bluuebunny/crossref_metadata_2025_split huggingface dataset:
TheTrichoplaxmicrobiome: the simplest animal lives in an intimate symbiosis with two intracellular bacteria
Authors: Gruber-Vodicka Harald R. , Leisch Nikolaus , Kleiner Manuel , Hinzke Tjorven , Liebeke Manuel , McFall-Ngai Margaret , Hadfield Michael G. , Dubilier Nicole 
Published: March 2019

Summary paragraphPlacozoa is an enigmatic phylum of simple, microscopic, marine metazoans. Although intracellular bacteria have been found in all members of this phylum, almost nothing is known about their identity, location and interactions with their host. We used metagenomic and metatranscriptomic sequencing of single host individuals, plus metaproteomic and imaging analyses, to show that the placozoanTrichoplaxH2 lives in symbiosis with two intracellular bacteria. One symbiont forms a new genus in the Midichloriaceae (Rickettsiales) and has a genomic repertoire similar to that of rickettsial parasites, but does not appear to express key genes for energy parasitism. Correlative microscopy and 3-D electron tomography revealed that this symbiont resides in an unusual location, the rough endoplasmic reticulum of its host’s internal fiber cells. The second symbiont belongs to the Margulisbacteria, a phylum without cultured representatives and not known to form intracellular associations. This symbiont lives in the ventral epithelial cells ofTrichoplax, likely metabolizes algal lipids digested by its host, and has the capacity to supplement the placozoan’s nutrition. Our study shows that even the simplest animals known have evolved highly specific and intimate associations with symbiotic, intracellular bacteria, and highlights that symbioses with microorganisms are a basal trait of animal life.
Dynamics of dual specificity phosphatases and their interplay with protein kinases in immune signaling
Authors: Subbannayya Yashwanth , Pinto Sneha M. , Bösl Korbinian , Prasad T. S. Keshava , Kandasamy Richard K. 
Published: March 2019

AbstractDual specificity phosphatases (DUSPs) have a well-known role as regulators of the immune response through the modulation of mitogen activated protein kinases (MAPKs). Yet the precise interplay between the various members of the DUSP family with protein kinases is not well understood. Recent multi-omics studies characterizing the transcriptomes and proteomes of immune cells have provided snapshots of molecular mechanisms underlying innate immune response in unprecedented detail. In this study, we focused on deciphering the interplay between members of the DUSP family with protein kinases in immune cells using publicly available omics datasets. Our analysis resulted in the identification of potential DUSP-mediated hub proteins including MAPK7, MAPK8, AURKA, and IGF1R. Furthermore, we analyzed the association of DUSP expression with TLR4 signaling and identified VEGF, FGFR and SCF-KIT pathway modules to be regulated by the activation of TLR4 signaling. Finally, we identified several important kinases including LRRK2, MAPK8, and cyclin-dependent kinases as potential DUSP-mediated hubs in TLR4 signaling. The findings from this study has the potential to aid in the understanding of DUSP signaling in the context of innate immunity. Further, this will promote the development of therapeutic modalities for disorders with aberrant DUSP signaling.
Low Mutational Load Allows for High Mutation Rate Variation in Gut Commensal Bacteria
Authors: Ramiro Ricardo S. , Durão Paulo , Bank Claudia , Gordo Isabel 
Published: March 2019

AbstractBacteria generally live in species-rich communities, such as the gut microbiota. Yet, little is known about bacterial evolution in natural ecosystems. Here, we followed the long-term evolution of commensalEscherichia coliin the mouse gut. We observe the emergence of polymorphism for mutation rate, ranging from wild-type levels to 1000-fold higher. By combining experiments, whole-genome sequencing andin silicosimulations, we identify the molecular causes and evolutionary conditions that allow these hypermutators to emerge and coexist within a complex microbiota. The hypermutator phenotype is caused by mutations in DNA polymerase III, which increase mutation rate by ~1000-fold (a mutation in the proofreading subunit) and stabilize hypermutator fitness (mutations in the catalytic subunit). The strong mutation rate variation persists for >1000 generations, with coexistence between lineages carrying 4 to >600 mutations. Thisin vivomolecular evolution pattern is consistent with deleterious mutations of ~0.01-0.001% fitness effects, 100 to 1000-fold lower than currentin vitroestimates. Despite large numbers of deleterious mutations, we identify multiple beneficial mutations that do not reach fixation over long periods of time. This indicates that the dynamics of beneficial mutations are not shaped by constant positive Darwinian selection but by processes leading to negative frequency-dependent or temporally fluctuating selection. Thus, microbial evolution in the gut is likely characterized by partial sweeps of beneficial mutations combined with hitchhiking of very slightly deleterious mutations, which take a long time to be purged but impose a very weak mutational load. These results are consistent with the pattern of genetic polymorphism that is emerging from metagenomics studies of the human gut microbiota, suggesting that we identified key evolutionary processes shaping the genetic composition of this community.
Absence of entourage: Terpenoids commonly found in Cannabis sativa do not modulate the functional activity of Δ9-THC at human CB1and CB2 receptors
Authors: Santiago Marina , Sachdev Shivani , Arnold Jonathon C , McGregor Iain S , Connor Mark 
Published: March 2019

AbstractIntroductionCompounds present in Cannabis sativa such as phytocannabinoids and terpenoids, may act in concert to elicit therapeutic effects. Cannabinoids such as Δ9-tetrahydrocannabinol (Δ9-THC) directly activate cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2), however, it is not known if terpenoids present in Cannabis also affect cannabinoid receptor signalling. Therefore, we examined 6 common terpenoids alone, and in combination with cannabinoid receptor agonists, on CB1 and CB2 signalling in vitro.Materials and MethodsPotassium channel activity in AtT20 FlpIn cells transfected with human CB1 or CB2 receptors was measured in real-time using FLIPR® membrane potential dye in a FlexStation 3 plate reader. Terpenoids were tested individually and in combination for periods up to 30 minutes. Endogenous somatostatin receptors served as a control for direct effects of drugs on potassium channels.Resultsα-Pinene, β-pinene, β-caryophyllene, linalool, limonene and β-myrcene (up to 30-100 µM) did not change membrane potential in AtT20 cells expressing CB1 or CB2, or affect the response to a maximally effective concentration of the synthetic cannabinoid CP55,940. The presence of individual or a combination of terpenoids did not affect the hyperpolarization produced by Δ9-THC (10µM): (CB1: control, 59±7%; with terpenoids (10 µM each) 55±4%; CB2: Δ9-THC 16±5%, with terpenoids (10 µM each) 17±4%). To investigate possible effect on desensitization of CB1 responses, all six terpenoids were added together with Δ9-THC and signalling measured continuously over 30 min. Terpenoids did not affect desensitization, after 30 minutes the control hyperpolarization recovered by 63±6%, in the presence of the terpenoids recovery was 61±5%.DiscussionNone of the six of the most common terpenoids in Cannabis directly activated CB1 or CB2, or modulated the signalling of the phytocannabinoid agonist Δ9-THC. These results suggest that if a phytocannabinoid-terpenoid entourage effect exists, it is not at the CB1 or CB2 receptor level. It remains possible that terpenoids activate CB1 and CB2 signalling pathways that do not involve potassium channels, however, it seems more likely that they may act at different molecular target(s) in the neuronal circuits important for the behavioural effect of Cannabis.
AgarFix: simple and accessible stabilization of challenging single-particle cryo-EM specimens through cross-linking in a matrix of agar
Authors: Adamus Klaudia , Le Sarah N. , Elmlund Hans , Boudes Marion , Elmlund Dominika 
Published: March 2019

AbstractCryogenic electron microscopy (cryo-EM) allows structure determination of macromolecular assemblies that have resisted other structural biology approaches because of their size and heterogeneity. These challenging multi-protein targets are typically susceptible to dissociation and/or denaturation upon cryo-EM grid preparation, and often require cross-linking prior to freezing. Several approaches for gentle on-column or in-tube crosslinking have been developed. On-column cross-linking is not widely applicable because of the poor separation properties of gel filtration techniques. In-tube crosslinking frequently causes sample aggregation and/or precipitation. Gradient-based cross-linking through the GraFix method is more robust, but very time-consuming and necessitates specialised expensive equipment. Furthermore, removal of the glycerol typically involves significant sample loss and may cause destabilization detrimental to the sample quality. Here, we introduce an alternative procedure: AgarFix (Agarose Fixation). The sample is embedded in an agarose matrix that keeps the molecules separated, thus preventing formation of aggregates upon cross-linking. Gentle cross-linking is accomplished by diffusion of the cross-linker into the agarose drop. The sample is recovered by diffusion or electroelution and can readily be used for cryo-EM specimen preparation. AgarFix requires minimal equipment and basic lab experience, making it widely accessible to the cryo-EM community.Graphical abstractHighlightsFragile protein complexes can be cross-linked while embedded in agaroseThe agarose matrix prevents formation of aggregates upon cross-linkingCross-linking in agarose is easy, fast, and requires no expensive equipmentThe sample can directly be used for negative stain or cryo-EM grid preparation
Improved CUT&RUN chromatin profiling and analysis tools
Authors: Meers Michael P. , Bryson Terri , Henikoff Steven 
Published: March 2019

AbstractWe previously described a novel alternative to Chromatin Immunoprecipitation, Cleavage Under Targets & Release Using Nuclease (CUT&RUN), in which unfixed permeabilized cells are incubated with antibody, followed by binding of a Protein A-Micrococcal Nuclease (pA/MNase) fusion protein (1). Upon activation of tethered MNase, the bound complex is excised and released into the supernatant for DNA extraction and sequencing. Here we introduce four enhancements to CUT&RUN: 1) a hybrid Protein A-Protein G-MNase construct that expands antibody compatibility and simplifies purification; 2) a modified digestion protocol that inhibits premature release of the nuclease-bound complex; 3) a calibration strategy based on carry-over ofE. coliDNA introduced with the fusion protein; and 4) a novel peak-calling strategy customized for the low-background profiles obtained using CUT&RUN. These new features, coupled with the previously described low-cost, high efficiency, high reproducibility and high-throughput capability of CUT&RUN make it the method of choice for routine epigenomic profiling.
Visual and auditory information shed light on savings mechanisms
Authors: White Olivier , Barbiero Marie , Maréchal Quentin , de Xivry Jean-Jacques Orban 
Published: March 2019

AbstractSuccessful completion of natural motor actions relies on feedback information delivered through different modalities, including vision and audition. The nervous system weights these sensory inflows according to the context and they contribute to the calibration and maintenance of internal models. Surprisingly, the influence of auditory feedback on the control of fine motor actions has only been scarcely investigated alone or together with visual feedback. Here, we tested how 46 participants learned a reaching task when they were provided with either visual, auditory or both feedback about terminal error. In the VA condition, participant received visual (V) feedback during learning and auditory (A) feedback during relearning. The AV group received the opposite treatment. A third group received visual and auditory feedback in both learning periods. Our experimental design allowed us to assess how learning with one modality transferred to relearning in another modality. We found that adaptation was high in the visual modality both during learning and relearning. It was absent in the learning period under the auditory modality but present in the relearning period (learning period was with visual feedback). An additional experiment suggests that transfer of adaptation between visual and auditory modalities occurs through a memory of the learned reaching direction that acts as an attractor for the reaching direction, and not via error-based mechanisms or an explicit strategy. This memory of the learned reaching direction allowed the participants to learn a task that they could not learn otherwise independently of any memory of errors or explicit strategy.
Keeping salamanders off the streets: Evaluating one of the first US amphibian road tunnels 30 years later
Authors: Hedrick Brandon P. , Vander Linden Abby , Cordero Samantha A. , Watt Edward , O’Roark Patrick M. , Cox Samantha L. , Sutherland Christopher 
Published: March 2019

AbstractCulverts are often installed under busy roads to help a variety of animals, from small frogs to bears, safely cross roads that bisect their habitats. One of the first roadway culvert systems designed specifically for amphibian use in the United States was installed along Henry Street in Amherst, Massachusetts in 1987 to protect spotted salamanders (Ambystoma maculatum). These salamanders cross Henry Street during their annual migration to their breeding pools. In recent years, anecdotal evidence from volunteers monitoring the site suggested that salamanders were no longer using the tunnels. To evaluate this concern we conducted salamander counts in 2016, 2017, and 2018 to quantify tunnel use. In 2016, only 11% of observed salamanders used the tunnels– a substantial decrease from 68% in 1988, one year after their installation, when the tunnels were last evaluated. Subsequently, we implemented two tunnel modifications in an effort to increase tunnel usage above the established 2016 baseline. Unfortunately, neither retrofit was successful. Previous studies have demonstrated that salamanders prefer minimum tunnel apertures of >0.4 m, so it is likely that the 0.2 m apertures here are inadequate. This may create differential light and humidity inside and outside the tunnels that is recognized by the salamanders. While many studies have evaluated amphibian tunnel use in lab and field settings, ours is one of the first studies to have examined tunnel usage data long after initial installation. These long-term data are critical for evaluating what factors are necessary for maintaining tunnels over decades-long time scales.
Visitors’ use of corridors in internal medicine wards
Authors: Morhayim Lusi 
Published: March 2019

Purpose
This paper aims to analyze visitors’ waiting behavior in corridors of an internal medicine ward in relation to concepts of territoriality and privacy.

Design/methodology/approach
Waiting activities, visitors’ room numbers and duration of activities were recorded on a floor plan. Results were tallied according to behavioral and architectural zones in which the activity took place.

Findings
Locations that are near patient rooms that provide visual and auditory access are largely used as territorial areas for non-privacy-required activities. Ends of corridors, secondary corridors and staircases were mainly used for activities that required some level of privacy such as grieving.

Research limitations/implications
As is true with post-occupancy evaluations in other single buildings, this research may not be generalizable to all internal medicine wards. Future research could measure whether responding to visitors’ spatial needs could result in lower density and sense of crowding in the corridors, as well as reduce stress and task interruptions and increase efficiency of patient-check rounds.

Practical implications
The findings indicate that internal medicine wards should include waiting areas near the patient rooms for visitors to be able to keep visual and auditory connection with their patients, as well as areas that provide privacy. This may help lower density, sense of crowding, distraction of medical staff, stress and burn-out and errors, as well as increase the efficiency of patient checks.

Originality/value
The ways in which architectural design of internal medicine corridors can support visitors’ activities and environmental needs such as territoriality and privacy is an issue that is rarely examined. This paper also adds an example from a non-Western culture, to a literature that is dominated by examples from Western cultures.
Perception of stakeholders on governance dimensions of the Islamic banking sector
Authors: Oladapo Ibrahim Abiodun , Arshad Roshayani , Muda Ruhaini , Hamoudah Manal Mohammed 
Published: March 2019

PurposeThe perception of different stakeholder groups on governance dimensions, such as transparency, accountability and ethics, in the Islamic banking sector is examined, given the global growth of Islamic banking and its purpose of enhancing economic growth and development throughShari’ah-compliant instruments. The purpose of this paper is to determine whether the stakeholders in Nigeria perceive each dimension differently.Design/methodology/approachThe data for the study were collected using a survey questionnaire. Simple random sampling was used to select the respondents. The respondents are customers, employees and shareholders of the Islamic banking sector in Nigeria.FindingsFindings show that ethics is highly perceived as the key dimension in governance for the Islamic banking sector, whilst a positive and significant relationship is observed between the variables. Based on the variance analysis, there were statistically significant differences in perception between the stakeholders groups in the Islamic banking system. However, similar positive perceptions are accorded towards the overall governance dimensions across stakeholder groups namely, customers, employees and shareholders.Originality/valueThis study will extend the current body of knowledge in the field of Islamic finance by providing insights into policy makers, operators and regulators of the Islamic banking sector in Nigeria on the prospective stakeholders’ level of perception of the governance dimension, which could form part of the solutions to many contemporary issues in the banking system. This contribution is important, considering the clear relationship among governance dimensions which should be viewed in light of Islamic ideals.
Why do all good things come to an end? An inquiry into the discontinuation of sport sponsor–sponsee relationships
Authors: van Rijn Mark , Kristal Samuel , Henseler Jörg 
Published: March 2019

Purpose
The purpose of this paper is to explore the reasons for the discontinuation of sports sponsor–sponsee relationships and categorize them. Despite the negative outcomes of a sponsorship dissolution, research on this topic is rather scarce.

Design/methodology/approach
The paper relies on an analysis of 24 historical cases and 19 in-depth interviews focusing on the Dutch soccer league. Several sponsorship disruptors are identified and clustered into four categories.

Findings
The four categories for sponsorship dissolution are the following: sponsor-related factors, sponsee-related factors, inter-relational factors and external factors. In total, ten sponsorship disruptors are identified: insufficient value creation, objectives achieved, sports results, signal to society, exclusivity, negativity, personal relationship, changed marketing strategy, financial situation and legislation and regulation.

Research limitations/implications
This study primarily investigates soccer sponsorship cases. Future research could investigate other sponsorship areas, which could yield different reasons for sponsorship termination.

Practical implications
Practitioners are advised to view the sponsorship relationship as a strategic alliance, rather than a resource, from the beginning of the sponsorship. A solid relational framework is needed, which is built around the elements of trust, commitment and collaborative communication. If such a foundation does not exist or has eroded, the sponsorship relationship is fragile and can be endangered by various factors.

Originality/value
This study uses inductive reasoning to devise a framework that enables sponsees to anticipate when sponsors are likely to discontinue their sponsorship such that the sponsees can take actions accordingly. Apart from validating existing reasons for sponsorship dissolution, this research also presents novel and previously undiscovered sponsorship disruptors.
The essential mix: six tools for strategy-making in the next decade
Authors: Wurthmann Kurt 
Published: March 2019

Purpose
The purpose of this paper is to provide a solution that helps reduce confusion about choice and usage of tools for strategy-making.

Design/methodology/approach
The approach is to present a classroom-tested system that integrates new methods for applying a parsimonious set of six widely used tools, within one, comprehensive, yet succinct, procedure for strategy-making.

Findings
Findings, based on years of development and use of the procedure as the basis for teaching MBA capstone courses in strategy, reveal that it facilitates rapid mastery of the underlying theory and practical application of the essential tools of strategy-making.

Practical implications
Practical implications include decreased tendencies for ad hoc or disjointed use of random sets of tools for strategy-making and increased capabilities to connect strategy-making and strategy-executing in an iterative process, as previous iterations of strategies that were executed by organizations are used to determine new strategies.

Originality/value
Characteristics of the procedure which are original include: merging outside-in and inside-out perspectives on strategy-making in one, succinct procedure; providing an approach with general applicability to diverse types of organizations; providing a systematic process for identifying and rating environmental characteristics, using shared, theory-based scales, applied to fully-cited, real-world data, thereby reducing reliance on unsubstantiated opinion, providing full traceability, and facilitating knowledge transfer across users and time; and linking strategy analysis to formulation. The procedure described in this article has value for professors, students, managers, consultants, and the broad spectrum of people throughout organizations who are engaged in strategy-making.
The narrative cleansing of Andrew Carnegie: entrepreneurial generativity as identity capital
Authors: Humphreys John H. , Hayek Mario Joseph , Novicevic Milorad M. , Haden Stephanie , Pickens Jared 
Published: March 2019

Purpose
The purpose of this paper is to proffer a reconstructed theoretic model of entrepreneurial generatively that accounts for personal and social identities in the narrative construction of entrepreneurial identity..

Design/methodology/approach
The authors followed general analytically structured history processes using the life of Andrew Carnegie to understand how generativity scripts aid in aligning personal and social identities in the formation of entrepreneurial identity.

Findings
The authors argue that Carnegie used entrepreneurial generativity as a form of redemptive identity capital during the narrative reconstruction of his entrepreneurial identity.

Originality/value
This paper extends Harvey et al.’s (2011) model of entrepreneurial philanthropy motivation by including forms of self-capital (psychological capital and self-identity capital) as part of the co-construction of entrepreneurial identity and proposing a reconstructed capital theoretic model of entrepreneurial generativity.