bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential brain ADRA2A and ADRA2C gene expression and epigenetic regulation in schizophrenia. Effect of antipsychotic drug treatment
Authors: Brocos-Mosquera Iria , Miranda-Azpiazu Patricia , Muguruza Carolina , Corzo-Monje Virginia , Morentin Benito , Meana J. Javier , Callado Luis F. , Rivero Guadalupe 
Published: December 2021

AbstractPostsynaptic α2A-adrenoceptor density is enhanced in the dorsolateral prefrontal cortex (DLPFC) of antipsychotic-treated schizophrenia subjects. This alteration might be due to transcriptional activation, and could be regulated by epigenetic mechanisms such as histone posttranslational modifications (PTMs). The aim of this study was to evaluate ADRA2A and ADRA2C gene expression (codifying for α2-adrenoceptor subtypes), and permissive and repressive histone PTMs at gene promoter regions in the DLPFC of subjects with schizophrenia and matched controls (n = 24 pairs). We studied the effect of antipsychotic (AP) treatment in AP-free (n = 12) and AP-treated (n = 12) subgroups of schizophrenia subjects and in rats acutely and chronically treated with typical and atypical antipsychotics. ADRA2A mRNA expression was selectively upregulated in AP-treated schizophrenia subjects (+93%) whereas ADRA2C mRNA expression was upregulated in all schizophrenia subjects (+53%) regardless of antipsychotic treatment. Acute and chronic clozapine treatment in rats did not alter brain cortex Adra2a mRNA expression but increased Adra2c mRNA expression. Both ADRA2A and ADRA2C promoter regions showed epigenetic modification by histone methylation and acetylation in human DLPFC. The upregulation of ADRA2A expression in AP-treated schizophrenia subjects might be related to observed bivalent chromatin at ADRA2A promoter region in schizophrenia (depicted by increased permissive H3K4me3 and repressive H3K27me3) and could be triggered by the enhanced H4K16ac at ADRA2A promoter. In conclusion, epigenetic predisposition differentially modulated ADRA2A and ADRA2C mRNA expression in DLPFC of schizophrenia subjects.
Dental Policy Lab 3: towards oral and dental health through partnership
Authors: Pitts Nigel B. , Newton J. Tim , Pow Ross , Miller Nicholas , Mayne Catherine 
Published: December 2021

AbstractThe third and last of the successful Alliance for a Cavity-Free Future (ACFF)/King's College London Dental Policy Lab series, held in 2019, focused on outlining how dental and oral health industries could benefit from enabling positive behaviour change in patients and the public, allowing progress towards caries reduction. During a two-day event, experts from across public health, dentists, global multi-national corporations and dental industry start-ups discussed the issue, collaboratively developing ideas around policy, technology, messaging and engagement for change. An analysis of the current trends in oral health laid out how the implications for industry and corporate social responsibility were identified as crucial. The report and accompanying infographic explored in this paper have been well received and acted as a catalyst for future developments in the area.
NLPR3 inflammasome inhibition alleviates hypoxic endothelial cell death in vitro and protects blood–brain barrier integrity in murine stroke
Authors: Bellut Maximilian , Papp Lena , Bieber Michael , Kraft Peter , Stoll Guido , Schuhmann Michael K. 
Published: December 2021

AbstractIn ischemic stroke (IS) impairment of the blood–brain barrier (BBB) has an important role in the secondary deterioration of neurological function. BBB disruption is associated with ischemia-induced inflammation, brain edema formation, and hemorrhagic infarct transformation, but the underlying mechanisms are incompletely understood. Dysfunction of endothelial cells (EC) may play a central role in this process. Although neuronal NLR-family pyrin domain-containing protein 3 (NLRP3) inflammasome upregulation is an established trigger of inflammation in IS, the contribution of its expression in EC is unclear. We here used brain EC, exposed them to oxygen and glucose deprivation (OGD) in vitro, and analyzed their survival depending on inflammasome inhibition with the NLRP3-specific drug MCC950. During OGD, EC death could significantly be reduced when targeting NLRP3, concomitant with diminished endothelial NLRP3 expression. Furthermore, MCC950 led to reduced levels of Caspase 1 (p20) and activated Gasdermin D as markers for pyroptosis. Moreover, inflammasome inhibition reduced the secretion of pro-inflammatory chemokines, cytokines, and matrix metalloproteinase-9 (MMP9) in EC. In a translational approach, IS was induced in C57Bl/6 mice by 60 mins transient middle cerebral artery occlusion and 23 hours of reperfusion. Stroke volume, functional outcome, the BBB integrity, and—in good agreement with the in vitro results—MMP9 secretion as well as EC survival improved significantly in MCC950-treated mice. In conclusion, our results establish the NLRP3 inflammasome as a critical pathogenic effector of stroke-induced BBB disruption by activating inflammatory signaling cascades and pyroptosis in brain EC.
USP3 promotes gastric cancer progression and metastasis by deubiquitination-dependent COL9A3/COL6A5 stabilisation
Authors: Wu Xiaosheng , Wang Hao , Zhu Danping , Chai Yixia , Wang Jing , Dai Weiyu , Xiao Yizhi , Tang Weimei , Li Jiaying , Hong Linjie , Pei Miaomiao , Zhang Jieming , Lin Zhizhao , Wang Jide , Li Aimin , Liu Side 
Published: December 2021

AbstractAs an important regulator of intracellular protein degradation, the mechanism of the deubiquitinating enzyme family in tumour metastasis has received increasing attention. Our previous study revealed that USP3 promotes tumour progression and is highly expressed in gastric cancer (GC). Herein, we report two critical targets, COL9A3 and COL6A5, downstream of USP3, via the isobaric tags for relative and absolute quantification technique. Mechanistically, we observed that USP3 interacted with and stabilised COL9A3 and COL6A5 via deubiquitination in GC. Importantly, we found that COL9A3 and COL6A5 were essential mediators of USP3-modulated oncogenic activity in vitro and in vivo. Examination of clinical samples confirmed that elevated expression of USP3, concomitant with increased COL9A3 and COL6A5 abundance, correlates with human GC progression. These data suggest that USP3 promotes GC progression and metastasis by deubiquitinating COL9A3 and COL6A5. These findings identify a mechanism of GC metastasis regarding USP3-mediated deubiquitinating enzyme activity and suggest potential therapeutic targets for GC management.
CircMTO1 suppresses hepatocellular carcinoma progression via the miR-541-5p/ZIC1 axis by regulating Wnt/β-catenin signaling pathway and epithelial-to-mesenchymal transition
Authors: Li Dandan , Zhang Jiawei , Yang Jing , Wang Jie , Zhang Runling , Li Jinming , Zhang Rui 
Published: December 2021

AbstractCircRNA mitochondrial tRNA translation optimization 1 (circMTO1) functions as a tumor suppressor usually and is related to the progression of many tumors, including hepatocellular carcinoma (HCC). CircMTO1 is downregulated in HCC as compared to adjacent nontumor tissue, which may suppress the HCC progression by certain signal pathways. However, the underlying signal pathway remains largely unknown. The interactions between circMTO1 and miR-541-5p were predicted through bioinformatics analysis and verified using pull-down and dual-luciferase reporter assays. CCK-8, transwell, and apoptosis assays were performed to determine the effect of miR-541-5p on HCC progression. Using bioinformatic analysis, dual-luciferase reporter assay, RT-qPCR, and western blot, ZIC1 was found to be the downstream target gene of miR-541-5p. The regulatory mechanisms of circMTO1, miR-541-5p, and ZIC1 were investigated using in vitro and in vivo rescue experiments. The results depicted that silencing circMTO1 or upregulating miR-541-5p expression facilitated HCC cell proliferation, migration, and invasion and inhibited apoptosis. CircMTO1 silencing upregulated the expression of downstream ZIC1 regulators of the Wnt/β-catenin pathway markers, β-catenin, cyclin D1, c-myc, and the mesenchymal markers N-cadherin, Vimentin, and MMP2, while the epithelial marker E-cadherin was downregulated. MiR-541-5p knockdown had the opposite effect and reversed the effect of circMTO1 silencing on the regulation of downstream ZIC1 regulators. Intratumoral injection of miR-541-5p inhibitor suppressed tumor growth and reversed the effect of circMTO1 silencing on the promotion of tumor growth in HCC. These findings indicated that circMTO1 suppressed HCC progression via the circMTO1/ miR-541-5p/ZIC1 axis by regulating Wnt/β-catenin signaling and epithelial-to-mesenchymal transition, making it a novel therapeutic target.
UBQLN4 is activated by C/EBPβ and exerts oncogenic effects on colorectal cancer via the Wnt/β-catenin signaling pathway
Authors: Tang Xiaolong , Liang Yahang , Sun Guorui , He Qingsi , Qu Hui , Gao Peng 
Published: December 2021

AbstractUbiquilin 4 (UBQLN4) is an important member of the ubiquitin-like protein family. An increasing number of studies have shown that UBQLN4 is an important regulator of tumorigenesis. Nevertheless, the biological function and detailed mechanisms of UBQLN4 in colorectal cancer (CRC) development and progression remain unclear. Here, we identified UBQLN4 upregulation in CRC tissues and it is positively associated with CRC size, TNM stage, and lymphatic metastasis. Patients with high UBQLN4 expression had a poor prognosis. Functionally, overexpression of UBQLN4 significantly promoted CRC cell proliferation, migration, and invasion, while UBQLN4 silencing elicited the opposite effect. This result was consistent with the conclusion that UBQLN4 expression correlated positively with the CRC size and lymphatic metastasis. In vivo, UBQLN4 silencing also inhibited tumor growth. Mechanistically, using gene set enrichment analysis (GSEA) and western blot experiments, we identified that UBQLN4 activated the Wnt/β-catenin signaling pathway to upregulate β-catenin and c-Myc expression, thereby promoting CRC proliferation, migration and invasion. A rescue experiment further verified this conclusion. Dual luciferase reporter, real-time quantitative PCR (RT-qPCR), western blot and chromatin immunoprecipitation (ChIP) assays indicated that the transcription factor CCAAT/enhancer-binding protein beta (C/EBPβ) directly bound to the UBQLN4 core promoter region and activated its transcription, upregulating β-catenin and c-Myc expression to promote CRC progression. Thus, our findings suggest that UBQLN4 is a key oncogene in CRC and may be a promising target for the diagnosis and treatment of patients with CRC.
Common microscopic origin of the phase transitions in Ta2NiS5 and the excitonic insulator candidate Ta2NiSe5
Authors: Windgätter Lukas , Rösner Malte , Mazza Giacomo , Hübener Hannes , Georges Antoine , Millis Andrew J. , Latini Simone , Rubio Angel 
Published: December 2021

AbstractThe structural phase transition in Ta2NiSe5 has been envisioned as driven by the formation of an excitonic insulating phase. However, the role of structural and electronic instabilities on crystal symmetry breaking has yet to be disentangled. Meanwhile, the phase transition in its complementary material Ta2NiS5 does not show any experimental hints of an excitonic insulating phase. We present a microscopic investigation of the electronic and phononic effects involved in the structural phase transition in Ta2NiSe5 and Ta2NiS5 using extensive first-principles calculations. In both materials the crystal symmetries are broken by phonon instabilities, which in turn lead to changes in the electronic bandstructure also observed in the experiment. A total energy landscape analysis shows no tendency towards a purely electronic instability and we find that a sizeable lattice distortion is needed to open a bandgap. We conclude that an excitonic instability is not needed to explain the phase transition in both Ta2NiSe5 and Ta2NiS5.
Importance of charge self-consistency in first-principles description of strongly correlated systems
Authors: Acharya Swagata , Pashov Dimitar , Rudenko Alexander N. , Rösner Malte , van Schilfgaarde Mark , Katsnelson Mikhail I. 
Published: December 2021

AbstractFirst-principles approaches have been successful in solving many-body Hamiltonians for real materials to an extent when correlations are weak or moderate. As the electronic correlations become stronger often embedding methods based on first-principles approaches are used to better treat the correlations by solving a suitably chosen many-body Hamiltonian with a higher level theory. The success of such embedding theories, often referred to as second-principles, is commonly measured by the quality of self-energy Σ which is either a function of energy or momentum or both. However, Σ should, in principle, also modify the electronic eigenfunctions and thus change the real space charge distribution. While such practices are not prevalent, some works that use embedding techniques do take into account these effects. In such cases, choice of partitioning, of the parameters defining the correlated Hamiltonian, of double-counting corrections, and the adequacy of low-level Hamiltonian hosting the correlated subspace hinder a systematic and unambiguous understanding of such effects. Further, for a large variety of correlated systems, strong correlations are largely confined to the charge sector. Then an adequate nonlocal low-order theory is important, and the high-order local correlations embedding contributes become redundant. Here we study the impact of charge self-consistency within two example cases, TiSe2 and CrBr3, and show how real space charge re-distribution due to correlation effects taken into account within a first-principles Green’s function-based many-body perturbative approach is key in driving qualitative changes to the final electronic structure of these materials.
Development of multi-angle fiber array for accurate measurement of flexion and rotation in human joints
Authors: Jeong Sang-Mi , Son Minkyun , Kang Youngsoo , Yang Jonguk , Lim Taekyung , Ju Sanghyun 
Published: December 2021

AbstractHerein, we have proposed a method that uses a highly stretchable and conductive fiber-based multi-angle fiber array, which precisely measures human joint motion in various degrees of freedom (flexion and rotation) at the shoulders, knees, and wrists in real time. By embedding conductive carbon nanotubes (CNTs) within spandex fibers of high elasticity and shape recovery ratio, we monitored joint motion stably without degrading the fiber’s conductivity even during repeated stretching and contraction of different lengths. The strain occurring in a specific direction was monitored using mapping images generated due to the change in resistance that occurred when 12 CNT-embedded spandex fibers arranged in radial lines at intervals of 15° were stretched or contracted by an external force. The proposed high-precision joint-monitoring technology measures human motion accurately and is applicable for use in wearable healthcare devices that require precise measurements.
Alpha-synuclein oligomers and small nerve fiber pathology in skin are potential biomarkers of Parkinson’s disease
Authors: Vacchi Elena , Senese Camilla , Chiaro Giacomo , Disanto Giulio , Pinton Sandra , Morandi Sara , Bertaina Ilaria , Bianco Giovanni , Staedler Claudio , Galati Salvatore , Gobbi Claudio , Kaelin-Lang Alain , Melli Giorgia 
Published: December 2021

AbstractThe proximity ligation assay (PLA) is a specific and sensitive technique for the detection of αSyn oligomers (αSyn-PLA), early and toxic species implicated in the pathogenesis of PD. We aimed to evaluate by skin biopsy the diagnostic and prognostic capacity of αSyn-PLA and small nerve fiber reduction in PD in a longitudinal study. αSyn-PLA was performed in the ankle and cervical skin biopsies of PD (n = 30), atypical parkinsonisms (AP, n = 23) including multiple system atrophy (MSA, n = 12) and tauopathies (AP-Tau, n = 11), and healthy controls (HC, n = 22). Skin biopsy was also analyzed for phosphorylated αSyn (P-αSyn) and 5G4 (αSyn-5G4), a conformation-specific antibody to aggregated αSyn. Intraepidermal nerve fiber density (IENFD) was assessed as a measure of small fiber neuropathy. αSyn-PLA signal was more expressed in PD and MSA compared to controls and AP-Tau. αSyn-PLA showed the highest diagnostic accuracy (PD vs. HC sensitivity 80%, specificity 77%; PD vs. AP-Tau sensitivity 80%, specificity 82%), however, P-αSyn and 5G4, possible markers of later phases, performed better when considering the ankle site alone. A small fiber neuropathy was detected in PD and MSA. A progression of denervation not of pathological αSyn was detected at follow-up and a lower IENFD at baseline was associated with a greater cognitive and motor decline in PD. A skin biopsy-derived compound marker, resulting from a linear discrimination analysis model of αSyn-PLA, P-αSyn, αSyn-5G4, and IENFD, stratified patients with accuracy (77.8%), including the discrimination between PD and MSA (84.6%). In conclusion, the choice of pathological αSyn marker and anatomical site influences the diagnostic performance of skin biopsy and can help in understanding the temporal dynamics of αSyn spreading in the peripheral nervous system during the disease. Skin denervation, not pathological αSyn is a potential progression marker for PD.
Magnetic particles and strings in iron langasite
Authors: Barts Evgenii , Mostovoy Maxim 
Published: December 2021

AbstractMagnetic topological defects can store and carry information. Replacement of extended defects, such as domain walls and Skyrmion tubes, by compact magnetic particles that can propagate in all three spatial directions may open an extra dimension in the design of magnetic memory and data processing devices. We show that such objects can be found in iron langasite, which exhibits a hierarchy of non-collinear antiferromagnetic spin structures at very different length scales. We derive an effective model describing long-distance magnetic modulations in this chiral magnet and find unusual two- and three-dimensional topological defects. The order parameter space of our model is similar to that of superfluid 3He-A, and the particle-like magnetic defect is closely related to the Shankar monopole and hedgehog soliton in the Skyrme model of baryons. Mobile magnetic particles stabilized in non-collinear antiferromagnets can play an important role in antiferromagnetic spintronics.
Preclinical evaluation of a candidate naked plasmid DNA vaccine against SARS-CoV-2
Authors: Lassaunière Ria , Polacek Charlotta , Gram Gregers J. , Frische Anders , Tingstedt Jeanette Linnea , Krüger Maren , Dorner Brigitte G. , Cook Anthony , Brown Renita , Orekov Tatyana , Putmon-Taylor Tammy , Campbell Tracey-Ann , Greenhouse Jack , Pessaint Laurent , Andersen Hanne , Lewis Mark G. , Fomsgaard Anders 
Published: December 2021

AbstractNew generation plasmid DNA vaccines may be a safe, fast and simple emergency vaccine platform for preparedness against emerging viral pathogens. Applying platform optimization strategies, we tested the pre-clinical immunogenicity and protective effect of a candidate DNA plasmid vaccine specific for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The DNA vaccine induced spike-specific binding IgG and neutralizing antibodies in mice, rabbits, and rhesus macaques together with robust Th1 dominant cellular responses in small animals. Intradermal and intramuscular needle-free administration of the DNA vaccine yielded comparable immune responses. In a vaccination-challenge study of rhesus macaques, the vaccine demonstrated protection from viral replication in the lungs following intranasal and intratracheal inoculation with SARS-CoV-2. In conclusion, the candidate plasmid DNA vaccine encoding the SARS-CoV-2 spike protein is immunogenic in different models and confers protection against lung infection in nonhuman primates. Further evaluation of this DNA vaccine candidate in clinical trials is warranted.
Mobile BCI dataset of scalp- and ear-EEGs with ERP and SSVEP paradigms while standing, walking, and running
Authors: Lee Young-Eun , Shin Gi-Hwan , Lee Minji , Lee Seong-Whan 
Published: December 2021

AbstractWe present a mobile dataset obtained from electroencephalography (EEG) of the scalp and around the ear as well as from locomotion sensors by 24 participants moving at four different speeds while performing two brain-computer interface (BCI) tasks. The data were collected from 32-channel scalp-EEG, 14-channel ear-EEG, 4-channel electrooculography, and 9-channel inertial measurement units placed at the forehead, left ankle, and right ankle. The recording conditions were as follows: standing, slow walking, fast walking, and slight running at speeds of 0, 0.8, 1.6, and 2.0 m/s, respectively. For each speed, two different BCI paradigms, event-related potential and steady-state visual evoked potential, were recorded. To evaluate the signal quality, scalp- and ear-EEG data were qualitatively and quantitatively validated during each speed. We believe that the dataset will facilitate BCIs in diverse mobile environments to analyze brain activities and evaluate the performance quantitatively for expanding the use of practical BCIs.
Dapagliflozin, metformin, monotherapy or both in patients with metabolic syndrome
Authors: Cheng Lan , Fu Qianyu , Zhou Longhua , Fan Yuqin , Liu Fenfen , Fan Yuanyuan , Zhang Xin , Lin Weiqing , Wu Xiaohe 
Published: December 2021

AbstractThe present study evaluated the effects of dapagliflozin, a SGLT2 inhibitor, or dapagliflozin plus metformin versus metformin monotherapy in patients with metabolic syndrome. This study included patients who admitted in Jiangxi Provincial People’s Hospital from January 1, 2017 to December 31, 2019 and were diagnosed with metabolic syndrome. A total of 248 participants were randomly assigned to divide into three groups: dapagliflozin group; metformin group; dapagliflozin in combined with metformin group. Dapagliflozin group and metformin group were associated with similar improvements in components of metabolic syndrome. Relative to dapagliflozin or metformin monotherapy, dapagliflozin combined with metformin provided greater improvements in components of metabolic syndrome. So did HOMA-IR scores, fasting plasma insulin and inflammatory indicators (hsCRP, PMN/HDL-C and Monocytes/HDL-C). Dapagliflozin improved all components of metabolic syndrome in patients with metabolic syndrome. Furthermore, dapagliflozin combined with metformin showed more meaningful improvements in any of components of metabolic syndrome than dapagliflozin or metformin monotherapy.