bluuebunny/crossref_metadata_2025_split huggingface dataset:
Methylation of BRD4 by PRMT1 regulates BRD4 phosphorylation and promotes ovarian cancer invasion
Authors: Liu Yi , Liu Hejing , Ye Miaomiao , Jiang Mengying , Chen Xin , Song Gendi , Ji Huihui , Wang Zhi-wei , Zhu Xueqiong 
Published: September 2023

AbstractBromodomain-containing protein 4 (BRD4), the major component of bromodomain and extra-terminal domain (BET) protein family, has important functions in early embryonic development and cancer development. However, the posttranslational modification of BRD4 is not well understood. Multiple approaches were used to explore the mechanism of PRMT1-mediated BRD4 methylation and to determine the biological functions of BRD4 and PRMT1 in ovarian cancer. Here we report that BRD4 is asymmetrically methylated at R179/181/183 by PRMT1, which is antagonized by the Jumonji-family demethylase, JMJD6. PRMT1 is overexpressed in ovarian cancer tissue and is a potential marker for poor prognosis in ovarian cancer patients. Silencing of PRMT1 inhibited ovarian cancer proliferation, migration, and invasion in vivo and in vitro. PRMT1-mediated BRD4 methylation was found to promote BRD4 phosphorylation. Compared to BRD4 wild-type (WT) cells, BRD4 R179/181/183K mutant-expressing cells showed reduced ovarian cancer metastasis. BRD4 arginine methylation is also associated with TGF-β signaling. Our results indicate that arginine methylation of BRD4 by PRMT1 is involved in ovarian cancer tumorigenesis. Targeting PRMT1-mediated arginine methylation may provide a novel diagnostic target and an effective therapeutic strategy for ovarian cancer treatment.
In vivo self-assembly and delivery of VEGFR2 siRNA-encapsulated small extracellular vesicles for lung metastatic osteosarcoma therapy
Authors: Yu Lingfeng , Fan Gentao , Wang Qingyan , Zhu Yan , Zhu Hao , Chang Jiang , Wang Zhen , Zhan Shoubin , Hua Xianming , She Diankun , Huang Jianhao , Wang Yicun , Zhao Jianning , Zhang Chen-Yu , Chen Xi , Zhou Guangxin 
Published: September 2023

AbstractThe prognosis of lung metastatic osteosarcoma (OS) remains disappointing. siRNA-based gene silencing of VEGFR2 is a promising treatment strategy for lung metastatic OS, but there is a lack of safe and efficient delivery systems to encapsulate siRNAs for in vivo administration. This study presented a synthetic biological strategy that remolds the host liver with synthesized genetic circuits for efficient in vivo VEGFR2 siRNA delivery. After being taken-up by hepatocytes, the genetic circuit (in the form of a DNA plasmid) reprogrammed the liver to drive the autonomous intrahepatic assembly and encapsulation of VEGFR2 siRNAs into secretory small extracellular vesicles (sEVs), thus allowing for the transport of self-assembled VEGFR2 siRNAs towards the lung. The results showed that our strategy was superior to the positive medicine (Apatinib) for OS lung metastasis in terms of therapeutic efficacy and toxic adverse effects and may provide a feasible and viable therapeutic solution for lung metastatic OS.
Comprehensive proteomics and meta-analysis of COVID-19 host response
Authors: Babačić Haris , Christ Wanda , Araújo José Eduardo , Mermelekas Georgios , Sharma Nidhi , Tynell Janne , García Marina , Varnaite Renata , Asgeirsson Hilmir , Glans Hedvig , Lehtiö Janne , Gredmark-Russ Sara , Klingström Jonas , Pernemalm Maria 
Published: September 2023

AbstractCOVID-19 is characterised by systemic immunological perturbations in the human body, which can lead to multi-organ damage. Many of these processes are considered to be mediated by the blood. Therefore, to better understand the systemic host response to SARS-CoV-2 infection, we performed systematic analyses of the circulating, soluble proteins in the blood through global proteomics by mass-spectrometry (MS) proteomics. Here, we show that a large part of the soluble blood proteome is altered in COVID-19, among them elevated levels of interferon-induced and proteasomal proteins. Some proteins that have alternating levels in human cells after a SARS-CoV-2 infection in vitro and in different organs of COVID-19 patients are deregulated in the blood, suggesting shared infection-related changes.The availability of different public proteomic resources on soluble blood proteome alterations leaves uncertainty about the change of a given protein during COVID-19. Hence, we performed a systematic review and meta-analysis of MS global proteomics studies of soluble blood proteomes, including up to 1706 individuals (1039 COVID-19 patients), to provide concluding estimates for the alteration of 1517 soluble blood proteins in COVID-19. Finally, based on the meta-analysis we developed CoViMAPP, an open-access resource for effect sizes of alterations and diagnostic potential of soluble blood proteins in COVID-19, which is publicly available for the research, clinical, and academic community.
Telomerase RNA-based aptamers restore defective myelopoiesis in congenital neutropenic syndromes
Authors: Martínez-Balsalobre Elena , García-Castillo Jesús , García-Moreno Diana , Naranjo-Sánchez Elena , Fernández-Lajarín Miriam , Blasco María A. , Alcaraz-Pérez Francisca , Mulero Victoriano , Cayuela María L. 
Published: September 2023

AbstractTelomerase RNA (TERC) has a noncanonical function in myelopoiesis binding to a consensus DNA binding sequence and attracting RNA polymerase II (RNA Pol II), thus facilitating myeloid gene expression. The CR4/CR5 domain of TERC is known to play this role, since a mutation of this domain found in dyskeratosis congenita (DC) patients decreases its affinity for RNA Pol II, impairing its myelopoietic activity as a result. In this study, we report that two aptamers, short single-stranded oligonucleotides, based on the CR4/CR5 domain were able to increase myelopoiesis without affecting erythropoiesis in zebrafish. Mechanistically, the aptamers functioned as full terc; that is, they increased the expression of master myeloid genes, independently of endogenous terc, by interacting with RNA Pol II and with the terc-binding sequences of the regulatory regions of such genes, enforcing their transcription. Importantly, aptamers harboring the CR4/CR5 mutation that was found in DC patients failed to perform all these functions. The therapeutic potential of the aptamers for treating neutropenia was demonstrated in several preclinical models. The findings of this study have identified two potential therapeutic agents for DC and other neutropenic patients.
CREB1-driven CXCR4hi neutrophils promote skin inflammation in mouse models and human patients
Authors: Chen Jiaoling , Bai Yaxing , Xue Ke , Li Zhiguo , Zhu Zhenlai , Li Qingyang , Yu Chen , Li Bing , Shen Shengxian , Qiao Pei , Li Caixia , Luo Yixin , Qiao Hongjiang , Dang Erle , Yin Wen , Gudjonsson Johann E. , Wang Gang , Shao Shuai 
Published: September 2023

AbstractNeutrophils have a pathogenic function in inflammation via releasing pro-inflammatory mediators or neutrophil extracellular traps (NETs). However, their heterogeneity and pro-inflammatory mechanisms remain unclear. Here, we demonstrate that CXCR4hi neutrophils accumulate in the blood and inflamed skin in human psoriasis, and correlate with disease severity. Compared to CXCR4lo neutrophils, CXCR4hi neutrophils have enhanced NETs formation, phagocytic function, neutrophil degranulation, and overexpression of pro-inflammatory cytokines and chemokines in vitro. This is accompanied by a metabolic shift in CXCR4hi neutrophils toward glycolysis and lactate release, thereby promoting vascular permeability and remodeling. CXCR4 expression in neutrophils is dependent on CREB1, a transcription factor activated by TNF and CXCL12, and regulated by de novo synthesis. In vivo, CXCR4hi neutrophil infiltration amplifies skin inflammation, whereas blockade of CXCR4hi neutrophils through CXCR4 or CXCL12 inhibition leads to suppression of immune responses. In this work, our study identifies CREB1 as a critical regulator of CXCR4hi neutrophil development and characterizes the contribution of CXCR4hi neutrophils to vascular remodeling and inflammatory responses in skin.
Altered ubiquitin signaling induces Alzheimer’s disease-like hallmarks in a three-dimensional human neural cell culture model
Authors: Maniv Inbal , Sarji Mahasen , Bdarneh Anwar , Feldman Alona , Ankawa Roi , Koren Elle , Magid-Gold Inbar , Reis Noa , Soteriou Despina , Salomon-Zimri Shiran , Lavy Tali , Kesselman Ellina , Koifman Naama , Kurz Thimo , Kleifeld Oded , Michaelson Daniel , van Leeuwen Fred W. , Verheijen Bert M. , Fuchs Yaron , Glickman Michael H. 
Published: September 2023

AbstractAlzheimer’s disease (AD) is characterized by toxic protein accumulation in the brain. Ubiquitination is essential for protein clearance in cells, making altered ubiquitin signaling crucial in AD development. A defective variant, ubiquitin B + 1 (UBB+1), created by a non-hereditary RNA frameshift mutation, is found in all AD patient brains post-mortem. We now detect UBB+1in human brains during early AD stages. Our study employs a 3D neural culture platform derived from human neural progenitors, demonstrating that UBB+1alone induces extracellular amyloid-β (Aβ) deposits and insoluble hyperphosphorylated tau aggregates. UBB+1competes with ubiquitin for binding to the deubiquitinating enzyme UCHL1, leading to elevated levels of amyloid precursor protein (APP), secreted Aβ peptides, and Aβ build-up. Crucially, silencing UBB+1expression impedes the emergence of AD hallmarks in this model system. Our findings highlight the significance of ubiquitin signalling as a variable contributing to AD pathology and present a nonclinical platform for testing potential therapeutics.
Exploration of cell state heterogeneity using single-cell proteomics through sensitivity-tailored data-independent acquisition
Authors: Petrosius Valdemaras , Aragon-Fernandez Pedro , Üresin Nil , Kovacs Gergo , Phlairaharn Teeradon , Furtwängler Benjamin , Op De Beeck Jeff , Skovbakke Sarah L. , Goletz Steffen , Thomsen Simon Francis , Keller Ulrich auf dem , Natarajan Kedar N. , Porse Bo T. , Schoof Erwin M. 
Published: September 2023

AbstractSingle-cell resolution analysis of complex biological tissues is fundamental to capture cell-state heterogeneity and distinct cellular signaling patterns that remain obscured with population-based techniques. The limited amount of material encapsulated in a single cell however, raises significant technical challenges to molecular profiling. Due to extensive optimization efforts, single-cell proteomics by Mass Spectrometry (scp-MS) has emerged as a powerful tool to facilitate proteome profiling from ultra-low amounts of input, although further development is needed to realize its full potential. To this end, we carry out comprehensive analysis of orbitrap-based data-independent acquisition (DIA) for limited material proteomics. Notably, we find a fundamental difference between optimal DIA methods for high- and low-load samples. We further improve our low-input DIA method by relying on high-resolution MS1 quantification, thus enhancing sensitivity by more efficiently utilizing available mass analyzer time. With our ultra-low input tailored DIA method, we are able to accommodate long injection times and high resolution, while keeping the scan cycle time low enough to ensure robust quantification. Finally, we demonstrate the capability of our approach by profiling mouse embryonic stem cell culture conditions, showcasing heterogeneity in global proteomes and highlighting distinct differences in key metabolic enzyme expression in distinct cell subclusters.
mRNA vaccines encoding fusion proteins of monkeypox virus antigens protect mice from vaccinia virus challenge
Authors: Hou Fujun , Zhang Yuntao , Liu Xiaohu , Murad Yanal M , Xu Jiang , Yu Zhibin , Hua Xianwu , Song Yingying , Ding Jun , Huang Hongwei , Zhao Ronghua , Jia William , Yang Xiaoming 
Published: September 2023

AbstractThe recent outbreaks of mpox have raised concerns over the need for effective vaccines. However, the current approved vaccines have either been associated with safety concerns or are in limited supply. mRNA vaccines, which have shown high efficacy and safety against SARS-CoV-2 infection, are a promising alternative. In this study, three mRNA vaccines are developed that encode monkeypox virus (MPXV) proteins A35R and M1R, including A35R extracellular domain -M1R fusions (VGPox 1 and VGPox 2) and a mixture of encapsulated full-length mRNAs for A35R and M1R (VGPox 3). All three vaccines induce early anti-A35R antibodies in female Balb/c mice, but only VGPox 1 and 2 generate detectable levels of anti-M1R antibodies at day 7 after vaccination. However, all three mRNA vaccine groups completely protect mice from a lethal dose of vaccinia virus (VACV) challenge. A single dose of VGPox 1, 2, and 3 provide protection against the lethal viral challenge within 7 days post-vaccination. Long-term immunity and protection were also observed in all three candidates. Additionally, VGPox 2 provided better passive protection. These results suggest that the VGPox series vaccines enhance immunogenicity and can be a viable alternative to current whole-virus vaccines to defend against mpox.
East Asian summer rainfall stimulated by subseasonal Indian monsoonal heating
Authors: Li Shixue , Sato Tomonori , Nakamura Tetsu , Guo Wenkai 
Published: September 2023

AbstractThe responses of the East Asian summer monsoon (EASM) to the Indian summer monsoon (ISM) have been the subject of extensive investigation. Nevertheless, it remains uncertain whether the ISM can serve as a predictor for the EASM. Here, on the basis of both observations and a large-ensemble climate model experiment, we show that the subseasonal variability of abnormal diabatic heating over India enhances precipitation over central East China, the Korean Peninsula, and southern Japan in June. ISM heating triggers Rossby wave propagation along the subtropical jet, promoting southerly winds over East Asia. The southerly winds helps steer anomalous mid-tropospheric warm advection and lower-tropospheric moisture advection toward East Asia, providing conditions preferential for rainband formation. Cluster analysis shows that, depending on jet structures, ISM heating can serve as a trigger as well as a reinforcer of the rainband.
Efficient combinatorial optimization by quantum-inspired parallel annealing in analogue memristor crossbar
Authors: Jiang Mingrui , Shan Keyi , He Chengping , Li Can 
Published: September 2023

AbstractCombinatorial optimization problems are prevalent in various fields, but obtaining exact solutions remains challenging due to the combinatorial explosion with increasing problem size. Special-purpose hardware such as Ising machines, particularly memristor-based analog Ising machines, have emerged as promising solutions. However, existing simulate-annealing-based implementations have not fully exploited the inherent parallelism and analog storage/processing features of memristor crossbar arrays. This work proposes a quantum-inspired parallel annealing method that enables full parallelism and improves solution quality, resulting in significant speed and energy improvement when implemented in analog memristor crossbars. We experimentally solved tasks, including unweighted and weighted Max-Cut and traveling salesman problem, using our integrated memristor chip. The quantum-inspired parallel annealing method implemented in memristor-based hardware has demonstrated significant improvements in time- and energy-efficiency compared to previously reported simulated annealing and Ising machine implemented on other technologies. This is because our approach effectively exploits the natural parallelism, analog conductance states, and all-to-all connection provided by memristor technology, promising its potential for solving complex optimization problems with greater efficiency.
Alteration of perivascular reflectivity on optical coherence tomography of branched retinal vein obstruction
Authors: Hwang Bo-Een , Kim Joo-Young , Kim Rae-Young , Kim Mirinae , Park Young-Geun , Park Young-Hoon 
Published: September 2023

AbstractThis study aimed to evaluate perivascular reflectivity in patients with branched retinal vascular obstruction (BRVO) using en-face optical coherence tomography (OCT). The study retrospectively analyzed 45 patients with recurrent BRVO, 30 with indolent BRVO, and 45 age- and sex-matched controls. Using a 3.0 × 3.0-mm deep capillary plexus slab on macular scans, OCT angiography (OCTA) and structural en-face OCT scans were divided into four quadrants. Obstructive quadrants of OCTA scans were binarized using a threshold value of mean + 2 standard deviation. The selected area of high signal strength (HSS) was applied to the structural en-face OCT scans, and the corrected mean perivascular reflectivity was calculated as the mean reflectivity on the HSS area/overall en-face OCT mean reflectivity. The same procedure was performed in the quadrants of the matched controls. Regression analysis was conducted on several factors possibly associated with corrected perivascular reflectivity. The perivascular reflectivity in the obstructive BRVO quadrant was significantly higher than in the indolent BRVO and control quadrants (P = 0.009, P = 0.003). Both univariate and multivariate regression analyses showed a significant correlation between the average number of intravitreal injections (anti-vascular endothelial growth factor or dexamethasone implant) per year and refractive errors and image binarization threshold and perivascular reflectivity (P = 0.011, 0.013, < 0.001/univariate; 0.007, 0.041, 0.005/multivariate, respectively). En-face OCT scans of the deep capillary plexus slab revealed higher perivascular reflectivity in recurrent BRVO eyes than in indolent BRVO and control eyes. The results also indicate a remarkable correlation between perivascular reflectivity and the average number of intravitreal injections, suggesting a link to recurrence rates.
Frugal day-ahead forecasting of multiple local electricity loads by aggregating adaptive models
Authors: Lambert Guillaume , Hamrouche Bachir , de Vilmarest Joseph 
Published: September 2023

AbstractThis paper focuses on day-ahead electricity load forecasting for substations of the distribution network in France; therefore, the corresponding problem lies between the instability of a single consumption and the stability of a countrywide total demand. Moreover, this problem requires to forecast the loads of over one thousand substations; consequently, it belongs to the field of multiple time series forecasting. To that end, the paper applies an adaptive methodology that provided excellent results at a national scale; the idea is to combine generalized additive models with state-space representations. However, extending this methodology to the prediction of over a thousand time series raises a computational issue. It is solved by developing a frugal variant that reduces the number of estimated parameters: forecasting models are estimated only for a few time series and transfer learning is achieved by relying on aggregation of experts. This approach yields a reduction of computational needs and their associated emissions. Several variants are built, corresponding to different levels of parameter transfer, to find the best trade-off between accuracy and frugality. The selected method achieves competitive results compared to individual models. Finally, the paper highlights the interpretability of the models, which is important for operational applications.
T cell exhaustion is associated with cognitive status and amyloid accumulation in Alzheimer’s disease
Authors: Grayson Jason M. , Short Samantha M. , Lee C. Jiah , Park Nuri , Marsac Caitlyn , Sette Alessandro , Lindestam Arlehamn Cecillia S. , Leng Xiaoyan I. , Lockhart Samuel N. , Craft Suzanne 
Published: September 2023

AbstractStudies over the last 100 years have suggested a link between inflammation, infectious disease, and Alzheimer’s Disease (AD). Understanding how the immune system changes during the development of AD may facilitate new treatments. Here, we studied an aging cohort who had been assessed for AD pathology with amyloid positron emission tomography and cognitive testing, and conducted high dimensional flow cytometry on peripheral blood mononuclear and cerebrospinal fluid cells. Participants were assigned a classification of being amyloid negative cognitively normal, amyloid positive cognitively normal (APCN), or amyloid positive mild cognitive impairment (APMCI), an early stage of AD. We observed major alterations in the peripheral innate immune system including increased myeloid and plasmacytoid dendritic cells in the blood of APMCI participants. When the adaptive immune system was examined, amyloid positive participants, regardless of cognitive status, had increased CD3+ T cells. Further analyses of CD4+ and CD8+ T cells revealed that APMCI participants had an increase in more differentiated phenotype T cells, such as effector memory and effector memory CD45RA expressing (TEMRA), compared to those with normal cognition. When T cell function was measured, we observed that T cells from APCN participants had increased IFNγ+GzB- producing cells compared to the other participants. In contrast, we demonstrate that APMCI participants had a major increase in T cells that lacked cytokine production following restimulation and expressed increased levels of PD-1 and Tox, suggesting these are exhausted cells. Rejuvenation of these cells may provide a potential treatment for AD.
Periodic, n-soliton and variable separation solutions for an extended (3+1)-dimensional KP-Boussinesq equation
Authors: Shao Chuanlin , Yang Lu , Yan Yongsheng , Wu Jingyu , Zhu Minting , Li Lingfei 
Published: September 2023

AbstractAn extended (3+1)-dimensional Kadomtsev–Petviashvili–Boussinesq equation is studied in this paper to construct periodic solution, n-soliton solution and folded localized excitation. Firstly, with the help of the Hirota’s bilinear method and ansatz, some periodic solutions have been derived. Secondly, taking Burgers equation as an auxiliary function, we have obtained n-soliton solution and n-shock wave. Lastly, we present a new variable separation method for (3+1)-dimensional and higher dimensional models, and use it to derive localized excitation solutions. To be specific, we have constructed various novel structures and discussed the interaction dynamics of folded solitary waves. Compared with the other methods, the variable separation solutions obtained in this paper not only directly give the analytical form of the solution u instead of its potential $$u_y$$

u
y

, but also provide us a straightforward approach to construct localized excitation for higher order dimensional nonlinear partial differential equation.