, Indeno[1,2,3-cd]pyrene, enhances allergic lung inflammation via aryl hydrocarbon receptor
Authors: Wong Tzu-Hsuan , Lee Chon-Lin , Su Hsiang-Han , Lee Chin-Lai , Wu Chao-Chien , Wang Chin-Chou , Sheu Chau-Chyun , Lai Ruay-Sheng , Leung Sum-Yee , Lin Chi-Cheng , Wei Yu-Feng , Wang Chien-Jen , Lin Yu-Chun , Chen Hua-Ling , Huang Ming-Shyan , Yen Jeng-Hsien , Huang Shau-Ku , Suen Jau-Ling 
Published: March 2018

AbstractChronic exposure to ambient polycyclic aromatic hydrocarbons (PAHs) is associated with asthma, but its regulatory mechanisms remain incompletely defined. We report herein that elevated levels of urinary 1-hydroxypyrene, a biomarker of PAH exposure, were found in asthmatic subjects (n = 39) as compared to those in healthy subjects (n = 43) living in an industrial city of Taiwan, where indeno[1,2,3-cd]pyrene (IP) was found to be a prominent PAH associated with ambient PM2.5. In a mouse model, intranasal exposure of mice with varying doses of IP significantly enhanced antigen-induced allergic inflammation, including increased airway eosinophilia, Th2 cytokines, including IL-4 and IL-5, as well as antigen-specific IgE level, which was absent in dendritic cell (DC)-specific aryl hydrocarbon receptor (AhR)-null mice. Mechanistically, IP treatment significantly altered DC’s function, including increased level of pro-inflammatory IL-6 and decreased generation of anti-inflammatory IL-10. The IP’s effect was lost in DCs from mice carrying an AhR-mutant allele. Taken together, these results suggest that chronic exposure to environmental PAHs may pose a significant risk for asthma, in which IP, a prominent ambient PAH in Taiwan, was shown to enhance the severity of allergic lung inflammation in mice through, at least in part, its ability in modulating DC’s function in an AhR-dependent manner.
Latitudinal trends in human primary activities: characterizing the winter day as a synchronizer
Authors: Martín-Olalla José María 
Published: March 2018

AbstractThis work analyzes time use surveys from 19 countries (17 European and 2 American) in the middle latitude (38–61 degree) accounting for 45% of world population in this range. Time marks for primary activities are contrasted against light/dark conditions. The analysis reveals winter sunrise synchronizes labor start time below 54 degree, occurring within winter civil twilight. Winter sunset is a source of synchronization for labor end times. Winter terminator punctuate meal times in Europe: dinner occurs 3 h after winter sunset time within 1 h; 40% narrower than variability of dinner local times. The sleep-wake cycle of laborers is shown to be related to winter sunrise whereas standard population’s appears to be irrespective of latitude. The significance of the winter terminator depends on two competing factors average labor time (~7 h30 m) and the shortest photoperiod. Winter terminator gains significance when both roughly matches. That is within a latitude range from 38 degree to 54 degree. The significance of winter terminator as a source of synchronization is also related to contemporary year round time schedules: the shortest photoperiod represents the worst case scenario the society faces.
The Cish SH2 domain is essential for PLC-γ1 regulation in TCR stimulated CD8+ T cells
Authors: Guittard Geoffrey , Dios-Esponera Ana , Palmer Douglas C. , Akpan Itoro , Barr Valarie A. , Manna Asit , Restifo Nicholas P. , Samelson Lawrence E. 
Published: March 2018

AbstractCish, participates within a multi-molecular E3 ubiquitin ligase complex, which ubiquitinates target proteins. It has an inhibitory effect on T cell activation mediated by PLC-γ1 regulation, and it functions as a potent checkpoint in CD8+ T cell tumor immunotherapy. To study the structural and functional relationships between Cish and PLC-γ1 during CD8+ T cell activation, we tested mutants of the Cish-SH2 (R107K) and D/BC (L222Q, C226Q) domains. We confirmed that Cish-SH2-specific binding was essential for PLC-γ1 ubiquitination and degradation. This domain was essential for the Cish-mediated inhibition of Ca2+ release upon TCR stimulation. No effect on inhibition of cytokine release was observed with SH2 or D/BC mutants, although the absence of Cish led to an increased release of IFN-γ and TNF-α. Using imaging we showed that Cish was expressed mostly in the cytoplasm and we did not see any Cish clustering at the plasma membrane upon stimulation. We conclude that the Cish-SH2 domain is essential for PLC-γ1 regulation in TCR-stimulated CD8+ T cells.
Highly efficient Fenton and enzyme-mimetic activities of NH2-MIL-88B(Fe) metal organic framework for methylene blue degradation
Authors: He Jianchuan , Zhang Yao , Zhang Xiaodan , Huang Yuming 
Published: March 2018

AbstractHere, we show that NH2-MIL-88B(Fe) can be used as a peroxidase-like catalyst for Fenton-like degradation of methylene blue (MB) in water. The iron-based NH2-MIL-88B(Fe) metal organic framework (MOF) was synthesized by a facile and rapid microwave heating method. It was characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, powder X-ray diffraction, and the Brunauer–Emmett–Teller method. The NH2-MIL-88B(Fe) MOF possesses intrinsic oxidase-like and peroxidase-like activities. The reaction parameters that affect MB degradation were investigated, including the solution pH, NH2-MIL-88B(Fe) MOF and H2O2 concentrations, and temperature. The results show that the NH2-MIL-88B(Fe) MOF exhibits a wide working pH range (pH 3.0–11.0), temperature tolerance, and good recyclability for MB removal. Under the optimal conditions, complete removal of MB was achieved within 45 min. In addition, removal of MB was above 80% after five cycles, showing the good recyclability of NH2-MIL-88B(Fe). The NH2-MIL-88B(Fe) MOF has the features of easy preparation, high efficiency, and good recyclability for MB removal in a wide pH range. Electron spin resonance and fluorescence probe results suggest the involvement of hydroxyl radicals in MB degradation. These findings provide new insight into the application of high-efficient MOF-based Fenton-like catalysts for water purification.
Rydberg interaction induced enhanced excitation in thermal atomic vapor
Authors: Kara Dushmanta , Bhowmick Arup , Mohapatra Ashok K. 
Published: March 2018

AbstractWe present the experimental demonstration of interaction induced enhancement in Rydberg excitation or Rydberg anti-blockade in thermal atomic vapor. We have used optical heterodyne detection technique to measure Rydberg population due to two-photon excitation to the Rydberg state. The anti-blockade peak which doesn’t satisfy the two-photon resonant condition is observed along with the usual two-photon resonant peak which can’t be explained using the model with non-interacting three-level atomic system. A model involving two interacting atoms is formulated for thermal atomic vapor using the dressed states of three-level atomic system to explain the experimental observations. A non-linear dependence of vapor density is observed for the anti-blockade peak which also increases with increase in principal quantum number of the Rydberg state. A good agreement is found between the experimental observations and the proposed interacting model. Our result implies possible applications towards quantum logic gates using Rydberg anti-blockade in thermal atomic vapor.
Metal behavior in the extremes of dynamics
Authors: Zubelewicz Aleksander 
Published: March 2018

AbstractWhen the rate of loading is faster than the rate at which material absorbs and converts energy to plastic work and damages, then there is an excess of energy that is partly stored in the material’s microstructure and the rest of it triggers micro-dynamic excitations. The additional storage necessitates the development of plastic flow constraints and is directly responsible for the observed dynamic strengthening. At extreme conditions, we find that the micro-excitations contribute to the dynamic behavior. The phenomena are universally observed in metals, frictional materials and polymers. In essence, strong dynamics creates conditions at which materials are pushed from equilibrium and temporarily reside in an excited state of behavior. This study is focused on the behavior of metals. The concept is incorporated into a mechanisms-based constitutive model and is examined for annealed OFHC copper.
Supplementation of Pelleted Hazel (Corylus avellana) Leaves Decreases Methane and Urinary Nitrogen Emissions by Sheep at Unchanged Forage Intake
Authors: Wang Shaopu , Terranova Melissa , Kreuzer Michael , Marquardt Svenja , Eggerschwiler Lukas , Schwarm Angela 
Published: March 2018

AbstractThis study is the first to quantify the effects of hazel (Corylus avellana) leaves on methane and urinary nitrogen emissions, digestibility, nitrogen and the energy balance of ruminants. Four experimental pellets were produced with 0, 30% and 60% hazel leaves, the latter also with 4% polyethylene glycol. Hazel leaves gradually replaced lucerne. The diet was composed of the pellets and grass hay (80%: 20%). Six adult sheep were allocated to all four treatments in a 6 × 4 crossover design. Including hazel leaves did not affect the feed intake, but it decreased the apparent digestibility of organic matter and fibre, especially at the high level. Methane emission was reduced by up to 25 to 33% per day, per unit of intake and per unit of organic matter digested. Urinary nitrogen excretion decreased by 33 to 72% with increasing levels of hazel leaves. The treatment with polyethylene glycol demonstrated that tannins in hazel leaves caused significant shares of the effects. In conclusion, the current results indicated a significant potential of hazel leaves as forage for ruminants to mitigate methane and urinary nitrogen emissions. Even high dietary hazel leaf proportions were palatable. The lower digestibility needs to be compensated with easily digestible diet ingredients.
Osteoarthritis-patterns, cardio-metabolic risk factors and risk of all-cause mortality: 20 years follow-up in patients after hip or knee replacement
Authors: Büchele G. , Günther K. P. , Brenner H. , Puhl W. , Stürmer T. , Rothenbacher D. , Brenner R. E. 
Published: March 2018

AbstractOsteoarthritis (OA) is a common musculoskeletal disorder and occur in different patterns. However, its impact on long-term all-cause-mortality is inconclusive. Study aims: Investigate 20-year all-cause-mortality in patients with hip/knee arthroplasty (recruited 1995/1996, N = 809) from the Ulm Osteoarthritis Study-cohort, in comparison to general population. Furthermore, to enlighten the triangle between baseline life-style and cardio-metabolic risk factors, phenotypic OA-patterns (laterality, generalization, cause) and all-cause-mortality. Mortality was assessed during 20 years follow-up. Standardized mortality ratios (SMR), adjusted odds ratios and hazard ratios (aHR) were calculated. After five years cohort-mortality was reduced compared to the general population, however 20 years later assimilated (SMR = 1.11; 95%-CI 0.73-1.49). OA-patterns were associated with age, cholesterol, and overweight/obesity. In comparison to primary OA decreased mortality was observed for patients with secondary OA (aHR = 0.76; 95%-CI 0.61-0.95) adjusted for age, smoking, overweight/obesity, diabetes, hypertension, cardiac insufficiency, uric acid, and lower cholesterol. There was no increased mortality in patients after 20 years follow-up compared to general population. Significantly decreased mortality in secondary compared to primary OA suggests a subtype-specific involvement of systemic co-factors in determination of all-cause-mortality. Because cardio-metabolic risk factors were associated with increased risk of bilateral OA and lower long-term survival, those risk factors should be consequently targeted in OA-patients.
Population genetic analysis of the recently rediscovered Hula painted frog (Latonia nigriventer) reveals high genetic diversity and low inbreeding
Authors: Perl R. G. Bina , Geffen Eli , Malka Yoram , Barocas Adi , Renan Sharon , Vences Miguel , Gafny Sarig 
Published: March 2018

AbstractAfter its recent rediscovery, the Hula painted frog (Latonia nigriventer) has remained one of the world’s rarest and least understood amphibian species. Together with its apparently low dispersal capability and highly disturbed niche, the low abundance of this living fossil calls for urgent conservation measures. We used 18 newly developed microsatellite loci and four different models to calculate the effective population size (Ne) of a total of 125 Hula painted frog individuals sampled at a single location. We compare the Ne estimates to the estimates of potentially reproducing adults in this population (Nad) determined through a capture-recapture study on 118 adult Hula painted frogs captured at the same site. Surprisingly, our data suggests that, despite Nad estimates of only ~234–244 and Ne estimates of ~16.6–35.8, the species appears to maintain a very high genetic diversity (HO = 0.771) and low inbreeding coefficient (FIS = −0.018). This puzzling outcome could perhaps be explained by the hypotheses of either genetic rescue from one or more unknown Hula painted frog populations nearby or by recent admixture of genetically divergent subpopulations. Independent of which scenario is correct, the original locations of these populations still remain to be determined.
NIPTmer: rapid k-mer-based software package for detection of fetal aneuploidies
Authors: Sauk Martin , Žilina Olga , Kurg Ants , Ustav Eva-Liina , Peters Maire , Paluoja Priit , Roost Anne Mari , Teder Hindrek , Palta Priit , Brison Nathalie , Vermeesch Joris R. , Krjutškov Kaarel , Salumets Andres , Kaplinski Lauris 
Published: March 2018

AbstractNon-invasive prenatal testing (NIPT) is a recent and rapidly evolving method for detecting genetic lesions, such as aneuploidies, of a fetus. However, there is a need for faster and cheaper laboratory and analysis methods to make NIPT more widely accessible. We have developed a novel software package for detection of fetal aneuploidies from next-generation low-coverage whole genome sequencing data. Our tool – NIPTmer – is based on counting pre-defined per-chromosome sets of unique k-mers from raw sequencing data, and applying linear regression model on the counts. Additionally, the filtering process used for k-mer list creation allows one to take into account the genetic variance in a specific sample, thus reducing the source of uncertainty. The processing time of one sample is less than 10 CPU-minutes on a high-end workstation. NIPTmer was validated on a cohort of 583 NIPT samples and it correctly predicted 37 non-mosaic fetal aneuploidies. NIPTmer has the potential to reduce significantly the time and complexity of NIPT post-sequencing analysis compared to mapping-based methods. For non-commercial users the software package is freely available at http://bioinfo.ut.ee/NIPTMer/.
Blocking distinct interactions between Glioblastoma cells and their tissue microenvironment: A novel multi-targeted therapeutic approach
Authors: Mettang Melanie , Meyer-Pannwitt Viola , Karpel-Massler Georg , Zhou Shaoxia , Carragher Neil O. , Föhr Karl Josef , Baumann Bernd , Nonnenmacher Lisa , Enzenmüller Stefanie , Dahlhaus Meike , Siegelin Markus D. , Stroh Sebastien , Mertens Daniel , Fischer-Posovszky Pamela , Schneider E. Marion , Halatsch Marc-Eric , Debatin Klaus-Michael , Westhoff Mike-Andrew 
Published: March 2018

AbstractDue to the highly invasive nature of Glioblastoma (GB), complete surgical resection is not feasible, while motile tumour cells are often associated with several specific brain structures that enhance treatment-resistance. Here, we investigate the therapeutic potential of Disulfiram and Carbenoxolone, that inhibit two distinct interactions between GB and the brain tissue microenvironment: stress-induced cell-matrix adhesion and gap junction mediated cell-cell communication, respectively. Increase in cell numbers of tumour-initiating cells, which are cultured in suspension as cell clusters, and adherent differentiated cells can be blocked to a similar extent by Carbenoxolone, as both cell populations form gap junctions, but the adherent differentiated cells are much more sensitive to Disulfiram treatment, which – via modulation of NF-κB signalling – interferes with cell-substrate adhesion. Interestingly, inducing adhesion in tumour-initiating cells without differentiating them does not sensitize for Disulfiram. Importantly, combining Disulfiram, Carbenoxolone and the standard chemotherapeutic drug Temozolomide reduces tumour size in an orthotopic mouse model. Isolating GB cells from their direct environment within the brain represents an important addition to current therapeutic approaches. The blockage of cellular interactions via the clinically relevant substances Disulfiram and Carbenoxolone, has distinct effects on different cell populations within a tumour, potentially reducing motility and/or resistance to apoptosis.