bluuebunny/crossref_metadata_2025_split huggingface dataset:
DYRK1A role in microtubule-based axonal transport regulates the retrograde dynamics of APP vesicles in human neurons
Authors: Bessone Iván Fernandez , Karmirian Karina , Goto-Silva Livia , Holubiec Mariana , Navarro Jordi L. , Martínez Emanuel , Saez Trinidad M.M. , Rehen Stevens , Falzone Tomás L. 
Published: February 2021

AbstractIn Alzheimer’s Disease (AD) the abnormal intracellular distribution of the amyloid precursor protein (APP) affects its processing and, consequently, the generation of Aβ. Axonal transport plays key roles in the neuronal distribution of APP. The dual-specificity-tyrosine phosphorylation-regulated-kinase-1A (DYRK1A) has been associated with AD onset since its overexpression was found in Down syndrome and sporadic AD patients. Experimental evidence confirmed that APP and tau phosphorylations are mediated by DYRK1A. Moreover, DYRK1A can regulate the cytoskeletal architecture by phosphorylation of both tubulin subunits and microtubule-associated proteins. Therefore, we tested whether DYRK1A has a role in APP axonal transport regulation.We developed highly-polarized human-derived neurons in 2D cultures. At day 14 after terminal plating we inhibited DYRK1A for 48hs with harmine (7.5 μM). DYRK1A overexpression was induced to perform live-cell imaging of APP-loaded vesicles in axons and analyzed transport dynamics. A custom-made MATLAB routine was developed to track and analyze single particle dynamics.Short-term harmine treatment reduced axonal APP vesicles density, due to a reduction in retrograde particles. Contrarily, DYRK1A overexpression enhanced axonal APP density, due to an increase in the retrograde and stationary component. Moreover, both harmine-mediated DYRK1A inhibition and DYRK1A overexpression revealed opposite phenotypes on single particle dynamics, affecting primarily dynein processivity. These results revealed an increased retrieval of distal APP vesicles in axons when DYRK1A is overexpressed and reinforce the suggestion that DYRK1A enhance APP endocytosis‥Taken together our results suggest that DYRK1A has a relevant role in the regulation of axonal transport and sub-cellular positioning of APP vesicles. Therefore, our work shed light on the role of DYRK1A in axonal transport regulation, and the putative use of harmine to restore axonal transport impairments.
Characterising ontogeny of quantity discrimination in zebrafish
Authors: Sheardown Eva , Torres-Perez Jose Vicente , Anagianni Sofia , Fraser Scott E. , Vallortigara Giorgio , Butterworth Brian , Miletto-Petrazzini Maria Elena , Brennan Caroline H. 
Published: February 2021

AbstractA sense of non-symbolic numerical magnitudes is widespread in the animal kingdom and has been documented in adult zebrafish. Here we investigated the ontogeny of this ability using a group size preference task in juvenile zebrafish. Fish showed group size preference from 21 days post fertilization (dpf) and reliably chose the larger group when presented with discriminations of between 1 vs. 3, 2 vs. 5 and 2 vs. 3 conspecifics but not 2 vs. 4 conspecifics. When the ratio between the number of conspecifics in each group was maintained at 1:2, fish could discriminate between 1 vs. 2 individuals and 3 vs. 6, but again, not when given a choice between 2 vs. 4 individuals. These findings are in agreement with studies in other species suggesting the systems involved in quantity representation do not operate separately from other cognitive mechanisms. Rather they suggest quantity processing in fish may be the result of an interplay between attentional, cognitive and memory-related mechanisms as in humans and other animals. Our results emphasise the potential of the use of zebrafish to explore the genetic and neural processes underlying the ontogeny and function of number cognition.
RHAMMB-mediated bifunctional nanotherapy targeting Bcl-xL and mitochondria for pancreatic neuroendocrine tumor treatment
Authors: Chen Xiang , Lee Seung Koo , Song Mei , Zhang Tiantian , Han Myung Shin , Chen Yao-Tseng , Chen Zhengming , Ma Xiaojing , Tung Ching-Hsuan , Du Yi-Chieh Nancy 
Published: March 2021

AbstractThe incidence of pancreatic neuroendocrine tumor (PNET) has continued to rise. Due to their indolent feature, PNET patients often present with incurable, metastatic diseases. Novel therapies are urgently needed. We have previously shown that Receptor for Hyaluronic Acid-Mediated Motility isoform B (RHAMMB) and Bcl-xL are upregulated in PNETs and both of them promote PNET metastasis. Because RHAMM protein is undetectable in most adult tissues, we hypothesized that RHAMMBcould be a gateway for nanomedicine delivery into PNETs. To test this, we developed RHAMMB-targeting nanoparticle. Inside this nanoparticle, we assembled siRNA against Bcl-xL (siBcl-xL) and mitochondria-fusing peptide KLA. We demonstratsed that RHAMMB-positive PNETs picked up the RHAMMB-targeting nanoparticles. siBcl-xL or KLA alone only killed 30% of PNET cells. In contrast, a synergistic killing effect was achieved with the co-delivery of siBcl-xL and KLA peptidein vitro. Unexpectedly, siBcl-xL induced cell death before reducing Bcl-xL protein levels. The systemically-injected RHAMMB-targeting nanoparticles carrying siBcl-xL and KLA peptide significantly reduced tumor burden in mice bearing RHAMMB-positive PNETs. Together, these findings indicate that the RHAMMB-targeting nanotherapy serves as a promising drug delivery system for PNET and possibly other malignancies upregulating RHAMMB. The combination of siBcl-xL and KLA peptide can be a therapy for PNET treatment.
The gene expression profile of the song control nucleus HVC shows sex specificity, hormone responsiveness, and species specificity among songbirds
Authors: Ko Meng-Ching , Frankl-Vilches Carolina , Bakker Antje , Gahr Manfred 
Published: March 2021

AbstractSinging occurs in songbirds of both sexes, but some species show typical degrees of sex-specific performance. We studied the transcriptional sex differences in the HVC, a brain nucleus critical for song pattern generation, of the forest weaver (Ploceus bicolor), the blue-capped cordon-bleu (Uraeginthus cyanocephalus), and the canary (Serinus canaria), which are species that show low, medium, and high levels of sex-specific singing, respectively. We observed persistent sex differences in gene expression levels regardless of the species-specific sexual singing phenotypes. We further studied the HVC transcriptomes of defined phenotypes of canary, known for its testosterone-sensitive seasonal singing. By studying both sexes of canaries during both breeding and nonbreeding seasons, nonbreeding canaries treated with testosterone, and spontaneously singing females, we found that the circulating androgen levels and sex were the predominant variables associated with the variations in the HVC transcriptomes. The comparison of natural singing with testosterone-induced singing in canaries of the same sex revealed considerable differences in the HVC transcriptomes. Strong transcriptional changes in the HVC were detected during the transition from nonsinging to singing in canaries of both sexes. Although the sex-specific genes of singing females shared little resemblance with those of males, our analysis showed potential functional convergences. Thus, male and female songbirds achieve comparable singing behaviours with sex-specific transcriptomes.
MEDICC2: whole-genome doubling aware copy-number phylogenies for cancer evolution
Authors: Kaufmann Tom L , Petkovic Marina , Watkins Thomas BK , Colliver Emma C , Laskina Sofya , Thapa Nisha , Minussi Darlan C , Navin Nicholas , Swanton Charles , Van Loo Peter , Haase Kerstin , Tarabichi Maxime , Schwarz Roland F 
Published: March 2021

Chromosomal instability (CIN) and somatic copy-number alterations (SCNA) play a key role in the evolutionary process that shapes cancer genomes. SC-NAs comprise many classes of clinically relevant events, such as localised amplifications, gains, losses, loss-of-heterozygosity (LOH) events, and recently discovered parallel evolutionary events revealed by multi-sample phasing. These events frequently appear jointly with whole genome doubling (WGD), a transformative event in tumour evolution involving tetraploidization of genomes preceded or followed by individual chromosomal copy-number changes and associated with an overall increase in structural CIN.While SCNAs have been leveraged for phylogeny reconstruction in the past, existing methods do not take WGD events into account and cannot model parallel evolution. They frequently make use of the infinite sites assumption, do not model horizontal dependencies between adjacent genomic loci and can not infer ancestral genomes. Here we present MEDICC2, a new phylogeny inference algorithm for allele-specific SCNA data that addresses these shortcomings. MEDICC2 dispenses with the infinite sites assumption, models parallel evolution and accurately identifies clonal and subclonal WGD events. It times SCNAs relative to each other, quantifies SCNA burden in single-sample studies and infers phylogenetic trees and ancestral genomes in multi-sample or single-cell sequencing scenarios with thousands of cells.We demonstrate MEDICC2’s ability on simulated data, real-world data of 2,778 single sample tumours from the Pan-cancer analysis of whole genomes (PCAWG), 10 bulk multi-region prostate cancer patients and two recent single-cell datasets of triple-negative breast cancer comprising several thousands of single cells.
Gibberellins target shoot-root growth, morpho-physiological and molecular pathways to induce cadmium tolerance in mung bean
Authors: Hakla Haroon Rashid , Sharma Shubham , Urfan Mohammad , Yadav Narendra Singh , Kotwal Dinesh , Pal Sikander 
Published: March 2021

AbstractCadmium (Cd) inhibits plant growth, perturb nutrient uptake and affect chloroplast ultra structure. Cd soil pollution is mainly contributed by excessive use of phosphate fertilizers, nickel Cd batteries, plating and sewage sludge. Research investigations deciphering role of Cd in affecting overall performance of mung bean is least understood. Likewise ameliorative effects of gibberellins (GAs) in Cd induced toxicity in mung bean are lesser known. In this context, effects of Cd stress (CdCl2, IC50−500 µM L−1) with or without GA3 application on mung bean (Vigna radiataL. Var. SML-668) plants were comprehensively investigated under controlled conditions. In brief, a total of 80 mung bean plants (15 days old of uniform height) were divided into four groups, with each group (n=20) subjected to four different treatments (Control, CdCl2,GA3, CdCl2+GA3), twice during the entire life cycle of mung bean plants (until harvest 85-90 days). Results revealed negative impacts of Cd stress on shoot morphometry (plant height, leaf surface area, stem diameter, shoot fresh weight, number of leaves, number of pods, length and diameter of pods), root morphometry (root length, root surface area, root dry weight, nodule number and nodule diameter), photosynthetic pigments and agronomic traits. GA3 ameliorated Cd stress by modulating shoot and root growth rates, improving overall plant metabolism, photosynthetic pigments, and shoot and root morphometry and transcript abundance ofVgPCS1,VgPCS2,VgCdRandVgIRT1. Current study proposes GA3 application for the effective management of Cd induced phytotoxicity in mung bean plants.
Are adaptive chemotherapy schedules robust? A three-strategy stochastic evolutionary game theory model
Authors: Dua R. , Ma Y. , Newton P.K. 
Published: March 2021

We investigate the robustness of adaptive chemotherapy schedules over repeated cycles and a wide range of tumor sizes. We introduce a non-stationary stochastic three-component fitness-dependent Moran process to quantify the variance of the response to treatment associated with multidrug adaptive schedules that are designed to mitigate chemotherapeutic resistance in an idealized (well-mixed) setting. The finite cell (Ntumor cells) stochastic process consists of populations of chemosensitive cells, chemoresistant cells to drug 1, and chemoresistant cells to drug 2, and the drug interactions can be synergistic, additive, or antagonistic. First, the adaptive chemoschedule is determined by using theN→ ∞ limit of the finite-cell process (i.e. the adjusted replicator equations) which is constructed by finding closed treatment response loops (which we call evolutionary cycles) in the three component phase-space. The schedules that give rise to these cycles are designed to manage chemoresistance by avoiding competitive release of the resistant cell populations. To address the question of how these cycles are likely to perform in practice over large patient populations with tumors across a range of sizes, we then consider the statistical variances associated with the approximate stochastic cycles for finiteN, repeating the idealized adaptive schedule over multiple periods. For finite cell populations, the error distributions remain approximately multi-Gaussian in the principal component coordinates through the first three cycles, with variances increasing exponentially with each cycle. As the number of cycles increases, the multi-Gaussian nature of the distribution breaks down due to the fact that one of the three subpopulations typically saturates the tumor (competitive release) resulting in treatment failure. This suggests that to design an effective and repeatable adaptive chemoschedule in practice will require a highly accurate tumor model and accurate measurements of the subpopulation frequencies or the errors will quickly (exponentially) degrade its effectiveness, particularly when the drug interactions are synergistic. Possible ways to extend the efficacy of the stochastic cycles in light of the computational simulations are discussed.Prepared for Special IssueUnderstanding the Evolutionary Dynamics and Ecology of Cancer Treatment Resistance, Ed. D. Basanta, Cancers (2021)
Multiple evolutionary origins reflect the importance of sialic acid transporters in the colonisation potential of bacterial pathogens and commensals
Authors: Severi Emmanuele , Rudden Michelle , Bell Andrew , Palmer Tracy , Juge Nathalie , Thomas Gavin H 
Published: March 2021

AbstractLocated at the tip of cell surface glycoconjugates, sialic acids are at the forefront of host-microbe interactions and, being easily liberated by sialidase enzymes, are used as metabolites by numerous bacteria, particularly by pathogens and commensals living on or near diverse mucosal surfaces. These bacteria rely on specific transporters for the acquisition of host-derived sialic acids. Here, we present the first comprehensive genomic and phylogenetic analysis of bacterial sialic acid transporters, leading to the identification of multiple new families and subfamilies. Our phylogenetic analysis suggests that sialic acid-specific transport has evolved independently at least 8 times during the evolution of bacteria, from within 4 of the major families/superfamilies of bacterial transporters, and we propose a robust classification scheme to bring together a myriad of different nomenclatures that exist to date. The new transporters discovered occur in diverse bacteria including Spirochaetes, Bacteroidetes, Planctomycetes, and Verrucomicrobia, many of which are species that have not been previously recognised to have sialometabolic capacities. Two subfamilies of transporters stand out in being fused to the sialic acid mutarotase enzyme, NanM, and these transporter fusions are enriched in bacteria present in gut microbial communities. We also provide evidence for a possible function of a sialic acid transporter component in chemotaxis that is independent of transport. Our analysis supports the increasing experimental evidence that competition for host-derived sialic acid is a key phenotype for successful colonisation of complex mucosal microbiomes, such that a strong evolutionary selection has occurred for the emergence of sialic acid specificity within existing transporter architectures.
Intrinsic variability of fluorescence calibrators impacts the assignment of MESF or ERF values to nanoparticles and extracellular vesicles by flow cytometry
Authors: Lozano-Andrés Estefanía , Van Den Broeck Tina , Wang Lili , Mehrpouyan Majid , Tian Ye , Yan Xiaomei , Wauben Marca H.M. , Arkesteijn Ger. J.A. 
Published: March 2021

AbstractFlow cytometry is commonly used to characterize nanoparticles (NPs) and extracellular vesicles (EVs) but results are often expressed in arbitrary units to indicate fluorescence intensity. This hampers interlaboratory and inter-platform comparisons. We investigated the use of molecules of equivalent soluble fluorophores (MESF)-beads for assignment of fluorescence values to NPs and EVs by comparing two FITC-MESF bead sets as calibrators on different flow cytometry platforms (BD Influx™, CytoFLEX LX™and SORP BD FACSCelesta™). Next, fluorescence signals of NPs and EVs were calibrated using different sets of FITC and PE-MESF beads. Fluorescence calibration using beads designed for cellular flow cytometry allowed inter-platform comparison. However, the intrinsic uncertainty in the fluorescence assignment to these MESF beads impacts the reliable assignment of MESF values to NPs and EVs based on extrapolation into the dim fluorescence range. Our findings demonstrate that the use of the same set of calibration materials (vendor and lot number) and the same number of calibration points, greatly improves robust interlaboratory and inter-platform comparison of fluorescent submicron sized particles.
Capturing the dynamics of interorganizational governance implementation: a process and cybernetic based conceptualization
Authors: Zhang Tao 
Published: February 2021

PurposeThe effectiveness of interorganizational governance is one of the most significant concerns of firms involved in supply chain management. Previous studies have extensively examined various interorganizational governance strategies. However, the dynamic and implementation details of interorganizational governance receive little attention, which leads to the defects of interorganizational governance literature. This study tries to explore this issue.Design/methodology/approachBased on the process and cybernetic view, this study conceptualized four interorganizational governance processes and their respective critical activities to capture the dynamic and implementation details of interorganizational governance. Furthermore, this study investigated the mapping of governance strategies into different critical activities, which unveil the various manifestations of governance strategies across these critical activities.FindingsFour interorganizational governance processes and their respective critical activities would overarch the dynamic and implementation details of governance strategies. Furthermore, various governance strategies also would have different manifestations across the critical activities of the four processes.Originality/valueThis paper fills the gaps in interorganizational governance literature in which the dynamic details of governance strategies are unclear. The new conceptualization provides a new paradigm for researchers to zoom in on the subtle dynamics of interorganizational governance. The new conceptualization indicates a few promising future research directions.
Nurses quality of work life: scale development and validation
Authors: TS Nanjundeswaraswamy 
Published: February 2021

PurposeThis is a systematically conducted study to design, develop and validate a measuring instrument to assess the nurses quality of work life (QWL) and determine the vital components of nurses' QWL.Design/methodology/approachIn this methodical study, vital dimensions of nurses QWL are identified using Pareto analysis; data and information were collected from 474 nurses through the structured questionnaire. By conducting exploratory factor analysis (EFA), the number of dimensions and items was reduced. Through the confirmatory factor analysis (CFA) using SPSS 21 software, nine predominant dimensions were confirmed, they are work environment, working condition, work–life balance, compensation, relationship and cooperation, stress at work, job satisfaction, career development and organization culture. Additional structural equation modeling (SEM) was done to determine the interrelationships between extracted nine components using AMOS. By performing different statistical tests like reliability test, content validity, construct validity, convergent, divergent validity and multicollinearity, the proposed nine-component nurses QWL instrument was validated.FindingsThe proposed measurement model explained 73.18% of total variance; reliability of the instrument Cronbach's alpha value is 0.902. Model fit indices like chi-square df (CMIN) = 685, df = 523, CMIN/DF = 1.310, goodness-of-fit index (GFI) = 0.965, adjusted goodness-of-fit index (AGFI) = 0.937, parsimony goodness-of-fit index (PGFI) = 0.918, incremental fir index (IFI) = 0.933, Tucker–Lewis index (TLI) = 0.921, comparative fit index (CFI) = 0.931 and root mean square error of approximation (RMSEA) = 0.036 fulfill the acceptable criteria. The nine factors nurses QWL measuring instrument is reliable and statistically valid.Research limitations/implicationsData were collected from 474 nurses, poor responses and time constraints.Practical implicationsHospitals are trying to improve the quality of patient caring by enhancing the nurses' skill sets, knowledge and attitude to meet global challenges. In this unstable business environment, hospitals face challenges like the high attrition rate and skilled nurses shortage. In this scenario, this study provides a valid instrument to measure the QWL of nurses to know the status of QWL, which will help to build a strategic plan to improve retention rate and to attract the talented workforce to the hospitals.Originality/valueAs a result, the scale developed in this study contributes to the body of the literature on nurses QWL. It seems to be more advantageous for carrying out further research in this field.