bluuebunny/crossref_metadata_2025 huggingface dataset:
Diversification of Transcription Factor NF-κB in Protists
Authors: Williams Leah M. , Sridhar Sainetra , Samaroo Jason , Adindu Ebubechi K. , Addanki Anvitha ,   BB522 Molecular Biology Laboratory, Aguirre Carrión Pablo J. , DiRusso Christopher J. , Rodriguez-Sastre Nahomie , Siggers Trevor , Gilmore Thomas D.
Published: March 2021

In this report, we investigate the evolution of transcription factor NF-κB by examining its structure, activity, and regulation in two protists using phylogenetic, cellular, and biochemical techniques. InCapsaspora owczarzaki(Co), we find that full-length NF-κB has an N-terminal DNA-binding domain and a C-terminal Ankyrin (ANK) repeat inhibitory domain, and its DNA-binding activity is more similar to metazoan NF-κB rather than Rel proteins. As with mammalian NF-κB proteins, removal of the ANK repeats is required forCo-NF-κB to enter the nucleus, bind DNA, and activate transcription. However, C-terminal processing ofCo-NF-κB is not induced by co-expression of IKK in human cells. Exogenously expressedCo-NF-κB localizes to the nucleus inCocells. NF-κB mRNA and DNA-binding levels differ across three life stages ofCapsaspora, suggesting distinct roles for NF-κB in these life stages. RNA-seq and GO analyses identify possible gene targets and biological functions ofCo-NF-κB. We also show that three NF-κB-like proteins from the choanoflagellateAcanthoeca spectabilis(As) all consist of primarily the N-terminal conserved Rel Homology domain sequences of NF-κB, and lack C-terminal ANK repeats. All threeAs-NF-κB proteins constitutively enter the nucleus of human and Co cells, but differ in their DNA-binding and transcriptional activation activities. Furthermore, all threeAs-NF-κB proteins can form heterodimers, indicating that NF-κB diversified into multi-subunit families at least two times during evolution. Overall, these results present the first functional characterization of NF-κB in a taxonomic kingdom other than Animalia and provide information about the evolution and diversification of this biologically important transcription factor.

Significance

These results represent the first functional characterization of the biologically important transcription factor NF-κB in a taxonomic kingdom other than Animalia. As such, they provide information on the evolutionary origins and basal diversification of NF-κB outside of metazoans. These results suggest that NF-κB plays life stage-specific roles inCapsaspora, the closest unicellular ancestor to all metazoans. Finally, the analysis of three NF-κB proteins in a single choanoflagellate indicates that choanoflagellates have subclasses of NF-κBs, which can form heterodimers, suggesting that NF-κB subunit expansion and diversification has occurred at least twice in evolution.
Anatomical and Functional Gradients Shape Dynamic Functional Connectivity in the Human Brain
Authors: Kong Xiaolu , Kong Ru , Orban Csaba , Peng Wang , Zhang Shaoshi , Anderson Kevin , Holmes Avram , Murray John D. , Deco Gustavo , van den Heuvel Martijn , Yeo B.T. Thomas
Published: March 2021

Large-scale biophysical circuit models can provide mechanistic insights into the fundamental micro-scale and macro-scale properties of brain organization that shape complex patterns of spontaneous brain activity. By allowing local synaptic properties to vary across brain regions, recent large-scale circuit models have demonstrated better fit to empirical observations, such as inter-regional synchrony averaged over several minutes, i.e. static functional connectivity (FC). However, most previous models do not capture how inter-regional synchrony patterns vary over timescales of seconds, i.e., time-varying FC dynamics. Here we developed a spatially-heterogeneous large-scale dynamical circuit model that allowed for variation in local circuit properties across the human cortex. We showed that parameterizing local circuit properties with both anatomical and functional gradients was necessary for generating realistic static and dynamical properties of resting-state fMRI activity. Furthermore, empirical and simulated FC dynamics demonstrated remarkably similar sharp transitions in FC patterns, suggesting the existence of multiple attractors. We found that time-varying regional fMRI amplitude tracked multi-stability in FC dynamics. Causal manipulation of the large-scale circuit model suggested that sensory-motor regions were a driver of FC dynamics. Finally, the spatial distribution of sensory-motor drivers matched the principal gradient of gene expression that encompassed certain interneuron classes, suggesting that heterogeneity in excitation-inhibition balance might shape multi-stability in FC dynamics.
GTP and lipids control self-assembly and functional promiscuity of Dynamin2 molecular machinery
Authors: Espadas Javier , Bocanegra Rebeca , Martinez-Galvez Juan Manuel , Largo Eneko , Baños-Mateos Soledad , Arrasate Pedro , Guisasola Julene Ormaetxea , Velasco-Olmo Ariana , Lillo Javier Vera , Ibarra Borja , Shnyrova Anna V. , Frolov Vadim A.
Published: March 2021

Dynamin2 GTPase (Dyn2) is a crucial player in clathrin-mediated endocytosis. Dyn2 is tetrameric in cytoplasm and self-assembles into functional units upon membrane binding. How the curvature activities and functionality of Dyn2 emerge during self-assembly and are regulated by lipids remains unknown. Here we reconstituted the Dyn2 self-assembly process using membrane nanotubes (NT) and vesicles and characterized it using single- molecule fluorescence microscopy, optical tweezers force spectroscopy and cryo-electron microscopy. On NTs, Dyn2 first forms small subhelical oligomers, which are already curvature active and display pronounced curvature sensing properties. Conical lipids and GTP promote their further self-assembly into helical machinery mediating the NT scission. In the presence of large unilamellar vesicles (LUVs), an alternative self- assembly pathway emerges where the subhelical oligomers form membrane tethering complexes mediating LUV-NT binding. Reconstitution of tethering in the LUV system revealed that lipid mixing is controlled by conical lipid species, divalents, GTP, and SH3 binding partners of Dyn2. In membranes with a high content of lipids with negative intrinsic curvature, cryo-EM revealed putative membrane contact sites made by Dyn2 clusters. On such membranes, with GTP lowered to 0.2 mM, both membrane fission and tethering activities become possible, indicating functional promiscuity of Dyn2.

We conclude that GTP and lipids control both extent and topology of Dyn2 functional self-assembly. The function of Dyn2 oligomers evolves from curvature sensing, seen in subhelical Dyn2 oligomers, to curvature creation and fission, seen in Dyn2 helices. Under specific circumstances, such as downregulation of SH3 partners of Dyn2 and GTP depletion, membrane tethering activity can emerge in membrane systems enriched with conical lipids. Hence the Dyn2 functionality is actively adapted to lipidome, explaining its large habitat in the cells and tissues.
Intertissue mechanical interactions shape the olfactory circuit in zebrafish
Authors: Monnot P , Gangatharan G , Baraban M , Pottin K , Cabrera M , Bonnet I , Breau MA
Published: March 2021

While the chemical signals guiding neuronal migration and axon elongation have been extensively studied, the influence of mechanical cues on these processes remains poorly studiedin vivo. Here, we investigate how mechanical forces exerted by surrounding tissues steer neuronal movements and axon extension during the morphogenesis of the olfactory placode in zebrafish. We mainly focus on the mechanical contribution of the adjacent eye tissue, which develops underneath the placode through extensive evagination and invagination movements. Using quantitative analysis of cell movements and biomechanical manipulations, we show that the developing eye exerts lateral traction forces on the olfactory placode through extracellular matrix, mediating proper morphogenetic movements and axon extension within the placode. Our data shed new light on the key participation of intertissue mechanical interactions in the sculpting of neuronal circuits.
Mobile elements habouring heavy metal and bacitracin resistance cassettes are common amongListeria monocytogenespersisting on dairy farms
Authors: Castro Hanna , Douillard Francois , Korkeala Hannu , Lindström Miia
Published: March 2021

Listeria monocytogenesis a food-borne pathogen and a resilient environmental saprophyte. Dairy farms are a reservoir ofL. monocytogenesand strains can persist on farms for years. Here, we sequenced the genomes of 250L. monocytogenesisolates to investigate the persistence and mobile genetic elements ofListeriainhabiting dairy farms. We performed a SNP-based phylogenomic analysis to identify 14 monophyletic clades ofL. monocytogenesthat persistent on the farms for ≥ 6 months. We found that prophages and other mobile genetic elements were on average more numerous among isolates in persistent than nonpersistent clades, and demonstrated that resistance genes against bacitracin, arsenic and cadmium were significantly more prevalent among isolates in persistent than nonpersistent clades. We identified a diversity of mobile elements among the 250 farm isolates, including three novel plasmids, three novel transposons and a novel prophage harbouring cadmium resistance genes. Several of the mobile elements we identified inListeriawere identical to the mobile elements ofEnterococci, indicative of recent transfer between these genera. Finally, we demonstrated that the CRISPR-casIIa system and a type II restriction-modification system were negatively associated with persistence on farms. Our findings suggest that mobile elements support the persistence ofL. monocytogeneson dairy farms and thatL. monocytogenesinhabiting the agroecosystem is a potential reservoir of mobile elements that may spread to the food industry.

Importance

Animal derived raw materials are an important source ofL. monocytogenesfor the food industry. Knowledge of the factors contributing to the pathogen’s transmission and persistence on farms are essential for designing effective strategies against the spread of the pathogen from farm to fork. An increasing body of evidence suggests that mobile genetic elements support the adaptation and persistence ofL. monocytogenesin the food industry, as these elements contribute to the dissemination of genes encoding favourable phenotypes, such as resilience against biocides and thermal stress. Understanding the role of farms as a potential reservoir of these elements is needed for managing the transmission of mobile elements across the food chain. BecauseL. monocytogenescoinhabits the farm ecosystem with a diversity of other bacterial species, it is important to assess the degree to which genetic elements are exchanged betweenListeriaand other species, as such exchanges may contribute to rise the novel resistance phenotypes.
Low pathogenic avian influenza virus infection retards colon microbiome diversification in two different chicken lines
Authors: Chrzastek Klaudia , Leng Joy , Zakaria Mohammad Khalid , Bialy Dagmara , La Ragione Roberto , Shelton Holly
Published: March 2021

A commensal microbiome regulates and is in turn regulated by viruses during host infection which can influence virus infectivity. In this study, analysis of colon microbiome population changes following a low pathogenicity avian influenza virus (AIV) of the H9N2 subtype infection of two different chicken breeds was conducted. Using 16S rRNA sequencing and subsequent data analysis we found reduced microbiome alpha diversity in the acute period of AIV infection (day 2-3) in both Rhode Island Red and VALO chicken lines. From day 4 post infection a gradual increase in diversity of the colon microbiome was observed, but the diversity did not reach the same level as in uninfected chickens by day 10 post infection, suggesting that AIV infection retards the natural accumulation of colon microbiome diversity, which may further influence chicken health following recovery from infection. Beta diversity analysis indicated differences in diversity between the chicken lines during and following acute influenza infection suggesting the impact of host gut microflora dysbiosis following H9N2 influenza virus infection could differ for different breeds.
Echolocation reverses information flow in a cortical vocalization network
Authors: García-Rosales Francisco , López-Jury Luciana , Gonzalez-Palomares Eugenia , Wetekam Johannes , Cabral-Calderín Yuranny , Kiai Ava , Kössl Manfred , Hechavarría Julio C.
Published: March 2021

The mammalian frontal and auditory cortices are important for vocal behaviour. Here, using local field potential recordings, we demonstrate for the first time that the timing and spatial pattern of oscillations in the fronto-auditory cortical network of vocalizing bats (Carollia perspicillata) predict the purpose of vocalization: echolocation or communication. Transfer entropy analyses revealed predominantly top-down (frontal-to-auditory cortex) information flow during spontaneous activity and pre-vocal periods. The dynamics of information flow depended on the behavioural role of the vocalization and on the timing relative to vocal onset. Remarkably, we observed the emergence of predominantly bottom-up (auditory-to-frontal cortex) information transfer patterns specific echolocation production, leading to self-directed acoustic feedback. Electrical stimulation of frontal areas selectively enhanced responses to echolocation sounds in auditory cortex. These results reveal unique changes in information flow across sensory and frontal cortices, potentially driven by the purpose of the vocalization in a highly vocal mammalian model.
Microbial diversity in raw milk and Sayram Ketteki from southern of Xinjiang, China
Authors: Gao DongLa , Wang Weihua , Han ZhanJiang , Xi Qian , Guo RuiCheng , Kuang PengCheng , Li DongLiang
Published: March 2021

Raw milk and fermented milk are rich in microbial resources, which are essential for the formation of texture, flavor and taste. In order to gain a deeper knowledge of the bacterial and fungal community diversity in local raw milk and home-made yogurts from Sayram town, Baicheng county, Akesu area, southern of Xinjiang, China,30 raw milk and 30 home-made yogurt samples were collected and experiment of high-throughput sequencing was implemented.The results of experiments revealed the species of fungi in raw milk was the most, and the species of bacteria in fermented milk was the least.Based on principal component analysis (PCA), it was found that the bacterial and fungal community structure differed in samples from two types of dairy products.And the presence of 15 bacterial and 12 fungal phyla, comprising 218 bacterial and 495 fungal genera respectively, among all samples. Firmicutes and Ascomycota,Lactobacillus and Candida were the predominant phyla and genera of bacteria and fungi, respectively. The results indicated that the microbial community of raw milk differs from home-made yogurts due to sampling location and manufacturing process. The study suggested that high-throughput sequencing could provide a better understanding of microbiological diversity as well as lay a theoretical foundation for selecting beneficial microbial resources from this natural yogurt.
Effect of nandrolone decanoate on healing of experimentally induced radial nonunion in rabbits (Oryctolagus cuniculus)
Authors: Dissenha Adrielly , Minto Bruno Watanabe , Calciolari Karina , Sargi Laís Fernanda , do Nascimento Lismara Castro , Del Lama Rocha Fabiana , Galindez Julián Andrés Sanjuán , de Lucena Dayvid Vianêis Farias , Dias Luis Gustavo Gosuen Gonçalves
Published: March 2021

The aim of this study was to evaluate the effect of nandrolone decanoate (ND) on treatment of bone nonunion in the radius of rabbits. Thirty-one, young adult, New Zealand White rabbits (Oryctolagus cuniculus) were allocated to one of four groups: nandrolone males (NMG), nandrolone females (NFG), placebo males (NPM), and placebo females (NPF). After bone nonunion of a 10 mm ostectomy of the radius was confirmed (45 days after surgery), the animals in the NMG and NFG groups received 10 mg/kg ND intramuscular once a week for four weeks, while placebo groups received intramuscular 0.9% NaCl solution. Radiographic, histopathologic, and densitometric parameters (DXA) were used to compared groups.

Results

No significant differences were observed radiographically. However, ND groups showed greater area (P=0.0258) and BMC (P=0.0140) in the densitometric evaluation. Histologically, the placebo group showed a predominance of primary bone tissue. Whereas, lamellary organizations of secondary bone and the presence of fibrocartilage were found in the ND group (P =0.006). In conclusion, ND promoted bone regeneration after the creation of a large defect in the radius of rabbits.
Primary brain cell infection byToxoplasma gondiireveals the extent and dynamics of parasite differentiation and its impact on neuron biology
Authors: Mouveaux Thomas , Roger Emmanuel , Gueye Alioune , Eysert Fanny , Huot Ludovic , Grenier-Boley Benjamin , Lambert Jean-Charles , Gissot Mathieu
Published: March 2021

Toxoplasma gondiiis a eukaryotic parasite that forms latent cysts in the brain of immunocompetent individuals. The latent parasite infection of the immune-privileged central nervous system is linked to most complications. With no drug currently available to eliminate the latent cysts in the brain of infected hosts, the consequences of neurons’ long-term infection are unknown. It has long been known thatT. gondiispecifically differentiates into a latent form (bradyzoite) in neurons, but how the infected neuron responds to the infection remains to be elucidated. We have established a newin vitromodel resulting in the production of mature bradyzoite cysts in brain cells. Using dual, host and parasite RNA-seq, we characterized the dynamics of differentiation of the parasite, revealing the involvement of key pathways in this process. Moreover, we identified how the infected brain cells responded to the parasite infection revealing the drastic changes that take place. We showed that neuronal-specific pathways are strongly affected, with synapse signaling being particularly affected, especially glutamatergic synapse signaling. The establishment of this newin vitromodel allows investigating both the dynamics of parasite differentiation and the specific response of neurons to the long-term infection by this parasite.
Arginine induced Streptococcus gordonii biofilm detachment using a novel rotating-disc rheometry method
Authors: Gloag Erin S. , Wozniak Daniel J. , Wolf Kevin L. , Masters James G. , Daep Carlo Amorin , Stoodley Paul
Published: March 2021

Oral diseases are one of the most common pathologies affecting human health. These diseases are typically associated with dental plaque-biofilms, through either build-up of the biofilm or dysbiosis of the microbial community. Arginine can disrupt dental plaque-biofilms, and maintain plaque homeostasis, making it an ideal therapeutic to combat the development of oral disease. Despite our understanding of the actions of arginine towards dental plaque-biofilms, it is still unclear how or if arginine effects the mechanical integrity of the dental plaque-biofilm. Here we adapted a rotating-disc rheometry assay, which is routinely used in marine microbial ecology, to study how arginine treatment of Streptococcus gordonii biofilms influences biofilm detachment from surfaces. We demonstrate that the assay is highly sensitive at quantifying the presence of biofilm and the detachment or rearrangement of the biofilm structure as a function of shear stress. We demonstrate that arginine treatment leads to earlier detachment of the biofilm, indicating that arginine treatment weakens the biofilm, making it more suspectable to removal by shear stresses. Our results add to the understanding that arginine targets biofilms by multifaceted mechanisms, both metabolic and physical, further promoting the potential of arginine as an active compound in dentifrices to maintain oral health.
Modeling the three-way feedback between cellular contractility, actin polymerization, and adhesion turnover resolves the contradictory effects of RhoA and Rac1 on endothelial junction dynamics
Authors: McEvoy Eoin , Sneh Tal , Moeendarbary Emad , Marino Gloria E. , Chen Xingyu , Escribano Jorge , Spill Fabian , Garcia-Aznar Jose Manuel , Weeraratna Ashani T. , Svitkina Tatyana M. , Kamm Roger D. , Shenoy Vivek B.
Published: March 2021

The formation and recovery of gaps in the vascular endothelium governs a wide range of physiological and pathological phenomena, from angiogenesis to atherosclerosis and tumor cell extravasation. However, the interplay between the mechanical and signaling processes that drive dynamic behavior in vascular endothelial cells is not well understood. In this study, we propose a chemo-mechanical model to investigate the maintenance of endothelial junctions as dependent on the crosstalk between actomyosin contractility, VE-cadherin bond turnover, and actin polymerization, which mediate the forces exerted on the cell-cell interface. Our theoretical model reveals that active cell tension can stabilize cadherin bonds within an adhesion, but excessive RhoA signaling can drive bond dissociation and junction failure. While Rac1-mediated actin polymerization aids gap closure, high levels of Rac1 may also facilitate junction weakening. Combining the modeling framework with novel experiments, we identify how dynamic rupture and heal cycles emerge and, further, describe why gaps tend to localize at multi-cell contacts. Beyond, our analysis also indicates that a critical balance between RhoA and Rac1 expression is required to maintain junction stability and limit endothelial dysfunction. The model predicts how pharmacological modulation of actin polymerization and cell contractility impacts junction stability, with predictions subsequently validated experimentally. Our proposed framework can help guide the development of therapeutics that target the Rho family of GTPases and downstream active mechanical processes.
Complex genetic architecture of three-dimensional craniofacial shape variation in domestic pigeons
Authors: Boer Elena F. , Maclary Emily T. , Shapiro Michael D.
Published: March 2021

Deciphering the genetic basis of vertebrate craniofacial variation is a longstanding biological problem with broad implications in evolution, development, and human pathology. One of the most stunning examples of craniofacial diversification is the adaptive radiation of birds, in which the beak serves essential roles in virtually every aspect of their life histories. The domestic pigeon (Columba livia) provides an exceptional opportunity to study the genetic underpinnings of craniofacial variation because of its unique balance of experimental accessibility and extraordinary phenotypic diversity within a single species. We used traditional and geometric morphometrics to quantify craniofacial variation in an F2 laboratory cross derived from the straight-beaked Pomeranian Pouter and curved-beak Scandaroon pigeon breeds. Using a combination of genome-wide quantitative trait locus scans and multi-locus modeling, we identified a set of genetic loci associated with complex shape variation in the craniofacial skeleton, including beak curvature, braincase shape, and mandible shape. Some of these loci control coordinated changes between different structures, while others explain variation in the size and shape of specific skull and jaw regions. We find that in domestic pigeons, a complex blend of both independent and coupled genetic effects underlie three-dimensional craniofacial morphology.
Preparation ofE. coliRNA polymerase transcription elongation complexes for systematic RNA assays
Authors: Strobel Eric J.
Published: March 2021

RNA folds into secondary and tertiary structures that can mediate diverse cellular functions. Understanding how RNA sequence directs the formation of biologically active structures requires approaches that can comprehensively assess how changes in an RNA sequence affect its structure and function. Towards this goal, I have developed a general method for purifyingE. coliRNA polymerase (RNAP) transcription elongation complexes (TECs) for use in systematic RNA assays. My approach depends on two constituent technologies: First, I have designed anE. coliσ70promoter that can be efficiently barcoded using a one-pot series of enzymatic reactions. Second, I have developed a strategy for purifying promoter-initiatedE. coliRNAP TECs by selective photo-elution from streptavidin-coated magnetic beads. Together, these methods establish a platform for the development of TEC Display assays in which the functional properties of RNA sequence variants can be recorded by fractionating and quantitatively barcoding a TEC library.
Structure Can Predict Function in the Human Brain: A Graph Neural Network Deep Learning Model of Functional Connectivity and Centrality Based on Structural Connectivity
Authors: Neudorf Josh , Kress Shaylyn , Borowsky Ron
Published: March 2021

Although functional connectivity and associated graph theory measures (e.g., centrality; how centrally important to the network a region is) are widely used in brain research, the full extent to which these functional measures are related to the underlying structural connectivity is not yet fully understood. Graph neural network deep learning methods have not yet been applied for this purpose, and offer an ideal model architecture for working with connectivity data given their ability to capture and maintain inherent network structure. This model applied here to predict functional connectivity and centrality from structural connectivity accounted for 89% of the variance in mean functional connectivity, 56% of the variance in individual-level functional connectivity, 99% of the variance in mean functional centrality, and 81% of the variance in individual-level functional centrality. This model provides a new benchmark for performance and represents a novel finding that functional centrality can be robustly predicted from structural connectivity. Regions of particular importance to the model’s performance as determined through lesioning are discussed, whereby regions with higher centrality have a higher impact on model performance. Future research on models of patient, demographic, or behavioural data can also benefit from this graph neural network method as it is ideally-suited for capturing connectivity and centrality in brain networks. These results have set a new benchmark for prediction of functional connectivity from structural connectivity, and models like this may ultimately lead to a way to predict functional connectivity in individuals who are unable to do fMRI tasks (e.g., non-responsive patients).
A model of Ponto-Geniculo-Occipital waves supports bidirectional control of cortical plasticity across sleep-stages
Authors: Shao Kaidi , Ramirez Villegas Juan F. , Logothetis Nikos K. , Besserve Michel
Published: March 2021

During sleep, cortical network connectivity likely undergoes both synaptic potentiation and depression through system consolidation and homeostatic processes. However, how these modifications are coordinated across sleep stages remains largely unknown. Candidate mechanisms are Ponto-Geniculo-Occipital (PGO) waves, propagating across several structures during Rapid Eye Movement (REM) sleep and the transitional stage from non-REM sleep to REM sleep (pre-REM), and exhibiting sleep stage-specific dynamic patterns. To understand their impact on cortical plasticity, we built an acetylcholine-modulated neural mass model of PGO wave propagation through pons, thalamus and cortex, reproducing a broad range of electrophysiological characteristics across sleep stages. Using a population model of Spike-Time-Dependent Plasticity, we show that cortical circuits undergo different transient regimes depending on the sleep stage, with different impacts on plasticity. Specifically, PGO-induced recurrent cortical activities lead to the potentiation of cortico-cortical synapses during pre-REM, and to their depression during REM sleep. Overall, these results shed light on how the dynamical properties of sleep events propagating to cortical circuits can favor different types of local plastic changes. The variety of events occurring across sleep stages may thus be instrumental in controlling the reorganization of cortical networks from one day to the next.

Significance statement

Considerable evidence supports rescaling of cortical synaptic connec-tions during sleep, requiring both long term potentiation to consolidate newly acquired memories, and long-term depression to maintain homeostatic levels of brain activity. However, which aspects of sleep activity contribute to this bidirectional control of plasticity remains unclear. This computational modeling study suggests that widespread transient phenomena called Ponto-geniculo-occipital (PGO) waves, have a sleep-stage dependent effect on plasticity. The alternation between sleep stages can thus be exploited in combination with spontaneously occurring transients, to trigger both up- and down-regulating effects on cortical connectivity, and may explain why the basic structure of sleep-cycles is a well-preserved property across mammalian species.
Encoding innate ability through a genomic bottleneck
Authors: Koulakov Alexei , Shuvaev Sergey , Lachi Divyansha , Zador Anthony
Published: March 2021

Abstract

Animals are born with extensive innate behavioral capabilities, which arise from neural circuits encoded in the genome. However, the information capacity of the genome is orders of magnitude smaller than that needed to specify the connectivity of an arbitrary brain circuit, indicating that the rules encoding circuit formation must fit through a “genomic bottleneck” as they pass from one generation to the next. Here we formulate the problem of innate behavioral capacity in the context of artificial neural networks in terms of lossy compression of the weight matrix. We find that several standard network architectures can be compressed by several orders of magnitude, yielding pre-training performance that can approach that of the fully-trained network. Interestingly, for complex but not for simple test problems, the genomic bottleneck algorithm also captures essential features of the circuit, leading to enhanced transfer learning to novel tasks and datasets. Our results suggest that compressing a neural circuit through the genomic bottleneck serves as a regularizer, enabling evolution to select simple circuits that can be readily adapted to important real-world tasks. The genomic bottleneck also suggests how innate priors can complement conventional approaches to learning in designing algorithms for artificial intelligence.
Fmrp regulates oligodendrocyte lineage cell specification and differentiation
Authors: Doll Caleb A. , Scott Kayt , Appel Bruce
Published: March 2021

Neurodevelopment requires the precise integration of a wide variety of neuronal and glial cell types. During early embryonic development, motor neurons and then oligodendrocyte precursor cells (OPCs) are specified from neural progenitors residing in the periventricular pMN progenitor domain of the spinal cord. Following gliogenesis, OPCs can differentiate as oligodendrocytes (OLs) – the myelinating glial cells of the central nervous system - or remain as OPCs. To generate unique cell types capable of highly divergent functions, these specification and differentiation events require specialized gene expression programs. RNA binding proteins (RBPs) regulate mRNA localization and translation in the developing nervous system and are linked to many neurodevelopmental disorders. One example is Fragile X syndrome (FXS), caused by the loss of the RBP fragile X mental retardation protein (FMRP). Importantly, infants with FXS have reduced white matter and we previously showed that zebrafish Fmrp is autonomously required in OLs to promote myelin sheath growth. We now find that Fmrp regulates cell specification in pMN progenitor cells and subsequently promotes differentiation of OPCs, such thatfmr1mutant zebrafish embryos generate excess OPCs and fewer differentiating OLs in the developing spinal cord. Although the early patterning of spinal progenitor domains appears largely normal infmr1mutants during early embryogenesis, Shh signaling is greatly diminished. Taken together, these results suggest cell stage-specific requirements for Fmrp in the specification and differentiation of oligodendrocyte lineage cells.
A high throughput SEC23 functional interaction screen reveals a role for focal adhesion and extracellular matrix signalling in the regulation of COPII subunit SEC23A
Authors: Jung Juan , Khan Muzamil Majid , Landry Jonathan , Halavatyi Aliaksandr , Machado Pedro , Reiss Miriam , Pepperkok Rainer
Published: March 2021

Proteins that enter the secretory pathway are transported from their place of synthesis in the Endoplasmic Reticulum to the Golgi complex by COPII coated carriers. The components of the COPII transport machinery have been well characterized, but the network of proteins that regulate these components in response to extracellular cues have remained largely elusive. The discovery of such regulatory proteins is crucial for understanding how cells integrate extracellular and intracellular information to fine-tune membrane traffic in the secretory pathway. A key group of proteins that plays a central role in the regulation of membrane traffic is associated with the cytoskeleton. Using high throughput microscopy of the well-established VSVG transport from the ER to the plasma membrane, we comprehensively screened 378 cytoskeleton-associated proteins for their functional interaction with the COPII components SEC23A and SEC23B using a double knockdown approach. Ranking of the transport effectors identified 20 cytoskeleton-associated proteins as the strongest functional interactors of SEC23, most of them not previously associated with the secretory pathway. Knockdown of a subgroup of these interactors (FERMT2, MACF1, MAPK8IP2, NGEF, PIK3CA, ROCK1), associated with cell adhesion, not only induced changes in focal adhesions and the expression of adhesion-related genes but led to the specific downregulation of SEC23A, a SEC23 paralogue that has been implicated in the secretion of extracellular matrix (ECM) components. Furthermore, SEC23A downregulation could also be recapitulated by plating cells on ECM and was dependent on focal adhesions function. Altogether, our results identify a network of cytoskeleton-associated proteins connecting focal adhesions and ECM-related signalling with the gene expression of the COPII secretory machinery.
Does one size fit all? CEO profiles and strategic management choices
Authors: Garcés-Galdeano Lucia , García-Olaverri Carmen , Huerta Emilio
Published: March 2021

Purpose

Upper echelons theory (UET) stands that cognitive bases of the CEO influence the field of vision and interpretation of the environment and affect its decisions about the firm. The main objective of the paper is to see if there are different CEO profiles, which can be associated with different strategic management choices.

Design/Methodology/approach

Using a representative sample of 1,236 small firms in high- and medium-high-technology, both in industrial and service sectors, the authors identify five CEO typologies through cluster analysis. The classification is based on CEO's personal characteristics such as education, tenure in the company or entrepreneurial experience. Multivariate analysis is carried out to establish the possible association between belonging to these clusters and some strategic decisions such as orientation towards innovation, efficiency or internationalisation. The unit of analysis is the firm focusing on the CEO.

Findings

The authors conclude that it is possible to classify the CEOs of these companies into five well-differentiated groups, with specific profiles. We find a significant association between belonging to a CEO profile and strategic choices taken in the firm. Managers who have been CEOs in several companies and have some entrepreneurial experience frequently guide the company towards innovation and internationalisation. CEOs with a lot of experience but limited to a single company often look for process efficiency.

Furthermore, it is observed that the belonging of these clusters is not evenly distributed in the group of companies analysed. Instead, depending on size and family / no family issues, the authors find a different presence of the CEO typologies.

Originality/value

The work provides relevant information in the field of small-, high- and medium-high-technology companies in relation to the profile of the CEO.
Collaborate to learn and learn to collaborate: a case of exploitative learning in the inter-organizational project
Authors: Liu Yan , Amini-Abyaneh Arash , Hertogh Marcel , Houwing Erik-Jan , Bakker Hans
Published: March 2021

Purpose

Management of inter-organizational projects focuses on the collective benefits of a group of organizations on a shared activity for a limited period and the coordination among them. However, how learning is facilitated in the inter-organizational project remains under-developed in the literature.

Design/methodology/approach

This research analyses the exploitative learning process in the longest tunnel project on land in the Netherlands realized in a densely populated area. Data were collected through archived documents, in-depth interviews, site visits in the ethnographic research to analyze the actors, the daily practices and social situations in projects.

Findings

The empirical findings indicate that exploitative learning is promoted positively between the owner and the contractor and internally within the contractor. The most significant change that the exploitative learning process has led to is the change in mindset toward the collaboration. Project culture is considered to be shaped by exploitative learning in the inter-organizational project. However, there is a gap between the transfer of knowledge from the inter-organizational project to the parent organization.

Originality/value

The findings have implications for understanding learning in the inter-organizational project setting.
Power outage and proactive service performance: the role of patient incivility and job stress
Authors: Yasin Raheel , Jan Ghulam
Published: March 2021

Purpose

Drawing from transactional stress and conservation of resource theories, this study untangles the relationship between power outage, patient incivility, job stress and proactive service performance. Further, this study also explores the mediating role of patient incivility and job stress.

Design/methodology/approach

A questionnaire-based survey was used, and data were collected from 275 healthcare professionals working in various public hospitals in Pakistan through convenience sampling. Structural equation modeling (SEM) via Smart PLS was used for data analysis.

Findings

Results revealed that power outage has significant positive impact on patient incivility and patient incivility has significant direct effect on job stress. Job stress has significant negative relationship with proactive service performance. Findings also confirmed that patient incivility mediates the relationship between power outage and job stress, and job stress mediates the relationship between patient incivility and proactive service performance.

Practical implications

This study helps the health administrators to think about the service standards of the public hospitals. Implications of this study are not limited to health sector. This study is useful for other service sectors where performance of employee affected by power outage. In addition to this, the current research helps to conduct research in other developing and underdeveloped countries which also face the problem of power outage.

Originality/value

This study marks the first step toward establishing power outage as an organizational behavior construct by demonstrating that power outage impacts significantly on proactive service performance. This study also explored the relationship between job stress and proactive service performance which was also not explored before.
“Testing the water” – prior-online market entry in China
Authors: Hardaker Sina , Zhang Ling
Published: March 2021

Purpose

The paper aims to investigate the new market entry strategy of the international grocery retailers Aldi Süd and Costco in China; analyzing if and how their prior-online market entry reflects a strategic response to organizational challenges in the Chinese market, which is a pioneer in the use of digital technologies and the provision of digital services.

Design/methodology/approach

The article identifies major challenges faced by international grocery retailers in China and discusses these with the help of the conceptual approach of embeddedness. The paper is based on expert interviews with senior executives of the two international retailers and other retail specialists and consultants.

Findings

The prior-online market entry by Aldi Süd and Costco represents a strategic response to organizational challenges that have to be faced in an increasingly challenging and highly digitalized Chinese market. Prior-online market entry allows the two retailers to experiment with the unique and heterogeneous Chinese market and build network and territorial embeddedness to facilitate the establishment of the physical store network. Both retailers utilize online stores to build relation and network with suppliers and customers and to understand Chinese consumer preferences. Yet, the localization strategy of Aldi Süd and Costco vary greatly.

Originality/value

Grocery retailers' prior-online expansion strategy has not yet been the focus of academic research. In regard to global grocery retailers, such as Aldi Süd and Costco, previous research argued that they were prepared to accept a lower expansion speed in order to expand at minimum risk and cost and mainly in countries which are regarded as having higher cultural proximity. The paper reveals the potential of the prior-online market entry strategy to change the internationalization behavior of grocery retailers. In addition, it contributes to the understanding of the evolution of market entry strategy into advanced digital economies in the coming new decade.
Prioritizing factors determining environmental responsibility using fuzzy analytical hierarchy process: evidence from India
Authors: Garg Aashish , Dhaliwal Ran Singh , Gupta Sanjay
Published: March 2021

Purpose

From the last few decades, environmental issues have become a global concern. Consumption activities are given much attention in the marketing literature, whenever the question about protecting the environment arises. The responsibility of the consumer toward the environment is a major concern and the purpose of this study is to prioritize factors responsible for determining environmental responsibility among young consumers. This research will provide valuable insights to the marketers in targeting those particular areas which according to young consumers are highly ranked/prioritized for being environmentally responsible.

Design/methodology/approach

In this study, data were collected from 400 young consumers from Punjab and Chandigarh. Fuzzy analytical hierarchy process (F-AHP) was applied to prioritize or rank the factors on the basis of significance for being environmentally responsible. The primary factors considered for further analysis were knowledge and awareness, attitude, green consumer value, emotional affinity toward nature, willingness to act and environment-related past behavior.

Findings

Results of the study depicted knowledge and awareness as the highest-ranked and prioritized factor for young consumers to become environmentally responsible, while environment-related past behavior emerged as the least important factor for consumers' environmental responsibility.

Research limitations/implications

Data were collected from the young consumers of Punjab and Chandigarh only and only a few factors of consumers' environmental responsibility were considered for further analysis which depicts the limitation of the study.

Practical implications

The research study is highly useful for the government and the business firms to target the highly prioritized factors of environmental responsibility which will promote green consumption practices and behavior among young consumers.

Originality/value

Previous researches have explored the factors of environmental responsibility and modeled their relationships. However, the present study has employed the multi-criteria decision-making technique to provide valuable insights for marketers, academicians and practitioners about the drivers of consumers' environmental responsibility which adds value to the existing knowledge base.
Costs and benefits of private tutoring programs: the South Korean case
Authors: Hultberg Patrik T. , Calonge David Santandreu , Choi Ty
Published: March 2021

Purpose

The purpose of the study is twofold: to offer a theoretical model that illuminates families' motivation to invest in private tutoring and to consider the implications of such investments in the context of South Korea. Given that parents invest in private tutoring for their child if the perceived expected benefits, at the time of enrollment, are greater than the direct and indirect costs of such tutoring, the study explores how private tutoring may affect educational inequities and possibly lead to inferior social outcomes.

Design/methodology/approach

A theoretical model based on the human capital approach was developed. Three questions based on stylized facts were addressed: (1) Why would a household send a child to private tutoring? (2) Why do different households invest in different amounts of private tutoring? (3) Why may a household over-invest in private tutoring?

Findings

The findings of this study indicate that the demand for private tutoring services decreases with the costs of private tutoring, while increasing as levels of academic readiness and aptitude, levels of household education, levels of current wealth and expected returns to private tutoring increase. These findings imply that private tutoring may exacerbate social inequities and cause an inferior social outcome, but that a government can influence the demand for tutoring through taxation.

Research limitations/implications

This study did not address the non-pecuniary benefits that may be derived from private tutoring. The most important limitation and potential source of weakness of the study is that the model is theoretical. These results therefore need to be interpreted with caution.

Practical implications

The study indicates the need for private households, as well as government officials, to carefully consider the costs and benefits of private tutoring in South Korea. Although the study focuses on South Korea, the findings may apply to other countries in which private tutoring offerings are prominent.

Social implications

The educational choices that families make for their children have important financial and social implications in all countries, but especially in South Korea. The important implication is that private tutoring will tend to aggravate educational and social inequality.

Originality/value

The existing body of research on private tutoring investment in South Korea suggests that the phenomenon is ubiquitous, growing and spreading to other countries. Furthermore, the motivation behind households' decisions to invest in private tutoring for their children is not always addressed in the published literature. Also, far too little attention has been paid to the economic impact private tutoring has on households and children, as well as society in general.