bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biomarker signatures of quality for nasal chondrocyte-derived engineered cartilage
Authors: Asnaghi M. Adelaide , Power Laura , Barbero Andrea , Haug Martin , Köppl Ruth , Wendt David , Martin Ivan 
Published: February 2020

AbstractThe definition of quality controls for cell therapy and engineered product manufacturing processes is critical for safe, effective, and standardized clinical implementation. Using the example context of cartilage grafts engineered from autologous nasal chondrocytes, currently used for articular cartilage repair in a phase II clinical trial, we outlined how gene expression patterns and generalized linear models can be introduced to define molecular signatures of identity, purity, and potency. We first verified that cells from the biopsied nasal cartilage can be contaminated by cells from a neighboring tissue, namely perichondrial cells, and discovered that they cannot deposit cartilaginous matrix. Differential analysis of gene expression enabled the definition of identity markers for the two cell populations, which were predictive of purity in mixed cultures. Specific patterns of expression of the same genes were significantly correlated with cell potency, defined as the capacity to generate tissues with histological and biochemical features of hyaline cartilage. The outlined approach can now be considered for implementation in a Good Manufacturing Practice setting, and offers a paradigm for other regenerative cellular therapies.
Development of Small Molecule MEIS Inhibitors that modulate HSC activity
Authors: Turan Raife Dilek , Albayrak Esra , Uslu Merve , Siyah Pinar , Alyazici Lamia Yazgi , Kalkan Batuhan Mert , Aslan Galip Servet , Yucel Dogacan , Aksoz Merve , Tuysuz Emre Can , Meric Neslihan , Durdagi Serdar , Gulbas Zafer , Kocabas Fatih 
Published: February 2020

AbstractMeis1, which belongs to TALE-type class of homeobox gene family, appeared as one of the key regulators of hematopoietic stem cell (HSC) self-renewal and a potential therapeutical target. However, small molecule inhibitors of MEIS1 remained unknown. This led us to develop inhibitors of MEIS1 that could modulate HSC activity. To this end, we have established a library of relevant homeobox family inhibitors and developed a high-throughputin silicoscreening strategy against homeodomain of MEIS proteins using the AutoDock Vina and PaDEL-ADV platform. We have screened over a million druggable small moleculesin silicoand selected putative MEIS inhibitors (MEISi) with no predicted cytotoxicity or cardiotoxicity. This was followed byin vitrovalidation of putative MEIS inhibitors using MEIS dependent luciferase reporter assays and analysis in theex vivoHSC assays. We have shown that small molecules named MEISi-1 and MEISi-2 significantly inhibit MEIS-luciferase reportersin vitroand induce murine (LSKCD34lowcells) and human (CD34+, CD133+, and ALDHhicells) HSC self-renewalex vivo. In addition, inhibition of MEIS proteins results in downregulation ofMeis1and MEIS1 target gene expression including Hif-1α, Hif-2α and HSC quiescence modulators. MEIS inhibitors are effectivein vivoas evident by induced HSC content in the murine bone marrow and downregulation of expression of MEIS target genes. These studies warrant identification of first-in-class MEIS inhibitors as potential pharmaceuticals to be utilized in modulation of HSC activity and bone marrow transplantation studies.
Genomic study of oral lichen planus and oral microbiome with RNAseq
Authors: Zhong Evelyn F. , Chang Andrea , Stucky Andres , Chen Xuelian , Mundluru Tarun , Khalifeh Mohammad , Sedghizadeh Parish P. 
Published: February 2020

ABSTRACTOral lichen planus (OLP) is a common chronic inflammatory disease affecting the oral mucosa. The pathogenesis of OLP is incompletely understood but is thought to be related to the immune system. As the oral cavity is a major reservoir and transmission gateway for bacteria, viruses, and fungi, the microbial composition of the oral cavity could play a role in the pathogenesis of OLP. However, due to limitations of analytic technology and incomplete knowledge of the microbial community in the oral cavity, it is not yet clear which pathogens are associated with OLP. Next-generation sequencing (NGS) is a powerful tool that can help to identify pathogens for many infectious diseases. In this study, we compared host cell gene expression profiles and microbial profiles from OLP patients and matched healthy individuals. We identified activation of the hepatocyte nuclear factor alpha (HNF4A) network in OLP patients and potential pathogens, includingCorynebacterium matruchotii, Fusobacterium periodonticum, Streptococcus intermedius, Streptococcus oralis, andPrevotella denticola. P. denticolais capable of activating the HNF4A gene network. Our findings shed light on the previously elusive association of OLP with various diseases like hepatitis, and indicate that OLP is a T-helper type 17 (Th17)-mediated mucosal inflammatory process. The molecular pathways and microbes identified here can inform future investigations into OLP pathogenesis and development of novel therapeutics for OLP treatment.
RootDigger: a root placement program for phylogenetic trees
Authors: Bettisworth Ben , Stamatakis Alexandros 
Published: February 2020

AbstractSummaryIn phylogenetic analysis, it is common to infer unrooted trees. Thus, it is unknown which node is the most recent common ancestor of all the taxa in the phylogeny. However, knowing the root location is desirable for downstream analyses and interpretation. There exist several methods to recover a root, such as midpoint rooting or rooting the tree at an outgroup. Non-reversible Markov models can also be used to compute the likelihood of a potential root position. We present a software calledRootDiggerwhich uses a non-reversible Markov model to compute the most likely root location on a given tree and to infer a confidence value for each possible root placement.Availability and implementationRootDiggeris available under the MIT licence athttps://github.com/computations/root_digger
The effect of terminal globular domains on the response of recombinant mini-spidroins to fiber spinning triggers
Authors: Finnigan William , Roberts Aled D. , Scrutton Nigel S. , Breitling Rainer , Blaker Jonny J. , Takano Eriko 
Published: February 2020

AbstractSpider silk spidroins consist of long repetitive protein strands, flanked by globular terminal domains. The globular domains are often omitted in recombinant spidroins, but are thought to be essential for the spiders’ natural spinning process. Mimicking this spinning process could be an essential step towards producing strong synthetic spider silk. Here we describe the production of a range of mini-spidroins with both terminal domains, and characterize their response to a number of biomimetic spinning triggers. Our results suggest that the inclusion of the terminal domains is needed to match the response to shear that native spidroins exhibit. Our results also suggest that a pH drop alone is insufficient to trigger assembly in a wet-spinning process, and must be combined with salting-out for effective fiber formation. With these insights, we applied these assembly triggers for relatively biomimetic wet spinning. This work adds to the foundation of literature for developing improved biomimetic spinning techniques, which ought to result in synthetic silk that more closely approximates the unique properties of native spider silk.
Unisexual flower initiation in the monoeciousQuercus suberL., a molecular approach
Authors: Sobral Rómulo , Silva Helena Gomes , Laranjeira Sara , Magalhães Joana , Andrade Luís , Alhinho Ana Teresa , Costa Maria Manuela Ribeiro 
Published: February 2020

AbstractSeveral plant species display a temporal separation of the male and female flower organ development to enhance outbreeding, however, little is known regarding the genetic mechanisms controlling this temporal separation.Quercus suberis a monoecious oak tree with accentuated protandry: in late winter, unisexual male flowers emerge adjacent to the swollen buds, whereas unisexual female flowers emerge in the axils of newly formed leaves formed during spring (4 to 8 weeks after male flowering). Here, phylogenetic profiling lead to the identification of cork oak homologs of key floral regulatory genes. The role of these cork oak homologs during flower development was identified with functional studies inArabidopsis thaliana. The expression profile of flower regulators (inducers and repressors) throughout the year, in leaves and buds, suggests that the development of male and female flowers may be preceded by separated induction events. Female flowers are most likely induced during the vegetative flush occurring in spring, whereas male flowers may be induced in early summer, staying enclosed within the pre-dormant buds, but complete their development before the vegetative flush of the following year, displaying a long period of anthesis that spans the dormant period. Results portray a genetic mechanism that may explain similar reproductive habits in other tree species.
seagull: lasso, group lasso and sparse-group lasso regularisation for linear regression models via proximal gradient descent
Authors: Klosa Jan , Simon Noah , Westermark Pål O. , Liebscher Volkmar , Wittenburg Dörte 
Published: February 2020

SummaryStatistical analyses of biological problems in life sciences often lead to high-dimensional linear models. To solve the corresponding system of equations, penalisation approaches are often the methods of choice. They are especially useful in case of multicollinearity which appears if the number of explanatory variables exceeds the number of observations or for some biological reason. Then, the model goodness of fit is penalised by some suitable function of interest. Prominent examples are the lasso, group lasso and sparse-group lasso. Here, we offer a fast and numerically cheap implementation of these operators via proximal gradient descent. The grid search for the penalty parameter is realised by warm starts. The step size between consecutive iterations is determined with backtracking line search. Finally, the package produces complete regularisation paths.Availability and implementationseagullis an R package that is freely available on the Comprehensive R Archive Network (CRAN;https://CRAN.R-project.org/package=seagull; vignette included). The source code is available onhttps://github.com/jklosa/seagull.Contactwittenburg@fbn-dummerstorf.de
Global Dynamic Molecular Profiles of Stomatal Lineage Cell Development by Single-Cell RNA Sequencing
Authors: Liu Zhixin , Zhou Yaping , Guo Jinggong , Li Jiaoai , Tian Zixia , Zhu Zhinan , Wang Jiajing , Wu Rui , Zhang Bo , Hu Yongjian , Sun Yijing , Shangguan Yan , Li Weiqiang , Li Tao , Hu Yunhe , Guo Chenxi , Rochaix Jean-David , Miao Yuchen , Sun Xuwu 
Published: February 2020

ABSTRACTThe regulation of stomatal lineage cell development has been extensively investigated. However a comprehensive characterization of this biological process based on single-cell transcriptome analysis has not yet been reported. Here, we performed RNA-seq on over 12,844 individual cells from the cotyledons of five-day-oldArabidopsis seedlings. We identified 11 cell clusters corresponding mostly to cells at specific stomatal developmental stages with a series of new marker genes. Comparative analysis of genes with the highest variable expression in these cell clusters revealed three transcriptional networks that regulate the development of mesophyll and guard cells, as well as the differentiation from protodermal to guard mother cells. We investigated the developmental dynamics of marker genes via pseudo-time analysis which revealed potential interactions between them. The identification of several novel marker genes suggests new regulatory mechanisms during development of stomatal cell lineage.
Extraembryonic endoderm cells induce neuroepithelial tissue in gastruloids
Authors: Bérenger-Currias Noémie M. L. P. , Mircea Maria , Adegeest Esmée , van den Berg Patrick R. , Feliksik Marleen , Hochane Mazène , Idema Timon , Tans Sander J. , Semrau Stefan 
Published: February 2020

SUMMARYStem-cell derivedin vitrosystems, such as organoids or embryoids, hold great potential for modelingin vivobiology and engineering living systems with novel functions. To unlock that potential, we need new ways to elicit higher-level organization. Here we show that adding extraembryonic endoderm (XEN) cells to mouse gastruloids leads to the formation of neural epithelia. By single-cell RNA-seq, imaging and differentiation experiments, we demonstrate the neural characteristics and spatial patterning of the epithelial tissue. We further show that the XEN cells differentiate reciprocally to a visceral endoderm-like state. Finally, we demonstrate that local inhibition of WNT signaling and production of a basement membrane by the XEN cells underlie the formation of the neuroepithelial tissue. In summary, we establish “XEN Enhanced Gastruloids” (XEGs) to explore heterotypic cellular interactions as a means to achieve complex, tissue-level organizationin vitro.
On Contamination of Symbolic Datasets
Authors: Pearson Antony , Lladser Manuel E. 
Published: February 2020

AbstractData taking values on discrete sample spaces are the embodiment of modern biological research. “Omics” experiments produce millions of symbolic outcomes in the form of reads (i.e., DNA sequences of a few dozens to a few hundred nucleotides). Unfortunately, these intrinsically non-numerical datasets are often highly contaminated, and the possible sources of contamination are usually poorly characterized. This contrasts with numerical datasets where Gaussian-type noise is often well-justified. To overcome this hurdle, we introduce the notion of latent weight, which measures the largest expected fraction of samples from a contaminated probabilistic source that conform to a model in a well-structured class of desired models. We examine various properties of latent weights, which we specialize to the class of exchangeable probability distributions. As proof of concept, we analyze DNA methylation data from the 22 human autosome pairs. Contrary to what it is usually assumed, we provide strong evidence that highly specific methylation patterns are overrepresented at some genomic locations when contamination is taken into account.
Emerging viruses in British Columbia salmon discovered via a viral immune response biomarker panel and metatranscriptomic sequencing
Authors: Mordecai Gideon J. , Di Cicco Emiliano , Günther Oliver P. , Schulze Angela D. , Kaukinen Karia H. , Li Shaorong , Tabata Amy , Ming Tobi J. , Ferguson Hugh W. , Suttle Curtis A. , Miller Kristina M. 
Published: February 2020

AbstractThe emergence of infectious agents poses a continual economic and environmental challenge to aquaculture production, yet the diversity, abundance and epidemiology of aquatic viruses are poorly characterised. In this study, we applied salmon host transcriptional biomarkers to identify and select fish in a viral disease state but only those that we also showed to be negative for established viruses. This was followed by metatranscriptomic sequencing to determine the viromes of dead and dying farmed Atlantic (Salmo salar) and Chinook (Oncorhynchus tshawytscha) salmon in British Columbia. We found that the application of the biomarker panel increased the probability of discovering viruses in aquaculture populations. We discovered viruses that have not previously been characterized in British Columbian Atlantic salmon farms. To determine the epidemiology of the newly discovered or emerging viruses we conducted high-throughput RT-PCR to reveal their prevalence in British Columbia (BC), and detected some of the viruses we first discovered in farmed Atlantic salmon in Chinook and sockeye salmon, suggesting a broad host range. Finally, we appliedin-situhybridisation to confirm infection and explore the tissue tropism of each virus.
High temporal resolution reveals simultaneous plasma membrane recruitment of the TPLATE complex subunits
Authors: Wang Jie , Mylle Evelien , Johnson Alexander , Besbrugge Nienke , De Jaeger Geert , Friml Jiří , Pleskot Roman , Van Damme Daniel 
Published: February 2020

AbstractThe TPLATE complex (TPC) is a key endocytic adaptor protein complex in plants. TPC contains six evolutionary conserved subunits and two plant specific subunits, AtEH1/Pan1 and AtEH2/Pan1, which are not associated with the hexameric subcomplex in the cytoplasm. To investigate the dynamic assembly of the octameric TPC at the plasma membrane (PM), we performed state-of-the-art dual-color live cell imaging at physiological and a lowered temperature. Our data show that lowering the temperature slows down endocytosis and thereby enhances the temporal resolution of the differential recruitment of endocytic components. Under both normal and lowered temperature conditions, the core TPC subunit TPLATE, and the AtEH/Pan1 proteins, exhibited simultaneous recruitment at the PM. These results, together with our co-localization analysis of different TPC subunits, allow us to conclude that in plant cells, TPC is not recruited to the PM sequentially but as an octameric complex.One sentence summaryLowering the temperature increases spatiotemporal resolution of protein recruitment at the plasma membrane.
Microbiota-Independent Antiviral Effects of Antibiotics on Enteric Viruses
Authors: Woods Acevedo Mikal A. , Pfeiffer Julie K. 
Published: February 2020

AbstractCoxsackieviruses primarily infect the gastrointestinal tract of humans, but they can disseminate systemically and cause severe disease. Using antibiotic treatment regimens to deplete intestinal microbes in mice, several groups have shown that bacteria promote oral infection with a variety of enteric viruses. However, it is unknown whether antibiotics have microbiota-independent antiviral effects for enteric viruses or whether antibiotics influence extra-intestinal, systemic infection. Here, we examined the effects of antibiotics on systemic enteric virus infection by performing intraperitoneal injections of either coxsackievirus B3 (CVB3) or poliovirus followed by quantification of viral titers. We found that antibiotic treatment reduced systemic infection for both viruses. Interestingly, antibiotics reduced CVB3 titers in germ-free mice, suggesting that antibiotic treatment alters CVB3 infection through a microbiota-independent mechanism. Overall, these data provide further evidence that antibiotics can have noncanonical effects on viral infection.
Eyring–Powell fluid flow through a circular pipe and heat transfer: full solutions
Authors: Mustafa Turkyilmazoglu 
Published: February 2020

Purpose
The purpose of this study is to examine the non-Newtonian physical model of Eyring–Powell fluid for the rheology inside a long circular pipe.

Design/methodology/approach
Although many research studies are available now on this topic, none gives full solutions explicitly accessible.

Findings
It is proven here that the hydrodynamically fully developed fluid flow acknowledges the exact solution, influenced by a non-Newtonian parameter as well as the adverse pressure gradient parameter prevailing the flow domain. These parameters are unified under a new parameter known as the generalized Eyring–Powell parameter. Without the presented analytical data, it is impossible to detect the validity range of such physical non-Newtonian solutions, which is shown to be restricted.

Originality/value
Full solution of the energy equation for the thermally fully developed laminar regime is also presented under the assumption of uniform wall temperature at the pipe wall. The physical impacts of pertinent parameters on the rheology of the non-Newtonian fluid with regard to the Reynolds number, Darcy friction factor and pressure drop are easy to interpret from the derived formulae. Particularly, a decrease in the centerline velocity and an increase in the rate of heat transfer are clarified for the considered flow configuration.
Access to health-care policies for refugees and asylum-seekers
Authors: El-Gamal Salma , Hanefeld Johanna 
Published: February 2020

Purpose
The influx of refugees and asylum-seekers over the past decade into the European Union creates challenges to the health systems of receiving countries in the preparedness and requisite adjustments to policy addressing the new needs of the migrant population. This study aims to examine and compare policies for access to health care and the related health outcomes for refugees and asylum-seekers settling both in the UK and Germany as host countries.

Design/methodology/approach
The paper conducted a scoping review of academic databases and grey literature for studies within the period 2010-2017, seeking to identify evidence from current policies and service provision for refugees and asylum-seekers in Germany and the UK, distilling the best practice and clarifying gaps in knowledge, to determine implications for policy.

Findings
Analysis reveals that legal entitlements for refugees and asylum-seekers allow access to primary and secondary health care free of charge in the UK versus a more restrictive policy of access limited to acute and emergency care during the first 15 months of resettlements in Germany. In both countries, many factors hinder the access of this group to normal health care from legal status, procedural hurdles and lingual and cultural barriers. Refugees and asylum-seeker populations were reported with poor general health condition, lower rates of utilization of health services and noticeable reliance on non-governmental organizations.

Originality/value
This paper helps to fulfill the need for an extensive research required to help decision makers in host countries to adjust health systems towards reducing health disparities and inequalities among refugees and asylum-seekers.
Health-seeking cultural patterns in the use of available healthcare services among refugee groups in south-central Kentucky
Authors: Ejike Chika , Lartey Grace , Capps Randy , Ciochetty David 
Published: February 2020

Purpose
Refugees resettle in the USA every year to escape genocide, famine, civil wars and crises in their countries. The diverse cultural identities of the refugee population in south-central Kentucky make it essential to research into their health-care usage patterns. The purpose of this study is to examine the health-seeking patterns of refugees in relation to their culture and the usage of available health services.

Design/methodology/approach
This is a descriptive correlational study that culled 110 refugees who completed self-administered or interviewer-administered semi-structured questionnaires. Questionnaires were translated into four different languages. T-tests and ANOVA assessed differences between variables.

Findings
Findings indicate that a demographic factor such as refugees’ nationality plays a role in both the access and use of health services [F (5, 98) = 4.29, p < 0.001]. Refugees’ beliefs and social factors such as acculturation (t = −2.03, p < 0.04) and having health insurance (t = −3.35, p <0.001) also affect the use of health services. The level of cultural competency of the health-care facility or provider as depicted by the presence of interpreters (t = 1.92, p < 0.05) was associated with increased use of the health services provided.

Research limitations/implications
The sample of refugees is only representative of the general refugee population in south-central Kentucky; hence, there is inadequate generalization.

Originality/value
Cultural diversity should be included in the health and policymaking debates that surround the refugee population of south-central Kentucky to ensure their well-being.