bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exosomes of adult human fibroblasts cultured on 3D silk fibroin nonwovens intensely stimulate neoangiogenesis
Authors: Hu Peng , Chiarini Anna , Wu Jun , Freddi Giuliano , Nie Kaiyu , Armato Ubaldo , Prà Ilaria Dal 
Published: February 2021

AbstractBackgroundBombyx mori silk fibroin is a biomacromolecule that allows the assembly of scaffolds for tissue engineering and regeneration purposes due to its cellular adhesiveness, high biocompatibility and low immunogenicity. Earlier work showed that two types of 3D silk fibroin nonwovens (3D-SFnws) implanted into mouse subcutaneous tissue were promptly vascularized via undefined molecular mechanisms. The present study used nontumorigenic adult human dermal fibroblasts (HDFs) adhering to a third type of 3D-SFnws to assess whether HDFs release exosomes whose contents promote neoangiogenesis.MethodsElectron microscopy imaging and physical tests defined the features of the novel carded/hydroentangled 3D-SFnws. HDFs were cultured on 3D-SFnws and polystyrene plates in an exosome-depleted medium. DNA amounts and D-glucose consumption revealed the growth and metabolic activities of HDFs on 3D-SFnws. CD9-expressing total exosome fractions were from conditioned media of 3D-SFnws and 2D polystyrene plates HDF cultures. Angiogenic growth factors (AGFs) in equal amounts of the two groups of exosomal proteins were analysed via double-antibody arrays. A tube formation assay using human dermal microvascular endothelial cells (HDMVECs) was used to evaluate the exosomes’ angiogenic power.ResultsThe novel features of the 3D-SFnws met the biomechanical requirements typical of human soft tissues. By experimental day 15, 3D-SFnws-adhering HDFs had increased 4.5-fold in numbers and metabolized 5.4-fold more D-glucose than at day 3 in vitro. Compared to polystyrene-stuck HDFs, exosomes from 3D-SFnws-adhering HDFs carried significantly higher amounts of AGFs, such as interleukin (IL)-1α, IL-4 and IL-8; angiopoietin-1 and angiopoietin-2; angiopoietin-1 receptor (or Tie-2); growth-regulated oncogene (GRO)-α, GRO-β and GRO-γ; matrix metalloproteinase-1; tissue inhibitor metalloproteinase-1; and urokinase-type plasminogen activator surface receptor, but lesser amounts of anti-angiogenic tissue inhibitor metalloproteinase-2 and pro-inflammatory monocyte chemoattractant protein-1. At concentrations from 0.62 to 10 μg/ml, the exosomes from 3D-SFnws-cultured HDFs proved their angiogenic power by inducing HDMVECs to form significant amounts of tubes in vitro.ConclusionsThe structural and mechanical properties of carded/hydroentangled 3D-SFnws proved their suitability for tissue engineering and regeneration applications. Consistent with our hypothesis, 3D-SFnws-adhering HDFs released exosomes carrying several AGFs that induced HDMVECs to promptly assemble vascular tubes in vitro. Hence, we posit that once implanted in vivo, the 3D-SFnws/HDFs interactions could promote the vascularization and repair of extended skin wounds due to burns or other noxious agents in human and veterinary clinical settings.
Innovative Thin-Layer Chromatography/Fluorescence Detection Approach for Sensitive and Specific Determination of Ledipasvir in Rats’ Feces and Pharmaceutical Dosage Form
Authors: Abdel-Lateef Mohamed A , Omar Mahmoud A , Ali Ramadan , Almahri Albandary , Derayea Sayed M 
Published: February 2021

Abstract
An innovative thin-layer chromatography method coupled with the fluorescence detection was developed for a specific estimation of ledipasvir. The separation was achieved on plates of silica gel 60 F254 using ethylacetate: hexane: acetonitrile: triethylamine; (6: 3.5: 1.5: 0.5, $\mathrm{v}/\mathrm{v}/\mathrm{v}/\mathrm{v}$) as a mobile phase system. The method involved the exposure of the developed thin-layer chromatography plate of ledipasvir to strong ultraviolet irradiation, resulting in a great enhancement in the fluorescence properties of ledipasvir. The irradiated plates were scanned after the excitation at 315 $\mathrm{nm}$. The method provided a sufficient separation of ledipasvir from sofosbuvir with ${R}_F$values of 0.28 and 0.36 for ledipasvir and sofosbuvir, respectively. The developed procedures were validated based on guidelines from the International Conference on Harmonization and Food and Drug Administration guidelines. The calibration curve was linear over the range of 5–50 $\mathrm{ng}/\mathrm{band}$. The excellent analytical features of the proposed method allow to the specific determination of ledipasvir in pharmaceutical tablets without interference from sofosbuvir or excipients. As the main elimination route for ledipasvir is via the fecal excretion (86%), the method was applied for the estimation of ledipasvir in fecal specimens with adequate recovery. In addition, the proposed method was applied for testing the content uniformity of ledipasvir in the pharmaceutical tablets.
Development and Validation of an LC–MS/MS Method for AC1LPSZG and Pharmacokinetics Application in Rats
Authors: Chen Yuan , Gao Xiuqing , Gupta Ritu , Ma Jing , Dere Ruhee , Liang Dong , Xie Huan 
Published: February 2021

Abstract
Promising preliminary clinical data have stimulated research on the use of the mammalian target of rapamycin (mTOR) inhibitors in lung cancer. AC1LPSZG is an mTOR inhibitor that can significantly reduce the viability in lung adenosquamous carcinoma cell line HTB-178 cells, showing potential benefits in effective control of non-small cell lung carcinomas. In this study, a sensitive LC–MS/MS analytical method for quantification of AC1LPSZG has been developed and optimized to a running time of 3 min per sample. A linear dose–response for quantification was observed over the range of 10–5000 ng/mL in rat plasma with required precision and accuracy. High extraction recovery was achieved in the ranges of 86.87–102.51% at QC levels from rat plasma without significant matrix effect. Stability profile of AC1LPSZG in rat plasma and in extract after protein precipitation suggested that samples should be processed within 6 h after collection and stored at −80 °C until analysis within 30 days. The method was successfully applied to plasma pharmacokinetics (PK) study of AC1LPSZG in rat, showing the plasma drug concentration followed a two-compartment model.
Emerging views of statin pleiotropy and cholesterol lowering
Authors: Yu Dongbo , Liao James K 
Published: February 2021

AbstractOver the past four decades, no class of drugs has had more impact on cardiovascular health than the 3-hydroxy-methylglutaryl coenzyme A reductase inhibitors or statins. Developed as potent lipid-lowering agents, statins were later shown to reduce morbidity and mortality of patients who are at risk for cardiovascular disease. However, retrospective analyses of some of these clinical trials have uncovered some aspects of their clinical benefits that may be additional to their lipid-lowering effects. Such ‘pleiotropic’ effects of statins garnered intense interest and debate over its contribution to cardiovascular risk reduction. This review will provide a brief background of statin pleiotropy, assess the available clinical evidence for and against their non-lipid-lowering benefits, and propose future research directions in this field.
The structural heart disease interventional imager rationale, skills and training: a position paper of the European Association of Cardiovascular Imaging
Authors: Agricola Eustachio , Ancona Francesco , Brochet Eric , Donal Erwan , Dweck Marc , Faletra Francesco , Lancellotti Patrizio , Mahmoud-Elsayed Hani , Marsan Nina Ajmone , Maurovich-Hovart Pal , Monaghan Mark , Ribeiro José , Sade Leyla Elif , Swaans Martin , Von Bardeleben Ralph Stephan , Wunderlich Nina , Zamorano Jose-Luis , Popescu Bogdan A , Cosyns Bernard , Edvardsen Thor ,   Reviewers: This document was reviewed by members of the 2018-2020 EACVI Scientific Documents Committee, Bertrand Philippe , Delgado Victoria , Gerber Bernard , Stankovic Ivan 
Published: February 2021

Abstract
Percutaneous therapeutic options for an increasing variety of structural heart diseases (SHD) have grown dramatically. Within this context of continuous expansion of devices and procedures, there has been increased demand for physicians with specific knowledge, skills, and advanced training in multimodality cardiac imaging. As a consequence, a new subspecialty of ‘Interventional Imaging’ for SHD interventions and a new dedicated professional figure, the ‘Interventional Imager’ with specific competencies has emerged. The interventional imager is an integral part of the heart team and plays a central role in decision-making throughout the patient pathway, including the appropriateness and feasibility of a procedure, pre-procedural planning, intra-procedural guidance, and post-procedural follow-up. However, inherent challenges exist to develop a training programme for SHD imaging that differs from traditional cardiovascular imaging pathways. The purpose of this document is to provide the standard requirements for the training in SHD imaging, as well as a starting point for an official certification process for SHD interventional imager.
Diagnosis and treatment of cardiac amyloidosis: a position statement of the ESC Working Group on Myocardial and Pericardial Diseases
Authors: Garcia-Pavia Pablo , Rapezzi Claudio , Adler Yehuda , Arad Michael , Basso Cristina , Brucato Antonio , Burazor Ivana , Caforio Alida L P , Damy Thibaud , Eriksson Urs , Fontana Marianna , Gillmore Julian D , Gonzalez-Lopez Esther , Grogan Martha , Heymans Stephane , Imazio Massimo , Kindermann Ingrid , Kristen Arnt V , Maurer Mathew S , Merlini Giampaolo , Pantazis Antonis , Pankuweit Sabine , Rigopoulos Angelos G , Linhart Ales 
Published: February 2021

Abstract
Cardiac amyloidosis is a serious and progressive infiltrative disease that is caused by the deposition of amyloid fibrils at the cardiac level. It can be due to rare genetic variants in the hereditary forms or as a consequence of acquired conditions. Thanks to advances in imaging techniques and the possibility of achieving a non-invasive diagnosis, we now know that cardiac amyloidosis is a more frequent disease than traditionally considered. In this position paper the Working Group on Myocardial and Pericardial Disease proposes an invasive and non-invasive definition of cardiac amyloidosis, addresses clinical scenarios and situations to suspect the condition and proposes a diagnostic algorithm to aid diagnosis. Furthermore, we also review how to monitor and treat cardiac amyloidosis, in an attempt to bridge the gap between the latest advances in the field and clinical practice.
Single-cell visualization of mir-9a and Senseless co-expression during Drosophila melanogaster embryonic and larval peripheral nervous system development
Authors: Gallicchio Lorenzo , Griffiths-Jones Sam , Ronshaugen Matthew 
Published: January 2021

Abstract
The Drosophila melanogaster peripheral nervous system (PNS) comprises the sensory organs that allow the fly to detect environmental factors such as temperature and pressure. PNS development is a highly specified process where each sensilla originates from a single sensory organ precursor (SOP) cell. One of the major genetic orchestrators of PNS development is Senseless, which encodes a zinc finger transcription factor (Sens). Sens is both necessary and sufficient for SOP differentiation. Senseless expression and SOP number are regulated by the microRNA miR-9a. However, the reciprocal dynamics of Senseless and miR-9a are still obscure. By coupling single-molecule FISH with immunofluorescence, we are able to visualize transcription of the mir-9a locus and expression of Sens simultaneously. During embryogenesis, we show that the expression of mir-9a in SOP cells is rapidly lost as Senseless expression increases. However, this mutually exclusive expression pattern is not observed in the third instar imaginal wing disc, where some Senseless-expressing cells show active sites of mir-9a transcription. These data challenge and extend previous models of Senseless regulation and show complex co-expression dynamics between mir-9a and Senseless. The differences in this dynamic relationship between embryonic and larval PNS development suggest a possible switch in miR-9a function. Our work brings single-cell resolution to the understanding of dynamic regulation of PNS development by Senseless and miR-9a.
In vivo transcriptome analysis provides insights into host-dependent expression of virulence factors by Yersinia entomophaga MH96, during infection of Galleria mellonella
Authors: Paulson Amber R , O’Callaghan Maureen , Zhang Xue-Xian , Rainey Paul B , Hurst Mark R H 
Published: January 2021

Abstract
The function of microbes can be inferred from knowledge of genes specifically expressed in natural environments. Here, we report the in vivo transcriptome of the entomopathogenic bacterium Yersinia entomophaga MH96, captured during initial, septicemic, and pre-cadaveric stages of intrahemocoelic infection in Galleria mellonella. A total of 1285 genes were significantly upregulated by MH96 during infection; 829 genes responded to in vivo conditions during at least one stage of infection, 289 responded during two stages of infection, and 167 transcripts responded throughout all three stages of infection compared to in vitro conditions at equivalent cell densities. Genes upregulated during the earliest infection stage included components of the insecticidal toxin complex Yen-TC (chi1, chi2, and yenC1), genes for rearrangement hotspot element containing protein yenC3, cytolethal distending toxin cdtAB, and vegetative insecticidal toxin vip2. Genes more highly expressed throughout the infection cycle included the putative heat-stable enterotoxin yenT and three adhesins (usher-chaperone fimbria, filamentous hemagglutinin, and an AidA-like secreted adhesin). Clustering and functional enrichment of gene expression data also revealed expression of genes encoding type III and VI secretion system-associated effectors. Together these data provide insight into the pathobiology of MH96 and serve as an important resource supporting efforts to identify novel insecticidal agents.
Global translational landscape of the Candida albicans morphological transition
Authors: Mundodi Vasanthakrishna , Choudhary Saket , Smith Andrew D , Kadosh David 
Published: January 2021

Abstract
Candida albicans, a major human fungal pathogen associated with high mortality and/or morbidity rates in a wide variety of immunocompromised individuals, undergoes a reversible morphological transition from yeast to filamentous cells that is required for virulence. While previous studies have identified and characterized global transcriptional mechanisms important for driving this transition, as well as other virulence properties, in C. albicans and other pathogens, considerably little is known about the role of genome-wide translational mechanisms. Using ribosome profiling, we report the first global translational profile associated with C. albicans morphogenesis. Strikingly, many genes involved in pathogenesis, filamentation, and the response to stress show reduced translational efficiency (TE). Several of these genes are known to be strongly induced at the transcriptional level, suggesting that a translational fine-tuning mechanism is in place. We also identify potential upstream open reading frames (uORFs), associated with genes involved in pathogenesis, and novel ORFs, several of which show altered TE during filamentation. Using a novel bioinformatics method for global analysis of ribosome pausing that will be applicable to a wide variety of genetic systems, we demonstrate an enrichment of ribosome pausing sites in C. albicans genes associated with protein synthesis and cell wall functions. Altogether, our results suggest that the C. albicans morphological transition, and most likely additional virulence processes in fungal pathogens, is associated with widespread global alterations in TE that do not simply reflect changes in transcript levels. These alterations affect the expression of many genes associated with processes essential for virulence and pathogenesis.
Genetic variation in aneuploidy prevalence and tolerance across Saccharomyces cerevisiae lineages
Authors: Scopel Eduardo F C , Hose James , Bensasson Douda , Gasch Audrey P 
Published: February 2021

Abstract
Individuals carrying an aberrant number of chromosomes can vary widely in their expression of aneuploidy phenotypes. A major unanswered question is the degree to which an individual’s genetic makeup influences its tolerance of karyotypic imbalance. Here we investigated within-species variation in aneuploidy prevalence and tolerance, using Saccharomyces cerevisiae as a model for eukaryotic biology. We analyzed genotypic and phenotypic variation recently published for over 1,000 S. cerevisiae strains spanning dozens of genetically defined clades and ecological associations. Our results show that the prevalence of chromosome gain and loss varies by clade and can be better explained by differences in genetic background than ecology. The relationships between lineages with high aneuploidy frequencies suggest that increased aneuploidy prevalence emerged multiple times in S. cerevisiae evolution. Separate from aneuploidy prevalence, analyzing growth phenotypes revealed that some genetic backgrounds—such as the European Wine lineage—show fitness costs in aneuploids compared to euploids, whereas other clades with high aneuploidy frequencies show little evidence of major deleterious effects. Our analysis confirms that chromosome gain can produce phenotypic benefits, which could influence evolutionary trajectories. These results have important implications for understanding genetic variation in aneuploidy prevalence in health, disease, and evolution.
Gender Disparities in Life Satisfaction After Retirement: The Roles of Leisure, Family, and Finances
Authors: Calasanti Toni , Carr Dawn , Homan Patricia , Coan Victoria 
Published: February 2021

Abstract

Background and Objectives
Recent research on life satisfaction in retirement explores gender differences but yields inconsistent patterns and does not consider gendered sources of satisfaction. We use a gender relations framework to examine whether women and men experience different changes in life satisfaction with retirement, and whether observed differences are a consequence of different assessments of the leisure, family, and financial situations that characterize their post-retirement lives.

Research Design and Methods
We use longitudinal data drawn from men and women in the Health and Retirement Study who transitioned into retirement between ages 62 and 72 for the first time between 2008 and 2016 (N = 593). We employ ordinary least squares regression and mediation tests to assess gender differences in overall and domain-specific life satisfaction (i.e., leisure, family, finances).

Results
Men reported increased life satisfaction following retirement, but women did not. No gender differences related to leisure or family life post-retirement emerged. Gender was associated with post-retirement satisfaction with finances (p &lt; .001), with men reporting higher financial satisfaction. Mediation models confirmed a gender disparity in overall life satisfaction mediated by satisfaction with finances post-retirement (p &lt; .01), explaining approximately one-third of the disparity.

Discussion and Implications
This study shows men derive greater improvements in life satisfaction in association with retirement than do women, and some of this disparity relates to women’s lower satisfaction with their finances. These findings should caution policy-makers from assuming how women’s increased labor force participation influences financial security in retirement, and encourage scholars to consider how gender influences subjective assessments of later life.
A self-similar dynamic rupture model based on the simplified wave-rupture analogy
Authors: Dahm T , Heimann S , Metz M , Isken M P 
Published: February 2021

SUMMARYThe investigation of stresses, faults, structure and seismic hazards requires a good understanding and mapping of earthquake rupture and slip. Constraining the finite source of earthquakes from seismic and geodetic waveforms is challenging because the directional effects of the rupture itself are small and dynamic numerical solutions often include a large number of free parameters. The computational effort is large and therefore difficult to use in an exploratory forward modelling or inversion approach. Here, we use a simplified self-similar fracture model with only a few parameters, where the propagation of the fracture front is decoupled from the calculation of the slip. The approximative method is flexible and computationally efficient. We discuss the strengths and limitations of the model with real-case examples of well-studied earthquakes. These include the Mw 8.3 2015 Illapel, Chile, megathrust earthquake at the plate interface of a subduction zone and examples of continental intraplate strike-slip earthquakes like the Mw 7.1 2016 Kumamoto, Japan, multisegment variable slip event or the Mw 7.5 2018 Palu, Indonesia, supershear earthquake. Despite the simplicity of the model, a large number of observational features ranging from different rupture-front isochrones and slip distributions to directional waveform effects or high slip patches are easy to model. The temporal evolution of slip rate and rise time are derived from the incremental growth of the rupture and the stress drop without imposing other constraints. The new model is fast and implemented in the open-source Python seismology toolbox Pyrocko, ready to study the physics of rupture and to be used in finite source inversions.
Glycosylation of recombinant rabbit immunoglobulins influences protease susceptibility as shown by comprehensive mass spectrometric glycan analysis
Authors: Friligou Irene , Gassner Jana , Knoblauch Dominic , Kagerer Gabriele , Popp Franziska , Voit Susanne , Engel Alfred M , Leinenbach Andreas , Steffen Wojtek , Haberger Markus , Tabarés Glòria 
Published: February 2021

AbstractRecombinant immunoglobulins (rIgGs) have become increasingly important as therapeutic agents and diagnostic tools in recent years. Genetic engineering allows the introduction of non-natural features such as the Sortase motif for site-directed labeling. In this study, the enzyme Sortase A (SrtA) was used for the proteolytic cleavage of rIgGs to produce their biotinylated Fab fragments by locating the cleavage site close to the hinge region. However, SrtA cleavage of engineered rabbit IgGs (rRb-IgGs) derived from human embryonic kidney (HEK) 293 cells showed significantly lower yields compared with their mouse counterparts. Nonrecombinant Rb-IgGs have N- and O-glycans, and the presence of O-glycans close to the hinge region of the rRb-IgGs might affect the susceptibility of these antibodies to SrtA cleavage. In addition, the glycosylation pattern of rIgGs differs depending on the host cell used for expression. Therefore, we analyzed the N- and O-glycans of various rRb-IgGs expressed in HEK293 cells, detecting and quantifying 13 different N-glycan and 3 different O-glycan structures. The distribution of the different detected glycoforms in our rRb-IgG N-glycan analysis is in agreement with previous studies on recombinant human IgG N-glycans, confirming the hypothesis that the host cell defines the glycosylation of the recombinant produced IgGs. O-glycosylation could be mapped onto the threonine residue within the hinge region sequence XPTCPPPX, as already described previously for nonrecombinant Rb-IgGs. Substitution of this threonine allowed an almost complete Fab fragment cleavage. Therefore, we could confirm the hypothesis that the O-glycans affect the SrtA activity, probably due to steric hindrance.