bluuebunny/crossref_metadata_2025_split huggingface dataset:
Atrogin1-induced loss of aquaporin 4 in myocytes leads to skeletal muscle atrophy
Authors: Chung Seok Won , Kim Ja-Yeon , Yoon Jong Pil , Suh Dong Won , Yeo Woo Jin , Lee Yong-Soo 
Published: August 2020

AbstractThe water channel aquaporin 4 (AQP4) regulates the flux of water across the cell membrane, maintaining cellular homeostasis. Since AQP4 is enriched in the sarcolemma of skeletal muscle, a functional defect in AQP4 may cause skeletal muscle dysfunction. To investigate a novel mechanism underlying skeletal muscle atrophy, we examined AQP4 expression and its regulation in muscle using the rotator cuff tear (RCT) model. Human and mouse AQP4 expression was significantly decreased in atrophied muscle resulting from RCT. The size and the number of myotubes were reduced following AQP4 knockdown. Atrogin 1-mediated ubiquitination of AQP4 was verified with an ubiquitination assay after immunoprecipitation of AQP4 with an anti-AQP4 antibody. In this study, we identified high mobility group box 1 (HMGB1) as a potent upstream regulator of atrogin 1 expression. Atrogin 1 expression was increased by recombinant mouse HMGB1 protein, and the HMGB1-induced atrogin 1 expression was mediated via NF-κB signaling. Our study suggests that loss of AQP4 appears to be involved in myocyte shrinkage after RCT, and its degradation is mediated by atrogin 1-dependent ubiquitination. HMGB1, in its function as a signaling molecule upstream of the ubiquitin ligase atrogin 1, was found to be a novel regulator of muscle atrophy.
Whole transcriptome analysis of bovine mammary progenitor cells by P-Cadherin enrichment as a marker in the mammary cell hierarchy
Authors: Martignani E. , Ala U. , Sheehy P. A. , Thomson P. C. , Baratta M. 
Published: August 2020

AbstractAdult bovine mammary stem cells possess the ability to regenerate in vivo clonal outgrowths that mimic functional alveoli. Commonly available techniques that involve immunophenotype-based cell sorting yield cell fractions that are moderately enriched, far from being highly purified. Primary bovine mammary epithelial cells segregated in four different populations according to the expression of P-Cadherin and CD49f. Sorted cells from each fraction were tested for the presence of lineage-restricted progenitors and stem cells. Only cells from the CD49fhigh/P-Cadherinnegsubpopulation were able to give rise to both luminal- and myoepithelial-restricted colonies in vitro and generate organized outgrowths in vivo, which are hallmarks of stem cell activity. After whole transcriptome analysis, we found gene clusters to be differentially enriched that relate to cell-to-cell communication, metabolic processes, proliferation, migration and morphogenesis. When we analyzed only the genes that were differentially expressed in the stem cell enriched fraction, clusters of downregulated genes were related to proliferation, while among the upregulated expression, cluster of genes related to cell adhesion, migration and cytoskeleton organization were observed. Our results show that P-Cadherin separates mammary subpopulations differentially in progenitor cells or mammary stem cells. Further we provide a comprehensive observation of the gene expression differences among these cell populations which reinforces the assumption that bovine mammary stem cells are typically quiescent.
MiR-940 promotes malignant progression of breast cancer by regulating FOXO3
Authors: Zhang Huayao , Peng Jingwen , Lai Jianguo , Liu Haiping , Zhang Zhiyuan , Li Xiangdi , Liang Baozhen , Chen Xuejun , Zou Baojia , Lin Siyuan , Zhang Lihua 
Published: August 2020

Abstract
Breast cancer (BC) is a common cancer with poor survival. The present study aimed to explore the effect of miR-940 on the process of BC cells and its target gene FOXO3. The expression of miR-940 was assessed in BC tissues and cells using qRT-PCR. Furthermore, the correlation between miR-940 and prognosis of BC patients from the TCGA database was analyzed. CCK8 assays and colony formation assays were used to explore the effect of miR-940 on BC cell proliferation. The invasion abilities were detected by transwell assays. Luciferase reporter assay was performed to scrutinize the relationship between miR-940 and FOXO3. Finally, rescue experiments were performed through FOXO3 down-regulation and miR-940 inhibitors by using CCK8 assays, colony formation assays and transwell assays. miR-940 was significantly up-regulated in BC cells and tissues. In addition, the high level of miR-940 correlated with poor survival of BC patients (P=0.023). CCK8 assays, colony formation assays and transwell assays indicated that miR-940 promoted the proliferation and invasion abilities of BC cells. The luciferase reporter assay suggested that miR-940 directly targeted FOXO3. Moreover, we found that the effect of si-FOXO3 was rescued by miR-940 inhibitors in BC cells. miR-940 may promote the proliferation and invasion abilities of BC cells by targeting FOXO3. Our study suggested that miR-940 could be a novel molecular target for therapies against BC.
Identification of biomarkers associated with synovitis in rheumatoid arthritis by bioinformatics analyses
Authors: Li Zhaoyan , Xu Meng , Li Ronghang , Zhu Zhengqing , Liu Yuzhe , Du Zhenwu , Zhang Guizhen , Song Yang 
Published: August 2020

Abstract
Objectives: Rheumatoid arthritis (RA) is the most common inflammatory arthritis in the world, but its underlying mechanism is still unclear. The present study aims to screen and verify the potential biomarkers of RA.
Methods: We searched the Gene Expression Omnibus (GEO) database for synovial expression profiling from different RA microarray studies to perform a systematic analysis. Functional annotation of differentially expressed genes (DEGs) was conducted, including GO enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The protein–protein interaction (PPI) networks of the DEGs were constructed based on data from the STRING database. The expression levels of the hub genes in normal membranes and RA synovium were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot system.
Results: A total of 444 differential expression genes were identified, including 172 up-regulated and 272 down-regulated genes in RA synovium compared with normal controls. The top ten hub genes; protein tyrosine phosphatase receptor type C (PTPRC), LCK proto-oncogene (LCK), cell division cycle 20 (CDC20), Jun proto-oncogene (JUN), cyclin-dependent kinase 1 (CDK1), kinesin family member 11 (KIF11), epidermal growth factor receptor (epidermal growth factor receptor (EGFR), vascular endothelial growth factor A (VEGFA), mitotic arrest deficient 2 like 1 (MAD2L1), and signal transducer and activator of transcription 1 (STAT1) were identified from the PPI network, and the expression level of VEGFA and EGFR was significantly increased in RA membranes (P&lt;0.05).
Conclusion: Our results indicate that the hub genes VEGFA and EGFR may have essential effects during the development of RA and can be used as potential biomarkers of RA.
High-redshift galaxy groups as seen by ATHENA/WFI
Authors: Zhang Chaoli , Ramos-Ceja Miriam E. , Pacaud Florian , Reiprich Thomas H. 
Published: August 2020

Context. The first massive galaxy groups in the Universe are predicted to have formed at redshifts well beyond two. Baryonic physics, like stellar and active galactic nuclei (AGN) feedback in this very active epoch, are expected to have left a strong imprint on the thermo-dynamic properties of these early galaxy groups. Therefore, observations of these groups are key to constrain the relative importance of these physical processes. However, current instruments are not sensitive enough to detect them easily and characterize their hot gas content.
Aims. In this work, we quantify the observing power of the Advanced Telescope for High ENergy Astrophysics (ATHENA), the future large X-ray observatory of the European Space Agency, for discovering and characterizing early galaxy groups at high redshifts. We also investigate how well ATHENA will constrain different feedback mechanisms.
Methods. We used the SImulation of X-ray TElescopes simulator to mimic ATHENA observations, and a custom-made wavelet-based algorithm to detect galaxy groups and clusters in the redshift range 0.5 ≤ z ≤ 4. We performed extensive X-ray spectral fitting in order to characterize their gas temperature and X-ray luminosity. In the simulations and their analysis, we took into account the main ATHENA instrumental features: background, vignetting, and point spread function degradation with off-axis angle, as well as all X-ray foreground and background components including a realistic AGN flux distribution. Different physically motivated thermo-dynamical states of galaxy groups were simulated and tested, including central AGN contamination, different scaling relation models (luminosity evolution), and distinct surface brightness profiles. Also, different ATHENA instrumental setups were tested, including both 15 and 19 mirror rows and the applied optical blocking filter.
Results. In the deep Wide Field Imager survey expected to be carried out during part of ATHENA’s first four years (the nominal mission lifetime) more than 10 000 galaxy groups and clusters at z ≥ 0.5 will be discovered. We find that ATHENA can detect ∼20 high-redshift galaxy groups with masses of M500 ≥ 5 × 1013 M⊙ and z ≥ 2, and almost half of them will have a gas temperature determined to a precision of ΔT/T ≤ 25%.
Conclusions. We demonstrate that high-redshift galaxy groups can be detected very efficiently as extended sources by ATHENA and that a key parameter determining the total number of such newly discovered sources is the area on the sky surveyed by ATHENA. We show that these observations have a very good potential to constrain the importance of different feedback processes in the early universe because of ATHENA’s ability not only to find the early groups but also to characterize their hot gas properties at the same time.
The effects of granulation and supergranulation on Earth-mass planet detectability in the habitable zone around F6-K4 stars
Authors: Meunier N. , Lagrange A.-M. 
Published: August 2020

Context. The detectability of exoplanets and the determination of their projected mass in radial velocity are affected by stellar magnetic activity and photospheric dynamics. Among those processes, the effect of granulation, and even more so of supergranulation, has been shown to be significant in the solar case. The impact for other spectral types has not yet been characterised.
Aims. Our study is aimed at quantifying the impact of these flows for other stars and estimating how such contributions affect their performance.
Methods. We analysed a broad array of extended synthetic time series that model these processes to characterise the impact of these flows on exoplanet detection for main sequence stars with spectral types from F6 to K4. We focussed on Earth-mass planets orbiting within the habitable zone around those stars. We estimated the expected detection rates and detection limits, tested the tools that are typically applied to such observations, and performed blind tests.
Results. We find that both granulation and supergranulation on these stars significantly affect planet mass characterisation in radial velocity when performing a follow-up of a transit detection: the uncertainties on these masses are sometimes below 20% for a 1 MEarth (for granulation alone or for low-mass stars), but they are much larger in other configurations (supergranulation, high-mass stars). For granulation and low levels of supergranulation, the detection rates are good for K and late G stars (if the number of points is large enough), but poor for more massive stars. The highest level of supergranulation leads to a very poor performance, even for K stars; this is both due to low detection rates and to high levels of false positives, even for a very dense temporal sampling over 10 yr. False positive levels estimated from standard false alarm probabilities sometimes significantly overestimate or underestimate the true level, depending on the number of points: it is, therefore, crucial to take this effect into account when analysing observations.
Conclusions. We conclude that granulation and supergranulation significantly affect the performance of exoplanet detectability. Future works will focus on improving the following three aspects: decreasing the number of false positives, increasing detection rates, and improving the false alarm probability estimations from observations.
Truth versus ignorance in democratic politics: An existentialist perspective on the democratic promise of political freedom
Authors: König Pascal D. 
Published: August 2020

AbstractExistentialist philosophy offers an understanding of how trying to eliminate ambiguities that inevitably mark the human condition only seemingly leads to freedom. This existentialist outlook can also serve to shed light on how democratic politics may similarly show tendencies which aim at overcoming immanent tensions. Such tendencies in democratic politics can be clarified using Sartre’s notion of ignorance – and truth as its counterpart. His concept of ignorance goes beyond merely facts or knowledge and refers to a mode of being. It expresses a subject’s desire to avoid, rather than confront, resistances stemming from the world. Based on a distinction of different forms in which this orientation can manifest itself, this article shows how democratic politics, too, can be threatened by ignorance as a way of doing politics. This ignorance comes in different guises which all express a desire to eliminate tensions that democratic politics cannot overcome without undermining itself.
Archetypal landscapes for deep neural networks
Authors: Verpoort Philipp C. , Lee Alpha A. , Wales David J. 
Published: August 2020

Significance
Deep neural networks have reached impressive predictive capability for many challenging tasks, yet it remains unclear why they work. Training neural networks involves minimizing a complex, high-dimensional, nonconvex loss function, yet, empirically, it proves possible to produce useful models without rigorous global optimization. To provide insight into this observation, we analyze the structure of the loss-function landscape of deep neural networks and show that it features either a single funnel or low barriers between minima. Such landscapes are relatively easy to optimize and are qualitatively different from the energy landscape of a structural glass. More generally, our results demonstrate how the methodology developed for exploring molecular energy landscapes can be exploited to extend our understanding of machine learning.
The duration of travel impacts the spatial dynamics of infectious diseases
Authors: Giles John R. , zu Erbach-Schoenberg Elisabeth , Tatem Andrew J. , Gardner Lauren , Bjørnstad Ottar N. , Metcalf C. J. E. , Wesolowski Amy 
Published: August 2020

Significance
The spatial dynamics of infectious-disease spread are driven by the biology of the pathogen and the connectivity patterns among human populations. Models of disease spread often use mobile-phone calling records to calculate the number of trips made among locations in the population, which is used as a proxy for population connectivity. However, the amount of time people spend in a destination (trip duration) also impacts the probability of onward disease transmission among locations. Here, we developed models that incorporate trip duration into the mechanism of disease spread, which helps us understand how fast and how far a pathogen might spread in a human population.
Objective assessment of stored blood quality by deep learning
Authors: Doan Minh , Sebastian Joseph A. , Caicedo Juan C. , Siegert Stefanie , Roch Aline , Turner Tracey R. , Mykhailova Olga , Pinto Ruben N. , McQuin Claire , Goodman Allen , Parsons Michael J. , Wolkenhauer Olaf , Hennig Holger , Singh Shantanu , Wilson Anne , Acker Jason P. , Rees Paul , Kolios Michael C. , Carpenter Anne E. 
Published: August 2020

Significance
We developed a strategy to avoid human subjectivity by assessing the quality of red blood cells using imaging flow cytometry and deep learning. We successfully automated traditional expert assessment by training a computer with example images of healthy and unhealthy morphologies. However, we noticed that experts disagree on ∼18% of cells, so instead of relying on experts’ visual assessment, we taught a deep-learning network the degradation phenotypes objectively from images of red blood cells sampled over time. Although training with diverse samples is needed to create and validate a clinical-grade model, doing so would eliminate subjective assessment and facilitate research. The time-based deep-learning strategy may also prove useful for other biological progressions, such as development and disease progression.
Universal motion of mirror-symmetric microparticles in confined Stokes flow
Authors: Georgiev Rumen N. , Toscano Sara O. , Uspal William E. , Bet Bram , Samin Sela , van Roij René , Eral Huseyin Burak 
Published: August 2020

SignificanceParticles of all shapes and sizes flowing through tight spaces are ever present in applications across length scales ranging from blood flow through tissue capillaries to industrial-scale processes. To date, separating these particles relies on methods employing external force fields. Currently underexplored, omnipresent fluid–structure interactions hold the key to shape-based separation independent of external intervention. By leveraging experiments, theory, and simulations, we show how the symmetry of a particle determines its overall trajectory: In particular, mirror-symmetric particles, both strongly and weakly confined, follow a universal path. We propose minimalistic scaling relations to describe how particle shape affects the parameterization of the universal path. These findings could be used to “program” particle trajectories in lab-on-a-chip devices and industrial separation processes.
A recurrent circuit implements normalization, simulating the dynamics of V1 activity
Authors: Heeger David J. , Zemlianova Klavdia O. 
Published: August 2020

Significance
A family of recurrent circuit models is proposed to explain the dynamics of neural activity in primary visual cortex (V1). Each of the models in this family exhibits steady-state output responses that are already known to fit a wide range of experimental data from diverse neural systems. These models can recapitulate the complex dynamics of V1 activity, including oscillations (so-called gamma oscillations, ∼30 to 80 Hz). This theoretical framework may also be used to explain key aspects of working memory and motor control. Consequently, the same circuit architecture is applicable to a variety of neural systems, and V1 can be used as a model system for understanding the neural computations in many brain areas.
Multiple timescales of neural dynamics and integration of task-relevant signals across cortex
Authors: Spitmaan Mehran , Seo Hyojung , Lee Daeyeol , Soltani Alireza 
Published: August 2020

Significance
The brain exhibits a tremendous amount of heterogeneity, and to make sense of this seemingly random system neuroscientists have explored various ideas to organize it into distinct areas, each performing certain computations. One such idea is the timescale at which neural response fluctuates. Here, we developed a comprehensive method to estimate multiple timescales in neural response and link these timescales to processing of task-relevant signals and behavioral adjustments. We found multiple types of timescales that increase across cortical areas in parallel while being independent of each other and of selectivity to task-relevant signals. Our results suggest that there are multiple independent mechanisms underlying generations of neural dynamics on different timescales.
Evaluating insecticide resistance across African districts to aid malaria control decisions
Authors: Moyes Catherine L. , Athinya Duncan K. , Seethaler Tara , Battle Katherine E. , Sinka Marianne , Hadi Melinda P. , Hemingway Janet , Coleman Michael , Hancock Penelope A. 
Published: August 2020

Significance
Malaria control in Africa largely relies on the use of insecticides to prevent mosquitoes from transmitting the malaria parasite to humans; however, these mosquitoes have evolved resistance to these insecticides. To manage this threat to malaria control, it is vital that we map locations where the prevalence of resistance exceeds thresholds defined by insecticide resistance management plans. A geospatial model and data from Africa are used to predict locations where thresholds of resistance linked to specific recommended actions are exceeded. This model is shown to provide more accurate next-year predictions than two simpler approaches. The model is used to generate maps that aid insecticide resistance management planning and that allow targeted deployment of interventions that counter specific mechanisms of resistance.
Two-step release of kinase autoinhibition in discoidin domain receptor 1
Authors: Sammon Douglas , Hohenester Erhard , Leitinger Birgit 
Published: August 2020

Significance
Receptor tyrosine kinases (RTKs) are proteins on the surface of animal cells that transmit signals into the cell. Binding of an extracellular signal protein to the RTK activates its intracellular enzyme (kinase). This process needs to be tightly controlled, as unwanted RTK activation can lead to disease. The discoidin domain receptors, DDR1 and DDR2, are unusual RTKs that are activated by a major structural protein, collagen. Here we show how the enzyme activity of DDR1 is inhibited by a protein segment outside of the kinase domain and how this inhibition is overcome by tyrosine phosphorylation. Our findings reveal an important regulatory mechanism of DDRs and open up avenues for inhibitor design in diseases caused by unwanted DDR signaling.
Genetic diversity of soil invertebrates corroborates timing estimates for past collapses of the West Antarctic Ice Sheet
Authors: Collins Gemma E. , Hogg Ian D. , Convey Peter , Sancho Leopoldo G. , Cowan Don A. , Lyons W. Berry , Adams Byron J. , Wall Diana H. , Green T. G. Allan 
Published: August 2020

Significance
Changes in the extent of ice sheets through evolutionary timescales have influenced the connectivity of soil invertebrate populations across the Antarctic landscape. We use genetic divergences to estimate isolation times for soil invertebrates along the Transantarctic Mountains. Four species of Collembola (Arthropoda) each showed genetically distinct populations at locations likely isolated for millions of years. Two further species were less genetically diverse although also range restricted. Our genetic data corroborate climate reconstructions and estimates of past warm periods of reduced ice and absent ice shelf in the Ross Sea region, during which time open seaways would have facilitated dispersal of Collembola, and possibly other taxa.
Brain-wide structural and functional disruption in mice with oligodendrocyte-specificNf1deletion is rescued by inhibition of nitric oxide synthase
Authors: Asleh Jad , Shofty Ben , Cohen Nadav , Kavushansky Alexandra , López-Juárez Alejandro , Constantini Shlomi , Ratner Nancy , Kahn Itamar 
Published: August 2020

SignificanceThis study assessed the effects of myelin decompaction on motor behavior and brain-wide structural and functional connectivity, and the effect of nitric oxide synthase inhibition byN-nitro-l-arginine methyl ester (L-NAME) on these imaging measures. We report that inducible oligodendrocyte-specific inactivation of theNf1gene, which causes myelin decompaction, results in reduced initial motor coordination. Using diffusion-based magnetic resonance imaging (MRI), we show reduced myelin integrity, and using functional MRI, we show reduced functional connectivity in awake passive mice. L-NAME administration results in rescue of the pathology at the mesoscopic level, as measured using imaging procedures that can be directly applied to humans to study treatment efficacy in clinical trials.