bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cervical Squamous Intraepithelial Lesions are Associated with Changes in the Vaginal Microbiota of Mexican Women
Authors: Nieves-Ramírez ME , Partida-Rodríguez O , Moran P , Serrano-Vázquez A , Pérez-Juárez H , Pérez-Rodríguez ME , Arrieta MC , Ximénez-García C , Finlay BB 
Published: February 2021

ABSTRACTCervical cancer is an important health concern worldwide and is one of the leading causes of deaths in Mexican women. Previous studies have shown changes in the female genital tract microbe community related to Human Papillomavirus (HPV) infection and cervical cancer, yet this link remains unexplored in many human populations. This study evaluated the vaginal bacterial community among Mexican women with pre-cancerous Squamous Intraepithelial Lesions (SIL). We sequenced the V3 region of the 16S rRNA gene (Illumina Miseq) in cervical samples from 300 Mexican women, including 157 patients with SIL, most of which were HPV positive, and 143 healthy women without HPV infection or SIL. Beta-diversity analysis showed that 14.6% of the variance in vaginal bacterial community structure is related to the presence of SIL. Presence of SIL was also associated with a higher species richness (Chao 1). MaAsLiN analysis yielded independent associations between SIL/HPV status and an increase in the relative abundanceBrachybacterium conglomeratum, as well as a decrease inSphingobium yanoikuyaeandLactobacillusspp. We also identified independent associations between HPV-16, the most common HPV subtype linked to SIL, andBrachybacterium conglomeratum. Our work indicates that the presence of SIL and HPV infection is associated with important changes in the vaginal microbiome, some of which may be specific to this human population.IMPORTANCEHPV plays a critical role in cervical carcinogenesis but is not sufficient for cervical cancer development, indicating involvement of other factors. Vaginal microbiota is an important factor in controlling infections caused by HPV and depending on its composition it can modulate the microenvironment in vaginal mucosa against viral infection. Ethnic and sociodemographic factors influence differences in vaginal microbiome composition, which underlies the dysbiotic patterns linked to HPV infection and cervical cancer across different women populations. Here, we provide evidence for associations between vaginal microbiota patterns and HPV infection, linked to ethnic and sociodemographic factor. To our knowledge, this is the first report ofBrevibacterium aureumandBrachybacterium conglomeratumspecies linked to HPV infection or SIL.
Genetic determinants of intrinsic antibiotic tolerance inMycobacterium avium
Authors: Matern William M. , Parker Harley , Danchik Carina , Hoover Leah , Bader Joel S. , Karakousis Petros C. 
Published: February 2021

AbstractMycobacterium aviumcomplex (MAC) is one of the most prevalent causes of nontuberculous mycobacteria pulmonary infection in the United States, yet it remains understudied. Current MAC treatment requires more than a year of intermittent to daily combination antibiotic therapy, depending on disease severity. In order to shorten and simplify curative regimens, it is important to identify the innate bacterial factors contributing to reduced antibiotic susceptibility, namely antibiotic tolerance genes. In this study, we performed a genome-wide transposon screen to elucidateM. aviumgenes that play a role in the bacterium’s tolerance to first- and second-line antibiotics. We identified a total of 193 uniqueM. aviummutants with significantly altered susceptibility to at least one of the four clinically used antibiotics we tested, including two mutants (in DFS55_00905 and DFS55_12730) with panhypersusceptibility. The products of the antibiotic tolerance genes we have identified may represent novel targets for future drug development studies aimed at shortening the duration of therapy for MAC infections.ImportanceThe prolonged treatment required to eradicateMycobacterium aviumcomplex (MAC) infection is likely due to the presence of subpopulations of antibiotic-tolerant bacteria with reduced susceptibility to currently available drugs. However, little is known about the genes and pathways responsible for antibiotic tolerance in MAC. In this study, we performed a forward genetic screen to identifyM. aviumantibiotic tolerance genes, whose products may represent attractive targets for the development of novel adjunctive drugs capable of shortening curative treatment for MAC infections.
Synergistic Activity of Minocycline and Rifampin in Combination with Antifungal Drugs againstCandida auris
Authors: Brennan-Krohn Thea , Friar Liam , Ditelberg Sarah , Kirby James E. 
Published: February 2021

ABSTRACTCandida aurisis an emerging multidrug-resistant fungal pathogen that spreads readily in healthcare settings and has caused numerous hospital outbreaks. Very few treatment options exist forC. aurisinfections. We evaluated the activity of all two-drug combinations of three antifungal agents (amphotericin B, caspofungin, and voriconazole) and two antibacterial agents (minocycline and rifampin) against a collection of 10C. aurisisolates using an automated, inkjet printer-assisted checkerboard array method. Three antibacterial-antifungal combinations (amphotericin B plus rifampin, amphotericin B plus minocycline, and caspofungin plus minocycline) demonstrated synergistic activity by checkerboard array against ≥90% of strains. The two amphotericin B-containing combinations were also synergistic using the time-kill synergy testing method. Our results suggest that combinations of antifungal and antibacterial agents may provide a promising avenue for treatment of this multidrug-resistant pathogen.
Expression patterns ofPlasmodium falciparum clonally variant genes at the onset of a blood infection in non-immune humans
Authors: Pickford Anastasia K. , Michel-Todó Lucas , Dupuy Florian , Mayor Alfredo , Alonso Pedro L. , Lavazec Catherine , Cortés Alfred 
Published: February 2021

AbstractClonally variant genes (CVGs) play fundamental roles in the adaptation ofPlasmodium falciparumparasites to the fluctuating conditions of the human host. However, their expression patterns under the natural conditions of the blood circulation have been characterized in detail only for a few specific gene families. Here we provide a detailed characterization of the completeP. falciparumtranscriptome across the full intraerythrocytic development cycle (IDC) at the onset of a blood infection in non-immune human volunteers. We found that the vast majority of transcriptional differences between parasites obtained from the volunteers and the parental parasite line maintained in culture occur in CVGs. Specifically, we observed a major increase in the transcript levels of most members of thepfmc-2tmandgbpfamilies and of specific genes of other families, in addition to previously reported changes invarandclag3genes expression. Large transcriptional differences correlate with changes in the distribution of heterochromatin, confirming their epigenetic nature. The analysis of parasites collected at different time points along the infection indicates that when parasites pass through transmission stages, the epigenetic memory at CVG loci is lost, resulting in a reset of their expression state and reestablishment of new epigenetic patterns.ImportanceThe ability of malaria parasites to adapt to changes in the human blood environment, where they produce long term infection associated with clinical symptoms, is fundamental for their survival. Clonally variant genes, regulated at the epigenetic level, play a major role in this adaptive process, as changes in the expression of these genes result in antigenic and functional alterations that enable immune evasion and provide phenotypic plasticity. However, the way these genes are expressed under the natural conditions of the human circulation or how their expression is affected by passage through transmission stages is not well understood. Here we provide a comprehensive characterization of the expression patterns of these genes at the onset of human blood infections, which reveals major differences within vitrocultured parasites and also distinctive alterations between different families of clonally variant genes. We also show that epigenetic patterns are erased and reestablished during transmission stages.
Operational and biochemical aspects of co-digestion (co-AD) from sugarcane vinasse, filter cake and deacetylation liquor
Authors: Volpi Maria Paula. C. , Ferraz Antonio Djalma N. , Franco Telma T. , Moraes Bruna S. 
Published: February 2021

ABSTRACTThis work performed co-AD from the vinasse and filter cake (from 1G ethanol production) and deacetylation liquor (from the pre-treatment of sugarcane straw for 2G ethanol production) in a semi-Continuous Stirred Tank Reactor (s-CSTR) aiming to provide optimum operational parameters for continuous CH4production. Using filter cake as co-substrate may allow the reactor to operate throughout the year, as it is available in the sugarcane off-season, unlike vinasse. A comparison was made from the microbial community of the seed sludge and the reactor sludge when CH4production stabilized. Lactate, butyrate and propionate fermentation routes were denoted at the start-up of the s-CSTR, characterizing the acidogenic phase: the Oxidation-Reduction Potential (ORP) values ranged from -800 to -100 mV. Once the methanogenesis was initiated, alkalizing addition was no longer needed as its demand by the microrganisms was supplied by the alkali-characteriscs of the deacetylation liquor. The gradual increase of the applied Organic Load Rates (OLR) allowed stabilization of the methanogenesis from 3.20 gVS L-1day-1: the highest CH4yield (230 NmLCH4gSV-1) and average organic matter removal efficiency (83% ± 13) was achieved at ORL of 4.16 gVS L-1day-1. The microbial community changed along the reactor operation, presenting different metabolic routes mainly due to the used lignocellulosic substrates. Bacteria from the syntrophic acetate oxidation (SAO) process coupled to hydrogenotrophic methanogenesis were predominant (∼ 2% Methanoculleus) during the CH4production stability. The overall results are useful as preliminary drivers in terms of visualizing the co-AD process in a sugarcane biorefinery integrated to scale.KeypoitnsIntegration of 1G2G sugarcane ethanol biorefinery from co-digestion of its residues Biogas production from vinasse, filter cake and deacetylation liquor in a semi-CSTR Lignicellulosic substrates affected the biochemical routes and microbial community Biomol confirmed the stablismenht of thermophilic community from mesophilic sludge
Discovery of a AhR flavonoid agonist that counter-regulates ACE2 expression in rodent models of inflammation and attenuates ACE2-SARS-CoV2 interaction in vitro
Authors: Biagioli Michele , Marchianò Silvia , Roselli Rosalinda , Giorgio Cristina Di , Bellini Rachele , Bordoni Martina , Gidari Anna , Sabbatini Samuele , Francisci Daniela , Fiorillo Bianca , Catalanotti Bruno , Distrutti Eleonora , Carino Adriana , Zampella Angela , Costantino Gabriele , Fiorucci Stefano 
Published: February 2021

AbstractThe severe acute respiratory syndrome (SARS)-CoV-2, a newly emerged coronavirus first identified in 2019, is the pathogenetic agent od Corona Virus Induced Disease (COVID)19. The virus enters the human cells after binding to the angiotensin converting enzyme (ACE) 2 receptor in target tissues. ACE2 expression is induced in response to inflammation. The colon expression of ACE2 is upregulated in patients with inflammatory bowel disease (IBD), highlighting a potential risk of intestinal inflammation in promoting viral entry in the human body. Because mechanisms that regulate ACE2 expression in the intestine are poorly understood and there is a need of anti-SARS-CoV2 therapies, we have settled to investigate whether natural flavonoids might regulate the expression of ACE2 in intestinal models of inflammation. The results of these studies demonstrated that pelargonidin, a natural flavonoid bind and activates the Aryl hydrocarbon Receptor (AhR) in vitro and reverses intestinal inflammation caused by chronic exposure to high fat diet or to the intestinal braking-barrier agent DSS in a AhR-dependent manner. In these two models, development of colon inflammation associated with upregulation of ACE2 mRNA expression. Colon levels of ACE2 mRNA were directly correlated with TNFα mRNA levels. In contrast to ACE2 the angiotensin 1-7 receptor MAS was downregulated in the inflamed tissues. Molecular docking studies suggested that pelargonidin binds a fatty acid binding pocket on the receptor binding domain of SARS-CoV2 Spike protein. In vitro studies demonstrated that pelargonidin significantly reduces the binding of SARS-CoV2 Spike protein to ACE2 and reduces the SARS-CoV2 replication in a concentration-dependent manner. In summary, we have provided evidence that a natural flavonoid might hold potential in reducing intestinal inflammation and ACE2 induction in the inflamed colon in a AhR-dependent manner.
Stratification of Chemotherapy-Treated Stage III Colorectal Cancer Patients Using Multiplexed Imaging and Single Cell Analysis of T Cell Populations
Authors: Stachtea Xanthi , Loughrey Maurice B. , Salvucci Manuela , Lindner Andreas U. , Cho Sanghee , McDonough Elizabeth , Sood Anup , Graf John , Santamaria-Pang Alberto , Corwin Alex , Laurent-Puig Pierre , Dasgupta Sonali , Van Schaeybroeck Sandra , Lawler Mark , Prehn Jochen H. M. , Ginty Fiona , Longley Daniel B 
Published: February 2021

AbstractColorectal cancer (CRC) has one of the highest cancer incidences and mortality rates. In stage III, postoperative chemotherapy benefits <20% of patients, while more than 50% will develop distant metastases. Predictive biomarkers for identification of patients with increased risk for disease recurrence are currently lacking, with progress in biomarker discovery hindered by the disease’s inherent heterogeneity. The immune profile of colorectal tumors has previously been found to have prognostic value. The aims of this study were to evaluate immune signatures in the tumor microenvironment (TME) using anin situmultiplexed immunofluorescence imaging and single cell analysis technology (Cell DIVE™). Tissue microarrays (TMAs) with up to three 1mm diameter cores per patient were prepared from 117 stage III CRC patients treated with adjuvant fluoropyrimidine/oxaliplatin chemotherapy. Single sections underwent multilplexed immunofluorescence with Cy3- and Cy5-conjugated antibodies for immune cell markers (CD45, CD3, CD4, CD8, FOXP3, PD1) and cell segmentation markers (DAPI, pan-cytokeratin, AE1, NaKATPase and S6). We applied a probabilistic multi-class, multi-label classification algorithm based on multi-parametric models to build statistical models of protein expression to classify immune cells. Expert annotations of immune cell markers were made on a range of images, and Support Vector Machines (SVM) were used to derive a statistical model for cell classification. Images were also manually scored independently by a Pathologist as ‘high’, ‘moderate’ or ‘low’, for stromal and total immune cell content. Excellent agreement was found between manual and total automated scores (p<0.0001). Higher levels of multi-marker classified regulatory T cells (CD3+CD4+FOXP3+PD1-) were significantly associated with disease-free survival (DFS) and overall-survival (OS) (p=0.049 and 0.032), compared to FOXP3 alone. Our results also showed that PD1- Tregs rather than PD1+ Tregs were associated with improved survival. Overall, compared to single markers, multi-marker classification provided more accurate quantitation of immune cells with greater potential for predicting patient outcomes.
Mammalian adipogenesis regulators (Aregs) exhibit robust non- and anti-adipogenic properties that arise with age and involve retinoic acid signalling
Authors: Zachara Magda , Rainer Pernille Y. , Russeil Julie M. , Hashimi Horia , Alpern Daniel , Ferrero Radiana , Litovchenko Maria , Deplancke Bart 
Published: February 2021

AbstractAdipose stem and precursor cells (ASPCs) give rise to adipocytes and determine the composition and plasticity of adipose tissue. Recently, several studies have demonstrated that ASPCs partition into at least three distinct cell subpopulations:Dpp4+ stem-like cells,Aoc3+ pre-adipocyte-like cells, and the enigmatic CD142+ cells. A great challenge now is to functionally characterize these distinct ASPC populations. Here, we focus on CD142+ ASPCs since discrepant properties have been assigned to this subpopulation, from adipogenic to non- and even anti-adipogenic. To address these inconsistencies, we comprehensively characterized mammalian subcutaneous CD142+ ASPCs across various sampling conditions. Our findings demonstrate that CD142+ ASPCs exhibit high molecular and phenotypic robustness, firmly supporting their non- and anti-adipogenic properties. However, these properties emerge in an age-dependent manner, revealing surprising temporal CD142+ ASPC behavioural alterations. Finally, using multi-omic and functional assays, we show that the inhibitory nature of these adipogenesis-regulatory CD142+ ASPCs (Aregs) is driven by specifically expressed secretory factors that cooperate with the retinoic acid signalling pathway to transform the adipogenic state of CD142− ASPCs into a non-adipogenic, Areg-like one.
Alternative developmental and transcriptomic responses to host plant water limitation in a butterfly metapopulation
Authors: Kahilainen Aapo , Oostra Vicencio , Somervuo Panu , Minard Guillaume , Saastamoinen Marjo 
Published: February 2021

AbstractPredicting how climate change affects biotic interactions and their evolution poses a challenge. Plant-insect herbivore interactions are particularly sensitive to climate change, as climate-induced changes in plant quality cascade into the performance of insect herbivores. Whereas the immediate survival of herbivore individuals depends on plastic responses to climate change induced nutritional stress, long-term population persistence via evolutionary adaptation requires genetic variation for these responses. In order to assess the prospects for population persistence under climate change, it is therefore crucial to characterise response mechanisms to climate change induced stressors, and quantify their variability in natural populations. Here, we test developmental and transcriptomic responses to water limitation induced host plant quality change in a Glanville fritillary butterfly (Melitaea cinxia) metapopulation. We combine nuclear magnetic resonance spectroscopy on the plant metabolome, larval developmental assays and an RNA seq analysis of the larval transcriptome. We observed that responses to feeding on water limited plants, in which amino acids and aromatic compounds are enriched, showed marked intrapopulation variation, with individuals of some families performing better on control and others on water limited plants. The transcriptomic responses were concordant with the developmental responses: Families exhibiting opposite developmental responses also produced opposite transcriptomic responses, e.g. in growth associated intracellular signalling. The opposite developmental and transcriptomic responses are associated with between families differences in organic compound catabolism and storage protein production. The results reveal heritable intrapopulation variability in plasticity, suggesting potential for evolutionary responses to drought-induced changes in host plant quality in the FinnishM. cinxiametapopulation.
Optimized cDICE for efficient reconstitution of biological systems in giant unilamellar vesicles
Authors: Van de Cauter Lori , Fanalista Federico , van Buren Lennard , De Franceschi Nicola , Godino Elisa , Bouw Sharon , Danelon Christophe , Dekker Cees , Koenderink Gijsje H. , Ganzinger Kristina A. 
Published: February 2021

AbstractGiant unilamellar vesicles (GUVs) are often used to mimic biological membranes in reconstitution experiments. They are also widely used in research on synthetic cells as they provide a mechanically responsive reaction compartment that allows for controlled exchange of reactants with the environment. However, while many methods exist to encapsulate functional biomolecules in GUVs, there is no one-size-fits-all solution and reliable GUV fabrication still remains a major experimental hurdle in the field. Here, we show that defect-free GUVs containing complex biochemical systems can be generated by optimizing a double-emulsion method for GUV formation called continuous droplet interface crossing encapsulation (cDICE). By tightly controlling environmental conditions and tuning the lipid-in-oil dispersion, we show that it is possible to significantly improve the reproducibility of high-quality GUV formation as well as the encapsulation efficiency. We demonstrate efficient encapsulation for a range of minimal systems including a minimal actin cytoskeleton, membrane-anchored DNA nanostructures, and a functional PURE (Protein synthesis Using Recombinant Elements) system. Our optimized cDICE method displays promising potential to become a standard method in biophysics and bottom-up synthetic biology.
Whole-body plethysmography revisited
Authors: Hülsmann Swen , Khan Amara , Hagos Liya , Hindermann Martin , Nägel Torsten , Dullin Christian 
Published: February 2021

AbstractWhole-body plethysmography (WBP) is an established method to determine physiological parameters and pathophysiological alteration of breathing in animals and animal models of a variety of diseases, reaching from pulmonary diseases to complex neurological syndromes. Although frequently used, there is ongoing debate about what exactly is measured by whole-body-plethysmography and how reliable the data derived from this method are? Here, we designed a simple device that can serve as an artificial lung model that enables a thorough evaluation of different predictions about and around whole-body plethysmography. Using our lung model, we confirmed that during WBP two components contribute to the pressure changes detected in the chamber: 1) the increase of the pressure due to heating and moistening of the air, termed as conditioning, during inspiration; 2) changes of chamber pressure that depend on airway resistance. Both components overlap and contribute to the temporal pressure-profile measured in the chamber or across the wall of the chamber. Our data showed that a precise measurement of the breathing volume appears to be hindered by at least two factors: 1) the unknown relative contribution of each of these components; 2) not only the air in the inspired volume is conditioned during inspiration, but also air within the residual volume and death space that is recruited during inspiration. Moreover, our data suggest that the expiratory negative pressure peak that is used to determine the so called “enhanced pause” (Penh) parameter is not a measure for airway resistance as such but rather a consequence of the animal’s response to the airway resistance, using active expiration to overcome the resistance by a higher thoracic pressure.