bluuebunny/crossref_metadata_2025 huggingface dataset:
How well do rudimentary plasticity rules predict adult visual object learning?
Authors: Lee Michael J. , DiCarlo James J.
Published: January 2023

A core problem in visual object learning is using a finite number of images of a new object to accurately identify that object in future, novel images. One longstanding, conceptual hypothesis asserts that this core problem is solved by adult brains through two connected mechanisms: 1) the re-representation of incoming retinal images as points in a fixed, multidimensional neural space, and 2) the optimization of linear decision boundaries in that space, via simple plasticity rules applied to a single downstream layer. Though this scheme is biologically plausible, the extent to which it explains learning behavior in humans has been unclear – in part because of a historical lack of image-computable models of the putative neural space, and in part because of a lack of measurements of human learning behaviors in difficult, naturalistic settings. Here, we addressed these gaps by 1) drawing from contemporary, image-computable models of the primate ventral visual stream to create a large set of testable learning models (n=2,408 models), and 2) using online psychophysics to measure human learning trajectories over a varied set of tasks involving novel 3D objects (n=371,000 trials), which we then used to develop (andpublicly release) empirical benchmarks for comparing learning models to humans. We evaluated each learning model on these benchmarks, and found that learning models that using specific, high-level contemporary representations are surprisingly aligned with human behavior. While no tested model explained the entirety of replicable human behavior, these results establish that rudimentary plasticity rules, when combined with appropriate visual representations, have high explanatory power in predicting human behavior with respect to this core object learning problem.

Author Summary

A basic conceptual hypothesis for how an adult brain learns to visually identify a new object is: 1) it re-represents images as points in a fixed, multidimensional space, then 2) it learns linear decision boundaries that separate images of a new object from others, using a single layer of plasticity. This hypothesis is considered biologically plausible, but gauging its power to explain human learning behavior has not been straightforward. In part, this is because it is difficult to model how brains re-represent images during object learning. However, ongoing efforts in neuroscience have led to the identification of specific, image-computable models that are at least partially accurate descriptions of the neural representations involved in primate vision. Here, we asked whether any of those representations, when combined them with simple plasticity rules, could make accurate predictions over a large body of human object learning behavioral measurements. We found that specific models could indeed explain a majority of our behavioral measurements, suggesting the rudimentary, biologically-plausible mechanisms considered here may be sufficient to explain a core aspect of human object learning.
Investigation of the Impact of Clonal Hematopoiesis on Severity and Pathophysiology of COVID-19 in Rhesus Macaques
Authors: Shin Tae-Hoon , Zhou Yifan , Lee Byung-Chul , Hong So Gun , Andrew Shayne F. , Flynn Barbara J. , Gagne Matthew , Todd John-Paul M. , Moore Ian N. , Cook Anthony , Lewis Mark G. , Foulds Kathryn E. , Seder Robert A. , Douek Daniel C. , Roederer Mario , Dunbar Cynthia E.
Published: January 2023

Clinical manifestations of COVID-19 vary widely, ranging from asymptomatic to severe respiratory failure with profound inflammation. Although risk factors for severe illness have been identified, definitive determinants remain elusive. Clonal hematopoiesis (CH), the expansion of hematopoietic stem and progenitor cells bearing acquired somatic mutations, is associated with advanced age and hyperinflammation. Given the similar age range and hyperinflammatory phenotype between frequent CH and severe COVID-19, CH could impact the risk of severe COVID-19. Human cohort studies have attempted to prove this relationship, but conclusions are conflicting. Rhesus macaques (RMs) are being utilized to test vaccines and therapeutics for COVID-19. However, RMs, even other species, have not yet been reported to develop late inflammatory COVID-19 disease. Here, RMs with either spontaneous DNMT3A or engineered TET2 CH along with similarly transplanted and conditioned controls were infected with SARS-CoV-2 and monitored until 12 days post-inoculation (dpi). Although no significant differences in clinical symptoms and blood counts were noted, an aged animal with naturalDNMT3ACH died on 10 dpi. CH macaques showed evidence of sustained local inflammatory responses compared to controls. Interestingly, viral loads in respiratory tracts were higher at every timepoint in the CH group. Lung sections from euthanasia showed evidence of mild inflammation in all animals, while viral antigen was more frequently detected in the lung tissues of CH macaques even at the time of autopsy. Despite the lack of striking inflammation and serious illness, our findings suggest potential pathophysiological differences in RMs with or without CH upon SARS-CoV-2 infection.

Highlights

No evidence of association between CH and COVID-19 clinical severity in macaques.

The presence of CH is associated with prolonged local inflammatory responses in COVID-19.

SARS-CoV-2 persists longer in respiratory tracts of macaques with CH following infection.
SARS-CoV-2 protein NSP2 enhances microRNA-mediated translational repression
Authors: Naeli Parisa , Zhang Xu , Harris Snell Patric , Chatterjee Susanta , Kamran Muhammad , Ladak Reese Jalal , Orr Nick , Duchaine Thomas , Sonenberg Nahum , Jafarnejad Seyed Mehdi
Published: January 2023

microRNAs (miRNAs) inhibit mRNA translation initiation by recruiting the GIGYF2/4EHP translation repressor complex to the mRNA 5’ cap structure. Viruses utilise miRNAs to impair the host antiviral immune system and facilitate viral infection by expressing their own miRNAs or co-opting cellular miRNAs. We recently reported that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) encoded non-structural protein 2 (NSP2) interacts with GIGYF2. This interaction is critical for blocking translation of theIfn1-bmRNA that encodes the cytokine Interferon-ß, and thereby impairs the host antiviral immune response. However, it is not known whether NSP2 also affects miRNA-mediated silencing. Here, we demonstrate the pervasive augmentation of the miRNA-mediated translational repression of cellular mRNAs by NSP2. We show that NSP2 interacts with Argonaute 2, the core component of the miRNA-Induced Silencing Complex (miRISC) and enhances the translational repression mediated by natural miRNA binding sites in the 3’ UTR of cellular mRNAs. Our data reveal an additional layer of the complex mechanism by which SARS-CoV-2 and likely other coronaviruses manipulate the host gene expression program through co-opting the host miRNA-mediated silencing machinery.
The predictive power of intrinsic timescale during the perceptual decision-making process across the mouse brain
Authors: Imani Elaheh , Hashemi Alireza , Radkani Setayesh , Egger Seth W. , Goudarzi Morteza Moazami
Published: January 2023

Across the cortical hierarchy, single neurons are characterized by differences in the extent to which they can sustain their firing rate over time (i.e., their “intrinsic timescale”). Previous studies have demonstrated that neurons in a given brain region mostly exhibit either short or long intrinsic timescales. In this study, we sought to identify populations of neurons that accumulate information over different timescales in the mouse brain and to characterize their functions in the context of a visual discrimination task. Thus, we separately examined the neural population dynamics of neurons with long or short intrinsic timescales across different brain regions. More specifically, we looked at the decoding performance of these neural populations aligned to different task variables (stimulus onset, movement). Taken together, our population-level findings support the hypothesis that long intrinsic timescale neurons encode abstract variables related to decision formation.

Furthermore, we investigated whether there was a relationship between how well a single neuron represents the animal’s choice or stimuli and their intrinsic timescale. We did not observe any significant relationship between the decoding of these task variables and a single neuron’s intrinsic timescale. In summary, our findings support the idea that the long intrinsic timescale population of neurons, which appear at different levels of the cortical hierarchy, are primarily more involved in representing the decision variable.
Circuit to target approach defines an autocrine myofibroblast loop that drives cardiac fibrosis
Authors: Miyara Shoval , Adler Miri , Bassat Elad , Divinsky Yalin , Umansky Kfir B. , Elkahal Jacob , Genzelinakh Alexander , Kain David , Lendengolts Daria , Shalit Tali , Gershovits Michael , Shakked Avraham , Zhang Lingling , Wang Jingkui , Kimchi Danielle M. , Baehr Andrea , Sarig Rachel , Kupatt Christian , Tanaka Elly M. , Medzhitov Ruslan , Mayo Avi , Alon Uri , Tzahor Eldad
Published: January 2023

Fibrosis is a broad pathology of excessive scarring with substantial medical implications. The fibrotic scar is produced by myofibroblasts that interact with macrophages. Fibrosis is a complex process involving thousands of factors, therefore, to better understand fibrosis and develop new therapeutic approaches, it is necessary to simplify and clarify the underlying concepts. Recently, we described a mathematical model for a macrophage-myofibroblast cell circuit, predicting two types of fibrosis - hot fibrosis with abundant macrophages and myofibroblasts, and cold fibrosis dominated by myofibroblasts alone. To test these concepts and intervention strategies in a medically relevant system, we use a widely studiedin-vivoinjury model for fibrosis, myocardial infarction (MI). We show that cold fibrosis is the final outcome of MI in both mice and pigs and demonstrate that fibrosis can shift toward healing in regenerative settings. MI begind with an increase of myofibroblasts and macrophages, followed by macrophage decline leading to persistent cold fibrosis (only myofibroblasts). During this process, fibroblasts, unlike macrophages, acquire distinct fate changes. Using mathematical modeling we predict that targeting of the autocrine signal for myofibroblast division could block cold fibrosis. We identify TIMP1 as an autocrine cardiac myofibroblast growth factorin-vitro. Treatment of adult mice after MI with anti-TIMP1 antibodies reduces fibrosisin-vivo. This study shows the utility of the concepts of hot and cold fibrosis and the feasibility of our circuit-to-target approach to reduce fibrosis after acute cardiac injury by inhibiting the myofibroblast autocrine loop.
Bridging the Gap: Exploring Neural Mechanisms of Facial Repetition Suppression through EEG and DCNNs
Authors: Lu Zitong , Ku Yixuan
Published: January 2023

Facial repetition suppression, a well-studied phenomenon characterized by decreased neural responses to repeated faces in visual cortices, remains a subject of ongoing debate regarding its underlying neural mechanisms. Recent advancements have seen deep convolutional neural networks (DCNNs) achieve human-level performance in face recognition. In our present study, we sought to compare brain activation patterns derived from human electroencephalogram (EEG) data with those generated by DCNNs. Employing reverse engineering techniques, we aimed to provide a novel perspective on the neural mechanisms underlying facial repetition suppression. Our approach involved employing brain decoding methods to investigate how representations of faces change with their familiarity in the human brain. Subsequently, we constructed two models for repetition suppression within DCNNs: the Fatigue model, which posits that stronger activation leads to greater suppression, and the Sharpening model, which suggests that weaker activation results in more pronounced suppression. To elucidate the neural mechanisms at play, we conducted cross-modal representational similarity analysis (RSA) comparisons between human EEG signals and DCNN activations. Our results revealed a striking similarity between human brain representations and those of the Fatigue DCNN, favoring the Fatigue model over the Sharpening hypothesis in explaining the facial repetition suppression effect. These representation analyses, bridging the human brain and DCNNs, offer a promising tool for simulating brain activity and making inferences regarding the neural mechanisms underpinning complex human behaviors.
The Labbing Project: A database management application for neuroimaging research
Authors: Baratz Zvi , Assaf Yaniv
Published: January 2023

The goal of this article is to present “The Labbing Project”; a novel neuroimaging data aggregation and preprocessing web application built with Django and VueJS. Neuroimaging data can be complex and time-consuming to work with, especially for researchers with limited programming experience. This web application aims to streamline the process of aggregating and preprocessing neuroimaging data by providing an intuitive, user-friendly interface that allows researchers to upload, organize, and preprocess their data with minimal programming requirements. The application utilizes Django, a popular Python web framework, to create a robust and scalable platform that can handle large volumes of data and accommodate the needs of a diverse user base. This robust infrastructure is complemented by a user-friendly VueJS frontend application, supporting commonplace data querying and extraction tasks. By automating common data processing tasks, this web application aims to save researchers time and resources, enabling them to focus on their research rather than data management.
Structure of the ISW1a complex bound to the dinucleosome
Authors: Li Lifei , Chen Kangjing , Sia Youyang , Hu Pengjing , Ye Youpi , Chen Zhucheng
Published: January 2023

Nucleosomes are basic repeating units of chromatin, and form regularly spaced arrays in cells. Chromatin remodelers alter the positions of nucleosomes, and are vital in regulating chromatin organization and gene expression. Here we report the cryoEM structure of chromatin remodeler ISW1a complex bound to the dinucleosome. Each subunit of the complex recognizes a different nucleosome. The motor subunit binds to the mobile nucleosome and recognizes the acidic patch through two arginine residues, and the DNA-binding module interacts with the entry DNA at the nucleosome edge. This nucleosome-binding mode provides the structural basis for linker DNA sensing of the motor. Notably, the Ioc3 subunit recognizes the disk face of the adjacent nucleosome through the H4 tail, the acidic patch and the nucleosomal DNA, which is important for the spacing activity in vitro, and for nucleosome organization and cell fitness in vivo. Together, these findings support the nucleosome spacing activity of ISW1a, and add a new mode of nucleosome remodeling in the context of a chromatin environment.
LptM promotes oxidative maturation of the lipopolysaccharide translocon by substrate binding mimicry
Authors: Yang Yiying , Chen Haoxiang , Corey Robin A. , Morales Violette , Quentin Yves , Froment Carine , Caumont-Sarcos Anne , Albenne Cécile , Burlet-Schiltz Odile , Ranava David , Stansfeld Phillip J. , Marcoux Julien , Ieva Raffaele
Published: January 2023

Insertion of lipopolysaccharide (LPS) into the outer membrane (OM) of Gram-negative bacteria is mediated by a druggable OM translocon consisting of a β-barrel membrane protein, LptD, and a lipoprotein, LptE. The β-barrel assembly machinery (BAM) assembles LptD together with LptE to form a plug-and-barrel structure. In the enterobacteriumEscherichia coli, formation of two native disulfide bonds in LptD controls LPS translocon activation. Here we report the discovery of LptM (formerly YifL), a conserved lipoprotein that assembles together with LptD and LptE at the BAM complex. We demonstrate that LptM stabilizes a conformation of LptD that can efficiently acquire native disulfide bonds and be released as mature LPS translocon by the BAM complex. Inactivation of LptM causes the accumulation of non-natively oxidized LptD, making disulfide bond isomerization by DsbC become essential for viability. Our structural prediction and biochemical analyses indicate that LptM binds to sites in both LptD and LptE that are proposed to coordinate LPS insertion into the OM. These results suggest that LptM facilitates oxidative maturation of LptD by mimicking LPS binding, thereby activating the LPS translocon.
Multiple independent components contribute to event-related potential correlates of conscious vision
Authors: Colombari Elisabetta , Railo Henry
Published: January 2023

Research has revealed two major event-related potential (ERP) markers of visual awareness: the earlier Visual Awareness Negativity (VAN, around 150–250 ms after stimulus onset), and the following Late Positivity (LP, around 300–500 ms after stimulus onset). Understanding the neural sources that give rise to VAN and LP is important in order to understand what kind of neural processes enable conscious visual perception. Although the ERPs afford high temporal resolution, their spatial resolution is limited because multiple separate sources sum up at the scalp level. In the present study, we sought to characterize the locations and time-courses of independent neural sources underlying the ERP correlates of visual awareness by means of Independent Component Analysis (ICA). ICA allows identifying and localizing the temporal dynamics of different neural sources that contribute to the ERP correlates of conscious perception. The present results show that while LP reflects a combination of multiple sources distributed among frontal, parietal and occipito-temporal cortex, the sources of VAN are localized to posterior areas including occipital and temporal cortex. In addition, our analysis reveals that activity in very early sources (roughly -100–100 ms after stimulus onset) in temporal and fronto-parietal cortices correlates with conscious vision.
Optimizing FreeSurfer’s Surface Reconstruction Parameters for Anatomical Feature Estimation
Authors: Baratz Zvi , Assaf Yaniv
Published: January 2023

Magnetic resonance imaging (MRI) is a powerful tool for non-invasive imaging of the human body. However, the quality and reliability of MRI data can be influenced by various factors, such as hardware and software configurations, image acquisition protocols, and preprocessing techniques. In recent years, the introduction of large-scale neuroimaging datasets has taken an increasingly prominent role in neuroscientific research. The advent of publicly available and standardized repositories has enabled researchers to combine data from multiple sources to explore a wide range of scientific inquiries. This increase in scale allows the study of phenomena with smaller effect sizes over a more diverse sample and with greater statistical power.

Other than the variability inherent to the acquisition of the data across sites, preprocessing and feature generation steps implemented in different labs introduce an additional layer of variability which may influence consecutive statistical procedures. In this study, we show that differences in the configuration of surface reconstruction from anatomical MRI using FreeSurfer results in considerable changes to the estimated anatomical features. In addition, we demonstrate the effect these differences have on within-subject similarity and the performance of basic prediction tasks based on the derived anatomical features.

Our results show that although FreeSurfer may be provided with either a T2w or a FLAIR scan for the same purpose of improving pial surface estimation (relative to based on the mandatory T1w scan alone), the two configurations have a distinctly different effect. In addition, our findings indicate that the similarity of within-subject scans and performance of a range of models for the prediction of sex and age are significantly effected, they are not significantly improved by either of the enhanced configurations. These results demonstrate the large extent to which elementary and sparsely reported differences in preprocessing workflow configurations influence the derived brain features.

The results of this study are meant to underline the importance of optimizing preprocessing procedures based on experimental results prior to their distribution and consecutive standardization and harmonization efforts across public datasets. In addition, preprocessing configurations should be carefully reported and included in any following analytical workflows, to account for any variation originating from such differences. Finally, other representations of the raw data should be explored and studied to provide a more robust framework for data aggregation and sharing.
LoxCode in vivo barcoding resolves epiblast clonal fate to fetal organs
Authors: Weber Tom S. , Biben Christine , Miles Denise C. , Glaser Stefan , Tomei Sara , Lin Michael , Kueh Andrew , Pal Martin , Zhang Stephen , Tam Patrick P. L. , Taoudi Samir , Naik Shalin H.
Published: January 2023

Much remains to be learned about the clonal fate of mammalian epiblast cellsin vivo. Here we develop a high diversity, high throughput, Cre recombinase-driven DNA LoxCode barcoding technology forin vivoclonal lineage tracing. E5.5 pre-gastrulation embryos were barcodedin uteroand epiblast clones later assessed for their contribution to a wide range of tissues and cell types in the E12.5 organogenesis-stage embryo. While a few epiblast clones contributed broadly to most tissues and cell types of the three germ layers, many clones were lineage biased towards either blood, ectoderm lineages, mesenchymal tissues or limbs. In addition to lineage bias, most epiblast clones were differentially fated for tissue types or descendants in tissues compartments across the body axes. Using a stochastic agent-based model of embryogenesis and LoxCode barcoding, we inferred and experimentally validated predicted cell fate biases as well as clonal compositions across tissues that are consistent with events of lineage segregation and shared trajectory of lineage differentiation. Our study has demonstrated the power of LoxCode barcoding in investigating multi-modal clonal fate at high throughput, thus enabling an in-depth interrogation of the clonal contribution of E5.5 epiblast cells to fetal tissues, organs and body parts.
Ethyl Maltol Disrupts Iron Homeostasis in SH-SY5Y Neuroblastoma Cell Line
Authors: Sun Yuchen , Bressler Joseph
Published: January 2023

Ethyl Maltol (EM) is a commonly used flavoring compound and has been reported to bind iron and facilitate iron transport. Because EM is highly lipophilic, the potential that it disrupts intracellular iron homeostasis was investigated. EM increased the labile iron pool in SH-SY5Y cells and increased iron-responsive protein activity using a reporter assay in the HEK293 cells. EM induced the expression of transferrin receptor 1 mRNA and decreased expression of ferritin light chain protein in SH-SY5Y cells. Expression of the iron-responsive protein amyloid precursor protein attenuated the effects of EM on these iron-responsive genes. EM treatment decreased cell viability and increased DNA damage. EM also induced the phosphorylation of p53 and the expression of the p53 regulated genes, p21 and 14-3-3σ. The expression of APP attenuated the effects of EM on viability, DNA damage, and the p53 response. Overall, we suggest that EM decreases cell viability through a mechanism involving the p53 pathway. The attenuated responses observed in cells expressing APP suggests that the effects of EM are due to disrupting iron homeostasis.
Systematic assessment of the contribution of structural variants to inherited retinal diseases
Authors: Wen Shu , Wang Meng , Qian Xinye , Li Yumei , Wang Keqing , Choi Jongsu , Pennesi Mark E. , Yang Paul , Marra Molly , Koenekoop Robert K. , Lopez Irma , Matynia Anna , Gorin Michael , Sui Ruifang , Yao Fengxia , Goetz Kerry , Porto Fernanda Belga Ottoni , Chen Rui
Published: January 2023

Despite increasing success in determining genetic diagnosis for patients with inherited retinal diseases (IRDs), mutations in about 30% of the IRD cases remain unclear or unsettled after targeted gene panel or whole exome sequencing. In this study, we aimed to investigate the contributions of structural variants (SVs) to settling the molecular diagnosis of IRD with whole-genome sequencing (WGS). A cohort of 755 IRD patients whose pathogenic mutations remain undefined was subjected to WGS. Four SV calling algorithms including include MANTA, DELLY, LUMPY, and CNVnator were used to detect SVs throughout the genome. All SVs identified by any one of these four algorithms were included for further analysis. AnnotSV was used to annotate these SVs. SVs that overlap with known IRD-associated genes were examined with sequencing coverage, junction reads, and discordant read pairs. PCR followed by Sanger sequencing was used to further confirm the SVs and identify the breakpoints. Segregation of the candidate pathogenic alleles with the disease was performed when possible. In total, sixteen candidate pathogenic SVs were identified in sixteen families, including deletions and inversions, representing 2.1% of patients with previously unsolved IRDs. Autosomal dominant, autosomal recessive, and X-linked inheritance of disease-causing SVs were observed in 12 different genes. Among these, SVs inCLN3, EYS, PRPF31were found in multiple families. Our study suggests that the contribution of SVs detected by short-read WGS is about 0.25% of our IRD patient cohort and is significantly lower than that of single nucleotide changes and small insertions and deletions.
Rare catechol-O-methyltransferase (COMT) missense variants are structurally unstable proteasome targets
Authors: Larsen Fia B. , Cagiada Matteo , Dideriksen Jonas , Stein Amelie , Lindorff-Larsen Kresten , Hartmann-Petersen Rasmus
Published: January 2023

Catechol-O-methyltransferase (COMT) is a key enzyme in the metabolism of catecholamines. Substrates of the enzyme include neurotransmitters such as dopamine and epinephrine, and therefore, COMT plays a central role in neurobiology. Since COMT also metabolises catecholamine drugs such as L-DOPA, variation in COMT activity could affect pharmacokinetics and drug availability. Certain COMT missense variants have been shown to display decreased enzymatic activity. Additionally, studies have shown that such missense variants may lead to loss-of-function induced by impaired structural stability, which results in activation of the protein quality control system and degradation by the ubiquitin-proteasome system. Here, we demonstrate that two rare missense variants of COMT are ubiquitylated and targeted for proteasomal degradation as a result of structural destabilisation and misfolding. This results in strongly reduced intracellular steady-state levels of the enzyme, which for the L135P variant is rescued upon binding to the COMT inhibitors entacapone and tolcapone. Our results reveal that the degradation is independent of the COMT isoform, as both soluble (S-COMT) and ER membrane-bound (MB-COMT) variants are degraded.In silicostructural stability predictions identify regions within the protein that are critical for stability overlapping with evolutionarily conserved residues, pointing towards other variants that are likely destabilised and degraded.
Generation of nanobodies acting as silent and positive allosteric modulators of the α7 nicotinic acetylcholine receptor
Authors: Li Qimeng , Nemecz Ákos , Aymé Gabriel , de la Bâtie Gabrielle Dejean , Prevost Marie S , Pons Stéphanie , Barilone Nathalie , Baachaoui Rayen , Maskos Uwe , Lafaye Pierre , Corringer Pierre-Jean
Published: January 2023

The α7 nicotinic acetylcholine receptor (nAChR), a potential drug target for treating cognitive disorders, mediates communication between neuronal and non-neuronal cells. Although many competitive antagonists, agonists, and partial-agonists have been found and synthesized, they have not led to effective therapeutic treatments. In this context, small molecules acting as positive allosteric modulators binding outside the orthosteric, acetylcholine, site have attracted considerable interest. Two single-domain antibody fragments, C4 and E3, against the extracellular domain of the human α7-nAChR were generated through alpaca immunization with cells expressing a human α7-nAChR/mouse 5-HT3A chimera, and are herein described. They bind to the α7-nAChR but not to the other major nAChR subtypes, α4β2 and α3β4. E3 acts as a slowly associating positive allosteric modulator, strongly potentiating the acetylcholine-elicited currents, while not precluding the desensitization of the receptor. An E3-E3 bivalent construct shows similar potentiating properties but displays very slow dissociation kinetics conferring quasi-irreversible properties. Whereas, C4 does not alter the receptor function, but fully inhibits the E3-evoked potentiation, showing it is a silent allosteric modulator competing with E3 binding. Both nanobodies do not compete with α-bungarotoxin, localizing at an allosteric extracellular binding site away from the orthosteric site. The functional differences of each nanobody, as well as the alteration of functional properties through nanobody modifications indicate the importance of this extracellular site. The nanobodies will be useful for pharmacological and structural investigations; moreover, they, along with the extracellular site, have a direct potential for clinical applications.
NEK1-Mediated Phosphorylation of YAP1 is key to Prostate Cancer Progression
Authors: Ghosh Ishita , Khalil Imtiaz Md , Mirza Rusella , King Judy , Olatunde Damilola , De Benedetti Arrigo
Published: January 2023

Understanding how Androgen-dependent PCa cells progress to independence and modify accordingly their transcriptional repertoire is the key to preventing mCRPC progression. We recently identified a novel axis of the Hippo pathway characterized by the sequential kinase cascade induced by androgen deprivation: AR−>TLK1B>NEK1>pYAP1-Y407 leading to CRPC adaptation. Phosphorylation of YAP-Y407 increases upon ADT or induction of DNA damage, correlated with the known increase in NEK1 expression/activity, and this is suppressed in the Y407F mutant. Dominant expression of YAP1-Y407F in Hek293 cells reprograms the YAP1-mediated transcriptome to reduced TEAD- and P73-regulated gene expression and mediates sensitivity to MMC. NEK1 haploinsufficient TRAMP mice display reduced YAP1 expression and if castrated fail to progress to overt prostate carcinomas, even while displaying reduced E-CAD expression in hyperplastic ductules. YAP1 overexpression, but not the Y407F mutant, transforms LNCaP cells to androgen independent growth and a mesenchymal morphology. Immunohistochemical examination of Prostate Cancer biopsies revealed that pYAP1-Y407 nuclear signal is low in samples of low-grade cancer but elevated in high GS specimens. We also found that J54, pharmacological inhibitor of the TLK1>NEK1>YAP1 nexus, leading to degradation of YAP1 can suppress the transcriptional reprogramming of LNCaP cells to Androgen-Independent growth and EMT progression even when YAP1-WT is overexpressed.
Right-handed Z-DNA at ultrahigh resolution: a tale of two hands and the power of the crystallographic method
Authors: Drozdzal Pawel , Manszewski Tomasz , Gilski Miroslaw , Brzezinski Krzysztof , Jaskolski Mariusz
Published: January 2023

The self-complementary L-d(CGCGCG)2 purine/pyrimidine hexanucleotide was crystallized in complex with the polyamine cadaverine and potassium cations. Since the oligonucleotide contained the enantiomeric 2′-deoxy-L-ribose, the Z-DNA duplex is right-handed, as confirmed by the ultrahigh-resolution crystal structure determined at 0.69 Å resolution. Although the X-ray diffraction data were collected at a very short wavelength (0.7085 Å), where the anomalous signal of the P and K atoms is very weak, the signal was sufficiently outstanding to clearly indicate the wrong hand when the structure was mistakenly solved assuming the presence of 2′-deoxy-D-ribose. The electron density clearly shows the entire cadaverinium dication, which has an occupancy of 0.53 and interacts with one Z-DNA duplex. The K+ cation, with an occupancy of 0.32, has an irregular coordination sphere that is formed by three OP atoms of two symmetry-related Z-DNA duplexes and one O5′ hydroxyl O atom, and is completed by three water sites, one of which is twofold disordered. The K+ site is complemented by a partial water molecule, the hydrogen bonds of which have the same lengths as the K—O bonds. The sugar-phosphate backbone assumes two conformations, but the base pairs do not show any sign of disorder.
Enhancing students’ understanding and performance in a distance-learning setting: evidence from an audit simulation at a GCC university
Authors: Elsayed Nader , Ismael Hazem Ramadan , Saadullah Shahriar M.
Published: January 2023

Purpose

Drawing on experiential learning theory (ELT), this study aims to examine students’ performance and perceptions after performing an experiential learning activity (ELA) by completing a mini-audit simulation (AS) on the purchase and cash disbursement processes in a distance-learning environment at a Gulf Cooperation Council (GCC) university.

Design/methodology/approach

Adopting a mixed-methods approach, we collected quantitative and qualitative data from 176 students using the grade centre on Blackboard and their responses to a semi-structured questionnaire.

Findings

The pre-and post-simulation tests indicate significant improvement in students’ understanding and performance after performing the mini-AS. The students’ responses also provide robust evidence of student engagement, active participation and positive recognition of the AS’s value.

Practical implications

This study has several implications: for the accounting education literature, how AS strengthens in-depth learning through the lens of ELT; for professional accounting bodies, informing the need to maximise the awareness and benefits of adopting simulations in accounting education and examination; and for educators, considering simulations in their ELAs to enhance student learning.

Originality/value

This study introduces a new authentic mini-AS instrument that can be adapted to a distance-learning setting, adds to the very limited studies in AS using ELT, uses a mixed-methods approach and explores students who learn in an Arabic-speaking country.
Does corporate governance quality improve credit ratings of financial institutions? Evidence from ownership and board structure
Authors: Mili Mehdi , Alaali Yusuf
Published: January 2023

Purpose

The purpose of this paper is to examine to which extent ownership and board structure improve financial institutions’ credit ratings.

Design/methodology/approach

Ordered Probit regression models were used to examine the association between corporate governance attributes and banks’ credit ratings. The sample consists of 97 publicly traded financial institutions on Gulf Cooperation Council (GCC) stock exchange markets and cover the period 2010–2019. All GCC countries were considered in this study which are United Arab Emirates, Saudi Arabia, Bahrain, Oman, Kuwait and Qatar.

Findings

The results show that banks’ credit ratings are positively associated with the size of the board of directors and with the number of female directors serving in the board of directors. And it is negatively associated with the frequency of board meetings. Furthermore, this study finds evidence that nonbank financial institutions’ credit ratings are positively associated with CEO duality and with frequency of board meetings. Also, this study shows that their credit ratings are negatively associated with the ownership percentage held by the major five shareholders and with the number of board members serving in the board of directors.

Originality/value

Unlike previous research, this study focuses on the effect of the role of two different corporate governance dimensions, namely, ownership and board structure on the rating of financial institutions. This paper contributes to the extant literature in various ways. It bridges the gap of this topic in the GCC region. And, unlike previous research, this study focused on the financial sector and divided the sample into banks and other financial institutions to examine both subsamples separately. Also, this study introduced new ownership and board structure variables for the purpose of investigating the impact of corporate governance on financial institutions’ credit ratings such as the presence of women in the board of directors.
The influence of knowledge creation process on customer relations management: evidence from Palestinian commercial banks
Authors: Abusharbeh Mohammed
Published: January 2023

Purpose

The purpose of this study is to examine the influence of knowledge creation (KC) process on customer relations management (CRM) in Palestinian commercial banks, taking into consideration which factors of KC process support the CRM system.

Design/methodology/approach

The study uses a quantitative research design wherein questionnaires have been used to collect data from 345 respondents in the Palestinian banking sector. Research hypotheses have been tested using multiple regression analysis.

Findings

The findings unveil that socialisation and combination processes have a positive impact on CRM. In contrast, internalisation process negatively affects CRM system, but outsourcing knowledge does not significantly affect CRM.

Research limitations/implications

Past studies empirically validated the success of CRM adaptation in the context of different industries. This study provides a new conceptual model which validates the influence of KC on CRM in the banking sector. It also affirms the integral role of KC in supporting CRM from an emerging country perspective like Palestine.

Practical implications

This study offers new insights into creating of knowledge by employees in supporting CRM. It will encourage future scholars to further explore the key dimensions of the KC process for a more detailed investigation at a workplace. This study suggests that banks’ directors and employees should behave in a social manner to support relationship with customers. This study also suggests facilitating knowledge from different resources in innovative ways, through encouraging creative thinking from experiences, using technology in sharing knowledge, focussing on appropriate training to resolve customers' problems and disseminating new knowledge among employees.

Originality/value

This study expands the body of knowledge on KC process in supporting CRM from an emerging country perspective. This study validates the influence of KC on CRM in the Palestinian banking sector. This sheds light on the integration of these two concepts.
Bringing clarity to the leadership of teaching and learning in higher education: a systematic review
Authors: Kinnunen Päivi , Ripatti-Torniainen Leena , Mickwitz Åsa , Haarala-Muhonen Anne
Published: January 2023

Purpose

The study aims to investigate the state of higher education (HE) leadership research after the intensified focus on teaching and learning (TL) in academia.

Design/methodology/approach

The authors clarify the use of key concepts in English-medium empirical journal articles published between 2017 and 2021 by analysing 64 publications through qualitative content analysis.

Findings

The analysed papers on leadership of TL in HE activate a number of concepts, the commonest concepts being academic leadership, distributed leadership, educational leadership, transformational leadership, leadership and transformative leadership. Even if the papers highlight partly overlapping aspects of leadership, the study finds a rationale for the use of several concepts in the HE context. Contrary to the expectation raised in earlier scholarship, no holistic framework evolves from within the recent research to reveal the contribution that leadership of TL makes to leadership in HE generally.

Research limitations/implications

Limitations: Nearly 40 per cent of the analysed articles are from the United States of America (USA), United Kingdom (UK), Australia and Canada, which leaves large areas of the world aside. Implications: The found geographical incoherence might be remediated and the research of leadership of TL in HE generally led forward by widening the cultural and situational diversity in the field.

Originality/value

This research contributes to an enhanced understanding of the field of leadership in TL in HE in that it frames the concepts used in recent research and makes the differences, similarities and rationale between concepts visible.
A systematic literature review of money mule: its roles, recruitment and awareness
Authors: Abdul Rani Mohd Irwan , Syed Mustapha Nazri Sharifah Nazatul Faiza , Zolkaflil Salwa
Published: January 2023

Purpose

This paper aims to provide a systematic literature review (SLR) on contemporary cardinal money mule issues.

Design/methodology/approach

This paper reviews the most common money mule themes in perpetrating financial crime activities, especially its roles, recruitment and awareness. A systematic review protocol called preferred reporting items for systematic review and meta-analysis protocols is adopted for this study.

Findings

Money mules are used by organized criminal groups (OCG) or fraudster to launder illicit funds from outrageous criminal activities. They allow their accounts to be used for money laundering by OCG. The attacker, OCG or fraudsters would layer the stolen funds using money mule accounts. These money mules are recruited using various approaches, oftentimes deceived by opulent lifestyles to captivate the interest of potential money mules.

Originality/value

This paper presents money mule awareness needed by accountant, bank employees and the society. It is an unprecedented SLR on money mule. This paper will be beneficial for future money mule researchers, enforcement agencies and practitioners in banking industry.
Signaling norm salience through perceived peer counterfeit consumption
Authors: Khan Sameeullah , Fazili Asif Iqbal , Bashir Irfan
Published: January 2023

Purpose

This paper aims to theorize that millennials' counterfeit buying behavior is partly driven by perceived peer counterfeit consumption – the perception that counterfeit luxury consumption is a norm within members of their own generation.

Design/methodology/approach

The research is based on two survey-based studies: Study 1 investigates the phenomenon on young millennials (n = 438) and Gen X (n = 374) using moderation analyses in PROCESS Macro; and Study 2 is based on young millennials (n = 643) and runs a partial least squares structural equation modeling model.

Findings

The findings reveal that perceived counterfeit consumption within own (vs other) generation leads to greater counterfeit purchase intention and this effect is stronger for young millennials (vs Gen X). Counterfeiting values (materialism, counterconformity and morality) strengthen the impact of perceived peer counterfeit consumption on the counterfeit purchase intention of young millennials, thereby establishing counterfeit luxury consumption as a salient norm.

Practical implications

To modify perceptions about peer counterfeiting norms, normative messages must communicate counterfeit avoidance among millennials through social media influencers. Luxury brand managers must focus on the experiential value of luxury and pursue unconventional luxury inspired by a sense of rebelliousness and independence.

Originality/value

This work demonstrates that millennials engage in counterfeit luxury consumption when they perceive it as a salient consumption norm among members of their own generation. It adds a novel construct of perceived counterfeit consumption and demonstrates the role of generation as a normative referent. The article provides a values-based motivational account of conformity to peer counterfeiting norms.
Investment strategies and coordination for green food supply chain: a further research considering the inputs of the blockchain-based traceability system
Authors: Liu Pan
Published: January 2023

Purpose

To study these issues, the authors chose a GFSC with one producer and one material supplier as research object, the supplier will offer green material to the producer and the producer will make green food using green production technology. Then, the authors proposed that consumers' perceived value was determined by the trustworthiness levels of the related green and quality-safety information provided by the supplier and the producer. Then, considering the trustworthiness levels of the green and quality information provided by the supplier and the producer, the authors improved the demand function. Afterwards, we constructed four investment models and their income models are built and then a cost-sharing and revenue-sharing contract (hereafter, CSRS) was adopted to coordinate the GFSC.

Design/methodology/approach

With the growth of consumers environmental awareness and life level, consumers' requirements for green and high quality food are growing. In recently years, to increase consumers' perceived trustworthiness on the product greenness and quality levels, stakeholders in green food supply chain (hereafter, GFSC) start to adopt the blockchain-based traceability system (hereafter, BLTS). For investors, they need to know the investment conditions and how to coordinate the GFSC.

Findings

(1) When the revenue-sharing coefficient is less than three-fourths and higher then a certain vaule, the cost-sharing and revenue-sharing contract can make the GFSC coordinate. (2) The investment cost threshold of the BLTS has a positive relationship with the trustworthiness improvement levels of the green and quality information, the green degree of food products and the quality of food products. (3) In the proposed four investment situations, as the growth of consumers perceived credibility coefficient about the greenness information and the quality information, chain members' revenues will increase. In addition, comparing with co-investing the BLTS, benefits of chain members are lower than them in the sole investment model.

Originality/value

(1) The demand function we proposed can help chain members forecast market demand to support production or ordering decisions. (2) The investment decision policies can offer a theoretical reference for chain members to use the BLTS. (3) The CSRS will offer the theoretical reference for coordinating the supply chain after using the BLTS. Furthermore, our study method can be referenced by other scholars. (4) The study method can offer a method reference for researchers who do a similar discussion in a manufacturing supply chain. Although, our research cannot guide the industrial practices, it can serve as a reference of the similar research in industry.