bluuebunny/crossref_metadata_2025_split huggingface dataset:
Loss of Ambra1 promotes melanoma growth and invasion
Authors: Di Leo Luca , Bodemeyer Valérie , Bosisio Francesca M. , Claps Giuseppina , Carretta Marco , Rizza Salvatore , Faienza Fiorella , Frias Alex , Khan Shawez , Bordi Matteo , Pacheco Maria P. , Di Martino Julie , Bravo-Cordero Jose J. , Daniel Colin J. , Sears Rosalie C. , Donia Marco , Madsen Daniel H. , Guldberg Per , Filomeni Giuseppe , Sauter Thomas , Robert Caroline , De Zio Daniela , Cecconi Francesco 
Published: May 2021

AbstractMelanoma is the deadliest skin cancer. Despite improvements in the understanding of the molecular mechanisms underlying melanoma biology and in defining new curative strategies, the therapeutic needs for this disease have not yet been fulfilled. Herein, we provide evidence that the Activating Molecule in Beclin-1-Regulated Autophagy (Ambra1) contributes to melanoma development. Indeed, we show that Ambra1 deficiency confers accelerated tumor growth and decreased overall survival in Braf/Pten-mutated mouse models of melanoma. Also, we demonstrate that Ambra1 deletion promotes melanoma aggressiveness and metastasis by increasing cell motility/invasion and activating an EMT-like process. Moreover, we show that Ambra1 deficiency in melanoma impacts extracellular matrix remodeling and induces hyperactivation of the focal adhesion kinase 1 (FAK1) signaling, whose inhibition is able to reduce cell invasion and melanoma growth. Overall, our findings identify a function for AMBRA1 as tumor suppressor in melanoma, proposing FAK1 inhibition as a therapeutic strategy for AMBRA1 low-expressing melanoma.
Data-driven reaction coordinate discovery in overdamped and non-conservative systems: application to optical matter structural isomerization
Authors: Chen Shiqi , Peterson Curtis W. , Parker John A. , Rice Stuart A. , Ferguson Andrew L. , Scherer Norbert F. 
Published: May 2021

AbstractOptical matter (OM) systems consist of (nano-)particle constituents in solution that can self-organize into ordered arrays that are bound by electrodynamic interactions. They also manifest non-conservative forces, and the motions of the nano-particles are overdamped; i.e., they exhibit diffusive trajectories. We propose a data-driven approach based on principal components analysis (PCA) to determine the collective modes of non-conservative overdamped systems, such as OM structures, and harmonic linear discriminant analysis (HLDA) of time trajectories to estimate the reaction coordinate for structural transitions. We demonstrate the approach via electrodynamics-Langevin dynamics simulations of six electrodynamically-bound nanoparticles in an incident laser beam. The reaction coordinate we discover is in excellent accord with a rigorous committor analysis, and the identified mechanism for structural isomerization is in very good agreement with the experimental observations. The PCA-HLDA approach to data-driven discovery of reaction coordinates can aid in understanding and eventually controlling non-conservative and overdamped systems including optical and active matter systems.
Regression plane concept for analysing continuous cellular processes with machine learning
Authors: Szkalisity Abel , Piccinini Filippo , Beleon Attila , Balassa Tamas , Varga Istvan Gergely , Migh Ede , Molnar Csaba , Paavolainen Lassi , Timonen Sanna , Banerjee Indranil , Ikonen Elina , Yamauchi Yohei , Ando Istvan , Peltonen Jaakko , Pietiäinen Vilja , Honti Viktor , Horvath Peter 
Published: May 2021

AbstractBiological processes are inherently continuous, and the chance of phenotypic discovery is significantly restricted by discretising them. Using multi-parametric active regression we introduce the Regression Plane (RP), a user-friendly discovery tool enabling class-free phenotypic supervised machine learning, to describe and explore biological data in a continuous manner. First, we compare traditional classification with regression in a simulated experimental setup. Second, we use our framework to identify genes involved in regulating triglyceride levels in human cells. Subsequently, we analyse a time-lapse dataset on mitosis to demonstrate that the proposed methodology is capable of modelling complex processes at infinite resolution. Finally, we show that hemocyte differentiation in Drosophila melanogaster has continuous characteristics.
CopulaNet: Learning residue co-evolution directly from multiple sequence alignment for protein structure prediction
Authors: Ju Fusong , Zhu Jianwei , Shao Bin , Kong Lupeng , Liu Tie-Yan , Zheng Wei-Mou , Bu Dongbo 
Published: May 2021

AbstractResidue co-evolution has become the primary principle for estimating inter-residue distances of a protein, which are crucially important for predicting protein structure. Most existing approaches adopt an indirect strategy, i.e., inferring residue co-evolution based on some hand-crafted features, say, a covariance matrix, calculated from multiple sequence alignment (MSA) of target protein. This indirect strategy, however, cannot fully exploit the information carried by MSA. Here, we report an end-to-end deep neural network, CopulaNet, to estimate residue co-evolution directly from MSA. The key elements of CopulaNet include: (i) an encoder to model context-specific mutation for each residue; (ii) an aggregator to model residue co-evolution, and thereafter estimate inter-residue distances. Using CASP13 (the 13th Critical Assessment of Protein Structure Prediction) target proteins as representatives, we demonstrate that CopulaNet can predict protein structure with improved accuracy and efficiency. This study represents a step toward improved end-to-end prediction of inter-residue distances and protein tertiary structures.
Protein analysis of extracellular vesicles to monitor and predict therapeutic response in metastatic breast cancer
Authors: Tian Fei , Zhang Shaohua , Liu Chao , Han Ziwei , Liu Yuan , Deng Jinqi , Li Yike , Wu Xia , Cai Lili , Qin Lili , Chen Qinghua , Yuan Yang , Liu Yi , Cong Yulong , Ding Baoquan , Jiang Zefei , Sun Jiashu 
Published: May 2021

AbstractMolecular profiling of circulating extracellular vesicles (EVs) provides a promising noninvasive means to diagnose, monitor, and predict the course of metastatic breast cancer (MBC). However, the analysis of EV protein markers has been confounded by the presence of soluble protein counterparts in peripheral blood. Here we use a rapid, sensitive, and low-cost thermophoretic aptasensor (TAS) to profile cancer-associated protein profiles of plasma EVs without the interference of soluble proteins. We show that the EV signature (a weighted sum of eight EV protein markers) has a high accuracy (91.1 %) for discrimination of MBC, non-metastatic breast cancer (NMBC), and healthy donors (HD). For MBC patients undergoing therapies, the EV signature can accurately monitor the treatment response across the training, validation, and prospective cohorts, and serve as an independent prognostic factor for progression free survival in MBC patients. Together, this work highlights the potential clinical utility of EVs in management of MBC.
Effect of bisphenol A on alterations of ICAM-1 and HLA-G genes expression and DNA methylation profiles in cumulus cells of infertile women with poor response to ovarian stimulation
Authors: Aftabsavad Somayeh , Noormohammadi Zahra , Moini Ashraf , Karimipoor Morteza 
Published: May 2021

AbstractThis study aimed to investigate the relationship between follicular fluid Bisphenol A (BPA) concentrations with alterations of ICAM-1 and HLA-G genes and proteins expression as well as methylation profiles in the cumulus cells of poor ovarian response (POR) women based on their healthy lifestyle habit. Eighty women under the age of 35 were divided into two groups: 1—POR without using plastic containers (n = 40) and 2—POR with using plastic containers (n = 40). The ICAM-1 and HLA-G genes and protein expressions were examined by the quantitative PCR and western blotting technique. The methylation pattern was investigated by the methylation-specific PCR. Total BPA in follicular fluid was measured with high-performance liquid chromatography technique and the detection limit was 1.14 ng/ml. ICAM-1 and HLA-G genes were differentially expressed between the two groups studied. ICAM-1, HLA-G genes, and protein expressions in group 1 were up-regulated compared to the second group (P < 0.05). While DNA methylation status in group 1 were decreased compared to the other group (P < 0.05). The concentration of BPA in the follicular fluid of group 1 was lower compared to the second group (P < 0.05). The oocyte quality and clinical pregnancy ratio showed significantly higher in group 1 than in the other ones (P < 0.05). The alteration of ICAM-1 and HLA-G gene expressions in POR women is probably related to BPA concentration. As a result Lifestyle habits may also affect the methylation pattern and protein levels in the cumulus cells of POR women. Additionally, lifestyle habits may be considered as a marker for ovulation, oocyte maturation, preimplantation, and clinical pregnancy process.
Community composition and functional prediction of prokaryotes associated with sympatric sponge species of southwestern Atlantic coast
Authors: Hardoim C. C. P. , Ramaglia A. C. M. , Lôbo-Hajdu G. , Custódio M. R. 
Published: May 2021

AbstractProkaryotes contribute to the health of marine sponges. However, there is lack of data on the assembly rules of sponge-associated prokaryotic communities, especially for those inhabiting biodiversity hotspots, such as ecoregions between tropical and warm temperate southwestern Atlantic waters. The sympatric species Aplysina caissara, Axinella corrugata, and Dragmacidon reticulatum were collected along with environmental samples from the north coast of São Paulo (Brazil). Overall, 64 prokaryotic phyla were detected; 51 were associated with sponge species, and the dominant were Proteobacteria, Bacteria (unclassified), Cyanobacteria, Crenarchaeota, and Chloroflexi. Around 64% and 89% of the unclassified operational taxonomical units (OTUs) associated with Brazilian sponge species showed a sequence similarity below 97%, with sequences in the Silva and NCBI Type Strain databases, respectively, indicating the presence of a large number of unidentified taxa. The prokaryotic communities were species-specific, ranging 56%–80% of the OTUs and distinct from the environmental samples. Fifty-four lineages were responsible for the differences detected among the categories. Functional prediction demonstrated that Ap. caissara was enriched for energy metabolism and biosynthesis of secondary metabolites, whereas D. reticulatum was enhanced for metabolism of terpenoids and polyketides, as well as xenobiotics’ biodegradation and metabolism. This survey revealed a high level of novelty associated with Brazilian sponge species and that distinct members responsible from the differences among Brazilian sponge species could be correlated to the predicted functions.
Effects of urethane and isoflurane on the sensory evoked response and local blood flow in the early postnatal rat somatosensory cortex
Authors: Shumkova Viktoria , Sitdikova Violetta , Rechapov Ildar , Leukhin Alexey , Minlebaev Marat 
Published: May 2021

AbstractFunctional studies in the central nervous system are often conducted using anesthesia. While the dose-dependent effects of anesthesia on neuronal activity have been extensively characterized in adults, little is known about the effects of anesthesia on cortical activity and cerebral blood flow in the immature central nervous system. Substitution of electrophysiological recordings with the less-invasive technique of optical intrinsic signal imaging (OIS) in vivo allowed simultaneous recordings of sensory-evoked functional response and local blood flow changes in the neonatal rat barrel cortex. Using OIS we characterize the effects of two widely used anesthetics—urethane and isoflurane. We found that both anesthetics suppressed the sensory-evoked optical intrinsic signal in a dose-dependent manner. Dependence of the cortical response suppression matched the exponential decay model. At experimental levels of anesthesia, urethane affected the evoked cortical response less than isoflurane, which is in agreement with the results of electrophysiological recordings demonstrated by other authors. Changes in oxygenation and local blood flow also showed negative correlation with both anesthetics. The high similarity in immature patterns of activity recorded in different regions of the developing cortex suggested similar principles of development regardless of the cortical region. Therefore the indicated results should be taken into account during functional explorations in the entire developing cortex. Our results also point to urethane as the anesthetic of choice in non-survival experimental recordings in the developing brain as it produces less prominent impairment of cortical neuronal activity in neonatal animals.
The epidemiological characteristics and effectiveness of countermeasures to contain coronavirus disease 2019 in Ningbo City, Zhejiang Province, China
Authors: Lao Xuying , Luo Li , Lei Zhao , Fang Ting , Chen Yi , Liu Yuhui , Ding Keqin , Zhang Dongliang , Wang Rong , Zhao Zeyu , Rui Jia , Zhu Yuanzhao , Xu Jingwen , Wang Yao , Yang Meng , Yi Bo , Chen Tianmu 
Published: May 2021

AbstractA novel coronavirus (SARS-CoV-2) has spread worldwide and led to high disease burden around the world. This study aimed to explore the key parameters of SARS-CoV-2 infection and to assess the effectiveness of interventions to control the coronavirus disease 2019 (COVID-19). A susceptible—exposed—infectious—asymptomatic—recovered (SEIAR) model was developed for the assessment. The information of each confirmed case and asymptomatic infection was collected from Ningbo Center for Disease Control and Prevention (CDC) to calculate the key parameters of the model in Ningbo City, China. A total of 157 confirmed COVID-19 cases (including 51 imported cases and 106 secondary cases) and 30 asymptomatic infections were reported in Ningbo City. The proportion of asymptomatic infections had an increasing trend. The proportion of elder people in the asymptomatic infections was lower than younger people, and the difference was statistically significant (Fisher’s Exact Test, P = 0.034). There were 22 clusters associated with 167 SARS-CoV-2 infections, among which 29 cases were asymptomatic infections, accounting for 17.37%. We found that the secondary attack rate (SAR) of asymptomatic infections was almost the same as that of symptomatic cases, and no statistical significance was observed (χ2 = 0.052, P = 0.819) by Kruskal–Wallis test. The effective reproduction number (Reff) was 1.43, which revealed that the transmissibility of SARS-CoV-2 was moderate. If the interventions had not been strengthened, the duration of the outbreak would have lasted about 16 months with a simulated attack rate of 44.15%. The total attack rate (TAR) and duration of the outbreak would increase along with the increasing delay of intervention. SARS-CoV-2 had moderate transmissibility in Ningbo City, China. The proportion of asymptomatic infections had an increase trend. Asymptomatic infections had the same transmissibility as symptomatic infections. The integrated interventions were implemented at different stages during the outbreak, which turned out to be exceedingly effective in China.
Determinants of peripapillary retinal nerve fiber layer’s grayscale value in normal eyes by spectral domain optical coherence tomography
Authors: Xie Xiaolin , Chen Binyao , Yang Jianling , Huang Chukai , Qiu Kunliang , Zheng Ce , Zhang Mingzhi 
Published: May 2021

AbstractTo determine and evaluate the distribution, variation, and determinants of peripapillary retinal nerve fiber layer (pRNFL) grayscale value with spectral-domain optical coherence tomography (SD-OCT) in normal eyes. In this cross-sectional study, three hundred ninety-seven normal eyes from 397 healthy Chinese adults aged 18–80 were consecutively recruited from a tertiary eye care center. An SD-OCT instrument took pRNFL imaging. We used a customized software to measure pRNFL parameters, including thickness and grayscale value. Univariable and multiple linear regression analyses were performed to examine the relationship between pRNFL grayscale value with ocular (e.g., axial length [A.L.], spherical equivalent [S.E.], intraocular pressure [IOP]), and systemic (e.g., age, sex) factors. A total of 397 eyes from 397 healthy subjects were included in the final analysis with mean (± SD) age 44.63 ± 16.43 years (range 18–80 years) and 196 (49.4%) males. The mean average of pRNFL grayscale value and thickness 164.82 ± 5.69 and 106.68 ± 8.89 μm, respectively. pRNFL grayscale value in nasal sectors (163.26 ± 9.31) was significantly lower comparing those in all other five sectors (all with p < 0.001)]. In multivariable analysis, average pRNFL grayscale value was independently correlated to older age (β = − 0.053, p = 0.002), longer axial length (β = − 0.664, p = 0.003), lower RPE grayscale value (β = 0.372, p < 0.001) and lower ImageQ (β = 0.658, p < 0.001). In this study, we provided normative SD-OCT data on the pRNFL grayscale value profile in nonglaucomatous eyes. Lower average pRNFL grayscale value was independently correlated to older age, longer axial length, lower RPE grayscale value, and lower ImageQ. These determinants should be considered when interpreting pRNFL grayscale value in glaucoma assessment.
A cautionary tale about using the apparent carbon accumulation rate (aCAR) obtained from peat cores
Authors: Young Dylan M. , Baird Andy J. , Gallego-Sala Angela V. , Loisel Julie 
Published: May 2021

AbstractThe carbon (C) accumulation histories of peatlands are of great interest to scientists, land users and policy makers. Because peatlands contain more than 500 billion tonnes of C, an understanding of the fate of this dynamic store, when subjected to the pressures of land use or climate change, is an important part of climate-change mitigation strategies. Information from peat cores is often used to recreate a peatland’s C accumulation history from recent decades to past millennia, so that comparisons between past and current rates can be made. However, these present day observations of peatlands’ past C accumulation rates (known as the apparent rate of C accumulation - aCAR) are usually different from the actual uptake or loss of C that occurred at the time (the true C balance). Here we use a simple peatland model and a more detailed ecosystem model to illustrate why aCAR should not be used to compare past and current C accumulation rates. Instead, we propose that data from peat cores are used with existing or new C balance models to produce reliable estimates of how peatland C function has changed over time.
A morphological analysis of activity-dependent myelination and myelin injury in transitional oligodendrocytes
Authors: Toth Eszter , Rassul Sayed Muhammed , Berry Martin , Fulton Daniel 
Published: May 2021

AbstractNeuronal activity is established as a driver of oligodendrocyte (OL) differentiation and myelination. The concept of activity-dependent myelin plasticity, and its role in cognition and disease, is gaining support. Methods capable of resolving changes in the morphology of individual myelinating OL would advance our understanding of myelin plasticity and injury, thus we adapted a labelling approach involving Semliki Forest Virus (SFV) vectors to resolve and quantify the 3-D structure of OL processes and internodes in cerebellar slice cultures. We first demonstrate the utility of the approach by studying changes in OL morphology after complement-mediated injury. SFV vectors injected into cerebellar white matter labelled transitional OL (TOL), whose characteristic mixture of myelinating and non-myelinating processes exhibited significant degeneration after complement injury. The method was also capable of resolving finer changes in morphology related to neuronal activity. Prolonged suppression of neuronal activity, which reduced myelination, selectively decreased the length of putative internodes, and the proportion of process branches that supported them, while leaving other features of process morphology unaltered. Overall this work provides novel information on the morphology of TOL, and their response to conditions that alter circuit function or induce demyelination.
A novel RLIM/RNF12 variant disrupts protein stability and function to cause severe Tonne–Kalscheuer syndrome
Authors: Bustos Francisco , Espejo-Serrano Carmen , Segarra-Fas Anna , Toth Rachel , Eaton Alison J. , Kernohan Kristin D. , Wilson Meredith J. , Riley Lisa G. , Findlay Greg M. 
Published: May 2021

AbstractTonne–Kalscheuer syndrome (TOKAS) is an X-linked intellectual disability syndrome associated with variable clinical features including craniofacial abnormalities, hypogenitalism and diaphragmatic hernia. TOKAS is caused exclusively by variants in the gene encoding the E3 ubiquitin ligase gene RLIM, also known as RNF12. Here we report identification of a novel RLIM missense variant, c.1262A>G p.(Tyr421Cys) adjacent to the regulatory basic region, which causes a severe form of TOKAS resulting in perinatal lethality by diaphragmatic hernia. Inheritance and X-chromosome inactivation patterns implicate RLIM p.(Tyr421Cys) as the likely pathogenic variant in the affected individual and within the kindred. We show that the RLIM p.(Tyr421Cys) variant disrupts both expression and function of the protein in an embryonic stem cell model. RLIM p.(Tyr421Cys) is correctly localised to the nucleus, but is readily degraded by the proteasome. The RLIM p.(Tyr421Cys) variant also displays significantly impaired E3 ubiquitin ligase activity, which interferes with RLIM function in Xist long-non-coding RNA induction that initiates imprinted X-chromosome inactivation. Our data uncover a highly disruptive missense variant in RLIM that causes a severe form of TOKAS, thereby expanding our understanding of the molecular and phenotypic spectrum of disease severity.
Future changes to the upper ocean Western Boundary Currents across two generations of climate models
Authors: Sen Gupta Alex , Stellema Annette , Pontes Gabriel M. , Taschetto Andréa S. , Vergés Adriana , Rossi Vincent 
Published: May 2021

AbstractWestern Boundary Currents (WBCs) are important for the oceanic transport of heat, dissolved gases and nutrients. They can affect regional climate and strongly influence the dispersion and distribution of marine species. Using state-of-the-art climate models from the latest and previousClimate Model Intercomparison Projects, we evaluate upper ocean circulation and examine future projections, focusing on subtropical and low-latitude WBCs. Despite their coarse resolution, climate models successfully reproduce most large-scale circulation features with ensemble mean transports typically within the range of observational uncertainty, although there is often a large spread across the models and some currents are systematically too strong or weak. Despite considerable differences in model structure, resolution and parameterisations, many currents show highly consistent projected changes across the models. For example, the East Australian Current, Brazil Current and Agulhas Current extensions are projected to intensify, while the Gulf Stream, Indonesian Throughflow and Agulhas Current are projected to weaken. Intermodel differences in most future circulation changes can be explained in part by projected changes in the large-scale surface winds. In moving to the latest model generation, despite structural model advancements, we find little systematic improvement in the simulation of ocean transports nor major differences in the projected changes.