bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endometrial Gap Junction Expression - Early Indicators of Endometriosis and Integral to Invasiveness
Authors: Chen Chen-Wei , Chavez Jeffery , Lin Li-Ling , Wang Chiou-Miin , Hsu Ya-Ting , Hart Matthew J. , Ruan Jianhua , Gillette Laurel , Burney Richard O. , Schenken Robert S. , Robinson Randal D. , Gaczynska Maria , Osmulski Pawel , Kirma Nameer B. , Nicholson Bruce J. 
Published: January 2021

AbstractEndometriosis is an invasive disease, and a leading cause of pain, infertility and disability among women, with an incidence 10 fold that of cancer. A more complete understanding of disease pathogenesis is essential for the development of non-surgical diagnostic assays and non-hormonal therapeutics. Avoidance of immune clearance and implantation of endometrial tissue on peritoneal surfaces are features of endometriosis lesion formation that overlap with cancer metastasis. Connexins, and the gap junctions they form, have been implicated in cancer progression, and may be associated endometriosis pathophysiology. Single cell transcriptomic profiling of endometrial epithelial and stromal cells from women with endometriosis reveals a striking and progressive shift in expression of connexins and related regulatory and junctional genes. We demonstrate that gap junction coupling between endometrial cells and the peritoneal mesothelium is dramatically induced, specifically in endometriosis patients, and is required for invasion by inducing breakdown of the mesothelial barrier function.
Inhalable textile microplastic fibers impair lung repair
Authors: van Dijk F. , Song S. , van Eck G.W.A , Wu X. , Bos I.S.T. , Boom D.H.A. , Kooter I.M. , Spierings D.C.J. , Wardenaar R. , Cole M. , Salvati A. , Gosens R. , Melgert B.N. 
Published: January 2021

AbstractSynthetic textiles shed fibers that accumulate indoors and this results in continuous exposure when indoors. High exposure to microplastic fibers in nylon flock workers has been linked to the development of airway and interstitial lung disease, but the exact health effects of microplastic fibers on the lungs are unknown. Here we determined effects of polyester and nylon textile microplastic fibers on airway and alveolar epithelial cells using human and murine lung organoids. We observed that particularly nylon microfibers had a negative impact on the growth and development of airway organoids. We demonstrated that this effect was mediated by components leaking from nylon. Moreover, our data suggested that microplastic textile fibers may especially harm the developing airways or airways undergoing repair. Our results call for a need to assess exposure and inhalation levels in indoor environments to accurately determine the actual risk of these fibers to human health.TeaserAirborne fibers shed from synthetic textiles, in particular nylon, can inhibit repair of the cells coating the airways
TREM2is thyroid hormone regulated making the TREM2 pathway druggable with ligands for thyroid hormone receptor
Authors: Ferrara Skylar J. , Chaudhary Priya , DeBell Margaret J. , Marracci Gail , Miller Hannah , Calkins Evan , Pocius Edvinas , Napier Brooke A. , Emery Ben , Bourdette Dennis , Scanlan Thomas S. 
Published: January 2021

AbstractTriggering receptor expressed on myeloid cells-2 (TREM2) is a cell surface receptor on macrophages and microglia that senses and responds to disease associated signals to regulate the phenotype of these innate immune cells. The TREM2 signaling pathway has been implicated in a variety of diseases ranging from neurodegeneration in the central nervous system to metabolic disease in the periphery. We report here thatTREM2is a thyroid hormone regulated gene and its expression in macrophages and microglia is stimulated by thyroid hormone. Both endogenous thyroid hormone and sobetirome, a synthetic thyroid hormone agonist drug, suppress pro-inflammatory cytokine production from myeloid cells including macrophages that have been treated with the SARS-CoV-2 spike protein which produces a strong, pro-inflammatory phenotype. Thyroid hormone agonism was also found to induce phagocytic behavior in microglia, a phenotype consistent with activation of the TREM2 pathway. The thyroid hormone antagonist NH-3 blocks the anti-inflammatory effects of thyroid hormone agonists and suppresses microglia phagocytosis. Finally, in a murine experimental autoimmune encephalomyelitis (EAE) multiple sclerosis model, treatment with Sob-AM2, a CNS-penetrating sobetirome prodrug, results in increasedTrem2expression in disease lesion resident myeloid cells which correlates with therapeutic benefit in the EAE clinical score and reduced damage to myelin. Our findings represent the first report of endocrine regulation ofTREM2and provide a unique opportunity to drug the TREM2 signaling pathway with orally active small molecule therapeutic agents.
Estimating the fundamental niche: accounting for the uneven availability of existing climates in the calibration area
Authors: Jiménez L. , Soberón J. 
Published: January 2021

AbstractStudies that question important conceptual and methodological aspects of the field of ecological niche modeling (and species distribution modeling) have cast doubts on whether it is possible to estimate the fundamental niche of a species using presence-only data. The main limitation in niche estimation is that presence data come from the realized niche, which is only a subset of the fundamental niche. Most of the existing methods lack the ability to overcome this limitation and therefore fit niches that resemble the realized niche. To obtain a more accurate estimate of the fundamental niche, we propose using the geographic region that is accessible to a species (based on its dispersal ability) to determine a sampling distribution, in environmental space, from which we can quantify the likelihood of observing a particular environmental combination in a sample of presence points. We incorporate this sampling distribution into a multivariate normal model (i.e., a Mahalanobis distance model) by creating a weight function that modifies the probabilities of observing different environmental combinations in a sample of presences. This modification accounts for the uneven availability of environmental conditions. We show that the parameters of this weighted-normal model can be approximated with a maximum likelihood estimation approach; and then used to draw ellipsoids (confidence regions) that represent the fundamental niche of the species. We illustrate the application of our model with two worked examples. First, we use presence data for an invasive species and an accessible area that includes only its native range to evaluate whether the fitted model predicts confirmed establishments of the species outside its native range. Second, we use presence data for closely related species with known accessible areas to demonstrate how the different dispersal abilities of the species constrain a classic Mahalanobis distance model. Overall, we show that accounting for the distribution of environmental conditions that are accessible to a species indeed affects the estimation of the ellipsoids used to model its fundamental niche.
Can we put Humpty Dumpty back together again? What does protein quantification mean in bottom-up proteomics?
Authors: Plubell Deanna L. , Käll Lukas , Webb-Robertson Bobbie-Jo , Bramer Lisa , Ives Ashley , Kelleher Neil L. , Smith Lloyd M. , Montine Thomas J. , Wu Christine C. , MacCoss Michael J. 
Published: January 2021

AbstractBottom-up proteomics provides peptide measurements and has been invaluable for moving proteomics into large-scale analyses. In bottom-up proteomics, protein parsimony and protein inference derived from these measured peptides are important for determining which protein coding genes are present. However, given the complexity of RNA splicing processes, and how proteins can be modified post-translationally, it is overly simplistic to assume that all peptides that map to a singular protein coding gene will demonstrate the same quantitative response. Accordingly, by assuming all peptides from a protein coding sequence are representative of the same protein we may be missing out on detecting important biological differences. To better account for the complexity of the proteome we need to think of new or better ways of handling peptide data.
INTEGRATION OF ENGINEERED “SPARK-CELL” SPHEROIDS FOR OPTICAL PACING OF CARDIAC TISSUE
Authors: Chua Christianne , Han Julie , Li Weizhen , Liu Wei , Entcheva Emilia 
Published: January 2021

AbstractOptogenetic methods for pacing of cardiac tissue can be realized by direct genetic modification of the cardiomyocytes to express light-sensitive actuators, such as channelrhodopsin-2, ChR2, or by introduction of light-sensitized non-myocytes that couple to the cardiac cells and yield responsiveness to optical pacing. In this study, we engineer three-dimensional “spark cells” spheroids, composed of ChR2-expressing human embryonic kidney cells, and characterize their morphology as function of cell density and time. These “spark-cell” spheroids are then deployed to demonstrate site-specific optical pacing of human stem-cell-derived cardiomyocytes (hiPSC-CMs) in 96-well format using non-localized light application and all-optical electrophysiology. We show that the spheroids can be handled using liquid pipetting and can confer optical responsiveness of cardiac tissue earlier than direct viral or liposomal genetic modification of the cardiomyocytes, with 24% providing reliable stimulation of the iPSC-CMs within 6 hours and >80% within 24 hours. Our results demonstrate a scalable, cost-effective method to achieve contactless optical stimulation of cardiac cell constructs that can be integrated in a robotics-amenable workflow for high-throughput drug testing.GRAPHICAL ABSTRACT
Antifungal effects of alantolactone onCandida albicans:anin vitrostudy
Authors: Liu Xin , Zhong Lili , Ma Zhiming , Sui Yujie , Xie Jia’nan , Ma Tonghui , Yang Longfei 
Published: January 2021

AbstractThe human fungal pathogenCandida albicanscan cause many kinds of infections, including biofilm infections on medical devices, while the available antifungal drugs are limited to only a few. In this study, alantolactone (Ala) demonstrated antifungal activities againstC. albicans, as well as otherCandidaspecies, with a MIC of 72 μg/mL. Ala could also inhibit the adhesion, yeast-to-hyphal transition, biofilm formation and development ofC. albicans. The exopolysaccharide of biofilm matrix and extracellular phospholipase production could also be reduced by Ala treatment. Ala could increase permeability ofC. albicanscell membrane and ROS contribute to the antifungal activity of Ala. Overall, the present study suggests that Ala may provide a promising candidate for developing antifungal drugs againstC. albicansinfections.
Specificity and selective advantage of an exclusion system in the integrative and conjugative element ICEBs1ofBacillus subtilis
Authors: Davis Kathleen P. , Grossman Alan D. 
Published: January 2021

AbstractIntegrative and conjugative elements (ICEs) are mobile genetic elements capable of transferring their own and other DNA. They contribute to the spread of antibiotic resistances and other important traits for bacterial evolution. Exclusion is a mechanism used by many conjugative plasmids and a few ICEs to prevent their host cell from acquiring a second copy of the cognate element. ICEBs1ofBacillus subtilishas an exclusion mechanism whereby the exclusion protein YddJ in a potential recipient inhibits the activity of the ICEBs1-encoded conjugation machinery in a potential donor. The target of YddJ-mediated exclusion is the conjugation protein ConG (a VirB6 homolog). Here we defined the regions of YddJ and ConG that confer exclusion specificity and determined the importance of exclusion to host cells. Using chimeras that had parts of ConG from ICEBs1and the closely related ICEBat1we identified a putative extracellular loop of ConG that conferred specificity for exclusion by the cognate YddJ. Using chimeras of YddJ from ICEBs1and ICEBat1we identified two regions in YddJ needed for exclusion specificity. We also found that YddJ-mediated exclusion reduced death of donor cells following conjugation into recipients. Donor death was dependent on the ability of transconjugants to themselves become donors and was reduced under osmo-protective conditions, indicating that death was likely due to alterations in the donor cell envelope caused by excessive conjugation. We postulate that elements that can have high frequencies of transfer likely evolved exclusion mechanisms to protect the host cells from excessive death.ImportanceHorizontal gene transfer is a driving force in bacterial evolution, responsible for the spread of many traits, including antibiotic and heavy metal resistances. Conjugation, one type of horizontal gene transfer, involves DNA transfer from donor to recipient cells through conjugation machinery and direct cell-cell contact. Exclusion mechanisms allow conjugative elements to prevent their host from acquiring additional copies of the element, and are highly specific enabling hosts to acquire heterologous elements. We defined regions of the exclusion protein and its target in the conjugation machinery that convey high specificity of exclusion. We found that exclusion protects donors from cell death during periods of high transfer. This is likely important for the element to enter new populations of cells.
The King’s College London Coronavirus Health and Experiences of Colleagues at King’s Study: SARS-CoV-2 antibody response in a higher education sample
Authors: Leightley Daniel , Vitiello Valentina , Wickersham Alice , Davis Katrina A.S. , Bergin-Cartwright Gabriella , Lavelle Grace , Stevelink Sharon A.M , Hotopf Matthew , Razavi Reza 
Published: January 2021

AbstractObjectiveTo assess the feasibility of home antibody testing as part of large-scale study, the King’s College London Coronavirus Health and Experiences of Colleagues at King’s (KCL CHECK).MethodsParticipants of the KCL CHECK study were sent a SureScreen Diagnostics COVID-19 IgG/IgM Rapid Test Cassette to complete at home in June 2020 (phase 1) and September 2020 (phase 2). Participants were asked to upload a test result image to a study website. Test result images and sociodemographic information were analysed by the research team.ResultsA total of n=2716 participants enrolled in the KCL CHECK study, with n=2003 (73.7%) and n=1825 (69.3%) consenting and responding to phase 1 and 2. Of these, n=1882 (93.9%; phase 1) and n=1675 (91.8%; phase 2) returned a valid result. n=123 (6.5%; phase 1) and n=91 (5.4%; phase 2) tested positive for SARS-CoV-2 antibodies. A total of n=1488 participants provided a result in both phases, with n=57 (3.8%) testing positive for SARS- CoV-2 antibodies across both phases, suggesting a reduction in the number of positive antibody results over time. Initial comparisons showed variation by age group, gender and clinical role.ConclusionsOur study highlights the feasibility of rapid, repeated and low-cost SARS-CoV-2 serological testing without the need for face-to-face contact.What is already known about this subject?Higher education institutions have a duty of care to minimise the spread and transmission of COVID-19 in its campuses, and among staff and students. The reopening of higher education buildings and campuses has brought about a mass movement of students, academics and support staff from across the UK. Serological antibody studies can assist by highlighting groups of people and behaviours associated with high risk of COVID-19.What are the new findings?We report a framework for SARS-CoV-2 serological antibody testing in an occupational group of postgraduate research students and current members of staff at King’s College London. Over two phases of data collection, 6.5% (phase 1) and 5.4% (phase 2) tested positive for SARS-CoV-2 antibodies, with only 3.8% testing positive for antibodies in both phases, suggesting a reduction in positive antibody results over time.How might this impact on policy or clinical practice in the foreseeable future?Our study highlights the feasibility of rapidly deploying low-cost and repeatable SARS-CoV-2 serological testing, without the need for face-to-face contact, to support the higher education system of the UK.
Public Views about COVID-19 “Immunity Passports”
Authors: Hall Mark A. , Studdert David M. 
Published: January 2021

ABSTRACTImportanceDiscovery of effective vaccines and increased confidence that infection confers extended protection against COVID-19 have renewed discussion of using immunity certificates or “passports” to selectively reduce ongoing public health restrictions.ObjectiveTo determine public views regarding government and private conferral of immunity privileges.Design and SettingNational on-line survey fielded in June 2020. Participants were randomly asked about either government “passports” or private “certificates” for COVID-19 immunity.ParticipantsAdults from a standing panel maintained for academic research, selected to approximate national demographics.Main Outcomes/MeasuresLevel of support/opposition to immunity privileges, and whether views vary based on: government vs. private adoption; demographics; political affiliation or views; or various COVID19-related attitudes and experiences.ResultsOf 1315 respondents, 45.2% supported immunity privileges, with slightly more favoring private certificates than government passports (48.1% vs 42.6%, p=0.04). Support was greater for using passports or certificates to enable returns to high-risk jobs or attendance at large recreational events than for returning to work generally. Levels of support did not vary significantly according to age groups, socioeconomic or employment status, urbanicity, political affiliation or views, or whether the respondent had chronic disease(s). However, estimates from adjusted analyses showed less support among women (Odds Ratio, 0.64; 95% Confidence Interval, 0.51 to 0.80), and among Hispanics (0.56; 0.40 to 0.78) and other minorities (0.58; 0.40 to 0.85) compared with whites, but not among blacks (0.83; 0.60 to 1.15). Support was much higher among those who personally wanted a passport or certificate (75.6% vs 24.4%) and much lower among those who believed this would harm the social fabric of their community (22.9% vs 77.1%).Conclusions and RelevancePublic views are divided on either government or private use of immunity certificates, but, prior to any efforts to politicize the issues, these views do not vary along usual political lines, nor by characteristics that indicate individual vulnerability to infection. Social consensus on the desirability of an immunity privileges programs may be difficult to achieve.Key PointsQuestionWhat are the public’s views on government or private use of immunity “passports” to selectively lift COVID-19 restrictions?FindingsViews are divided and do not vary substantially according to political affiliation or many demographic factors. Support is greater among men but lower among Hispanics and those who believe that immunity privileges would harm the social fabric of society.MeaningSocial consensus will be difficult to achieve on the appropriateness of immunity privileges.
An Updated Investigation Prior To COVID-19 Vaccination Program In Indonesia: Full-Length Genome Mutation Analysis Of SARS-CoV-2
Authors: Nidom Reviany V. , Indrasari Setyarina , Normalina Irine , Nidom Astria N. , Afifah Balqis , Dewi Lestari , Putra Andra Kusuma , Ansori Arif N. M. , Kusala Muhammad K. J. , Alamudi Mohammad Y. , Nidom Chairul A. 
Published: January 2021

ABSTRACTIntroductionIndonesia kick-started the big project of COVID-19 vaccination program in January 2021 by employed vaccine to the president of Indonesia. The outbreak and rapid transmission of COVID-19 have endangered the global health and economy. This study aimed to investigate the full-length genome mutation analysis of 166 Indonesian SARS-CoV-2 isolates as 12 January 2021.MethodsAll data of isolates was extracted from the Global Initiative on Sharing All Influenza Data (GISAID) EpiCoV database. CoVsurver was employed to investigate the full-length genome mutation analysis of all isolates. Furthermore, this study also focused on the unlocking of mutation in Indonesian SARS-CoV-2 isolates S protein. WIV04 isolate that was originated from Wuhan, China was used as a virus reference according to CoVsurver default. All data was visualized using GraphPad Prism software, PyMOL, and BioRender.ResultsThis study result showed that a full-length genome mutation analysis of 166 Indonesian SARS-CoV-2 isolates was successfully discovered. Every single mutation in S protein was described and then visualised by employing BioRender. Furthermore, it also found that D614G mutation appeared in 103 Indonesian SARS-CoV-2 isolates.ConclusionTo sum up, this study helps to observe the spread of the COVID-19 transmission. However, it would like to propose that the epidemiological surveillance and genomics studies might be improved on COVID-19 pandemic in Indonesia.
Profiling acetogenic community dynamics in anaerobic digesters - comparative analyses using next-generation sequencing and T-RFLP
Authors: Singh Abhijeet , Müller Bettina , Schnürer Anna 
Published: January 2021

ABSTRACTAcetogens play a key role in anaerobic degradation of organic material and in maintaining biogas process efficiency. Profiling this community and its temporal changes can help evaluate process stability and function, especially under disturbance/stress conditions, and avoid complete process failure. The formyltetrahydrofolate synthetase (FTHFS) gene can be used as a marker for acetogenic community profiling in diverse environments. In this study, we developed a new high-throughput FTHFS gene sequencing method for acetogenic community profiling and compared it with conventional T-RFLP of the FTHFS gene, 16S rRNA gene-based profiling of the whole bacterial community, and indirect analysis via 16S rRNA profiling of the FTHFS gene-harbouring community. Analyses and method comparisons were made using samples from two laboratory-scale biogas processes, one operated under stable control and one exposed to controlled overloading disturbance. Comparative analysis revealed satisfactory detection of the bacterial community and its changes for all methods, but with some differences in resolution and taxonomic identification. FTHFS gene sequencing was found to be the most suitable and reliable method to study acetogenic communities. These results pave the way for community profiling in various biogas processes and in other environments where the dynamics of acetogenic bacteria have not been well studied.GRAPHICAL ABSTRACTONE SENTENCE SUMMARYOur high-throughput FTHFS gene AmpSeq method for barcoded samples and unsupervised analysis with AcetoScan accurately reveals temporal dynamics of acetogenic community structure in anaerobic digesters.
CUT&RUNTools 2.0: A pipeline for single-cell and bulk-level CUT&RUN and CUT&Tag data analysis
Authors: Yu Fulong , Sankaran Vijay G. , Yuan Guo-Cheng 
Published: January 2021

AbstractGenome-wide profiling of transcription factor binding and chromatin states is a widely-used approach for mechanistic understanding of gene regulation. Recent technology development has enabled such profiling at single-cell resolution. However, an end-to-end computational pipeline for analyzing such data is still lacking. To fill this gap, we have developed a flexible pipeline for analysis and visualization of single-cell CUT&RUN and CUT&Tag data, which provides functions for sequence alignment, quality control, dimensionality reduction, cell clustering, data aggregation, and visualization. Furthermore, it is also seamlessly integrated with the functions in original CUT&RUNTools for population-level analyses. As such, this provides a valuable toolbox for the community.