bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanical alterations of the hippocampus in the APP/PS1 Alzheimer’s disease mouse model
Authors: Antonovaite Nelda , Hulshof Lianne A. , Huffels Christiaan F.M. , Hol Elly M. , Wadman Wytse J. , Iannuzzi Davide 
Published: December 2020

AbstractThere is increasing evidence of altered tissue mechanics in neurodegeneration. However, due to difficulties in mechanical testing procedures and the complexity of the brain, there is still little consensus on the role of mechanics in the onset and progression of neurodegenerative diseases. In the case of Alzheimer’s disease (AD), magnetic resonance elastography (MRE) studies have indicated viscoelastic differences in the brain tissue of AD and healthy patients. However, there is a lack of viscoelastic data from contact mechanical testing at higher spatial resolution. Therefore, we report viscoelastic maps of the hippocampus obtained by a dynamic indentation on brain slices from the APP/PS1 mouse model where individual brain regions are resolved. A comparison of viscoelastic parameters shows that regions in the hippocampus of the APP/PS1 mice are significantly stiffer than wild-type (WT) mice and have increased viscous dissipation. Furthermore, indentation mapping at the cellular scale directly on the plaques and their surroundings did not show local alterations in stiffness although overall mechanical heterogeneity of the tissue was high (SD~40%). Therefore, reported mechanical alterations at a tissue scale indicates global remodeling of the brain tissue structure.
Multi-dimensional transcriptome analysis reveals modulation of cholesterol metabolism as highly integrated response to brain injury
Authors: Gourain Victor , Armant Olivier , Lübke Luisa , Diotel Nicolas , Rastegar Sepand , Strähle Uwe 
Published: December 2020

AbstractBackgroundZebrafish is an attractive model to investigate regeneration of the nervous system. Despite major progress in our understanding of the underlying processes, the transcriptomic changes are largely unknown. We analysed the transcriptome of the regenerating telencephalon for changes in the expression of mRNAs, their splice variants and investigated the putative role of regulatory RNAs in the modulation of these transcriptional changes.ResultsProfound changes in the expression of genes and their splice variants engaged in many distinct processes were observed. As exemplified by the coordinated regulation of the cholesterol synthesizing enzymes and transporters, the genome responded to injury of the telencephalon in a multi-tiered manner with distinct and interwoven changes in expression of enzymes, transporters and their regulatory molecules. This coordinated genomic response involved a decrease of the mRNA of the key transcription factor SREBF2, induction of microRNAs(miR- 182, miR-155, miR-146, miR-31)targeting cholesterol genes, shifts in abundance of splice variants as well as regulation of long non-coding RNAs.ConclusionsDifferential transcription and splicing are important processes in response to injury of the telencephalon. Cholesterol metabolism is switched from synthesis to relocation of cholesterol. Based on ourin silicoanalysis, this switch involves complementary and synergistic inputs by different regulatory principles. Our studies suggest that adaptation of cholesterol metabolism appears to be a key process involved in regeneration of the injured zebrafish brain.
Pharmacoinformatics based elucidation and designing of potential inhibitors againstPlasmodium falciparumto target importin α/β mediated nuclear importation
Authors: Oany Arafat Rahman , Pervin Tahmina , Moni Mohammad Ali 
Published: December 2020

AbstractPlasmodium falciparum, the prime causative agent of malaria, is responsible for 4, 05,000 deaths per year and fatality rates are higher among the children aged below 5 years. The emerging distribution of the multi-drug resistantP. falciparumbecomes a worldwide concern, so the identification of unique targets and novel inhibitors is a prime need now. In the present study, we have employed pharmacoinformatics approaches to analyze 265 lead-like compounds from PubChem databases for virtual screening. Thereafter, 15 lead-like compounds were docked within the active side pocket of importin alpha. Comparative ligand properties and absorption, distribution, metabolism, excretion, and toxicity (ADMET) profile were also assessed. Finally, a novel inhibitor was designed and assessed computationally for its efficacy. From the comparative analysis we have found that our screened compounds possess better results than the existing lead ivermectin; having the highest binding energy of −15.6 kcal/mol, whereas ivermectin has −12.4kcal/mol. The novel lead compound possessed more fascinating output without deviating any of the rules of Lipinski. It also possessed higher bioavailability and the drug-likeness score of 0.55 and 0.71, respectively compared to ivermectin. Furthermore, the binding study was confirmed by molecular dynamics simulation over 25 ns by evaluating the stability of the complex. Finally, all the screened compounds and the novel compound showed promising ADMET properties likewise. To end, we hope that our proposed screened compounds, as well as the novel compound, might give some advances to treat malaria efficiently in vitro and in vivo.
Vaccinomics Approach for Scheming Potential Epitope-Based Peptide Vaccine by Targeting L-protein of Marburg Virus
Authors: Pervin Tahmina , Oany Arafat Rahman 
Published: December 2020

AbstractMarburg virus is one of the world’s most threatening diseases, causing extreme hemorrhagic fever, with a death rate of up to ninety percent. The Food and Drug Administration (FDA) currently not authorized any treatments or vaccinations for the hindrance and post-exposure of the Marburg virus. In the Present study, the vaccinomics methodology was adopted to design a potential novel peptide vaccine against the Marburg virus, targeting RNA-directed RNA polymerase (L). A total of 48 L-proteins from diverse variants of the Marburg virus were collected from the NCBI GenBank server and used to classify the best antigenic protein leading to predict equally T and B-cell epitopes. Initially, the top 26 epitopes were evaluated for the attraction with major histocompatibility complex (MHC) class I and II alleles. Finally, four prospective central epitopes NLSDLTFLI, FRYEFTRHF, YRLRNSTAL, and YRVRNVQTL were carefully chosen. Among these, FRYEFTRHF and YRVRNVQTL peptides showed 100% conservancy. Though YRLRNSTAL showed 95.74% conservancy, it demonstrated the highest combined score as T cell epitope (2.5461) and population coverage of 94.42% among the whole world population. The epitope was found non-allergenic, and docking interactions with human leukocyte antigens (HLAs) also verified. Finally, in vivo analysis of the recommended peptides might contribute to the advancement of an efficient and exclusively prevalent vaccine that would be an active route to impede the virus spreading.
Centrosome-dependent microtubule organization sets the conditions for axon formation
Authors: Meka Durga Praveen , Kobler Oliver , Wuesthoff Souhaila , Schwanke Birgit , Krisp Christoph , Schmuelling Nessa , Rueter René , Ruecker Tabitha , Schlüter Hartmut , Fornasiero Eugenio F. , Calderon de Anda Froylan 
Published: December 2020

AbstractMicrotubule remodeling is critical during axon development when the more stable microtubules populate the axon. It is not completely understood, however, how this local cytoskeleton remodeling is coordinated. The centrosome, the main microtubule-organizing center (MTOC), has been suggested to be crucial for axon specification1–5. Conversely, it was proposed that axon elongation is independent of centrosomal functions6. Here we report that microtubule dynamics in early neurons follow a radial organization which establishes the conditions for the axon formation. Using high-resolution microscopy of early developing neurons, we demonstrate that few somatic acetylated microtubules are restricted near the centrosome. At later stages, however, acetylated microtubules spread out in the soma and concentrate in the growing axon. Furthermore, live-imaging of the microtubule plus-end binding protein EB3 in early differentiating neurons shows that growing microtubules have increased length and growth speed near the MTOC, suggesting local differences that might favor axon selection. Importantly, due to the lack of somatic stable/acetylated microtubules in early developing neurons, disruption of the F-actin cytoskeleton does not induce multiple axons, as it does at later stages of differentiation. Finally, we demonstrate that overexpression of the centrosomal protein 120 (Cep120), known for promoting microtubule acetylation and stabilization, induces multiple axons, while its downregulation decreases the content of proteins regulating microtubule dynamics and stability, hence hampering axon formation. Collectively, our data show that early centrosome-dependent microtubule organization contributes to axon formation.
An Ultrasensitive Biosensor for Quantifying the Interaction of SARS-CoV-2 and Its Receptor ACE2 in Cells andin vitro
Authors: Yang Xiaolong , Liu Lidong , Hao Yawei , So Yee Wah , Emami Sahar Sarmasti , Zhang Derek , Gong Yanping , Sheth Prameet M. , Wang Yu Tian 
Published: December 2020

ABSTRACTThe severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is currently spreading and mutating with increasing speed worldwide. Therefore, there is an urgent need for a simple, sensitive, and high-throughput (HTP) assay to quantify virus-host interaction in order to quickly evaluate infectious ability of mutant virus and develop or validate virus-inhibiting drugs. Here we have developed an ultrasensitive bioluminescent biosensor to evaluate virus-cell interaction by quantifying the interaction between SARS-CoV-2 receptor binding domain (RBD) and its cellular receptor angiotensin-converting enzyme 2 (ACE2) both in living cells andin vitro. We have successfully used this novel biosensor to analyze SARS-CoV-2 RBD mutants, and evaluated candidate small molecules (SMs), antibodies, and peptides that may block RBD:ACE2 interaction. This simple, rapid and HTP biosensor tool will significantly expedite detection of viral mutants and anti-COVID-19 drug discovery processes.
Translational control ofMPS1links protein synthesis with the initiation of cell division and spindle pole body duplication inSaccharomyces cerevisiae
Authors: Blank Heidi M. , Alonso Annabel , Fabritius Amy S. , Winey Mark , Polymenis Michael 
Published: December 2020

ABSTRACTProtein synthesis underpins cell growth and controls when cells commit to a new round of cell division at a point in late G1 of the cell cycle called Start. Passage through Start also coincides with the duplication of the microtubule-organizing centers, the yeast spindle pole bodies, which will form the two poles of the mitotic spindle that segregates the chromosomes in mitosis. The conserved Mps1p kinase governs the duplication of the spindle pole body inSaccharomyces cerevisiae. Here, we show that theMPS1transcript has a short upstream open reading frame that represses the synthesis of Mps1p. Mutating theMPS1uORF makes the cells smaller, accelerates the appearance of Mps1p in late G1, and promotes completion of Start. Monitoring the spindle pole body in the cell cycle using structured illumination microscopy revealed that mutating theMPS1uORF enabled cells to duplicate their spindle pole body earlier at a smaller cell size. The accelerated Start ofMPS1uORF mutants depends on the G1 cyclin Cln3p and the transcriptional repressor Whi5p but not on the Cln1,2p G1 cyclins. These results identify growth inputs in mechanisms that control duplication of the microtubule-organizing center and implicate these processes in the coupling of cell growth with division.
In vitroTargeting of Transcription Factors to Control the Cytokine Release Syndrome in COVID-19
Authors: Santoso Clarissa S. , Li Zhaorong , Rottenberg Jaice T. , Liu Xing , Shen Vivian X. , Fuxman Bass Juan I. 
Published: December 2020

AbstractTreatment of the cytokine release syndrome (CRS) has become an important part of rescuing hospitalized COVID-19 patients. Here, we systematically explored the transcriptional regulators of inflammatory cytokines involved in the COVID-19 CRS to identify candidate transcription factors (TFs) for therapeutic targeting using approved drugs. We integrated a resource of TF-cytokine gene interactions with single-cell RNA-seq expression data from bronchoalveolar lavage fluid cells of COVID-19 patients. We found 581 significantly correlated interactions, between 95 TFs and 16 cytokines upregulated in the COVID-19 patients, that may contribute to pathogenesis of the disease. Among these, we identified 19 TFs that are targets of FDA approved drugs. We investigated the potential therapeutic effect of 10 drugs and 25 drug combinations on inflammatory cytokine production in peripheral blood mononuclear cells, which revealed two drugs that inhibited cytokine production and numerous combinations that show synergistic efficacy in downregulating cytokine production. Further studies of these candidate repurposable drugs could lead to a therapeutic regimen to treat the CRS in COVID-19 patients.
Comparative Study on Acyl Transferases in Fatty Acid and Polyketide Synthases
Authors: Stegemann Franziska , Grininger Martin 
Published: December 2020

AbstractFatty acid and polyketide synthases (FASs and PKSs) synthesize physiologically and pharmaceutically important products by condensation of acyl building blocks. In both multidomain enzymes, the acyl transferase (AT) is the key player responsible for the selection of these acyl units for further processing. In this study, the AT domains of different PKS systems are kinetically described in their substrate selectivity, AT–Acyl carrier protein (ACP) domain-domain interaction, and enzymatic kinetic properties. The ATs of modular PKSs, the proteins assembling the most intricate polyketides, turned out to be significantly slower than ATs from iterative FAS and PKS systems, but also more substrate specific. We explain these substantially different properties by the phylogenetically early splitting of species. For the AT of the 6-deoxyerythronolide B synthase (DEBS), the interaction with ACP is analyzed in detail by site-directed mutagenesis of interface residues. Among others, a surface exposed arginine (R850) was replaced by three different residues, leading to mutants with severely different kinetics that cannot be explained by simple effects. Our study enlarges the understanding of ATs in its molecular properties, and is similarly a call for thorough AT-centered PKS engineering strategies.
Evolution of primate protomusicality via locomotion
Authors: Schruth David M. , Templeton Christopher N. , Holman Darryl J. , Smith Eric A. 
Published: December 2020

AbstractAnimals communicate acoustically to report location and identity to conspecifics. More complex patterning of calls can also function as displays to potential mates and as territorial advertisement. Music and song are terms often reserved only for humans and birds, but elements of both forms of acoustic display are also found in non-human primates. While theories on proximate functions abound, ultimate drivers of specific call structures are less well understood. We hypothesized that spatio-temporal precision in landing during perilous arboreal locomotion favored the evolution of musical calling in early primates—vastly preceding the origin of more music-like behavior in hominoids and subsequent emergence of music in later hominids. We test this locomotion-based hypothesis on the origins of proto-musicality using spectrographic depictions of vocal repertoires of modern day primates and corresponding estimates of locomotor activity. Phylogenetically controlled regression analysis of 54 primate species reveals that arboreal locomotion and monogamy are robust influences on complex calling patterns while controlling for other socioecological variables. Given that these findings rest primarily upon a handful of deep branching points in the primate tree, we conclude that this coevolution likely occurred very slowly, occupying on the order of tens of millions of years.LicenseAttribution-NoDerivatives 4.0 International (CC BY-ND 4.0)
Consumers' environmental responsibility and their purchase of local food: evidence from a large-scale survey
Authors: Bimbo Francesco , Russo Carlo , Di Fonzo Antonella , Nardone Gianluca 
Published: December 2020

PurposeThe paper explores whether consumers' environmentally sustainable attitudes and behaviors (e.g. saving water, energy, etc.) are associated with high frequency of local food purchases. The study uses a large sample of individual data collected across all Italian regions as well as accounts for the respondents' socioeconomic characteristics.Design/methodology/approachThe analysis uses a large sample of individual-level data (n = 21,081) collected by the Italian National Bureau of Statistics in the annual Italian Multipurpose Households Survey (MHS). Data contain individual information on the frequency of local food purchases as well as socioeconomic characteristics and environmentally friendly attitudes and behaviors. Data were analyzed using a multivariate ordered logit regression.FindingsResults indicate that individuals sensitive to environmental issues and adopting sustainable behaviors are more likely to purchase local food products than others. Also, age, education and occupational status positively are associated with a high frequency of local food purchases. Reading food nutrition labels, living in small communities as well as buying organic products are strong predictors of a higher frequency of local food choices.Originality/valueThe role of individual sustainable attitudes and behaviors in local food purchases has been marginally investigated in the literature. We addressed the issue by jointly accounting for several individual-related characteristics potentially shaping such relation. To the best of authors’ knowledge, the authors use the largest sample ever used to explore the individual's local food purchases in Italy.
Critical capabilities of improving supply chain resilience in industrialized construction in Hong Kong
Authors: Ekanayake E.M.A.C. , Shen Geoffrey , Kumaraswamy Mohan M. 
Published: December 2020

PurposeIndustrialized construction (IC) has accelerated the technological advancements of construction supply chains (SCs) in Hong Kong (HK). However, the usually fragmented IC SCs often lead to friction and turbulence that retard their performance. Streamlining these workflows call for resilient SCs that can proactively overcome various vulnerabilities and avoid disruptions. Having identified supply chain capabilities (SCC) as essential precursors to supply chain resilience (SCR), this paper reports on a vital segment of a study on SCC for IC in HK that focused here on critical SCC (CSCC). Specifically, this paper aims at identifying and probing the CSCC for improving SCR in IC in HK.Design/methodology/approachAfter drawing on the plentiful relevant literature, an empirical study using a questionnaire survey and interviews was conducted following the multi-stage methodological framework of this study. Relevant significance analysis of the collected data enabled the selection of CSCC. Next, factor analysis facilitated grouping them under nine underlying components.FindingsThe results reveal 41 CSCC pertinent to achieve resilient SCs in IC in HK under critical capability components of resourcefulness, flexibility, capacity, adaptability, efficiency, financial strength, visibility, anticipation and dispersion.Originality/valueIt is expected that industry practitioners would benefit from prior knowledge of CSCC and their levels of criticalities, so as to prioritize integrating them suitably into SC processes, to develop value-enhanced-resilient SCs. Further, these findings lay the foundations for developing a powerful evaluation model to assess, then improve, SCR in IC in HK by mapping the identified CSCC with relevant critical vulnerabilities, based on study outcomes.
BIM framework for the specification of information requirements in energy-related projects
Authors: Sanhudo Luís , Poças Martins João , Ramos Nuno M.M. , Almeida Ricardo M.S.F. , Rocha Ana , Pinto Débora , Barreira Eva , Simões M. Lurdes 
Published: December 2020

PurposeThis paper aims to further the discussion on Building Information Modelling (BIM) legal requirements, providing a framework with key energy parameters capable of supporting the Appointing Party in the definition of the Exchange Information Requirements (EIR) for a BIM project appointment. The EIR is described in ISO-19650–1:2018 as a fundamental step in the information delivery cycle.Design/methodology/approachA literature review on the topic of BIM energy analysis was completed to identify current knowledge gaps and support the need for the proposed framework. Afterwards, the framework was established based on the review findings and the authors’ domain knowledge. The applicability of the proposed framework was assessed through a case study, where several energy simulations were performed in three different design stages of the same BIM model.FindingsThis study identified a lack of standards and legislation capable of supporting the Appointing Party in the definition of energy-related BIM requirements. To this end, a new framework is proposed to mediate existing practices, linking prior knowledge with BIM’s new reality. The study showcases the applicability of the framework, identifying that the performance of different energy studies involves distinct Level of Development (LOD) requirements, which in turn have an impact on the modelling time and cost.Originality/valueA BIM framework for the specification of information requirements in energy-related projects was developed to support the Appointing Party. The framework presents appropriate parameters for energy analysis in each design stage, as well as the suitable LOD for the BIM model.
Consumer susceptibility to social influence in new product diffusion networks: how does network location matter?
Authors: Zhang Honghong , Gong Xiushuang 
Published: December 2020

Purpose
This study aims to empirically investigate how susceptibility to social influence in new product adoption varies with one’s structural location in a social network.

Design/methodology/approach
The social network data were collected based on a sociometric network survey with 589 undergraduate students. Social network analysis and ordinary least squares regression analyses were used to test the hypotheses.

Findings
This study finds that consumers with high degree centrality (i.e. hubs) who have a large number of connections to others and consumers with high betweenness centrality (i.e. bridges) who connect otherwise distant groups in social networks are both less sensitive to informational influence from others. More importantly, the authors find evidence that consumers with moderate levels of degree/betweenness centrality are more susceptible to normative influence and status competition than those with low or high degree/betweenness centrality. The inverse-U patterns in the above relations are consistent with middle-status conformity and anxiety.

Research limitations/implications
This research complements social influence and new product diffusion research by documenting important contingencies (i.e. network locations) in consumer susceptibility to different types of social influence from a social network perspective.

Practical implications
The findings will assist marketers to leverage social influence by activating relevant social ties with effective messages in their network marketing strategies.

Originality/value
This research provides a better understanding of the mechanisms driving susceptibility to social influence in new product diffusion.