bluuebunny/crossref_metadata_2025 huggingface dataset:
Distinguishing the neural correlates of perceptual awareness and post-perceptual processing
Authors: Cohen Michael A. , Ortego Kevin , Kyroudis Andrew , Pitts Michael
Published: January 2020

To identify the neural correlates of perceptual awareness, researchers often compare the differences in neural activation between conditions in which an observer is or is not aware of a stimulus. While intuitive, this approach often contains a critical limitation: In order to link brain activity with perceptual awareness, observers traditionally report the contents of their perceptual experience. However, relying on observers’ reports is problematic because it is difficult to know if the neural responses being measured are associated with conscious perception or with post-perceptual processes involved in the reporting task (i.e., working memory, decision-making, etc.). To address this issue, we combined a standard visual masking paradigm with a recently developed “no-report” paradigm in male/female human participants. In the visual masking paradigm, observers saw images of animals and objects that were visible or invisible depending on their proximity to masks. Meanwhile, on half of the trials, observers reported the contents of their perceptual experience (i.e., report condition), while on the other half of trials they refrained from reporting about their experiences (i.e., no-report condition). We used electroencephalography (EEG) to examine how visibility interacts with reporting by measuring the P3b event related potential (ERP), one of the proposed canonical “signatures” of conscious processing. Overall, we found a robust P3b in the report condition, but no P3b whatsoever in the no-report condition. This finding suggests that the P3b itself is not a neural signature of conscious processing and highlights the importance of carefully distinguishing the neural correlates of perceptual awareness from post-perceptual processing.

Significance statement

What are the neural signatures that differentiate conscious and unconscious processing in the brain? Perhaps the most well-established candidate signature is the P3b event-related potential (ERP), a late slow wave that appears when observers are aware of a stimulus, but disappears when a stimulus fails to reach awareness. Here, however, we found that the P3b does not track what observers areperceivingbut instead tracks what observers arereporting. When observers are aware of simple visual stimuli, the P3b is nowhere to be found unless observers are reporting the contents of their experience. These results challenge the well-established notion of the P3b as a neural marker of awareness and highlight the need for new approaches to the neuroscience of consciousness.
Cryo-EM structures of cardiac thin filaments reveal the 3D architecture of troponin
Authors: Oda Toshiyuki , Yanagisawa Haruaki , Wakabayashi Takeyuki
Published: January 2020

Troponin is an essential component of striated muscle and it regulates the sliding of actomyosin system in a calcium-dependent manner. Despite its importance, the structure of troponin has been elusive due to its high structural heterogeneity. In this study, we analyzed the 3D structures of murine cardiac thin filaments using a cryo-electron microscope equipped with a Volta phase plate (VPP). Contrast enhancement by a VPP enabled us to reconstruct the entire repeat of the thin filament. We determined the orientation of troponin relative to F-actin and tropomyosin, and characterized the interactions between troponin and tropomyosin. This study provides a structural basis for understanding the molecular mechanism of actomyosin system.
Modular and Distinct Plexin-A4/FARP2/Rac1 Signaling Controls Dendrite Morphogenesis
Authors: Danelon Victor , Goldner Ron , Martinez Edward , Gokhman Irena , Wang Kimberly , Yaron Avraham , Tran Tracy S.
Published: January 2020

Diverse neuronal populations with distinct cellular morphologies coordinate the complex function of the nervous system. Establishment of distinct neuronal morphologies critically depends on signaling pathways that control axonal and dendritic development. The Sema3A-Nrp1/PlxnA4 signaling pathway promotes cortical neuron basal dendrite arborization but also repels axons. However, the downstream signaling components underlying these disparate functions of Sema3A signaling are unclear. Using the novelPlxnA4KRK-AAAknock-in male and female mice, generated by CRISPR/cas9, we show here that the KRK motif in the PlxnA4 cytoplasmic domain is required for Sema3A-mediated cortical neuron dendritic elaboration but is dispensable for inhibitory axon guidance. The RhoGEF FARP2, which binds to the KRK motif, shows identical functional specificity as the KRK motif in the PlxnA4 receptor. We find that Sema3A activates the small GTPase Rac1, and that Rac1 activity is required for dendrite elaboration but not axon growth cone collapse. This work identifies a novel Sema3A-Nrp1/PlxnA4/FARP2/Rac1 signaling pathway that specifically controls dendritic morphogenesis but is dispensable for repulsive guidance events. Overall, our results demonstrate that the divergent signaling output from multifunctional receptor complexes critically depends on distinct signaling motifs, highlighting the modular nature of guidance cue receptors and its potential to regulate diverse cellular responses.

Significance Statement

The proper formation of axonal and dendritic morphologies is crucial for the precise wiring of the nervous system that ultimately leads to the generation of complex functions in an organism. The Semaphorin3A-Neuropilin1/Plexin-A4 signaling pathway has been shown to have multiple key roles in neurodevelopment, from axon repulsion to dendrite elaboration. This study demonstrates that three specific amino acids, the KRK motif within the Plexin-A4 receptor cytoplasmic domain, are required to coordinate the downstream signaling molecules to promote Sema3A-mediated cortical neuron dendritic elaboration, but not inhibitory axon guidance. Our results unravel a novel Semaphorin3A-Plexin-A4 downstream signaling pathway and shed light on how the disparate functions of axon guidance and dendritic morphogenesis are accomplished by the same extracellular ligandin vivo.
EWS-FLI1 regulates and cooperates with core regulatory circuitry in Ewing sarcoma
Authors: Shi Xianping , Zheng Yueyuan , Jiang Liling , Zhou Bo , Yang Wei , Li Liyan , Ding Lingwen , Huang Moli , Gery Sigal , Lin De-Chen , Koeffler H. Phillip
Published: January 2020

Core regulatory circuitry (CRC)-dependent transcriptional network is critical for developmental tumors in children and young adults carrying few gene mutations. However, whether and how CRC contributes to transcription regulation in Ewing sarcoma is unknown. Here, we identify and functionally validate a CRC “trio” constituted by three transcription factors (TFs): KLF15, TCF4 and NKX2-2, in Ewing sarcoma cells. Epigenomic analyses demonstrate that EWS-FLI1, the primary fusion driver for this cancer, directly establishes super-enhancers of each of these three TFs to activate their transcription. In turn, KLF15, TCF4 and NKX2-2 co-bind to their own and each other’s super-enhancers and promoters, forming an inter-connected auto-regulatory loop. Functionally, CRC factors contribute significantly to cell proliferation of Ewing sarcoma bothin vitroandin vivo, and are all overexpressed in this cancer. Mechanistically, CRC factors exhibit prominent capacity of co-regulating the epigenome in cooperation with EWS-FLI1, occupying 77.2% of promoters and 55.6% of enhancers genome-wide. Downstream, CRC TFs coordinately regulate gene expression networks in Ewing sarcoma, directly controlling important signaling pathways for cancer, such as lipid metabolism pathway, PI3K/AKT and MAPK signaling pathways. Together, molecular characterization of the oncogenic CRC model advances our understanding of the biology of Ewing sarcoma. Moreover, this study identifies CRC-downstream genes and signaling pathways, which may contain potential targets for therapeutic intervention for this malignancy.
Identifying Causal Variants by Fine Mapping Across Multiple Studies
Authors: LaPierre Nathan , Taraszka Kodi , Huang Helen , He Rosemary , Hormozdiari Farhad , Eskin Eleazar
Published: January 2020

Increasingly large Genome-Wide Association Studies (GWAS) have yielded numerous variants associated with many complex traits, motivating the development of “fine mapping” methods to identify which of the associated variants are causal. Additionally, GWAS of the same trait for different populations are increasingly available, raising the possibility of refining fine mapping results further by leveraging different linkage disequilibrium (LD) structures across studies. Here, we introduce multiple study causal variants identification in associated regions (MsCAVIAR), a method that extends the popular CAVIAR fine mapping framework to a multiple study setting using a random effects model. MsCAVIAR only requires summary statistics and LD as input, accounts for uncertainty in association statistics using a multivariate normal model, allows for multiple causal variants at a locus, and explicitly models the possibility of different SNP effect sizes in different populations. In a trans-ethnic, trans-biobank Type 2 Diabetes analysis, we show that MsCAVIAR returns causal set sizes that are over 20% smaller than those given by current state of the art methods for trans-ethnic fine-mapping.
Genetic interactions shaping evolutionary trajectories in an RNA virus population
Authors: Chang Chang , Bianco Simone , Acevedo Ashley , Tang Chao , Andino Raul
Published: January 2020

A quantitative understanding of evolution rests on the analysis of the mutation accumulation process in biological populations, but is largely limited to high-frequency mutations due to the resolution of conventional sequencing technologies. Here, we examine the mutation composition of a poliovirus population over multiple passages using a highly-accurate sequencing strategy, that enables detection of up to 99% of all possible mutations, most of which are present at low-frequency. This data informs a mathematical model describing trajectory patterns of individual mutations to understand the type of interactions shaping population dynamics. We identify mutations consistent with a locus-independent behavior, and others deviating from that simple model by interactions. Clonal interference, followed by hitchhiking, appear to be the most prevalent interactions in the virus population. Epistasis, while presents, but does not significantly affect the distribution of mutational fitness on the short time scale examined in our study. Our study provides a comprehensive analysis of the allelic composition and how mutation rate, fitness, epistasis, clonal interference and hitchhiking influence population dynamics and evolution.
A comparative ‘omics approach to candidate pathogenicity factor discovery in the brain-eating amoebaNaegleria fowleri
Authors: Herman Emily K. , Greninger Alex , van der Giezen Mark , Ginger Michael L. , Ramirez-Macias Inmaculada , Miller Haylea C. , Morgan Matthew J. , Tsaousis Anastasios D. , Velle Katrina , Vargová Romana , Rodrigo Najle Sebastian , MacIntyre Georgina , Muller Norbert , Wittwer Mattias , Zysset-Burri Denise C. , Elias Marek , Slamovits Claudio , Weirauch Matthew , Fritz-Laylin Lillian , Marciano-Cabral Francine , Puzon Geoffrey J. , Walsh Tom , Chiu Charles , Dacks Joel B.
Published: January 2020

Of the 40 describedNaegleriaspecies, onlyN. fowlerican establish infection in humans, killing almost invariably within two weeks. In the brain, the amoeba performs piece-meal ingestion, or trogocytosis, of brain material causing massive inflammation. Conversely, its close relativeNaegleria gruberi, which is used as a laboratory model organism, is non-pathogenic. The exact pathogenicity factors distinguishingN. fowlerifrom its harmless relatives are unclear. We have here taken an -omics approach to understandingN. fowleribiology and infection at the system level. We provide the first analysis of genomic diversity between strains, finding little conservation in synteny but high conservation in protein complement. We also demonstrate that theN. fowlerigenome encodes a similarly complete cellular repertoire to that found inN. gruberi. Our comparative genomic analysis, together with a transcriptomic analysis of low versus high pathogenicityN. fowlericultured in a mouse infection model, allowed us to construct a model of cellular systems involved in pathogenicity and furthermore provides ~500 novel candidate pathogenicity factors in this currently rare but highly fatal pathogen.
C subunit of the ATP synthase is an amyloidogenic channel-forming peptide: possible implications in mitochondrial pathogenesis
Authors: Amodeo Giuseppe Federico , Lee Brenda Yasie , Krilyuk Natalya , Filice Carina Teresa , Valyuk Denis , Otzen Daniel , Noskov Sergey , Leonenko Zoya , Pavlov Evgeny V.
Published: January 2020

The c subunit is an inner mitochondrial membrane (IMM) protein and is an integral part of the F0complex of the ATP synthase. Under physiological conditions, this short 75 residue-long peptide folds into an α-helical hairpin and forms oligomers spanning the lipid bilayer. In addition to its physiological role, the c subunit has been proposed as a key participant in stress-induced IMM permeabilization by the mechanism of calcium-induced permeability transition. However, the molecular mechanism of the c subunit participation in IMM permeabilization is not completely understood. Here we used fluorescence spectroscopy, atomic force microscopy and black lipid membrane methods to gain insights into the structural and functional properties of c subunit protein that make it relevant to mitochondrial toxicity. We discovered that c subunit is an amyloidogenic peptide that can spontaneously fold into β-sheets and self-assemble into fibrils and oligomers. C subunit oligomers exhibited ion channel activity in lipid membranes. We propose that the toxic effects of c subunit might be linked to its amyloidogenic properties and are driven by mechanisms similar to those of neurodegenerative polypeptides such as Aβ and α-synuclein.
Evolutionary context-integrated deep sequence modeling for protein engineering
Authors: Luo Yunan , Vo Lam , Ding Hantian , Su Yufeng , Liu Yang , Qian Wesley Wei , Zhao Huimin , Peng Jian
Published: January 2020

Protein engineering seeks to design proteins with improved or novel functions. Compared to rational design and directed evolution approaches, machine learning-guided approaches traverse the fitness landscape more effectively and hold the promise for accelerating engineering and reducing the experimental cost and effort. A critical challenge here is whether we are capable of predicting the function or fitness of unseen protein variants. By learning from the sequence and large-scale screening data of characterized variants, machine learning models predict functional fitness of sequences and prioritize new variants that are very likely to demonstrate enhanced functional properties, thereby guiding and accelerating rational design and directed evolution. While existing generative models and language models have been developed to predict the effects of mutation and assist protein engineering, the accuracy of these models is limited due to their unsupervised nature of the general sequence contexts they captured that is not specific to the protein being engineered. In this work, we propose ECNet, a deep-learning algorithm to exploit evolutionary contexts to predict functional fitness for protein engineering. Our method integrated local evolutionary context from homologous sequences that explicitly model residue-residue epistasis for the protein of interest, as well as the global evolutionary context that encodes rich semantic and structural features from the enormous protein sequence universe. This biologically motivated sequence modeling approach enables accurate mapping from sequence to function and provides generalization from low-order mutants to higher-orders. Through extensive benchmark experiments, we showed that our method outperforms existing methods on ∼50 deep mutagenesis scanning and random mutagenesis datasets, demonstrating its potential of guiding and expediting protein engineering.
Pterostilbene Protects Cochlea from Ototoxicity in Streptozotocin-Induced Diabetic Rats by Inhibiting the Apoptosis
Authors: Özdaş Sibel , Taştekin Bora , Gürgen Seren G. , Özdaş Talih , Pelit Aykut , Erkan Sanem O. , Tuhanioğlu Birgül , Görgülü Orhan
Published: January 2020

Objectives/Hypothesis

Diabetes mellitus (DM) causes ototoxicity by inducing oxidative stress, microangiopathy, and apoptosis in the cochlear sensory hair cells. The natural anti-oxidant pterostilbene (PTS) (trans-3,5-dimethoxy-4-hydroxystylbene) has been reported to relieve oxidative stress and apoptosis in DM, but its role in diabetic-induced ototoxicity is unclear. This study aimed to investigate the effects of dose-dependent PTS on the cochlear cells of streptozotocin (STZ)-induced diabetic rats.

Methods

The study included 30 albino male Wistar rats that were randomized into five groups: non-diabetic control (Control), diabetic control (DM), and diabetic rats treated with intraperitoneal PTS at 10, 20, or 40 mg/kg/day during the four-week experimental period (DM+ PTS10, DM + PTS20, and DM + PTS40). Distortion product otoacoustic emission (DPOAE) tests were performed at the beginning and end of the study. At the end of the experimental period, apoptosis in the rat cochlea was investigated using caspase-8, cytochrome-c, and terminal deoxyribonucleotidyl transferase-mediated dUTP-biotin end labeling (TUNEL). Quantitative real-time polymerase chain reaction was used to assess the mRNA expression levels of the following genes:CASP-3, BCL-associated X protein (BAX), andBCL-2. Body weight, blood glucose, serum insulin, and malondialdehyde (MDA) levels in the rat groups were evaluated.

Results

The mean DPOAE amplitude in the DM group was significantly lower than the means of the other groups (0.9–8 kHz; P < 0.001 for all). A dose-dependent increase of the mean DPOAE amplitudes was observed with PTS treatment (P < 0.05 for all). The caspase-8 and cytochrome-c protein expressions and the number of TUNEL-positive cells in the hair cells of the Corti organs of the DM rat group were significantly higher than those of the PTS treatment and control groups (DM > DM + PTS10 > DM + PTS20 > DM + PTS40 > Control; P < 0.05 for all). PTS treatment also reduced cell apoptosis in a dose-dependent manner by increasing the mRNA expression of the anti-apoptosisBCL2gene and by decreasing the mRNA expressions of both the pro-apoptosisBAXgene and its effectorCASP-3in a dose-dependent manner (P < 0.05 compared to DM for all). PTS treatment significantly improved the metabolic parameters of the diabetic rats, such as body weight, blood glucose, serum insulin, and MDA levels, consistent with our other findings (P < 0.05 compared to DM for all).

Conclusion

PTS decreased the cochlear damage caused by diabetes, as confirmed by DPOAE, biochemical, histopathological, immunohistochemical, and molecular findings. This study reports the first in vivo findings to suggest that PTS may be a protective therapeutic agent against diabetes-induced ototoxicity.
Human MAIT cell cytolytic effector proteins synergize to overcome carbapenem resistance inEscherichia coli
Authors: Boulouis Caroline , Sia Wan Rong , Gulam Muhammad Yaaseen , Teo Jocelyn Qi Min , Phan Thanh Kha , Mak Jeffrey Y. W. , Fairlie David P. , Poon Ivan K. H. , Koh Tse Hsien , Bergman Peter , Wang Lin-Fa , Kwa Andrea Lay Hoon , Sandberg Johan K. , Leeansyah Edwin
Published: January 2020

Mucosa-associated invariant T (MAIT) cells are abundant antimicrobial T cells in humans, and recognize antigens derived from the microbial riboflavin biosynthetic pathway presented by the MHC-Ib-related protein (MR1). However, the mechanisms responsible for MAIT cell antimicrobial activity are not fully understood, and the efficacy of these mechanisms against antibiotic resistant bacteria has not been explored. Here, we show that MAIT cells mediate MR1-restricted antimicrobial activity againstE. coliclinical strains in a manner dependent on the activity of cytolytic proteins, but independent of production of pro-inflammatory cytokines or induction of apoptosis in infected cells. The combined action of the pore-forming antimicrobial protein granulysin and the serine protease granzyme B released in response to TCR-mediated recognition of MR1-presented antigen is essential to mediate control against both cell-associated and free-livingE. coli. Furthermore, MAIT cell-mediated bacterial control extend to multidrug-resistantE. coliprimary clinical isolates additionally resistant to carbapenems, a class of last resort antibiotics. Notably, high levels of granulysin and granzyme B in the MAIT cell secretomes directly damage bacterial cells by increasing their permeability, rendering initially resistantE. colisusceptible to the bactericidal activity of carbapenems. These findings define the role of cytolytic effector proteins in MAIT cell-mediated antimicrobial activity, and indicate that granulysin and granzyme B synergize to restore carbapenem bactericidal activity and overcome carbapenem resistance inE. coli.

One Sentence Summary

Potent antimicrobial activity of human MAIT cells overcomes carbapenem-resistance in control ofEscherichia coli
Coalescence of rhizobial communities in soil interacts with fertilization and determines the assembly of rhizobia in root nodules
Authors: Ramoneda Josep , Le Roux Johannes , Stadelmann Stefanie , Frossard Emmanuel , Frey Beat , Gamper Hannes Andres
Published: January 2020

Soil microbial community coalescence, whereby entire microbial communities mix and compete in a new environmental setting, is a widespread phenomenon whose applicability for targeted root microbiome assembly has not been studied. Using a legume shrub adapted to nutrient poor soil, we tested for the first time how the assembly of communities of rhizobial root nodule symbionts is affected by the interaction of coalescence and fertilization. Seedlings of the rooibos [Aspalathus linearis(Burm.f.) Dahlg.], were raised in pairwise mixtures of soil from cultivated and uncultivated land of five farms, as well as the individual mixture components. A fragment of the symbiosis maker gene,nodA, was sequenced to characterize the taxonomic turnover of the rhizobia associated with all root nodules at the age of eight month. Soil mixing promoted taxonomic turnover in the rhizobial communities, while fertilization amplified such turnover by increasing the number of rhizobia that became more abundant after soil mixing. Soil mixing and fertilization had a synergistic effect on the abundance of a particular taxon, which was rare in the component soils but became highly abundant in fertilized plants raised in soil mixtures. These findings provide the first evidence that fertilizer addition can interact with soil microbial community coalescence, probably through increasing the chances for rare strains to prioritize root nodule colonization. The combination of soil mixing and fertilizer addition may be a still unexplored measure to (re)introduce root microbial mutualists in arable land.
Fusion Pore Formation Observed During SNARE-Mediated Vesicle Fusion with Pore-Spanning Membranes
Authors: Mühlenbrock P. , Herwig K. , Vuong L. , Mey I. , Steinem C.
Published: January 2020

Planar pore-spanning membranes (PSMs) have been shown to be a versatile tool to resolve docking and elementary steps of the fusion process with single large unilamellar vesicles (LUVs). However, in previous studies, we monitored only lipid mixing and did not gather information about the formation of fusion pores. To address this important step of the fusion process, we entrapped sulforhodamine B at self-quenching concentrations into LUVs containing the v-SNARE synaptobrevin 2, which were docked and fused with lipid-labeled PSMs containing the t-SNARE acceptor complex ΔN49 prepared on porous silicon substrates. By dual color spinning disc fluorescence microcopy with a time resolution of 20 ms, we could unambiguously distinguish between bursting vesicles and fusion pore formation. Owing to the aqueous compartment underneath the PSMs, vesicle bursting turned out to be an extremely rare event (< 0.01 %). From the time-resolved dual color fluorescence time traces, we were able to identify different fusion pathways including remaining three-dimensional postfusion structures with released content and flickering fusion pores. Our results on fusion pore formation and lipid diffusion from the PSM into the fusing vesicle let us conclude that the content release, i.e., fusion pore formation follows the merger of the two lipid membranes by only about 40 ms.

STATEMENT OF SIGNIFICANCE

Despite great efforts to developin vitrofusion assays to understand the process of neuronal fusion, there is still a huge demand to provide single vesicle fusion assays that simultaneously report on all intermediate states including three-dimensional postfusion structures and fusion pore formation including flickering pores without the underlying artifact of vesicle bursting. Here, we show that pore-spanning membranes (PSMs) are ideal candidates to fulfill these demands. Owing to their planarity and the second aqueous compartments, they are readily accessible by fluorescence microscopy and provide sufficient space so that vesicle bursting becomes negligible. Dual color fluorescence microscopy allows distinguishing between different fusion intermediates and fusion pathways such as “kiss and run” fusion as well as flickering fusion pores.
Loss of Caveolin-1 and caveolae leads to increased cardiac cell stiffness and functional decline of the adult zebrafish heart
Authors: Grivas Dimitrios , González-Rajal Álvaro , Rodríguez Carlos Guerrero , Garcia Ricardo , de la Pompa José Luis
Published: January 2020

Caveolin-1 is the main structural protein of caveolae, small membrane invaginations involved in signal transduction and mechanoprotection. Here, we generatedcav1-KOzebrafish lacking Cav1 and caveolae, and investigated the impact of this loss on adult heart function and response to cryoinjury. We found that cardiac function was impaired in adultcav1-KOfish, which showed a significantly decreased ejection fraction and heart rate. Using atomic force microscopy, we detected an increase in the stiffness of epicardial cells and cortical myocardium lacking Cav1/caveolae. This loss of cardiac elasticity might explain the decreased cardiac contraction and function. Surprisingly,cav1-KOmutants were able to regenerate their heart after a cryoinjury but showed a transient decrease in cardiomyocyte proliferation.
Golgi SM protein Sly1 promotes productivetrans-SNARE complex assembly through multiple mechanisms
Authors: Duan M. , Gao G. , Banfield D.K. , Merz A.J.
Published: January 2020

SNARE chaperones of the Sec1/mammalian Unc-18 (SM) family have critical roles in SNARE-mediated membrane fusion. Using SNARE and Sly1 mutants, and a newin vitroassay of fusion, we separate and assess proposed mechanisms through which Sly1 augments fusion: (i) opening the closed conformation of the Qa-SNARE Sed5; (ii) close-range tethering of vesicles to target organelles, mediated by the Sly1-specific regulatory loop; and (iii) preferential nucleation of productivetrans-SNARE complexes. We show that all three mechanisms are important and operate in parallel, and we present evidence that close-range tethering is particularly important fortrans-complex assembly whencis-SNARE assembly is a competing process. In addition, the autoinhibitory N-terminal Habc domain of Sed5 has at least two positive activities: the Habc domain is needed for correct Sed5 localization, and it directly promotes Sly1-dependent fusion. Remarkably, “split Sed5,” with the Habc domain present only as a soluble fragment, is functional bothin vitroandin vivo.
Pulmonary ductal coarctation and left pulmonary artery interruption; pathology and role of neural crest and second heart field during development
Authors: Gittenberger-de Groot Adriana C. , Peterson Joshua C. , Wisse Lambertus J. , Roest Arno A.W. , Poelmann Robert E. , Bökenkamp Regina , Elzenga Nynke J. , Hazekamp Mark , Bartelings Margot M. , Jongbloed Monique R.M. , DeRuiter Marco C.
Published: January 2020

Background In a normal neonatal heart the ductus arteriosus forms the direct continuity of the pulmonary trunk to the descending aorta being the main channel for the prenatal blood flow. The pulmonary arteries originate separately from the pulmonary trunk. In congenital heart malformations with pulmonary stenosis to atresia there is often an abnormal lateral DA to left pulmonary artery connection combined with a localised narrowing (pulmonary ductal coarctation / PDC) or even interruption. We investigated embryonic remodelling and pathogenesis of this area Material and methods Normal development was studied in WntCre reporter mice (E10.0-12.5) for neural crest cells and Nkx2.5 immunostaining for second heart field cells. Data were compared to stage matched human embryos including histopathology of neonatal specimen, and a VEGF120/120 mutant mouse strain developing pulmonary atresia. Results Normal mouse and human embryos showed that, in the early embryo, the mid-pharyngeal endothelial plexus, partly covered by second heart field, connected side-ways to the 6 th pharyngeal arch artery (PAA). The ventral segment of this PAA effectively formed the proximal pulmonary artery. The origin of the cells encasing the endothelial tubes differed significantly. The dorsal 6 th PAA segment (future DA on the left side) was solely surrounded by neural crest cells. The ventral segment had a dual outer lining with neural crest cells laterally and second heart field cells medially, while the distal pulmonary artery was covered by neither of these cells. The asymmetric contribution of second heart field to the future pulmonary trunk on the left side of the aortic sac (so-called pulmonary push) was evident. During remodelling the ventral segment of the 6 th PAA became incorporated into the pulmonary trunk leading to a separate connection of the left and right pulmonary arteries to the latter. The VEGF120/120 embryos showed a severely stunted pulmonary push and later on a variety of vascular anomalies in the DA to pulmonary artery connections. Conclusion Side-way connection of the DA to the left pulmonary artery is a congenital anomaly. The primary problem is a stunted development of the second heart field-derived pulmonary push leading to pulmonary stenosis/atresia and a subsequent lack of proper incorporation of the ventral segment of the 6 th PAA into the aortic sac. Clinically, the aberrant smooth muscle tissue of the DA should be addressed to prohibit development of severe PDC or even interruption of the left pulmonary artery.
The first coordination compound of deprotonated 2-bromonicotinic acid: crystal structure of a dinuclear paddle-wheel copper(II) complex
Authors: Politeo Nives , Pisačić Mateja , Đaković Marijana , Sokol Vesna , Kukovec Boris-Marko
Published: January 2020

A copper(II) dimer with the deprotonated anion of 2-bromonicotinic acid (2-BrnicH), namely, tetrakis(μ-2-bromonicotinato-κ2
O:O′)bis[aquacopper(II)](Cu—Cu), [Cu2(H2O)2(C6H3BrNO2)4] or [Cu2(H2O)2(2-Brnic)4], (1), was prepared by the reaction of copper(II) chloride dihydrate and 2-bromonicotinic acid in water. The copper(II) ion in 1 has a distorted square-pyramidal coordination environment, achieved by four carboxylate O atoms in the basal plane and the water molecule in the apical position. The pair of symmetry-related copper(II) ions are connected into a centrosymmetric paddle-wheel dinuclear cluster [Cu...Cu = 2.6470 (11) Å] via four O,O′-bridging 2-bromonicotinate ligands in the syn-syn coordination mode. In the extended structure of 1, the cluster molecules are assembled into an infinite two-dimensional hydrogen-bonded network lying parallel to the (001) plane via strong O—H...O and O—H...N hydrogen bonds, leading to the formation of various hydrogen-bond ring motifs: dimeric R
2
2(8) and R
2
2(16) loops and a tetrameric R
4
4(16) loop. The Hirshfeld surface analysis was also performed in order to better illustrate the nature and abundance of the intermolecular contacts in the structure of 1.
Cognitive dissonance revisited
Authors: Brooksbank Roger , Fullerton Sam
Published: January 2020

Purpose

In revisiting Festinger's theory of cognitive dissonance, this paper seeks to go beyond traditional business-to-consumer (B2C) research parameters and explore the full extent of its potential application within a New Zealand business-to-business (B2B) purchasing context.

Design/methodology/approach

The study's core findings are based on four separate focus group discussions with B2B salespeople. Responses were recorded and analysed according to the manifest content of the discussions. These focus groups were preceded by, and followed up with, two other enquiries that sought the perspectives of B2B buyers.

Findings

Intended for use as a learning tool for aspiring B2B salespeople and their instructors, a new typology of four generic potential post-decision ‘cognitive states’ is proposed, which, depending on the scenario at hand, will likely reflect the buyer's mindset.

Research limitations/implications

The generalisation of findings may be somewhat limited because the focus groups were drawn from a convenience sample totalling just 20 practitioners. Some participants might also have felt slightly constrained, leading to opinions that are subject to bias.

Practical implications

Examples of differing buying scenarios are profiled and explained from the perspective of their implications for salespeople. Suggestions as to how sellers can best accommodate the post-decision cognitive states experienced by their buyers are delineated.

Originality/value

Conventional wisdom suggests that post-purchase cognitive dissonance is the sole ‘cognitive state’ towards which a B2B salesperson needs to be attuned to for the purpose of taking some form of accommodating action. However, this study indicates that three other states relating to the aftermath of a buyer's decision, whether a purchase is made or not, also merit attention.
Carroll’s dimensions and CSR disclosure: empirical evidence from Pakistan
Authors: Hamid Samreen , Riaz Zahid , Azeem Syed Muhammad Waqar
Published: January 2020

Purpose

This study aims to ascertain the relevance of Carroll’s four dimensions of corporate social responsibility (CSR), namely, economic, legal, ethical and discretionary in a dynamic regulatory context of a developing economy – Pakistan.

Design/methodology/approach

This study has operationalized these dimensions as four categories of CSR disclosure index. This disclosure index measured the relevance of CSR dimensions by examining CSR disclosure practices of Pakistan Stock Exchange-100 index firms.

Findings

The authors have found that the firms of Pakistan disclose more information pertaining to discretionary dimension of CSR than economic, legal and ethical dimensions. Interestingly, the authors have observed that after the enactment of state regulation, there is an increasing trend of the overall CSR disclosure level at a decreasing rate.

Practical implications

For policymakers, these findings imply that firms tend to perceive law as a box-ticking exercise and refrain to involve in those CSR activities that can have both strategic and societal benefits over the long run. These finding imply for business managers that if they will not undertake CSR notion seriously then the policymakers will take statutory initiatives to curtail the greenwashing effect and these initiatives can lead to higher transaction costs.

Originality/value

This study presents evidence about the relevance of Carroll’s four dimensions of CSR in a developing economy. The evidence shows that the CSR disclosure in developing economy continues to take a largely philanthropic form thereby dominating other CSR dimensions namely ethical, legal and economic. These findings also confirm that CSR practices are context-dependent and these cannot be isolated from their unique social context.
Sustainability evaluation of additive manufacturing processes using grey-based approach
Authors: Agrawal Rohit , S. Vinodh
Published: January 2020

Purpose

Sustainable manufacturing facilitates the development of products with lower environmental impact. Additive manufacturing (AM) processes are incorporated with sustainable characteristics such as minimum material consumption, energy efficiency and minimum transportation. The purpose of this paper is to report a study on sustainability evaluation of AM process using a grey-based approach.

Design/methodology/approach

Sustainable AM process is gaining importance. From this viewpoint, this paper presents the evaluation of sustainability of AM process. The evaluation model includes 3 enablers, 18 criteria and 54 attributes. Grey-based approach is used for sustainability evaluation. Expert inputs are used for computing the grey index. Expert inputs are obtained and they are aggregated at three levels to calculate the overall grey performance index, which indicates sustainability level of AM processes. Furthermore, weaker areas are identified through determination of grey performance importance index (GPII) values.

Findings

The calculated grey index is (3.510, 16.177), which implies that AM process is sustainable. Weaker attributes are determined on the basis of the computation of GPII values.

Practical implications

The study has been executed on the basis of the opinion from experts with practical experience. Hence, the inferences are found to be practically feasible. The identified weaker attributes from the study would enable the manufacturers and practitioners to focus more on weaker areas for enhancing the sustainability of AM processes. The study has made an evaluation from sustainability perspective of AM processes, which would enable practitioners to assess AM processes from TBL sustainability orientation.

Originality/value

The development of sustainability evaluation model and application of a grey-based approach for assessment of AM process are the original contributions of this study.
A hybrid model for energy efficient spectrum sensing in cognitive radio
Authors: Bhowmik Mahua , P. Malathi P. Malathi
Published: January 2020

Purpose

Cognitive radio (CR) plays a very important role in enabling spectral efficiency in wireless communication networks, where the secondary user (SU) allows the licensed primary users (PUs). The purpose of this paper is to develop a prediction model for spectrum sensing in CR.

Design/methodology/approach

This paper proposes a hybrid prediction model, called krill-herd whale optimization-based actor critic neural network and hidden Markov model (KHWO-ACNN-HMM). The spectral bands are determined optimally using the proposed hybrid prediction model for allocating the spectrum bands to the PUs. For better sensing, the eigenvalue based on cooperative sensing used in CR. Finally, a hybrid model is designed by hybridizing KHWO-ACNN and HMM to enhance the accuracy of sensing. The predicted results of KHWO-ACNN and HMM are combined by a fusion model, for which a weighted entropy fusion is employed to determine the free spectrum available in CRs.

Findings

The performance of the prediction model is evaluated based on metrics, such as probability of detection, probability of false alarm, throughput and sensing time. The proposed spectrum sensing method achieves maximum probability of detection of 0.9696, minimum probability of false alarm rate as 0.78, minimum throughput of 0.0303 and the maximum sensing time of 650.08 s.

Research implications

The proposed method is useful in various applications, including authentication applications, wireless medical networks and so on.

Originality/value

A hybrid prediction model is introduced for energy efficient spectrum sensing in CR and the performance of the proposed model is evaluated with the existing models. The proposed hybrid model outperformed the other techniques.
New configurations in Brazilian agribusiness: rural warehouse condominiums
Authors: Filippi Amanda Cristina Gaban , Guarnieri Patricia , Carvalho José Márcio , Reis Silvia Araújo , da Cunha Cleyzer Adrian
Published: January 2020

Purpose

The purpose of this paper is to analyze the development of rural warehouses condominiums (or “condos”) as new rural configurations in the Brazilian agribusiness from the perspective of the theory of collective action.

Design/methodology/approach

A systematic literature review was complemented with multiple case studies based on interviews and direct observation. Content analysis was used to interpret the secondary and primary data.

Findings

Rural warehouse condos can be characterized as a collective action which is a new business model in Brazilian agribusiness. This new initiative has several advantages: reduction of the warehouse deficit and other logistical bottlenecks; strategic commercialization of production; reduction of logistical costs; inclusion of smallholders in the economy and, consequently, the generation of income for smallholders and their participation in the market.

Research limitations/implications

The study used a qualitative approach and findings and discussion are inherently interpretative.

Social implications

Understanding the organization of rural warehouse condos supports the inclusion of smallholding farmers and income generation. This creates a social benefit through rural growth and economic development. Some constraints related to the lack of public policies, specific credit lines in financial institutions, the problem of non-regularized rural areas, lack of transparency and conflicts among the members can limit expansion.

Originality/value

Rural warehouse condos are expanding mainly in the south region of Brazil, where smallholders are concentrated. In this new configuration, they can engage in an association to obtain several benefits, such as reduced logistics costs, better access to financing and increased bargaining power with suppliers. As this research dealt with a relatively new and poorly studied topic, it contributes to the development of new studies to map innovative warehousing practices.
Exploring entrepreneurial-group formation by smallholder Burundian farmers
Authors: Mupfasoni Bélyse , Kessler Aad , Lans Thomas , Ngenzebuke Rama Lionel
Published: January 2020

Purpose

The purpose of this paper is to analyze the role of specific internal states (i.e. the set of sustainable values and motivations) that underlie group formation and joint business idea identification of farmer groups in the context of Burundi.

Design/methodology/approach

Quantitative and qualitative data were combined in this study. Quantitative data were analyzed using basic statistics. Qualitative data were collected in focus group discussions with farmer groups.

Findings

Findings revealed that groups are not just formed on the basis of homophily (same level of internal states) but also on “compensation” and “committed leadership.” Moreover, prior sustainable behavior of members influences sustainability of new group business ideas and the nature (e.g. focus on farming) of that business idea.

Research limitations/implications

As this study was done at an early stage of group formation and does not include group dynamics over a longer period of time, further monitoring of the groups is needed to examine if the observed motivation persists.

Originality/value

Although there is a vast amount of literature on entrepreneurial and top management teams, literature on the (early) mechanisms of entrepreneurial group formation in an emerging economy and rural context is relatively scarce.
Managers’ regulatory focus, temporal focus and exploration–exploitation activities
Authors: Tuncdogan Aybars , Dogan Ismail Cagri
Published: January 2020

Purpose

The purpose of this paper is to examine and gain further insight into the potential link between regulatory focus and exploration–exploitation at the individual manager level. More specifically, the authors hypothesised that temporal focus would act as a mediator in the relationship between managers’ regulatory foci and exploration–exploitation activities.

Design/methodology/approach

A survey was conducted with 541 managers from the USA. The model was tested using OLS regression models, followed by bootstrapped multiple-mediation analyses.

Findings

Managers’ promotion and prevention foci are associated with the extent to which they focus on the past, the present and the future, which is related to managers’ exploration and exploitation activities.

Research limitations/implications

The findings rely on self-report data.

Practical implications

This paper examines the chronic strategic tendencies of managers with different levels of promotion and prevention focus – in particular, the timeframes they are likely to focus on and exploration–exploitation levels they are likely to engage in. In doing so, this paper provides managers a way to detect and overcome their chronic strategic shortcomings.

Originality/value

This paper not only examines the link between regulatory focus and exploration–exploitation at the individual level, but also provides further insights regarding the nature of this relationship. More specifically, by putting forward temporal focus as a mediator of this relationship, this study contributes to the ongoing discussion about the potential link between regulatory focus and exploration–exploitation, and poses new questions for future research.
Brand engagement and experience in online services
Authors: Khan Imran , Hollebeek Linda D. , Fatma Mobin , Islam Jamid Ul , Rahman Zillur
Published: January 2020

Purpose

The purpose of this study is to assess the mediating role of brand trust and commitment in the relationship of brand engagement and brand experience with brand loyalty in the online service context.

Design/methodology/approach

To achieve the study’s objective, 414 users of virtual service brands, predominantly in the online banking, airline and hotel sectors, were surveyed.

Findings

Both brand engagement and experience exert direct effects on brand trust and commitment, as well as indirect effects on brand commitment (via brand trust) and service brand loyalty (via brand commitment).

Research limitations/implications

This paper adds to the literature by incorporating brand engagement, experience, trust and commitment into a unifying framework. The framework emphasizes brand trust and commitment’s mediating role in the relationship that brand engagement and experience share with brand commitment and loyalty in the online service context.

Practical implications

Marketers should formulate online brand engagement and experience strategies that strengthen customer brand trust and commitment, which are expected to exert a significant brand loyalty-enhancing effect.

Originality/value

Brand engagement and experience were validated as key drivers of brand trust and commitment, thereby further substantiating their role as important strategic metrics. Moreover, the role of commitment as a mediating factor in the association between brand engagement and experience and their respective impact on brand loyalty has been verified. Although the findings suggest that improved brand engagement/experience contributes to brand loyalty, this effect transpires only though brand commitment.