bluuebunny/crossref_metadata_2025 huggingface dataset:
Selective neuroimmune modulation by type I interferon drives neuropathology and neurologic dysfunction following traumatic brain injury
Authors: Todd Brittany P. , Luo Zili , Gilkes Noah , Chimenti Michael S. , Peterson Zeru , Mix Madison , Harty John T. , Nickl-Jockschat Thomas , Ferguson Polly J. , Bassuk Alexander G. , Newell Elizabeth A.
Published: June 2023

Accumulating evidence suggests that type I interferon (IFN-I) signaling is a key contributor to immune cell-mediated neuropathology in neurodegenerative diseases. Recently, we demonstrated a robust upregulation of type I interferon-stimulated genes in microglia and astrocytes following experimental traumatic brain injury (TBI). The specific molecular and cellular mechanisms by which IFN-I signaling impacts the neuroimmune response and neuropathology following TBI remains unknown. Using the lateral fluid percussion injury model (FPI) in adult male mice, we demonstrated that IFN α/β receptor (IFNAR) deficiency resulted in selective and sustained blockade of type I interferon-stimulated genes following TBI as well as decreased microgliosis and monocyte infiltration. Phenotypic alteration of reactive microglia also occurred with diminished expression of molecules needed for MHC class I antigen processing and presentation following TBI. This was associated with decreased accumulation of cytotoxic T cells in the brain. The IFNAR-dependent modulation of the neuroimmune response was accompanied by protection from secondary neuronal death, white matter disruption, and neurobehavioral dysfunction. These data support further efforts to leverage the IFN-I pathway for novel, targeted therapy of TBI.
The consequences of tetraploidy onCaenorhabditis elegansphysiology and sensitivity to chemotherapeutics
Authors: Misare Kelly R. , Ampolini Elizabeth A. , Gonzalez Hyland C. , Sullivan Kaitlan A. , Li Xin , Miller Camille , Sosseh Bintou , Dunne Jaclyn B. , Voelkel-Johnson Christina , Gordon Kacy L. , Hartman Jessica H.
Published: June 2023

Polyploid cells contain more than two copies of each chromosome. Polyploidy has important roles in development, evolution, and tissue regeneration/repair, and can arise as a programmed polyploidization event or be triggered by stress. Cancer cells are often polyploid.C. elegansnematodes are typically diploid, but stressors such as heat shock and starvation can trigger the production of tetraploid offspring. In this study, we utilized a recently published protocol to generate stable tetraploid strains ofC. elegansand compared their physiological traits and sensitivity to two DNA-damaging chemotherapeutic drugs, cisplatin and doxorubicin. As prior studies have shown, tetraploid worms are approximately 30% longer, shorter-lived, and have a smaller brood size than diploids. We investigated the reproductive defect further, determining that tetraploid worms have a shorter overall germline length, a higher rate of germ cell apoptosis, more aneuploidy in oocytes and offspring, and larger oocytes and embryos. We also found that tetraploid worms are modestly protected from growth delay from the chemotherapeutics but are similarly or more sensitive to reproductive toxicity. Transcriptomic analysis revealed differentially expressed pathways that may contribute to sensitivity to stress. Overall, this study reveals the phenotypic consequences of whole-animal tetraploidy inC. elegans.
Continuous Measures of Decision-Difficulty Captured Remotely: I. Mouse-tracking sensitivity extends to tablets and smartphones
Authors: Zuk Alexandra A. Ouellette , Bertrand Jennifer K. , Chapman Craig S.
Published: June 2023

As decisions require actions to have an effect on the world, measures derived from movements such as using a mouse to control a cursor on a screen provide powerful and dynamic indices of decision-making. In this first of a set of two studies, we replicated classic reach-decision paradigms across computers, tablets, and smartphones, we show that portable touch-devices can sensitively capture decision-difficulty. We see this in pre- and during-movement temporal and motoric measures across diverse decision domains. We found touchscreen interactions to more sensitively reflect decision-difficulty during movement compared to computer interactions, and the latter to be more sensitive before movement initiation. Paired with additional evidence for the flexibility and unique utility of pre- and during-movement measures, this substantiates the use of widely available touch-devices to massively extend the reach of decision science. We build upon this in the second study in this series (Bertrand et al., 2023) with the use of webcam eye-tracking to further elucidate, earlier in time, the decision process. This subsequent work provides additional support for tools that enable remote collection of rich decision data in ecologically-valid environments.
Reducing the Bacterial Lag Phase Through Methylated Compounds: Insights from Algal-Bacterial Interactions
Authors: Sperfeld Martin , Narváez-Barragán Delia A. , Malitsky Sergey , Frydman Veronica , Yuda Lilach , Rocha Jorge , Segev Einat
Published: June 2023

The bacterial lag phase is a key period for resuming growth. Despite its significance, the lag phase remains underexplored, particularly in environmental bacteria. Here, we explore the lag phase of the model marine bacteriumPhaeobacter inhibenswhen it transitions from starvation to growth with a microalgal partner. Utilizing transcriptomics and13C-labeled metabolomics, our study reveals that methylated compounds, which are abundantly produced by microalgae, shorten the bacterial lag phase. Our findings underscore the significance of methyl groups as a limiting factor during the lag phase and demonstrate that methyl groups can be harvested from algal compounds and assimilated through the methionine cycle. Furthermore, we show that methylated compounds, characteristic of photosynthetic organisms, induce variable reductions in lag times among bacteria associated with algae and plants. These findings highlight the adjustability of the bacterial lag phase and emphasize the importance of studying bacteria in an environmental context.

One-Sentence Summary:

Bacteria use algal compounds as a metabolic shortcut to transition from starvation to growth.
Catalytic growth in a shared enzyme pool ensures robust control of centrosome size
Authors: Banerjee Deb Sankar , Banerjee Shiladitya
Published: June 2023

Accurate regulation of centrosome size is essential for ensuring error-free cell division, and dysregulation of centrosome size has been linked to various pathologies, including developmental defects and cancer. While a universally accepted model for centrosome size regulation is lacking, prior theoretical and experimental works suggest a centrosome growth model involving autocatalytic assembly of the pericentriolar material. Here we show that the autocatalytic assembly model fails to explain the attainment of equal centrosome sizes, which is crucial for error-free cell division. Incorporating latest experimental findings into the molecular mechanisms governing centrosome assembly, we introduce a new quantitative theory for centrosome growth involving catalytic assembly within a shared pool of enzymes. Our model successfully achieves robust size equality between maturing centrosome pairs, mirroring cooperative growth dynamics observed in experiments. To validate our theoretical predictions, we compare them with available experimental data and demonstrate the broad applicability of the catalytic growth model across different organisms, which exhibit distinct growth dynamics and size scaling characteristics.
Neuronal Activation of the Gαq Protein EGL-30/GNAQ Late in Life Rejuvenates Cognition Across Species
Authors: Stevenson Morgan E. , Bieri Gregor , Kaletsky Rachel , Ange Jonathan St. , Remesal Laura , Pratt Karishma J. B. , Zhou Shiyi , Weng Yifei , Murphy Coleen T. , Villeda Saul A.
Published: June 2023

Cognitive decline is perhaps the most devastating aging loss. EGL-30/GNAQ and Gαq signaling pathways are highly conserved betweenC. elegansand mammals. We find that activation of EGL-30 in aged worms at least triples memory span, and we wondered if this highly conserved pathway could also improve memory in very old mice. MurineGnaqis enriched in hippocampal excitatory neurons and declines with age. Furthermore, GNAQ gain-of-function significantly improved memory in aged mice: GNAQ(gf)in hippocampal neurons of 24-month-old mice rescued age-related impairments in health metrics and long-term memory. Single-nucleus RNAseq revealed gene expression changes related to synaptic function, axon guidance, and learning and memory pathways. Several worm orthologs of mouse genes upregulated by GNAQ(gf) overexpression are required for EGL-30(gf)-dependent memory improvement. These results demonstrate that the molecular and genetic pathways betweenC. elegansand mammals are highly conserved, as activation of EGL-30/GNAQ, a pathway first identified in worms, rejuvenates cognitive function in two-year old mice (the equivalent of 70-80 yo humans). To our knowledge, this is the oldest age an intervention has successfully improved age-related cognitive decline.

One-Sentence Summary

Neuronal activation of the Gαq protein EGL-30/GNAQ restores long-term memory at old age in worms and mice.
DREADD-mediated amygdala activation is sufficient to induce anxiety-like responses in young nonhuman primates
Authors: Mueller Sascha A.L. , Oler Jonathan A. , Roseboom Patrick H. , Aggarwal Nakul , Kenwood Margaux M. , Riedel Marissa K. , Elam Victoria R. , Olsen Miles E. , DiFilippo Alexandra H. , Christian Bradley T. , Hu Xing , Galvan Adriana , Boehm Matthew A. , Michaelides Michael , Kalin Ned H.
Published: June 2023

Anxiety disorders are among the most prevalent psychiatric disorders, with symptoms often beginning early in life. To model the pathophysiology of human pathological anxiety, we utilized Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) in a nonhuman primate model of anxious temperament to selectively increase neuronal activity of the amygdala. Subjects included 10 young rhesus macaques; 5 received bilateral infusions of AAV5-hSyn-HA-hM3Dq into the dorsal amygdala, and 5 served as controls. Subjects underwent behavioral testing in the human intruder paradigm following clozapine or vehicle administration, prior to and following surgery. Behavioral results indicated that clozapine treatment post-surgery increased freezing across different threat-related contexts in hM3Dq subjects. This effect was again observed approximately 1.9 years following surgery, indicating the long-term functional capacity of DREADD-induced neuronal activation. [11C]deschloroclozapine PET imaging demonstrated amygdala hM3Dq-HA specific binding, and immunohistochemistry revealed that hM3Dq-HA expression was most prominent in basolateral nuclei. Electron microscopy confirmed expression was predominantly on neuronal membranes. Together, these data demonstrate that activation of primate amygdala neurons is sufficient to induce increased anxiety-related behaviors, which could serve as a model to investigate pathological anxiety in humans.
Precision-engineered biomimetics: the human fallopian tube
Authors: Crawford Ashleigh J. , Forjaz André , Bhorkar Isha , Roy Triya , Schell David , Queiroga Vasco , Ren Kehan , Kramer Donald , Bons Joanna , Huang Wilson , Russo Gabriella C. , Lee Meng-Horng , Schilling Birgit , Wu Pei-Hsun , Shih Ie-Ming , Wang Tian-Li , Kiemen Ashley , Wirtz Denis
Published: June 2023

The fallopian tube has an essential role in several physiological and pathological processes from pregnancy to ovarian cancer. However, there are no biologically relevant models to study its pathophysiology. The state-of-the-art organoid model has been compared to two-dimensional tissue sections and molecularly assessed providing only cursory analyses of the model’s accuracy. We developed a novel multi-compartment organoid model of the human fallopian tube that was meticulously tuned to reflect the compartmentalization and heterogeneity of the tissue’s composition. We validated this organoid’s molecular expression patterns, cilia-driven transport function, and structural accuracy through a highly iterative platform wherein organoids are compared to a three-dimensional, single-cell resolution reference map of a healthy, transplantation-quality human fallopian tube. This organoid model was precision-engineered to match the human microanatomy.

One sentence summary

Tunable organoid modeling and CODA architectural quantification in tandem help design a tissue-validated organoid model.
Lineage motifs: developmental modules for control of cell type proportions
Authors: Tran Martin , Askary Amjad , Elowitz Michael B.
Published: June 2023

In multicellular organisms, cell types must be produced and maintained in appropriate proportions. One way this is achieved is through committed progenitor cells that produce specific sets of descendant cell types. However, cell fate commitment is probabilistic in most contexts, making it difficult to infer progenitor states and understand how they establish overall cell type proportions. Here, we introduce Lineage Motif Analysis (LMA), a method that recursively identifies statistically overrepresented patterns of cell fates on lineage trees as potential signatures of committed progenitor states. Applying LMA to published datasets reveals spatial and temporal organization of cell fate commitment in zebrafish and rat retina and early mouse embryo development. Comparative analysis of vertebrate species suggests that lineage motifs facilitate adaptive evolutionary variation of retinal cell type proportions. LMA thus provides insight into complex developmental processes by decomposing them into simpler underlying modules.
Strain-dependent effects on neurobehavioral and seizure phenotypes inScn2aK1422Emice
Authors: Echevarria-Cooper Dennis M. , Hawkins Nicole A. , Kearney Jennifer A.
Published: June 2023

Pathogenic variants inSCN2Aare associated with a range of neurodevelopmental disorders (NDD). Despite being largely monogenic,SCN2A-related NDD show considerable phenotypic variation and complex genotype-phenotype correlations. Genetic modifiers can contribute to variability in disease phenotypes associated with rare driver mutations. Accordingly, different genetic backgrounds across inbred rodent strains have been shown to influence disease-related phenotypes, including those associated withSCN2A-related NDD. Recently, we developed a mouse model of the variantSCN2A-p.K1422E that was maintained as an isogenic line on the C57BL/6J (B6) strain. Our initial characterization of NDD phenotypes in heterozygousScn2aK1422Emice revealed alterations in anxiety-related behavior and seizure susceptibility. To determine if background strain affects phenotype severity in theScn2aK1422Emouse model, phenotypes of mice on B6 and [DBA/2JxB6]F1 hybrid (F1D2) strains were compared.

Convergent evidence from neurobehavioral assays demonstrated lower anxiety-like behavior inScn2aK1422Emice compared to wild-type and further suggested that this effect is more pronounced on the B6 background compared to the F1D2 background. Although there were no strain-dependent differences in occurrence of rare spontaneous seizures, response to the chemoconvulsant kainic acid revealed differences in seizure generalization and lethality risk, with variation based on strain and sex. Continued examination of strain-dependent effects in theScn2aK1422Emouse model could reveal genetic backgrounds with unique susceptibility profiles that would be relevant for future studies on specific traits and enable the identification of highly penetrant phenotypes and modifier genes that could provide clues about the primary pathogenic mechanism of the K1422E variant.
Importin α accumulates in micronuclei and associates with genomic instability in human cancer cells
Authors: Miyamoto Yoichi , Kisanuki Reo , Oshima Rieko , Yoshimura Shige H , Yokota Mutsumi , Maehara Kazumitsu , Hata Chiaki , Tachibana Taro , Koike Masato , Ohkawa Yasuyuki , Katagiri Toyomasa , Yoneda Yoshihiro , Oka Masahiro , Saitoh Hisato
Published: June 2023

Micronuclei (MN), are membrane-enclosed structures that contain DNA or chromatin, are biomarkers of genome instability. Here, we report that importin α, a key nuclear transport factor, is highly concentrated in the MN of cultured human cancer cells. Notably, it is not uniformly distributed, but is localized to approximately 40% of the MN. This selective localization is characterized by an uncorrelated distribution relative to importin β1, CAS/CSE1L, and Ran, suggesting that the nucleocytoplasmic recycling of importin α is uncontrolled in the MN. We found that the subset of importin α-positive MN exhibits collapsed nuclear envelopes and compromised barrier functions. In addition to an association with euchromatin regions, we identified that chromatin-regulating molecules potentially interact with importin α and noted a significant reduction in the mobility of importin α within MN. These observations indicate that a unique state is established in importin α-enriched structures. Importantly, our findings reveal a mutually exclusive relationship between the accumulation of importin α and RAD51, a protein involved in homologous recombination repair, in MN. These results suggest that importin α is an unrecognized molecular marker for assessing genomic stability in human cancer cells.
Activation of M1 cholinergic receptors in mouse somatosensory cortex enhances information processing and improves detection behaviour
Authors: Mishra Wricha , Kheradpezhouh Ehsan , Arabzadeh Ehsan
Published: June 2023

An important function of the brain is to form accurate representations of the world around us. To optimise sensory representations based on the demands of the environment, activity of cortical neurons is regulated by neuromodulators such as Acetylcholine (ACh). As such, ACh is implicated in cognitive functions including attention, arousal and sleep cycles. However, it is not clear how specific ACh receptors shape the baseline activity of cortical neurons and their evoked response to sensory stimuli. Here, we investigate the role of a densely expressed muscarinic ACh receptor 1 (M1) in information processing in the mouse primary somatosensory cortex (vS1) and in the animal’s sensitivity in detecting vibrotactile stimuli. We show that M1 activation significantly enhances the evoked response of vS1 neurons and the reversal of this enhancement by blocking M1. In addition, we demonstrate that M1 activation results in faster and more reliable neuronal responses, which is manifested by a significant reduction in response latencies and the trial-to-trial variability in neuronal activity. At the population level, M1 activation reduces the network synchrony and thus enhances the capacity of vS1 neurons in conveying sensory information. Consistent with the neuronal findings, we show that M1 activation significantly improves performances in a vibrotactile detection task. Overall, the M1-mediated enhancement in sensory efficiency reflects a multiplicative gain modulation at the neuronal level, resembling the changes observed during high attention states.
Recall tempo of Hebbian sequences depends on the interplay of Hebbian kernel with tutor signal timing
Authors: Farrell Matthew , Pehlevan Cengiz
Published: June 2023

Understanding how neural circuits generate sequential activity is a longstanding challenge. While foundational theoretical models have shown how sequences can be stored as memories with Hebbian plasticity rules, these models considered only a narrow range of Hebbian rules. Here we introduce a model for arbitrary Hebbian plasticity rules, capturing the diversity of spike-timing-dependent synaptic plasticity seen in experiments, and show how the choice of these rules and of neural activity patterns influences sequence memory formation and retrieval. In particular, we derive a general theory that predicts the speed of sequence replay. This theory lays a foundation for explaining how cortical tutor signals might give rise to motor actions that eventually become “automatic”. Our theory also captures the impact of changing the speed of the tutor signal. Beyond shedding light on biological circuits, this theory has relevance in artificial intelligence by laying a foundation for frameworks whereby slow and computationally expensive deliberation can be stored as memories and eventually replaced by inexpensive recall.
DIETS: a simple and sensitive assay to measure and control the intake of complex solid foods, like high-fat diets, inDrosophila
Authors: Thakare Manikrao R. , Choudhary Prerana , Pydah Bhavna , Sunke Suhas , Yadav R Sai Prathap , Agrawal Pavan , Das Gaurav
Published: June 2023

The fruit flyDrosophila melanogaster offers a powerful model to study how diet affects the body and brain. However, existing methods for measuring their food intake often rely on dyes or tags mixed with food, which can be inaccurate due to how the flies absorb and eliminate them. Capillary-based assays like CAFE directly measure consumption, but only work with liquids and shorten fly lifespan. Additionally, capillary assays are incompatible with delivering viscous foods like high-fat diets. Even solidified high-fat diets tend to be sticky death traps for flies. Another longstanding challenge for fly researchers is that dietary restriction in flies involves diluting food, leading to compensatory feeding. To address these shortcomings, we have developed DIETS, a sensitive feeding assay that can be implemented even in low-resource settings. DIETS eliminates the need for labels and directly weighs the solid food consumed by small groups of flies over extended periods of hours to weeks. It allows us to deliver precise amounts of food to flies and implement accurate dietary restrictions. Importantly, DIETS is compatible with studying energy-dense high-fat diets. Using DIETS, we observed that, unlike a high-sugar diet, an isocaloric high-fat diet did not improve the flies’ ability to withstand starvation, even though they consumed more calories and had higher fat deposition.
Time for What? Dissociating Explicit Timing Tasks Through Electrophysiological Signatures
Authors: Bueno Fernanda D. , Nobre Anna C. , Cravo André M.
Published: June 2023

Estimating durations between hundreds of milliseconds and seconds is essential for several daily tasks. Explicit timing tasks, which require participants to estimate durations to make a comparison (time for perception) or to reproduce them (time for action), are often used to investigate psychological and neural timing mechanisms. Recent studies have proposed that mechanisms may depend on specific task requirements. In this study, we conducted electroencephalogram (EEG) recordings on human participants as they estimated intervals in different task contexts to investigate the extent to which timing mechanisms depend on the nature of the task. We compared the neural processing of identical visual reference stimuli in two different tasks, in which stimulus durations were either perceptually compared or motorically reproduced in separate experimental blocks. Using multivariate pattern analyses, we could successfully decode the duration and the task of reference stimuli. We found evidence for both overlapping timing mechanisms across tasks as well as recruitment of task-dependent processes for comparing intervals for different purposes. Our findings suggest both core and specialised timing functions are recruited to support explicit timing tasks.
Cell type-specific contributions to a persistent aggressive internal state in femaleDrosophila
Authors: Chiu Hui , Robie Alice A. , Branson Kristin M. , Vippa Tanvi , Epstein Samantha , Rubin Gerald M. , Anderson David J. , Schretter Catherine E.
Published: June 2023

Persistent internal states are important for maintaining survival-promoting behaviors, such as aggression. In femaleDrosophila melanogaster, we have previously shown that individually activating either aIPg or pC1d cell types can induce aggression. Here we investigate further the individual roles of these cholinergic, sexually dimorphic cell types, and the reciprocal connections between them, in generating a persistent aggressive internal state. We find that a brief 30-second optogenetic stimulation of aIPg neurons was sufficient to promote an aggressive internal state lasting at least 10 minutes, whereas similar stimulation of pC1d neurons did not. While we previously showed that stimulation of pC1e alone does not evoke aggression, persistent behavior could be promoted through simultaneous stimulation of pC1d and pC1e, suggesting an unexpected synergy of these cell types in establishing a persistent aggressive state. Neither aIPg nor pC1d show persistent neuronal activity themselves, implying that the persistent internal state is maintained by other mechanisms. Moreover, inactivation of pC1d did not significantly reduce aIPg-evoked persistent aggression arguing that the aggressive state did not depend on pC1d-aIPg recurrent connectivity. Our results suggest the need for alternative models to explain persistent female aggression.
Spatially and temporally distinct patterns of expression for VPS10P domain receptors in human cerebral organoids
Authors: Febbraro Fabia , Breum Andersen Helena Hørdum , Willnow Thomas E.
Published: June 2023

Vacuolar protein sorting 10 protein (VPS10P) domain receptors are a unique class of intracellular sorting receptors that emerge as major risk factors associated with psychiatric and neurodegenerative diseases, including bipolar disorders, autism, schizophrenia, as well as Alzheimer’s disease and frontotemporal dementia. Yet, the lack of suitable experimental models to study receptor functions in the human brain has hampered elucidation of receptor actions in brain disease. Here, we have adapted protocols in human cerebral organoids to the detailed characterization of VPS10P domain receptor expression during development and in mature brain tissue, including single-cell RNA sequencing. Our studies uncovered spatial and temporal patterns of expression unique to individual receptor species in the human brain. WhileSORL1expression is abundant in stem cells andSORCS1peaks at onset of neurogenesis,SORT1andSORCS2show increasing expression with maturation of neuronal and non-neuronal cell types, arguing for distinct functions in development versus the adult brain. In neurons, subcellular localization also distinguishes between two types of receptors, either mainly localized to the cell soma (SORL1andSORT1) or also to neuronal projections (SORCS1andSORCS2), suggesting divergent functions in protein sorting between Golgi and the endo-lysosomal system or along axonal and dendritic tracks. Taken together, our findings provide an important resource concerning temporal, spatial, and subcellular patterns of VPS10P domain receptor expression in cerebral organoids for further elucidation of receptor (dys)functions causative of behavioral and cognitive defects of the human brain.
Midbrain encodes sound detection behavior without auditory cortex
Authors: Lee Tai-Ying , Weissenberger Yves , King Andrew J , Dahmen Johannes C
Published: June 2023

Hearing involves analyzing the physical attributes of sounds and integrating the results of this analysis with other sensory, cognitive and motor variables in order to guide adaptive behavior. The auditory cortex is considered crucial for the integration of acoustic and contextual information and is thought to share the resulting representations with subcortical auditory structures via its vast descending projections. By imaging cellular activity in the corticorecipient shell of the inferior colliculus of mice engaged in a sound detection task, we show that the majority of neurons encode information beyond the physical attributes of the stimulus and that the animals’ behavior can be decoded from the activity of those neurons with a high degree of accuracy. Surprisingly, this was also the case in mice in which auditory cortical input to the midbrain had been removed by bilateral cortical lesions. This illustrates that subcortical auditory structures have access to a wealth of non-acoustic information and can, independently of the auditory cortex, carry much richer neural representations than previously thought.
Peripheral direct current suppresses physiologically evoked nociceptive responses at the spinal cord in rodent models of pain
Authors: Su Tom F. , Hamilton Jack D. , Guo Yiru , Potas Jason R. , Shivdasani Mohit N. , Moalem-Taylor Gila , Fridman Gene Y. , Aplin Felix P.
Published: June 2023

Electrical neuromodulation is an established non-pharmacological treatment for chronic pain. However, existing devices using pulsatile stimulation are not suitable for all types of chronic pain. Direct current stimulation is a recently developed technology which shows better selectivity for small-diameter fibres. We investigated if this selectivity could be applied to preferentially suppress nociceptive signalling. We applied direct current to the sciatic nerve of rats and compared its effects on spinal activity produced by physiological (non-electrical) stimuli delivered to the foot. Tests were performed across models of neuropathic and inflammatory pain to further clarify potential clinical applications. We found that direct current could effectively suppress activity relating to painful stimuli in both pain models tested. These findings strongly support the use of direct current neuromodulation for chronic pain relief, and suggest that it may be effective at treating a broader range of aberrant pain conditions than existing devices.
Parkinson’s VPS35[D620N] mutation induces LRRK2 mediated lysosomal association of RILPL1 and TMEM55B
Authors: Pal Prosenjit , Taylor Matthew , Lam Pui Yiu , Tonelli Francesca , Hecht Chloe A. , Lis Pawel , Nirujogi Raja S. , Phung Toan K. , Dickie Emily A. , Wightman Melanie , Macartney Thomas , Pfeffer Suzanne R. , Alessi Dario R.
Published: June 2023

The Parkinson’s VPS35[D620N] mutation causes lysosome dysfunction enhancing LRRK2 kinase activity. We find the VPS35[D620N] mutation alters expression of ∼350 lysosomal proteins and stimulates LRRK2 phosphorylation of Rab proteins at the lysosome. This recruits the phosphoRab effector protein RILPL1 to the lysosome where it binds to the lysosomal integral membrane protein TMEM55B. We identify highly conserved regions of RILPL1 and TMEM55B that interact and design mutations that block binding. In mouse fibroblasts, brain, and lung, we demonstrate that the VPS35 [D620N] mutation reduces RILPL1 levels, in a manner reversed by LRRK2 inhibition. Knock-out of RILPL1 enhances phosphorylation of Rab substrates and knock-out of TMEM55B increases RILPL1 levels. The lysosomotropic agent LLOMe, also induced LRRK2 kinase mediated association of RILPL1 to the lysosome, but to a lower extent than the D620N mutation. Our study uncovers a pathway through which dysfunctional lysosomes resulting from the VPS35[D620N] mutation recruit and activate LRRK2 on the lysosomal surface, driving assembly of the RILPL1-TMEM55B complex.
Effects of psychogenic stress on oxidative stress and antioxidant capacity at different growth stages
Authors: Lee Sangun , Itagaki Atsunori , Satoh Atsuko , Sugimoto Issei , Saito Takumi , Tatehana Haruka
Published: June 2023

This study examined the psychogenic stress (PS) effects on changes in oxidative stress and the antioxidant capacity of an organism at different growth stages. The experimental animals were male Wistar rats of five different ages from growth periods (GPs) to old age. The growth stages were randomly classified into control (C) and experimental (PS) groups. PS was performed using restraint and water immersion once daily for 3 h for 4 weeks. Reactive oxygen metabolites (d-ROMs) and the biological antioxidant potential (BAP) were measured before and after the experiment. In addition, the liver and adrenal glands were removed, and the wet weight was measured. The d-ROM and BAP of all growth stages given PS increased significantly. The d-ROM in the C group without PS increased significantly in GPs while decreased significantly in old-aged. In addition, the BAP of the C group in GP and early adulthood were all significantly elevated. There were significant differences in organ weights between the C and PS groups at all growth stages. Oxidative stress and antioxidant capacity differed depending on the organism’s developmental status and growth stage, and PS also showed different effects. In particular, the variability in oxidative stress was remarkable, suggesting that the effect of PS was more significant in the organism’s immature organs.
A comparative analysis of dry sliding wear characterization of textile wastes (cotton/jute fabrics) reinforced nano fly ash filled epoxy based hybrid composites
Authors: Rana Baldev Singh , Bhushan Gian , Chandna Pankaj
Published: June 2023

Purpose

The purpose of current study deals with the development and wear testing of jute and cotton fiber reinforced with nano fly ash-based epoxy composites. Performance of waste cotton fabric nano hybrid composites are compared with waste jute fabric nano hybrid composites.

Design/methodology/approach

Basic hand layup technique was used to develop composites. To optimize the parameters and design of experiments, Taguchi design was implemented to test wear rate and co-efficient of friction as per ASTM standards. Performance of waste cotton fabric nano hybrid composites is compared with waste jute fabric nano hybrid composites.

Findings

Result shows that nano fly ash lowers the wear rate and co-efficient of friction in developed composites. Findings reveals that hybrid composites of waste jute Fabric with 3 Wt.% of nano fly ash performed best amongst all composites developed. Morphology of nano composites worn out surfaces are also analyzed through SEM.

Practical implications

Practically, textile waste, i.e. jute, cotton and nano fly ash (thermal power plant) all wastes, is used to develop composites for multi-function application.

Social implications

Wastes are reused and recycled to develop epoxy-based composites for sustainable structures in aviation.

Originality/value

To the best of the authors’ knowledge, nano fly ash and jute, cotton combination is used for the first time to develop and test for wear application.
Operation design of a robot logistics system considering demand fluctuations in the hotel industry
Authors: Liu Jiahao , Gu Tao , Liao Zhixue
Published: June 2023

Purpose

The purpose of this paper is to consider three factors, namely, intra-week demand fluctuations, interrelationship between the number of robots and order scheduling and conflicting objectives (i.e. cost minimization and customer satisfaction maximization), to optimize the robot logistics system.

Design/methodology/approach

The number of robots and the sequence of delivery orders are first optimized using the heuristic algorithm NSGACoDEM, which is designed using genetic algorithm and composite difference evolution. The superiority of this method is then confirmed by a case study of a four-star grade hotel in South Korea and several comparative experiments.

Findings

Two performance metrics reveal the superior performance of the proposed approach compared to other baseline approaches. Results of comparative experiments found that the consideration of three influencing factors in the operation design of a robot logistic system can effectively balance cost and customer satisfaction over the course of a week in hotel operation and optimize robot scheduling flexibility.

Practical implications

The results of this study reveal that numerous factors (e.g. intra-week demand fluctuations) can optimize the performance efficiency of robots. The proposed algorithm can be used by hotels to overcome the influence of intra-week demand fluctuations on robot scheduling flexibility effectively and thereby enhance work efficiency.

Originality/value

The design of a novel algorithm in this study entails enhancing the current robot logistics system. This algorithm can successfully manage cost and customer satisfaction during off-seasons and peak seasons in the hotel industry while offering diversified schemes to various types of hotels.
Environmental costs, environmental disclosure, and tax avoidance: evidence from mining and energy companies in Indonesia and Australia
Authors: Rini Rima Kusuma , Adhariani Desi , Sari Dahlia
Published: June 2023

Purpose

This study aims to investigate the association between corporate tax avoidance and environmental costs and disclosure in Indonesia and Australia for the research period 2015–2019. This study also analyzes corporate strategies for overcoming public concerns about tax avoidance activities, namely, the trade-off legitimacy and risk reduction strategies, through two mechanisms: the mediation and moderation roles of environmental disclosure on the relationship between environmental costs and tax avoidance activities.

Design/methodology/approach

The data consists of 675 and 235 observations for Australia and Indonesia, respectively, which were analyzed quantitatively using panel regression.

Findings

The results showed that the trade-off legitimacy or risk reduction strategies are not found to be implemented by companies in Indonesia, while in Australia, corporations use the trade-off legitimacy strategy to reduce risk and overcome the negative impact of tax avoidance activities. The results also provide empirical evidence on the impact of environmental costs on environmental disclosure in both countries.

Originality/value

This study contributes to the literature by providing the latest evidence on the role of environmental costs on environmental disclosure, which has rarely been investigated in previous studies.
Management control for process orientation: a systematic literature review of configurations and packages
Authors: Brenner Markus , Wald Andreas , Gleich Ronald
Published: June 2023

Purpose

Process orientation is important for improving organizational performance. The process view is considered a key enabler of digital transformation, and thus management control systems (MCS) are expected to incorporate this view. However, the existing body of knowledge is fragmented, as different process approaches are often considered independently following a reductionist view of control practices. This paper aims to provide recommendations for further research as well as guidance for practice by a systematic review of the state of research of MC for process orientation. It is based on both a comprehensive view to MC using an MCS package approach and a comprehensive view of process orientation.

Design/methodology/approach

A systematic literature review addressing major types of process orientation approaches was performed by applying the comprehensive MC framework of Malmi and Brown. The results were synthesized and propositions were developed.

Findings

All components of the MC framework, as well as MCS packages, are highly relevant for process orientation. Propositions regarding configurations of MC for process orientation show directions for future research. However, comprehensive considerations of packages and of individual components, especially cultural controls, remain scarce in the literature.

Originality/value

To the best of the authors‘ knowledge, this paper is the first of its kind to provide a comprehensive, structured overview of MC for process orientation, applying a nonreductionist view, based on an MCS Package approach, and consolidating the so far fragmented view of different process approaches.
A participatory practice-informed research agenda for the historical sanctuary of Machupicchu: first experience in Peru
Authors: Chuspe Zans María Elena , Barrera Rosario , Escalante Ernesto , Aragon Israel
Published: June 2023

Purpose

A research-practice team was convened for the Machupicchu World Heritage Site to participate in the Heritage Place Lab (HPL), with the goal of building a practice-informed research agenda designed to support the management needs of the site.

Design/methodology/approach

The agenda was built based on both the HPL methodology and a complementary one.

Findings

The proposed agenda centres on three research priorities: (1) Ecosystem services and well-being, (2) local sustainable development and cultural heritage, and (3) mixed-heritage research integration for conservation.

Practical implications

These priorities address conflicts between the two agencies that manage the site and a lack of awareness of heritage values in contrast to economic interests.

Originality/value

The article proposes new research-informed strategies for joint working between the managing agencies of a site where conservation needs conflict with public use demands, representing the first such case for Peru.
Financial development and economic diversification in Qatar: does Islamic finance matters
Authors: Shawtari Fekri Ali , Elsalem Bilal Ahmad , Salem Milad Abdelnabi , Shah Mohamed Eskandar
Published: June 2023

Purpose

The financial system plays an essential role in facilitating the intermediation process for economic growth. Policymakers stress on achieving a well-developed and regulated financial system to achieve economic development and resiliency. Using data from the State of Qatar, this paper aims to examine the impact of financial development indicator on economic growth; the impact of financial development indicator on hydrocarbon and nonhydrocarbon sector; the impact of Islamic banking on hydrocarbon and nonhydrocarbon economic growth.

Design/methodology/approach

The research uses quarterly data from 2007 to 2019 and adopts autoregressive distributed lag cointegration techniques to test the long- and short-run dynamic relationship between various measures of financial development and economic growth.

Findings

The results present evidence of long-term cointegration between overall financial development indicator and economic growth. Furthermore, the authors document the existence of long-term relationship between financial development and nonhydrocarbon sector. However, there is a lack of evidence on the long-run relationship between financial development and the hydrocarbon sector. Notwithstanding, Islamic banking contributes to overall economic development, as well as to the nonhydrocarbon sector.

Practical implications

This paper offers policymakers with insights to evaluate measures to diversify the economy. It also assists decision-makers in promoting Islamic finance, particularly to the banking sector as a vital contributor to economic growth.

Originality/value

To the best of the author’s knowledge, this paper is the first to evaluate financial development and economic growth for the case of Qatar in light of recent developments in Islamic finance.
Mindful self-compassion training program in the family caregivers of patients with cancer: a quasi-experimental study
Authors: Ranjbar Noei Fatemeh , Atashi Vajihe , Ashouri Elaheh
Published: June 2023

Purpose

High levels of depression and anxiety in the family caregivers of a patient with cancer affect their quality of life. The purpose of this study was to investigate the effects of a mindful self-compassion (MSC) training program on self-compassion in the family caregivers of patients with cancer.

Design/methodology/approach

In 2020, this quasi-experimental study used convenience sampling to select 92 family caregivers of patients with cancer presenting to the oncology ward of Seyed-Al-Shohada Hospital, Isfahan, Iran. The subjects randomly assigned to two groups participated in an online MSC program for 1.5 months. All the participants completed a self-compassion scale (Neff) before, immediately after and one month after the intervention. The data were analyzed using the Mann–Whitney U test, the Chi-squared test, the LSD test, the t-test and repeated measures ANOVA.

Findings

The total mean score of self-compassion, respectively, obtained as 64.64 ± 8.23 and 64.44 ± 4.94 in the experimental and control groups before the intervention significantly increased to 81.15 ± 7.94 and 64.06 ± 5.22 immediately after and 78.94 ± 8.22 and 64.22 ± 4.85 one month after the intervention (P < 0.001).

Practical implications

Given the potential for negative psychological impacts for patients, caregivers and clinicians in cancer care, the online MSC program can be recommended to support and reduce psychological distress in them.

Originality/value

This paper examined the effect of the online MSC program on self-compassion in the family caregivers of patients with cancer and can contribute to our understanding of the value of integrating mental health of caregivers and care of patients with cancer.
The persuasive effects of social media narrative PSAs on COVID-19 vaccination intention among unvaccinated young adults: the mediating role of empathy and psychological reactance
Authors: Ko Youngjee , Kim Hanyoung , Seo Youngji , Han Jeong-Yeob , Yoon Hye Jin , Lee Jongmin , Seo Ja Kyung
Published: June 2023

Purpose

Successful social marketing campaign to promote COVID-19 vaccination for the unvaccinated relies on increasing positive reactions but also reducing negative responses to persuasive messages. This study aims to investigate the relative effects of narrative vs non-narrative public service announcements (PSAs) promoting COVID-19 vaccination on both positive and negative reactions. Using social media as a tool for disseminating marketing campaigns provides a great opportunity to examine the effectiveness of narrative PSAs on vaccination intention, especially among unvaccinated young adults, who were the target audience of the social marketing. This study explores the role of empathy and psychological reactance as underlying mechanisms.

Design/methodology/approach

An experiment involving unvaccinated young adults was conducted with a one-factor, two-condition (message type: narrative vs non-narrative) design.

Findings

Results indicated that the narrative (vs non-narrative) PSAs led to greater empathy. While no direct effects of message type emerged on psychological reactance or vaccination intention, results of a serial multi-mediator model confirmed that empathy and psychological reactance mediated the effects of message type on vaccination intention.

Originality/value

The study extends the understanding of narrative persuasion by examining an underlying mechanism behind narrative persuasion in a COVID-19 PSA. This study provides empirical evidence of the important role of empathy in processing narrative PSAs. Moreover, the current study expands narrative persuasion’s applicability to COVID-19 vaccination intervention messages for unvaccinated young adults, highlighting the effectiveness of narrative persuasion as a social marketing communication tool.
Do congruent perceptions of an ethical leader and one's supervisor impact job-related outcomes? Testing mechanisms and boundaries
Authors: Coyle Patrick Terrence , Biermeier-Hanson Benjamin
Published: June 2023

Purpose

The authors integrate social cognitive theory with social exchange theory to examine how subordinates' perceptions of leader-member exchange (LMX) and moral disengagement mediate the relationship between congruence on implicit leadership theories (ILTs) of ethical leaders and characteristics recognized in one's supervisor (ethical ILT–supervisor alignment) and subsequent engagement-related outcomes (engagement attitudes, job satisfaction and supervisor-directed deviance). The authors then examine romance of leadership (ROL) as a moderator of these relationships.

Design/methodology/approach

The authors tested the theorized indirect effects and boundary conditions in a moderated mediation model using 180 working adults over three time points, in a polynomial regression framework using a block variable approach.

Findings

The authors found moderated indirect effects between ethical ILT–supervisor alignment and work-related outcomes via LMX and moral disengagement. ROL served as a boundary condition, such that the high levels bolstered the positive effects of ethical ILT–supervisor alignment.

Originality/value

The study results suggest that examining ethical leadership through the lens of implicit theories may be fruitful and highlight the importance of accounting for context when assessing the impact of ILTs.