bluuebunny/crossref_metadata_2025_split huggingface dataset:
Flow cytometry with cell sorting and sequencing as a tool for the study of the Humboldt Current krill stomach microbiota
Authors: Henriquez-Castillo Carlos , Franco-Cisterna Belén , Murillo Alejandro A. , Ulloa Osvaldo , Riquelme-Bugueño Ramiro 
Published: September 2020

ABSTRACTEuphausiids (or krill) are important contributors to marine biomass and key players in marine pelagic trophic webs. Euphausiids stomachs represent a specific niche for microbes that participate in the digestion of the host dietary components. To date, methods for the study of the diversity and function of these microorganisms remain complex. Often, bacterial ribosomal sequences obtained from lysates of stomachs are overrepresented by organisms from the surrounding environment. Flow cytometry with cell sorting (FC-CS) have become a powerful technique to study microbial community structure but also for the study of population genomics of gut-associated bacteria, even at a single-cell level.In this study, we used FC-CS and sequencing of the bacterial 16S rRNA gene to study the microorganisms inhabiting the stomach of the Humboldt Current krill,Euphausia mucronata. This approach was complemented with DNA extraction and sequencing from whole lysate stomachs as described for other crustacean species.Non-specific amplification was not retrieved in the polymerase chain reaction (PCR) from cells sorted, opposite to the observed using the DNA from the whole lysate. Sequences obtained from the whole stomach DNA were enriched in picocyanobacteria, meanwhile, sequences retrieved from cells sorted belonged almost exclusively toBalneolasp. of the new phylum, Balneolaeota. This study represents, to our knowledge, the first report ofBalneolasp. in the stomach for any organism inhabiting the Humboldt Current System (HCS).Our results suggest that the stomach-associated microbiota can be characterized by FC-CS and sequencing by manual scraping of the stomach coupled with the DNA extraction and sequencing. This work represents a baseline for similar studies of other mesozooplankton groups. The implementation of this technique might complement future studies on host-microbes’ interaction and their implications on the marine pelagic food web.
A COVID-19 vaccine candidate using SpyCatcher multimerization of the SARS-CoV-2 spike protein receptor-binding domain induces potent neutralising antibody responses
Authors: Tan Tiong Kit , Rijal Pramila , Rahikainen Rolle , Keeble Anthony H. , Schimanski Lisa , Hussain Saira , Harvey Ruth , Hayes Jack W.P. , Edwards Jane. C. , McLean Rebecca K. , Martini Veronica , Pedrera Miriam , Thakur Nazia , Conceicao Carina , Dietrich Isabelle , Shelton Holly , Ludi Anna , Wilsden Ginette , Browning Clare , Zagrajek Adrian K. , Bialy Dagmara , Bhat Sushant , Stevenson-Leggett Phoebe , Hollinghurst Philippa , Tully Matthew , Moffat Katy , Chiu Chris , Waters Ryan , Gray Ashley , Azhar Mehreen , Mioulet Valerie , Newman Joseph , Asfor Amin S. , Burman Alison , Crossley Sylvia , Hammond John A. , Tchilian Elma , Charleston Bryan , Bailey Dalan , Tuthill Tobias J. , Graham Simon P. , Malinauskas Tomas , Huo Jiandong , Tree Julia A. , Buttigieg Karen R. , Owens Raymond J. , Caroll Miles W. , Daniels Rodney S. , McCauley John W. , Huang Kuan-Ying A. , Howarth Mark , Townsend Alain R. 
Published: September 2020

ABSTRACTThere is dire need for an effective and affordable vaccine against SARS-CoV-2 to tackle the ongoing pandemic. In this study, we describe a modular virus-like particle vaccine candidate displaying the SARS-CoV-2 spike glycoprotein receptor-binding domain (RBD) using SpyTag/SpyCatcher technology (RBD-SpyVLP). Low doses of RBD-SpyVLP in a prime-boost regimen induced a strong neutralising antibody response in mice and pigs that was superior to convalescent human sera. We evaluated antibody quality using ACE2 blocking and neutralisation of cell infection by pseudovirus or wild-type SARS-CoV-2. Using competition assays with a monoclonal antibody panel, we showed that RBD-SpyVLP induced a polyclonal antibody response that recognised all key epitopes on the RBD, reducing the likelihood of selecting neutralisation-escape mutants. The induction of potent and polyclonal antibody responses by RBD-SpyVLP provides strong potential to address clinical and logistic challenges of the COVID-19 pandemic. Moreover, RBD-SpyVLP is highly resilient, thermostable and can be lyophilised without losing immunogenicity, to facilitate global distribution and reduce cold-chain dependence.
STABILITY ANALYSIS OF A SIGNALING CIRCUIT WITH DUAL SPECIES OF GTPASE SWITCHES
Authors: Stolerman Lucas M. , Ghosh Pradipta , Rangamani Padmini 
Published: September 2020

AbstractGTPases are molecular switches that regulate a wide range of cellular processes, such as organelle biogenesis, position, shape, and function, vesicular transport between organelles, and signal transduction. These hydrolase enzymes operate by toggling between an active “ON”) guanosine triphosphate (GTP)-bound state and an inactive (“OFF”) guanosine diphosphate (GDP)-bound state; such a toggle is regulated by GEFs (guanine nucleotide exchange factors) and GAPs (GTPase activating proteins). Here we propose a model for a network motif between monomeric (m) and trimeric (t) GTPases assembled exclusively in eukaryotic cells of multicellular organisms. We develop a system of ordinary differential equations in which these two classes of GT-Pases are interlinked conditional to their ON/OFF states within a motif through coupling and feedback loops. We provide explicit formulae for the steady states of the system and perform classical local stability analysis to systematically investigate the role of the different connections between the GTPase switches. Interestingly, a coupling of the active mGTPase to the GEF of the tGTPase was sufficient to provide two locally stable states: one where both active/inactive forms of the mGTPase can be interpreted as having low concentrations and the other where both m- and tGTPase have high concentrations. Moreover, when a feedback loop from the GEF of the tGTPase to the GAP of the mGTPase was added to the coupled system, two other locally stable states emerged, both having the tGTPase inactivated and being interpreted as having low active tGTPase concentrations. Finally, the addition of a second feedback loop, from the active tGT-Pase to the GAP of the mGTPase, gives rise to a family of steady states that can be parametrized by a range of inactive tGTPase concentrations. Our findings reveal that the coupling of these two different GTPase motifs can dramatically change their steady state behaviors and shed light on how such coupling may impact signaling mechanisms in eukaryotic cells.
Massively parallel identification of causal variants underlying gene expression differences in a yeast cross
Authors: Renganaath Kaushik , Cheung Rocky , Day Laura , Kosuri Sriram , Kruglyak Leonid , Albert Frank W. 
Published: September 2020

AbstractSequence variation in regulatory DNA alters gene expression and shapes genetically complex traits. However, the identification of individual, causal regulatory variants is challenging. Here, we used a massively parallel reporter assay to measure thecis-regulatory consequences of 5,832 natural DNA variants in the promoters of 2,503 genes in the yeastSaccharomyces cerevisiae. We identified 451 causal variants, which underlie genetic loci known to affect gene expression. Several promoters harbored multiple causal variants. In five promoters, pairs of variants showed non-additive, epistatic interactions. Causal variants were enriched at conserved nucleotides, tended to have low derived allele frequency, and were depleted from promoters of essential genes, which is consistent with the action of negative selection. Causal variants were also enriched for alterations in transcription factor binding sites. Models integrating these features provided modest, but statistically significant, ability to predict causal variants. This work revealed a complex molecular basis forcis-acting regulatory variation.
Identifying Isl1 genetic lineage in the developing olfactory system and in GnRH-1 neurons
Authors: Taroc Ed Zandro M. , Katreddi Raghu Ram , Forni Paolo E. 
Published: September 2020

AbstractDuring embryonic development, symmetric ectodermal thickenings (olfactory placodes) give rise to several cell types that comprise the olfactory system, such as those that form the terminal nerve ganglion (TN), gonadotropin releasing hormone-1 (GnRH-1) neurons and other migratory neurons in rodents. Even though the genetic heterogeneity among these cell types are documented, unidentified cell populations arising from the olfactory placode remain. One candidate to identify placodal derived neurons in the developing nasal area is the transcription factor Isl1, which was recently identified in GnRH-3 neurons of the terminal nerve in fish, as well as expression in neurons of the nasal migratory mass. Here, we analyzed the Isl1 genetic lineage in chemosensory neuronal populations in the nasal area and migratory GnRH-1 neurons in mice usingin-situhybridization, immunolabeling a Tamoxifen inducible Isl1CreERTand a constitutive Isl1Creknock-in mouse lines. In addition, we also performed conditional Isl1 ablation in developing GnRH neurons. We found Isl1 lineage across non sensory cells of the respiratory epithelium and sustentacular cells of OE and VNO. We identified a population of transient embryonic Isl1+ neurons in the olfactory epithelium and sparse Isl1+ neurons in postnatal VNO. Isl1 is expressed in almost all GnRH neurons and in approximately half of the other neuron populations in the Migratory Mass. However, Isl1 conditional ablation alone does not significantly compromise GnRH-1 neuronal migration or GnRH-1 expression, suggesting compensatory mechanisms. Further studies will elucidate the functional and mechanistic role of Isl1 in development of migratory endocrine neurons.
INPP5Dexpression is associated with risk for Alzheimer’s disease and induced by plaque-associated microglia
Authors: Tsai Andy P. , Lin Peter Bor-Chian , Dong Chuanpeng , Moutinho Miguel , Casali Brad T. , Liu Yunlong , Lamb Bruce T. , Landreth Gary E. , Oblak Adrian L. , Nho Kwangsik 
Published: September 2020

AbstractBackgroundAlzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, robust microgliosis, neuroinflammation, and neuronal loss. Genome-wide association studies recently highlighted a prominent role for microglia in late-onset AD (LOAD). Specifically, inositol polyphosphate-5-phosphatase (INPP5D), also known as SHIP1, is selectively expressed in brain microglia and has been reported to be associated with LOAD. AlthoughINPP5Dis likely a crucial player in AD pathophysiology, its role in disease onset and progression remains unclear.MethodsWe performed differential gene expression analysis to investigateINPP5Dexpression in LOAD and its association with plaque density and microglial markers using transcriptomic (RNA-Seq) data from the Accelerating Medicines Partnership for Alzheimer’s Disease (AMP-AD) cohort. We also performed quantitative real-time PCR, immunoblotting, and immunofluorescence assays to assess INPP5D expression in the 5xFAD amyloid mouse model.ResultsDifferential gene expression analysis found thatINPP5Dexpression was upregulated in LOAD and positively correlated with amyloid plaque density. In addition, in 5xFAD mice,Inpp5dexpression increased as the disease progressed, and selectively in plaque-associated microglia. IncreasedInpp5dexpression levels in 5xFAD mice were abolished entirely by depleting microglia with the colony-stimulating factor receptor-1 antagonist PLX5622.ConclusionsOur findings show thatINPP5Dexpression increases as AD progresses, predominantly in plaque-associated microglia. Importantly, we provide the first evidence that increasedINPP5Dexpression might be a risk factor in AD, highlightingINPP5Das a potential therapeutic target. Moreover, we have shown that the 5xFAD mouse model is appropriate for studyingINPP5Din AD.
Identification of activity-inducedEgr3-dependent genes reveals genes associated with DNA damage response and schizophrenia
Authors: Marballi Ketan K , Alganem Khaled , Brunwasser Samuel J , Barkatullah Arhem , Meyers Kimberly T , Campbell Janet M , Mccullumsmith Robert R , Gallitano Amelia L 
Published: September 2020

AbstractBioinformatics and network studies have identified the immediate early gene transcription factor early growth response 3 (EGR3) as a master regulator of genes differentially expressed in the brains of patients with neuropsychiatric illnesses ranging from schizophrenia and bipolar disorder to Alzheimer’s disease. However, few studies have identified and validatedEgr3-dependent genes in the mammalian brain. We have previously shown thatEgr3is required for stress-responsive behavior, memory, and hippocampal long-term depression in mice. To identifyEgr3-dependent genes that may regulate these processes, we conducted an expression microarray on hippocampi from wildtype (WT) andEgr3-/-mice following electroconvulsive seizure (ECS), a stimulus that induces maximal expression of immediate early genes includingEgr3. We identified 71 genes that were differentially expressed between WT andEgr3-/-mice one hour following ECS. Bioinformatic analyses showed that many of these are altered in schizophrenia. Ingenuity pathway analysis revealed the GADD45 (growth arrest and DNA-damage-inducible) family (Gadd45b, Gadd45g) as the leading category of differentially expressed genes. Together with differentially expressed genes in the AP-1 transcription factor family genes (Fos, Fosb), and the centromere organization proteinCenpa, these results revealed thatEgr3is required for activity-dependent expression of genes involved in the DNA damage response. Our findings implicate EGR3 as gene critical for the expression of genes that are disrupted in schizophrenia and reveal a novel requirement for EGR3 in the expression of genes involved in activity-induced DNA damage response.
Application of fuzzy DEA and machine learning algorithms in efficiency estimation of paddy producers of rural Eastern India
Authors: Nandy Anirban , Singh Piyush Kumar 
Published: September 2020

PurposeData envelopment analysis (DEA) has wide applications in the agricultural sector to evaluate the efficiency with crisp input and output data. However, in agricultural production, impreciseness and uncertainty in data are common. As a result, the data obtained from farmers vary. This impreciseness in crisp data can be represented in fuzzy sets. This paper aims to employ a combination of fuzzy data envelopment analysis (FDEA) approach to yield crisp DEA efficiency values by converting the fuzzy DEA model into a linear programming problem and machine learning algorithms for better evaluation and prediction of the variables affecting the farm efficiency.Design/methodology/approachDEA applications are focused on the use of a common two-step approach to find crucial factors that affect efficiency. It is important to identify impactful variables for minimizing production adversities. In this study, first, FDEA was applied for efficiency estimation and ranking of the paddy growers. Second, the support vector machine (SVM) and random forest (RF) were used for identifying the key leading factors in efficiency prediction.FindingsThe proposed research was conducted with 450 paddy growers. In comparison to the general DEA approach, the FDEA model evaluates fuzzy DEA efficiency giving the user the flexibility to measure the performance at different possibility levels.Originality/valueThe use of machine learning applications introduces advanced strategies and important factors influencing agricultural production, which may help future research in farms' performance.
Exploring integrated supply chain performance in healthcare: a service provider perspective
Authors: Srivastava Shefali , Singh Rohit Kr 
Published: September 2020

PurposeThe paper identifies the antecedents and consequences of integrated supply chain performance (ISCP) in healthcare systems.Design/methodology/approachBased on a review of the literature constructs of supply chain flexibility (SCF), employee relationships (ERs), organizational orientation (OO) and knowledge exchange (KE) were identified as antecedents of ISCP, and patient centricity (PC) emerged as its consequence. This structural relationship was tested using partial least square structural equation modeling (PLS-SEM).FindingsERs, SCF, OO and KE positively impacted the performance of an integrated healthcare supply chain. Furthermore, enhanced ISCP in operational processes of the hospital positively influenced patient centeredness and care quality.Research limitations/implicationsPaper contributes by identifying antecedents and consequences of ISCP. Future researchers may explore the inter-relationships among the antecedents of ISCP.Practical implicationsInsights from this study will help practitioners in enhancing hospital operations by integrating processes along the healthcare service supply chain and developing a patient-centric approach.Social implicationsThis paper highlights how PC may be achieved by focusing on a facilitative internal environment. This understanding may help in designing processes that deliver health as a social good in an effective manner.Originality/valueThe empirical evidence from this study can help hospitals integrate their functions, thus, enabling them to deliver quality care.
Bank performance variability and strands of inflationary conditions
Authors: Abaidoo Rexford , Anyigba Hod 
Published: September 2020

PurposeThis study seeks to examine the extent to which strands of inflationary related conditions (inflation expectations, inflation uncertainty and realized inflation); macroeconomic uncertainty and the likelihood of recessionary conditions influence performance indicators in the US banking sector over a specified time period.Design/methodology/approachThe study adopts seemingly unrelated regression model (SUR) advanced by Zellner (1962) in its examination of how specific strands of inflationary conditions, and other adverse macroeconomic conditions influence performance dynamics in the US banking sector.FindingsEmpirical evidence suggest that among various adverse macroeconomic conditions examined, inflation expectations and macroeconomic uncertainty tend to have significant constraining impact on key performance indicators in the US banking sector than other conditions examined. Comparatively, this study finds that inflation expectations and macroeconomic uncertainty tend to have much more constraining impact on return on equity, than on return on assets in the US banking sector. Results further suggest that among the three bank performance indicators examined, net interest margin is the least vulnerable bank performance indicator to various adverse macroeconomic conditions examined in the study.Practical implicationsApart from the various empirical results noted above, this study's findings are projected to help inform strategic planning decisions among institutions in the banking sector. The various findings could, for instance, inform policies and operational strategies geared toward reducing vulnerability associated with specific performance indicators such as return on equity. This reduction could be achieved by critically examining how the various performance indicators react to individual adverse macroeconomic conditions examined in this study. The process could ultimately help in developing tailored measures/procedures aimed at reducing how susceptible key performance indicators are to the various adverse macroeconomic conditions. This study's findings could also provide the platform for more adaptive policies aimed at minimizing the effects of noted macroeconomic conditions on operational efficiency in the banking sector.Originality/valueThe uniqueness of this study, compared to related ones found in the literature, stems from its treatment of three variant of related strands of macroeconomic condition (different variant of inflationary conditions) in the same framework in its empirical analysis.
Graduate Attributes Assessment Program
Authors: ElAtia Samira , Ipperciel Donald , Zaiane Osmar , Bakhshinategh Behdad , Thibaudeau Patrick 
Published: September 2020

PurposeIn this paper, the challenging and thorny issue of assessing graduate attributes (GAs) is addressed. An interdisciplinary team at The University of Alberta ----developed a formative model of assessment centered on students and instructor interaction with course content.Design/methodology/approachThe paper starts by laying the theoretical groundwork on which this novel GA assessment tool is based, that is, competency-based education, assessment theory and GA assessment. It follows with a description of the online assessment tool for GAs that was developed in the course of this project.FindingsThe online assessment tool for GAs targets three types of stakeholders: (1) students, who self-assess in terms of GAs, (2) instructors, who use the tool to define the extent to which each GA should be inculcated in their course and (3) administrators, who receive aggregate reports based on the data gathered by the system for high-level analysis and decision-making. Collected data by students and professors advance formative assessment of these transversal skills and assist administration in ensuring the GAs are addressed in academic programs. Graduate attributes assessment program (GAAP) is also a space for students to build a personal portfolio that would be beneficial to highlight their skills for potential employers.Research limitations/implicationsThis research has strong implications for the universities, since it can help institutions, academics and students achieve better results in their practices. This is done by demonstrating strong links between theory and practice. Although this tool has only been used within the university setting by students, instructors and administrators (for self-, course and teaching and program improvement), it could increase its social and practical impact by involving potential employers and increase our understanding of student employability. Moreover, because the tool collects data on a continuous basis, it lends itself to many possible applications in educational data mining,Practical implicationsThe GAAP can be used and adapted to various educational contexts. The plugin can be added to any Learning Management System (LMS), and students can have access to their data and results throughout their education.Social implicationsThe GAAP allows institutions to provide a longitudinal formative assessment of students’ graduate attributes acquisition. It provides solid and valid evidence of students’ progress in a way that would advance society and citizenship.Originality/valueTo date, the GAAP is the first online interactive platform that has been developed to longitudinally assess the acquisition of GAs during a complete academic cycle/cohort. It provides a unique space where students and instructors interact with assessment scales and with concrete data for a complete university experience profile.