bluuebunny/crossref_metadata_2025_split huggingface dataset:
Induction of a local muscular dystrophy using electroporation in vivo: an easy tool for screening therapeutics
Authors: Derenne Aline , Tassin Alexandra , Nguyen Thuy Hang , De Roeck Estelle , Jenart Vincianne , Ansseau Eugénie , Belayew Alexandra , Coppée Frédérique , Declèves Anne-Emilie , Legrand Alexandre 
Published: July 2020

AbstractIntramuscular injection and electroporation of naked plasmid DNA (IMEP) has emerged as a potential alternative to viral vector injection for transgene expression into skeletal muscles. In this study, IMEP was used to express the DUX4 gene into mouse tibialis anterior muscle. DUX4 is normally expressed in germ cells and early embryo, and silenced in adult muscle cells where its pathological reactivation leads to Facioscapulohumeral muscular dystrophy. DUX4 encodes a potent transcription factor causing a large deregulation cascade. Its high toxicity but sporadic expression constitutes major issues for testing emerging therapeutics. The IMEP method appeared as a convenient technique to locally express DUX4 in mouse muscles. Histological analyses revealed well delineated muscle lesions 1-week after DUX4 IMEP. We have therefore developed a convenient outcome measure by quantification of the damaged muscle area using color thresholding. This method was used to characterize lesion distribution and to assess plasmid recirculation and dose–response. DUX4 expression and activity were confirmed at the mRNA and protein levels and through a quantification of target gene expression. Finally, this study gives a proof of concept of IMEP model usefulness for the rapid screening of therapeutic strategies, as demonstrated using antisense oligonucleotides against DUX4 mRNA.
Adaptive time scales in recurrent neural networks
Authors: Quax Silvan C. , D’Asaro Michele , van Gerven Marcel A. J. 
Published: July 2020

AbstractRecent experiments have revealed a hierarchy of time scales in the visual cortex, where different stages of the visual system process information at different time scales. Recurrent neural networks are ideal models to gain insight in how information is processed by such a hierarchy of time scales and have become widely used to model temporal dynamics both in machine learning and computational neuroscience. However, in the derivation of such models as discrete time approximations of the firing rate of a population of neurons, the time constants of the neuronal process are generally ignored. Learning these time constants could inform us about the time scales underlying temporal processes in the brain and enhance the expressive capacity of the network. To investigate the potential of adaptive time constants, we compare the standard approximations to a more lenient one that accounts for the time scales at which processes unfold. We show that such a model performs better on predicting simulated neural data and allows recovery of the time scales at which the underlying processes unfold. A hierarchy of time scales emerges when adapting to data with multiple underlying time scales, underscoring the importance of such a hierarchy in processing complex temporal information.
Non-backtracking walks reveal compartments in sparse chromatin interaction networks
Authors: Polovnikov K. , Gorsky A. , Nechaev S. , Razin S. V. , Ulianov S. V. 
Published: July 2020

AbstractChromatin communities stabilized by protein machinery play essential role in gene regulation and refine global polymeric folding of the chromatin fiber. However, treatment of these communities in the framework of the classical network theory (stochastic block model, SBM) does not take into account intrinsic linear connectivity of the chromatin loci. Here we propose the polymer block model, paving the way for community detection in polymer networks. On the basis of this new model we modify the non-backtracking flow operator and suggest the first protocol for annotation of compartmental domains in sparse single cell Hi-C matrices. In particular, we prove that our approach corresponds to the maximum entropy principle. The benchmark analyses demonstrates that the spectrum of the polymer non-backtracking operator resolves the true compartmental structure up to the theoretical detectability threshold, while all commonly used operators fail above it. We test various operators on real data and conclude that the sizes of the non-backtracking single cell domains are most close to the sizes of compartments from the population data. Moreover, the found domains clearly segregate in the gene density and correlate with the population compartmental mask, corroborating biological significance of our annotation of the chromatin compartmental domains in single cells Hi-C matrices.
Temporal variations in ambient air quality indicators in Shanghai municipality, China
Authors: Chen Yuanyuan , Bai Yang , Liu Hongtao , Alatalo Juha M. , Jiang Bo 
Published: July 2020

AbstractOfficial data on daily PM2.5, PM10, SO2, NO2, CO, and maximum 8-h average O3 (O3_8h) concentrations from January 2015 to December 2018 were evaluated and air pollution status and dynamics in Shanghai municipality were examined. Factors affecting air quality, including meteorological factors and socio-economic indicators, were analyzed. The main findings were that: (1) Overall air quality status in Shanghai municipality has improved and number of days meeting ‘Chinese ambient air quality standards’ (CAAQS) Grade II has increased. (2) The most frequent major pollutant in Shanghai municipality is O3 (which exceeded the standard on 110 days in 2015, 84 days in 2016, 126 days in 2017, 113 days in 2018), followed by PM2.5 (120days in 2015, 104 days in 2016, 67 days in 2017, 61 days in 2018) and NO2 (50 days in 2015, 67 days in 2016, 79 days in 2017, 63 days in 2018). (3) PM2.5 pollution in winter and O3 pollution in summer are the main air quality challenges in Shanghai municipality. (4) Statistical analysis suggested that PM2.5, PM10, SO2 and NO2 concentrations were significantly negatively associated with precipitation (Prec) and atmosphere temperature (T) (p < 0.05), while the O3 concentration was significantly positively associated with Prec and T (p < 0.05). Lower accumulation of PM, SO2, NO2, and CO and more serious O3 pollution were revealed during months with higher temperature and more precipitation in Shanghai. The correlation between the socio-economic factors and the air pollutants suggest that further rigorous measures are needed to control PM2.5 and that further studies are needed to identify O3 formation mechanisms and control strategies. The results provide scientific insights into meteorological factors and socio-economic indicators influencing air pollution in Shanghai.
An exploratory cross-sectional study of subclinical vascular damage in patients with polymyalgia rheumatica
Authors: Scrivo Rossana , Silvestri Valeria , Ciciarello Francesco , Sessa Paola , Rutigliano Iolanda , Sestili Cristina , La Torre Giuseppe , Barbati Cristiana , Altobelli Alessio , Alessandri Cristiano , Ceccarelli Fulvia , Di Franco Manuela , Priori Roberta , Riccieri Valeria , Sili Scavalli Antonio , Spinelli Francesca Romana , Agati Luciano , Fedele Francesco , Gossetti Bruno , Conti Fabrizio , Valesini Guido 
Published: July 2020

AbstractThe aim of the study was to investigate the presence of subclinical vascular damage in polymyalgia rheumatica (PMR). We enrolled PMR patients having major cardiovascular risk factors (MCVRF) and, as controls, patients with MCVRF. All underwent: color Doppler ultrasound to evaluate the common carotid intima-media thickness (IMT), the anterior–posterior abdominal aortic diameter (APAD), and the prevalence of carotid artery stenosis; the cardio-ankle vascular index (CAVI) to measure arterial stiffness together with the ankle-brachial index (ABI) to investigate the presence of lower-extremity peripheral arterial disease. Finally, we measured the serum levels of adipocytokines implicated in vascular dysfunction. As a result, 48 PMR and 56 MCVRF patients were included. An increase of IMT (1.07/0.8–1.2 vs 0.8/0.8–1.05; p = 0.0001), CAVI (8.7/7.8–9.3 vs 7.6/6.9–7.8; p < 0.0001) and APAD values (21.15/18.1–25.6 vs 18/16–22; p = 0.0013) was found in PMR patients with respect to controls. No differences were reported in the prevalence of carotid artery stenosis or ABI values between the two groups. A significant correlation between IMT and CAVI in PMR and MCVRF subjects (r2 = 0.845 and r2 = 0.556, respectively; p < 0.01) was found. Leptin levels (pg/mL; median/25th–75th percentile) were higher in PMR than in MCVRF subjects (145.1/67–398.6 vs 59.5/39.3–194.3; p = 0.04). Serum levels of adiponectin (ng/mL) were higher in PMR patients (15.9/10.65–24.1 vs 6.1/2.8–22.7; p = 0.01), while no difference in serum levels of resistin (ng/mL) was found between PMR and MCVRF subjects (0.37/0.16–0.66 vs 0.26/0.14–1.24). Our study shows an increased subclinical vascular damage in PMR patients compared to those with MCVRF, paving the way for further studies aimed at planning primary cardiovascular prevention in this population.
Phosphorylation of steroid receptor coactivator-3 (SRC-3) at serine 857 is regulated by the p38MAPK-MK2 axis and affects NF-κB-mediated transcription
Authors: Shrestha Anup , Bruckmueller Henrike , Kildalsen Hanne , Kaur Gurjit , Gaestel Matthias , Wetting Hilde Ljones , Mikkola Ingvild , Seternes Ole-Morten 
Published: July 2020

AbstractSteroid receptor coactivator-3 (SRC-3) regulates the activity of both nuclear hormone receptors and a number of key transcription factors. It is implicated in the regulation of cell proliferation, inflammation and in the progression of several common cancers including breast, colorectal and lung tumors. Phosphorylation is an important regulatory event controlling the activities of SRC-3. Serine 857 is the most studied phospho-acceptor site, and its modification has been reported to be important for SRC-3-dependent tumor progression. In this study, we show that the stress-responsive p38MAPK-MK2 signaling pathway controls the phosphorylation of SRC-3 at S857 in a wide range of human cancer cells. Activation of the p38MAPK-MK2 pathway results in the nuclear translocation of SRC-3, where it contributes to the transactivation of NF-kB and thus regulation of IL-6 transcription. The identification of the p38MAPK-MK2 signaling axis as a key regulator of SRC-3 phosphorylation and activity opens up new possibilities for the development and testing of novel therapeutic strategies to control both proliferative and metastatic tumor growth.
Bioluminescence for in vivo detection of cell-type-specific inflammation in a mouse model of uveitis
Authors: John Sarah , Rolnick Kevin , Wilson Leslie , Wong Silishia , Van Gelder Russell N. , Pepple Kathryn L. 
Published: July 2020

AbstractThis study reports the use of cell-type-specific in vivo bioluminescence to measure intraocular immune cell population dynamics during the course of inflammation in a mouse model of uveitis. Transgenic lines expressing luciferase in inflammatory cell subsets (myeloid cells, T cells, and B cells) were generated and ocular bioluminescence was measured serially for 35 days following uveitis induction. Ocular leukocyte populations were identified using flow cytometry and compared to the ocular bioluminescence profile. Acute inflammation is neutrophilic (75% of ocular CD45 + cells) which is reflected by a significant increase in ocular bioluminescence in one myeloid reporter line on day 2. By day 7, the ocular T cell population increases to 50% of CD45 + cells, leading to a significant increase in ocular bioluminescence in the T cell reporter line. While initially negligible (< 1% of CD45 + cells), the ocular B cell population increases to > 4% by day 35. This change is reflected by a significant increase in the ocular bioluminescence of the B cell reporter line starting on day 28. Our data demonstrates that cell-type-specific in vivo bioluminescence accurately detects changes in multiple intraocular immune cell populations over time in experimental uveitis. This assay could also be useful in other inflammatory disease models.
Strain-induced topological phase transition with inversion of the in-plane electric polarization in tiny-gap semiconductor SiGe monolayer
Authors: Lee Kyu Won , Lee Cheol Eui 
Published: July 2020

AbstractOur density functional theory calculations show that tiny-gap semiconductor SiGe monolayer is a quantum valley Hall insulator with a spontaneous electric polarization and, under a small biaxial strain, undergoes a topological phase transition between the states with opposite valley Chern numbers. The topological phase transition entails abrupt inversion of the in-plane electric polarization corresponding to inversion of the sublattice pseudospin polarization, while the out-of-plane electric polarization shows a linear response to the biaxial strain as well as to the perpendicular electric field regardless of the phase transition. Thus, the quantum valley Hall state entails in-plane ferroelectricity corresponding to a sublattice pseudospin ferromagnetism.
Visibly constraining an agent modulates observers’ automatic false-belief tracking
Authors: Low Jason , Edwards Katheryn , Butterfill Stephen A. 
Published: July 2020

AbstractOur motor system can generate representations which carry information about the goals of another agent’s actions. However, it is not known whether motor representations play a deeper role in social understanding, and, in particular, whether they enable tracking others’ beliefs. Here we show that, for adult observers, reliably manifesting an ability to track another’s false belief critically depends on representing the agent’s potential actions motorically. One signature of motor representations is that they can be disrupted by constraints on an observed agent’s action capacities. We therefore used a ‘mummification’ technique to manipulate whether the agent in a visual ball-detection task was free to act or whether he was visibly constrained from acting. Adults’ reaction times reliably reflected the agent’s beliefs only when the agent was free to act on the ball and not when the agent was visibly constrained from acting. Furthermore, it was the agent’s constrained action capabilities, rather than any perceptual novelty, that determined whether adult observers’ reaction times reliably reflected the agent’s beliefs. These findings signal that our motor system may underpin more of social cognition than previously imagined, and, in particular, that motor representations may underpin automatic false-belief tracking.
Aging increases the systemic molecular degree of inflammatory perturbation in patients with tuberculosis
Authors: Oliveira-de-Souza Deivide , Vinhaes Caian L. , Arriaga María B. , Kumar Nathella Pavan , Queiroz Artur T. L. , Fukutani Kiyoshi F. , Babu Subash , Andrade Bruno B. 
Published: July 2020

AbstractTuberculosis (TB) is a chronic infection that can affect individuals of all ages. The description of determinants of immunopathogenesis in TB is of tremendous interest due to the perspective of finding a reliable host-directed therapy to reduce disease burden. The association between specific biomarker profiles related to inflammation and the diverse clinical disease presentations in TB has been extensively studied in adults. However, relatively scarce data on profiling the inflammatory responses in pediatric TB are available. Here, we employed the molecular degree of perturbation (MDP) score adapted to plasma biomarkers in two distinct databanks from studies that examined either adults or children presenting with pulmonary or extrapulmonary disease. We used multidimensional statistical analyses to characterize the impact of age on the overall changes in the systemic inflammation profiles in subpopulation of TB patients. Our findings indicate that TB results in significant increases in molecular perturbation, with the highest values being detected in adult patients. Furthermore, there were unique differences in the biomarker perturbation patterns and the overall degree of inflammation according to disease site and age. Importantly, the molecular degree of perturbation was not influenced by sex. Our results revealed that aging is an important determinant of the differences in quality and magnitude of systemic inflammatory perturbation in distinct clinical forms of TB.
Transcriptional repression of PTEN in neural cells using CRISPR/dCas9 epigenetic editing
Authors: Moses C. , Hodgetts S. I. , Nugent F. , Ben-Ary G. , Park K. K. , Blancafort P. , Harvey A. R. 
Published: July 2020

AbstractAfter damage to the adult mammalian central nervous system (CNS), surviving neurons have limited capacity to regenerate and restore functional connectivity. Conditional genetic deletion of PTEN results in robust CNS axon regrowth, while PTEN repression with short hairpin RNA (shRNA) improves regeneration but to a lesser extent, likely due to suboptimal PTEN mRNA knockdown using this approach. Here we employed the CRISPR/dCas9 system to repress PTEN transcription in neural cells. We targeted the PTEN proximal promoter and 5′ untranslated region with dCas9 fused to the repressor protein Krüppel-associated box (KRAB). dCas9-KRAB delivered in a lentiviral vector with one CRISPR guide RNA (gRNA) achieved potent and specific PTEN repression in human cell line models and neural cells derived from human iPSCs, and induced histone (H)3 methylation and deacetylation at the PTEN promoter. The dCas9-KRAB system outperformed a combination of four shRNAs targeting the PTEN transcript, a construct previously used in CNS injury models. The CRISPR system also worked more effectively than shRNAs for Pten repression in rat neural crest-derived PC-12 cells, and enhanced neurite outgrowth after nerve growth factor stimulation. PTEN silencing with CRISPR/dCas9 epigenetic editing may provide a new option for promoting axon regeneration and functional recovery after CNS trauma.
Therapeutic vaccine-mediated Gag-specific CD8+ T-cell induction under anti-retroviral therapy augments anti-virus efficacy of CD8+ cells in simian immunodeficiency virus-infected macaques
Authors: Nakamura-Hoshi Midori , Takahara Yusuke , Matsuoka Saori , Ishii Hiroshi , Seki Sayuri , Nomura Takushi , Yamamoto Hiroyuki , Sakawaki Hiromi , Miura Tomoyuki , Tokusumi Tsuyoshi , Shu Tsugumine , Matano Tetsuro 
Published: July 2020

AbstractAnti-retroviral therapy (ART) can inhibit HIV proliferation but not achieve virus eradication from HIV-infected individuals. Under ART-based HIV control, virus-specific CD8+ T-cell responses are often reduced. Here, we investigated the impact of therapeutic vaccination inducing virus-specific CD8+ T-cell responses under ART on viral control in a macaque AIDS model. Twelve rhesus macaques received ART from week 12 to 32 after simian immunodeficiency virus (SIV) infection. Six of them were vaccinated with Sendai virus vectors expressing SIV Gag and Vif at weeks 26 and 32, and Gag/Vif-specific CD8+ T-cell responses were enhanced and became predominant. All macaques controlled viremia during ART but showed viremia rebound after ART cessation. Analysis of in vitro CD8+ cell ability to suppress replication of autologous lymphocytes-derived SIVs found augmentation of anti-SIV efficacy of CD8+ cells after vaccination. In the vaccinated animals, the anti-SIV efficacy of CD8+ cells at week 34 was correlated positively with Gag-specific CD8+ T-cell frequencies and inversely with rebound viral loads at week 34. These results indicate that Gag-specific CD8+ T-cell induction by therapeutic vaccination can augment anti-virus efficacy of CD8+ cells, which may be insufficient for functional cure but contribute to more stable viral control under ART.
Deletion of TRPV4 enhances in vitro wound healing of murine esophageal keratinocytes
Authors: Boudaka Ammar , Saito Claire T. , Tominaga Makoto 
Published: July 2020

AbstractTransient receptor potential vanilloid 4 (TRPV4) is a non-selective cation channel that is widely expressed in different body tissues and plays several physiological roles. This channel is highly expressed in esophageal keratinocytes where its activation mediates ATP release. However, whether TRPV4 has a role in wound healing of esophageal keratinocytes is unclear. In this study, we demonstrated that both cell migration and proliferation were slower in wild-type esophageal keratinocytes compared to cells having TRPV4 knockout. Our results suggest that TRPV4-mediated release of ATP from esophageal keratinocytes contributes to a decrease in the rate of in vitro wound healing via the ATP degradation product adenosine, which acts on A2B adenosine receptors.
Prediction of malaria transmission drivers in Anopheles mosquitoes using artificial intelligence coupled to MALDI-TOF mass spectrometry
Authors: Nabet Cécile , Chaline Aurélien , Franetich Jean-François , Brossas Jean-Yves , Shahmirian Noémie , Silvie Olivier , Tannier Xavier , Piarroux Renaud 
Published: July 2020

AbstractVector control programmes are a strategic priority in the fight against malaria. However, vector control interventions require rigorous monitoring. Entomological tools for characterizing malaria transmission drivers are limited and are difficult to establish in the field. To predictAnophelesdrivers of malaria transmission, such as mosquito age, blood feeding andPlasmodiuminfection, we evaluated artificial neural networks (ANNs) coupled to matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry (MS) and analysed the impact on the proteome of laboratory-rearedAnopheles stephensimosquitoes. ANNs were sensitive toAnophelesproteome changes and specifically recognized spectral patterns associated with mosquito age (0–10 days, 11–20 days and 21–28 days), blood feeding andP. bergheiinfection, with best prediction accuracies of 73%, 89% and 78%, respectively. This study illustrates that MALDI-TOF MS coupled to ANNs can be used to predict entomological drivers of malaria transmission, providing potential new tools for vector control. Future studies must assess the field validity of this new approach in wild-caught adultAnopheles. A similar approach could be envisaged for the identification of blood meal source and the detection of insecticide resistance inAnophelesand to other arthropods and pathogens.
Interactive machine learning for soybean seed and seedling quality classification
Authors: de Medeiros André Dantas , Capobiango Nayara Pereira , da Silva José Maria , da Silva Laércio Junio , da Silva Clíssia Barboza , dos Santos Dias Denise Cunha Fernandes 
Published: July 2020

AbstractNew computer vision solutions combined with artificial intelligence algorithms can help recognize patterns in biological images, reducing subjectivity and optimizing the analysis process. The aim of this study was to propose an approach based on interactive and traditional machine learning methods to classify soybean seeds and seedlings according to their appearance and physiological potential. In addition, we correlated the appearance of seeds to their physiological performance. Images of soybean seeds and seedlings were used to develop models using low-cost approaches and free-access software. The models developed showed high performance, with overall accuracy reaching 0.94 for seeds and seedling classification. The high precision of the models that were developed based on interactive and traditional machine learning demonstrated that the method can easily be used to classify soybean seeds according to their appearance, as well as to classify soybean seedling vigor quickly and non-subjectively. The appearance of soybean seeds is strongly correlated with their physiological performance.