bluuebunny/crossref_metadata_2025_split huggingface dataset:
MLL3/MLL4 methyltransferase activities control early embryonic development and embryonic stem cell differentiation in a lineage-selective manner
Authors: Xie Guojia , Lee Ji-Eun , Senft Anna D. , Park Young-Kwon , Chakraborty Shreeta , Thompson Joyce J. , Liu Chengyu , Macfarlan Todd S. , Rocha Pedro P. , Peng Weiqun , Ge Kai 
Published: September 2020

AbstractH3K4me1 methyltransferases MLL3 (KMT2C) and MLL4 (KMT2D) are critical for enhancer activation, cell differentiation and development. However, roles of MLL3/4 enzymatic activities and MLL3/4-mediated enhancer H3K4me1 in these processes remain unclear. Here, we report that constitutive elimination of both MLL3 and MLL4 enzymatic activities leads to gastrulation failure and early embryonic lethality in mice. However, selective elimination of MLL3/4 enzymatic activities in embryonic, but not extraembryonic, lineages leaves gastrulation largely intact. Consistently, embryonic stem cells (ESCs) lacking MLL3/4 enzymatic activities can differentiate towards the three embryonic germ layers but show aberrant differentiation to extraembryonic endoderm and trophectoderm. The failure in extraembryonic endoderm differentiation can be attributed to markedly reduced enhancer-binding of the lineage-determining transcription factor GATA6. Furthermore, we show that MLL3/4-catalyzed H3K4me1 is largely dispensable for enhancer activation during ESC differentiation. Together, our findings suggest a lineage-selective, but enhancer activation-independent, role of MLL3/4 methyltransferase activities in early embryonic development and embryonic stem cell differentiation.
Sequence-specific model for predicting peptide collision cross-section values in proteomic ion mobility spectrometry
Authors: Chang Chih-Hsiang , Yeung Darien , Spicer Victor , Krokhin Oleg , Ishihama Yasushi 
Published: September 2020

ABSTRACTThe contribution of peptide amino-acid sequence to collision cross-section values (CCS) has been investigated using a dataset of ∼134,000 peptides of four different charge states (1+ to 4+). The migration data was acquired using a two-dimensional LC/trapped ion mobility spectrometry/quadrupole/time-of-flight MS analysis of HeLa cell digests created using 7 different proteases and was converted to CCS values. Following the previously reported modeling approaches using intrinsic size parameters (ISP), we extended this methodology to encode the position of individual residues within a peptide sequence. A generalized prediction model was built by dividing the dataset into 8 groups (four charges for both tryptic/non-tryptic peptides). Position dependent ISPs were independently optimized for the eight subsets of peptides, resulting in prediction accuracy of ∼0.981 for the entire population of peptides. We find that ion mobility is strongly affected by the peptide’s ability to solvate the positively charged sites. Internal positioning of polar residues and proline leads to decreased CCS values as they improve charge solvation; conversely, this ability decreases with increasing peptide charge due to electrostatic repulsion. Furthermore, higher helical propensity and peptide hydrophobicity result in preferential formation of extended structures with higher than predicted CCS values. Finally, acidic/basic residues exhibit position dependent ISP behaviour consistent with electrostatic interaction with the peptide macro-dipole, which affects the peptide helicity.
Light quality signals generated by vegetation shade facilitate acclimation to reduced light quantity in shade-avoider plants
Authors: Morelli Luca , Paulišić Sandi , Qin Wen-Ting , Roig-Villanova Irma , Rodriguez-Concepcion Manuel , Martinez-Garcia Jaime F. 
Published: September 2020

SUMMARYWhen growing in search for light, plants can experience continuous or occasional shading by other plants. Plant proximity causes a decrease in the ratio of red to far red light (low R:FR) due to the preferential absorbance of red light and reflection of far red light by photosynthetic tissues of neighboring plants. This signal is often perceived before actual shading causes a reduction in photosynthetically active radiation (low PAR).Here we investigated elongation, photosynthesis and photoacclimation responses in several Brassicaceae species to explore the possible connections between low R:FR and low PAR.A negative correlation was found in shade-tolerantCardamine hirsutaand shade-avoiderArabidopsis thalianaseedlings (e.g., shade-tolerance was associated with a good adaptation to low PAR but a poor or null response to low R:FR exposure). However, they could be genetically uncoupled. Most interestingly, exposure to low R:FR of shade-avoider plants improved their photoacclimation to low PAR by triggering changes in photosynthesis-related gene expression, pigment accumulation and chloroplast ultrastructure.These results indicate that low R:FR signaling unleashes molecular, metabolic and developmental responses that allow shade-avoider plants (including most crops) to adjust their photosynthetic capacity in anticipation of eventual shading by nearby plants.
Single-component, self-assembling, protein nanoparticles presenting the receptor binding domain and stabilized spike as SARS-CoV-2 vaccine candidates
Authors: He Linling , Lin Xiaohe , Wang Ying , Abraham Ciril , Sou Cindy , Ngo Timothy , Zhang Yi , Wilson Ian A. , Zhu Jiang 
Published: September 2020

ABSTRACTVaccination against SARS-CoV-2 provides an effective tool to combat the COIVD-19 pandemic. Here, we combined antigen optimization and nanoparticle display to develop vaccine candidates for SARS-CoV-2. We first displayed the receptor-binding domain (RBD) on three self-assembling protein nanoparticle (SApNP) platforms using the SpyTag/SpyCatcher system. We then identified heptad repeat 2 (HR2) in S2 as the cause of spike metastability, designed an HR2-deleted glycine-capped spike (S2GΔHR2), and displayed S2GΔHR2 on SApNPs. An antibody column specific for the RBD enabled tag-free vaccine purification. In mice, the 24-meric RBD-ferritin SApNP elicited a more potent neutralizing antibody (NAb) response than the RBD alone and the spike with two stabilizing proline mutations in S2 (S2P). S2GΔHR2 elicited two-fold-higher NAb titers than S2P, while S2GΔHR2 SApNPs derived from multilayered E2p and I3-01v9 60-mers elicited up to 10-fold higher NAb titers. The S2GΔHR2-presenting I3-01v9 SApNP also induced critically needed T-cell immunity, thereby providing a promising vaccine candidate.ONE-SENTENCE SUMMARYThe SARS-CoV-2 receptor binding domain and S2GΔHR2 spike elicited potent immune responses when displayed on protein nanoparticles as vaccine candidates.
Selective activation of FZD7 promotes mesendodermal differentiation of human pluripotent stem cells
Authors: Gumber Diana , Do Myan , Kumar Neya Suresh , Wu Christina C. N. , Carson Dennis , Gaasterland Terry , Willert Karl 
Published: September 2020

AbstractWNT proteins are secreted symmetry breaking signals that interact with cell surface receptors of the FZD family to regulate a multitude of developmental processes. Studying selectivity between WNTs and FZDs has been hampered by the paucity of purified WNT proteins and by their apparent non-selective interactions with the FZD receptors. Here we describe an engineered protein, called F7L6, comprised of antibody-derived single chain variable fragments that selectively binds to human FZD7 and the co-receptor LRP6. F7L6 potently activates WNT/β-catenin signaling in a manner similar to Wnt3a. In contrast to Wnt3a, F7L6 engages only FZD7 and none of the other FZD proteins. Treatment of human pluripotent stem (hPS) cells with F7L6 initiates transcriptional programs similar to those observed during primitive streak formation and subsequent gastrulation in the mammalian embryo. This demonstrates that selective engagement and activation of FZD7 signaling is sufficient to promote mesendodermal differentiation of hPS cells.
Contextual effects in sensorimotor adaptation adhere to associative learning rules
Authors: Avraham Guy , Taylor Jordan A. , Breska Assaf , Ivry Richard B. , McDougle Samuel D. 
Published: September 2020

ABSTRACTTraditional associative learning tasks focus on the formation of associations between salient events and arbitrary stimuli that predict those events. This is exemplified in cerebellar-dependent delay eyeblink conditioning, where arbitrary cues such as a light or tone act as conditioning stimuli that predict aversive sensations at the cornea. Here we ask if a similar framework could be applied to another type of cerebellar-dependent sensorimotor learning – sensorimotor adaptation. Models of sensorimotor adaptation posit that the introduction of an environmental perturbation results in an error signal that is used to update an internal model of a sensorimotor map for motor planning. Here we take a step towards an integrative account of these two forms of cerebellar-dependent learning, examining the relevance of core concepts from associative learning for sensorimotor adaptation. Using a visuomotor adaptation reaching task, we paired movement-related feedback with neutral auditory or visual contextual cues that served as conditioning stimuli (CSs). Trial-by trial changes in feedforward movement kinematics exhibited three key signatures of associative learning: Differential conditioning, sensitivity to the CS-US interval, and compound conditioning. Moreover, after compound conditioning, a robust negative correlation was observed between responses to the two elemental CSs of the compound (i.e., overshadowing), consistent with the additivity principle posited by theories of associative learning. The existence of associative learning effects in sensorimotor adaptation provides a proof-of-concept for linking cerebellar- dependent learning paradigms within a common theoretical framework.
Optimal transcriptional regulation of cellular responses to sudden environmental shifts
Authors: Schultz Daniel , Tsimring Lev S. 
Published: September 2020

ABSTRACTCellular responses to sudden changes in their environment require prompt expression of the correct levels of the appropriate enzymes. These enzymes are typically regulated by transcription factors that sense the presence of inducers and control gene expression for the duration of the response. The specific choice of regulatory strategy depends on the characteristics of each cell response, with the pattern of gene expression dictated by parameters such as the affinity of the transcription factor to its binding sites and the strength of the promoters it regulates. Although much is known about how gene regulation determines the dynamics of cell responses, we still lack a framework to understand how the many different regulatory strategies evolved in natural systems relate to the constraints imposed by the selective pressures acting in each particular case. Here, we analyze a dynamical model of a cell response where expression of a transcriptionally repressed enzyme is induced by a sudden exposure to its substrate. We identify strategies of gene regulation that optimize the response for different types of selective pressures, which we define as a set of costs associated with substrate, enzyme and repressor intracellular concentrations during the response. We find that regulated responses happen within a defined region in the parameter space. While responses to costly (toxic) substrates favor the usage of strongly self-regulated repressors, responses where expression of enzyme is more costly than its substrate favor the usage of constitutively expressed repressors. There is only a very narrow range of selective pressures that would favor weakly self-regulated repressors. This framework can be used to infer which costs and benefits are most critical in the evolution of natural examples of cellular responses, and to predict how a response can optimize its regulation when transported to a new environment with different demands.
Design and application of PneuNets bending actuator
Authors: Zhao Shiwei , Li Daochun , Xiang Jinwu 
Published: September 2020

Purpose
The purpose of this study is to propose an improved design of PneuNets bending actuator which aims at obtaining larger deflection with the same magnitude of pressure. The PneuNets bending actuator shows potential application in the morphing trailing edge concept.

Design/methodology/approach
Finite element method is used to investigate the characteristics of the improved design bending actuator. Multiobjective optimal design of the PneuNets bending actuator is proposed based on the Gauss process regression models.

Findings
The maximum deflection is obtained when the height of the beams is smaller than half the height of the chambers. The spacing between chambers (beam length) has little effect on the deflection. Larger spacing could be used to reduce the actuator weight.

Originality/value
With the same pressure magnitude, the deflection of the improved design bending actuator is much larger than that of the baseline configuration. PneuNets bending actuator could increase the continuity of the aerodynamic surface compared to other actuators.
Modeling supply chain enablers for effective resilience
Authors: Agarwal Nishtha , Seth Nitin , Agarwal Ashish 
Published: September 2020

PurposeThe study aims at creating a sequence of implementing supply chain enablers to achieve a greater efficiency in the combination by establishing relationship among them.Design/methodology/approachTo build resilience capability in supply chain, enablers have been first identified through literature review and experts' opinion. The shortlisting of enablers is done in a brainstorming session having experts from academia and industry. The methodology Automated Layout Design Program (ALDEP), which is being used for creating facility layout, is applied to understand the relationship among the enablers for a resilient supply chain.FindingsThe methodology ALDEP is applied to explore relationship among five enablers shortlisted after discussion with experts. The layout matrix with the highest score between enablers is taken as a basis to establish relationship between two enablers that an organization can use to build a resilient supply chain.Originality/valueThe study uses a novel method helping organizations to build resilient supply chains. This study will not only provide a starting point but also provide an entire model for building a resilient supply chain.
Validity and reliability of a wearable insole pressure system for measuring gait parameters to identify safety hazards in construction
Authors: Antwi-Afari Maxwell Fordjour , Li Heng , Seo JoonOh , Anwer Shahnawaz , Yevu Sitsofe Kwame , Wu Zezhou 
Published: September 2020

PurposeConstruction workers are frequently exposed to safety hazards on sites. Wearable sensing systems (e.g. wearable inertial measurement units (WIMUs), wearable insole pressure system (WIPS)) have been used to collect workers' gait patterns for distinguishing safety hazards. However, the performance of measuring WIPS-based gait parameters for identifying safety hazards as compared to a reference system (i.e. WIMUs) has not been studied. Therefore, this study examined the validity and reliability of measuring WIPS-based gait parameters as compared to WIMU-based gait parameters for distinguishing safety hazards in construction.Design/methodology/approachFive fall-risk events were conducted in a laboratory setting, and the performance of the proposed approach was assessed by calculating the mean difference (MD), mean absolute error (MAE), mean absolute percentage error (MAPE), root mean square error (RMSE) and intraclass correlation coefficient (ICC) of five gait parameters.FindingsComparable results of MD, MAE, MAPE and RMSE were found between WIPS-based gait parameters and the reference system. Furthermore, all measured gait parameters had validity (ICC = 0.751) and test-retest reliability (ICC = 0.910) closer to 1, indicating a good performance of measuring WIPS-based gait parameters for distinguishing safety hazards.Research limitations/implicationsOverall, this study supports the relevance of developing a WIPS as a noninvasive wearable sensing system for identifying safety hazards on construction sites, thus highlighting the usefulness of its applications for construction safety research.Originality/valueThis is the first study to examine the performance of a wearable insole pressure system for identifying safety hazards in construction.
Impact value and sustainable, well-being centred service systems
Authors: Simmonds Hamish , Gazley Aaron 
Published: September 2020

Purpose
This paper aims to develop impact value (IV), both theoretically and practically, to better account for the processes of value creation within complex service ecosystems.

Design/methodology/approach
This conceptual paper connects the complex systems nature of service ecosystems and the complexity of issues of sustainability and well-being to the need for a conceptual and analytical extension of value within service ecosystems.

Findings
This paper defines IV as enhancement or diminishment of the potential of stakeholders (beyond the service beneficiary), to transfer or transform resources in the future, based on direct and indirect involvement in the processes of value-in-exchange and value-in-use creation.

Research limitations/implications
This paper provides an initial exploration of the theoretical and practical extension of value through the IV concept.

Practical implications
Sustainable service ecosystems require actors to understand their role in the service process and account for the impact pathways of their value creation activities. This paper proposes a framework for developing sustainable strategies to account for IV.

Originality/value
This research expands service research’s core concept of value by integrating the complex systems nature of service ecosystems, sustainability and well-being. IV provides a means to address the systemic impact pathways of service and value creation processes and bridge idiosyncratic value-in-use and broader system viability concepts.
Fairness, legitimacy and the regulation of home-sharing platforms
Authors: Newlands Gemma , Lutz Christoph 
Published: September 2020

PurposeThe purpose of this study is to contribute to current hospitality and tourism research on the sharing economy by studying the under-researched aspects of regulatory desirability, moral legitimacy and fairness in the context of home-sharing platforms (e.g. Airbnb).Design/methodology/approachThree separate 2×1 between-subjects experimental vignette surveys are used to test the effects of three types of fairness (procedural, interpersonal and informational) on two outcomes: moral legitimacy and regulatory desirability.FindingsThe results of the research show that high perceived fairness across all three types increases moral legitimacy and reduces regulatory desirability. Respondents who perceive a fictional home-sharing platform to be fair consider it to be more legitimate and want it to be less regulated.Research limitations/implicationsFollowing established practices and reducing external validity, the study uses a fictional scenario and a fictional company for the experimental vignette. The data collection took place in the UK, prohibiting cultural comparisons.Practical implicationsThe research is useful for home-sharing platform managers by showing how they can boost moral legitimacy and decrease regulatory desirability through a strong focus on fairness. It can also help policymakers and consumer protection advocates by providing evidence about regulatory desirability and how it is affected by fairness perceptions.Originality/valueThe study adds to hospitality and tourism research by offering theoretically meaningful and practically relevant conclusions about the importance of fairness in driving stakeholder opinions about home-sharing platforms.
Misperception of entrepreneurship and its consequences for the perception of entrepreneurial failure – the German case
Authors: Kuckertz Andreas , Berger Elisabeth S.C. , Prochotta Alicia 
Published: September 2020

PurposeThis study aims to investigate how Germans' misperceptions of the nature of entrepreneurship influence their attitudes towards entrepreneurial failure.Design/methodology/approachAdopting a multivariate regression analysis, the study used data collected from a commercial online market research panel (N = 2,027) reflecting the overall German working population. Attitudinal items on business failure were used to measure the study variables. The study controlled for age, education, employment status, gender, income, whether the respondent knows a failed entrepreneur and the German federal state in which the respondent resides.FindingsThe findings suggest that reservations about failed entrepreneurs become stronger as misperceptions of the nature of entrepreneurship worsen. The results also show that failure reservations vary regionally over the 16 German federal states.Practical implicationsNationwide efforts regarding the stimulation of entrepreneurship and the acceptance of entrepreneurial failure are insufficient for removing failure reservations, as they neglect regional cultural differences. The results suggest that it is not enough just to invest in efforts to create a failure-friendly culture, and that a better general education about the realities of entrepreneurship is a prerequisite.Originality/valueThe study generates insights into how the overall population in an innovation-driven economy perceives entrepreneurship and entrepreneurial failure. Moreover, the work delves into the reasons why parts of German society reject failed entrepreneurs. Hence, this study can aid the drafting of effective policy initiatives at the regional and national levels.