bluuebunny/crossref_metadata_2025 huggingface dataset:
Near-native state imaging by cryo-soft-X-ray tomography reveals remodelling of multiple cellular organelles during HSV-1 infection
Authors: Nahas Kamal L. , Connor Viv , Scherer Katharina M. , Kaminski Clemens F. , Harkiolaki Maria , Crump Colin M. , Graham Stephen C.
Published: October 2021

Herpes simplex virus-1 (HSV-1) is a large, enveloped DNA virus and its assembly in the cell is a complex multi-step process during which viral particles interact with numerous cellular compartments such as the nucleus and organelles of the secretory pathway. Transmission electron microscopy and fluorescence microscopy are commonly used to study HSV-1 infection. However, 2D imaging limits our understanding of the 3D geometric changes to cellular compartments that accompany infection and sample processing can introduce morphological artefacts that complicate interpretation. In this study, we used soft X-ray tomography to observe differences in whole-cell architecture between HSV-1 infected and uninfected cells. To protect the near-native structure of cellular compartments we used a non-disruptive sample preparation technique involving rapid cryopreservation, and a fluorescent reporter virus was used to facilitate correlation of structural changes with the stage of infection in individual cells. We observed viral capsids and assembly intermediates interacting with nuclear and cytoplasmic membranes. Additionally, we observed differences in the morphology of specific organelles between uninfected and infected cells. The local concentration of cytoplasmic vesicles at the juxtanuclear compartment increased and their mean width decreased as infection proceeded, and lipid droplets transiently increased in size. Furthermore, mitochondria in infected cells were elongated and highly branched, suggesting that HSV-1 infection alters the dynamics of mitochondrial fission/fusion. Our results demonstrate that high-resolution 3D images of cellular compartments can be captured in a near-native state using soft X-ray tomography and have revealed that infection causes striking changes to the morphology of intracellular organelles.

Importance

Ultrastructural changes to the morphology and organization of cellular compartments during herpes simplex virus-1 (HSV-1) infection have not previously been studied under near-physiological conditions. In this study, soft X-ray tomography was used to image the ultrastructure of vitrified cells during HSV-1 infection, identifying striking changes to the abundance and organization of cytoplasmic vesicles and mitochondria. The concentration of vesicles in the juxtanuclear region increased with time post infection, which could represent an increasing supply of vesicles to support capsid envelopment, and there is a transient increase in the size of lipid droplets in infected cells. Furthermore, we show that mitochondria elongate and form highly-branched networks as infection progresses. These findings offer insight into stages of virion morphogenesis and the cellular response to infection, highlighting the utility of cryo-soft-X-ray tomography for monitoring the near-native state ultrastructure of infected cells.
The BrightEyes-TTM: an Open-Source Time-Tagging Module for Single-Photon Microscopy
Authors: Rossetta Alessandro , Slenders Eli , Donato Mattia , Perego Eleonora , Diotalevi Francesco , Lanzanó Luca , Koho Sami , Tortarolo Giorgio , Crepaldi Marco , Vicidomini Giuseppe
Published: October 2021

Fluorescence laser-scanning microscopy (LSM) is experiencing a revolution thanks to the introduction of new asynchronous read-out single-photon (SP) array detectors. These detectors give access to an entirely new set of single-photon information typically lost in conventional fluorescence LSM, thus triggering a new imaging/spectroscopy paradigm – the so-called singlephoton LSM (SP-LSM). The revolution’s outcomes are, from one side, the blooming of new SP-LSM techniques and tailored SP array detectors; from the other side, the need for data-acquisition (DAQ) systems effectively supporting such innovations. In particular, there is a growing need for DAQ systems capable of handling the high throughput and high temporal resolution information generated by the single-photon detectors. To fill this gap, we developed an open-source multi-channel timetagging module (TTM) based on a field-programmable-gatearray (FPGA), that can temporally tag single-photon events – with 30 ps precision – and synchronisation events – with 4 ns precision. Furthermore, being an open-access project, the TTM can be upgraded, modified, and customized by the microscopy-makers. We connected the TTM to a fluorescence LSM equipped with a single-photon avalanche diode (SPAD) bi-dimensional array detector, and we implemented fluorescence lifetime image scanning microscopy (FLISM) and, for the first time, fluorescence lifetime fluctuation spectroscopy (FLFS). We expect that our BrigthEyes-TTM will support the microscopy community to spread SP-LSM in many life science labs.
The coordination of replication initiation with growth rate in Escherichia coli
Authors: Knöppel Anna , Broström Oscar , Gras Konrad , Fange David , Elf Johan
Published: October 2021

Escherichia coli coordinates replication and division cycles by initiating replication at approximately the same size per chromosome at all growth rates. By tracking replisomes in individual cells through thousands of division cycles, we have dissected the mechanism behind this precise process. We have characterized wild-type cells grown under different conditions and also many mutants related to the expression and binding states of the initiator protein DnaA. This rich data set allowed us to compare the relative importance of all previously described control systems. We found that the replication initiation size regulation is not strongly dependent on the absolute concentration of DnaA, nor does it depend on active dnaA expression. Replication initiation is also not consistently triggered by cell division or replication termination. In contrast, some of the factors that convert DnaA between its ATP- and ADP-bound states have a strong effect on initiation size. We suggest a plausible model for DnaA-ATP mediated triggering of initiation at fast growth, where regulatory inactivation of DnaA (RIDA) is the main system for monitoring the number of chromosomes during active replication.
Carriage of antibiotic resistant bacteria in endangered and declining Australian pinniped pups
Authors: Fulham Mariel , McDougall Fiona , Power Michelle , McIntosh Rebecca R. , Gray Rachael
Published: October 2021

The rapid emergence of antimicrobial resistance (AMR) is a major concern for wildlife and ecosystem health globally. Genetic determinants of AMR have become indicators of anthropogenic pollution due to their greater association with humans and rarer presence in environments less affected by humans. The objective of this study was to determine the distribution and frequency of the class 1 integron, a genetic determinant of AMR, in both the faecal microbiome and inEscherichia coliisolated from neonates of three pinniped species. Australian sea lion (Neophoca cinerea), Australian fur seal (Arctocephalus pusillus doriferus) and long-nosed fur seal (Arctocephalus forsteri) pups from eight breeding colonies along the Southern Australian coast were sampled between 2016-2019. DNA from faecal samples (n=309) and fromE.coli(n=795) isolated from 884 faecal samples were analysed for class 1 integrons using PCRs targeting the conserved integrase gene (intI) and the gene cassette array. Class 1 integrons were detected inA.p.doriferusandN.cinereapups sampled at seven of the eight breeding colonies investigated in 4.85% of faecal samples (n=15) and 4.52% ofE.coliisolates (n=36). Integrons were not detected in anyA.forsterisamples. DNA sequencing of the class 1 integron gene cassette array identified diverse genes conferring resistance to four antibiotic classes. The relationship between class 1 integron carriage and the concentration of five trace elements and heavy metals was also investigated, finding no significant association. The results of this study add to the growing evidence of the extent to which antimicrobial resistant bacteria are polluting the marine environment. As AMR determinants are frequently associated with bacterial pathogens, their occurrence suggests that these pinniped species are vulnerable to potential health risks. The implications for individual and population health as a consequence of AMR carriage is a critical component of ongoing health investigations.
Analytical performance of a highly sensitive system to detect gene variants using next-generation sequencing for lung cancer companion diagnostics
Authors: Kato Kikuya , Okami Jiro , Nakamura Harumi , Honma Keiichiro , Sato Yoshiharu , Nakamura Seiji , Kukita Yoji , Nakatsuka Shin-ichi , Higashiyama Masahiko
Published: October 2021

The recent increase in the number of molecular-targeted agents for non-small cell lung carcinoma and the corresponding target genes has led to the demand for the simultaneous testing of multiple genes. Although gene panels that use next-generation sequencing (NGS) are ideal for this purpose, conventional panels require a high tumor content, and biopsy samples often do not meet this requirement. We developed a new NGS panel, called a compact panel, to accommodate biopsy samples without restricting tumor content. The panel was characterized by high sensitivity, with detection limits for mutations of 0.14%, 0.20%, 0.48%, 0.24%, and 0.20% forEGFRexon 19 deletion, L858R, T790M,BRAFV600E, andKRASG12C, respectively. Mutation detection also had a high quantitative ability, with correlation coefficients ranging from 0.966 to 0.992. The threshold for fusion detection was 1%. The panel exhibited good concordance with the approved tests. Identity rates are as follows:EGFRpositive, 100% (95% confidence interval, 95.5-100);EGFRnegative, 90.9 (82.2-96.3);BRAFpositive, 100 (59.0-100);BRAFnegative, 100 (94.9-100);KRASG12C positive, 100 (92.7-100);KRASG12C negative, 100 (93.0-100);ALKpositive, 96.7 (83.8-99.9);ALKnegative, 98.4 (97.2-99.2);ROS1positive, 100 (66.4-100);ROS1negative, 99.0 (94.6-100);METpositive, 98.0 (89.0-99.9);METnegative 100 (92.8-100);RETpositive, 93.8 (69.8-100);RETnegative, 99.8 (94.9-100). The analytical performance showed that the compact panel could handle various types of biopsy samples obtained by routine clinical practice without requiring strict pathological monitoring, as in the case of conventional NGS panels.
ConTreeDP: A consensus method of tumor trees based on maximum directed partition support problem
Authors: Fu Xuecong , Schwartz Russell
Published: October 2021

Phylogenetic inference has become a crucial tool for interpreting cancer genomic data, but continuing advances in our understanding of somatic mutability in cancer, genomic technologies for profiling it, and the scale of data available have created a persistent need for new algorithms able to deal with these challenges. One particular need has been for new forms of consensus tree algorithms, which present special challenges in the cancer space for dealing with heterogeneous data, short evolutionary time scales, and rapid mutation by a wide variety of somatic mutability mechanisms. We develop a new consensus tree method for clonal phylogenetics, ConTreeDP, based on a formulation of the Maximum Directed Partition Support Consensus Tree (MDPSCT) problem. We demonstrate theoretically and empirically that our approach can efficiently and accurately compute clonal consensus trees from cancer genomic data.

Availability: https://github.com/CMUSchwartzLab/ConTreeDP
Tagging active neurons by soma-targeted Cal-Light
Authors: Hyun Jung Ho , Nagahama Kenichiro , Namkung Ho , Mignocchi Neymi , Hannan Patrick , Krüssel Sarah , Kwak Chuljung , McElroy Abigail , Liu Bian , Cui Mingguang , Lee Seunghwan , Lee Dongmin , Huganir Richard L. , Sawa Akira , Kwon Hyung-Bae
Published: October 2021

Verifying causal effects of neural circuits is essential for proving direct a circuit-behavior relationship. However, techniques for tagging only active neurons with high spatiotemporal precision remain at the beginning stages. Here we developed the soma-targeted Cal-Light (ST-Cal-Light) which selectively converts somatic calcium rise triggered by action potentials into gene expression. Such modification simultaneously increases the signal-to-noise ratio (SNR) of reporter gene expression and reduces the light requirement for successful labeling. Because of the enhanced efficacy, the ST-Cal-Light enables the tagging of functionally engaged neurons in various forms of behaviors, including context-dependent fear conditioning, leverpressing choice behavior, and social interaction behaviors. We also targeted kainic acid-sensitive neuronal populations in the hippocampus which subsequently suppressed seizure symptoms, suggesting ST-Cal-Light’s applicability in controlling disease-related neurons. Furthermore, the generation of a conditional ST-Cal-Light knock-in (KI) mouse provides an opportunity to tag active neurons in a region- or cell-type specific manner via crossing with other Cre-driver lines. Thus, the versatile ST-Cal-Light system links somatic action potentials to behaviors with high temporal precision, and ultimately allows functional circuit dissection at a single cell resolution.
Feature distribution learning by passive exposure
Authors: Pascucci David , Ceylan Gizay , Kristjánsson Árni
Published: October 2021

Humans can rapidly estimate the statistical properties of groups of stimuli, including their average and variability. But recent studies of so-called Feature Distribution Learning (FDL) have shown that observers can quickly learn even more complex aspects of feature distributions. In FDL, observers learn the full shape of a distribution of features in a set of distractor stimuli and use this information to improve visual search: response times (RT) are slowed if the target feature lies inside the previous distractor distribution, and the RT patterns closely reflect the distribution shape. FDL requires only a few trials and is markedly sensitive to different distribution types. It is unknown, however, whether our perceptual system encodes feature distributions automatically and by passive exposure, or whether this learning requires active engagement with the stimuli. In two experiments, we sought to answer this question. During an initial exposure stage, participants passively viewed a display of 36 lines that included one orientation singleton or no singletons. In the following search display, they had to find an oddly oriented target. The orientations of the lines were determined either by a Gaussian or a uniform distribution. We found evidence for FDL only when the passive trials contained an orientation singleton. Under these conditions, RT’s decreased as a function of the orientation distance between the target and the exposed distractor distribution. These results suggest that FDL can occur by passive exposure, but only if an orientation singleton appears during exposure to the distribution.
Neuronal hemoglobin induces loss of dopaminergic neurons in mouse Substantia nigra, cognitive deficits and cleavage of endogenous α-synuclein
Authors: Chiara Santulli , Carlotta Bon , Elena De Cecco , Marta Codrich , Joanna Narkiewicz , Pietro Parisse , Fabio Perissinotto , Claudio Santoro , Francesca Persichetti , Giuseppe Legname , Stefano Espinoza , Stefano Gustincich
Published: October 2021

Backgroud

Parkinson’s disease (PD) presents the selective loss of A9 dopaminergic (DA) neurons of Substantia Nigrapars compacta(SNpc) and the presence of intracellular aggregates called Lewy bodies. α-synuclein (α-syn) species truncated at the carboxy terminal (C-terminal) accumulate in pathological inclusions and promote α-syn aggregation and toxicity.

Hemoglobin (Hb) is the major oxygen carrier protein in erythrocytes. In addition, Hb is expressed in A9 DA neurons where it influences mitochondrial activity. Hb overexpression increases cells’ vulnerability in a neurochemical model of PDin vitroand forms cytoplasmic and nucleolar aggregates upon short-term overexpression in mouse SNpc.

Methods

α and β-globin chains were co-expressed in DA cells of SNpcin vivoupon stereotaxic injections of an Adeno-Associated Virus isotype 9 (AAV9) and in DA iMN9D cellsin vitro.

Results

Long-term Hb over-expression in SNpc induced the loss of about 50% of DA neurons, a mild motor impairment and deficits in recognition and spatial working memory. Hb triggered the formation of endogenous α-synuclein C-terminal truncated species. Similar α-syn fragments were foundin vitroin DA iMN9D cells over-expressing α and β-globins when treated with pre-formed α-syn fibrils.

Conclusion

Our study positions Hb as a relevant player in PD pathogenesis for its ability to trigger DA cells’ lossin vivoand the formation of C-terminal α-synuclein fragments.
Whole genome sequences of Treponema pallidum subsp. endemicum isolated from Cuban patients: the non-clonal character of isolates suggests a persistent human infection rather than a single outbreak
Authors: Vrbová Eliška , Noda Angel A. , Grillová Linda , Rodríguez Islay , Forsyth Allyn , Oppelt Jan , Šmajs David
Published: October 2021

Bejel (endemic syphilis) is a neglected non-venereal disease caused by Treponema pallidum subsp. endemicum (TEN). Although it is mostly present in hot, dry climates, a few cases have been found outside of these areas. The aim of this work was the sequencing and analysis of TEN isolates obtained from “syphilis patients” in Cuba, which is not considered an endemic area for bejel.

Genomes were obtained by pool segment genome sequencing or direct sequencing methods, and the bioinformatics analysis was performed according to an established pipeline.

We obtained four genomes with 100%, 81.7%, 52.6%, and 21.1% of broad coverage, respectively. The sequenced genomes revealed a non-clonal character, with nucleotide variability ranging between 0.2–10.3 nucleotide substitutions per 100 kbp among the TEN isolates. Nucleotide changes affected 27 genes, and the analysis of the completely sequenced genome also showed a recombination event between tprC and tprI, in TP0488 as well as in the intergenic region between TP0127–TP0129.

Despite limitations in the quality of samples affecting broad sequencing coverage, the determined non-clonal character of the isolates suggests a persistent infection in the Cuban population rather than a single outbreak caused by imported case.

Author summary

The incidence of venereal syphilis has greatly increased in the last years, however endemic syphilis (bejel) which have been considered as a disease restricted to dry arid areas such as the Sahel and the Middle East, remain as a neglected disease. In Cuba, which is a tropical country, several bejel cases were unexpectedly detected few years ago in “syphilis” patients with no records of travel abroad or sex with foreign partners. In this study, we explored the whole genome sequences from four of the Cuban Treponema pallidum subsp. endemicum (TEN) isolates and the substantial genetic diversity detected among them suggests a persistent infection of TEN within the human population rather than a single outbreak of a TEN isolate introduced from an area where it is typically endemic. This finding has significant implications on this neglected and also possibly tropical disease in terms of geographical/temporal distribution, and highlights the importance of keeping in mind neglected diseases in apparently non-endemic areas.
Rapid brain development and reduced neuromodulator titres correlate with host shifts in Rhagoletis pomonella
Authors: Kharva Hinal , Feder Jeffrey L. , Hahn Daniel A , Olsson Shannon B.
Published: October 2021

Host shifts are considered a key generator of insect biodiversity. For insects, adaptation to new host plants often requires changes in larval/pupal development and behavioural preference towards new hosts. Neurochemicals play key roles in both development and behaviour, and therefore provide a potential source for such synchronization. Here, we correlated life history timing, brain development, and corresponding levels of 14 neurochemicals in Rhagoletis pomonella (Diptera: Tephritidae), a species undergoing ecological speciation through an ongoing host shift from hawthorn to apple fruit. These races exhibit differences in pupal diapause timing as well as adult behavioural preference with respect to their hosts. This difference in behavioral preference is coupled with differences in neurophysiological response to host volatiles. We found that apple race pupae exhibited adult brain morphogenesis three weeks faster after an identical simulated winter than the hawthorn race, which correlated with significantly lower titres of several neurochemicals. In some cases, particularly biogenic amines, differences in titres were reflected in the mature adult stage, when host preference is exhibited. In summary, life history timing, neurochemical titre, and brain development can be coupled in this speciating system, providing new hypotheses for the origins of new species through host shifts.
Repetition-attenuation of auditory N1 is modulated by the phonological representations of spoken word-forms
Authors: Yue Jinxing , Wang Peng , Li Jiayin , Li Zhipeng , Liang Xia , He Yifei
Published: October 2021

Repeated auditory stimuli are usually found to elicit attenuated peak amplitude of the N1 component of the event related brain potential (ERP). While the repetition-attenuation of the auditory N1 has been found sensitive to some cognitive factors, less is known whether and how the representational properties of stimuli influence this physiological phenomenon. To further address this issue, we focus on the phonological representations of spoken word-forms, and hypothesise modulatory roles of two phonological features: the lexicality and its usage frequency of a word-form. To test this, we used a short-term habituation design with a factorial combination of the two features at two levels each (i.e., lexicality (real versus pseudo word-form) × frequency (high versus low frequency)). EEG was recorded from 30 native Mandarin-speaking participants while they were passively delivered with stimulations trains. Each train consisted of five presentation positions (S1 ∼ S5), on which one word-form is presented repeatedly, separated by a brief, constant interstimulus interval. At the fourth presentation position (S4), we found greater N1 attenuation in low-frequency pseudo word-forms than in low-frequency real and high-frequency pseudo word-forms, respectively. The results support our representational modulation hypothesis, and provides the first evidence that representations of different phonological features interactively modulate the N1 repetition-attenuation. The brain function that underlies the phonological effects of the representational modulation on N1 repetition-attenuation might be sensory filtering.
Dynamic Instability of Dendrite Tips Generates the Highly Branched Morphologies of Sensory Neurons
Authors: Shree Sonal , Sutradhar Sabyasachi , Trottier Olivier , Tu Yuhai , Liang Xin , Howard Jonathon
Published: October 2021

The highly ramified arbors of neuronal dendrites provide the substrate for the high connectivity and computational power of the brain. Altered dendritic morphology is associated with neuronal diseases. Many molecules have been shown to play crucial roles in shaping and maintaining dendrite morphology. Yet, the underlying principles by which molecular interactions generate branched morphologies are not understood. To elucidate these principles, we visualized the growth of dendrites throughout larval development ofDrosophilasensory neurons and discovered that the tips of dendrites undergo dynamic instability, transitioning rapidly and stochastically between growing, shrinking, and paused states. By incorporating these measured dynamics into a novel, agent-based computational model, we showed that the complex and highly variable dendritic morphologies of these cells are a consequence of the stochastic dynamics of their dendrite tips. These principles may generalize to branching of other neuronal cell-types, as well as to branching at the subcellular and tissue levels.
Composite receptive fields in the mouse auditory cortex
Authors: Lu Sihao , Steadman Mark , Ang Grace W. Y. , Kozlov Andrei S.
Published: October 2021

Abstract

A central question in sensory neuroscience is how neurons represent complex natural stimuli. This process involves multiple steps of feature extraction to obtain a condensed, categorical representation useful for classification and behavior. It has previously been shown that central auditory neurons in the starling have composite receptive fields composed of multiple features when probed with conspecific songs. Whether this property is an idiosyncratic characteristic of songbirds, a group of highly specialized vocal learners, or a generic characteristic of central auditory systems in different animals is, however, unknown. To address this question, we have recorded responses from auditory cortical neurons in mice, and characterized their receptive fields using mouse ultrasonic vocalizations (USVs) as a natural and ethologically relevant stimulus and pitch-shifted starling songs as a natural but ethologically irrelevant control stimulus. We have found that auditory cortical neurons in the mouse display composite receptive fields with multiple excitatory and inhibitory subunits. Moreover, this was the case with either the conspecific or the heterospecific vocalizations. We then trained the sparse filtering algorithm on both classes of natural stimuli to obtain statistically optimal features, and compared the natural and artificial features using UMAP, a dimensionality-reduction algorithm previously used to analyze mouse USVs and birdsongs. We have found that the receptive-field features obtained with the mouse USVs and those obtained with the pitch-shifted starling songs clustered together, as did the sparse-filtering features. However, the natural and artificial receptive-field features clustered mostly separately. These results indicate that composite receptive fields are likely a generic property of central auditory systems in different classes of animals. They further suggest that the quadratic receptive-field features of the mouse auditory cortical neurons are natural-stimulus invariant.
Variable inhibition of unwinding rates of DNA catalyzed by the SARS-Cov-2 (COV19) helicase nsp13 by structurally distinct single DNA lesions
Authors: Sales A.H. , Ciervo S. , Lupoli T. , Shafirovich V. , Geacintov N.E.
Published: October 2021

The SARS 2 (Covid 19) helicase nsp13 plays a critically important role in the replication of the Corona virus by unwinding double-stranded RNA (and DNA) with a 5’⟶3’ strand polarity. Here we explored the impact of single, structurally defined covalent DNA lesions on the helicase activity of nsp13 in aqueous solutions, The objectives were to derive mechanistic insights into the relationships between the structures of DNA lesions, the DNA distortions that they engender, and the inhibition of helicase activity. The lesions included two bulky stereoisomeric N2-guanine adducts derived from the reactions of benzo[a]pyrene diol epoxide with DNA. The trans-adduct assumes a minor groove conformation, while the cis-product adopts a base-displaced intercalated conformation. The non-bulky DNA lesions included the intra-strand cross-linked thymine dimers, the cis-syn-cyclobutane pyrimidine dimer, and the pyrimidine (6−4) pyrimidone photoproduct. All four lesions strongly inhibit the helicase activity of nsp13, The UV photolesions feature a 2 - 5-fold smaller inhibition of the nsp13 unwinding activity than the bulky DNA adducts, and the kinetics of these two pairs of DNA lesions are also different. The connections between the structural features of these four DNA lesions and their impact on nsp13 unwinding efficiencies are discussed.
SWI/SNF chromatin remodeler complex within the reward pathway is required for behavioral adaptations to stress
Authors: Zayed Abdallah , Baranowski Camille , Compagnion Anne Claire , Vernochet Cécile , Karaki Samah , de Cuttoli Romain Durand , Saint-Jour Estefani , Bhattacharya Soumee , Marti Fabio , Vanhoutte Peter , Yaniv Moshe , Faure Philippe , Barik Jacques , Amar Laurence , Tronche François , Parnaudeau Sebastien
Published: October 2021

Stress exposure is a cardinal risk factor for most psychiatric diseases. Preclinical and clinical studies point to changes in gene expression involving epigenetic modifications within mesocorticolimbic brain circuits. Brahma (BRM) and Brahma-Related-Gene-1 (BRG1) are ATPase subunits of the SWI/SNF complexes involved in chromatin remodeling, a process essential to enduring plastic changes in gene expression. Here, we show that repeated social defeat induces changes in BRG1 nuclear distribution. The inactivation of the Brg1/Smarca4 gene within dopamine-innervated regions or the constitutive inactivation of the Brm/Smarca2 gene leads to resilience to repeated social defeat and decreases the behavioral responses to cocaine without impacting midbrain dopamine neurons activity. Within striatal medium spiny neurons Brg1 gene inactivation reduces the expression of stress- and cocaine-induced immediate early genes, increases levels of heterochromatin and at a global scale decreases chromatin accessibility. Altogether these data demonstrate the pivotal function of SWI/SNF complexes in behavioral and transcriptional adaptations to salient environmental challenges.
pVHL regulates protein stability of TCF/LEF transcription factor family via ubiquitin-independent proteasomal degradation
Authors: Wang Caixia , Rong Xiaozhi , Zhang Haifeng , Wang Bo , Bai Yan , Liu Yunzhang , Lu Ling , Li Yun , Sun Yonghua , Zhao Chengtian , Zhou Jianfeng
Published: October 2021

The Wnt/β-catenin signaling pathway plays key roles in development and adult tissue homeostasis by controlling cell proliferation and cell fate decisions. In this pathway, transcription factors TCF/LEFs are the key components to repress target gene expression by recruiting co-repressors or to activate target gene expression by recruiting β-catenin when the Wnt signals are absent or present, respectively. While progress has been made in our understanding of Wnt signaling regulation, the underlying mechanism that regulates the protein stability of the TCF/LEF family is far less clear. Here, we show that von Hippel-Lindau protein (pVHL), which is the substrate recognition component in an E3 ubiquitin ligase complex, controls TCF/LEF protein stability. Unexpectedly, pVHL directly binds to TCF/LEFs and promotes their proteasomal degradation independent of E3 ubiquitin ligase activity. Knockout of vhl in zebrafish embryos leads to a reduction of dorsal habenular neurons and this effect is upstream of dorsal habenular neurons phenotype in tcf7l2-null mutants. Our study uncovers a previously unknown mechanism for the protein stability regulation of the TCF/LEF transcription factors and demonstrates that pVHL contains a 26S proteasome binding domain that drives ubiquitin-independent proteasomal degradation. These findings provide new insights into the ubiquitin-independent actions of pVHL and uncover novel mechanistical regulation of Wnt/β-catenin signaling.
Angiomotin isoform 2 promotes binding of PALS1 to KIF13B at the base of primary cilia and suppresses ciliary elongation
Authors: Morthorst Stine Kjær , Nielsen Camilla , Farinelli Pietro , Anvarian Zeinab , Rasmussen Christina Birgitte R. , Serra-Marques Andrea , Grigoriev Ilya , Altelaar Maarten , Fürstenberg Nicoline , Ludwig Alexander , Akhmanova Anna , Christensen Søren Tvorup , Pedersen Lotte Bang
Published: October 2021

The kinesin-3 motor KIF13B functions in endocytosis, vesicle transport, and regulation of ciliary length and signaling. Direct binding of the membrane-associated guanylate kinase (MAGUK) DLG1 to KIF13B’s MAGUK-binding stalk (MBS) domain relieves motor autoinhibition and promotes microtubule plus end-directed cargo transport. Here we characterize Angiomotin isoform 2 (Ap80) as a novel KIF13B interactor that promotes binding of another MAGUK, the polarity protein and Crumbs complex component PALS1, to KIF13B. Live cell imaging analysis indicated that Ap80 is concentrated at the base of primary cilia and recruits PALS1 to this site, but is not itself a cargo of KIF13B. Consistent with a ciliary function for Ap80, its depletion led to elongated primary cilia while its overexpression caused ciliary shortening. Our results suggest that Ap80 may specifically activate KIF13B cargo binding at the base of primary cilia to regulate ciliary length.
Opsonization by non-neutralizing antibodies can confer protection to SARS-CoV-2 despite Spike-dependent modulation of phagocytosis
Authors: Bahnan Wael , Wrighton Sebastian , Sundwall Martin , Bläckberg Anna , Höglund Urban , Larsson Olivia , Khakzad Hamed , Godzwon Magdalena , Walle Maria , Elder Elizabeth , Happonen Lotta , André Oscar , Ahnlide Johannes Kumra , Hellmark Thomas , Wendel-Hansen Vidar , Wallin Robert PA , Malmström Johan , Malmström Lars , Ohlin Mats , Rasmussen Magnus , Nordenfelt Pontus
Published: October 2021

Spike-specific antibodies are central to effective COVID19 immunity. Research efforts have focused on antibodies that neutralize the ACE2-Spike interaction but not on non-neutralizing antibodies. Antibody-dependent phagocytosis is an immune mechanism enhanced by opsonization, where typically, more bound antibodies trigger a stronger phagocyte response. Here, we show that Spike-specific antibodies, dependent on concentration, can either enhance or reduce Spike-bead phagocytosis by monocytes independently of the antibody neutralization potential. Surprisingly, we find that both convalescent patient plasma and patient-derived monoclonal antibodies lead to maximum opsonization already at low levels of bound antibodies and is reduced as antibody binding to Spike protein increases. Moreover, we show that this Spike-dependent modulation of opsonization seems to affect the outcome in an experimental SARS-CoV-2 infection model. These results suggest that the levels of anti-Spike antibodies could influence monocyte-mediated immune functions and propose that non-neutralizing antibodies could confer protection to SARS-CoV-2 infection by mediating phago-cytosis.
Impact of perceived brand localness and globalness on brand authenticity to predict brand attitude: a cross-cultural Asian perspective
Authors: Safeer Asif Ali , Chen Yun , Abrar Muhammad , Kumar Nilesh , Razzaq Amar
Published: October 2021

Purpose

The study aims to investigate the impact of perceived brand localness (PBL) and perceived brand globalness (PBG) on brand authenticity (BA) to predict consumers' attitudes toward local and global brands in two Asian markets. Further, the study examines the moderating role of uncertainty avoidance (UA) after controlling the effects of brand familiarity (BF) in Asian markets (China and Pakistan).

Design/methodology/approach

In accordance with the non-probability technique and through an online survey, the study collected 1,880 responses (on local and global brands) from China and Pakistan. Partial least square structural equation modeling (PLS-SEM) is the most robust technique applied to examine the proposed hypotheses in the Asian environment.

Findings

After controlling the effects of BF, the findings revealed that PBL and PBG positively influenced consumers' perceptions of BA, which had a significant impact on consumers' brand attitudes toward both local and global brands in Asian markets. Further, the research identified that BA was an essential mediator from the Asian perspective. The interaction effects of UA and PBL on BA were discovered positively significant in Pakistan, whereas the effects of UA and PBG on BA were found negatively significant in Pakistan and had no effects in China.

Research limitations/implications

The research focused on two Asian countries (China and Pakistan). However, future researchers may collect additional data from other Asian countries in order to generalize the findings in all Asian markets.

Practical implications

The research assists local and global managers in designing and implementing various targeting, positioning and segmentation strategies for successfully managing businesses in Asian markets.

Originality/value

The novel research is based on signaling theory that contributes to the local and global branding domains from the Asian perspective (China and Pakistan).
Managerial ability and intellectual capital disclosure
Authors: Rajabalizadeh Javad , Oradi Javad
Published: October 2021

Purpose

While prior research in the area of intellectual capital (IC) disclosure has mainly focused on firm, board and audit committee characteristics, there is little research on whether managerial characteristics are associated with IC disclosure. This study aims to examine the relationship between managerial ability (MA) and the extent of IC disclosure.

Design/methodology/approach

The study sample comprises 1,098 firm-year observations of Iranian listed firms during 2012–2017. This study uses the checklist developed by Liet al.(2008) and adopts a content analysis approach and calculates the IC disclosure index in 62 dimensions within three categories: human capital, structural capital and relational capital. To measure MA, this study uses the managerial ability score (MA-Score) developed by Demerjianet al.(2012) for Iranian firms.

Findings

The results show that MA is significantly and negatively associated with the overall extent of IC disclosure and all the three components of IC (human capital, structural capital and relational capital). Further analysis shows that the interaction between MA and firm performance is positive and significant, suggesting that the negative relationship between MA and IC disclosure is less pronounced for high-performing firms. This study addresses the potential endogeneity issue by using the propensity score matching approach. The findings are also robust to the alternative measure of MA.

Originality/value

This study contributes to both the MA literature and the IC disclosure literature. To the best of the authors' knowledge, this study is the first to provide empirical evidence on the relationship between MA and IC disclosure.
The effect of social and ethical practices on environmental disclosure: evidence from an international ESG data
Authors: Chouaibi Salim , Affes Habib
Published: October 2021

Purpose

Given the rising global interest in the environmental, social and governance (ESG) index, the purpose of this paper is to investigate the impact of social and ethical practices on the firm’s environmental disclosure level.

Design/methodology/approach

To test the study’s hypotheses, the authors applied linear regressions with a data panel using the Thomson Reuters ASSET4 and Bloomberg database from seven countries in analyzing data of 523 listed companies selected from the ESG index between 2005 and 2017. Similarly, as an extension of the research and to address the potential unobserved heterogeneity and the dynamic endogeneity, the authors exploited the dynamic dimension of the data set through the generalized moment method (GMM) and estimated the impact of the one-year lagged value of the environmental disclosure.

Findings

The empirical results indicate a growing interest in corporate social responsibility (CSR) and ethical practices over the past decade. Besides, companies with a strong social and ethical commitment obtain significantly higher environmental disclosure scores. The results found with the GMM technique indicate the existence of dependence and continuity in environmental disclosure over time.

Practical implications

The research enables the information user to assess the transparency of the company as well as the quality of the information disclosed on its environment and its future growth opportunities in a context where the approach of business ethics occupies a central position in business valuation. The reached results suggest that the institutional and/or cultural factors affect top management’s environmental reporting behavior regarding the quality of published information.

Originality/value

This paper explores, for the first time, the effect of the social and ethical practices of ESG companies with seven different nationalities as well as its dynamic effect on the adoption of an environmental transparency strategy.
Does board independence influence asset redeployability? Evidence from a quasi-natural experiment
Authors: Padungsaksawasdi Chaiyuth , Treepongkaruna Sirimon , Jiraporn Pornsit , Uyar Ali
Published: October 2021

Purpose

Exploiting an exogenous regulatory shock and a novel measure of asset redeployability, this paper aims to explore the effect of independent directors on asset redeployability. In particular, the authors use an innovative measure of asset redeployability recently developed by Kim and Kung (2016). This novel index has been rapidly adopted in recent literature.

Design/methodology/approach

Relying on a quasi-natural experiment, the authors execute a difference-in-difference analysis based on an exogenous regulatory shock to board independence. To mitigate endogeneity and demonstrate causation, the authors also perform propensity score matching, instrumental-variable analysis and Oster’s (2019) approach for testing coefficient stability.

Findings

The difference-in-difference estimates show that firms forced to raise board independence have significantly fewer redeployable assets after the shock than those not required to change board composition. This is consistent with the managerial myopia hypothesis. Subject to more intense monitoring, managers behave more myopically, focusing more on assets that are currently useful to the firm and less on redeployability in the future.

Originality/value

The study makes key contributions to the literature. First, the study is the first to examine the effect of board governance on asset redeployability. Second, the authors exploit an innovative index of asset redeployability that has been recently constructed in the literature. Third, by using a natural experiment, the results are much more likely to reflect causality than merely an association.
Between the assessment centre and reality: how and why biographical psychology makes human resource management more effective
Authors: Rudnev Evgeny
Published: October 2021

Purpose

The article makes a conceptual contribution to the substantiation of the foundations in personnel management for the development and decision-making in personnel assessment based on the biographical method.

Design/methodology/approach

When substantiating the scientific direction, a comparative analysis, a comparison of the theoretical provisions of leadership and the methodology of personnel assessment, a critical appraisal of the assessment centre and biographical method were used.

Findings

Modern science contains information about effective leadership and few grounds for objective selection for leadership positions. Why do some individuals become leaders in the churches, while others become leaders of business corporations? The accepted assessment tools allow obtaining information about the candidate, but do not have a scientific basis for making a decision about leadership in recruiting. Biographical psychology brings together leadership theories and assessment tools; it allows to establish a connection between developmental psychology, social, applied and organizational psychology and provides the integration of various directions in science. It allows a deeper understanding of the relationship between a person's biographical facts and his/her suitability in the profession to justify the reasons for leadership, as well as the grounds for selection for managerial positions.

Originality/value

Substantiation of biographical psychology will allow in the future to legitimize the conduct of such studies, to come closer to the truth in the selection for leadership and not only positions, to understand the connection between the biography of leader and organizational culture. Biographical psychology will contribute to the creation of scientific basis for recruiting. To consider biographical factors more significantly (gender, age, sexual orientation, differences in personal development, and not just executive experience in the resume), this will reduce the economic costs of introducing and supporting costly procedures in organizations, as well as increasing the objectivity of the assessment and selection of personnel in organizations.
“We should at least have basic survival skills, right?”: young males support mandatory food skills education
Authors: Zhang Lucy Yixuan , Simonds Kristen , Matthews June
Published: October 2021

Purpose

This study explored young males' suggestions for food skills education in three domains: food selection and planning, food preparation and food safety and storage. It also solicited young males' perspectives on mandatory food skills education.

Design/methodology/approach

This descriptive qualitative study employed a semi-structured interview guide. A one-page list of food skills was provided to each participant to form a consistent basis for the interviews. Data were analyzed using the constant comparative method.

Findings

Forty-four young men aged 17 to 35 participated in the study. Thirty-seven supported mandatory education for food skills. Gender stereotypes around food skills were identified as a barrier to young males enrolling in elective food skills courses. When asked how food skills should be taught, the two main strategies mentioned were “online” and “hands-on.” Most participants identified skills in the food preparation domain as essential to include in the curriculum, although some recognized the importance of incorporating skills from all three domains.

Practical implications

Understanding important characteristics of effective food skills education for young males may increase their participation in school, virtual and community-based food skills education. Curricular content should consider young males' interests and baseline competencies and emphasize practical hands-on skills. Mandatory food skills education in secondary schools for all genders represents a comprehensive solution.

Originality/value

This study is among the first to report young males' opinions on crucial components of, and methods for, effective food skills education for this population.
A study of boundedly rational behaviour in housing choice: evidence from Malaysia
Authors: Tan Consilz
Published: October 2021

Purpose

Housing choice is always a complicated decision with its dual functions as a roof over the head and as an investment good. This paper aims to investigate the boundedly rational behaviours that affect the housing choice three bounded behaviours play roles in explaining the decision-making behaviour of homebuyers when they acquire/sell a property. These behaviours are endowment effect, loss aversion and herding, which have implications on the decision-making process.

Design/methodology/approach

The research is based on cross-sectional questionnaires and collected from 587 respondents. Factor analysis and reliability tests were used to identify the latent construct of bounded rational housing choice behaviour. In the meantime, the study used one-way analysis of variance (ANOVA) to examine whether there are any differences in the housing choice based on the respondents’ demographic backgrounds.

Findings

The findings indicated that a total of 11 items were reduced to three factors that accounted for the decision-making in housing choice. There are significant differences in herding behaviour amongst respondents with different level of education and their purpose of looking for a house.

Research limitations/implications

This paper helps to identify latent constructs that shed light on the housing choice, especially on the bounded rational behaviour.

Originality/value

This is one of the few studies to explore boundedly rational behaviours in housing choice from the angle of homebuyers. Previous studies addressed housing choice in terms of price, demand and supply in general but not on individual homebuyers. The results will be useful to developers, policymakers, homebuyers as well as scholars in understanding the decision-making process in housing choice.