bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell cycle dependence of apoptosis photo-triggered using peptide-photosensitizer conjugate
Authors: Kim Hyungjin , Watanabe Sho , Kitamatsu Mizuki , Watanabe Kazunori , Ohtsuki Takashi 
Published: November 2020

AbstractInvestigation of the relevance between cell cycle status and the bioactivity of exogenously delivered biomacromolecules is hindered by their time-consuming cell internalization and the cytotoxicity of transfection methods. In this study, we addressed these problems by utilizing the photochemical internalization (PCI) method using a peptide/protein-photosensitizer conjugate, which enables immediate cytoplasmic internalization of the bioactive peptides/proteins in a light-dependent manner with low cytotoxicity. To identify the cell-cycle dependent apoptosis, a TatBim peptide-photosensitizer conjugate (TatBim-PS) with apoptotic activity was photo-dependently internalized into HeLa cells expressing a fluorescent ubiquitination-based cell cycle indicator (Fucci2). Upon irradiation, cytoplasmic TatBim-PS internalization exceeded 95% for all cells classified in the G1, S, and G2/M cell cycle phases with no significant differences between groups. TatBim-PS-mediated apoptosis was more efficiently triggered by photoirradiation in the G1/S transition than in the G1 and S/G2/M phases, suggesting high sensitivity of the former phase to Bim-induced apoptosis. Thus, the cell cycle dependence of Bim peptide-induced apoptosis was successfully investigated using Fucci2 indicator and the PCI method. Since PCI-mediated cytoplasmic internalization of peptides is rapid and does not span multiple cell cycle phases, the Fucci-PCI method constitutes a promising tool for analyzing the cell cycle dependence of peptides/protein functions.
A physical memristor based Muthuswamy–Chua–Ginoux system
Authors: Ginoux Jean-Marc , Muthuswamy Bharathwaj , Meucci Riccardo , Euzzor Stefano , Di Garbo Angelo , Ganesan Kaliyaperumal 
Published: November 2020

AbstractIn 1976, Leon Chua showed that a thermistor can be modeled as a memristive device. Starting from this statement we designed a circuit that has four circuit elements: a linear passive inductor, a linear passive capacitor, a nonlinear resistor and a thermistor, that is, a nonlinear “locally active” memristor. Thus, the purpose of this work was to use a physical memristor, the thermistor, in a Muthuswamy–Chua chaotic system (circuit) instead of memristor emulators. Such circuit has been modeled by a new three-dimensional autonomous dynamical system exhibiting very particular properties such as the transition from torus breakdown to chaos. Then, mathematical analysis and detailed numerical investigations have enabled to establish that such a transition corresponds to the so-called route to Shilnikov spiral chaos but gives rise to a “double spiral attractor”.
Butyrate induced Tregs are capable of migration from the GALT to the pancreas to restore immunological tolerance during type-1 diabetes
Authors: Jacob Neenu , Jaiswal Shivani , Maheshwari Deep , Nallabelli Nayudu , Khatri Neeraj , Bhatia Alka , Bal Amanjit , Malik Vivek , Verma Savita , Kumar Rakesh , Sachdeva Naresh 
Published: November 2020

AbstractType-1 diabetes (T1D) is an autoimmune disease caused by progressive loss of insulin-producing beta cells in the pancreas. Butyrate is a commensal microbial-derived metabolite, implicated in intestinal homeostasis and immune regulation. Here, we investigated the mechanism of diabetes remission in non-obese diabetic (NOD) mice following butyrate administration. Sodium butyrate (150 mM) was administered to female NOD mice in drinking water after the onset of hyperglycemia (15–25 weeks age) and at 4 weeks of age (early-intervention group). Butyrate administration reduced the progression of hyperglycemia in diabetic mice and delayed onset of diabetes in the early-intervention group with a reduction in insulitis. Butyrate administration increased regulatory T cells (Tregs) in the colon, mesenteric lymph nodes, Peyer’s patches, and its protective effects diminished upon depletion of Tregs. Further, an increase in α4β7, CCR9, and GPR15 expressing Tregs in the pancreatic lymph nodes (PLN) and pancreas in butyrate-treated mice suggested migration of gut-primed Tregs towards the pancreas. Finally, the adoptive transfer experiments demonstrated that induced Tregs from gut-associated lymphoid tissue can migrate towards the pancreas and PLN and delay the onset of diabetes. Our results thus suggest that early administration of butyrate can restore immunological tolerance during T1D via induction of Tregs with migratory capabilities.
Identification of early liver toxicity gene biomarkers using comparative supervised machine learning
Authors: Smith Brandi Patrice , Auvil Loretta Sue , Welge Michael , Bushell Colleen Bannon , Bhargava Rohit , Elango Navin , Johnson Kamin , Madak-Erdogan Zeynep 
Published: November 2020

AbstractScreening agrochemicals and pharmaceuticals for potential liver toxicity is required for regulatory approval and is an expensive and time-consuming process. The identification and utilization of early exposure gene signatures and robust predictive models in regulatory toxicity testing has the potential to reduce time and costs substantially. In this study, comparative supervised machine learning approaches were applied to the rat liver TG-GATEs dataset to develop feature selection and predictive testing. We identified ten gene biomarkers using three different feature selection methods that predicted liver necrosis with high specificity and selectivity in an independent validation dataset from the Microarray Quality Control (MAQC)-II study. Nine of the ten genes that were selected with the supervised methods are involved in metabolism and detoxification (Car3, Crat, Cyp39a1, Dcd, Lbp, Scly, Slc23a1, and Tkfc) and transcriptional regulation (Ablim3). Several of these genes are also implicated in liver carcinogenesis, including Crat, Car3 and Slc23a1. Our biomarker gene signature provides high statistical accuracy and a manageable number of genes to study as indicators to potentially accelerate toxicity testing based on their ability to induce liver necrosis and, eventually, liver cancer.
Features of entropy optimization on MHD couple stress nanofluid slip flow with melting heat transfer and nonlinear thermal radiation
Authors: Mabood F. , Yusuf T. A. , Bognár Gabriella 
Published: November 2020

AbstractNumerical analysis is performed for magnetohydrodynamics (MHD) couple stress nanofluid flow over a stretching sheet with melting and nonlinear radiation. The second law of thermodynamics is also incorporated with first-order slip. Nanofluid characteristics for thermophoresis and Brownian moments are encountered. The system that comprises differential equations of partial derivatives is remodeled into the system of differential equations via similarity transformations and then solved numerically through the Runge–Kutta–Fehlberg fourth-fifth (RKF-45) order technique. The physical parameters, which emerges from the derived system are discussed in graphical format. The significant outcomes of the current investigation are that the velocity field decays for a higher magnetic parameter. Another, important outcome of the study is both temperature and concentration are increasing functions of the first-order slip. Nusselt and Sherwood numbers are decreasing with an increase in magnetic strength. Further, Bejan number augment due to enhancement in the first-order slip and couple stress fluid parameters whereas a differing tendency is shown for magnetic and radiation parameters.
HDL cholesterol efflux capacity is inversely associated with subclinical cardiovascular risk markers in young adults: The cardiovascular risk in Young Finns study
Authors: Hunjadi Monika , Lamina Claudia , Kahler Patrick , Bernscherer Tamara , Viikari Jorma , Lehtimäki Terho , Kähönen Mika , Hurme Mikko , Juonala Markus , Taittonen Leena , Laitinen Tomi , Jokinen Eero , Tossavainen Päivi , Hutri-Kähönen Nina , Raitakari Olli , Ritsch Andreas 
Published: November 2020

AbstractThe atherogenic process begins already in childhood and progresses to symptomatic condition with age. We investigated the association of cholesterol efflux capacity (CEC) and vascular markers of subclinical atherosclerosis in healthy, young adults. CEC was determined in 2282 participants of the Young Finns study using cAMP treated 3H-cholesterol-labeled J774 cells. The CEC was correlated to baseline and 6-year follow-up data of cardiovascular risk factors and ultrasound measurements of arterial structure and function. CEC was higher in women, correlated with total cholesterol, HDL-C, and apolipoprotein A-I, but not with LDL-C or apolipoprotein B. Compared to the lowest CEC quartile, the highest CEC quartile was significantly associated with high CRP levels and inversely associated with adiponectin. At baseline, high CEC was associated with decreased flow-mediated dilation (FMD) and carotid artery distensibility, as well as an increased Young's modulus of elasticity, indicating adverse changes in arterial structure, and function. The association reversed with follow-up FMD data, indicating the interaction of preclinical parameters over time. A higher CEC was directly associated with a lower risk of subclinical atherosclerosis at follow-up. In young and healthy subjects, CEC was associated with important lipid risk parameters at baseline, as in older patients and CAD patients, but inversely with early risk markers for subclinical atherosclerosis.
Alcohol induces TGFβ1 via downregulation of miR-1946a in murine lung fibroblast
Authors: Fan Xian , Mills Stephen T. , Kaalla Mevelyn J. , Sueblinvong Viranuj 
Published: November 2020

AbstractExaggerated transforming growth factor-beta 1 (TGFβ1) expression worsens fibroproliferation following bleomycin-induced lung injury in alcohol-fed mice. MicroRNA (miR)-1946a is predicted to bind to the TGFβ1 3′ untranslated region (UTR), thereby inhibiting its transcription. We hypothesize that alcohol suppresses miR-1946a and induces TGFβ1. Primary murine lung fibroblasts (PLFs) were cultured ± alcohol, miR-1946a mimic or inhibitor, and TGFβ1 signaling inhibitors. miR-1946a was analyzed after alcohol treatment in vitro and in vivo. TGFβ1 expression and TGFβ1 3′UTR-luciferase activity was quantified. We showed that alcohol suppressed miR-1946a in the alcohol-fed mouse lungs and PLFs. MiR-1946a inhibitor increased TGFβ1 expression in the fibroblast. MiR-1946a mimic treatment suppressed TGFβ1 gene expression and TGFβ1 3′UTR activity. Overexpression of miR1946a inhibited alcohol-induced TGFβ1 gene and protein expression as well as alcohol-induced TGFβ1 and α-smooth muscle actin (SMA) protein expression in PLFs. In conclusion, miR-1946a modulates TGFβ1 expression through direct interaction with TGFβ1 3′UTR. These findings identify a novel mechanism by which alcohol induces TGFβ1 in the lung.
Characteristics, injuries, and clinical outcomes of geriatric trauma patients in Japan: an analysis of the nationwide trauma registry database
Authors: Miyoshi Yukari , Kondo Yutaka , Hirano Yohei , Ishihara Tadashi , Sueyoshi Koichiro , Okamoto Ken , Tanaka Hiroshi 
Published: November 2020

AbstractGeriatric trauma is a major socio-economic problem, especially among the aging Japanese society. Geriatric people are more vulnerable to trauma than younger people; thus, their outcomes are often severe. This study evaluates the characteristics of geriatric trauma divided by age in the Japanese population. We evaluated trauma characteristics in patients (n = 131,088) aged ≥ 65 years by segregating them into 2 age-based cohorts: age 65–79 years (65–79 age group; n = 70,707) and age ≥ 80 years (≥ 80 age group; n = 60,381). Clinical characteristics such as patient background, injury mechanism, injury site and severity, treatment, and outcome were examined. Injuries among men were more frequent in the 65–79 age group (58.6%) than in the ≥ 80 age group (36.3%). Falls were the leading cause of trauma among the 65–79 age group (56.7%) and the ≥ 80 age group (78.9%). In-hospital mortality was 7.7% in the 65–79 age group and 6.6% in the ≥ 80 age group. High fall in the ≥ 80 age group showed 30.5% mortality. The overall in-hospital mortality was 11.8% (the 65–79 age group, 12.3%; the ≥ 80 age group, 11.2%). Most hospitalized patients were transferred to another hospital (the 65–79 age group, 52.5%; the ≥ 80 age group, 66.2%). We demonstrated the epidemiological characteristics of Japanese geriatric trauma patients. The overall in-hospital mortality was 11.8%, and fall injury in the ≥ 80 age group required caution of trauma care.
Reflection-mode virtual histology using photoacoustic remote sensing microscopy
Authors: Bell Kevan , Abbasi Saad , Dinakaran Deepak , Taher Muba , Bigras Gilbert , van Landeghem Frank K. H. , Mackey John R. , Haji Reza Parsin 
Published: November 2020

AbstractHistological visualizations are critical to clinical disease management and are fundamental to biological understanding. However, current approaches that rely on bright-field microscopy require extensive tissue preparation prior to imaging. These processes are both labor intensive and contribute to creating significant delays in clinical feedback for treatment decisions that can extend to 2–3 weeks for standard paraffin-embedded tissue preparation and interpretation, especially if ancillary testing is needed. Here, we present the first comprehensive study on the broad application of a novel label-free reflection-mode imaging modality known as photoacoustic remote sensing (PARS) for visualizing salient subcellular structures from various common histopathological tissue preparations and for use in unprocessed freshly resected tissues. The PARS modality permits non-contact visualizations of intrinsic endogenous optical absorption contrast to be extracted from thick and opaque biological targets with optical resolution. The technique was examined both as a rapid assessment tool that is capable of managing large samples (> 1 cm2) in under 10 min, and as a high contrast imaging modality capable of extracting specific biological contrast to simulate conventional histological stains such as hematoxylin and eosin (H&E). The capabilities of the proposed method are demonstrated in a variety of human tissue preparations including formalin-fixed paraffin-embedded tissue blocks and unstained slides sectioned from these blocks, including normal and neoplastic human brain, and breast epithelium involved with breast cancer. Similarly, PARS images of human skin prepared by frozen section clearly demonstrated basal cell carcinoma and normal human skin tissue. Finally, we imaged unprocessed murine kidney and achieved histologically relevant subcellular morphology in fresh tissue. This represents a vital step towards an effective real-time clinical microscope that overcomes the limitations of standard histopathologic tissue preparations and enables real-time pathology assessment.
Dam and reservoir removal projects: a mix of social-ecological trends and cost-cutting attitudes
Authors: Habel Michal , Mechkin Karl , Podgorska Krescencja , Saunes Marius , Babiński Zygmunt , Chalov Sergey , Absalon Damian , Podgórski Zbigniew , Obolewski Krystian 
Published: November 2020

AbstractThe removal of dams and reservoirs may seem to be an unforeseen and sometimes controversial step in water management. The removal of barriers may be different for each country or region, as each differs greatly in terms of politics, economy and social and cultural awareness. This paper addresses the complex problem of removing dams on rivers and their connected reservoirs. We demonstrate the scales of the changes, including their major ecological, economic, and social impacts. Arguments and approaches to this problem vary across states and regions, depending on the political system, economy and culture, as confirmed by the qualitative and quantitative intensities of the dam removal process and its global geographical variation. The results indicate that the removal of dams on rivers and their connected reservoirs applies predominantly to smaller structures (< 2.5 m). The existing examples provide an important conclusion that dams and reservoirs should be considered with regard to the interrelations between people and the environment. Decisions to deconstruct hydraulic engineering structures (or, likewise, to construct them) have to be applied with scrutiny. Furthermore, all decision-making processes have to be consistent and unified and thus developed to improve the lack of strategies currently implemented across world.
Inequalities in lung cancer mortality trends in Brazil, 2000–2015
Authors: Fernandes Gisele Aparecida , Menezes Fabrício dos Santos , Silva Luiz Felipe , Antunes José Leopoldo Ferreira , Toporcov Tatiana Natasha 
Published: November 2020

AbstractThe present study was conducted to evaluate the socioeconomic inequality related to lung cancer mortality rates and trends between 2000 and 2015 according to gender in Brazil. We retrieved the death records for cases of lung cancer (ICD-10 C33 C34) from 2000 to 2015 in adults age 30 years and older in Brazilian Regions from official databases (DATASUS) and corrected for ill-defined causes. The Prais-Winsten regression method and Pearson correlation were applied. The results were considered statistically significant when p < 0.05. The correlation between the lung cancer mortality rates and the HDI decreased when the rates for the first and last years of the historical series were compared in men (r = 0.77; r = 0.58) and women (r = 0.64; r = 0.41). However, the correlation between the trends in the lung cancer mortality rates and the HDI was negative in men (r = − 0.76) and women (r = − 0.58), indicating larger reductions (or smaller additions) among the Federative Units with the highest HDI, in contrast to trends reflecting a greater increase in those with the lowest HDI. Our results suggest a relevant inequality in the trends of mortality from lung cancer in Brazil.
Identification and analysis of miRNAs in IR56 rice in response to BPH infestations of different virulence levels
Authors: Nanda Satyabrata , Yuan San-Yue , Lai Feng-Xia , Wang Wei-Xia , Fu Qiang , Wan Pin-Jun 
Published: November 2020

AbstractRice production and sustainability are challenged by its most dreadful pest, the brown planthopper (Nilaparvata lugensStål, BPH). Therefore, the studies on rice-BPH interactions and their underlying mechanisms are of high interest. The rice ontogenetic defense, such as the role of microRNAs (miRNAs) has mostly been investigated against the pathogens, with only a few reports existing against the insect infestations. Thus, revealing the involvement of rice miRNAs in response to BPH infestations will be beneficial in understanding these complex interactions. In this study, the small RNA profiling of the IR56 rice in response to separate BPH infestations of varied virulence levels identified the BPH-responsive miRNAs and revealed the differential transcript abundance of several miRNAs during a compatible and incompatible rice-BPH interaction. The miRNA sequence analysis identified 218 known and 28 novel miRNAs distributed in 54 miRNA families. Additionally, 138 and 140 numbers of differentially expressed (DE) miRNAs were identified during the compatible and incompatible interaction, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed the target gene candidates of DE miRNAs (including osa-miR2871a-3p, osa-miR172a, osa-miR166a-5p, osa-miR2120, and osa-miR1859) that might be involved in the IR56 rice defense responses against BPH infestation. Conversely, osa-miR530-5p, osa-miR812s, osa-miR2118g, osa-miR156l-5p, osa-miR435 and two of the novel miRNAs, including novel_16 and novel_52 might negatively modulate the IR56 rice defense. The expressional validation of the selected miRNAs and their targets further supported the IR56 rice defense regulatory network. Based on our results, we have proposed a conceptual model depicting the miRNA defense regulatory network in the IR56 rice against BPH infestation. The findings from the study add further insights into the molecular mechanisms of rice-BPH interactions and will be helpful for the future researches.
Identification and characterization of satellite DNAs in two-toed sloths of the genus Choloepus (Megalonychidae, Xenarthra)
Authors: Sena Radarane Santos , Heringer Pedro , Valeri Mirela Pelizaro , Pereira Valéria Socorro , Kuhn Gustavo C. S. , Svartman Marta 
Published: November 2020

AbstractCholoepus, the only extant genus of the Megalonychidae family, is composed of two living species of two-toed sloths: Choloepus didactylus and C. hoffmanni. In this work, we identified and characterized the main satellite DNAs (satDNAs) in the sequenced genomes of these two species. SATCHO1, the most abundant satDNA in both species, is composed of 117 bp tandem repeat sequences. The second most abundant satDNA, SATCHO2, is composed of ~ 2292 bp tandem repeats. Fluorescence in situ hybridization in C. hoffmanni revealed that both satDNAs are located in the centromeric regions of all chromosomes, except the X. In fact, these satDNAs present some centromeric characteristics in their sequences, such as dyad symmetries predicted to form secondary structures. PCR experiments indicated the presence of SATCHO1 sequences in two other Xenarthra species: the tree-toed sloth Bradypus variegatus and the anteater Myrmecophaga tridactyla. Nevertheless, SATCHO1 is present as large tandem arrays only in Choloepus species, thus likely representing a satDNA exclusively in this genus. Our results reveal interesting features of the satDNA landscape in Choloepus species with the potential to aid future phylogenetic studies in Xenarthra and mammalian genomes in general.
Clustering of Alzheimer’s and Parkinson’s disease based on genetic burden of shared molecular mechanisms
Authors: Emon Mohammad Asif , Heinson Ashley , Wu Ping , Domingo-Fernández Daniel , Sood Meemansa , Vrooman Henri , Corvol Jean-Christophe , Scordis Phil , Hofmann-Apitius Martin , Fröhlich Holger 
Published: November 2020

AbstractOne of the visions of precision medicine has been to re-define disease taxonomies based on molecular characteristics rather than on phenotypic evidence. However, achieving this goal is highly challenging, specifically in neurology. Our contribution is a machine-learning based joint molecular subtyping of Alzheimer’s (AD) and Parkinson’s Disease (PD), based on the genetic burden of 15 molecular mechanisms comprising 27 proteins (e.g. APOE) that have been described in both diseases. We demonstrate that our joint AD/PD clustering using a combination of sparse autoencoders and sparse non-negative matrix factorization is reproducible and can be associated with significant differences of AD and PD patient subgroups on a clinical, pathophysiological and molecular level. Hence, clusters are disease-associated. To our knowledge this work is the first demonstration of a mechanism based stratification in the field of neurodegenerative diseases. Overall, we thus see this work as an important step towards a molecular mechanism-based taxonomy of neurological disorders, which could help in developing better targeted therapies in the future by going beyond classical phenotype based disease definitions.