bluuebunny/crossref_metadata_2025 huggingface dataset:
The kallikrein-kinin system is falling into pieces: bradykinin fragments are biological active peptides
Authors: Souza-Silva Igor Maciel , de Paula Cristiane Amorim , Santos Anderson Kenedy , de Oliveira Vívian Louise Soares , da Rocha Isabella Domingos , Antunes Maísa Mota , Barbosa Cordeiro Lídia Pereira , Teixeira Vanessa Pereira , Scalzo Júnior Sérgio Ricardo Aluotto , Amaral Flávio Almeida , Resende Jarbas Magalhães , Peliky Fontes Marco Antônio , Menezes Gustavo Batista , Guatimosim Silvia , Souza Santos Robson Augusto , Verano-Braga Thiago
Published: September 2020

Background and purpose

Bradykinin [BK-(1-9)] is an endogenous peptide involved in many physiological and pathological processes, such as cardiovascular homeostasis and inflammation. The central dogma of the kallikrein-kinin system is that BK-(1-9) fragments are biologically inactive. In this manuscript, we proposed to test whether these fragments were indeed inactive.

Experimental Approach

Nitric oxide (NO) was quantified in human, mouse and rat cells loaded with DAF-FM after stimulation with BK-(1-9), BK-(1-7), BK-(1-5) and BK-(1-3). We used adult male rat aortic ring preparation to test vascular reactivity mediated by BK-(1-9) fragments. Changes in blood pressure and heart rate was measured in conscious adult male rats by intraarterial catheter method.

Key results

BK-(1-9) induced NO production in all cell types tested by B2 receptor activation. BK-(1-7), BK-(1-5) and BK-(1-3) also induced NO production in all tested cell types but this response was independent of the activation of B1 receptor and/or B2 receptor. BK-(1-7), BK-(1-5) or BK-(1-3) induced only vasorelaxant effect and in a concentration-dependent fashion. Vasorelaxant effects for BK-(1-7), BK-(1-5) or BK-(1-3) were independent of the kinin receptors. Different administration routes (i.e., intravenous or intra-arterial) did not affect the observed hypotension induced by BK-(1-7), BK-(1-5) or BK-(1-3). Importantly, these observations diverged from the BK-(1-9) results, highlighting that indeed the BK-(1-9) fragments do not seem to act via the classical kinin receptors.

Conclusions and implications

In conclusion, BK-(1-7), BK-(1-5) and BK-(1-3) are biologically active components of the kallikrein-kinin system. Importantly, observed pathophysiological outcomes of these peptides are independent of B1R and/or B2R activation.
W-RESP: Well-Restrained Electrostatic Potential Derived Charges. Revisiting the Charge Derivation Model
Authors: Janeček Michal , Kührová Petra , Mlýnský Vojtěch , Otyepka Michal , Šponer Jiří , Banáš Pavel
Published: September 2020

Representation of electrostatic interactions by a Coulombic pair-wise potential between atom-centered partial charges is a fundamental and crucial part of empirical force fields used in classical molecular dynamics simulations. The broad success of the AMBER force field family originates mainly from the restrained electrostatic potential (RESP) charge model, which derives partial charges to reproduce the electrostatic field around the molecules. However, description of the electrostatic potential around molecules by standard RESP may be biased for some types of molecules. In this study, we modified the RESP charge derivation model to improve its description of the electrostatic potential around molecules, and thus electrostatic interactions in the force field. In particular, we re-optimized the atomic radii for definition of the grid points around the molecule, redesigned the restraining scheme and included extra point charges. The RESP fitting was significantly improved for aromatic heterocyclic molecules. Thus, the suggested W-RESP(-EP) charge derivation model showed clear potential for improving the performance of the nucleic acid force fields, for which poor description of nonbonded interactions, such as underestimated base pairing, makes it difficult to describe the folding free energy landscape of small oligonucleotides.
Feeding recombinant Royalactin: Measures of improved lifespan and mitochondrial function inCaenorhabditis elegans
Authors: Li Xia , Ingram Thomas L. , Wang Ying , Derecka Kamila , Courtier Nathan , Piana Mattia , Hardy Ian C. W. , Chakrabarti Lisa , Stöger Reinhard
Published: September 2020

Ageing, the decline of biological functions over time, is inherent to eukaryotes. Female honeybees attain a long-lived queen phenotype upon continuous consumption of royal jelly, whereas restricted supply of this nutritional substance promotes the development of worker bees, which are short-lived. An abundant protein found within royal jelly is major royal jelly protein 1 (MRJP1), also known as ‘Royalactin’. Health- and lifespan promoting effects have been attributed to Royalactin in species from diverse animal taxa, suggesting it acts on phylogenetically conserved physiological processes. Here, we explore the effects of feeding the nematodeCaenorhabditis eleganswithEscherichia colithat express a recombinant form of Royalactin (RArec). We confirm that consumption of RArecincreases body size, improves locomotion and extends lifespan. We discover a link between Royalactin and mitochondria, organelles which play a key part in the ageing process: both spare respiratory capacity and morphology indicate improved mitochondrial function in RArecfedC. elegans. These results demonstrate the feasibility of using recombinant Royalactin to gain further insight into processes of healthy ageing in many species.

RArecproduction allows insight into potential beneficial effects across species.
Systematic variation in the temperature dependence of bacterial carbon use efficiency
Authors: Smith Thomas P. , Clegg Tom , Bell Thomas , Pawar Samrāt
Published: September 2020

Understanding the temperature dependence of carbon use efficiency (CUE) is critical for understanding microbial physiology, population dynamics, and community-level responses to changing environmental temperatures1,2. Currently, microbial CUE is widely assumed to decrease with temperature3,4. However, this assumption is based largely on community-level data, which are influenced by many confounding factors5, with little empirical evidence at the level of individual strains. Here, we experimentally characterise the CUE thermal response for a diverse set of environmental bacterial isolates. We find that contrary to current thinking, bacterial CUE typically responds either positively to temperature, or has no discernible temperature response, within biologically meaningful temperature ranges. Using a global data-synthesis, we show that our empirical results are generalisable across a much wider diversity of bacteria than have previously been tested. This systematic variation in the thermal responses of bacterial CUE stems from the fact that relative to respiration rates, bacterial population growth rates typically respond more strongly to temperature, and are also subject to weaker evolutionary constraints. Our results provide fundamental new insights into microbial physiology, and a basis for more accurately modelling the effects of shorter-term thermal fluctuations as well as longer-term climatic warming on microbial communities.
Synchronous and Asynchronous Response in Dynamically Perturbed Proteins
Authors: Erkip Albert , Hacisuleyman Aysima , Erman Batu , Erman Burak
Published: September 2020

We developed a Dynamic Gaussian Network Model to study perturbation and response in proteins. The model is based on the solution of the Langevin equation in the presence of noise and perturbation. A residue is perturbed periodically with a given frequency and the response of other residues is determined in terms of a storage and loss modulus of the protein. The amount of work lost upon periodic perturbation and the residues that contribute significantly to the lost work is determined. The model shows that perturbation introduces new dynamic correlations into the system with time delayed synchronous and asynchronous components. Residues whose perturbation induces large correlations in the protein and those that do not lead to correlations may be identified. The model is used to investigate the dynamic modulation of nanobodies. Despite its simplicity, the model explains several features of perturbation and response such as the role of loops and linkers in perturbation, dispersion of work of perturbation, and information transfer through preexisting pathways, all shown to be important factors in allostery.
The mitochondrial surface receptor Tom70 protects the cytosol against mitoprotein-induced stress
Authors: Backes Sandra , Bykov Yury S. , Räschle Markus , Zhou Jialin , Lenhard Svenja , Krämer Lena , Mühlhaus Timo , Bibi Chen , Jann Cosimo , Smith Justin D. , Steinmetz Lars M. , Rapaport Doron , Storchová Zuzana , Schuldiner Maya , Boos Felix , Herrmann Johannes M.
Published: September 2020

Most mitochondrial proteins are synthesized as precursors in the cytosol and post-translationally transported into mitochondria. The mitochondrial surface protein Tom70 acts at the interface of the cytosol and mitochondria.In vitroimport experiments identified Tom70 as targeting receptor, particularly for hydrophobic carriers. Usingin vivomethods and high content screens, we revisited the question of Tom70 function and considerably expanded the set of Tom70-dependent mitochondrial proteins. We demonstrate that the crucial activity of Tom70 is its ability to recruit cytosolic chaperones to the outer membrane. Indeed, tethering an unrelated chaperone-binding domain onto the mitochondrial surface complements most of the defects caused by Tom70 deletion. Tom70-mediated chaperone recruitment reduces the proteotoxicity of mitochondrial precursor proteins, in particular of hydrophobic inner membrane proteins. Thus, our work suggests that the predominant function of Tom70 is to tether cytosolic chaperones to the outer mitochondrial membrane, rather than to serve as a mitochondria-specifying targeting receptor.
Autophagy induced accumulation of lipids inpgrl1andpgr5ofChlamydomonas reinhardtiiunder high light
Authors: Chouhan Nisha , Devadasu Elsin Raju , Yadav Ranay Mohan , Subramanyam Rajagopal
Published: September 2020

Chlamydomonas (C) reinhardtiicells (wild-type CC125 and137AH, and cyclic electron transport dependant mutantspgrl1andpgr5) were grown in high light 500 µmol photons m−2s−1where the growth was significantly enhanced after three days. The starch and lipid contents were also increased; however, starch content was decreased inpgr5. Further, the Nile Red fluorescence shows that a significant amount of lipid bodies were observed inpgr5cells under high light. Similarly, the electron micrographs show that large vacuoles were formed in high light stress despite the change in stacks of grana structure. We also observed increased production of reactive oxygen species (ROS) that could lead to autophagy. Inline, a significant increase of ATG8 protein was noticed inpgr5, which is a hallmark characteristic for autophagy formation. Consequently, the triacylglycerol (TAG) content was increased due to DGAT and PDAT enzymes’ expression, especially inpgr5. Here, the TAG synthesis would have been obtained from degraded membrane lipids inpgr5. Additionally, mono, polyunsaturated, and saturated fatty acids were identified more in the high light condition. Our study shows that the high light induces ROS, leads to autophagy and TAGs accumulation, which is stored as an energy source to acclimatize the algae.
TIMEOR: a web-based tool to uncover temporal regulatory mechanisms from multi-omics data
Authors: Conard Ashley Mae , Goodman Nathaniel , Hu Yanhui , Perrimon Norbert , Singh Ritambhara , Lawrence Charles , Larschan Erica
Published: September 2020

Uncovering how transcription factors (TFs) regulate their targets at the DNA, RNA and protein levels over time is critical to define gene regulatory networks (GRNs) in normal and diseased states. RNA-seq has become a standard method to measure gene regulation using an established set of analysis steps. However, none of the currently available pipeline methods for interpreting ordered genomic data (in time or space) use time series models to assign cause and effect relationships within GRNs, are adaptive to diverse experimental designs, or enable user interpretation through a web-based platform. Furthermore, methods which integrate ordered RNA-seq data with transcription factor binding data are urgently needed. Here, we present TIMEOR (Trajectory Inference and Mechanism Exploration with Omics data in R), the first web-based and adaptive time series multi-omics pipeline method which infers the relationship between gene regulatory events across time. TIMEOR addresses the critical need for methods to predict causal regulatory mechanism networks between TFs from time series multi-omics data. We used TIMEOR to identify a new link between insulin stimulation and the circadian rhythm cycle. TIMEOR is available athttps://github.com/ashleymaeconard/TIMEOR.git.
The adaptive value of tandem communication in ants: insights from an agent-based model
Authors: Goy Natascha , Glaser Simone M. , Grüter Christoph
Published: September 2020

Social animals often share information about the location of resources, such as a food source or a new nest-site. One well-studied communication strategy in ants is tandem running, whereby a leader guides a recruit to a resource. Tandem running is considered an example of animal teaching because a leader adjusts her behaviour and invests time to help another ant to learn the location of a resource more efficiently. Tandem running also has costs, such as waiting inside the nest for a leader and a reduced walking speed. Whether and when these costs outweigh the benefits of tandem running is not well understood. We developed an agent-based simulation model to investigate the conditions that favour communication by tandem running during foraging. We predicted that the spatio-temporal distribution of food sources, colony size and the ratio of scouts and recruits affect colony foraging success. Our results suggest that communication is favoured when food sources are hard to find, of variable quality and long lasting. These results mirror the findings of simulations of honeybee communication. Scouts locate food sources faster than tandem followers in some environments, suggesting that tandem running may fulfil the criteria of teaching only in some situations. Furthermore, tandem running was only beneficial above a critical colony size threshold. Taken together, our model suggests that there is a considerable parameter range that favours colonies that do not use communication, which could explain why many social insects with small colony sizes forage solitarily.
Heme oxygenase-1 affects cytochrome P450 function through the formation of heteromeric complexes: Interactions between CYP1A2 and heme oxygenase-1
Authors: Connick J. Patrick , Reed James R. , Cawley George F. , Backes Wayne L.
Published: September 2020

Heme oxygenase 1 (HO-1) and the cytochromes P450 (P450s) are endoplasmic reticulum-bound enzymes that rely on the same protein, NADPH-cytochrome P450 reductase (POR), to provide the electrons necessary for substrate metabolism. Although the HO-1 and P450 systems are interconnected due to their common electron donor, they generally have been studied separately. As the expression of both HO-1 and P450s are affected by xenobiotic exposure, changes in HO-1 expression can potentially affect P450 function, and conversely, changes in P450 expression can influence HO-1. The goal of this study was to examine interactions between the P450 and HO-1 systems. Using bioluminescence resonance energy transfer (BRET), HO-1 formed HO-1•P450 complexes with CYP1A2, CYP1A1, and CYP2D6, but not all P450s. Studies then focused on the HO-1/CYP1A2 interaction. CYP1A2 formed a physical complex with HO-1 that was stable in the presence of POR. As expected, both HO-1 and CYP1A2 formed BRET-detectable complexes with POR. Whereas the POR•CYP1A2 complex was readily disrupted by the addition of HO-1, the POR•HO-1 complex was not significantly affected by the addition of CYP1A2. Interestingly, enzyme activities did not follow this pattern. Whereas BRET data suggested substantial inhibition of CYP1A2-mediated 7-ethoxyresorufin deethylation in the presence of HO-1, its activity was actually stimulated at subsaturating POR. In contrast, HO-1-mediated heme metabolism was inhibited at subsaturating POR. These results indicate that HO-1 and CYP1A2 form a stable complex and have mutual effects on the catalytic behavior of both proteins that cannot be explained by simple competition for POR.
Identification of Hyal2-expressing tumor-associated myeloid cells in cancer: implications for cancer-related inflammation through enhanced hyaluronan degradation
Authors: Dominguez Gutierrez Paul R. , Kwenda Elizabeth P. , Donelan William , O’Malley Padraic , Crispen Paul L. , Kusmartsev Sergei
Published: September 2020

Increased presence of myeloid derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) in tumor tissue has been extensively reported. These cells represent a major constituent of tumor infiltrate and exhibit a distinct phenotype with immunosuppressive and tolerogenic functions. However, their role in the regulation of hyaluronan (HA) metabolism in the tumor microenvironment has not been established. Here we describe a novel function of tumor-associated myeloid cells related to the enhanced breakdown of extracellular HA in human bladder cancer tissue leading to accumulation of small HA fragments with MW <20 kDa. Increased fragmentation of extracellular HA and accumulation of low molecular weight HA (LMW-HA) in tumor tissue was associated with elevated production of multiple inflammatory cytokines, chemokines, and angiogenic factors. The fragmentation of HA by myeloid cells was mediated by the membrane-bound enzyme hyaluronidase 2 (Hyal2). The increased numbers of Hyal2+CD11b+myeloid cells were detected in the tumor tissue as well as in the peripheral blood of bladder cancer patients. Co-expression of CD33 suggests that these cells belong to monocytic myeloid-derived suppressor cells. HA-degrading function of Hyal2-expressing MDSCs could be enhanced by exposure to tumor-conditioned medium, and IL-1β was identified as one of factors involved in the stimulation of Hyal2 activity. CD44-mediated signaling plays an important role in the regulation of HA-degrading activity of Hyal2-expressing myeloid cells, since engagement of CD44 receptor with specific monoclonal antibody triggered translocation of Hyal2 enzyme to the cellular surface and also stimulated secretion of IL-1β. Taken together, this work identifies the Hyal2-expressing tumor-associated myeloid cells, and links these cells to the accumulation of LMW-HA in the tumor microenvironment and cancer-related inflammation and angiogenesis.
Promoter-proximal elongation regulates transcription in archaea
Authors: Blombach Fabian , Fouqueau Thomas , Matelska Dorota , Smollett Katherine , Werner Finn
Published: September 2020

Recruitment of RNA polymerase and initiation factors to the promoter is the only known mechanisms for transcription activation and repression in archaea. Whether any of the subsequent steps towards productive transcription elongation is involved in regulation is not known. We characterised how the basal transcription machinery is distributed along genes in the archaeonSulfolobus solfataricus.We discovered a distinct early elongation phase where RNA polymerases sequentially recruit the elongation factors Spt4/5 and Elf1 to form the transcription elongation complex (TEC) before the TEC escapes into productive transcription. TEC escape is rate-limiting for transcription output during exponential growth. Oxidative stress causes changes in TEC escape that correlate with changes in the transcriptome. Our results thus establish that TEC escape contributes to the basal promoter strength and facilitates transcription regulation. Impaired TEC escape coincides with the accumulation of initiation factors at the promoter and recruitment of termination factor aCPSF1 to the early TEC. This suggests two possible mechanisms for how TEC escape limits transcription, physically blocking upstream RNA polymerases during transcription initiation and premature termination of early TECs.
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

H3K4me1 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

The 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

When 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

Vaccination 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 SUMMARY

The 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

WNT 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

Traditional 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

Cellular 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

Purpose

The 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/approach

To 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.

Findings

The 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/value

The 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

Purpose

Construction 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/approach

Five 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.

Findings

Comparable 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/implications

Overall, 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/value

This 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

Purpose

The 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/approach

Three 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.

Findings

The 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/implications

Following 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 implications

The 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/value

The 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

Purpose

This study aims to investigate how Germans' misperceptions of the nature of entrepreneurship influence their attitudes towards entrepreneurial failure.

Design/methodology/approach

Adopting 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.

Findings

The 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 implications

Nationwide 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/value

The 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.
Trust based authentication scheme (tbas) for cloud computing environment with Kerberos protocol using distributed controller and prevention attack
Authors: Anbu Malar M.B. Benjula , J. Prabhu
Published: September 2020

Purpose

This paper aims to discuss the Silver and Golden ticket exploits that usually exists in the existing systems. To overcome these challenges, the data is first encrypted and then the ticket is granted to the validated user. The users are validated using the user privileges. The security levels of the proposed model are compared with the existing models and provide a better performance using the Key Distribution Centre (KDC). The number of authentication and authorization levels present in the existing and proposed model is also evaluated.

Design/methodology/approach

The methodology designed in this paper is discussed in this section. The existing models are designed in such a way that the client ID first asked to send an authorization request to the Authentication Server. The server looks up the user in its database and then sends back a ticket generated by it to the client to obtain services for the Service center. Numerous models have some additional features to these systems where the theme of KDC was introduced. The Key Distribution Centre (KDC), which is a set of nodes in a network where the data could be distributed and stored, such that any kind of attack on a single KDC will not impact other KDC and the data stored in it. The nodes other than the KDC in the network are termed as the slave nodes. The slave nodes communicate with each other within the network depending on the topology of the entire network. In this paper, the authors have used the Kerberos protocol for adding more security functions in the entire network. The system developed consists of a client, server and a set of nodes connected to each other in a ring fashion.

Findings

The proposed model provides security to the information being used by making use of the Kerberos protocol. Additional features and algorithms such as the use of the ticket-granting approach have been added at the protocol to make it more secure than the existing models. The ticket generation is done at the server-side that makes the user have proper authentication to make use of the services available from the server-side. The model is designed in such a way that it could remain operational even during the time of denial of service. As future work, use of machine learning and deep learning could be used to predict the attack on the network well before it is being misused.

Originality/value

The paper discusses the Silver and Golden ticket exploits that usually exists in the existing systems. To overcome these challenges, the data is first encrypted and then the ticket is granted to the validated user. The users are validated using the user privileges. The security levels of the proposed model are compared with the existing models and provide a better performance using the Key Distribution Centre (KDC). The number of authentication and authorization levels present in the existing and proposed model is also evaluated.
Alternative transportation education: implementing an innovative module
Authors: McKenna Kelly , Altringer Levi
Published: September 2020

Purpose

This study aims to investigate the Colorado state university (CSU) MOVES online, transportation module, which was implemented for the dual purpose of promoting alternative modes of transportation and while providing students with the information and skills necessary to comfortably and safely commute on and around campus without a personal motor vehicle.

Design/methodology/approach

This mixed methods research tests the effect of the CSU MOVES transportation module on students’ familiarity, comfortability and knowledgeability, the researchers investigate within- and across-group changes in student survey responses over time.

Findings

The educational transportation module had an immediate and significant impact on the students’ familiarity, comfortability and knowledgeability regarding alternative and active transportation methods and this effect lasted over the semester. In addition, participating students experienced much larger gains in their knowledgeability of safe active transportation practices.

Research limitations/implications

The CSU MOVES survey data was limited in multiple ways, including self-selection into participation and completion of the transportation module, as well as the small sample size and lack of an authentic control group.

Originality/value

Universities and colleges across the country are becoming critically aware of issues surrounding transportation on and around campus and CSU is one of the first universities to join together with the local community to implement a transportation education module. Transportation initiatives have been motivated by multiple factors such as the supply of and demand for parking on and around campuses, sustainability efforts to reduce carbon emissions associated with university operations and the promotion of student health through active lifestyle practices.