bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel vaccine strategy using quick and easy conversion of bacterial pathogens to unnatural amino acid-auxotrophic suicide derivatives
Authors: Nagasawa Yuya , Nakayama Momoko , Kato Yusuke , Ogawa Yohsuke , Aribam Swarmistha Devi , Tsugami Yusaku , Iwata Taketoshi , Mikami Osamu , Sugiyama Aoi , Onishi Megumi , Hayashi Tomohito , Eguchi Masahiro
Published: September 2023

We propose a novel strategy for quick and easy preparation of suicide live vaccine candidates against bacterial pathogens. This method requires only the transformation of one or more plasmids carrying genes encoding for two types of biological devices, an unnatural amino acid (uAA) incorporation system and toxin-antitoxin systems in which translation of the antitoxins requires the uAA incorporation.Escherichia coliBL21-AI laboratory strains carrying the plasmids were viable in the presence of the uAA, whereas the free toxins killed these strains after removal of the uAA. The survival time after uAA removal could be controlled by the choice of uAA incorporation system and toxin-antitoxin systems. Multilayered toxin-antitoxin systems suppressed escape frequency to less than 1 escape per 109generations in the best case. This conditional suicide system also worked inSalmonella entericaandE. coliclinical isolates. TheS. entericavaccine strains were attenuated with a >105-fold lethal dose. Serum IgG response and protection against the parental pathogenic strain were confirmed. In addition, the liveE. colivaccine strain was significantly more immunogenic and provided greater protection than a formalin-inactivated vaccine. The liveE. colivaccine was not detected after inoculation, presumably because the uAA is not present in the host animals or in the natural environment. These results suggest that this strategy provides a novel way to rapidly produce safe and highly immunogenic live bacterial vaccine candidates.

Significance

Live vaccines are the oldest vaccines with a history of more than 200 years. Due to their strong immunogenicity, live vaccines are still an important category of vaccines today. However, the development of live vaccines has been challenging due to the difficulties in achieving a balance between safety and immunogenicity. In recent decades, the frequent emergence of various new and old pathogens at risk of causing pandemics has highlighted the need for rapid vaccine development processes. We have pioneered the use of unnatural amino acids to control gene expression and to conditionally kill host bacteria as a biological containment system. This report highlights a quick and easy conversion of bacterial pathogens into live vaccine candidates using this containment system.
Unveiling IRF4-steered regulation of context-dependent effector programs in Th17 and Treg cells
Authors: Gabele Anna , Sprang Maximilian , Cihan Mert , Dietzen Sarah , Klein Matthias , Harms Gregory , Ziesmann Tanja , Pape Katrin , Wasser Beatrice , Gomez-Zepeda David , Braband Kathrin , Delacher Michael , Lemmermann Niels , Bittner Stefan , Andrade-Navarro Miguel A. , Tenzer Stefan , Bopp Tobias , Distler Ute
Published: September 2023

The transcription factor interferon regulatory factor 4 (IRF4) is crucial for the differentiation and fate determination of pro-inflammatory T helper (Th)17 and the functionally opposing group of immunomodulatory regulatory T (Treg) cells. However, molecular mechanisms of how IRF4 steers diverse transcriptional programs in Th17 and Treg cells are far from being definitive. To unveil IRF4-driven lineage determination in Th17 and Treg cells, we integrated data derived from affinity-purification and full mass spectrometry-based proteome analysis with chromatin immune precipitation sequencing (ChIP-Seq). This allowed the characterization of subtype-specific molecular programs and the identification of novel, previously unknown IRF4 interactors in the Th17/Treg context, such as RORγt, AHR, IRF8, BACH2, SATB1, and FLI1. Moreover, our data reveal that most of these transcription factors are recruited to IRF composite elements for the regulation of cell type-specific transcriptional programs providing a valuable resource for studying IRF4-mediated gene regulatory programs in pro- and anti-inflammatory immune responses.
Song distinguishability predicts reproductive isolation between subspecies of the dark-eyed junco
Authors: Hourihan Sarah , Hudson Emily , Du’Mottuchi Ximena León , Beach Emily , Smith Sydnie , Creanza Nicole
Published: September 2023

The dark-eyed junco (Junco hyemalis) has experienced rapid phenotypic diversification within the last 18,000 years, resulting in several subspecies that reside in partially overlapping regions across North America. These subspecies have distinct plumage and morphology. If members of a subspecies disproportionately mate with one another, we would expect genetic differences to accumulate between the subspecies. In parallel, their learned songs could also accumulate changes. If song is used by individuals to recognize members of their own subspecies during mate selection, which would prevent the production of less fit hybrid offspring between subspecies, then song differences might co-localize with subspecies boundaries. Here, we quantify 10 song features to explore subspecies-level song variation using song recordings from community-science databases. We build a machine learning classifier to measure how accurately the subspecies’ songs can be distinguished from one another. Here, we show that songs of dark-eyed junco subspecies exhibit significant song-feature differences. However, these differences do not necessarily lead to distinguishability between subspecies. Notably, we find that subspecies pairs with adjacent ranges that do not hybridize have much more distinguishable songs, and also more evidence for genetic differentiation, than pairs that are known to hybridize. Thus, song distinguishability appears to have predictive power about which subspecies will hybridize, suggesting that song might play a role in reinforcing certain subspecies boundaries more than others. Finally, we analyze subspecies-level song differences alongside available genetic data and geographic coordinates to characterize the current evolutionary landscape of the dark-eyed junco subspecies complex. We observe geographic signal in the song and genetic data, indicating that individuals who share a range are more likely to share song characteristics and be genetically similar. This study illuminates the existence of subspecies-level song differences in the dark-eyed junco and provides further clarity on the role learned song plays in reinforcing reproductive boundaries between dark-eyed junco subspecies.
maskNMF: A denoise-sparsen-detect approach for extracting neural signals from dense imaging data
Authors: Pasarkar Amol , Kinsella Ian , Zhou Pengcheng , Wu Melissa , Pan Daisong , Fan Jiang Lan , Wang Zhen , Abdeladim Lamiae , Peterka Darcy S. , Adesnik Hillel , Ji Na , Paninski Liam
Published: September 2023

A number of calcium imaging methods have been developed to monitor the activity of large populations of neurons. One particularly promising approach, Bessel imaging, captures neural activity from a volume by projecting within the imaged volume onto a single imaging plane, therefore effectively mixing signals and increasing the number of neurons imaged per pixel. These signals must then be computationally demixed to recover the desired neural activity. Unfortunately, currently-available demixing methods can perform poorly in the regime of high imaging density (i.e., many neurons per pixel). In this work we introduce a new pipeline (maskNMF) for demixing dense calcium imaging data.

The main idea is to first denoise and temporally sparsen the observed video; this enhances signal strength and reduces spatial overlap significantly. Next we detect neurons in the sparsened video using a neural network trained on a library of neural shapes. These shapes are derived from segmented electron microscopy images input into a Bessel imaging model; therefore no manual selection of “good” neural shapes from the functional data is required here. After cells are detected, we use a constrained non-negative matrix factorization approach to demix the activity, using the detected cells’ shapes to initialize the factorization. We test the resulting pipeline on both simulated and real datasets and find that it is able to achieve accurate demixing on denser data than was previously feasible, therefore enabling faithful imaging of larger neural populations. The method also provides good results on more “standard” two-photon imaging data. Finally, because much of the pipeline operates on a significantly compressed version of the raw data and is highly parallelizable, the algorithm is fast, processing large datasets faster than real time.
Differential effects of acute and prolonged morphine withdrawal on motivational and goal-directed control over reward-seeking behavior
Authors: Halbout Briac , Hutson Collin , Agrawal Stuti , Springs Zachary A. , Ostlund Sean B.
Published: September 2023

Opioid addiction is a relapsing disorder marked by uncontrolled drug use and reduced interest in normally rewarding activities. The current study investigated the impact of spontaneous withdrawal from chronic morphine exposure on emotional, motivational, and cognitive processes involved in regulating the pursuit and consumption of natural food rewards in male rats. In Experiment 1, rats experiencing acute morphine withdrawal lost weight and displayed somatic signs of drug dependence. However, hedonically-driven sucrose consumption was significantly elevated, suggesting intact and potentially heightened emotional reward processing. In Experiment 2, rats undergoing acute morphine withdrawal displayed reduced motivation when performing an effortful response for palatable food reward. Subsequent reward devaluation testing revealed that acute withdrawal also disrupted their ability to exert flexible goal-directed control over their reward-seeking behavior. Specifically, morphine-withdrawn rats displayed insensitivity to reward devaluation both when relying on prior action-outcome learning and when given direct feedback about the consequences of their actions. In Experiment 3, rats tested after prolonged morphine withdrawal displayed heightened rather than diminished motivation for food rewards and retained their ability to engage in flexible goal-directed action selection. However, brief re-exposure to morphine was sufficient to impair motivation and disrupt goal-directed action selection, though in this case insensitivity to reward devaluation was only observed in the presence of morphine-paired context cues and in the absence of response-contingent feedback. We suggest that these opioid-withdrawal induced deficits in motivation and goal-directed control may contribute to addiction by interfering with the pursuit of adaptive alternatives to drug use.
Single-cell resolution functional networks during sleep are segregated into spatially intermixed modules
Authors: Kiyooka Daiki , Oomoto Ikumi , Kitazono Jun , Kobayashi Midori , Matsubara Chie , Kobayashi Kenta , Murayama Masanori , Oizumi Masafumi
Published: September 2023

The neural mechanisms responsible for the reduction of consciousness during sleep remain elusive. Previous studies investigating macro/mesoscale neural data have suggested that functional networks are segregated into spatially localized modules, and that these modules are more segregated during sleep than during wakefulness. However, large-scale single-cell resolution functional networks remain largely unexplored. Here, we simultaneously recorded the activities of up to 10,000 cortical neurons from multiple brain regions in mice during wakefulness and sleep using a fast, single-cell resolution, and wide-field-of-view two-photon calcium imaging technique. We examined how networks were integrated or segregated between brain states in terms of modularity and spatial distribution in the cortex. We found that modularity during non-rapid eye movement sleep was higher than that during wakefulness, indicating a more segregated network. However, these modules were not spatially localized but rather intermixed across regions in both states. Our results provide novel insights into differences in the cellular-scale organization of functional networks during altered states of consciousness.
Management of very severe tungiasis cases through repeated community-based treatment with a dimeticone oil formula: a longitudinal study in a hyperendemic region in Uganda
Authors: McNeilly Hannah , Mutebi Francis , Thielecke Marlene , Reichert Felix , Banalyaki Mike B. , Arono Rebecca , Mukone George , Feldmeier Hermann
Published: September 2023

Tungiasis (sand flea disease) is a neglected tropical disease that is endemic in sub-Saharan Africa and Latin America. Tungiasis causes pain, mobility restrictions, stigmatisation, and reduced life quality. Very severe cases with hundreds of sand fleas have been described, but treatment of such cases has never been studied systematically.

During a larger community-based tungiasis control programme in a hyperendemic region in Karamoja, northeastern Uganda, 96 very severe tungiasis cases were identified and treated with the dimeticone formula NYDA®. They were repeatedly followed-up and treated again when necessary. The present study traces tungiasis frequency, intensity, and morbidity among these 96 individuals over two years.

At baseline, very severe tungiasis occurred in all age groups, including young children. Throughout the intervention, tungiasis frequency decreased from 100% to 25.8% in this group. The overall number of embedded sand fleas in this group dropped from 15,648 to 158, and the median number of embedded sand fleas among the tungiasis cases decreased from 141 to 4. Walking difficulties were reported in 96.9% at the beginning and in 4.5% at the end of the intervention.

Repeated treatment with the dimeticone formula over two years was a successful strategy to manage very severe cases in a hyperendemic community. Treatment of very severe cases is essential to control the spread and burden of tungiasis in endemic communities.
Enteral Vs Oral Nutrition in non-interrupted compliance with chemoradiotherapy in subjects with esophageal cancer
Authors: Chacón Corena Ayder , Chacón Chacón Hernando , Vargas Moranth Rusvelt , Sierra Maury Grey
Published: September 2023

Background

Esophageal cancer (EC) generates malnutrition, added to the adverse effects of chemoradiotherapy. It is important to avoid intratreatment interruptions to improve survival. The objective is to evaluate the effect of Enteral Nutrition (EN) Vs Oral Nutrition (ON) in compliance without interruptions of chemoradiotherapy in adults with esophageal cancer, in two centers of La Plata Argentina, during 2014-2019.

Methods

Retrospective cohort study. 76 subjects participated, 34 with EN and 46 with ON. Independent variable: type of nutrition, dependent variable: compliance with chemoradiotherapy; potentially confusing variables: sex, age, comorbidities, risk factors, and cancer stages. The percentages of qualitative variables were compared through Chi2 and the T test for the quantitative ones. The RR (95% CI) was calculated by comparing the interruptions in both groups. A crude and adjusted RR analysis was performed, stratifying by sex and clinical variables.

Results

34 subjects had EN and 42 ON; mean age: 65.9 (SD +/-: 10.5) and 68.4 (SD +/-: 9.9) respectively. In both groups, most participants with interruptions were men, in advanced stages, with radical treatment and a diagnosis of carcinoma. In the EN group, 44.12% had interruptions, compared to 14.3% of ON (p <0.05). The group with EN interrupted a mean of 9.9 days (SD +/-: 5.9) and ON: 8.3 (SD +/-: 9.2) (p> 0.05).

Conclusion

The group with EN presented more interruptions, therefore it is not recommended for use prophylactically, only if necessary.
Clinical Performance of SARS-CoV-2 Rapid Antigen Tests: A Systematic Review and Meta-Analysis
Authors: Germic Nina , Hayer Johannes , Feng Qian
Published: September 2023

Objectives

We conducted a meta-analysis of RAT diagnostic accuracy for SARS-CoV-2 infections, and further evaluated test sensitivity versus the presence of symptoms, days post symptom onset (DPSO), sample viral load, and sample type (i.e. direct swabs versus specimens stored in transport media).

Methods

Three databases were searched systematically for performance evaluations of the Roche-distributed SDB SARS-CoV-2 Rapid Antigen Test (Roche/SDB RAT) through March 2022. If the Roche/SDB RAT was compared with any of 9 commonly available antigen tests, data from these tests were also included.

Results

Overall sensitivity of RATs among different manufacturers and study cohorts varied between 36.0% (95% CI: 24.0-50.1) and 79.4% (95% CI: 64.8-89.0). Roche/SDB RATs demonstrated a competitive performance with a pooled (including off-label use) sensitivity of 70.0%, and nearly 100% specificity in included studies. The Roche/SDB RATs exhibited reliable sensitivity in patients with a relatively high viral load (96.6% [95% CI: 95.2-98.2] for Ct≤25). Roche/SDB RATs were more sensitive in symptomatic patients within the first 7 DPSO (85.5% [95% CI: 81.2-88.4]), and when used to test direct swabs (74.4% [95% CI: 69.7-80.3]).

Conclusion

RATs show reliable performance in clinical settings and should be considered when rapid diagnosis of SARS-CoV-2 infection is critical.

HIGHLIGHTS

Meta-analysis of 86 studies of SARS-CoV-2 rapid antigen test (RAT) performance

RAT performance supports near-patient testing for early COVID-19 diagnosis

RAT specificity is high and sensitivity is reliable in those with high viral load

RAT sensitivity in symptomatic patients is higher than in asymptomatic individuals

RAT sensitivity is higher for direct swabs compared to swabs in transport media
Vaccination coverage and adverse events following a reactive vaccination campaign against hepatitis E in Bentiu displaced persons camp, South Sudan
Authors: Nesbitt Robin , Asilaza Vincent Kinya , Gignoux Etienne , Koyuncu Aybüke , Gitahi Priscillah , Nkemenang Patrick , Duncker Jetske , Antier Zelie , Haile Melat , Gakima Primitive , Wamala Joseph , Loro Frederick Beden , Biem Duol , Rull Monica , Azman Andrew S. , Rumunu John , Ciglenecki Iza
Published: September 2023

Introduction

Hepatitis E (HEV) genotypes 1 and 2 are a common cause of jaundice and acute viral hepatitis that can cause large-scale outbreaks. HEV infection is associated with adverse fetal outcomes and case fatality risks up to 26% among pregnant women. An efficacious three-dose recombinant vaccine (Hecolin®) has been licensed in China since 2011 but until 2022, had not been used for outbreak response despite a 2015 WHO recommendation. The first ever mass vaccination campaign against hepatitis E in response to an outbreak was implemented in 2022 in Bentiu internally displaced persons camp in South Sudan targeting 27,000 residents 16-40 years old, including pregnant women.

Methods

We conducted a vaccination coverage survey using simple random sampling from a sampling frame of all camp shelters following the third round of vaccination. For survey participants vaccinated in the third round in October, we asked about the onset of symptoms experienced within 72 hours of vaccination. During each of the three vaccination rounds, passive surveillance of adverse events following immunisation (AEFI) was put in place at vaccination sites and health facilities in Bentiu IDP camp.

Results

We surveyed 1,599 individuals and found that self-reported coverage with one or more dose was 86% (95% CI 84-88%), 73% (95% CI 70-75%) with two or more doses and 58% (95% CI 55-61%) with three doses. Vaccination coverage did not differ significantly by sex or age group. We found no significant difference in coverage of at least one dose between pregnant and non-pregnant women, although coverage of at least two and three doses was 8 and 14 percentage points lower in pregnant women. The most common reasons for non-vaccination were temporary absence or unavailability, reported by 60% of unvaccinated people. Passive AEFI surveillance captured few mild AEFI, and through the survey we found that 91 (7.6%) of the 1,195 individuals reporting to have been vaccinated in October 2022 reported new symptoms starting within 72 hours after vaccination, most commonly fever, headache or fatigue.

Conclusions

We found a high coverage of at least one dose of the Hecolin vaccine following three rounds of vaccination, and no severe AEFI. The vaccine was well accepted and well tolerated in the Bentiu IDP camp community and should be considered for use in future outbreak response.
Association Patterns of Antisocial Personality Disorder across Substance Use Disorders
Authors: Low Aislinn , Stiltner Brendan , Nunez Yaira Z. , Adhikari Keyrun , Deak Joseph D. , Pietrzak Robert H. , Kranzler Henry R. , Gelernter Joel , Polimanti Renato
Published: September 2023

There is a high prevalence of antisocial personality disorder (ASPD) in individuals affected by substance use disorders (SUD). However, there is limited information on the specific patterns of association of ASPD with SUD severity and specific SUD diagnostic criteria. We investigated the association of alcohol, cannabis, cocaine, opioid, and tobacco use disorders (AUD, CanUD, CocUD, OUD, and TUD, respectively) in 1,660 individuals with ASPD and 6,640 controls matched by sex (24% female), age, and racial/ethnic background in a sample ascertained for addiction-related traits. Generalized linear regressions were used to test the association of ASPD with the five DSM-5 SUD diagnoses, their severity (i.e., mild, moderate, severe), and their individual diagnostic criteria. We found that ASPD is associated with the diagnosis and severity of AUD (Odds Ratio, ORs=1.89 and 1.25), CanUD (ORs=2.13 and 1.32), and TUD (ORs=1.50 and 1.21) (ps<.003). Of the specific diagnostic criteria, the “hazardous use” criterion showed the strongest association with ASPD across the five SUDs investigated (from ORTUD=1.88 to ORCanUD=1.37). However, when criteria of different SUDs were included in the same model, ASPD was independently associated only with TUD “hazardous use” and CocUD “attempts to quit”. Attempting to quit cocaine was inversely related to the presence of ASPD and remained significant (OR=0.57, 95% confidence interval = 0.36-0.89) after controlling for interactive effects with sex. The current work provides novel insights into how different SUDs, their severity, and their diagnostic criteria associate with ASPD, potentially furthering our understanding of the impact of polysubstance addiction on mental health.
Different populations of midbrain neurons control the production of distinct acoustic categories of vocalization
Authors: Ziobro Patryk , Woo Yena , He Zichen , Tschida Katherine
Published: September 2023

Animals produce different acoustic types of vocalizations in different behavioral contexts. The midbrain periaqueductal gray (PAG) is obligatory for vocal production (Jürgens, 1994, 2002, 2009), but how midbrain circuits are organized to control the production of different vocalization types remains unknown. To test whether a single population of midbrain neurons regulates the production of different vocalization types, we applied intersectional methods to selectively ablate a population of midbrain neurons required for the production of ultrasonic vocalizations (USVs) in mice. We find that although ablation of these PAG-USV neurons blocks USV production in both males and females, these neurons are not required for the production of squeaks. Our findings provide strong evidence that distinct populations of midbrain neurons control the production of different acoustic categories of vocalizations.
Genomic consequences of isolation and inbreeding in an island dingo population
Authors: Leon-Apodaca Ana V. , Kumar Manoharan , del Castillo Andres , Conroy Gabriel C. , Lamont Robert W , Ogbourne Steven , Cairns Kylie M. , Borburgh Liz , Behrendorff Linda , Subramanian Sankar , Szpiech Zachary A.
Published: September 2023

Dingoes come from an ancient canid lineage that originated in East Asia around 8000-11,000 years BP. As Australia’s largest terrestrial predator, dingoes play an important ecological role. A small, protected population exists on a world heritage listed offshore island, K’gari (formerly Fraser Island). Concern regarding the persistence of dingoes on K’gari has risen due to their low genetic diversity and elevated inbreeding levels. However, whole-genome sequencing data is lacking from this population. Here, we include five new whole-genome sequences of K’gari dingoes. We analyze a total of 18 whole genome sequences of dingoes sampled from mainland Australia and K’gari to assess the genomic consequences of their demographic histories. Long (>1 Mb) runs of homozygosity (ROH) — indicators of inbreeding — are elevated in all sampled dingoes. However, K’gari dingoes showed significantly higher levels of very long ROH (>5 Mb), providing genomic evidence for small population size, isolation, inbreeding, and a strong founder effect. Our results suggest that, despite current levels of inbreeding, the K’gari population is purging strongly deleterious mutations, which, in the absence of further reductions in population size, may facilitate the persistence of small populations despite low genetic diversity and isolation. However, there may be little to no purging of mildly deleterious alleles, which may have important long-term consequences, and should be considered by conservation and management programs.

SIGNIFICANCE

A long-standing question in conservation genetics is whether long-term isolation and elevated levels of inbreeding always leads to inevitable population extinction. Here we conduct the first-ever whole-genome analysis of a population of dingoes living in long-term isolation on an island off the coast of Australia (K’gari). We show that these animals are beset by very low genetic diversity, likely the result of extensive inbreeding, and an elevated number of deleterious homozygotes. However, our results suggest that these dingoes are likely purging highly deleterious alleles, which may have allowed them to persist long term despite their extremely small population (<200 individuals).
State dependent constraints on claustrocortical communication and function
Authors: Marriott Brian A. , Do Alison D. , Portet Coline , Thellier Flora , Goutagny Romain , Jackson Jesse
Published: September 2023

Neural activity in the claustrum has been associated with a range of vigilance states, yet the activity patterns and efficacy of synaptic communication of identified claustrum neurons have not been thoroughly determined. Here we show that claustrum neurons projecting to the retrosplenial cortex were most active during synchronized cortical states such as non-rapid-eye-movement (NREM) sleep and were suppressed during increased cortical desynchronization in arousal, movement, and REM sleep. The efficacy of claustrocortical signaling was also increased during NREM and diminished during movement due in part to increased cholinergic tone. Finally, claustrum activation during NREM sleep enhanced memory consolidation through the phase-resetting of cortical delta waves. Therefore, claustrocortical communication is constrained to function most effectively during cognitive processes associated with synchronized cortical states, such as memory consolidation.

Key Points

Claustrum neurons are suppressed/activated during desynchronized/synchronized cortical states

Claustrocortical connectivity is increased in non-REM and suppressed during movement

Claustrocortical communication is heightened during low cholinergic tone

Claustrum – modulated cortical delta waves enhance the consolidation of a labile memory
Myosin1G promotes Nodal signaling to control Zebrafish Left-Right asymmetry
Authors: Kurup Akshai Janardhana , Bailet Florian , Fürthauer Maximilian
Published: September 2023

Myosin1D (Myo1D) has recently emerged as a conserved regulator of animal LR asymmetry that governs the morphogenesis of the central LR Organizer (LRO). In addition to Myo1D, the zebrafish genome encodes the closely related Myo1G. While Myo1G also controls LR asymmetry, we show that it does so through an entirely different mechanism. Myo1G promotes the Nodal-mediated transfer of laterality information from the LRO to target tissues. At the cellular level, Myo1G is associated with endosomes positive for the TGFβ signaling adapter SARA.myo1gmutants have fewer SARA-positive Activin receptor endosomes and a reduced responsiveness to Nodal ligands that results in a delay of left-sided Nodal propagation and tissue-specific laterality defects in organs that are most distant from the LRO. Beyond LR asymmetry, Myo1G promotes signaling by different Nodal ligands in other biological contexts. Our findings therefore identify Myo1G as a novel positive regulator of the Nodal signaling pathway.
Ventromedial Prefrontal Cortex and Basolateral Amygdala Projections to Ventromedial Striatum Encode Active Avoidance Behavior
Authors: Bullock Teagan E. , Gunaydin Lisa A.
Published: September 2023

Active avoidance is a fundamental defensive behavior, defined as performing a voluntary action to escape a noxious stimulus. Active avoidance serves as an adaptive response to threat, ensuring safety. In individuals with anxiety disorders and post-traumatic stress disorder, avoidance behavior can become maladaptive when even safe situations are avoided, at great psychosocial cost. Corticostriatal and amygdalostriatal pathways have been implicated in active avoidance, though their role in learning and expression of this behavior is not fully understood. Projections from the ventromedial prefrontal cortex (vmPFC) to the ventromedial striatum (VMS) have been shown to regulate a variety of defensive behaviors; however, their role in active avoidance has not previously been examined. Additionally, basolateral amygdala (BLA) projections to the VMS have been shown to promote active avoidance in studies utilizing pharmacological inactivation and optogenetic inhibition, though in vivo real time neural activity in this pathway has not been recorded during active avoidance learning. Here we utilized fiber photometry for in vivo recordings of neural activity in vmPFC-VMS and BLA-VMS projections during active avoidance learning and expression. We implemented a two-way signaled active avoidance paradigm in which a light cue served as the conditioned stimulus (CS) signaling an impending foot shock. We examined changes in neural activity in these two projections during CS presentation, onset of active avoidance, and conditioned freezing. We found that vmPFC-VMS projections develop learning-related increases in activity at CS onset across training, while BLA-VMS projections do not show learning-related encoding of the CS. Additionally, we found that both vmPFC-VMS and BLA-VMS projections develop an increase in activity at avoidance onset. No changes in neural activity were observed during cued freezing in either vmPFC-VMS or BLA-VMS projections. Together these results indicate that vmPFC-VMS projections encode both CS and avoidance, while BLA-VMS projections may simply encode avoidance. Finally, we utilized optogenetic inhibition of vmPFC-VMS projections during the CS to investigate the necessity of this pathway for expression of active avoidance behavior. We found that inhibition of vmPFC-VMS projections attenuates learned active avoidance behavior, indicating that activity in this pathway is required for proper active avoidance. In summary, our results demonstrate task-relevant encoding of active avoidance behavior in vmPFC-VMS and BLA-VMS projections.
Strategic sensemaking by social entrepreneurs: creating strategies for social innovation
Authors: Price Michael , Wong Nicholas , Harvey Charles , Maclean Mairi
Published: September 2023

Purpose

This study explores how a small minority of social entrepreneurs break free from third sector constraints to conceive, create and grow non-profit organisations that generate social value at scale in new and innovative ways.

Design/methodology/approach

Six narrative case histories of innovative social enterprises were developed based on documents and semi-structured interviews with founders and long serving executives. Data were coded “chrono-processually”, which involves locating thoughts, events and actions in distinct time periods (temporal bracketing) and identifying the processes at work in establishing new social ventures.

Findings

This study presents two core findings. First, the paper demonstrates how successful social entrepreneurs draw on their lived experiences, private and professional, in driving the development and implementation of social innovations, which are realised through application of their capabilities as analysts, strategists and resources mobilisers. These capabilities are bolstered by personal legitimacy and by their abilities as storytellers and rhetoricians. Second, the study unravels the complex processes of social entrepreneurship by revealing how sensemaking, theorising, strategizing and sensegiving underpin the core processes of problem specification, the formulation of theories of change, development of new business models and the implementation of social innovations.

Originality/value

The study demonstrates how social entrepreneurs use sensemaking and sensegiving strategies to understand and address complex social problems, revealing how successful social entrepreneurs devise and disseminate social innovations that substantially add value to society and bring about beneficial social change. A novel process-outcome model of social innovation is presented illustrating the interconnections between entrepreneurial cognition and strategic action.
Digitalization of customer service in small and medium-sized enterprises: drivers for the development and improvement
Authors: Costa Ana Carolina Ferreira , Capelo Neto Fernando , Espuny Maximilian , Rocha Aglaé Baptista Torres da , Oliveira Otávio José de
Published: September 2023

Purpose

Small and medium-sized enterprises (SMEs) are fundamental to the socioeconomic development of a country or region. They directly contribute to increasing employment generation and improving income distribution. Despite the importance of SMEs, there are still opportunities for developing works that support and guide SMEs to use digital technologies, especially to digitalize their customer service. Therefore, this work aims to propose drivers containing recommendations for developing and improving the digitalization of customer service in SMEs.

Design/methodology/approach

This work uses a qualitative approach to systematize the main SMEs' characteristics and identify the boosting elements of the digitalization of customer service in the scientific literature. To this end, the authors conducted a content analysis of the most influential empirical and theoretical articles on the theme published from 2016 to 2021 in the Scopus database.

Findings

This work identified 38 boosting elements of the digitalization of customer service based on the scientific literature. These elements were grouped into six drivers for developing and improving the digitalization of customer service. The drivers contain recommendations that were adapted for SMEs according to their characteristics and based on the experience of the authors of this work.

Originality/value

This work contributes to promoting socioeconomic development, providing important solutions for managers and owners of SMEs to improve their customer service. The proposed drivers support and encourage the use of digital technologies for developing and improving customer service, overcoming the challenges of digitalization in these companies. Thus, SMEs will be able to increase the satisfaction of their customers and improve their competitiveness.
How trust incongruence affects continuance intention in Peer-to-Peer accommodation service: transaction and consumption risks as moderators
Authors: Guo Yanping , Xiong Bingqing , Sun Yongqiang , Lim Eric Tze Kuan , Tan Chee-Wee
Published: September 2023

Purpose

Peer-to-Peer Accommodation Service (P2PAS) has emerged as a novel paradigm that enables consumers to book temporary accommodation through P2PAS platforms (online transaction), and then reside in hosts' rooms (offline consumption). Due to potential variance in performance and conflict of interest between hosts and platforms, consumers may differ in their trust perceptions of the two parties, which in turn affects consumers' continuous usage of P2PAS. To this end, the authors endeavor to unravel the effect of consumers' trust incongruence on continuance intention, and to further elucidate the moderating influence of transaction and consumption risks on this relationship. This paper aims to discuss the aforementioned objectives.

Design/methodology/approach

This study collected data through an online survey of 408 P2PAS consumers. Polynomial modeling and response surface analysis were conducted to validate the hypothesized relationships.

Findings

Response surface analysis reveals that trust incongruence did not significantly affect consumers' continuance intention. However, continuance intention would be greater when TP was higher than TH compared with when TH was higher than TP. Furthermore, the analytical results suggest that trust incongruence exerts greater negative effect on continuance intention when transaction and consumption risks were high.

Originality/value

First, the study marks a paradigm shift in conceptualizing the incongruence between TP and TH as a determinant of consumers' continuance intention toward P2PAS. Second, the authors derive a typology of risks that is contextualized to P2PAS. Finally, the authors establish transaction and consumption risks as boundary conditions influencing the effects of trust incongruence on consumers' continuance intention toward P2PAS.
Stakeholder expectations, inter-organizational coordination and procurement practices among humanitarian organizations
Authors: Mutebi Henry , Aryatwijuka Wilbroad , Rukundo Aloysious , Twongyirwe Ronald , Tumwebembeire Naster , Tugiramasiko Miriam
Published: September 2023

Purpose

This paper aims to examine the interconnectedness between stakeholder expectations (SE), inter-organizational coordination (IOC) and procurement practices within humanitarian organizations (HOs) based in Uganda.

Design/methodology/approach

Employing a quantitative cross-sectional design, data were gathered from 43 HOs and analyzed using SmartPLS 4.0.8.3. Variance-based structural equation models (VB-SEMs) were employed to examine both direct and indirect effects.

Findings

The findings show a significantly positive relationship between SE, IOC and procurement practices. Additionally, the mediating role of IOC in the relationship between SE and procurement practices is evident.

Research limitations/implications

While this study offers insights into procurement practices in HOs, the use of a quantitative approach might limit capturing dynamic changes over time. Future research could benefit from a nuanced approach involving interviews and longitudinal studies to uncover incremental changes.

Practical implications

During relief management, HOs need to understand their SE through information sharing and capacity building. This understanding can aid in selecting procurement practices that align with SE and ensure the delivery of relief.

Originality/value

Leveraging stakeholder theory, this research contributes to the understanding of how SE and IOC influence the adoption of procurement practices in HOs during relief delivery.
The family-level of generational involvement: impact on the nexus between entrepreneurial orientation and business performance among small family businesses
Authors: Liew Mei Xuan , Loo Yoke Mei
Published: September 2023

Purpose

The aim of this study was to obtain evidence of the practical significance of the generational involvement (GI) of top management teams (TMT) on the nexus between entrepreneurial orientation (EO) and business performance (BP) in small family businesses (SFBs).

Design/methodology/approach

This study employed a questionnaire survey of 112 Malaysian SFBs. The data was analyzed using descriptive analysis, hierarchical multiple regression analysis and a two-way interaction model.

Findings

The results indicate that SFBs have a positive EO–BP nexus. However, the study found that TMT-GI has a negative effect on EO and reduces the positive nexus between EO and BP. Specifically, higher levels of GI were associated with lower levels of EO and weaker BP.

Research limitations/implications

The study raises the necessity for SFBs to seek out a management mechanism and structure to balance the entrepreneurial boundary between the family-level and the business-level when there is increased GI. Additionally to the current, incorporating family TMT-related human ecology aspect of GI with the family business field could lead to a new research value stream.

Practical implications

The results of this study will enable family business decision makers and TMT to better understand the importance of considering family factors in their management strategies.

Originality/value

This analysis highlights the spatial relation of family-level logic in dominating EO–BP nexus at intervals in SFBs, where family factor of TMT-GI will be a key moderator.
Does CSR affect investment efficiency? The moderating role of company reputation
Authors: Afrin Sharmina , Rahman Md. Mominur
Published: September 2023

Purpose

The purpose of the paper is to investigate the association between corporate social responsibility (CSR) and investment efficiency (INE) in Bangladeshi pharmaceutical companies and to explore the moderating role of corporate reputation in this relationship.

Design/methodology/approach

The paper employs a two-step method, with stage 1 involving the development of a theoretical model using the literature's strategic framework and stage 2 using structural equation modelling (SEM) to investigate the relationships between variables. The data set used in the analysis includes 296 responses from senior executives/managers and subordinates at Bangladeshi pharmaceutical firms.

Findings

The study finds that CSR activities that focus on customers, employees and the community significantly affect INE, as well as the extended stakeholders, and that company reputation moderates this relationship. The effect of CSR on INE differs between well-established companies and business firms with favourable reputations.

Practical implications

The paper contributes to understanding the relationship between CSR and INE in a developing country context and highlights the importance of corporate reputation in this relationship. The findings suggest that companies can enhance their INE through CSR initiatives and that a positive reputation can strengthen this relationship further.

Originality/value

The study adds to the limited literature on CSR and INE in developing countries and provides new insights into the moderating role of corporate reputation in this relationship.
The moderating role of gamification toward intentions to use mobile payments applications in Bahrain: an integrated approach
Authors: Akhtar Mohammed Anam , Sarea Adel , Khan Imran , Khan Khurram Ajaz , Singh Madhvendra Pratap
Published: September 2023

Purpose

Using an integrated theoretical model, this study aims to examine the moderating role of gamification in influencing intentions to use mobile payment applications in Bahrain.

Design/methodology/approach

The current examination happens to be the first approximation in the context of Bahrain wherein an extended TPB-based model integrating variables from TAM and UTAUT2 is used along with gamification and situational influence to examine the intentions to use m-payment applications.

Findings

The findings revealed that among the variates of the TPB, AT and PB significantly affect the intentions (IN) to use m-payment applications in Bahrain, but SN fails to affect intentions, similarly SI also fails to affect intentions thereby proving that the pandemic fails to drive the intention of the population under study toward using m-payment applications. However, when the application offers gamification (GM) features, SI significantly affects intentions through GM, thus experience along with situation drives intentions and this becomes the major theoretical contribution of the study.

Practical implications

This examination offers useful practical implications in the form of the findings revealing that GM affects intentions to use m-payment applications and that GM moderates the relationship between perceived risk (PR) and IN, as well as SI and IN, which can be used by the service providers to improve the user experience and achieve better acceptance of their application.

Originality/value

The novelty of the study lies in testing the integrated theoretical model in the context of a GCC nation, Bahrain.
Blended acquisition with temporally signatured/modulated and spatially dispersed source array: Concept and method
Authors: Ishiyama Tomohide
Published: September 2023

We introduce a blended‐acquisition method: temporally signatured and/or modulated and spatially dispersed source array. The former, signatured and dispersed source array has much less constraints in the encoding with operational flexibility, allowing non‐uniform sampling and non‐patterned shooting both in the space and time dimension. The latter, modulated and dispersed source array allows straightforward deblending by filtering and physically separating frequency channels in the frequency domain. We demonstrate our method by synthesizing the blended acquisition followed by deblended‐data‐reconstruction processing in order to discuss the virtues. The examples show that this method could make the blended‐acquisition encoding and operations indeed simple and robust; the same is true for the deblending processing.
Geochemical factors impacting nitrifying communities in sandy sediments
Authors: Wilson Stephanie J. , Song Bongkeun , Anderson Iris C.
Published: September 2023

Sandy sediment beaches covering 70% of non‐ice‐covered coastlines are important ecosystems for nutrient cycling along the land‐ocean continuum. Subterranean estuaries (STEs), where groundwater and seawater meet, are hotspots for biogeochemical cycling within sandy beaches. The STE microbial community facilitates biogeochemical reactions, determining the fate of nutrients, including nitrogen (N), supplied by groundwater. Nitrification influences the fate of N, oxidising reduced dissolved inorganic nitrogen (DIN), making it available for N removal. We used metabarcoding of 16S rRNA genes and quantitative PCR (qPCR) of ammonia monooxygenase (amoA) genes to characterise spatial and temporal variation in STE microbial community structure and nitrifying organisms. We examined nitrifier diversity, distribution and abundance to determine how geochemical measurements influenced their distribution in STEs. Sediment microbial communities varied with depth (p‐value = 0.001) and followed geochemical gradients in dissolved oxygen (DO), salinity, pH, dissolved inorganic carbon and DIN. Genetic potential for nitrification in the STE was evidenced by qPCR quantification of amoA genes. Ammonia oxidiser abundance was best explained by DIN, DO and pH. Our results suggest that geochemical gradients are tightly linked to STE community composition and nitrifier abundance, which are important to determine the fate and transport of groundwater‐derived nutrients to coastal waters.