bluuebunny/crossref_metadata_2025_split huggingface dataset:
VTA glutamatergic projections to the nucleus accumbens suppress psychostimulant-seeking behavior
Authors: Barbano M. Flavia , Qi Jia , Chen Emma , Mohammad Uzma , Espinoza Orlando , Candido Marcos , Wang Huiling , Liu Bing , Hahn Suyun , Vautier François , Morales Marisela 
Published: June 2024

AbstractConverging evidence indicates that both dopamine and glutamate neurotransmission within the nucleus accumbens (NAc) play a role in psychostimulant self-administration and relapse in rodent models. Increased NAc dopamine release from ventral tegmental area (VTA) inputs is critical to psychostimulant self-administration and NAc glutamate release from prelimbic prefrontal cortex (PFC) inputs synapsing on medium spiny neurons (MSNs) is critical to reinstatement of psychostimulant-seeking after extinction. The regulation of the activity of MSNs by VTA dopamine inputs has been extensively studied, and recent findings have demonstrated that VTA glutamate neurons target the NAc medial shell. Here, we determined whether the mesoaccumbal glutamatergic pathway plays a role in psychostimulant conditioned place preference and self-administration in mice. We used optogenetics to induce NAc release of glutamate from VTA inputs during the acquisition, expression, and reinstatement phases of cocaine- or methamphetamine-induced conditioned place preference (CPP), and during priming-induced reinstatement of cocaine-seeking behavior. We found that NAc medial shell release of glutamate resulting from the activation of VTA glutamatergic fibers did not affect the acquisition of cocaine-induced CPP, but it blocked the expression, stress- and priming-induced reinstatement of cocaine- and methamphetamine CPP, as well as it blocked the priming-induced reinstatement of cocaine-seeking behavior after extinction. These findings indicate that in contrast to the well-recognized mesoaccumbal dopamine system that is critical to psychostimulant reward and relapse, there is a parallel mesoaccumbal glutamatergic system that suppresses reward and psychostimulant-seeking behavior.
TRIM26 deficiency enhancing liver regeneration through macrophage polarization and β-catenin pathway activation
Authors: Li Tingting , Zhong Wei , Li Mengqi , Shao Zile , Zhang Gongye , Wang Weiwei , Gao Zhixing , Tan Xuemei , Xu Ziyi , Luo Fanghong , Song Gang 
Published: June 2024

AbstractLiver regeneration is a complex process involving the crosstalk between parenchymal and non-parenchymal cells, especially macrophages. However, the underlying mechanisms remain incompletely understood. Here, we identify the E3 ubiquitin ligase TRIM26 as a crucial regulator of liver regeneration. Following partial hepatectomy or acute liver injury induced by carbon tetrachloride, Trim26 knockout mice exhibit enhanced hepatocyte proliferation compared to wild-type controls, while adeno-associated virus (AAV)-mediated overexpression of Trim26 reverses the promotional effects. Mechanistically, Trim26 deficiency promotes the recruitment of macrophages to the liver and their polarization towards pro-inflammatory M1 phenotype. These M1 macrophages secrete Wnts, including Wnt2, which subsequently stimulate hepatocyte proliferation through the activation of Wnt/β-catenin signaling. In hepatocytes, Trim26 knockdown reduces the ubiquitination and degradation of β-catenin, thereby further enhancing Wnt/β-catenin signaling. Pharmacological inhibition of Wnt/β-catenin pathway by ICG-001 or depletion of macrophages by clodronate liposomes diminishes the pro-regenerative effects of Trim26 deficiency. Moreover, bone marrow transplantation experiments provide evidence that Trim26 knockout in myeloid cells alone can also promote liver regeneration, highlighting the critical role of macrophage Trim26 in this process. Taken together, our study uncovers TRIM26 as a negative regulator of liver regeneration by modulating macrophage polarization and Wnt/β-catenin signaling in hepatocytes, providing a potential therapeutic target for promoting liver regeneration in clinical settings.
ASAH1 facilitates TNBC by DUSP5 suppression-driven activation of MAP kinase pathway and represents a therapeutic vulnerability
Authors: Reddi Kiran Kumar , Chava Suresh , Chabattula Siva Chander , Edwards Yvonne J. K. , Singh Kamaljeet , Gupta Romi 
Published: June 2024

AbstractTriple-negative breast cancer (TNBC) is a subtype of breast cancer that is prone to metastasis and therapy resistance. Owing to its aggressive nature and limited availability of targeted therapies, TNBC is associated with higher mortality as compared to other forms of breast cancer. In order to develop new therapeutic options for TNBC, we characterized the factors involved in TNBC growth and progression. Here, we demonstrate that N-acylsphingosine amidohydrolase 1 (ASAH1) is overexpressed in TNBC cells and is regulated via p53 and PI3K-AKT signaling pathways. Genetic knockdown or pharmacological inhibition of ASAH1 suppresses TNBC growth and progression. Mechanistically, ASAH1 inhibition stimulates dual-specificity phosphatase 5 (DUSP5) expression, suppressing the mitogen-activated protein kinase (MAPK) pathway. Furthermore, pharmacological cotargeting of the ASAH1 and MAPK pathways inhibits TNBC growth. Collectively, we unmasked a novel role of ASAH1 in driving TNBC and identified dual targeting of the ASAH1 and MAPK pathways as a potential new therapeutic approach for TNBC treatment.
Crosstalk between CAFs and tumour cells in head and neck cancer
Authors: Li Xinyang , González-Maroto Celia , Tavassoli Mahvash 
Published: June 2024

AbstractHead and neck squamous cell carcinomas (HNSCCs) are amongst the most aggressive, complex, and heterogeneous malignancies. The standard of care treatments for HNC patients include surgery, radiotherapy, chemotherapy, or their combination. However, around 50% do not benefit while suffering severe toxic side effects, costing the individuals and society. Decades have been spent to improve HNSCC treatment outcomes with only limited success. Much of the research in HNSCC treatment has focused on understanding the genetics of the HNSCC malignant cells, but it has become clear that tumour microenvironment (TME) plays an important role in the progression as well as treatment response in HNSCC. Understanding the crosstalk between cancer cells and TME is crucial for inhibiting progression and treatment resistance. Cancer-associated fibroblasts (CAFs), the predominant component of stroma in HNSCC, serve as the primary source of extra-cellular matrix (ECM) and various pro-tumoral composites in TME. The activation of CAFs in HNSCC is primarily driven by cancer cell-secreted molecules, which in turn induce phenotypic changes, elevated secretive status, and altered ECM production profile. Concurrently, CAFs play a pivotal role in modulating the cell cycle, stemness, epithelial-mesenchymal transition (EMT), and resistance to targeted and chemoradiotherapy in HNSCC cells. This modulation occurs through interactions with secreted molecules or direct contact with the ECM or CAF. Co-culture and 3D models of tumour cells and other TME cell types allows to mimic the HNSCC tumour milieu and enable modulating tumour hypoxia and reprograming cancer stem cells (CSC). This review aims to provide an update on the development of HNSCC tumour models comprising CAFs to obtain better understanding of the interaction between CAFs and tumour cells, and for providing preclinical testing platforms of current and combination with emerging therapeutics.
Mobilization and activation of tumor-infiltrating dendritic cells inhibits lymph node metastasis in intrahepatic cholangiocarcinoma
Authors: Sun Bao-Ye , Wang Zhu-Tao , Chen Ke-Zhu , Song Yang , Wu Jing-Fang , Zhang Dai , Sun Guo-Qiang , Zhou Jian , Fan Jia , Hu Bo , Yi Yong , Qiu Shuang-Jian 
Published: June 2024

AbstractLymph node metastasis (LNM) facilitates distant tumor colonization and leads to the high mortality in patients with intrahepatic cholangiocarcinoma (ICC). However, it remains elusive how ICC cells subvert immune surveillance within the primary tumor immune microenvironment (TIME) and subsequently metastasize to lymph nodes (LNs). In this study, scRNA-seq and bulk RNA-seq analyses identified decreased infiltration of dendritic cells (DCs) into primary tumor sites of ICC with LNM, which was further validated via dual-color immunofluorescence staining of 219 surgically resected ICC samples. Tumor-infiltrating DCs correlated with increased CD8+ T cell infiltration and better prognoses in ICC patients. Mechanistically, β-catenin-mediated CXCL12 suppression accounted for the impaired DC recruitment in ICC with LNM. Two mouse ICC cell lines MuCCA1 and mIC-23 cells were established from AKT/NICD or AKT/YAP-induced murine ICCs respectively and were utilized to construct the footpad tumor LNM model. We found that expansion and activation of conventional DCs (cDCs) by combined Flt3L and poly(I:C) (FL-pIC) therapy markedly suppressed the metastasis of mIC-23 cells to popliteal LNs. Moreover, β-catenin inhibition restored the defective DC infiltration into primary tumor sites and reduced the incidence of LNM in ICC. Collectively, our findings identify tumor cell intrinsic β-catenin activation as a key mechanism for subverting DC-mediated anti-tumor immunity in ICC with LNM. FL-pIC therapy or β-catenin inhibitor could merit exploration as a potential regimen for mitigating ICC cell metastasis to LNs and achieving effective tumor immune control.
Claustrum neurons projecting to the anterior cingulate restrict engagement during sleep and behavior
Authors: Atlan Gal , Matosevich Noa , Peretz-Rivlin Noa , Marsh-Yvgi Idit , Zelinger Noam , Chen Eden , Kleinman Timna , Bleistein Noa , Sheinbach Efrat , Groysman Maya , Nir Yuval , Citri Ami 
Published: June 2024

AbstractThe claustrum has been linked to attention and sleep. We hypothesized that this reflects a shared function, determining responsiveness to stimuli, which spans the axis of engagement. To test this hypothesis, we recorded claustrum population dynamics from male mice during both sleep and an attentional task (‘ENGAGE’). Heightened activity in claustrum neurons projecting to the anterior cingulate cortex (ACCp) corresponded to reduced sensory responsiveness during sleep. Similarly, in the ENGAGE task, heightened ACCp activity correlated with disengagement and behavioral lapses, while low ACCp activity correlated with hyper-engagement and impulsive errors. Chemogenetic elevation of ACCp activity reduced both awakenings during sleep and impulsive errors in the ENGAGE task. Furthermore, mice employing an exploration strategy in the task showed a stronger correlation between ACCp activity and performance compared to mice employing an exploitation strategy which reduced task complexity. Our results implicate ACCp claustrum neurons in restricting engagement during sleep and goal-directed behavior.
Molecular motor tug-of-war regulates elongasome cell wall synthesis dynamics in Bacillus subtilis
Authors: Middlemiss Stuart , Blandenet Matthieu , Roberts David M. , McMahon Andrew , Grimshaw James , Edwards Joshua M. , Sun Zikai , Whitley Kevin D. , Blu Thierry , Strahl Henrik , Holden Séamus 
Published: June 2024

AbstractMost rod-shaped bacteria elongate by inserting new cell wall material into the inner surface of the cell sidewall. This is performed by class A penicillin binding proteins (PBPs) and a highly conserved protein complex, the elongasome, which moves processively around the cell circumference and inserts long glycan strands that act as barrel-hoop-like reinforcing structures, thereby giving rise to a rod-shaped cell. However, it remains unclear how elongasome synthesis dynamics and termination events are regulated to determine the length of these critical cell-reinforcing structures. To address this, we developed a method to track individual elongasome complexes around the entire circumference of Bacillus subtilis cells for minutes-long periods using single-molecule fluorescence microscopy. We found that the B. subtilis elongasome is highly processive and that processive synthesis events are frequently terminated by rapid reversal or extended pauses. We found that cellular levels of RodA regulate elongasome processivity, reversal and pausing. Our single-molecule data, together with stochastic simulations, show that elongasome dynamics and processivity are regulated by molecular motor tug-of-war competition between several, likely two, oppositely oriented peptidoglycan synthesis complexes associated with the MreB filament. Altogether these results demonstrate that molecular motor tug-of-war is a key regulator of elongasome dynamics in B. subtilis, which likely also regulates the cell shape via modulation of elongasome processivity.
On-chip photodetection of angular momentums of vortex structured light
Authors: Dai Mingjin , Wang Chongwu , Sun Fangyuan , Wang Qi Jie 
Published: June 2024

AbstractStructured vortex light with orbital angular momentum (OAM) shows great promise for high-bandwidth optical communications, quantum information and computing, optical tweezers, microscopy, astronomy, among others. Generating, controlling, and detecting of vortex light by all-electrical means is at the heart of next generation nanophotonic platforms. However, on-chip electrical photodetection of structured vortex light remains challenging. Here, we propose an on-chip photodetector based on 2D broadband thermoelectric material (PdSe2) with a well-designed spin-Hall couplers to directly characterize angular momentum modes of vortex structured light. Photothermoelectric responses in the PdSe2 nanoflake, excited by the focusing surface plasmons, show a magnitude proportional to the total angular momentum modes of the infrared vortex beams, thereby achieving direct detection of spin and orbital angular momentum, as well as the chirality and ellipticity of scalar vortex lights. Our works provide a promising strategy for developing on-chip angular momentum optoelectronic devices, which play a key role in the next-generation high-capacity optical communications, quantum information and computing, imaging, and other photonic systems.
Machine learning enhanced analysis of EBSD data for texture representation
Authors: Wanni J. , Bronkhorst C. A. , Thoma D. J. 
Published: June 2024

AbstractGenerating reduced-order, synthetic grain structure datasets that accurately represent the measured grain structure of a material is important for reducing the cost and increasing the accuracy of computational crystal plasticity efforts. This study introduces a machine-learning-based approach, termed texture adaptive clustering and sampling (TACS), for generating representative Euler angle datasets that accurately mimic the crystallographic texture. The TACS approach employs K-means clustering and density-based sampling in a closed-loop iteration to create representative Euler angle datasets. Proof-of-principle experiments were performed on rolled and recrystallized low-carbon steel. Validation of the TACS approach was extended to twenty-two datasets, varying lattice structures, and complex crystallographic textures, thereby encompassing a broad range of materials and crystal structures. Kolmogorov-Smirnov (K-S) test comparisons underscore the performance of the TACS approach over traditional electron backscatter diffraction EBSD dataset reduction techniques, with average K-S test scores nearing 0.9, indicating a high-fidelity representation of the original datasets. In contrast, conventional methods display scores below 0.3, indicating less reliability of the structure representation. The independence of the TACS approach from material texture and its capability to autonomously generate datasets with predetermined data points demonstrates its unbiased potential in streamlining dataset preparation for crystallographic analysis.
Systemic prime mucosal boost significantly increases protective efficacy of bivalent RSV influenza viral vectored vaccine
Authors: Bissett Cameron , Belij-Rammerstorfer Sandra , Ulaszewska Marta , Smith Holly , Kailath Reshma , Morris Susan , Powers Claire , Sebastian Sarah , Sharpe Hannah R. , Allen Elizabeth R. , Wang Ziyin , Cunliffe Robert F. , Sallah Hadijatou J. , Spencer Alexandra J. , Gilbert Sarah , Tregoning John S. , Lambe Teresa 
Published: June 2024

AbstractAlthough licensed vaccines against influenza virus have been successful in reducing pathogen-mediated disease, they have been less effective at preventing viral infection of the airways and current seasonal updates to influenza vaccines do not always successfully accommodate viral drift. Most licensed influenza and recently licensed RSV vaccines are administered via the intramuscular route. Alternative immunisation strategies, such as intranasal vaccinations, and “prime-pull” regimens, may deliver a more sterilising form of protection against respiratory viruses. A bivalent ChAdOx1-based vaccine (ChAdOx1-NP + M1-RSVF) encoding conserved nucleoprotein and matrix 1 proteins from influenza A virus and a modified pre-fusion stabilised RSV A F protein, was designed, developed and tested in preclinical animal models. The aim was to induce broad, cross-protective tissue-resident T cells against heterotypic influenza viruses and neutralising antibodies against RSV in the respiratory mucosa and systemically. When administered via an intramuscular prime-intranasal boost (IM-IN) regimen in mice, superior protection was generated against challenge with either RSV A, Influenza A H3N2 or H1N1. These results support further clinical development of a pan influenza & RSV vaccine administered in a prime-pull regimen.
Molecular signatures of premature aging in Major Depression and Substance Use Disorders
Authors: Onisiforou Anna , Zanos Panos , Georgiou Polymnia 
Published: June 2024

AbstractMajor depressive disorder (MDD) and substance-use disorders (SUDs) often lead to premature aging, increasing vulnerability to cognitive decline and other forms of dementia. This study utilized advanced systems bioinformatics to identify aging “signatures” in MDD and SUDs and evaluated the potential for known lifespan-extending drugs to target and reverse these signatures. The results suggest that inhibiting the transcriptional activation of FOS gene family members holds promise in mitigating premature aging in MDD and SUDs. Conversely, antidepressant drugs activating the PI3K/Akt/mTOR pathway, a common mechanism in rapid-acting antidepressants, may accelerate aging in MDD patients, making them unsuitable for those with comorbid aging-related conditions like dementia and Alzheimer’s disease. Additionally, this innovative approach identifies potential anti-aging interventions for MDD patients, such as Deferoxamine, Resveratrol, Estradiol valerate, and natural compounds like zinc acetate, genistein, and ascorbic acid, regardless of comorbid anxiety disorders. These findings illuminate the premature aging effects of MDD and SUDs and offer insights into treatment strategies for patients with comorbid aging-related conditions, including dementia and Alzheimer’s disease.
High-resolution transcriptome datasets during embryogenesis of plant-parasitic nematodes
Authors: Wang Xueyu , Guo Zhiqing , Dai Dadong , Xie Chuanshuai , Zhao Ziwei , Zheng Jinshui , Sun Ming , Peng Donghai 
Published: June 2024

AbstractUnderstanding the transcriptional regulatory characteristics throughout the embryogenesis of plant-parasitic nematodes is crucial for elucidating their developmental processes’ uniqueness. However, a challenge arises due to the lack of suitable technical methods for synchronizing the age of plant-parasitic nematodes embryo, it is difficult to collect detailed transcriptome data at each stage of embryonic development. Here, we recorded the 11 embryonic developmental time-points of endophytic nematode Meloidogyne incognita (isolated from Wuhan, China), Heterodera glycines (isolated from Wuhan, China), and Ditylenchus destructor (isolated from Jinan, China) species, and constructed transcriptome datasets of single embryos of these three species utilizing low-input smart-seq2 technology. The datasets encompassed 11 complete embryonic development stages, including Zygote, 2-cell, 4-cell, 8-cell, 24–44 cell, 64–78 cell, Comma, 1.5-fold, 2-fold, Moving, and L1, each stage generated four to five replicates, resulting in a total of 162 high-resolution transcriptome libraries. This high-resolution cross-species dataset serves as a crucial resource for comprehending the embryonic developmental properties of plant-parasitic nematodes and for identifying functional regulatory genes during embryogenesis.
Computed tomography reconstructions of burrow networks for the Opheliid polychaete, Armandia cirrhosa
Authors: Howman Rebecca M. , Mavrogordato Mark N. , Alverez-Borges Fernando , Solan Martin 
Published: June 2024

AbstractThe morphology and architecture of structures formed by sediment-dwelling invertebrates, such as excavations or burrows, are often assumed to be characteristic of a given species, consistent across a range of environmental conditions, and used to categorise species contributions to ecosystem functioning. However, very few investigations use non-invasive high-resolution techniques capable of determining fine scale variations in burrow form and complexity, or consider whether or not the form of the burrow is context dependent. Here, we provide replicate high-resolution micro-focus computed tomography data for the complete burrow systems of the Opheliid polychaete, Armandia cirrhosa, across a range of salinity and habitat conditions. These data provide reference models which can be used by ecologists investigating intraspecific variation in species traits and organism-sediment interactions and, more generally, by those tasked with pattern and shape recognition of objects that are morphologically highly variable and which adjust their architecture with changing circumstance or context.
Numerical study of diffusive fish farm system under time noise
Authors: Yasin Muhammad Waqas , Ahmed Nauman , Saeed Jawaria , Baber Muhammad Zafarullah , Ali Syed Mansoor , Akgül Ali , Muhammad Shah , Hassani Murad Khan , Ali Mubasher 
Published: June 2024

AbstractIn the current study, the fish farm model perturbed with time white noise is numerically examined. This model contains fish and mussel populations with external food supplied. The main aim of this work is to develop time-efficient numerical schemes for such models that preserve the dynamical properties. The stochastic backward Euler (SBE) and stochastic Implicit finite difference (SIFD) schemes are designed for the computational results. In the mean square sense, both schemes are consistent with the underlying model and schemes are von Neumann stable. The underlying model has various equilibria points and all these points are successfully gained by the SIFD scheme. The SIFD scheme showed positive and convergent behavior for the given values of the parameter. As the underlying model is a population model and its solution can attain minimum value zero, so a solution that can attain value less than zero is not biologically possible. So, the numerical solution obtained by the stochastic backward Euler is negative and divergent solution and it is not a biological phenomenon that is useless in such dynamical systems. The graphical behaviors of the system show that external nutrient supply is the important factor that controls the dynamics of the given model. The three-dimensional results are drawn for the various choices of the parameters.