bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Nanoluciferase biosensor to investigate endogenous chemokine secretion and receptor binding
Authors: White Carl W. , Pfleger Kevin D. G. , Hill Stephen J. 
Published: August 2020

SummarySecreted chemokines are critical mediators of cellular communication that elicit intracellular signalling by binding membrane-bound receptors. Here we demonstrate the development and use of a sensitive real-time approach to quantify secretion and receptor binding of native chemokines in live cells to better understand their molecular interactions and function. CRISPR/Cas9 genome-editing was used to tag the chemokine CXCL12 with the Nanoluciferase fragment HiBiT. CXCL12 secretion was subsequently monitored and quantified by luminescence output. Binding of tagged CXCL12 to either chemokine receptors or membrane glycosaminoglycans could be monitored due to the steric constraints of Nanoluciferase complementation. Furthermore, binding of native CXCL12-HiBiT to AlexaFluor488-tagged CXCR4 chemokine receptors could also be distinguished from glycosaminoglycan binding and pharmacologically analysed using BRET. These live cell approaches combine the sensitivity of Nanoluciferase with CRISPR/Cas9 genome-editing to detect, quantify and monitor binding of low levels of native secreted proteins in real time.
Gigantic Genomes Can Provide Empirical Tests of TE Dynamics Models — An Example from Amphibians
Authors: Wang Jie , Itgen Michael W. , Wang Huiju , Gong Yuzhou , Jiang Jianping , Li Jiatang , Sun Cheng , Sessions Stanley K. , Mueller Rachel Lockridge 
Published: August 2020

AbstractTransposable elements (TEs) are a major determinant of eukaryotic genome size. The collective properties of a genomic TE community reveal the history of TE/host evolutionary dynamics and impact present-day host structure and function, from genome to organism levels. In rare cases, TE community/genome size has greatly expanded in animals, associated with increased cell size and altered anatomy and physiology. We characterize the TE landscape of the genome and transcriptome in an amphibian with a giant genome — the caecilianIchthyophis bannanicus, which we show has a genome size of 12.2 Gb. Amphibians are an important model system because the clade includes independent cases of genomic gigantism. TheI. bannanicusgenome differs compositionally from other giant amphibian genomes, but shares a low rate of ectopic-recombination-mediated deletion. We examine TE activity using expression and divergence plots; TEs account for 15% of somatic transcription, and most superfamilies appear active. We quantify TE diversity in the caecilian, as well as other vertebrates with a range of genome sizes, using diversity indices commonly applied in community ecology. We synthesize previous models integrating TE abundance, diversity, and activity, and we test whether the caecilian meets model predictions for genomes with high TE abundance. We propose thorough, consistent characterization of TEs to strengthen future comparative analyses. Such analyses will ultimately be required to reveal whether the divergent TE assemblages found across convergent gigantic genomes reflect fundamental shared features of TE/host genome evolutionary dynamics.
Computational approach and functional analysis of thePectobacterium carotovorum subsp. carotovorumlow-molecular weight bacteriocin Carocin S2
Authors: Wang Jyun-Wei , Lagitnay Ruchi Briam James S. , Derilo Reymund C. , Wu Jian-Li , Chuang Duen-Yau 
Published: August 2020

AbstractPectobacterium carotovorum subsp. Carotovorum3F3 is a gram-negative phyto-parasitic enterobacterium. This strain is a producer of Carocin S2 bacteriocin, which comprises of two proteins of different sizes. Carocin S2K (killer protein) which is responsible for antibiotic resistance and Carocin S2I (immunity protein) which inhibits the antibiotic activity.The present study aimed to predict the structure and functional properties of Carocin S2. Computational approaches utilizing various bioinformatic tools predicted that Carocin S2 is a putative membrane protein having the N-terminal at the extracellular side and the central domain at the coiled-coil region. Carocin S2 was predicted to have three domains, the translocation domains, receptor binding domain and the killer domain. Moreover, the killer domain was calculated to have the catalytic cleft. The in-vivo assays confirmed that for Carocin S2K, bound immunity protein was not a pre-requisite for cell attachment or translocation. The site-directed mutagenesis experiment led us to hypothesized the hydrolysis mechanism of Carocin S2.The predicted structure of Carocin S2K provided a system of understanding on the biochemical and structural function which led to the mechanism of Carocin S2. It revealed that the role of immunity protein to Carocin S2 is not a pre-requisite for translocation pathway. Furthermore, this research led to hypothesized a hydrolytic mechanism of Carocin S2 to target the tRNA.
De Novo Assembly of a Chromosome-Scale Reference Genome for the Northern FlickerColaptes auratus
Authors: Hruska Jack P. , Manthey Joseph D. 
Published: August 2020

ABSTRACTThe northern flicker,Colaptes auratus, is a widely distributed North American woodpecker and a long-standing focal species for the study of ecology, behavior, phenotypic differentiation, and hybridization. We present here a highly contiguousde novogenome assembly ofC. auratus,the first such assembly for the species and the first published chromosome-level assembly for woodpeckers (Picidae). The assembly was generated using a combination of short-read Chromium 10x and long-read PacBio sequencing, and further scaffolded with chromatin conformation capture (Hi-C) reads. The resulting genome assembly is 1.378 Gb in size, with a scaffold N50 of 43.948 Mb and a scaffold L50 of 11. This assembly contains 87.4 % - 91.7 % of genes present across four sets of universal single-copy orthologs found in tetrapods and birds. We annotated the assembly both for genes and repetitive content, identifying 18,745 genes and a prevalence of ~ 28.0 % repetitive elements. Lastly, we used four-fold degenerate sites from neutrally evolving genes to estimate a mutation rate forC. auratus, which we estimated to be 4.007 × 10−9substitutions / site / year, about 1.5x times faster than an earlier mutation rate estimate of the family. The highly contiguous assembly and annotations we report will serve as a resource for future studies on the genomics ofC. auratusand comparative evolution of woodpeckers.
A robust and versatile nanobody platform for drug delivery
Authors: Shen Zhuolun , Xiang Yufei , Vegara Sandra , Chen Apeng , Xiao Zhengyun , Santiago Ulises , Jin Changzhong , Sang Zhe , Luo Jiadi , Chen Kong , Schneidman-Duhovny Dina , Camacho Carlos , Calero Guillermo , Hu Baoli , Shi Yi 
Published: August 2020

AbstractTherapeutic and diagnostic efficacies of numerous small biomolecules and chemical compounds are hampered by the short half-lives. Here we report the development of a repertoire of diverse, high-affinity albumin-nanobodies (NbHSA) to facilitate drug delivery. By integrating biophysics, and hybrid structural biology, we have systematically characterized the NbHSAfor albumin binding, mapped the epitopes, and resolved the architecture of a tetrameric Nb-albumin complex. We employed quantitative proteomics for accurate, multiplex Nb pharmacokinetic analysis. Using a humanized albumin mouse model, we found that the NbHSAhas outstanding pharmacokinetics; the most stable NbHSAhas a 771-fold T1/2improvement compared with a control Nb. Interestingly, the pharmacokinetics of NbHSAis related to their biophysical and structural properties. To demonstrate the utility of NbHSA, we developed a highly stable NbHSA-hIL-2 cytokine conjugate “Duraleukin” and confirmed its improved anticancer properties than hIL-2 alone. We envision that this high-quality Nb resource will advance research into novel biotherapeutics.
Brain Amyloid and the Transition to Dementia in Down Syndrome
Authors: Keator David B. , Doran Eric , Taylor Lisa , Phelan Michael J. , Hom Christy , Tseung Katherine , van Erp Theo G.M. , Potkin Steven G. , Brickman Adam M. , Rosas Diana H. , Yassa Michael A. , Silverman Wayne , Lott Ira T. 
Published: August 2020

AbstractINTRODUCTIONDown syndrome (DS) is associated with elevated risk for Alzheimer’s disease (AD) due to beta amyloid (Aβ) lifelong accumulation. We hypothesized that the spatial distribution of brain Aβ predicts future dementia conversion in individuals with DS.METHODSWe acquired18F-Florbetapir PET scans from 19 nondemented individuals with DS at baseline and monitored them for four years, with five individuals transitioning to dementia. Machine learning classification determined features on18F-Florbetapir standardized uptake value ratio (SUVR) maps that predicted transition.RESULTSIn addition to “AD signature” regions including the inferior parietal cortex, temporal lobes, and the cingulum, we found that Aβ cortical binding in the prefrontal and superior frontal cortices distinguished subjects who transitioned to dementia. Classification did well in predicting transitioners.DISCUSSIONOur study suggests that specific regional profiles of brain amyloid in older adults with DS may predict cognitive decline and are informative in evaluating the risk for dementia.HighlightsRegional [18F]-Florbetapir PET predicts future transition to dementia in Downs Syndrome.Increased amyloid in prefrontal, inferior parietal, superior frontal, rostral middle frontal, and posterior cingulate cortices detect transitioiners, with prefrontal and superior frontal being best overall.Amyloid PET-based classification able to discriminate between transitioners and non-transitioners.
Activity of the GHRH Antagonist MIA602 and its Underlying Mechanisms of Action in sarcoidosis
Authors: Zhang Chongxu , Tian Runxia , Dreifus Emilee M , Holt Gregory , Cai Renzhi , Griswold Anthony , Bejarano Pablo , Jackson Robert , Schally Andrew V. , Mirsaeidi Mehdi 
Published: August 2020

AbstractGrowth hormone releasing hormone (GHRH) is a potent stimulator of GH secretion from the pituitary gland. Although GHRH is essential for the growth of immune cells, the regulatory effects of its antagonist in granulomatous disease remains unknown. Here, we report expression of GHRH receptor (R) in human tissue with sarcoidosis granuloma and demonstrate the anti-inflammatory effects of MIA602 (a GHRH antagonist) in twoin vitrohuman granuloma models and anin vivogranuloma model. MIA602 decreases levels of IL2, IL12, and IL17A inin vitrogranuloma model.We show further that the anti-inflammatory effect of MIA602 appears to be mediated by reduction in CD45++CD68+cells in granulomatous tissue and upregulation in PD-1 expression in macrophages.In analysis of expression of proteins involved in the mitochondrial stage of apoptosis, we show that MIA602 increases the levels of caspase 3, BCL-xL/BAK dimer, and MCl-1/Bak dimer in granuloma. These findings indicate that MIA602 may not induce apoptosis.The clinical relevance of our findings further suggest that HGRH-R is potentially a target for treatment of granulomatous disease and MIA602 possibly a novel therapeutic agent for sarcoidosis.
Prom1 expression does not mark a stem/progenitor population in the mouse oviduct epithelium
Authors: Ford Matthew J , Yamanaka Yojiro 
Published: August 2020

SummaryThe oviduct or fallopian tube is the site of fertilization and preimplantation embryonic development. The epithelium lining the oviduct consists of multiciliated and secretory cells, which support fertilization and preimplantation development, however, its homeostasis still remains poorly understood. CD133/Prom1has been used to identify adult stem cell populations in various organs and often associated with cancer stem cell property. Using a Cre-recombinase based lineage tracing strategy, we found that CD133/Prom1expression was not associated with a stem/progenitor population in the oviduct but marked a sub population of multiciliated and secretory cells which did not propagate. Interestingly,Prom1expressing secretory cells rapidly transition to multiciliated cells and progressively migrate to the tips of epithelial folds in the ampulla. Our results show that CD133/Prom1expression cannot be used as a progenitor/stem cell marker in the mouse oviduct.
Coherence Shifts in Attribute Evaluations
Authors: Lee Douglas G. , Holyoak Keith J. 
Published: August 2020

AbstractIn five experiments, people repeatedly judged individual options with respect to both overall value and attribute values. When required to choose between two snacks, each differing in two attributes (pleasure and nutrition), people’s assessments of value shifted from pre- to post-choice in the direction that spread the alternatives further apart so as to favor the winner, thereby increasing confidence in the choice. This shift was observed not only for ratings of overall value, but also for each of the two individual attributes. The magnitude of the coherence shift increased with choice difficulty as measured by the difference in initial ratings of overall value for the two options, as well as with a measure of attribute disparity (the degree to which individual attributes “disagree” with one another as to which option is superior). In Experiments 2-5, tasks other than explicit choice generated the same qualitative pattern of value changes, confidence, and response time. These findings support the hypothesis that active consideration of options, whether or not explicitly related to value, automatically refines the mental value representations for the options, which in turn allows them to be more precisely distinguished when later included in a value-based choice set.
Multifractality in postural sway supports quiet eye training in aiming tasks: A study of golf putting
Authors: Jacobson Noah , Berleman-Paul Quinn , Mangalam Madhur , Kelty-Stephen Damian G. , Ralston Christopher 
Published: August 2020

AbstractThe ‘quiet eye’ (QE) approach to visually-guided aiming behavior invests fully in perceptual information’s potential to organize coordinated action. Sports psychologists refer to QE as the stillness of the eyes during aiming tasks and increasingly into self- and externally-paced tasks. Amidst the ‘noisy’ fluctuations of the athlete’s body, quiet eyes might leave fewer saccadic interruptions to the coupling between postural sway and optic flow. Postural sway exhibits fluctuations whose multifractal structure serves as a robust predictor of visual and haptic perceptual responses. Postural sway generates optic flow centered on an individual’s eye height. We predicted that perturbing the eye height by attaching wooden blocks below the feet would perturb the putting more so in QE-trained participants than participants trained technically. We also predicted that QE’s efficacy and responses to perturbation would depend on multifractality in postural sway. Specifically, we predicted that less multifractality would predict more adaptive responses to the perturbation and higher putting accuracy. Results showed that lower multifractality led to more accurate putts, and the perturbation of eye height led to less accurate putts, particularly for QE-trained participants. Models of radial error (i.e., the distance between the ball’s final position and the hole) indicated that lower estimates of multifractality due to nonlinearity coincided with a more adaptive response to the perturbation. These results suggest that reduced multifractality may act in a context-sensitive manner to restrain motoric degrees of freedom to achieve the task goal.
Partial Inhibition of Mitochondrial Complex I Reduces Tau Pathology and Improves Energy Homeostasis and Synaptic Function in 3xTg-AD Male and Female Mice
Authors: Stojakovic Andrea , Chang Su-Youne , Nesbitt Jarred , Pichurin Nicholas P. , Ostroot Mark A. , Trushina Eugenia 
Published: August 2020

AbstractBackgroundAccumulation of hyperphosphorylated Tau (pTau) protein is associated with synaptic dysfunction in Alzheimer’s disease (AD). We previously demonstrated that neuroprotection in familial mouse models of AD could be achieved by targeting mitochondria complex I (MCI) and activating the adaptive stress response. Efficacy of this strategy on pTau-related pathology remained unknown.ObjectiveTo investigate the effect of specific MCI inhibitor tricyclic pyrone compound CP2 on pTau levels, memory function, long term potentiation (LTP), and energy homeostasis in 18-month-old 3xTg-AD mice and explore the potential mechanisms.MethodsCP2 was administered to male and female 3xTg-AD mice from 3.5 - 18 months of age. Cognitive function was assessed using the Morris water maze test. Glucose metabolism was measured in periphery using a glucose tolerance test and in the brain using fluorodeoxyglucose F18 positron-emission tomography (FDG-PET). LTP was evaluated using electrophysiology in the hippocampus. The expression of key proteins associated with neuroprotective mechanisms were assessed by western blotting.ResultsChronic CP2 treatment restored synaptic activity and cognitive function, increased levels of synaptic proteins, improved glucose metabolism and energy homeostasis in male and female 3xTg-AD mice. Significant reduction of human pTau in the brain was associated with increased activity of protein phosphatase of type 2A (PP2A), reduced activity of cyclin-dependent kinase 5 (CDK5) and glycogen synthase kinase 3β (GSK3β).ConclusionCP2 treatment protected against synaptic dysfunction and memory impairment in symptomatic 3xTg-AD mice, and reduced levels of human pTau, indicating that targeting mitochondria with small molecule specific MCI inhibitors represents a promising strategy for AD.
Flexible assertive community treatment for individuals with mild intellectual disability or borderline intellectual functioning: client variables associated with treatment outcome
Authors: Neijmeijer Laura , Korzilius Hubert , Kroon Hans , Nijman Henk , Didden Robert 
Published: August 2020

PurposeRecent research on flexible assertive community treatment (FACT) for individuals with mild intellectual disabilities (MID) or borderline intellectual functioning (BIF) has shown positive results. This paper aims to identify which client variables are associated with treatment outcome of FACT.Design/methodology/approachAnalyses were performed on assessments made during a six-year longitudinal study in The Netherlands. Data comprised assessments of 281 clients with at least 2 measurements. Treatment outcome was measured by the learning disability version of the Health of the Nation Outcomes Scales. Demographic variables and dynamic risk variables of the short version of the Dynamic Risk Outcome Scales were selected as potential predictor variables of outcome. Data were analysed using linear mixed models.FindingsLimited awareness of the need for treatment, limited treatment motivation and cooperation, limited social skills, impulsivity and substance abuse were significantly associated with worse treatment outcome. None of the demographic variables influenced treatment outcome significantly, and neither did intelligence quotient or having a judicial or civil measure.Research limitations/implicationsBecause of the observational design, no causal inferences can be drawn.Practical implicationsThis study produces guidelines regarding nature and scope of the treatment supply and the competences of professionals working in FACT MID/BIF teams.Originality/valueThis paper encourages other countries to make assertive outreach available for people with MID/BIF on a larger scale, taking into account the acquired insights.
Market-oriented CSR implementation in SMEs with sustainable innovations: an action research approach
Authors: Sundström Agneta , Hyder Akmal S. , Chowdhury Ehsanul Huda 
Published: August 2020

PurposeThe purpose of the study is to identify and analyze critical mediating and moderating market intelligence challenges faced by the SMEs when implementing corporate social responsibility (CSR) based on an applied market-oriented business model (MOBM).Design/methodology/approachFocusing on developing CSR-integrated market intelligence, this study uses an action research method by analyzing four case studies. Data is collected through interviews, interactive and knowledge-sharing meetings and on-site observations. The study is part of a larger European Union project using the developed MOBM to follow the four companies' CSR implementation and learning process over a 14-month period. The action research includes seven meetings; between these, the researchers introduced the SMEs to different business focus areas, where CSR is a vital part of the MOBM.FindingsThis study shows that the SMEs are too technology-focused and have little initial idea of how to integrate CSR advantages for market intelligence into their internationalization. The MOBM model offers insights and knowledge on the strength and weakness of the internal organization to meet challenges in internationalization.Originality/valueVia case study and action research, this study spotlights the challenges that SMEs face in the CSR implementation process and how they deal with those challenges to develop market intelligence competence internally. Instead of following a traditional research approach, the current study applies a CSR-based method where the SMEs go through a knowledge development process that originated from a theoretically designed MOBM.
Does CSR reporting indicate strong corporate governance?
Authors: Chan Siew H. , Creel Timothy S. , Song Qian , Yurova Yuliya V. 
Published: August 2020

PurposeThis study aims to investigate the relationship between companies filing versus those not filing corporate social responsibility (CSR) reports and corporate governance.Design/methodology/approachThe websites of US publicly traded companies were examined for commitment to CSR or sustainability reporting based on the preparation of voluntary reports. This information provided the CSR measure, the key independent variable in this study. The data used to compute discretionary accruals (based on the modified Jones model) were obtained from Compustat. Data on auditor tenure were retrieved from Audit Analytics. The number of members and financial experts on an audit committee were gathered from proxy reports filed with the US Securities and Exchange Commission.FindingsCompanies filing CSR reports have higher audit quality, higher audit committee quality, increased auditor tenure and lower auditor dismissal compared to those not filing CSR reports. The findings support stakeholder theory.Research limitations/implicationsThis study’s utilization of multiple measures of corporate governance provides insight into the robustness of the relationship between CSR reporting and corporate governance. Further, this research uses a different measure of CSR reporting; that is, companies that voluntarily prepared separate CSR reports following or not following the Global Reporting Initiative (GRI) guidelines compared to reports prepared following the GRI guidelines. This approach increases the size and diversity (i.e. industries) of the sample (Kolk, 2003; Waddock and Graves, 1997).Practical implicationsThe findings suggest that companies engage in CSR reporting to indicate strong corporate governance.Originality/valueThis study uses multiple measures of corporate governance to demonstrate the positive relationship between CSR behavior (measured via filing of CSR reports) and corporate governance.