bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular characterization of Wdr13 knockout female mice uteri: a model for human endometrial hyperplasia
Authors: Singh Shalu , Pavuluri Sivapriya , Jyothi Lakshmi B. , Biswa Bhim B. , Venkatachalam Bharathi , Tripura Chaturvedula , Kumar Satish 
Published: September 2020

AbstractEndometrial hyperplasia (EH) is a condition where uterine endometrial glands show excessive proliferation of epithelial cells that may subsequently progress into endometrial cancer (EC). Modern lifestyle disorders such as obesity, hormonal changes and hyperinsulinemia are known risk factors for EH. A mouse strain that mimics most of these risk factors would be an ideal model to study the stage-wise progression of EH disease and develop suitable treatment strategies. Wdr13, an X-linked gene, is evolutionarily conserved and expressed in several tissues including uteri. In the present study, Wdr13 knockout female mice developed benign proliferative epithelium that progressed into EH at around one year of age accompanied by an increase in body weight and elevated estradiol levels. Molecular characterization studies revealed increase in ERα, PI3K and a decrease in PAX2 and ERβ proteins in Wdr13 mutant mice uteri. Further, a decrease in the mRNA levels of cell cycle inhibitors, namely; p21 and cyclin G2 was seen. Leukocyte infiltration was observed in the uterine tissue of knockout mice at around 12 months of age. These physiological, molecular and pathological patterns were similar to those routinely seen in human EH disease and demonstrated the importance of WDR13 in mice uterine tissue. Thus, the genetic loss of Wdr13 in these mice led to mimicking of the human EH associated metabolic disorders making Wdr13 knockout female mice a potential animal model to study human endometrial hyperplasia.
Liquid/solution-based microfluidic quantum dots light-emitting diodes for high-colour-purity light emission
Authors: Kawamura Masahiro , Kuwae Hiroyuki , Kamibayashi Takumi , Oshima Juro , Kasahara Takashi , Shoji Shuichi , Mizuno Jun 
Published: September 2020

AbstractOrganic light-emitting diodes (OLEDs) using a liquid organic semiconductor (LOS) are expected to provide extremely flexible displays. Recently, microfluidic OLEDs were developed to integrate and control a LOS in a device combined with microfluidic technology. However, LOS-based OLEDs show poor-colour-purity light emissions owing to their wide full width at half maximum (FWHM). Here we report liquid/solution-based microfluidic quantum dots light-emitting diodes (QLEDs) for high-colour-purity light emission. Microfluidic QLEDs contain liquid materials of LOS for a backlight and QDs solutions as luminophores. The microfluidic QLED exhibits red, green, and blue light emissions and achieves the highest light colour purity ever reported among LOS-based devices for green and red lights with narrow FWHMs of 26.2 nm and 25.0 nm, respectively. Additionally, the effect of the channel depth for the luminophore on the peak wavelength and FWHM is revealed. The developed device extends the capabilities of flexible microfluidic OLEDs-based and QDs-based displays.
DEP-Dots for 3D cell culture: low-cost, high-repeatability, effective 3D cell culture in multiple gel systems
Authors: Henslee Erin A. , Dunlop Carina M. , de Mel Christine M. , Carter Emily A. , Abdallat Rula G. , Camelliti Patrizia , Labeed Fatima H. 
Published: September 2020

AbstractIt is known that cells grown in 3D are more tolerant to drug treatment than those grown in dispersion, but the mechanism for this is still not clear; cells grown in 3D have opportunities to develop inter-cell communication, but are also closely packed which may impede diffusion. In this study we examine methods for dielectrophoresis-based cell aggregation of both suspension and adherent cell lines, and compare the effect of various drugs on cells grown in 3D and 2D. Comparing viability of pharmacological interventions on 3D cell clusters against both suspension cells and adherent cells grown in monolayer, as well as against a unicellular organism with no propensity for intracellular communication, we suggest that 3D aggregates of adherent cells, compared to suspension cells, show a substantially different drug response to cells grown in monolayer, which increases as the IC50is approached. Further, a mathematical model of the system for each agent demonstrates that changes to drug response are due to inherent changes in the system of adherent cells from the 2D to 3D state. Finally, differences in the electrophysiological membrane properties of the adherent cell type suggest this parameter plays an important role in the differences found in the 3D drug response.
An ossifying bridge – on the structural continuity between the Achilles tendon and the plantar fascia
Authors: Zwirner Johann , Zhang Ming , Ondruschka Benjamin , Akita Keichi , Hammer Niels 
Published: September 2020

AbstractHighly regular aligned trabeculae are found in the superficial posterior and inferior calcaneus appearing to connect the Achilles tendon (AT) to the plantar fascia (PF) in a bridge-like manner. This provides a morphological basis for the stretching-based heel pain treatment. However, the continuity of collagen fibres between the AT and the PF remains debated controversially to date. The given study morphologically investigated the AT-calcaneus-PF complex using histology and plastination. Moreover, the AT-calcaneus-PF complex was biomechanically mapped based on 13 sub-regions with a total of 76 tested samples. Regular calcaneal trabeculae were surrounded by tendon-like collagen fibre bundles and adipocytes. The orientation of calcaneal trabeculae was further closely related to the course of the PF collagen fibre bundles. The pooled biomechanical analysis revealed low elastic moduli (minimum = 4 MPa) and ultimate tensile strengths of the decalcified calcaneal samples (minimum = 0.4 MPa) and the calcaneal periostea (minimum = 2 MPa) and high respective values (elastic modulus maximum of 144 MPa; ultimate tensile strength maximum of 29 MPa) for the PF samples compared to the other sub-regions. This study provides structural evidence for a morphological connection between the AT and PF via the highly aligned calcaneal trabeculae of the posterior calcaneus. The AT-calcaneus-PF complex was biomechanically mapped to allow for an assessment of its site-dependent mechanical characteristics.
Insufficiently complex unique-molecular identifiers (UMIs) distort small RNA sequencing
Authors: Saunders Klay , Bert Andrew G. , Dredge B. Kate , Toubia John , Gregory Philip A. , Pillman Katherine A. , Goodall Gregory J. , Bracken Cameron P. 
Published: September 2020

AbstractThe attachment of unique molecular identifiers (UMIs) to RNA molecules prior to PCR amplification and sequencing, makes it possible to amplify libraries to a level that is sufficient to identify rare molecules, whilst simultaneously eliminating PCR bias through the identification of duplicated reads. Accurate de-duplication is dependent upon a sufficiently complex pool of UMIs to allow unique labelling. In applications dealing with complex libraries, such as total RNA-seq, only a limited variety of UMIs are required as the variation in molecules to be sequenced is enormous. However, when sequencing a less complex library, such as small RNAs for which there is a more limited range of possible sequences, we find increased variation in UMIs are required, even beyond that provided in a commercial kit specifically designed for the preparation of small RNA libraries for sequencing. We show that a pool of UMIs randomly varying across eight nucleotides is not of sufficient depth to uniquely tag the microRNAs to be sequenced. This results in over de-duplication of reads and the marked under-estimation of expression of the more abundant microRNAs. Whilst still arguing for the utility of UMIs, this work demonstrates the importance of their considered design to avoid errors in the estimation of gene expression in libraries derived from select regions of the transcriptome or small genomes.
hADSCs derived extracellular vesicles inhibit NLRP3inflammasome activation and dry eye
Authors: Yu Chaoqun , Chen Peng , Xu Jing , Liu Yaning , Li Hui , Wang Linna , Di Guohu 
Published: September 2020

AbstractThe present study was set out to address the therapeutic efficacy of human adipose tissue stem cells derived extracellular vesicles (hADSC-Evs) in a mouse model of dry eye disease and to investigate the underlying mechanisms involved. hADSC-Evs eye drops were topically administered to mice that subjected to desiccating stress (DS). Clinical parameters of ocular surface damage were assessed with fluorescein staining, tear production and PAS staining. For in vitro studies, cell viability assay and TUNEL staining were performed in human corneal epithelial cells (HCECs) treated with hADSC-Evs under hyperosmotic media. In addition, immunofluorescent staining, Real-time PCR (qRT-PCR) and Western blots were used to evaluated NLRP3, ASC, caspase-1, and IL-1β expression levels. Compared with vehicle control mice, topical hADSC-Evs treated mice showed decreased corneal epithelial defects, increased tear production, decreased goblet cell loss, as well as reduced inflammatory cytokines production. In vitro, hADSC-Evs could protect HCECs against hyperosmotic stress-induced cell apoptosis. Mechanistically, hADSC-Evs treatment suppressed the DS induced rises in NLRP3 inflammasome formation, caspase-1 activation and IL-1β maturation. In conclusion, hADSC-Evs eye drops effectively suppress NLRP3 inflammatory response and alleviate ocular surface damage in dry eye disease.
Exploring the relationship between air pollution and meteorological conditions in China under environmental governance
Authors: Liu Yansui , Zhou Yang , Lu Jiaxin 
Published: September 2020

AbstractExtensive studies have been carried out on the impact of human activities on air pollution, but systematic investigation on the relationship between air pollutant and meteorological conditions is still insufficient, especially in the context of China’s site scale and recent comprehensive environmental pollution control. Here, we used a spatial interpolation technology to establish a set of data sets of pollutants and meteorological elements that are spatially matched at 896 stations in China to reveal the air pollutant-meteorological interactions between 2014 and 2019. We found that air pollution and meteorological elements have obvious seasonal and regional characteristics. Over the last few years, the concentration of most air pollutants in China has dropped significantly except for O3. The increase in O3 concentration was closely related to the decrease of particulate matter and NO2 concentration. The concentration of most air pollutants was affected by meteorological conditions, but the level of impact depended on the type of pollutants and varied across regions. The concentration of air pollutants at most stations was significantly negatively correlated with wind speed, precipitation and relative humidity, but positively correlated with atmospheric pressure. As the latitude increases, the impact of temperature on the concentration of air pollutants becomes more obvious. To effectively control air pollution, it is further urgent to reveal the relationship between air pollution and meteorological conditions based on long-term daily or real-time data.
Sedative drugs modulate the neuronal activity in the subthalamic nucleus of parkinsonian patients
Authors: Benady Amit , Zadik Sean , Eimerl Dan , Heymann Sami , Bergman Hagai , Israel Zvi , Raz Aeyal 
Published: September 2020

AbstractMicroelectrode recording (MER) is often used to identify electrode location which is critical for the success of deep brain stimulation (DBS) treatment of Parkinson’s disease. The usage of anesthesia and its’ impact on MER quality and electrode placement is controversial. We recorded neuronal activity at a single depth inside the Subthalamic Nucleus (STN) before, during, and after remifentanil infusion. The root mean square (RMS) of the 250–6000 Hz band-passed signal was used to evaluate the regional spiking activity, the power spectrum to evaluate the oscillatory activity and the coherence to evaluate synchrony between two microelectrodes. We compare those to new frequency domain (spectral) analysis of previously obtained data during propofol sedation. Results showed Remifentanil decreased the normalized RMS by 9% (P < 0.001), a smaller decrease compared to propofol. Regarding the beta range oscillatory activity, remifentanil depressed oscillations (drop from 25 to 5% of oscillatory electrodes), while propofol did not (increase from 33.3 to 41.7% of oscillatory electrodes). In the cases of simultaneously recorded oscillatory electrodes, propofol did not change the synchronization while remifentanil depressed it. In conclusion, remifentanil interferes with the identification of the dorsolateral oscillatory region, whereas propofol interferes with RMS identification of the STN borders. Thus, both have undesired effect during the MER procedure.Trial registration: NCT00355927 and NCT00588926.
Ontological approach to the knowledge systematization of a toxic process and toxic course representation framework for early drug risk management
Authors: Yamagata Yuki , Yamada Hiroshi 
Published: September 2020

AbstractVarious types of drug toxicity can halt the development of a drug. Because drugs are xenobiotics, they inherently have the potential to cause injury. Clarifying the mechanisms of toxicity to evaluate and manage drug safety during drug development is extremely important. However, toxicity mechanisms, especially hepatotoxic mechanisms, are very complex. The significant exposure of liver cells to drugs can cause dysfunction, cell injury, and organ failure in the liver. To clarify potential risks in drug safety management, it is necessary to systematize knowledge from a consistent viewpoint. In this study, we adopt an ontological approach. Ontology provides a controlled vocabulary for sharing and reusing of various data with a computer-friendly manner. We focus on toxic processes, especially hepatotoxic processes, and construct the toxic process ontology (TXPO). The TXPO systematizes knowledge concerning hepatotoxic courses with consistency and no ambiguity. In our application study, we developed a toxic process interpretable knowledge system (TOXPILOT) to bridge the gaps between basic science and medicine for drug safety management. Using semantic web technology, TOXPILOT supports the interpretation of toxicity mechanisms and provides visualizations of toxic courses with useful information based on ontology. Our system will contribute to various applications for drug safety evaluation and management.
Body dimensions of the extinct giant shark Otodus megalodon: a 2D reconstruction
Authors: Cooper Jack A. , Pimiento Catalina , Ferrón Humberto G. , Benton Michael J. 
Published: September 2020

AbstractInferring the size of extinct animals is fraught with danger, especially when they were much larger than their modern relatives. Such extrapolations are particularly risky when allometry is present. The extinct giant shark †Otodus megalodonis known almost exclusively from fossilised teeth. Estimates of †O. megalodonbody size have been made from its teeth, using the great white shark (Carcharodon carcharias) as the only modern analogue. This can be problematic as the two species likely belong to different families, and the position of the †Otoduslineage within Lamniformes is unclear. Here, we infer †O. megalodonbody dimensions based on anatomical measurements of five ecologically and physiologically similar extant lamniforms:Carcharodon carcharias,Isurus oxyrinchus,Isurus paucus,Lamna ditropisandLamna nasus. We first assessed for allometry in all analogues using linear regressions and geometric morphometric analyses. Finding no evidence of allometry, we made morphological extrapolations to infer body dimensions of †O. megalodonat different sizes. Our results suggest that a 16 m †O. megalodonlikely had a head ~ 4.65 m long, a dorsal fin ~ 1.62 m tall and a tail ~ 3.85 m high. Morphometric analyses further suggest that its dorsal and caudal fins were adapted for swift predatory locomotion and long-swimming periods.
QSPR models for predicting the adsorption capacity for microplastics of polyethylene, polypropylene and polystyrene
Authors: Li Miao , Yu Haiying , Wang Yifei , Li Jiagen , Ma Guangcai , Wei Xiaoxuan 
Published: September 2020

AbstractMicroplastics have become an emerging concerned global environmental pollution problem. Their strong adsorption towards the coexisting organic pollutants can cause additional environmental risks. Therefore, the adsorption capacity and mechanisms are necessary information for the comprehensive environmental assessments of both microplastics and organic pollutants. To overcome the lack of adsorption information, five quantitative structure–property relationship (QSPR) models were developed for predicting the microplastic/water partition coefficients (log Kd) of organics between polyethylene/seawater, polyethylene/freshwater, polyethylene/pure water, polypropylene/seawater, and polystyrene/seawater. All the QSPR models show good fitting ability (R2 = 0.811–0.939), predictive ability (Q2ext = 0.835–0.910, RMSEext = 0.369–0.752), and robustness (Qcv2 = 0.882–0.957). They can be used to predict the Kd values of organic pollutants (such as polychlorinated biphenyls, chlorobenzene, polycyclic aromatic hydrocarbons, antibiotics perfluorinated compounds, etc.) under different pH conditions. The hydrophobic interaction has been indicated as an important mechanism for the adsorption of organic pollutants to microplastics. In sea waters, the role of hydrogen bond interaction in adsorption is considerable. For polystyrene, π–π interaction contributes to the partitioning. The developed models can be used to quickly estimate the adsorption capacity of organic pollutants on microplastics in different types of water, providing necessary information for ecological risk studies of microplastics.
AVPR1A distribution in the whole C57BL/6J mouse neonate
Authors: Day Katherine R. , Coleman Alexis , Greenwood Maria A. , Hammock Elizabeth A. D. 
Published: September 2020

AbstractThe neuropeptide arginine vasopressin (AVP) plays significant roles in maintaining homeostasis and regulating social behavior. In vaginally delivered neonates, a surge of AVP is released into the bloodstream at levels exceeding release during life-threatening conditions such as hemorrhagic shock. It is currently unknown where the potential sites of action are in the neonate for these robust levels of circulating AVP at birth. The purpose of this study is to identify the location of AVP receptor 1a (AVPR1A) sites as potential peripheral targets of AVP in the neonatal mouse. RT-qPCR analysis of a sampling of tissues from the head demonstrated the presence ofAvpr1amRNA, suggesting local peripheral translation. Using competitive autoradiography in wildtype (WT) and AVPR1A knockout (KO) postnatal day 0 (P0) male and female mice on a C57BL/6J background, specific AVPR1A ligand binding was observed in the neonatal mouse periphery in sensory tissues of the head (eyes, ears, various oronasal regions), bone, spinal cord, adrenal cortex, and the uro-anogenital region in the neonatal AVPR1A WT mouse, as it was significantly reduced or absent in the control samples (AVPR1A KO and competition). AVPR1A throughout the neonatal periphery suggest roles for AVP in modulating peripheral physiology and development of the neonate.
Mitochondrial genomes illuminate the evolutionary history of the Western honey bee (Apis mellifera)
Authors: Tihelka Erik , Cai Chenyang , Pisani Davide , Donoghue Philip C. J. 
Published: September 2020

AbstractWestern honey bees (Apis mellifera) are one of the most important pollinators of agricultural crops and wild plants. Despite the growth in the availability of sequence data for honey bees, the phylogeny of the species remains a subject of controversy. Most notably, the geographic origin of honey bees is uncertain, as are the relationships among its constituent lineages and subspecies. We aim to infer the evolutionary and biogeographical history of the honey bee from mitochondrial genomes. Here we analyse the full mitochondrial genomes of 18A. melliferasubspecies, belonging to all major lineages, using a range of gene sampling strategies and inference models to identify factors that may have contributed to the recovery of incongruent results in previous studies. Our analyses support a northern African or Middle Eastern origin ofA. mellifera. We show that the previously suggested European and Afrotropical cradles of honey bees are the result of phylogenetic error. Monophyly of the M, C, and O lineages is strongly supported, but the A lineage appears paraphyletic.A. melliferacolonised Europe through at least two pathways, across the Strait of Gibraltar and via Asia Minor.
Partitioned gradient-index phononic crystals for full phase control
Authors: Hyun Jaeyub , Kim Miso , Choi Wonjae 
Published: September 2020

AbstractGradient-index phononic crystals (GRIN-PC), characterized by layers with spatially changing refractive indices, have recently been investigated as part of the effort to realize flat lenses in acoustic and elastic regimes. Such gradient-index lens must be inversely designed from the corresponding refractive indices in order to manipulate the target wave. Unfortunately, estimating the index of this type of lens is not straightforward and requires substantial iterative computation in general, which greatly limits the applicability of GRIN-PC to flat lenses. In this work, we propose a novel design of a GRIN-PC in which neighboring layers are separated by partitions, thus preventing waves in each layer from interacting with other layers. This partitioned GRIN-PC design enables us readily to control the phase gradient accurately at the lens’ end, resulting in direct calculation of indices for target wave manipulation. A detailed methodology for partitioned GRIN-PC based collimator and Bessel-beam generator is proposed and experimentally validated to confirm the versatile use of our design in wave engineering applications.
RFX5 promotes the progression of hepatocellular carcinoma through transcriptional activation of KDM4A
Authors: Chen Dong-Bo , Xie Xing-Wang , Zhao Yang-Jing , Wang Xue-Yan , Liao Wei-Jia , Chen Pu , Deng Kang-Jian , Fei Ran , Qin Wan-Ying , Wang Jiang-Hua , Wu Xu , Shao Qi-Xiang , Wei Lai , Chen Hong-Song 
Published: September 2020

AbstractRegulatory factor X-5 (RFX5) represents a key transcription regulator of MHCII gene expression in the immune system. This study aims to explore the molecular mechanisms and biological significance of RFX5. Firstly, by analyzing ENCODE chromatin immunoprecipitation (ChIP)-seq in HepG2 and TCGA RNA-seq data, we discovered lysine-specific demethylase 4A (KDM4A), also named JMJD2A, to be a major downstream target gene of RFX5. Moreover, RFX5 was verified to bind directly to the KDM4A’s promoter region and sequentially promoted its transcription determined by the ChIP-PCR assay and luciferase assay. In addition, RFX5-dependent regulation of KDM4A was demonstrated in HCC. Compared with adjacent non-tumor tissues, the expression levels of KDM4A were significantly raised in HCC tumor tissues. Notably, elevated levels of KDM4A were strongly correlated with HCC patient prognosis. Functionally, KDM4A overexpression largely rescued the growth inhibitory effects of RFX5 deletion, highlighting KDM4A as a downstream effector of RFX5. Mechanistically, the RFX5-KDM4A pathway promoted the progression of the cell cycle from G0/G1 to S phase and was protective against cell apoptosis through regulation of p53 and its downstream genes in HCC. In conclusion, RFX5 could promote HCC progression via transcriptionally activating KDM4A expression.