bluuebunny/crossref_metadata_2025 huggingface dataset:
ENHANCED EFFICIENCY OF RNA-GUIDED CAS12a VERSUS CAS9 TRANSGENE KNOCK-IN AND ACTIVITY AT ASCHISTOSOMA MANSONIGENOME SAFE HARBOR
Authors: Moescheid Max F. , Wisitphongpun Prapakorn , Mann Victoria H. , Quack Thomas , Grunau Christoph , Grevelding Christoph G. , Ittiprasert Wannaporn , Brindley Paul J.
Published: September 2023

Recently, we reported programmed Cas9 mediated insertion of a reporter gene into a gene safe harbor site, GSH1, ofSchistosoma mansonivia homology-directed repair (HDR) using overlapping guide RNAs. Here, we report efficient and precise CRISPR/Cas12a-mediated homology directed insertion (knockin, KI) of a 5’ C6-PEG10-modified double-stranded transgene bearing microhomology arms, 50 nt in length, at GSH1. At the outset, we undertook bioinformatic and computational analysis following by experimental verification of the regulatory activity of endogenous schistosome ubiquitin (SmUbi) promoter and terminator, to drive strong reporter gene expression. Green fluorescent protein activity driven by SmUbi followed electroporation-mediated transfection of schistosome eggs. HDR induced by RNA-guided CRISPR/Cas12a, which releases overhanging DNA strands of 18-24, delivered more efficient KI than CRISPR/Cas9. In this non-model pathogen, programmed KI facilitated precise chromosomal integration of the reporter-gene with at GSH1. The approach advances schistosome transgenesis field and may also advance functional genomics and transfection methods in related parasitic and non-parasitic helminths, which hitherto lack these tools.

Author summary

Genome editing (CRISPR) technology is revolutionizing advances in biology, medicine, and agriculture. Transgenesis approaches are integral in diverse applications including gene therapy, biotherapeutics, deciphering host-pathogen interactions, and enhancements in agricultural production. Parasitic worms that are responsible for infectious diseases including neglected tropical diseases (NTDs), which cause substantial morbidity and mortality. NTDs mainly occur in the Global South, and they are responsible for a disease burden that exceeds that caused by malaria and tuberculosis. Infections with parasitic helminths also are responsible for immense economic burden in the agriculture. Tools for functional genomics in parasitic helminths are limited. Access to CRISPR-based approaches can be expected to hasten development of drug and/or vaccine targets for these diseases. Here, we focused on the helminthSchistosoma mansoni, a water borne parasite of humans, and which is endemic in Africa, and northeastern South America. To advance the state of the art in laboratory techniques currently used to study the biology and pathogenesis of this and related pathogens, we evaluated a spectrum of technological approaches aimed at improved current lab practice in this field. The findings demonstrated that specific technical and chemical modifications, including deploying a DNA cutting enzyme termed Cas12a along with a transgene with chemically modified short flanking sequences (homology arms) provided improved gene editing efficiency for this schistosome.
Manufacturing DNA in E. coli yields higher fidelity DNA thanin vitroenzymatic synthesis
Authors: Hersch Steven J. , Chandrasekaran Siddarth , Lam Jamie , Nafissi Nafiseh , Slavcev Roderick A.
Published: September 2023

The rise of biotechnologies such as gene therapy have brought DNA vectors to the forefront of pharmaceutical development. The quality of the genetic starting material plays a pivotal role in determining the quality of the final product. In this study we examined the fidelity of DNA replication using enzymatic methods (in vitro) compared to plasmid DNA producedin vivoinE. coli. Next-generation sequencing approaches predominantly rely onin vitropolymerases, which have inherent limitations in sensitivity. To address this challenge, we introduce a novel assay based on loss-of-function (LOF) mutations in the conditionally toxicsacBgene. Our findings show that DNA production inE. coliresults in significantly fewer LOF mutations (approximately 80-to 3000-fold less) compared to various enzymatic DNA synthesis methods. This includes the most accurate PCR polymerase (Q5) and a commonly employed rolling circle amplification (RCA) DNA polymerase (Phi29). These results suggest that using low-fidelity starting material DNA synthesizedin vitroby PCR or RCA may introduce a substantial number of impurities, potentially affecting the quality and yield of final pharmaceutical products. In summary, our study underscores that DNA synthesizedin vitrohas a significantly higher mutation rate than DNA produced traditionally inE. coli. Therefore, utilizingin vitroenzymatically-produced DNA in biotechnology and biomanufacturing may entail considerable fidelity-related risks, while DNA starting material derived fromE. colisubstantially mitigates this risk, enhancing overall quality in the production processes.
Analysis of 26S Proteasome Activity Across Arabidopsis Tissues
Authors: Ganapathy Jagadeesan , Hand Katherine A. , Shabek Nitzan
Published: September 2023

Plants utilize the ubiquitin proteasome system (UPS) to orchestrate numerous essential cellular processes, including the rapid responses required to cope with abiotic and biotic stresses. The 26S proteasome serves as the central catalytic component of the UPS that allows for proteolytic degradation of ubiquitin-conjugated proteins in a highly specific manner. Despite the increasing number of studies employing cell-free degradation assays to dissect the pathways and target substrates of the UPS, the precise extraction methods of highly potent tissues remain unexplored. Here, we utilize a fluorogenic reporting assay using two extraction methods to survey proteasomal activity in differentArabidopsis thalianatissues. This study provides new insights into the enrichment of activity and varied presence of proteasomes in specific plant tissues.
BrainLM: A foundation model for brain activity recordings
Authors: Caro Josue Ortega , Fonseca Antonio H. de O. , Averill Christopher , Rizvi Syed A. , Rosati Matteo , Cross James L. , Mittal Prateek , Zappala Emanuele , Levine Daniel , Dhodapkar Rahul M. , Han Insu , Karbasi Amin , Abdallah Chadi G. , van Dijk David
Published: September 2023

Abstract

We introduce the Brain Language Model (BrainLM), a foundation model for brain activity dynamics trained on 6,700 hours of fMRI recordings. Utilizing self-supervised masked-prediction training, BrainLM demonstrates proficiency in both fine-tuning and zero-shot inference tasks. Fine-tuning allows for the accurate prediction of clinical variables like age, anxiety, and PTSD as well as forecasting of future brain states. Critically, the model generalizes well to entirely new external cohorts not seen during training. In zero-shot inference mode, BrainLM can identify intrinsic functional networks directly from raw fMRI data without any network-based supervision during training. The model also generates interpretable latent representations that reveal relationships between brain activity patterns and cognitive states. Overall, BrainLM offers a versatile and interpretable framework for elucidating the complex spatiotemporal dynamics of human brain activity. It serves as a powerful “lens” through which massive repositories of fMRI data can be analyzed in new ways, enabling more effective interpretation and utilization at scale. The work demonstrates the potential of foundation models to advance computational neuroscience research.
Predicting fungal secondary metabolite activity from biosynthetic gene cluster data using machine learning
Authors: Riedling Olivia , Walker Allison S. , Rokas Antonis
Published: September 2023

Fungal secondary metabolites (SMs) play a significant role in the diversity of ecological communities, niches, and lifestyles in the fungal kingdom. Many fungal SMs have medically and industrially important properties including antifungal, antibacterial, and antitumor activity, and a single metabolite can display multiple types of bioactivities. The genes necessary for fungal SM biosynthesis are typically found in a single genomic region forming biosynthetic gene clusters (BGCs). However, whether fungal SM bioactivity can be predicted from specific attributes of genes in BGCs remains an open question. We adapted previously used machine learning models for predicting SM bioactivity from bacterial BGC data to fungal BGC data. We trained our models to predict antibacterial, antifungal, and cytotoxic/antitumor bioactivity on two datasets: 1) fungal BGCs (dataset comprised of 314 BGCs), and 2) fungal (314 BGCs) and bacterial BGCs (1,003 BGCs); the second dataset was our control since a previous study using just the bacterial BGC data yielded prediction accuracies as high as 80%. We found that the models trained only on fungal BGCs had balanced accuracies between 51-68%, whereas training on bacterial and fungal BGCs yielded balanced accuracies between 61-74%. The lower accuracy of the predictions from fungal data likely stems from the small number of BGCs and SMs with known bioactivity; this lack of data currently limits the application of machine learning approaches in studying fungal secondary metabolism. However, our data also suggest that machine learning approaches trained on bacterial and fungal data can predict SM bioactivity with good accuracy. With more than 15,000 characterized fungal SMs, millions of putative BGCs present in fungal genomes, and increased demand for novel drugs, efforts that systematically link fungal SM bioactivity to BGCs are urgently needed.
Discovery of specific activity of 2-HPA acting on the membrane progestin receptor α (paqr7) by purification of natural products from the marine algaePadina
Authors: Amin Mohammad Tohidul , Acharjee Mrityunjoy , Sarwar Jyoti Md. Maisum , Rezanujjaman Md. , Hassan Md. Maksudul , Hossain Md. Forhad , Ahamed Saokat , Kodani Shinya , Tokumoto Toshinobu
Published: September 2023

Membrane progestin receptors (mPRs) are members of the progestin and adipoQ (PAQR) receptor family that are stimulated by endogenous steroids to initiate rapid intracellular signalling through a nongenomic pathway. Previously, water-soluble compounds with mPRα-binding activity from the marine algaePadina arborescenswere fractionated by HPLC steps. In this study, the structure of one of the major compounds in the fraction was identified as 2-hydroxypentanoic acid (2-HPA) using Nuclear Magnetic Resonance spectroscopy. 2-HPA showed a substantial competitive binding affinity for hmPRα in the GQD-hmPRα binding assay. In contrast, synthetic structural analogues of 2-HPA showed no competitive binding activity. The physiological activity of 2-HPA and its analogues was then investigated usingin vitrogoldfish andin vivozebrafish oocyte maturation and ovulation assays. As with the hmPRα binding assay, only 2-HPA showed inhibitory activity on oocyte maturation and ovulation of fish oocytes. Furthermore, the inhibitory activity of 2-HPA was compared between S- and R-type 2-HPA. The results showed that both types had the same level of activity. These results indicate that 2-HPA, found as a secreted compound fromPadina arborescens, is a novel mPRα antagonist and its chemical structure is highly restricted to show its activity.
Alström Syndrome protein Alms1 is required for maintaining meiotic centriole engagement in spermatocytes ofDrosophila
Authors: Hou Yanan , Wu Zhimao , Wei Qing
Published: September 2023

Maintaining proper mother-daughter centriole engagement is crucial for controlling centrosome numbers and ensuring accurate cell division in both mitosis and meiosis. However, the mechanism responsible for this maintenance remains unclear. Here, we report that theDrosophilahomolog of human ciliopathy gene Alström Syndrome 1 (Alms1) is required for maintaining centriole engagement during spermatocyte meiosis. We demonstrated that deletion of Alms1 results in premature centriole disengagement in prophase of meiosis I, leading to the formation of multipolar spindles and abnormal cell division inDrosophilaspermatocytes. Further studies reveal that Alms1 localizes to the proximal centrioles, and functions downstream of cartwheel protein Sas-6 to regulate centriole engagement, and its highly conserved ALMS motif is required for Alms1’s function in centriole engagement. Moreover, we show that the centriole size and pericentriolar materials (PCM) have antagonistic roles on maintaining centriole engagement inalms1mutant flies. Our findings highlight the critical role of Alms1 as a “glue protein” in maintaining mother-daughter centriole pair cohesion, potentially advancing our comprehension of the pathogenesis of Alström Syndrome.

Significance statement

Alström syndrome (AS) is a human ciliopathy that results from mutations in the ALMS1 gene inherited in an autosomal recessive manner. Elucidating the roles of ALMS1 and the underlying molecular mechanisms of AS is of paramount importance. In this study, usingDrosophilamodel, we discovered that ALMS1 is localized at the proximal centrioles, and is crucial for the proper centriole engagement, spindle polarity, cell division in spermatocytes. Our findings reveal the new role of ALSM1 in maintaining centriole engagement, and suggest that non-ciliary function of ALMS1 may contribute to the pathogenesis of Alström Syndrome, warranting further investigation.
NOC1 is a Direct MYC Target, and Its Protein Interactome Dissects Its Activity in Controlling Nucleolar Function
Authors: Manara Valeria , Radoani Marco , Belli Romina , Peroni Daniele , Destefanis Francesca , Angheben Luca , Tome Gabriele , Tebaldi Toma , Bellosta Paola
Published: September 2023

The nucleolus is a subnuclear compartment critical in ribosome biogenesis and cellular stress responses. These mechanisms are governed by a complex interplay of proteins, including NOC1, a member of the NOC family of nucleolar proteins responsible for controlling rRNA processing and ribosomal maturation. This study reveals a novel relationship between NOC1 and MYC transcription factor, known for its crucial role in controlling ribosomal biogenesis, cell growth, and proliferation. Here, we demonstrate that NOC1 functions as a direct target of MYC, as it is transcriptionally induced through a functional MYC-binding E-box sequence in the NOC1 promoter region. Furthermore, protein interactome analysis reveals that NOC1-complex includes the nucleolar proteins NOC2 and NOC3 and other nucleolar components such as Nucleostemin1 Ns1 transporters of ribosomal subunits and components involved in rRNA processing and maturation. In response to MYC, NOC1 expression and localization within the nucleolus significantly increase, suggesting a direct functional link between MYC activity and NOC1 function. Notably, NOC1 over-expression leads to the formation of large nuclear granules and enlarged nucleoli, which co-localize with nucleolar fibrillarin and Ns1. Additionally, we demonstrate that NOC1 expression is necessary for Ns1 nucleolar localization, suggesting a role for NOC1 in maintaining nucleolar structure. Finally, the co-expression of NOC1 and MYC enhances the formation of abnormal structures formed by NOC1 within the nucleolus, outlining another aspect of NOC1 and MYC cooperation in nucleolar dynamics.

This study also reveals an enrichment with NOC1 with few proteins involved in RNA processing, modification, and splicing. Moreover, proteins such as Ythdc1, Flacc, and splenito are known to mediate N6-methyladenosine (m6A) methylation of mRNAs in nuclear export, revealing NOC1’s potential involvement in coordinating RNA splicing and nuclear mRNA export.

In summary, we uncovered novel roles for NOC1 in nucleolar homeostasis and established its direct connection with MYC in the network governing nucleolar structure and function. These findings also highlight NOC1’s interaction with proteins relevant to specific RNA functions, suggesting a broader role in addition to its control of nucleolar homeostasis and providing new insight that can be further investigated.
Temporal and Spatial Analysis of Event-Related Potentials in Response to Color Saliency Differences Among Various Color Vision Types
Authors: Takahashi Naoko , Sawayama Masataka , Chen Xu , Motomura Yuki , Takeichi Hiroshige , Miyauchi Satoru , Hiramatsu Chihiro
Published: September 2023

Individuals with minority color vision phenotypes have been reported to exhibit enhanced color discrimination and color recognition, which deviate from predictions based on their receptoral sensitivities. However, the specific mechanisms underlying this enhanced sensitivity remain unclear. In this study, we examined the commonality and diversity of neural activity between typical and anomalous trichromats in response to differences in color saliency. Electroencephalography was recorded during an oddball task, in which participants discriminated each of two target stimuli, blue-green and red, from a green standard stimulus. The chromaticity of the stimulus was identical across participants, whereas the relationship of saliency between the target stimuli was expected to be reversed between color vision types. The spatiotemporal dynamics of event-related potentials (ERPs) were analyzed using cluster-based permutation tests. Typical trichromats demonstrated faster behavioral and neural responses to the more salient red target stimulus, with pronounced neural activity spreading from the occipital to the parietal regions in the comparison between the target stimuli. Anomalous trichromats also exhibited similar temporal patterns toward the more salient target stimulus when each target stimulus was compared with the green standard stimulus, indicating comparable processing toward saliency across color vision types. Although a similarity was observed, neither behavioral nor neural responses in anomalous trichromats reflected saliency contrast differences. In addition, a comparative analysis of ERPs between color vision types did not reveal any distinct differences in either target stimulus. Given the large variations in color sensitivity in individuals with anomalous trichromacy, further investigation is required to understand the detailed neural processing in individuals with various color vision types.
The CUL4-DDB1-DCAF1 E3 ubiquitin ligase complex regulates PLK4 protein levels to prevent premature centriole duplication
Authors: Grossmann Josina , Kratz Anne-Sophie , Kordonsky Alina , Prag Gali , Hoffmann Ingrid
Published: September 2023

Centrioles play important roles in the assembly of centrosomes and cilia. Centriole duplication occurs once per cell cycle and is dependent on polo-like kinase 4 (PLK4). To prevent centriole amplification, which is a hallmark of cancer, PLK4 protein levels need to be tightly regulated. Here, we show that the Cullin(CUL)4A/B-DDB1-DCAF1, CRL4DCAF1, E3 ligase targets PLK4 for degradation in human cells. DCAF1 binds and ubiquitylates PLK4 in G2 phase to prevent premature centriole duplication in mitosis. In contrast to the regulation of PLK4 by SCFβ-TrCP, the interaction between PLK4 and DCAF1 is independent of PLK4 kinase activity and mediated by polo-boxes 1 and 2 of PLK4, suggesting that DCAF1 promotes PLK4 ubiquitylation independently of β-TrCP. Thus, the SCFSlimb/β-TrCPpathway, targeting PLK4 for ubiquitylation based on its phosphorylation state and CRL4DCAF1, which ubiquitylates PLK4 by binding to the conserved PB1-PB2 domain, appear to be complementary ways to control PLK4 abundance to prevent centriole overduplication.
Three-dimensional markerless motion capture of multiple freely behaving monkeys for automated characterization of social behavior
Authors: Matsumoto Jumpei , Kaneko Takaaki , Kimura Kei , Negrete Salvador Blanco , Guo Jia , Suda-Hashimoto Naoko , Kaneko Akihisa , Morimoto Mayumi , Nishimaru Hiroshi , Setogawa Tsuyoshi , Go Yasuhiro , Shibata Tomohiro , Nishijo Hisao , Takada Masahiko , Inoue Ken-ichi
Published: September 2023

Given their high sociality and close evolutionary distance to humans, monkeys are an essential animal model for unraveling the biological mechanisms underlying human social behavior and elucidating the pathogenesis of diseases exhibiting abnormal social behavior. However, behavioral analysis of naturally behaving monkeys requires manual counting of various behaviors, which has been a bottleneck due to problems in throughput and objectivity. Here, we developed a three-dimensional markerless motion capture system that utilized multi-view data for robust tracking of individual monkeys and accurate reconstruction of the three-dimensional poses of multiple monkeys living in groups. Validation analysis in two monkey groups revealed that the system enabled the characterization of individual social dispositions and relationships through automated detection of various social events. Analyses of social looking facilitated the investigation of adaptive behaviors in a social group. These results suggest that this motion capture system will significantly enhance our ability to analyze primate social behavior.
Rat Wetness Response: Sensory Cues, Behavior & Fur-based Drying
Authors: Triumph Attah Augustine , Negrón-Moreno Paola N. , Amigo-Duran Macarena , Zhang Linghua , Kenngott Max , Brecht Michael , Clemens Ann M.
Published: September 2023

It never rains in standard lab-confinements; thus we have limited understanding of animal reactions to water and wetness. To address this issue, we sprayed water on different body parts of rats and measured drying and fur temperature by thermal imaging while manipulating behavior, sensory cues and fur. Spraying water on rats resulted in fur changes (hair clumping, apex formation), grooming, shaking, and scratching. Anesthesia abolished behavioral responses, interfered with fur changes, and slowed drying. Spraying water on different body parts resulted in differential behavioral drying responses. Spraying the head resulted in grooming and shaking responses; water evaporated twice as fast as water sprayed on the animal’s back or belly. We observed no effect of whisker removal on post-water-spraying behavior. In contrast, local anesthesia of dorsal facial skin reduced post-water-spraying behavioral responses. Shaving of head fur drastically enhanced post-water-spraying behaviors, but reduced water loss during drying; indicating that fur promotes evaporation, acting in tandem with behavior to mediate drying. Excised wet fur patches dried and cooled faster than shaved excised wet skin. Water was sucked into distal hair tips, where it evaporated. We propose the wet-fur-heat-pump-hypothesis; fur might extract heat required for drying by cooling ambient air.

Abstract Figure
Double dissociation of spontaneous alpha-band activity and pupil-linked arousal on additive and multiplicative perceptual gain
Authors: Pilipenko April , Samaha Jason
Published: September 2023

Perception is a probabilistic process dependent on external stimulus properties and one’s internal state. However, which internal states influence perception and via what mechanisms remain debated. We studied how spontaneous alpha-band activity (8-12 Hz) and pupil fluctuations impact visual detection and confidence across stimulus contrast levels (i.e., the contrast response function or CRF). We found that weak pre-stimulus alpha power induced an “additive” shift in the CRF, whereby stimuli were reported present more frequently at all contrast levels, including contrast of zero (i.e., false alarms). Conversely, pre-stimulus pupil size had a “multiplicative” effect on detection such that stimuli occurring during large pupil states (putatively corresponding to higher arousal) were perceived more frequently as contrast increased. Signal detection modeling reveals that alpha power changes detection criteria equally across the CRF but not detection sensitivity (d’) whereas pupil-linked arousal modulated sensitivity, particularly for higher contrasts. Interestingly, pupil size and alpha power were positively correlated, meaning that some of the effect of alpha on detection may be mediated by pupil fluctuations. However, pupil-independent alpha still induced an additive shift in the CRF corresponding to a criterion effect. Our data imply that weak alpha boosts detection and confidence by an additive factor, rather than by a multiplicative scaling of contrast responses, a profile which captures the effect of pupil-linked arousal. We suggest that alpha-power and arousal fluctuations have dissociable effects on behavior. Alpha reflects the baseline level of visual excitability, which can vary independent of arousal.

Significance statement

Nearly a century ago, brain waves around 8-13 Hz (the “alpha-band”) were discovered and linked to visual processing and cortical arousal. However, the precise way that alpha activity shapes perception and relates to arousal is unsettled. We recorded pupillometry and EEG while subjects detected and reported confidence for visual stimuli with varying intensity. Stimuli occurring during states of strong alpha were seen less often, regardless of intensity level, suggesting alpha exerts subtractive inhibition on perception and confidence. Pupil size (a proxy for arousal) was found to correlate with alpha yet, surprisingly, has a different effect on perception. Small pupil lowered perceptual sensitivity more as stimulus intensity increased. Our findings reveal distinct effects of alpha activity and arousal on visual perception.
Competition and Synergy of Arp2/3 and Formins in Nucleating Actin Waves
Authors: Chua Xiang Le , Tong Chee San , Xŭ X.J. , Su Maohan , Xiao Shengping , Wu Xudong , Wu Min
Published: September 2023

The assembly and disassembly of actin filaments and their regulatory proteins are crucial for maintaining cell structure or changing physiological state. However, because of the tremendous global impact of actin on diverse cellular processes, dissecting the specific role of actin regulatory proteins remains challenging. In this study, we employ actin waves that propagate on the cortex of mast cell to investigate the interplay between formins and the Arp2/3 complex in the nucleating and turnover of cortical actin. Our findings reveal that the recruitment of FMNL1 and mDia3 precedes the Arp2/3 complex in cortical actin waves. Membrane and GTPase-interaction can drive oscillations of FMNL1 in an actin-dependent manner, but active Cdc42 waves or constitutively-active FMNL1 mutant can form without actin waves. In addition to the apparent coordinated assembly of formins and Arp2/3, we further reveal their antagonism, where inhibition of Arp2/3 complex by CK-666 led to a transient increase in the recruitment of formins and actin polymerization. Our analysis suggest that the antagonism could not be explained for the competition between FMNL1 and Arp2/3 for monomeric actin. Rather, it is regulated by a limited pool of their common upstream regulator, Cdc42, whose level is negatively regulated by Arp2/3. Collectively, our study highlights the multifaceted interactions, cooperative or competitive, between formins and Arp2/3 complex, in the intricate and dynamic control of actin cytoskeletal network.
Pharmacological modulation of developmental and synaptic phenotypes in human SHANK3 deficient stem cell-derived neuronal models
Authors: Thibaudeau Amandine , Schmitt Karen , François Louise , Chatrousse Laure , Hoffmann David , Cousin Loïc , Weiss Amélie , Vuidel Aurore , Jacob Christina B , Sommer Peter , Benchoua Alexandra , Wilbertz Johannes H
Published: September 2023

One sentence summary

This study describes the use of SHANK3 deficient stem cell-derived neuronal models to screen and characterize small molecules that partially rescued developmental and synaptic defects related to Phelan-McDermid syndrome (PMDS).

Phelan-McDermid syndrome (PMDS) arises from mutations in the terminal region of chromosome 22q13, impacting theSHANK3gene. The resulting deficiency of the postsynaptic density scaffolding protein SHANK3 is associated with autism spectrum disorder (ASD). We examined 12 different PMDS patient and CRISPR-engineered stem cell-derived neuronal models and controls and found that reduced expression of SHANK3 leads to neuronal hyperdifferentiation, increased synapse formation, and decreased neuronal activity. We performed automated imaging-based screening of 7,120 target-annotated small molecules and identified three compounds that rescued SHANK3-dependent neuronal hyperdifferentiation. One compound, Benproperine, rescued the decreased colocalization of Actin Related Protein 2/3 Complex Subunit 2 (ARPC2) with ß-actin and rescued increased synapse formation in SHANK3 deficient neurons when administered early during differentiation. Neuronal activity was only mildly affected, highlighting Benproperine’s effects as a neurodevelopmental modulator. This study demonstrates that small molecular compounds that reverse developmental phenotypes can be identified in human neuronal PMDS models.
Maternal IL-10 restricts fetal emergency myelopoiesis
Authors: Collins Amélie , Swann James W. , Proven Melissa A. , Patel Chandani M. , Mitchell Carl A. , Kasbekar Monica , Dellorusso Paul V. , Passegué Emmanuelle
Published: September 2023

Neonates, in contrast to adults, are highly susceptible to inflammation and infection. Here we investigate how late fetal liver (FL) mouse hematopoietic stem and progenitor cells (HSPC) respond to inflammation, testing the hypothesis that deficits in engagement of emergency myelopoiesis (EM) pathways limit neutrophil output and contribute to perinatal neutropenia. We show that despite similar molecular wiring as adults, fetal HSPCs have limited production of myeloid cells at steady state and fail to activate a classical EM transcriptional program. Moreover, we find that fetal HSPCs are capable of responding to EM-inducing inflammatory stimuliin vitro, but are restricted by maternal anti-inflammatory factors, primarily interleukin-10 (IL-10), from activating EM pathwaysin utero. Accordingly, we demonstrate that loss of maternal IL-10 restores EM activation in fetal HSPCs but at the cost of premature parturition. These results reveal the evolutionary trade-off inherent in maternal anti-inflammatory responses that maintain pregnancy but render the fetus unresponsive to EM activation signals and susceptible to infection.

HIGHLIGHTS

The structure of the HSPC compartment is conserved from late fetal to adult life.

Fetal HSPCs have diminished steady-state myeloid cell production compared to adult.

Fetal HSPCs are restricted from engaging in emergency myelopoiesis by maternal IL-10.

Restriction of emergency myelopoiesis may explain neutropenia in septic neonates.

eTOC BLURB

Fetal hematopoietic stem and progenitor cells are restricted from activating emergency myelopoiesis pathways by maternal IL-10, resulting in inadequate myeloid cell production in response to inflammatory challenges and contributing to neonatal neutropenia.
Probing learning through the lens of changes in circuit dynamics
Authors: Marschall Owen , Savin Cristina
Published: September 2023

Despite the success of dynamical systems as accounts of circuit computation and observed behavior, our understanding of how dynamical systems evolve over learning is very limited. Here we develop a computational framework for extracting core dynamical systems features of recurrent circuits across learning and analyze the properties of these meta-dynamics in model analogues of several brain-relevant tasks. Across learning algorithms and tasks we find a stereotyped path to task mastery, which involves the creation of dynamical systems features and their refinement to a stable solution. This learning universality reveals common principles in the organization of recurrent neural networks in service to function and highlights some of the challenges in reverse engineering learning principles from chronic population recordings of neural activity.
Bottled Water-Problem in Campus
Authors: Chandwani Rajesh , Varkkey Biju , Kadamberi Vidya
Published: September 2023

The case is based on heated e-mail conversations connected to the delivery of clean bottled water in the campus of a reputed research institute in southern India. The exchange between Tara Sharma (Programme Manager) and Shreejith Nair (Group Head-Engineering Service and Estate) relate to the quality of services provided. The case highlights the viewpoints of various stakeholders involved in the open conversation. This case focusses on the behaviour of a set of underperforming employees associated with a contractor, the reasons, among others, being lack of training and quality awareness. However, training alone cannot be assumed as the only correct solution for handling underperformance. The stakeholders involved need to ascertain the cause of underperformance by analysing whether it is a “Can't Do” –“Won't Do” problem, and identify the ways of dealing with it.
Shaping online and offline informal learning networks in off-site construction projects: a proximity perspective
Authors: Liu Kangning , Hwang Bon-Gang , Jia Jianyao , Man Qingpeng , Zhang Shoujian
Published: September 2023

Purpose

Informal learning networks are critical to response to calls for practitioners to reskill and upskill in off-site construction projects. With the transition to the coronavirus disease 2019 (COVID-19) pandemic, social media-enabled online knowledge communities play an increasingly important role in acquiring and disseminating off-site construction knowledge. Proximity has been identified as a key factor in facilitating interactive learning, yet which type of proximity is effective in promoting online and offline knowledge exchange remains unclear. This study takes a relational view to explore the proximity-related antecedents of online and offline learning networks in off-site construction projects, while also examining the subtle differences in the networks' structural patterns.

Design/methodology/approach

Five types of proximity (physical, organizational, social, cognitive and personal) between projects members are conceptualized in the theoretical model. Drawing on social foci theory and homophily theory, the research hypotheses are proposed. To test these hypotheses, empirical case studies were conducted on two off-site construction projects during the COVID-19 pandemic. Valid relational data provided by 99 and 145 project members were collected using semi-structured interviews and sociometric questionnaires. Subsequently, multivariate exponential random graph models were developed.

Findings

The results show a discrepancy arise in the structural patterns between online and offline learning networks. Offline learning is found to be more strongly influenced by proximity factors than online learning. Specifically, physical, organizational and social proximity are found to be significant predictors of offline knowledge exchange. Cognitive proximity has a negative relationship with offline knowledge exchange but is positively related to online knowledge exchange. Regarding personal proximity, the study found that the homophily effect of hierarchical status merely emerges in offline learning networks. Online knowledge communities amplify the receiver effect of tenure. Furthermore, there appears to be a complementary relationship between online and offline learning networks.

Originality/value

Proximity offers a novel relational perspective for understanding the formation of knowledge exchange connections. This study enriches the literature on informal learning within project teams by revealing how different types of proximity shape learning networks across different channels in off-site construction projects.
Machine learning approach for the prediction of mixed lubrication parameters for different surface topographies of non-conformal rough contacts
Authors: Prajapati Deepak Kumar , Katiyar Jitendra Kumar , Prakash Chander
Published: September 2023

Purpose

This study aims to use a machine learning (ML) model for the prediction of traction coefficient and asperity load ratio for different surface topographies of non-conformal rough contacts.

Design/methodology/approach

The input data set for the ML model is generated using a mixed-lubrication model. Surface topography parameters (skewness, kurtosis and pattern ratio), rolling speed and hardness are used as input features in the multi-layer perceptron (MLP) model. The hyperparameter tuning and fivefold cross-validation are also performed to minimize the overfitting.

Findings

From the results, it is shown that the MLP model shows excellent accuracy (R2 > 90%) on the test data set for making the prediction of mixed lubrication parameters. It is also observed that engineered rough surfaces with high negative skewness, low kurtosis and isotropic surface patterns exhibit a significant low traction coefficient. It is also concluded that the MLP model gives better accuracy in comparison to the random forest regression model based on the training and testing data sets.

Originality/value

Mixed lubrication parameters are predicted by developing a regression-based MLP model. The machine learning model is trained using several topography parameters, which are vital in the mixed-EHL regime because of the lack of regression-fit expressions in previous works. The accuracy of MLP with random forest models is also compared.
The effect of social commerce attributes on customer engagement: an empirical investigation
Authors: Busalim Abdelsalam , Hollebeek Linda D. , Lynn Theo
Published: September 2023

Purpose

Social commerce (s-commerce) offers community-based platforms that facilitate customer-to-customer interactions and the development of customers' social shopping-based experience. While prior research has addressed the role of customer engagement (CE) in boosting s-commerce-based sales and performance, insight into the effect of s-commerce attributes on CE remains tenuous. Addressing this gap, this study examines the role of specific s-commerce attributes (i.e. community, collaboration, interactivity and social dynamics) on CE, which is, in turn, proposed to impact customers' repurchase- and electronic word of mouth (eWOM) intention.

Design/methodology/approach

A web-based survey was deployed to target users of a popular s-commerce platform, Etsy.com. Partial least squares structural equation modeling (PLS-SEM) was, then, used to analyze the survey data collected from 390 users.

Findings

The results reveal that the four examined attributes positively affect CE. The findings also demonstrate CE's positive effect on customers' repurchase- and eWOM intention.

Originality/value

Though CE has been identified as a key s-commerce performance indicator, little remains known about the role of specific s-commerce attributes in driving CE, as, therefore, explored in this research. Specifically, the authors examine the role of s-commerce-based community, collaboration, interactivity and social dynamics on CE. Their analyses also corroborate that CE, in turn, drives customers' post-purchase (i.e. repurchase/eWOM) intention. Managerially, our findings can be used to develop more engaging s-commerce platforms.
Enterprise social media usage and social cyberloafing: an empirical investigation using the JD-R model
Authors: Ma Liang , Zhang Xin , Yu Peng
Published: September 2023

Purpose

One of the most important challenges confronting enterprise managers is that of controlling employees' social cyberloafing. The use of enterprise social media entails opportunities for cyberloafing. However, previous research on how enterprise social media use affects cyberloafing is rather limited. Using the job demands-resources (JD-R) model, this paper proposes a research model to investigate the relationship between enterprise social media usage and employees' social cyberloafing behavior.

Design/methodology/approach

Structural equation modeling was performed to test the research model and hypotheses. Surveys were conducted in an online platform in China, generating 510 employees' data for analysis.

Findings

First, both public social media and private social media used for work-related and social-related purposes have a positive effect on employees' job engagement. Further, job engagement has a negative effect on employees' social cyberloafing. Second, the use of public social media for work-related and social-related purposes has no effect on employees' emotional exhaustion. However, work-related private social media usage has a negative effect on employees' emotional exhaustion, and social-related private social media usage has a positive effect on employees' emotional exhaustion. Further, employees' emotional exhaustion has a positive effect on employees' social cyberloafing. Third, there are significant differences in the effects of enterprise social media on employees' social cyberloafing between male and female employees.

Originality/value

First, this paper contributes to the social cyberloafing literature by establishing a relationship between enterprise social media usage and social cyberloafing in relation to the dual influence mechanism. Second, it contributes to the JD-R model by clarifying how the use of enterprise social media with different motivations affects social cyberloafing through a mediation mechanism, namely, an enabling mechanism and a burden mechanism. Third, this paper also contributes to the social cyberloafing literature by revealing the boundary condition, namely gender, between enterprise social media use and employees' social cyberloafing.
The impacts of food certificate adoption on e-commerce income among small online agri-food sellers
Authors: Permani Risti , Sahara Sahara , Satria Dias , Suprehatin Suprehatin , Nuryartono Nunung
Published: September 2023

Purpose

This paper aims to assess the determinants of food certificate adoption and analyse the impacts of food certificates on e-commerce income among small online agri-food sellers in Indonesia.

Design/methodology/approach

The authors used data from an online survey of 228 small-online agri-food sellers in East Java, Indonesia. This study aims to focus on two food certificates: a mandatory Halal (Islamic dietary law) certificate and the P-IRT certificate, a food safety certificate for home-based businesses. A maximum simulated likelihood (MSL) estimator was employed to account for selection bias and endogeneity.

Findings

The study highlights the continued importance of certification in agri-food markets, including e-commerce and the need to consider the degree of substitutability and resource allocation between multiple food certificates. It finds that online agri-food sellers adopting the Halal certificate earn two to three times higher compared to non-adopters. Conversely, the gross income per month from e-commerce sales is 78% lower among those adopting the P-IRT certificate. Moreover, access to regulatory information sources motivates the likelihood of adopting food certificates. In contrast, the business size, marketing channels, contractual relationship and management capabilities are insignificant factors for the adoption of any of the Halal and P-IRT certificate combinations.

Research limitations/implications

Results from this research might be specific to the context of the focus study area, thereby reducing their generalisability. In addition to gathering representative samples, future research should also capture more complex dimensions of food certificates. These include the cost of acquiring food certificates, online sellers' perceptions of food certificate adoption, and emerging topics such as group certification and the use of technology.

Originality/value

To the authors' knowledge, this research is one of the first studies investigating the adoption of food certificates within the e-commerce setting. This study also contributes to the small number of studies looking at multiple certificate adoption and food certificate issues from the retailers' perspectives
Matching intra-functional integration with inter-firm IT linkage to facilitate flexibility for customers
Authors: Wang Shu , Liu Jing , Park Kihyun , Kang Mingu , Dai Fei
Published: September 2023

Purpose

This study aims to suggest a moderated mediation model addressing how internal integration interacts with information technology (IT) link with external customers to meet customer needs more efficiently and effectively.

Design/methodology/approach

This study tests the proposed hypotheses by using 268 data collected from manufacturing firms worldwide.

Findings

The results of this study reveal that internal integration plays a very important role in promoting customer satisfaction directly and indirectly by enhancing the ability to meet customers’ flexibility needs. In addition, the results show that IT link with customers strengthens this indirect influencing relationship.

Originality/value

By combining IT connectedness with external customers with internal capability, this study provides valuable insights into how manufacturing firms apply internal integration more effectively to enhance customer satisfaction.
The relationship between economic complexity and green economy with earnings management
Authors: Ahmadi Zainab , Salehi Mahdi , Rahmani Mahmoud
Published: September 2023

Purpose

This study aims to analyze the relationship between economic complexity (EC) and the green economy (GE) with the real and accrual earnings management (REM and AEM) of the listed companies on the Iranian stock exchange. The authors study whether EC and the GE can affect REM and AEM.

Design/methodology/approach

The authors used a multiple regression model based on the panel data and a fixed effect model to test hypotheses. The sample includes 1,351 companies listed on the Tehran Stock Exchange from 2014 to 2021.

Findings

The results show a positive and significant relationship between EC and the GE with REM and AEM.

Originality/value

Considering the importance of a GE and since this research is the first to address the mentioned topic in emerging markets, it provides helpful insights for financial statement users, analysts and legal entities. Our study fills the literature gap and promotes knowledge regarding its relevant literature. Examining this relationship portrays the latest research perspectives in this field. The information from this study can assist in environmental management decision-making and relevant policymaking, promoting the movement toward sustainable development.
Determinants of litigation risk in the Jordanian financial sector: the role of firm-specific indicators
Authors: Taha Rana , Taha Noor , Ananzeh Husam
Published: September 2023

Purpose

This study aims to examine the impact of firm indicators on litigation risk in the Jordanian financial sector from 2017 to 2021, where the relationship between firm indicators and litigation risk in the Jordanian financial sector is a crucial area of research that can help financial institutions understand the factors that increase their probability of litigation risk.

Design/methodology/approach

The sample for this study comprised 92 publicly traded financial firms listed on the Amman Stock Exchange. The study used a quantitative research approach to analyse the relationship between four firm indicators (profitability, firm size, leverage and age) and their impact on litigation risk in the Jordanian financial sector from 2017 to 2021.

Findings

Our findings reveal that firm size has a significant positive impact on litigation risk, whereas profitability was found to have no significant impact on litigation risk. Moreover, the authors found that financial leverage substantially positively impacts litigation risk levels. However, the firm age was found to have no significant impact on litigation risk.

Originality/value

The results provide valuable insights into factors contributing to litigation risk in the Jordanian financial sector and the findings can inform strategic decisions for financial firms as they seek to manage litigation risk and improve financial performance. The study contributes to the existing literature on litigation risk by examining the impact of multiple firm indicators on litigation risk in the context of the Jordanian financial sector.