bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modulation of the cAMP levels with a conserved actinobacteria phosphodiesterase enzyme reduces antimicrobial tolerance in mycobacteria
Authors: Thomson Michael , Nunta Kanokkan , Cheyne Ashleigh , liu Yi , Garza-Garcia Acely , Larrouy-Maumus Gerald 
Published: August 2020

AbstractAntimicrobial tolerance (AMT) is the gateway to the development of antimicrobial resistance (AMR) and is therefore a major issue that needs to be addressed.The second messenger cyclic-AMP (cAMP), which is conserved across all taxa, is involved in propagating signals from environmental stimuli and converting these into a response. In bacteria, such asM. tuberculosis,P. aeruginosa,V. choleraeandB. pertussis, cAMP has been implicated in virulence, metabolic regulation and gene expression. However, cAMP signalling in mycobacteria is particularly complex due to the redundancy of adenylate cyclases, which are enzymes that catalyse the formation of cAMP from ATP, and the poor activity of the only known phosphodiesterase (PDE) enzyme, which degrades cAMP into 5’- AMP.Based on these two features, the modulation of this system with the aim of investigating cAMP signalling and its involvement in AMT in mycobacteria id difficult.To address this pressing need, we identified a new cAMP-degrading phosphodiesterase enzyme (Rv1339) and used it to significantly decrease the intrabacterial levels of cAMP in mycobacteria. This analysis revealed that this enzyme increased the antimicrobial susceptibility ofM. smegmatismc2155. Using a combination of metabolomics, RNA-sequencing, antimicrobial susceptibility assays and bioenergetics analysis, we were able to characterize the molecular mechanism underlying this increased susceptibility.This work represents an important milestone showing that the targeting of cAMP signalling is a promising new avenue for antimicrobial development and expands our understanding of cAMP signalling in mycobacteria.
One-step multiple site-specific base editing by direct embryo injection for precision and pyramid pig breeding
Authors: Song Ruigao , Wang Yu , Zheng Qiantao , Yao Jing , Cao Chunwei , Wang Yanfang , Zhao Jianguo 
Published: August 2020

AbstractPrecise and simultaneous acquisition of multiple beneficial alleles in the genome to improve pig performance are pivotal for making elite breeders. Cytidine base editors (CBEs) have emerged as powerful tools for site-specific single nucleotide replacement. Here, we compare the editing efficiency of four CBEs in porcine embryonic cells and embryos to show that hA3A-BE3-Y130F and hA3A-eBE3-Y130F consistently results in higher base-editing efficiency and lower toxic effects to in vitro embryo development. We also show that zygote microinjection of hA3A-BE3-Y130F results in one-step generation of pigs (3BE pigs) harboring C-to-T point mutations, including a stop codon in CD163 and in MSTN and induce beneficial allele in IGF2. The 3BE pigs showed improved growth performance, hip circumference, food conversion rate. Our results demonstrate that CBEs can mediate high throughput genome editing by direct embryo microinjection. Our approach allows immediate introduction of novel alleles for beneficial traits in transgene-free animals for pyramid breeding.
An inside look at a biofilm: Pseudomonas aeruginosa flagella bio-tracking
Authors: Ozer Eden , Yaniv Karin , Chetrit Einat , Boyarski Anastasya , Meijler Michael M. , Berkovich Ronen , Kushmaro Ariel , Alfonta Lital 
Published: August 2020

AbstractThe opportunistic pathogen,Pseudomonas aeruginosa, a flagellated bacterium, is one of the top model organisms for studying biofilm formation. In order to elucidate the role of the bacteria flagella in biofilm formation, we developed a new tool for flagella bio-tracking. We have site-specifically labeled the bacterial flagella by incorporating an unnatural amino acid into the flagella monomer via genetic code expansion. This enabled us to label and track the bacterial flagella during biofilm maturation. Direct, live imaging revealed for the first-time presence and synthesis of flagella throughout the biofilm lifecycle. To ascertain the possible role of the flagella in the strength of a biofilm we produced a “flagella knockout” strain and compared its biofilm to that of the wild type strain. Results showed a one order of magnitude stronger biofilm structure in the wild type in comparison to the flagella knockout strain. This suggests a newly discovered structural role for bacterial flagella in biofilm structure, possibly acting as a scaffold. Based on our findings we suggest a new model for biofilm maturation dynamic and underscore the importance of direct evidence from within the biofilm.
AI aided design of epitope-based vaccine for the induction of cellular immune responses against SARS-CoV-2
Authors: Mazzocco G. , Niemiec I. , Myronov A. , Skoczylas P. , Kaczmarczyk J. , Sanecka-Duin A. , Gruba K. , Król P. , Drwal M. , Szczepanik M. , Pyrc K. , Stępniak P. 
Published: August 2020

AbstractThe heavy burden imposed by the COVID-19 pandemic on our society triggered the race towards the development of therapies or preventive strategies. Among these, antibodies and vaccines are particularly attractive because of their high specificity, low probability of drug-drug interaction, and potentially long-standing protective effects. While the threat at hand justifies the pace of research, the implementation of therapeutic strategies cannot be exempted from safety considerations. There are several potential adverse events reported after the vaccination or antibody therapy, but two are of utmost importance: antibody-dependent enhancement (ADE) and cytokine storm syndrome (CSS). On the other hand, the depletion or exhaustion of T-cells has been reported to be associated with worse prognosis in COVID-19 patients. This observation suggests a potential role of vaccines eliciting cellular immunity, which might simultaneously limit the risk of ADE and CSS. Such risk was proposed to be associated with FcR-induced activation of proinflammatory macrophages (M1) by Fu et al. 2020 and Iwasaki et al. 2020. All aspects of the newly developed vaccine (including the route of administration, delivery system, and adjuvant selection) may affect its effectiveness and safety. In this work we use a novel in silico approach (based on AI and bioinformatics methods) developed to support the design of epitope-based vaccines. We evaluated the capabilities of our method for predicting the immunogenicity of epitopes. Next, the results of our approach were compared with other vaccine-design strategies reported in the literature. The risk of immuno-toxicity was also assessed. The analysis of epitope conservation among otherCoronaviridaewas carried out in order to facilitate the selection of peptides shared across different SARS-CoV-2 strains and which might be conserved in emerging zootic coronavirus strains. Finally, the potential applicability of the selected epitopes for the development of a vaccine eliciting cellular immunity for COVID-19 was discussed, highlighting the benefits and challenges of such an approach.
Many ways to make darker flies: Intra- and inter-specific variation inDrosophilabody pigmentation components
Authors: Lafuente Elvira , Alves Filipa , King Jessica G , Peralta Carolina M , Beldade Patrícia 
Published: August 2020

ABSTRACTBody pigmentation is an evolutionarily diversified and ecologically relevant trait that shows variation within and between species, and important roles in animal survival and reproduction. Insect pigmentation, in particular, provides some of the most compelling examples of adaptive evolution and its ecological and genetic bases. Yet, while pigmentation includes multiple aspects of color and color pattern that may vary more or less independently, its study frequently focuses on one single aspect. Here, we develop a method to quantify color and color pattern inDrosophilabody pigmentation, decomposing thorax and abdominal pigmentation into distinct measurable traits, and we quantify different sources of variation in those traits. For each body part, we measured overall darkness, as well as four other pigmentation properties distinguishing between background color and color of the darker pattern elements that decorate the two body parts. By focusing on two standardD. melanogasterlaboratory populations, we show that pigmentation components vary and co-vary in different manners depending on sex, genetic background, and developmental temperature. By studying three natural populations ofD. melanogasteralong a latitudinal cline and five otherDrosophilaspecies, we then show that evolution of lighter or darker bodies can be achieved by changing distinct component traits. Our study underscores the value of detailed phenotyping for a better understanding of phenotypic variation and diversification, and the ecological pressures and genetic mechanisms underlying them.
Voltage imaging using transgenic mouse lines expressing the GEVI ArcLight in two olfactory cell types
Authors: Platisa Jelena , Zeng Hongkui , Madisen Linda , Cohen Lawrence B. , Pieribone Vincent A , Storace Douglas A. 
Published: August 2020

AbstractGenetically encoded voltage indicators (GEVIs) allow for cell-specific optical recordings of membrane potential changes in defined cell populations. One tool that would further their use in thein vivomammalian brain is transgenic reporter animals that facilitate precise and repeatable targeting with high expression levels. The present literature on the development and use of transgenic mouse lines as vehicles for GEVI expression is limited. Here we report the firstin vivoexperiments using a transgenic reporter mouse for the GEVI ArcLight (Ai86(TITL-ArcLight)), which utilizes a Cre/tTA dependent expression system (TIGRE 1.0). Following pairing to appropriate Cre- and tTA transgenic mice, we report two mouse lines with ArcLight expression restricted to olfactory sensory neurons (OMP-ArcLight), and a subpopulation of interneurons that include periglomerular and granule cells (Emx1-ArcLight) in the olfactory bulb (OB). The ArcLight expression in these lines was sufficient forin vivoimaging of odorant responses in single trials. Odor responses were measured in the OB using epifluorescence and 2-photon imaging. The voltage responses were odor-specific and concentration-dependent, and confirmed earlier conclusions from calcium measurements. This study shows that the ArcLight Ai86(TITL-ArcLight) transgenic line is a flexible genetic tool that can be used to record neuronal electrical activity of a variety of cell types with a signal-to-noise ratio that is comparable to previous reports using viral transduction.
A Phased Canis lupus familiaris Labrador Retriever Reference Genome Utilizing High Molecular Weight DNA Extraction Methods and High Resolution Sequencing Technologies
Authors: Player Robert A. , Forsyth Ellen R. , Verratti Kathleen J. , Mohr David W. , Scott Alan F. , Bradburne Christopher E. 
Published: August 2020

ABSTRACTReference genome fidelity is critically important for genome wide association studies (GWAS), yet many are incomplete or too dissimilar from the study population. A typical whole genome sequencing approach implies short-read technologies resulting in fragmented assemblies with regions of ambiguity low complexity. Further information is lost by economic necessity when genotyping populations, as lower resolution technologies such as genotyping arrays are commonly utilized. Here we present a phased reference genome for Canis lupus familiaris utilizing high molecular weight sequencing technologies. We tested wet lab and bioinformatic approaches to demonstrate a minimum workflow to generate the 2.4 gigabase genome for a Labrador Retriever. The resulting de novo assembly required eight Oxford Nanopore R9.4 flowcells (~23X depth) and running a 10X Genomics library on the equivalent of one lane of an Illumina NovaSeq S1 flowcell (~88X depth), bringing the cost of generating a nearly complete reference genome to less than $10K. Mapping of publicly available short-read data from ten Labrador Retrievers against this breed-specific reference resulted in an average of approximately 1% more aligned reads compared to mapping against the current gold standard reference (CanFam3.1, p<0.001), indicating a more complete breed-specific reference. An average 15% reduction of variant calls was observed from the same mapped data, which increases the chance of identifying low effect size variants in a GWAS. We believe that by incorporating the cost to produce a full genome assembly into any large-scale canine genotyping study, an investigator can make an informed cost/benefit analysis regarding genotyping technology.
Postsynaptic potential energy as determinant of synaptic plasticity
Authors: Chen Huan-Wen , Xie Li-Juan , Wang Yi-Jun , Zhang Hang 
Published: August 2020

AbstractMetabolic energy can be used as a unified principle to control neuronal activity. However, whether and how metabolic energy alone can determine the outcome of synaptic plasticity remains unclear. In this study, a computational model of synaptic plasticity that is completely determined by energy is proposed. A simple quantitative relationship between synaptic plasticity and postsynaptic potential energy is established. Synaptic weight is directly proportional to the difference between the baseline potential energy and the suprathreshold potential energy and is constrained by the maximum energy supply. Results show that the energy constraint improves the performance of synaptic plasticity and avoids setting the hard boundary of synaptic weights. With the same set of model parameters, our model can reproduce several classical experiments in homo and heterosynaptic plasticity. The proposed model can explain the interaction mechanism of Hebbian and homeostatic plasticity at the cellular level, thereby providing a new way to deeply understand the characteristics of learning and memory.
Green competencies: insights and recommendations from a systematic literature review
Authors: Cabral Clement , Dhar Rajib Lochan 
Published: August 2020

PurposeThis study conceptualises the construct – green competencies. The concept is in the niche stage and needs further elaboration. Hence, to address the research gap, this study follows the steps proposed by Tranfield et al. (2003). The major part of the study comprises descriptive analysis and thematic analysis. Descriptive analysis of the selected 66 articles was examined with the classification framework, which contains year-wise distribution, journal-wise distribution, the focus of the concept, the economic sector, and dimensions of sustainable development. The paper conducts a thematic analysis of the following research questions. What are the green competencies and their conceptual definition? What are their dimensions?Design/methodology/approachThis paper applies a systematic literature review of green competencies literature, extends the state-of-the-art using the natural resource-based view, and discusses future research directions for academicians and practitioners.FindingsIn recent years, there was considerable interest in green competencies (GC), as reflected in the surge of articles published in this genre. This paper asserts that green competencies are a multidimensional construct comprised of green knowledge, green skills, green abilities, green attitudes, green behaviours, and green awareness.Originality/valueDespite the significance of green competencies, there has been a dearth of study to define the constructs and identify the dimensions. Hence, this study addresses the literature gap by conceptualisation and discusses dimensions of the construct.
Choice experiments in non-market value analysis: some methodological issues
Authors: Koemle Dieter , Yu Xiaohua 
Published: August 2020

PurposeThis paper reviews the current literature on theoretical and methodological issues in discrete choice experiments, which have been widely used in non-market value analysis, such as elicitation of residents' attitudes toward recreation or biodiversity conservation of forests.Design/methodology/approachWe review the literature, and attribute the possible biases in choice experiments to theoretical and empirical aspects. Particularly, we introduce regret minimization as an alternative to random utility theory and sheds light on incentive compatibility, status quo, attributes non-attendance, cognitive load, experimental design, survey methods, estimation strategies and other issues.FindingsThe practitioners should pay attention to many issues when carrying out choice experiments in order to avoid possible biases. Many alternatives in theoretical foundations, experimental designs, estimation strategies and even explanations should be taken into account in practice in order to obtain robust results.Originality/valueThe paper summarizes the recent developments in methodological and empirical issues of choice experiments and points out the pitfalls and future directions both theoretically and empirically.
Case study on renewable energy in New York: bridging the gap between promise and reality
Authors: Tomoiaga Alin Simion , Ammar Salwa , Freund Christopher 
Published: August 2020

Purpose
The assessment of the achievement of the goal is data driven and uses analytical modeling of the forecasted demand and the projected electrical power generated capacities. The analysis is based on compiled granular observations and is compared to reported aggregated information. The model takes into account changes in demand patterns such as the increase in the use of electric cars, and decreased demand because of improving efficiencies and behind-the-meter generation.

Design/methodology/approach
This case study is designed to examine one of the major goals of New York State (NYS) Governor Andrew Cuomo’s energy plan, namely, that 50% of all electric generation will come from renewable energy resources by the year 2030. The aim is to compare the aspiration of the political policy with the reality of its implementation.

Findings
The analyses describe a measurable gap between the achievement of the stated goal and the projected reality. The paper includes discussions on the nature of this gap and factors that could potentially further increase this deficit.

Practical implications
In addition, the paper highlights the need to recognize the complexities of projecting the future and difficulty of developing aggressive contingencies given practical and political constraints.

Originality/value
This paper provides a data-driven independent assessment of the NYS’ current energy plan and highlights important issues for consideration if the political promise is ever to become a reality.
Changing in sync with societal preferences: LEGO masters strategic alliances
Authors: Srikant Chethan D. , Lessard Bethany 
Published: August 2020

Purpose
Changes in societal preferences can have a significant impact on the business strategy of companies. This paper aims to illustrate the utility of strategic alliances in channelizing societal preferences.

Design/methodology/approach
LEGO and its many strategic alliances are carefully examined to illustrate the need for considering strategic alliances from a societal preference perspective. LEGO’s strategic alliances are juxtaposed with two major societal trends of the past few decades, environmental movement and multiple efforts toward greater inclusivity.

Findings
The following important lessons are elaborated for helping business organizations pursuing strategic alliances: long-term orientation should not become an excuse for complacency, need for alignment of organizations within the strategic alliance, strategic alliances should be viewed as a bidirectional channel for influence and attending to internal transformations is crucial for success.

Originality/value
This paper deviates from the traditional treatment of strategic alliances as a business arrangement that only drives financial performance but instead provides insights into how strategic alliances can be connected to changing societal preferences. It also challenges the received wisdom in the academic literature on strategic alliance, which is dominated by some very restrictive theoretical perspectives.
The historic (wrong) turn in management and organizational studies
Authors: Bowden Bradley 
Published: August 2020

Purpose
Management history has in the past 15 years witnessed growing enthusiasm for “critical” research methodologies associated with the so-called “historic turn”. This paper aims to argue, however, that the “historic turn” has proved to an “historic wrong turn”, typically associated with confused and contradictory positions. In consequence, Foucault’s belief that knowledge is rooted in discourse, and that both are rooted in external structures of power, is used while simultaneously professing advocacy of White’s understanding that history is fictive, the product of the historian’s imagination.

Design/methodology/approach
This paper explores the intellectual roots of the historic (wrong) turn in the idealist philosophies of Nietzsche, Croce, Foucault, White and Latour as well as the critiques that have been made of those theories from within “critical” or “Left” theoretical frameworks.

Findings
Failing to properly acknowledge the historical origin of their ideas and/or the critiques of those ideas – and misrepresenting all contrary opinion as “positivist” – those associated with the historic (wrong) turn replicate the errors of their theoretical champions. The author thus witnesses a confusion of ontology (the nature of being) and epistemology (the nature of knowledge) and, consequently, of “facts” (things that exist independently of our fancy), “evidence” (how ascertain knowledge of a fact) and “interpretation” (how I connect evidence to explain an historical outcome).

Originality/value
Directed toward an examination of the conceptual errors that mark the so-called “historic turn” in management studies, this article argues that the holding contradictory positions is not an accidental by-product of the “historic turn”. Rather, it is a defining characteristic of the genre.
Price discrimination in political advertising: Evidence from the 2012 presidential election
Authors: Moshary Sarah 
Published: August 2020

AbstractIn 2010, the US Supreme Court loosened contribution limits to Political Action Committees (PACs), sparking fears that big donors could exert outsize influence on elections by funding PAC advertising. However, PACs are potentially handicapped when buying advertising time; data from 2012 reveal that PACs pay 32% above regulated campaign rates. I estimate a model of demand for advertising by PACs, exploiting the misalignment of state and media market borders to address price endogeneity. I find that prices reflect willingness‐to‐pay for viewer demographics rather than media bias. The estimates further suggest that network‐owned stations discriminate more successfully than do local affiliates.