bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combined blockade of CXCR4 and PD-1 enhances intratumoral dendritic cell activation and immune responses against HCC
Authors: Morita Satoru , Shigeta Kohei , Lei Pin-Ji , Kobayashi Tatsuya , Kikuchi Hiroto , Matsui Aya , Huang Peigen , Pittet Mikael , Duda Dan G. 
Published: November 2023

AbstractImmune checkpoint inhibitors (ICIs) have transformed systemic therapy for unresectable hepatocellular carcinoma (HCC). Nevertheless, their efficacy is limited to a small percentage of patients, leaving an opportunity for enhancement through synergistic combination therapies. We tested here the combined blockade of programmed death receptor 1 (PD-1) and CXCR4, a receptor for CXCL12 and a key mediator of immunosuppression in the tumor microenvironment in orthotopic grafted and autochthonous models of HCC. We evaluated tumor growth and survival outcomes and examined the underlying mechanisms using immunofluorescence, flow cytometry, RNA-sequencing, and transgenic mice experiments. Combined anti-CXCR4/PD-1 therapy had a robust impact on tumor growth and significantly prolonged survival in all murine preclinical models. The combination treatment successfully reprogrammed antigen-presenting cells, revealing the role of conventional type 1 dendritic cells (cDC1s) in the tumor microenvironment. Moreover, DC reprogramming enhanced anti-cancer immunity by facilitating CD8 T-cell accumulation and activation in the HCC tissue. The effectiveness of the anti-CXCR4 antibody/ICI combination treatment was compromised entirely inBatf3-KO mice deficient in cDC1 cells. Thus, combined ICI therapy with an anti-CXCR4 antibody has the potential to augment the anti-cancer effects and improve survival outcomes in HCC via reprogramming intra-tumoral cDC1 cells.
The Bundles of Intercrossing Fibers of the Extensor Mechanism of the Fingers Greatly Influence the Transmission of Muscle Forces
Authors: Dogadov Anton A , Valero-Cuevas Francisco J , Serviere Christine , Quaine Franck 
Published: November 2023

AbstractThe extensor mechanism is a tendinous structure that plays an important role in finger function. It transmits forces from several intrinsic and extrinsic muscles to multiple bony attachments along the finger via sheets of collagen fibers. The most important attachments are located at the base of the second and third phalanges (proximal and distal attachments, respectively). How the forces from the muscles contribute to the forces at the attachment points, however, is not fully known. In addition to the well-accepted medial and lateral bands, there exist two layers of intercrossing fiber bundles (superficial interosseous medial fiber layer and deeper extensor lateral fiber layer), connecting them. In contrast to its common idealization as a minimal network of distinct strings, we built a numerical model consisting of fiber bundles to evaluate the role of multiple intercrossing fibers in the production of static finger forces. We compared this more detailed model of the extensor mechanism to the idealized minimal network that only includes the medial and lateral bands. We find that including bundles of intercrossing fibers significantly affects force transmission, which itself depends on finger posture. In a mid-flexion posture (metacarpal joint MCP = 45°; proximal interphalangeal joint PIP = 45°; distal interphalangeal joint DIP = 10°) the force transmitted by the lateral fibers is 40% lower than in a more pronounced flexed posture (MCP = 90°; PIP = 90°; DIP = 80°). We conclude that the intercrossing fiber bundles — traditionally left out in prior models since Zancolli’s simplification — play an important role in force transmission and variation of the latter with posture.
Transcriptome analysis of the mouse fetal and adult rete ovarii and surrounding tissues
Authors: Anbarci Dilara N. , O’Rourke Rebecca , Xiang Yu , Peters Derek T. , Capel Blanche , McKey Jennifer 
Published: November 2023

AbstractThe rete ovarii (RO) is an epithelial structure that arises during fetal development in close proximity to the ovary and persists throughout adulthood in mice. However, the functional significance of the RO remains elusive, and it has been absent from recent discussions of female reproductive anatomy. The RO comprises three distinct regions: the intraovarian rete (IOR) within the ovary, the extraovarian rete (EOR) in the periovarian tissue, and the connecting rete (CR) linking the EOR and IOR. We hypothesize that the RO plays a pivotal role in maintaining ovarian homeostasis and responding to physiological changes. To uncover the nature and function of RO cells, we conducted transcriptome analysis, encompassing bulk, single-cell, and nucleus-level sequencing of both fetal and adult RO tissues using thePax8-rtTA; Tre- H2B-GFPmouse line, where all RO regions express nuclear GFP. This study presents three datasets, which highlight RO-specific gene expression signatures and reveal differences in gene expression across the three RO regions during development and in adulthood. The integration and rigorous validation of these datasets will advance our understanding of the RO’s roles in ovarian development, female maturation, and adult female fertility.Short narrativeThis study employs comprehensive bulk, single cell and single nucleus transcriptome analysis to uncover gene expression signatures of the fetal and adult rete ovarii (RO).
Fluorescent Peptide-based Probe for the Detection of Alpha-synuclein Aggregates in the Gut
Authors: Sim Rachel , Lee Jeremy , Chieng Joey , Tan Ko Hui , Lim Grace , Foo Aaron , Wong Sunny Hei , Lim Kah Leong , Liang Kaicheng 
Published: November 2023

AbstractBackgroundParkinson’s disease (PD) is diagnosed clinically by motor symptoms, with no molecular diagnostic test currently available. By the time motor symptoms manifest, significant irreversible neurodegeneration has already occurred, limiting the effectiveness of neuroprotective therapies and drug interventions. Recent identification of pathological alpha-synuclein (α-syn) aggregates in the gastrointestinal (GI) tract of prodromal PD patients offer a potential avenue for early disease diagnosis. This study aims to explore specific fluorescence labelling of α-syn aggregates in the GI tract using a peptide-based probe for early diagnosis of PD.MethodsWe used primary hippocampal neuronal cells and wild-type mouse tissues with the addition of pre-formed α-syn fibrils to identify the most suitable peptide fluorescent probe (P1) for staining α-syn aggregates in cells and tissues. We validated the probe labelling in GI tract tissues from three mouse models, including PFF-injected mice and two transgenic PD mouse strains. We quantified labelling accuracy by confocal imaging and protein analysis.ResultsWe found thatP1labelled α-syn aggregates with high accuracy (87% in comparison to Serine129-phosphorylated α-syn antibody) and high specificity for labelling their aggregated forms over monomeric forms. In GI tract tissues,P1labelled α-syn aggregates across tissue layers (mucosa, sub-mucosa, muscularis externa) and achieved comparable performance to antibody staining. Higher degree of probe labelling was found in older mice due to increased accumulation of α-syn aggregates with ageing. Notably, α-syn aggregates were readily detectable in the colonic mucosae usingP1, indicating the potential use of this probe for early PD diagnosis during colonic examinations like colonoscopy.ConclusionWe have developed a peptide-based fluorescent probe and demonstrated its rapid and specific labelling of α-syn aggregates. We highlight the probe’s ability to label these aggregates rapidly over α-syn monomers and survey the abundance of α-syn aggregates throughout the entire length of the GI tract. These support the further development ofP1as a specific fluorescent imaging biomarker for colonic α-syn aggregates for the early detection of PD.
A modular toolbox for the optogenetic deactivation of transcription
Authors: Muench Philipp , Fiumara Matteo , Southern Nicholas , Coda Davide , Aschenbrenner Sabine , Correia Bruno , Gräff Johannes , Niopek Dominik , Mathony Jan 
Published: November 2023

AbstractLight-controlled transcriptional activation is a commonly used optogenetic strategy that allows researchers to regulate gene expression with high spatiotemporal precision. The vast majority of existing tools are, however, limited to light-triggered induction of gene expression. Here, we inverted this mode of action and created two complementary optogenetic systems capable of efficiently terminating transcriptional activation in response to blue light. First, we designed highly compact regulators, by photo-controlling VP16 transactivation peptide exposure. Then, applying a two-hybrid strategy, we engineered LOOMINA (lightoff-operatedmodularinductor of transcriptionalactivation), a versatile transcriptional control platform for mammalian cells that is highly adaptable and compatible with various effector proteins. Leveraging the flexibility of CRISPR systems, we integrated LOOMINA with Cas9 as a DNA-binding domain to control transcription from various endogenous promoters with exceptionally high dynamic ranges in multiple cell lines, including neuron-like cells. Both functionally and mechanistically, LOOMINA represents a valuable addition to the optogenetic repertoire for transcriptional regulation.
Neuronal functional connectivity is impaired in a layer dependent manner near the chronically implanted microelectrodes
Authors: Chen Keying , Forrest Adam , Gonzalez Burgos Guillermo , Kozai Takashi D.Y. 
Published: November 2023

AbstractObjectiveThis study aims to reveal longitudinal changes in functional network connectivity within and across different brain structures near the chronically implanted microelectrode. While it is well established that the foreign-body response (FBR) contributes to the gradual decline of the signals recorded from brain implants over time, how does the FBR impact affect the functional stability of neural circuits near implanted Brain-Computer Interfaces (BCIs) remains unknown. This research aims to illuminate how the chronic FBR can alter local neural circuit function and the implications for BCI decoders.ApproachThis study utilized multisite Michigan-style microelectrodes that span all cortical layers and the hippocampal CA1 region to collect spontaneous and visually-evoked electrophysiological activity. Alterations in neuronal activity near the microelectrode were tested assessing cross-frequency synchronization of LFP and spike entrainment to LFP oscillatory activity throughout 16 weeks after microelectrode implantation.Main ResultsThe study found that cortical layer 4, the input-receiving layer, maintained activity over the implantation time. However, layers 2/3 rapidly experienced severe impairment, leading to a loss of proper intralaminar connectivity in the downstream output layers 5/6. Furthermore, the impairment of interlaminar connectivity near the microelectrode was unidirectional, showing decreased connectivity from Layers 2/3 to Layers 5/6 but not the reverse direction. In the hippocampus, CA1 neurons gradually became unable to properly entrain to the surrounding LFP oscillations.SignificanceThis study provides a detailed characterization of network connectivity dysfunction over long-term microelectrode implantation periods. This new knowledge could contribute to the development of targeted therapeutic strategies aimed at improving the health of the tissue surrounding brain implants and potentially inform engineering of adaptive decoders as the FBR progresses. Our study’s understanding of the dynamic changes in the functional network over time opens the door to developing interventions for improving the long-term stability and performance of intracortical microelectrodes.
Dynamic Fading Memory and Expectancy Effects in Monkey Primary Visual Cortex
Authors: Yiling Yang , Klon-Lipok Johanna , Shapcott Katharine , Lazar Andreea , Singer Wolf 
Published: November 2023

AbstractIn order to investigate the involvement of primary visual cortex (V1) in working memory (WM), parallel, multisite recordings of multiunit activity were obtained from monkey V1 while the animals performed a delayed match-to-sample (DMS) task. During the delay period, V1 population firing rate vectors maintained a lingering trace of the sample stimulus that could be reactivated by intervening impulse stimuli that enhanced neuronal firing. This fading trace of the sample did not require active engagement of the monkeys in the DMS task and likely reflects the intrinsic dynamics of recurrent cortical networks in lower visual areas. This renders an active, attention-dependent involvement of V1 in the maintenance of working memory contents unlikely. By contrast, population responses to the test stimulus depended on the probabilistic contingencies between sample and test stimuli. Responses to tests that matched expectations were reduced which agrees with concepts of predictive coding.
Neural correlates of perisaccadic visual mislocalization in extrastriate cortex
Authors: Weng Geyu , Akbarian Amir , Clark Kelsey , Noudoost Behrad , Nategh Neda 
Published: November 2023

AbstractWhen interacting with the visual world using saccadic eye movements (saccades), the perceived location of visual stimuli becomes biased, a phenomenon called perisaccadic mislocalization, which is indeed an exemplar of the brain’s dynamic representation of the visual world. However, the neural mechanism underlying this altered visuospatial perception and its potential link to other perisaccadic perceptual phenomena have not been established. Using a combined experimental and computational approach, we were able to quantify spatial bias around the saccade target (ST) based on the perisaccadic dynamics of extrastriate spatiotemporal sensitivity captured by statistical models. This approach could predict the perisaccadic spatial bias around the ST, consistent with the psychophysical studies, and revealed the precise neuronal response components underlying representational bias. These findings also established the crucial role of response remapping toward ST representation for neurons with receptive fields far from the ST in driving the ST spatial bias. Moreover, we showed that, by allocating more resources for visual target representation, visual areas enhance their representation of the ST location, even at the expense of transient distortions in spatial representation. This potential neural basis for perisaccadic ST representation, also supports a general role for extrastriate neurons in creating the perception of stimulus location.
Change in RhoGAP and RhoGEF availability drives transitions in cortical patterning and excitability inDrosophila
Authors: Jackson Jonathan A. , Denk-Lobnig Marlis , Kitzinger Katherine A. , Martin Adam C. 
Published: November 2023

SummaryActin cortex patterning and dynamics are critical for cell shape changes. These dynamics undergo transitions during development, often accompanying changes in collective cell behavior. While mechanisms have been established for individual cells’ dynamic behaviors, mechanisms and specific molecules that result in developmental transitions in vivo are still poorly understood. Here, we took advantage of two developmental systems inDrosophila melanogasterto identify conditions that altered cortical patterning and dynamics. We identified a RhoGEF and RhoGAP pair whose relocalization from nucleus to cortex results in actomyosin waves in egg chambers. Furthermore, we found that overexpression of a different RhoGEF and RhoGAP pair resulted in actomyosin waves in the early embryo, during which RhoA activation precedes actomyosin assembly and RhoGAP recruitment by ∼4 seconds. Overall, we showed a mechanism involved in inducing actomyosin waves that is essential for oocyte development and is general to other cell types.
Hyperactivation of MEK1 in cortical glutamatergic neurons results in projection axon deficits and aberrant motor learning
Authors: Bjorklund George R. , Rees Katherina P. , Balasubramanian Kavya , Hewitt Lauren T. , Nishimura Kenji , Newbern Jason M. 
Published: November 2023

AbstractAbnormal Extracellular Regulated Kinase 1/2 (ERK1/2) signaling is linked to multiple neurodevelopmental diseases, especially the RASopathies, which typically exhibit ERK1/2 hyperactivation in neurons and non-neuronal cells. To better understand how excitatory neuron-autonomous ERK1/2 activity regulates the development of the mouse motor cortex, we conditionally expressed a hyperactive MEK1S217/221Evariant usingNex/NeuroD6:Cre. Our results show that MEK1S217/221Eexpression led to persistent hyperactivation of ERK1/2 in neocortical axons, but not excitatory neuron somas or nuclei. We noted reduced axonal arborization of multiple subcortical target domains in mutants and reduced cortical expression of the activity dependent gene, ARC. These changes did not coincide with significant differences in voluntary locomotor activity or motor performance in the accelerating rotarod task. However, motor learning in a single-pellet retrieval task was significantly diminished inNex/NeuroD6:Cre;MEK1S217/221Emutants. Restriction of MEK1S217/221Eexpression to layer V cortical neurons recapitulated axonal outgrowth deficits, however, had no effect on motor learning. Collectively, these results indicate that within the cortex, glutamatergic neuron-autonomous hyperactivation of MEK1 is sufficient to drive deficits in axon outgrowth, activity dependent gene expression, and skilled motor learning.Summary statementMEK-ERK1/2 hyperactivation in developing cortical excitatory neurons is sufficient to decrease long-range axonal outgrowth, which coincides with reduced Arc expression and deficits in aspects of skilled motor learning by adulthood.
What happens after product rebranding: understanding the interrelational effect of brand attachment, brand distinctiveness and consumer attitudes on brand loyalty
Authors: Mensah Isaac , Brew Yaw 
Published: November 2023

PurposeProduct rebranding is increasingly popular, but brand managers are sceptical about its implications on brand loyalty (BL). Given the limited empirical literature on the subject, this study examines the interrelational effect of brand attachment (BA), brand distinctiveness (BD) and consumer attitudes (CA) towards product rebranding on brand loyalty (BL).Design/methodology/approachThe study adopted the quantitative survey design and used questionnaire to gather data from 349 consumers of rebranded water, alcoholic and non-alcoholic beverages. Structural equation modelling was used to analyse the data. This study integrates psychology theories into brand management research to propose and test a holistic model.FindingsThe study found a significant effect of BA on CA toward product rebranding, and CA toward product rebranding fully mediates the relationship between BA and BL. Furthermore, BD has a significant effect on BL, and further moderates the relationship between BA and BL.Originality/valueThis study offers a fresh theoretical foundation, conceptual clarity and understanding of how rebranding specific brand elements affect the attitudes and BL of consumers who are emotionally connected to a brand. This paper offers practical insights into the implication of product rebranding on CA, BD and BL. It reveals a holistic guidance to brand managers on how to use their unique knowledge about their consumers to create distinctive brands and emotional affection, passion and connections to their brands.
A closer look at geographical indicators: how food labels influence product values, authenticity and willingness to pay premium prices
Authors: Ho Kenneth Fu Xian , Liu Fang , Tarabashkina Liudmila 
Published: November 2023

PurposeThe effects of country-of-origin (COO) cues on product evaluations are well documented. However, research on the relative effects of COO compared to other geographical indicators, such as region-of-origin (ROO), on food purchases is still limited. This study investigates how geographical origin labels influence consumers' perceptions of product value and authenticity of foreign food, as well as subsequent purchase intention (PI) and willingness to pay premium prices (WTPPP). The moderating role of health consciousness on these relationships is also examined due to the coronavirus disease 2019 (COVID-19) pandemic.Design/methodology/approachThis study uses a between-subjects experimental design conducted with 300 middle- and high-income Chinese consumers aged between 25 and 50 years. Hypotheses were tested using structural equation modelling.FindingsWhilst under both COO and ROO cues, all five product values positively influenced consumers' WTPPP, only functional, economic and novelty values influenced PI. The ROO cue performed significantly better than the COO cue in eliciting functional, economic and novelty value perceptions, which triggered stronger PI and willingness to pay a premium price. These relationships were mediated by product authenticity (PA) and moderated by consumers' health consciousness (HC).Practical implicationsBecause food labels provide salient product information that facilitates consumers' evaluation of products, marketers should assess which product value perceptions they wish to enhance and then choose the appropriate geographical indicators for their labelling strategies.Originality/valueThis study identifies the effects of COO and ROO cues on product values, authenticity, PI and WTPPP. It also provides valuable insights into the role of HC on consumers' purchase decisions, which also aids in understanding the impact of global crises on food purchases.
Do Indian banks perform better in corporate governance than other SAARC nations? An empirical analysis
Authors: Alam Mahfooz , Akhtar Shakeb , Al-Faryan Mamdouh Abdulaziz Saleh 
Published: November 2023

Purpose
This paper aims to investigate the role of corporate governance on the bank profitability of Indian banks vis-à-vis South Asian Association for Regional Cooperation (SAARC) nations.

Design/methodology/approach
For the Corporate Governance Index, the authors examined board accountability, transparency and disclosure and audit committee, while Tobin’s Q, return on equity and return on assets are used to measure the bank’s profitability. The study used a two-stage analysis based on balanced panel data for robust findings. Sample of this study consists of 60 commercial banks from India and 60 banks from SAARC nations for the period of 2009–2021. This study used panel regression and a generalized method of moment approach using the CAMELS framework on banking industry-specific variables to determine their respective impacts.

Findings
The findings of this study suggest that board accountability is positive and significantly affects the profitability of banks as indicated by return on assets, return on equity and Tobin’s Q. In contrast, the audit committee has a positive and insignificant impact on return on assets, return on equity and Tobin’s Q, while transparency and disclosure have a negative and significant impact on these metrics. Furthermore, the country dummy result shows a significant positive impact on all the bank performance parameters, implying that Indian banks have the highest degree of convergence with corporate governance as compared to other SAARC nations.

Research limitations/implications
This study provides insight to the regulators, policymakers and financial institutions to evaluate the role of corporate governance in emerging economies. However, the findings of the study should be interpreted with caution, as the results are sensitive to the disparity between India and other SAARC nations' government policies, climatic circumstances and cultural or religious traditions.

Originality/value
To the best of the authors’ knowledge, this is the first attempt to gauge the performance of Indian banks vis-à-vis SAARC nations using the CAMELS framework approach. Further, findings of this study suggest some novel evidence tying corporate governance quality with the profitability of banks among SAARC nations.