bluuebunny/crossref_metadata_2025_split huggingface dataset:
Representations of context and context-dependent values in vmPFC compete for guiding behavior
Authors: Moneta Nir , Garvert Mona M. , Heekeren Hauke R. , Schuck Nicolas W. 
Published: March 2021

AbstractValue representations in ventromedial prefrontal-cortex (vmPFC) are known to guide the choice between options. But the value of an option can be different in different task contexts. Goal-directed behavior therefore requires to know the current context and associated values of options, and to flexibly switch between value representations in a task-dependent manner. We tested whether task-relevant and -irrelevant values influence behavior and asked whether both values are represented together with context signals in vmPFC. Thirty-five participants alternated between tasks in which stimulus color or motion predicted rewards. As expected, neural activity in vmPFC and choices were largely driven by task-relevant values. Yet, behavioral and neural analyses indicate that participants also retrieved the values of irrelevant features, and computed which option would have been best in the alternative context. Investigating the probability distributions over values and contexts encoded in multivariate fMRI signals, we find that vmPFC maintains representations of the current context, i.e. task state, the value associated with it, and the hypothetical value of the alternative task state. Crucially, we show that evidence for irrelevant value signals in vmPFC relates to behavior on multiple levels, competes with expected value signals, and interacts with task state representations. Our results thus suggest that different value representations are represented in parallel and imply a link between neural representations of task states, their associated values and their influence on behavior. This sheds new light on vmPFC’s role in decision making, bridging between a hypothesized role in mapping observations onto the task states of a mental map, and computing value expectations for alternative states.
A squalene-hopene cyclase inSchizosaccharomyces japonicusrepresents a eukaryotic adaptation to sterol-independent anaerobic growth
Authors: Bouwknegt Jonna , Wiersma Sanne J. , Ortiz-Merino Raúl A. , Doornenbal Eline S. R. , Buitenhuis Petrik , Giera Martin , Müller Christoph , Pronk Jack T. 
Published: March 2021

AbstractBiosynthesis of sterols, which are key constituents of canonical eukaryotic membranes, requires molecular oxygen. Anaerobic protists and deep-branching anaerobic fungi are the only eukaryotes in which a mechanism for sterol-independent growth has been elucidated. In these organisms, tetrahymanol, formed through oxygen-independent cyclization of squalene by a squalene-tetrahymanol cyclase, acts as a sterol surrogate. This study confirms an early report (Bulder (1971), Antonie Van Leeuwenhoek, 37, 353–358) thatSchizosaccharomyces japonicusis exceptional among yeasts in growing anaerobically on synthetic media lacking sterols and unsaturated fatty acids. Mass spectrometry of lipid fractions of anaerobically grownSch. japonicusshowed the presence of hopanoids, a class of cyclic triterpenoids not previously detected in yeasts, including hop-22(29)-ene, hop-17(21)-ene, hop-21(22)-ene and hopan-22-ol. A putative gene inSch. japonicusshowed high similarity to bacterial squalene-hopene cyclase (SHC) genes and in particular to those ofAcetobacterspecies. No orthologs of the putativeSch. japonicusSHC were found in other yeast species. Expression of theSch. japonicusSHC gene (Sjshc1) inSaccharomyces cerevisiaeenabled hopanoid synthesis and supported ergosterol-independent anaerobic growth, thus confirming that one or more of the hopanoids produced by SjShc1 can act as ergosterol surrogate in anaerobic yeast cultures. Use of hopanoids as sterol surrogates represents a previously unknown adaptation of eukaryotic cells to anaerobic growth. The fast sterol-independent anaerobic growth ofSch. japonicusis an interesting trait for developing robust fungal cell factories for application in anaerobic industrial processes.Significance statementBiosynthesis of sterols requires oxygen. This study identifies a previously unknown evolutionary adaptation in a eukaryote, which enables anaerobic growth in absence of exogenous sterols. A squalene-hopene cyclase, proposed to have been acquired by horizontal gene transfer from an acetic acid bacterium, is implicated in a unique ability of the yeastSchizosaccharomyces japonicusto synthesize hopanoids and grow in anaerobic, sterol-free media. Expression of this cyclase in S.cerevisiaeconfirmed that at least one of its hopanoid products acts as sterol-surrogate. The involvement of hopanoids in sterol-independent growth of this yeast provides new leads for research into the structure and function of eukaryotic membranes, and into the development of sterol-independent yeast cell factories for application in anaerobic processes.
A bacterial effector counteracts host autophagy by promoting degradation of an autophagy component
Authors: Leong Jia Xuan , Raffeiner Margot , Spinti Daniela , Langin Gautier , Franz-Wachtel Mirita , Guzman Andrew R. , Kim Jung-Gun , Pandey Pooja , Minina Alyona E. , Macek Boris , Hafrén Anders , Bozkurt Tolga O. , Mudgett Mary Beth , Börnke Frederik , Hofius Daniel , Üstün Suayib 
Published: March 2021

AbstractBeyond its role in cellular homeostasis, autophagy plays anti- and pro-microbial roles in host-microbe interactions, both in animals and plants. One prominent role of anti-microbial autophagy is to degrade intracellular pathogens or microbial molecules, in a process termed xenophagy. Consequently, microbes evolved mechanisms to hijack or modulate autophagy to escape elimination. Although well-described in animals, the extent to which xenophagy contributes to plant-bacteria interactions remains unknown. Here, we provide evidence thatXanthomonas campestrispv.vesicatoria (Xcv)suppresses host autophagy by utilizing type-III effector XopL. XopL interacts with and degrades the autophagy component SH3P2 via its E3 ligase activity to promote infection. Intriguingly, XopL is targeted for degradation by defense-related selective autophagy mediated by NBR1/Joka2, revealing a complex antagonistic interplay between XopL and the host autophagy machinery. Our results implicate plant antimicrobial autophagy in depletion of a bacterial virulence factor and unravels an unprecedented pathogen strategy to counteract defense-related autophagy.
Mutational escape from the polyclonal antibody response to SARS-CoV-2 infection is largely shaped by a single class of antibodies
Authors: Greaney Allison J. , Starr Tyler N. , Barnes Christopher O. , Weisblum Yiska , Schmidt Fabian , Caskey Marina , Gaebler Christian , Cho Alice , Agudelo Marianna , Finkin Shlomo , Wang Zijun , Poston Daniel , Muecksch Frauke , Hatziioannou Theodora , Bieniasz Paul D. , Robbiani Davide F. , Nussenzweig Michel C. , Bjorkman Pamela J. , Bloom Jesse D. 
Published: March 2021

AbstractMonoclonal antibodies targeting a variety of epitopes have been isolated from individuals previously infected with SARS-CoV-2, but the relative contributions of these different antibody classes to the polyclonal response remains unclear. Here we use a yeast-display system to map all mutations to the viral spike receptor-binding domain (RBD) that escape binding by representatives of three potently neutralizing classes of anti-RBD antibodies with high-resolution structures. We compare the antibody-escape maps to similar maps for convalescent polyclonal plasma, including plasma from individuals from whom some of the antibodies were isolated. The plasma-escape maps most closely resemble those of a single class of antibodies that target an epitope on the RBD that includes site E484. Therefore, although the human immune system can produce antibodies that target diverse RBD epitopes, in practice the polyclonal response to infection is dominated by a single class of antibodies targeting an epitope that is already undergoing rapid evolution.
Synthesis of the NarP response regulator of nitrate respiration inEscherichia coliis regulated at multiple levels by Hfq and small RNAs
Authors: Brosse Anaïs , Walburger Anne , Magalon Axel , Guillier Maude 
Published: March 2021

ABSTRACTTwo-component systems (TCS) and small RNAs (sRNA) are widespread regulators that participate in the response and the adaptation of bacteria to their environments. They mostly act at the transcriptional and post-transcriptional levels, respectively, and can be found integrated in regulatory circuits, where TCSs control sRNAs transcription and/or sRNAs post-transcriptionally regulate TCSs synthesis.In response to nitrate and nitrite, the paralogous NarQ-NarP and NarX-NarL TCSs regulate the expression of genes involved in anaerobic respiration of these alternative electron acceptors. In addition to the previously reported repression of NarP synthesis by the SdsN137sRNA, we show here that RprA, another Hfq-dependent sRNA, also negatively controlsnarP. Interestingly, the repression ofnarPby RprA actually relies on two independent controls. The first isviathe direct pairing of the central region of RprA to thenarPtranslation initiation region and presumably occurs at the translation initiation level. In contrast, the second control requires only the very 5’ end of thenarPmRNA, which is targeted, most likely indirectly, by the full-length or the shorter, processed, form of RprA. In addition, our results raise the possibility of a direct role of Hfq innarPcontrol, further illustrating the diversity of post-transcriptional regulation mechanisms in the synthesis of TCSs.
CRISPR-Targeted CAR Gene Insertion Using Cas9/RNP and AAV6 Enhances Anti-AML Activity of Primary NK Cells
Authors: Kararoudi Meisam Naeimi , Likhite Shibi , Elmas Ezgi , Yamamoto Kenta , Schwartz Maura , Sorathia Kinnari , de Souza Fernandes Pereira Marcelo , Devin Raymond D , Lyberger Justin M , Behbehani Gregory K , Chakravarti Nitin , Moriarity Branden S. , Meyer Kathrin , Lee Dean A. 
Published: March 2021

AbstractHuman peripheral blood natural killer (NK) cells have intense antitumor activity and have been used successfully in several clinical trials. Modifying NK cells with a chimeric antigen receptor (CAR) can improve their targeting and increase specificity. Recently, we described an efficient method for gene targeting in NK cells using Cas9/ribonucleoprotein (RNP) complexes. Here we combined this approach with single-stranded (ss) or self-complementary (sc) Adeno-associated virus (AAV)-mediated gene delivery for gene insertion into a safe-harbor locus using a wide variety of homology arms for homology repair (HR) and non-homologous directed CRISPR-assisted insertion tagging (CRISPaint) approaches. For proof-of-concept, we generated mCherry-expressing primary NK cells and determined that sc vectors with 300bp homology arms had optimal transduction efficiency. Then, we generated CD33-targeting CAR NK cells with differing transmembrane and signaling domains (CD4/4-1BB+CD3ζ and NKG2D/2B4+CD3ζ) and expanded them on CSTX002 feeder cells. Expansion kinetics were unaltered and the expanded NK cells maintained high CAR expression (mean 68% CAR+). The CD33-CAR-NK cells showed increased activation markers and enhanced antileukemic activity with improved killing kinetics against CD33-positive acute myeloid leukemia (AML) cell lines and primary samples. Using targeted sequencing we demonstrated the accuracy of CAR gene insertion in human primary NK cells genome. Site-directed insertion using RNP and scAAV6 is an efficient method for stable genetic transfer into primary NK cells that has broad potential for fundamental discovery and therapeutic applications.
β-Carotene oxidation products - function and safety
Authors: Burton Graham W. , Mogg Trevor J. , Riley William W. , Nickerson James G. 
Published: March 2021

Abstractβ-Carotene oxidation products have newly discovered bioactivity in plants and animals. Synthetic fully oxidized β-carotene (OxBC) has application in supporting livestock health, with potential human applications. The safety of synthetic OxBC has been evaluated. An Ames test showed weak-to-moderate mutagenicity in only one cell line at high concentrations. A mouse micronucleus assay established a non-toxic dose of 1800 mg/kg body weight, and no bone marrow micronuclei were induced. Plant sources of β-carotene inevitably contain varying levels of natural OxBC. Vegetable powders and dried forages can be especially rich. Intakes of natural OxBC for humans and livestock alike have been estimated. The exposure range for humans (1-22 mg/serving) is comparable to the safe intake of β-carotene (<15 mg/d). In livestock, OxBC in alfalfa can contribute ~550-850 mg/head/d for dairy cattle but in forage-deficient poultry feed much less (~1 ppm). Livestock intake of supplemental synthetic OxBC is comparable to OxBC potentially available from traditional plant sources. Human intake of synthetic OxBC in meat from livestock fed OxBC is similar to a single serving of food made with carrot powder. It is concluded that consumption of synthetic OxBC at levels comparable to natural OxBC is safe for humans and animals.
Tight nanoscale clustering of Fcγ-receptors using DNA origami promotes phagocytosis
Authors: Kern Nadja , Dong Rui , Douglas Shawn M. , Vale Ronald D. , Morrissey Meghan A. 
Published: March 2021

AbstractMacrophages destroy pathogens and diseased cells through Fcγ receptor (FcγR)-driven phagocytosis of antibody-opsonized targets. Phagocytosis requires activation of multiple FcγRs, but the mechanism controlling the threshold for response is unclear. We developed a DNA origami-based engulfment system that allows precise nanoscale control of the number and spacing of ligands. When the number of ligands remains constant, reducing ligand spacing from 17.5 nm to 7 nm potently enhances engulfment, primarily by increasing efficiency of the engulfment-initiation process. Tighter ligand clustering increases receptor phosphorylation, as well as proximal downstream signals. Increasing the number of signaling domains recruited to a single ligand-receptor complex was not sufficient to recapitulate this effect, indicating that clustering of multiple receptors is required. Our results suggest that macrophages use information about local ligand densities to make critical engulfment decisions, which has implications for the mechanism of antibody-mediated phagocytosis and the design of immunotherapies.
Is public healthcare healthy? The role of emotional exhaustion
Authors: López-Cabarcos M. Ángeles , López-Carballeira Analía , Ferro-Soto Carlos 
Published: March 2021

PurposeThis study analyzes the mediating effect of emotional exhaustion between certain job demands (workload, role conflict, and influence at work) and employees' work attitudes (affective commitment and turnover intention) in public healthcare. Furthermore, it analyzes the moderating effect of possibilities for development and the degree of freedom at work between the above-mentioned job demands and emotional exhaustion.Design/methodology/approachA total of 512 healthcare professionals participated in the study. The data were analyzed using structural equation modeling and a hierarchical multiple regression analysis.FindingsThe results show that emotional exhaustion fully mediates the relationship between job demands (workload and role conflict) and work attitudes (affective commitment and turnover intention). Moreover, the possibilities for development and degree of freedom at work moderate the relationship between role conflict and emotional exhaustion.Practical implicationsStrategies should be designed to prevent employees from becoming emotionally exhausted and lead them to feel more motivated, which results in a more effective public healthcare service.Originality/valueThis study stresses the importance of analyzing the role of emotional exhaustion in the public healthcare context. It demonstrates the mediating role of this variable between several antecedents and consequences, and it analyzes whether other relevant variables can moderate the negative effects of emotional exhaustion.
Hermite polynomial normal transformation for structural reliability analysis
Authors: Wang Jinsheng , Aldosary Muhannad , Cen Song , Li Chenfeng 
Published: March 2021

Purpose
Normal transformation is often required in structural reliability analysis to convert the non-normal random variables into independent standard normal variables. The existing normal transformation techniques, for example, Rosenblatt transformation and Nataf transformation, usually require the joint probability density function (PDF) and/or marginal PDFs of non-normal random variables. In practical problems, however, the joint PDF and marginal PDFs are often unknown due to the lack of data while the statistical information is much easier to be expressed in terms of statistical moments and correlation coefficients. This study aims to address this issue, by presenting an alternative normal transformation method that does not require PDFs of the input random variables.

Design/methodology/approach
The new approach, namely, the Hermite polynomial normal transformation, expresses the normal transformation function in terms of Hermite polynomials and it works with both uncorrelated and correlated random variables. Its application in structural reliability analysis using different methods is thoroughly investigated via a number of carefully designed comparison studies.

Findings
Comprehensive comparisons are conducted to examine the performance of the proposed Hermite polynomial normal transformation scheme. The results show that the presented approach has comparable accuracy to previous methods and can be obtained in closed-form. Moreover, the new scheme only requires the first four statistical moments and/or the correlation coefficients between random variables, which greatly widen the applicability of normal transformations in practical problems.

Originality/value
This study interprets the classical polynomial normal transformation method in terms of Hermite polynomials, namely, Hermite polynomial normal transformation, to convert uncorrelated/correlated random variables into standard normal random variables. The new scheme only requires the first four statistical moments to operate, making it particularly suitable for problems that are constraint by limited data. Besides, the extension to correlated cases can easily be achieved with the introducing of the Hermite polynomials. Compared to existing methods, the new scheme is cheap to compute and delivers comparable accuracy.
The interplay between financial rules, trust and power in strategic partnerships in the construction industry
Authors: Koolwijk Jelle , van Oel Clarine , Bel Mirjam 
Published: March 2021

Purpose
To explore how and why the social structures of strategic partnerships are shaped by actors and how these interrelate with a team's interpersonal relationships over time. Grasping the complexity of this interplay is essential if we want to comprehend what actually goes on in these partnerships and understand why actors often disengage from them.

Design/methodology/approach
In three cases, 14 in-depth interviews were held with knowledgeable actors about important events and activities that influenced the relationships between partners. Interview data were triangulated with journals kept by the lead author, who participated as an engaged scholar in the three cases. Because this study took an interdisciplinary approach, new insights could evolve from the multi-level analysis.

Findings
Trust has a moderating effect on the relation between open-book accounting and the degree of control a dominant party wants to exercise. When the level of control is raised, this can signal distrust to the other partners, which can harm the relationship. When partners feel more dependent on each other's capabilities to reach their long-term goals, the parties seem to be less likely to put the blame on one of the partners in the case of undesirable events.

Practical implications
Managers should be aware of their power position and acknowledge the effects of power on their relationships. If long-term and close collaboration does not emerge in their partnership, it may be due to how they use their power position.

Originality/value
Thanks to the interdisciplinary approach, this is the first study that shows the significance of trust and power in maintaining strategic partnerships in the construction industry, and how trust can affect the financial rules of actors.
Using issue logs to improve construction project performance
Authors: Shalwani Amirali , Lines Brian 
Published: March 2021

PurposeThe Project Management Body of Knowledge recommends the use of issue logs as a best practice to minimize the potential project cost and schedule growth. Although the broader topic of project control has been widely studied in the construction literature, the specific application of issue logs has remained relatively understudied. This study aims to analyze the extent and consistency with which construction teams utilize issue logs and the corresponding project performance outcomes.Design/methodology/approachA dataset of 5,635 individual issues was gathered from the final issue logs of 881 small building projects delivered via the design–bid–build method. Differences between groups were determined using the Kruskal–Wallis H test with post hoc testing via the Mann–Whitney U test with pairwise comparison.FindingsThe results showed that, on average, project teams who used issue logs to a greater extent achieved a 3.1 to 4.3% reduction in cost growth and a 5.3 to 12.3% reduction in schedule growth. This result shows that issue logs can be used to improve construction project performance in the areas of cost and schedule.Originality/valueThis result provides a contribution to practitioners, wherein project teams should be encouraged to establish their issue management practices early in the project schedule to encourage greater issue log usage for the remainder of the project.