bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting endothelial ERG to mitigate vascular regression and neuronal ischemia in retinopathies
Authors: Ma Eric , Schafer Christopher M. , Xie Jun , Rudenko Yelyzaveta , Knapp John T. H. , Randi Anna M. , Birdsey Graeme M. , Griffin Courtney T. 
Published: December 2024

ABSTRACTRetinopathy of prematurity (ROP) and diabetic retinopathy (DR) are ocular disorders in which a loss of retinal vasculature leads to ischemia followed by a compensatory neovascularization response. In mice, this is modeled using oxygen-induced retinopathy (OIR), whereby neonatal animals are transiently housed under hyperoxic conditions that result in central retina vessel regression and subsequent neovascularization. Using endothelial cell (EC)-specific gene deletion, we found that loss of two ETS-family transcription factors, ERG and FLI1, led to regression of OIR-induced neovascular vessels but failed to improve visual function, suggesting that relevant retinal damage occurs prior to and independently of neovascularization. Turning our attention to the initial stage of OIR, we found that hyperoxia repressed ERG expression in retinal ECs of wild type mice, raising the possibility that oxygen-induced ERG downregulation promotes vessel regression during the initiation of OIR-induced pathology. We therefore developed a murine model of EC-specific ERG overexpression and found it sufficient to prevent hyperoxia-induced vascular regression, neuronal cell death, and neovascularization in the OIR model. Importantly, ERG overexpression also improved visual function in OIR-challenged mice. Moreover, we show that both ERG and FLI1 are downregulated in the retinal vessels of human patients with early stages of DR, suggesting that neovascular disorders of the eye may share common mechanisms underlying pathological retinal capillary regression. Collectively, these data suggest that the regulation of vascular regression by EC-expressed ETS transcription factors may be adapted towards novel therapeutic approaches for the prevention and/or alleviation of ocular neovascular disorders.
RELATIONSHIP BETWEEN ACTUAL STRESS AND IN SITU MORPHOLOGICAL CHANGES IN THE MECHANICAL BEHAVIOR OF BIOMIMETIC POROUS HIERARCHICAL SCAFFOLDS
Authors: Marchiori Gregorio , Sancisi Nicola , Tozzi Gianluca , Zingales Massimiliano , Prezioso Gaia , Visani Andrea , Zucchelli Andrea , Sensini Alberto 
Published: December 2024

AbstractThis study investigates the evolution with strain of the material volume fraction (i.e., porosity) and geometry in porous scaffolds to obtain a more accurate description of their stress-strain behavior.Single bundles and hierarchical structures (8 bundles enveloped by a membrane) were produced by electrospinning as tendon/ligament scaffolds. They underwent a micro-tomographyin situtensile test. Apparent and net stress were obtained using the initial sample cross-section and material volume fraction to normalize axial force. Micro-tomography revealed sample morphology change with strain to calculate the actual stress-strain. Moreover, nanofibers arrangement was revealed by scanning electron microscopy on both bundles and membranes.The description of the mechanical response significantly changed using evolving morphometry (actual stress-strain) instead of initial static one (apparent stress-strain), for both single bundle and hierarchical structure. The actual elastic modulus of the single bundles (583±97 MPa) was statistically higher than that of the hierarchical structures (163±107 MPa). This is related to the membrane, membrane-bundle and inter-bundle interactions. In the hierarchical structure, portions of the material resisting traction are constituted by nanofibers not aligned with the load. The different definitions for the stress-strain behavior allow different accuracy levels depending on the experimental complexity.The evolution of morphology with deformation can significantly affect the description of the mechanical response of porous scaffolds. This has a double impact in practical applications: at the body scale, it allows a better comparison between the scaffold behavior and the target tissue; at the cellular scale, it predicts the actual substrate stiffness that cells will face.Graphical Abstract
The effects of object category training on the responses of macaque inferior temporal cortex are consistent with performance-optimizing updates within a visual hierarchy
Authors: Sörensen Lynn K. A. , DiCarlo James J. , Kar Kohitij 
Published: December 2024

AbstractHow does the primate brain coordinate plasticity to support its remarkable ability to learn object categories? To address this question, we measured the consequences of category learning on the macaque inferior temporal (IT) cortex, a key waypoint along the ventral visual stream that is known to support object recognition. First, we observed that neural activity across task-trained monkeys’ IT showed increased object category selectivity, enhanced linear separability (of categories), and overall more categorical representations compared to those from task-naïve monkeys. To model how these differences could arise, we next developed a computational hypothesis-generation framework of the monkeys’ learning process using anatomically-mapped artificial neural network (ANN) models of the primate ventral stream that we combined with various choices of learning algorithms. Our simulations revealed that specific gradient-based, performance-optimizing updates of the ANN’s internal representations substantially approximated the observed changes in the IT cortex. Notably, we found that such models predict novel training-induced phenomena in the IT cortex, including changes in category-orthogonal representations and IT’s alignment with behavior. This convergence between experimental and modeling results suggests that plasticity in the visual ventral stream follows principles of task optimization that are well approximated by gradient descent. We propose that models like the ones developed here could be used to make accurate predictions about visual plasticity in the ventral stream and its transference – or lack thereof – to any future test image.
A Blueprint of Sex-Specific Neuronal Regulation inthe C. elegansNervous System at Single-Cell Resolution
Authors: Haque Rizwanul , Setty Hagar , Lorenzo Ramiro , Stelzer Gil , Rotkopf Ron , Salzberg Yehuda , Goldman Gal , Kumar Sandeep , Halber Shiraz Nir , Leifer Andrew M. , Schneidman Elad , Laurent Patrick , Oren-Suissa Meital 
Published: December 2024

ABSTRACTSex-specific behaviors within a species are often attributed to variances in neuronal wiring and molecular signatures. However, how the genetic sex shapes the molecular architecture of the nervous system at a single neuron level is still unknown. To address this gap, we used single-cell RNA-sequencing (scRNA-seq) to profile the transcriptome of the sex-shared nervous system of adult male and hermaphroditeCaenorhabditis elegans. By ranking neurons based on the degree of molecular dimorphism, we uncover novel sexually dimorphic neurons such as PLM neurons, where functional dimorphism was corroborated by diminished posterior touch responses in hermaphrodites. We identify sex-specific regulators of mechanosensory behavior and neuronal function by combining our dataset with reverse genetic screens. While most sex-shared neurons retain their neurotransmitter identity, the male neuropeptide connectome undergoes substantial remodeling, with most of the neuropeptides showing a male-bias expression. This reinforces the notion that neuropeptides are crucial for diversifying connectome outputs. Furthermore, by correlating gene expression with outgoing synaptic connectivity, we identified regulatory candidates for synaptic wiring, including both shared and sex-specific genes. This comprehensive resource provides foundational insights into the molecular drivers of sexual dimorphism, facilitating future exploration of regulatory mechanisms and their impact on sex-specific behaviors in higher organisms.Abstract Figure
Effect of flicker-induced retinal stimulation of mice revealed by full-field electroretinography
Authors: Rai Milan , Lakshmanan Yamunadevi , Choi Kai Yip , Chan Henry Ho-lung 
Published: December 2024

AbstractPurposeTo investigate the effects of brief flickering light stimulation (FLS) on retinal electrophysiology and its blood flow in normal C57BL6J mice.MethodsRetinal blood flow (RBF) and full-field electroretinography (ffERG) were measured before and after a 60-second long FLS (12 Hz, 0.1 cd·s/m2) in a cohort of 8-12 weeks old C57BL6J mice (n=10) under anaesthetic and light-adapted conditions. A separate set of age-matched mice (n=9) underwent RBF and ffERG measurements before and after steady light stimulation (SLS) at 1 cd/m2under similar conditions. The changes in RBF (arterial and venous flow) and ffERG responses (amplitudes and implicit times of a- and b-wave) were analyzed.ResultsFLS significantly increased both arterial (p=0.003) and venous (p=0.018) blood flow as well as b-wave amplitudes (p=0.017) compared to SLS, which did not have any significant changes in both RBF and ERG. However, no significant differences were found in other ffERG responses (amplitude and implicit time of a-wave and b-wave implicit time) between the two groups after light stimulation. An increase in b-wave amplitude was positively associated with increase in both arterial (r=0.655, p=0.040) and venous blood flow (r=0.638, p=0.047) in the FLS group.ConclusionsTransient FLS induced a significant increase in both RBF and electro-retinal activity, but such increase was not observed after SLS. Our results suggest the role of FLS, which exerts metabolic stress on the retina, in triggering retinal neurovascular coupling.
Chemically-inducible CRISPR/Cas9 circuits for ultra-high dynamic range gene perturbation
Authors: Srinivasan Rajini , Sun Tao , Sandles Azalia , Wu Diana , Wang Liang , Heidersbach Amy , Ho Clark , Xie Shiqi , Ng Andrew , Haley Benjamin 
Published: December 2024

AbstractCRISPR/Cas9 technologies provide unique capabilities for modeling disease and understanding gene-to-phenotype connections. In cultured cells, chemical-mediated control of Cas9 activity can limit off-target effects and enable mechanistic study of essential genes. However, widely-used Tet-On systems often show “leaky” Cas9 expression, leading to unintended edits, as well as weak activity upon induction. Leakiness can be distinctly problematic in the context of Cas9 nuclease activity, which may result in cumulative DNA damage and degradation of the target cell genome over time. To overcome these deficiencies, we established transgenic platforms that minimize Cas9 functionality in the off-state along with maximized and uncompromised on-state gene editing efficiency. By combining conditional destabilization and inhibition of Cas9, we developed an all-in-one (one or multiple guide RNAs and Cas9) ultra-tight, Tet-inducible system with exceptional dynamic range (on vs. off-state) across various cell lines and targets. As an alternative to Tet-mediated induction, we created a branaplam-regulated splice switch module for low-baseline and robust Cas9 activity control. Lastly, for circumstances where DNA damage needs to be avoided, we constructed a dual-control, Tet-inducible CRISPRi module for tight and potent transcriptional silencing. This upgraded suite of inducible CRISPR systems has broad applications for numerous cell types and experimental conditions.
Pathological α-synuclein elicits granulovacuolar degeneration independent of tau
Authors: Dues Dylan J. , Erb Madalynn L. , Kasen Alysa , Vatsa Naman , Williams Erin T. , Nguyen An Phu Tran , Henderson Michael X. , Moore Darren J. 
Published: December 2024

AbstractBackgroundPathologic heterogeneity is a hallmark of Lewy body dementia (LBD), yet the impact of Lewy pathology on co-pathologies is poorly understood. Lewy pathology, containing α-synuclein, is often associated with regional tau pathology burden in LBD. Similarly, granulovacuolar degeneration bodies (GVBs) have been associated with tau pathology in Alzheimer’s disease. Interestingly, GVBs have been detected in a broad range of neurodegenerative conditions including both α-synucleinopathies and tauopathies. Despite the frequent co-occurrence, little is known about the relationship between α-synuclein, tau, and granulovacuolar degeneration.MethodsWe developed a mouse model of limbic-predominant α-synucleinopathy by stereotactic injection of α-synuclein pre-formed fibrils (PFFs) into the basal forebrain. This model was used to investigate the relationship of α-synuclein pathology with tau and GVB formation.ResultsOur model displayed widespread α-synuclein pathology with a limbic predominant distribution. Aberrantly phosphorylated tau accumulated in a subset of α-synuclein inclusion-bearing neurons, often colocalized with lysosomes. Many of these same neurons also contained CHMP2b- and CK1δ-positive granules, established markers of GVBs, which suggests a link between tau accumulation and GVB formation. Despite this observation, GVBs were also detected in tau-deficient mice following PFF-injection, suggesting that pathological α-synuclein alone is sufficient to elicit GVB formation.ConclusionsOur findings support that α-synuclein pathology can independently elicit granulovacuolar degeneration. The frequent co-accumulation of tau and GVBs suggests a parallel mechanism of cellular dysfunction. The ability of α-synuclein pathology to drive GVB formation in the absence of tau highlights the broader relevance of this process to neurodegeneration with relevance to the pathobiology of LBD.
The trade-off between innovation value and risk: the roles of external venture capital and internal innovation assets
Authors: Xiao Ting , Yang Zhi , Jiang Yanhui , Huang Shitong , Lu Chongyu 
Published: December 2024

PurposeResearch generally believes that both corporate venture capital (CVC) and independent venture capital (IVC) promote the innovation value of entrepreneurial ventures, but their roles in innovation risk remain unclear. To reveal the bright and dark sides of CVC and IVC, we compare their influence on innovation performance and performance variability of entrepreneurial ventures as well as their interaction effects with innovation assets through physical and intellectual assets.Design/methodology/approachThis study uses a panel dataset consisting of 630 high-tech ventures and the Heckman selection model to test the hypotheses and correct the endogenous problems.FindingsWe find that CVC improves the innovation performance of entrepreneurial ventures but at the cost of increasing their performance variability, whereas IVC is the opposite. We also find the combination effect of external and internal capital of entrepreneurial ventures. CVC and IVC complement intellectual assets to enhance innovation performance and dance with physical assets to reduce variability.Originality/valueWe use a value-risk dyadic perspective to reveal the bright side and dark side of CVC and IVC. We unveil the interplay mechanism between internal and external capital of entrepreneurial ventures and develop some kinds of capital configuration strategies to balance innovation value and risk.
The role of masculine and feminine gender enactment in hospitality leadership
Authors: Russen Michelle , Dawson Mary , Legendre Tiffany 
Published: December 2024

Purpose
The stereotypical assumptions of what it means to be hegemonically masculine and to be a leader are aligned in current society, potentially creating role incongruity for anyone who does not fit into this definition. The purpose of this study is to investigate whether masculine and feminine leadership traits of men and women hospitality managers affect employees’ intention to trust leaders and organizational attractiveness.

Design/methodology/approach
Explanatory mixed methods were used. First, two experiments (Study 1 = woman manager, n = 137; Study 2 = man manager, n = 117) were conducted with current hospitality employees to test the interaction of masculine versus feminine enactment and the leadership gender composition (3%, 23% or 53% women) on organizational attractiveness and intent to trust the leader. Results did not align with the theories; therefore, three focus groups were held with 13 current hospitality employees.

Findings
Results indicate a shift toward the preference for communal (feminine) characteristics in hospitality leadership with a balance of masculine traits.

Research limitations/implications
The influence of managers’ gender-related behaviors on trust and organizational attractiveness goes beyond their physical gender traits, indicating that gender plays a more crucial role than previously understood.

Originality/value
By using role congruity theory and hegemonic masculinity, this study offers a nuanced understanding of masculine and feminine gender enactment and broadens leadership theory by including the perspectives of nonhegemonic men and assertive women.
Community-level risk awareness and disaster preparedness: an exploratory investigation of Quetta, Balochistan
Authors: Ainuddin Syed , Suriyachan Chamawong , Aruninta Ariya , Aldrich Daniel , Sher Mohammad Abida 
Published: December 2024

Purpose
The purpose of this study is to foster disaster risk reduction as identified by the Sendai Framework through understanding disaster risk mitigation and strengthening disaster preparedness at the community level.

Design/methodology/approach
Using qualitative and quantitative data from Quetta, Balochistan, the team collected primary data from 400 households using stratified random sampling with proportionate allocation through a survey questionnaire, along with fieldwork and group discussions. SPSS was used for the survey data for analysis. This paper identifies factors that promote community resilience through raising community awareness, preparedness and reducing risk.

Findings
Natural hazards including seismic shocks and their consequences such as avalanches and landslides remain serious challenges to vulnerable communities in developing and developed nations around the world. The results of this study reveal that despite being in an active fault zone with large-scale earthquakes, most respondents had little interaction with warning systems, no engagement with planning efforts and a minimum knowledge of evacuation procedures.

Practical implications
This study provides policy guidance to government and non-government agencies to optimize disaster management activities in pre- and post-disaster situations.

Originality/value
To the best if the authors knowledge, the study is the first of its kind in the study area focusing on risk reduction strategies including up-grading bottom-up engagement and community risk mitigation through grassroots educational outreach to build resilience and reduce community vulnerability to natural disasters.
The influence of perceived music quality, atmosphere and place on music festival visitors' behavioural intentions: satisfaction and subjective well-being’s mediating roles
Authors: Çiki Kartal Doğukan , Öğretmenoğlu Mert , Huang Ting-Yen 
Published: December 2024

PurposeThis research investigates the effect of festival attributes such as music quality, atmosphere and place on music festival visitors' behavioural intentions, particularly focusing on how visitors’ satisfaction and their subjective well-being mediate these relationships.Design/methodology/approachThis research was designed as quantitative research to reveal the relationships between music quality, place and atmosphere with visitors' behavioural intentions. Structural equation modelling was used to test the relationships between the constructs using data from 256 festival attendees in Edirne.FindingsThe results reveal that perceived music quality and atmosphere significantly enhance visitors’ satisfaction, which in turn positively impacts word-of-mouth intention and subjective well-being. Moreover, subjective well-being positively and significantly affects visitors' revisit intentions. Finally, visitors’ satisfaction mediates the relationship between perceived music quality and word-of-mouth intention.Originality/valueIt is one of the first studies to investigate the mediating effects of visitor satisfaction and subjective well-being on the relationships between perceived music quality, atmosphere, place and the behavioural intentions of music festival attendees. Furthermore, the present study provides not only empirical support for the theoretical frameworks but also offers practical insights for festival organizers on enhancing visitor experiences to improve behavioural outcomes.
A quantitative analysis of ESG disclosure and financial performance in renewable energy companies: a two-step approach using unsupervised machine learning
Authors: Parashar Mayank , Jaiswal Ritika , Sharma Manish 
Published: December 2024

Purpose
In the era of Industry 5.0, understanding the balance between environmental, social, and governance (ESG) and firm performance is crucial for mitigating climate change and enhancing financial outcomes. This paper aims to analyze the effect of ESG disclosure on the financial performance (FP) of renewable and clean energy (RCE) companies, focusing on the combined ESG disclosure and individual E, S, and G disclosure scores.

Design/methodology/approach
The study analyzed a panel data sample from 2015–2021, covering 41 RCE companies. By applying the K-means++ clustering technique, the research also explored how firm-specific features influence the relationship between ESG disclosure and FP. The Bloomberg database and audited financial reports were used to gather the data for the study.

Findings
The findings indicate that increased ESG disclosure positively influences FP. Further, a significant positive relationship exists between FP and a company’s E and S disclosure. However, firm-specific characteristics significantly influence this relationship. Findings suggest that a company’s commitment to comprehensive ESG efforts enhances financial efficiency rather than increasing costs.

Originality/value
This study adds to the ESG-FP literature by emphasizing global RCE companies, a key player in sustainability. Further, to the best of the author’s knowledge, the study’s uniqueness is attributed to its application of a two-step approach, combining ESG-FP analysis with K-means++ clustering to account for firm-specific characteristics. It also uniquely examines the individual impact of E, S, and G disclosure on the FP of global RCE companies. The findings offer valuable insights for businesses and policymakers in developing strategies that improve profitability while addressing climate change risks.