bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of compression forces on different mesenchymal stem cell types regarding orthodontic indication
Authors: Radermacher Chloé , Craveiro Rogerio B , Jahnen-Dechent Wilhelm , Beier Justus P , Bülow Astrid , Wolf Michael , Neuss Sabine 
Published: August 2024

Abstract
The potential of stem cells, for example upper periodontal ligament stem cells from the maxilla (u-PDLSC) and from the mandible (l-PDLSC), adipose-derived mesenchymal stem cells (AD-MSC), and bone marrow-derived mesenchymal stem cells (BM-MSC), with respect to periodontal remodeling and orthodontic treatment is of great importance. In this work, we focus on the comprehensive adaptability of different stem cell types to mechanical forces with the aim to better understanding cell behavior and to refine a new mechanistic approach to investigate periodontal remodeling. We comprehensively analyze stem cells and observe distinct morphological and proliferation changes under compression in dependence on stem cell type. The cell signaling of extracellular signal-regulated kinase (ERK) and protein kinase B, also called AKT, and their respective phosphorylation shows diverse responses to compression. Additionally, vascular endothelial growth factor and hepatocyte growth factor secretion were reduced under mechanical stress in all cell types, with cell-specific variations. Osteoprotegerin secretion was reduced under compression, particularly in u-PDLSC. At least, diverse soluble receptors of NF-kB-ligand secretion patterns among cell types under pressure were observed, providing crucial insights into bone metabolism. These findings offer a deeper understanding of the behavior of mesenchymal stem cells under mechanical stimuli, highlighting their roles in bone remodeling, wound healing, and tissue regeneration in orthodontic and regenerative medicine contexts. Our results underscore the potential of u-PDLSC, l-PDLSC, and AD-MSC in periodontal regeneration, with AD-MSC showing notable resilience under compression, indicating its promising role for further investigation for orthodontic research. While these findings are encouraging, further research is essential to fully comprehend the mechanism of stem cell-based periodontal therapies.
Integrative single-cell and spatial transcriptomic analyses identify a pathogenic cholangiocyte niche and TNFRSF12A as therapeutic target for biliary atresia
Authors: Xiao Man-Huan , Ma Dong , Wu Sihan , Huang Zaoli , Liang Peishi , Chen Huadong , Zhong Zhihai , Li Wei , Wang Fen , Tang Yanlai , Liu Juncheng , Jiang Hong , Feng Xuyang , Luo Zhenhua 
Published: August 2024

Background and Aims:
Biliary atresia (BA) is a devastating fibroinflammatory biliary disease that is the leading indication for pediatric liver transplants worldwide. Although cholangiocytes are the primary target cells, the pathogenic mechanisms involving cholangiocytes remain elusive. Here, we aimed to characterize the pathogenic role of cholangiocytes in BA.

Approach and Results:
Integration of single-cell RNA sequencing of 12 liver tissues (from 9 BA and 3 controls) and the spatial transcriptome of another four liver sections (from 2 BA and 2 controls) provided a comprehensive spatial liver cell atlas of BA. In particular, we identified a cholangiocyte-enriched spatial niche with infiltration of activated HSCs, activated portal fibroblasts, macrovascular endothelial cells, and TREM2+ macrophages that were elevated in the portal triad of BA. This niche was positively correlated with bile duct profiles, liver fibrosis, and poor survival in 2 independent cohorts of patients with BA. Using integrative bioinformatics analyses to mine the cell-cell communication and regulatory network in BA cholangiocytes, we uncovered the fibroinflammatory phenotype of cholangiocytes with TNFSF12-TNFRSF12A as a significant signal. Genetic ablation or blockade of TNFRSF12A suppresses liver injury, inflammation, and bile duct profiles in a mouse model of disease. Using human biliary organoids, we revealed that BA organoids expressed higher levels of CCL2 in response to TNFSF12 stimulation and promoted monocyte chemotaxis via the CCL2-CCR2 axis.

Conclusions:
Pathogenic cholangiocytes-enriched niche identifies TNFRSF12A as a potential therapeutic target for BA.
D4-Chip Reveals Impaired T Cell Function in Sepsis: Insights from Plasma Microenvironment Analysis and Mitochondrial Targeted Therapy
Authors: Liu Lijuan , Wang Ruoyu , Pu Xuexue , Zha Yutao , Yang Xiao , Fang Xiao , Liu Yong , Shao Min , Zhu Ling , Ren Xiaoou , Deng Guoqing , Yang Ke 
Published: August 2024

Abstract

Background
Sepsis, a systemic inflammation syndrome initiated by infection, poses significant challenges due to its intricate pathophysiology. T cells play a crucial role in combating infections during sepsis. Despite previous observations indicating T cell dysfunction in sepsis, reliable in-vitro detection methods were lacking, and the factors influencing these impairments remained unclear.

Methods
We developed a novel method using the D4-Chip to assess sepsis T cell migration function. This microfluidic platform enabled precise analysis of migration function under controlled conditions. Additionally, We explored the impact of the plasma microenvironment on T cell behavior, along with the redox environment in sepsis, and assessed the potential efficacy of Mitoquinone mesylate (MitoQ), a mitochondrial-targeted drug.

Results
Our findings revealed impaired migration function in sepsis T cells compared to healthy controls. Interestingly, sepsis plasma enhanced the migration of healthy T cells, yet incubation with healthy plasma did not fully restore migration impairments in sepsis T cells. Subsequent investigations uncovered a significant increase in NADH/NAD+ levels in sepsis T cells, with healthy T cells exposed to various sepsis plasma conditions also showing elevated NADH/NAD+ levels. Importantly, MitoQ normalized abnormal intracellular NADH/NAD+ levels and enhanced the migration ability of T cells.

Conclusions
Short-term incubation with sepsis plasma does not directly inhibit T cell migration but instead affects T cell function by disrupting the intracellular redox environment. Improving the intracellular redox environment of sepsis patients contributes to restoring impaired migration and proliferation, with MitoQ demonstrating therapeutic potential.
Optimization of TMS target engagement: novel evidence based on combined TMS–EEG and dMRI tractography of brain circuitry
Authors: Lioumis Pantelis , Roine Timo , Granö Ida , Aydogan Dogu Baran , Ukharova Elena , Souza Victor H. , Kičić Dubravko , Ilmoniemi Risto J. , Makris Nikos 
Published: August 2024

AbstractNeuromodulation is based on the principle that brain stimulation produces plastic changes in cerebral circuitry. Given the intersubject structural and functional variability, neuromodulation has a personalized effect in the brain. Moreover, because of cerebral dominance and interhemispheric functional and structural differences in the same individual, the characterization of specific brain circuitries involved is currently not feasible. This notion is extremely important for neuromodulation treatments applied in neuropsychiatry. Specifically, the efficacy of the neuromodulation treatments is critically dependent on the anatomical precision of the brain target and the circuitry which has been affected. However, a complete understanding of how the brain behaves under stimulation needs a combined characterization of its neurophysiological response. This can be achieved by TMS–EEG guided by current multimodal neuroimaging techniques in real time. Herein, we present novel data based on dMRI tractography-guided TMS–EEG on one healthy young adult volunteer.
Physical activity modifies the metabolic profile of CD4+ and CD8+ T cell subtypes at rest and upon activation in older adults
Authors: Withnall Edward , Hazeldine Jon , Llibre Alba , Duggal Niharika A. , Lord Janet M. , Sardeli Amanda V. 
Published: August 2024

AbstractAging reduces the functional competence of T cells. T cell metabolism regulates their function, with mitochondrial defects in mice resulting in aged phenotypes, including accelerated senescence. Physical activity (PA) maintains T cell function in older adults, although the mechanisms underlying this effect are poorly understood. This study examined the effects of aging on the metabolic profile of T cell subsets and investigated whether PA could improve metabolic function in T cells from older donors. We recruited nine young adults (23 ± 3y) and 19 healthy older adults who had high PA (HPA, N=9, 75.5 ± 4.7y) or low PA levels (LPA, N=10, 76.4 ± 2.1y), based on their moderate-to-vigorous PA scores. We investigated the metabolic profiles of CD4+ and CD8+ T cells at rest and post-activation (PMA and ionomycin), via SCENITH flow cytometry. Compared to young adults, older adults had higher mitochondrial dependence (MD) in unstimulated CD4+ and CD8+ naive, effector memory (EM) and central memory (CM); and higher protein synthesis in CD4+ EM, CD4+ naïve, CD8+ EM, suggesting higher energetic demand in T cells with aging. Upon activation there was a lower reduction in MD of CD4+ EMRA and CD8+ EMRA; and a greater increase in IL-6 and TNFα expression in CD8+ cells of older than young adults, indicative of impaired metabolic flexibility with aging. PA effects were more prominent in unstimulated CD8+ cells, where HPA had lower glucose dependence (GD) for overall CD8+, CD8+EM and a trend to higher MD in CD8+ CM than LPA. Upon activation, HPA had a lower increase in CD4+ TNFα expression and trended to have a higher reduction in MD of overall CD4+ and a higher reduction in GD of CD4+ EMRA, than LPA. This suggests a lower metabolic demand in CD4+ T cells of HPA. We concluded that PA could modify T cell metabolic profile at rest, and following activation, in older adults, which may explain the better T cell function in physically active older individuals.
Stacked MXene/PEDOT-PSS Electrode Fiber for High-Performance Recording and Stimulation
Authors: Gou Shuchun , Li Peixuan , Yang Shu , Bi Guoqiang , Du Zhanhong 
Published: August 2024

AbstractThe development of microelectrodes with high electrical performance is imperative, particularly for invasive interfaces such as deep brain stimulation (DBS) electrodes. MXene, a new family of 2D early transition metal carbides or nitrides, exhibits outstanding electrical properties and has been researched to improve bioelectronic interface. Through a wet spinning process, we fabricate MXene/PEDOT-PSS electrode fibers measuring 30 μm in diameter, exhibiting an electrical conductivity of 2.16 ± 1.46 × 10^5 S/m and notably low interfacial impedance. The excellent cathodic charge storage capacity (CSCc) and charge injection capacity (CIC) lead to their high performance in recording or stimulation. The electrode fibers are electrochemically stable, biocompatible, magnetic resonance imaging (MRI)-compatible, and demonstrate excellent performance in electromyography (EMG), electrocardiograph (ECG), cortical recording and subthalamic nuclei deep brain stimulation (STN-DBS) experiments.
Effects of Release of TSG-6 from Heparin Hydrogels on Supraspinatus Muscle Regeneration
Authors: Pearson Joseph J. , Mao Jiahui , Temenoff Johnna S. 
Published: August 2024

ABSTRACTMuscle degeneration after rotator cuff tendon tear is a significant clinical problem. In these experiments, we developed a poly(ethylene glycol)-based injectable granular hydrogel containing two heparin derivatives (fully sulfated (Hep) and fully desulfated (Hep-)) as well as a matrix metalloproteinase-sensitive peptide to promote sustained release of Tumor Necrosis Factor Stimulated Gene 6 (TSG-6) over 14+ daysin vivoin a rat model of rotator cuff muscle injury. The hydrogel formulations demonstrated similar release profilesin vivo, thus facilitating comparisons between delivery from heparin derivatives on level of tissue repair in two different areas of muscle (near the myotendious junction (MTJ) and in the muscle belly (MB)) that have been shown previously to have differing responses to rotator cuff tendon injury. We hypothesized that sustained delivery of TSG-6 would enhance the anti-inflammatory response following rotator cuff injury through macrophage polarization, and that release from a fully sulfated heparin derivative (Hep) would potentiate this effect throughout the muscle. Inflammatory/immune cells, satellite cells, and fibroadipogenic progenitor cells, were analyzed by flow cytometery 3 and 7 days after injury and hydrogel injection, while metrics of muscle healing were examined via immunohistochemistry up to Day 14. Results showed controlled delivery of TSG-6 from Hep caused heightened macrophage response (Day 14 macrophages, 4.00 ± 1.85% single cells, M2a, 3.27 ± 1.95% single cells) and increased markers of early muscle regeneration (embryonic heavy chain staining) by Day 7, particularly in the MTJ region of the muscle, compared to release from desulfated heparin hydrogels. This work provides a novel strategy for localized, controlled delivery of TSG-6 to enhance muscle healing after rotator cuff tear.IMPACT STATEMENTRotator cuff tear is a significant problem that can cause muscle degeneration. In this study, a hydrogel particle system was developed for sustained release of an anti-inflammatory protein, Tumor Necrosis Factor Stimulated Gene 6 (TSG-6), to injured muscle. Release of the protein from a fully sulfated heparin hydrogel-based carrier demonstrated greater changes in amount inflammatory cells and more early regenerative effects than a less-sulfated carrier. Thus, this work provides a novel strategy for localized, controlled delivery of an anti-inflammatory protein to enhance muscle healing after rotator cuff tear.
Behavioral and neural correlates of diverse conditioned fear responses in male and female rats
Authors: Mitchell Julia R. , Vincelette Lindsay , Tuberman Samantha , Sheppard Vivika , Bergeron Emmett , Calitri Roberto , Clark Rose , Cody Caitlyn , Kannan Akshara , Keith Jack , Parakoyi Abigail , Pikus MaryClare , Vance Victoria , Ziane Leena , Brenhouse Heather , Laine Mikaela A. , Shansky Rebecca M. 
Published: August 2024

AbstractPavlovian fear conditioning is a widely used tool that models associative learning in rodents. For decades the field has used predominantly male rodents and focused on a sole conditioned fear response: freezing. However, recent work from our lab and others has identified darting as a female-biased conditioned response, characterized by an escape-like movement across a fear conditioning chamber. It is also accompanied by a behavioral phenotype: Darters reliably show decreased freezing compared to Non-darters and males and reach higher velocities in response to the foot shock (“shock response”). However, the relationship between shock response and conditioned darting is not known. This study investigated if this link is due to differences in general processing of aversive stimuli between Darters, Non-darters and males. Across a variety of modalities, including corticosterone measures, the acoustic startle test, and sensitivity to thermal pain, Darters were found not to be more reactive or sensitive to aversive stimuli, and, in some cases, they appear less reactive to Non-darters and males. Analyses of cFos activity in regions involved in pain and fear processing following fear conditioning identified discrete patterns of expression among Darters, Non-darters, and males exposed to low and high intensity foot shocks. The results from these studies further our understanding of the differences between Darters, Non-darters and males and highlight the importance of studying individual differences in fear conditioning as indicators of fear state.
A deficiency screen identifies genomic regions critical for sperm head-tail connection
Authors: Galletta Brian J. , Konstantinidou Parthena , Haase Astrid D. , Rusan Nasser M. 
Published: August 2024

AbstractA stable connection between the sperm head and tail is critical for fertility in species with flagellated sperm. The head-tail coupling apparatus (HTCA) serves as the critical link between the nucleus (head) and the axoneme (tail) via the centriole. To identify regions of theDrosophila melanogastergenome that contain genetic elements that influence HTCA formation, we undertook a two part screen using theDrosophiladeficiency (Df) kit. For this screen, we utilized a sensitized genetic background that overexpresses the pericentriolar material regulatory protein Pericentrin-Like Protein (PLP). We had previously shown that PLP overexpression (PLPOE) disrupts the head-tail connection in some spermatids, but not to a degree sufficient to reduce fertility. In the first step of the screen we tested for Dfs that in combination with PLPOEcause a reduction in fertility. We ultimately identified 11 regions of the genome that showed an enhanced fertility defect when combined with PLP overexpression. In the second step of the screen we tested these Dfs for their ability to enhance the HTCA defect caused by PLPOE, finding six. We then tested smaller Dfs to narrow the region of the genome that contained these enhancers. To further analyze the regions of the genome removed by these Dfs, we examined the expression patterns of the genes within these Dfs in publicly available datasets of RNAseq ofDrosophilatissues and snRNAseq ofDrosophilatestes. In total, our analysis suggests that some of these Dfs may contain a single gene that might influence HTCA formation and / or fertility, while others appear to be regions of the genome especially rich in testis-expressed genes that might affect the HTCA because of complex, multi-gene interactions.Article SummaryWe perform a genetic enhancer deficiency screen to uncover genomic regions required for proper sperm head-tail connection. We identified 6 regions and provide insight into these regions using publicly available RNA sequence data. Our data reveal that these regions are exceptionally rich in testes specific genes. Further analysis using small deficiencies resulted in two classes of enhancers: one class likely enhances head-tail connection by disrupting multiple genes, while the second class might house a single gene responsible for the reduction in fertility.
Molecular Mechanisms ofCoxiella burnetiiFormalin Fixed Cellular Vaccine Reactogenicity
Authors: Fratzke A. P. , Szule J. A. , Butler S. M. , van Schaik E. J. , Samuel J. E. 
Published: August 2024

AbstractLocal and systemic reactogenic responses to Q-VAX® have prevented licensing of this vaccine outside of Australia. These reactogenic responses occur in previously sensitize individuals and have not been well defined at the cellular level, in part because many studies have been done in guinea pigs that have limited molecular tools. We previously characterized a mouse model of reactogenicity where local reactions sites showed an influx of CD8+ and IFNγ-expressing IL17a+ CD4+ T cells consistent with a Th1 delayed-type hypersensitivity. In this study we determined using depletion and adoptive transfer experiments that both anti-Coxiellaantibodies and CD4+ T cells were essential for localized reactions at the site of vaccination. Furthermore, IFNγ depletion showed significant histological changes at the local reaction sites demonstrating the essential nature of this cytokine to reactogenicity. In addition to the cells and cytokines required for this response, we determined WCV material remained at the site of vaccination for at least 26 weeks post-injection. Transmission electron microscopy of these sites demonstrated intact rod-shaped bacteria at 2 weeks post-injection and partially degraded bacteria within macrophages at 26 weeks post-injection. Finally, since SCVs are an environmentally stable form, we determined that local reactions were more severe when the WCV material was prepared with higher levels of SCVs compared to typical WCV or with higher levels of LCV. These studies support the hypothesis that antigen persistence at the site of injection contributes to this reactogenicity and that anti-Coxiellaantibodies, CD4+ T cells, and IFNγ each contribute to this process.
TUSCAN: Tumor segmentation and classification analysis in spatial transcriptomics
Authors: Zang Chenxuan , Guo Charles C. , Wei Peng , Li Ziyi 
Published: August 2024

AbstractThe identification of tumor cells is pivotal to understanding tumor heterogeneity and the tumor microenvironment. Recent advances in spatially resolved transcriptomics (SRT) have revolutionized the way that transcriptomic profiles are characterized and have enabled the simultaneous quantification of transcript locations in intact tissue samples. SRT is a promising alternative method of studying gene expression patterns in spatial domains. Nevertheless, the precise detection of tumor regions within intact tissue remains a great challenge. The common way of identifying tumor cells is via tumor-specific marker gene expression signatures, which is highly dependent on marker accuracy. Another effective approach is through aneuploid copy number events, as most types of cancer exhibit copy number abnormalities. Here, we introduce a novel computational method, called TUSCAN (TUmor Segmentation and Classification ANalysis in spatial transcriptomics), which constructs a spatial copy number variation profile to improve the accuracy of tumor region identification. TUSCAN combines the gene information from SRT data and the hematoxylin-and-eosin-staining image to annotate tumor sections and other benign tissues. We benchmark the performance of TUSCAN and several existing methods through the application to multiple datasets from different SRT platforms. We demonstrate that TUSCAN can effectively delineate tumor regions, with improved accuracy compared to other approaches. Additionally, the output of TUSCAN provides interpretable clonal evolution inferences that may lead to novel insights into disease development and potential druggable targets.