bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neurotropic EV71 causes encephalitis by engaging intracellular TLR9 to elicit neurotoxic IL12-p40-iNOS signaling
Authors: Lai Rai-Hua , Chow Yen-Hung , Chung Nai-Hsiang , Chen Tsan-Chi , Shie Feng-Shiun , Juang Jyh-Lyh 
Published: April 2022

AbstractBrainstem encephalitis, a manifestation of severe enterovirus 71 (EV71) infection, is an acute excessive inflammatory response. The mechanisms underlying its development remain poorly understood. Usually neurotropic viruses trigger acute host immune response by engaging cell surface or intracellular receptors. Here, we show that EV71 engagement with intracellular receptor TLR9 elicits IL-12p40-iNOS signaling causing encephalitis in mice. We identified IL-12p40 to be the only prominent cytokine-induced at the early infection stage in the brainstem of mice subjected to a lethal dose of EV71. The upregulated IL-12p40 proteins were expressed in glial cells but not neuronal cells. To better understand the role of IL-12p40 in severe EV71 infection, we treated the EV71-infected mice with an antibody against IL-12p40 and found the mortality rate, brainstem inflammation, and gliosis to be markedly reduced, suggesting that the acute IL-12p40 response plays a critical role in the pathogenesis of brainstem encephalitis. Mechanistically, intracellular TLR9 was found essential to the activation of the IL-12p40 response. Blocking TLR9 signaling with CpG-ODN antagonist ameliorated IL-12p40 response, brainstem inflammation, and limb paralysis in mice with EV71-induced encephalitis. We further found the glial IL-12p40 response might damage neurons by inducing excess production of neurotoxic NO by iNOS. Overall, EV71 engagement with intracellular TLR9 was found to elicit a neurotoxic glial response via IL12p40-iNOS signaling contributing to the neurological manifestation of EV71 infection. This pathway could potentially be targeted for the treatment of brainstem encephalitis.
Fatty acid-binding protein 4 is a therapeutic target for septic acute kidney injury by regulating inflammatory response and cell apoptosis
Authors: Wang Bo , Xu Jun , Ren Qian , Cheng Lu , Guo Fan , Liang Yan , Yang Letian , Tan Zhouke , Fu Ping , Ma Liang 
Published: April 2022

AbstractSepsis is a systemic inflammatory state in response to infection, and concomitant acute kidney injury (AKI) significantly increases morbidity and mortality. Growing evidence suggests that fatty acid-binding protein 4 (FABP4) is critically involved in kidney diseases, while its role in septic AKI remains unknown. Here, FABP4 was mainly upregulated in renal tubular epithelial cells (RTECs) following cecal ligation and puncture (CLP)- or lipopolysaccharide (LPS)-induced septic AKI. FABP4 inhibition by genetic deletion or BMS309403 treatment both attenuated kidney dysfunction and pathological injury in CLP- or LPS-treated mice. Notably, RTEC-specific deletion of FABP4 also showed similar renoprotective effects. Moreover, FABP4 inhibition alleviated inflammation and apoptosis in CLP-injured kidneys and LPS-stimulated mouse tubular epithelial cells. Mechanistically, TLR4 blockage improved sepsis-induced kidney injury, as well as suppressed c-Jun phosphorylation and FABP4 expression, where c-Jun knockdown also inhibited LPS-stimulated FABP4 level. Meanwhile, FABP4 inhibition reduced the elevated phosphorylated c-Jun, while the levels of TLR4 and MyD88 were uninfluenced. Collectively, the increased FABP4 in RTECs is dependent on TLR4/c-Jun signaling activation and contributes to kidney injury, by forming a positive feedback loop with c-Jun to aggravate inflammation and apoptosis in septic AKI. Thus, FABP4 may be a therapeutic target for septic AKI.
BNIP3 (BCL2 interacting protein 3) regulates pluripotency by modulating mitochondrial homeostasis via mitophagy
Authors: Liu Kun , Zhao Qian , Sun Hongyan , Liu Lei , Wang Chaoqun , Li Zheng , Xu Youqing , Wang Liang , Zhang Lin , Zhang Honghai , Chen Quan , Zhao Tongbiao 
Published: April 2022

AbstractAutophagy-mediated mitochondrial degradation plays pivotal roles in both the acquisition and maintenance of pluripotency, but the molecular mechanisms that link autophagy-mediated mitochondrial homeostasis to pluripotency regulation are unclear. Here, we identified that the mitophagy receptor BNIP3 regulates pluripotency. In mouse ESCs, depletion of BNIP3 caused accumulation of aberrant mitochondria accompanied by decreased mitochondrial membrane potential, increased production of reactive oxygen species (ROS), and reduced ATP generation, which led to compromised self-renewal and differentiation. Impairment of mitophagy by knockdown of BNIP3 inhibited mitochondrial clearance during pluripotency induction, resulting in decreased reprogramming efficiency. These defects were rescued by reacquisition of wild-type but not LIR-deficient BNIP3 expression. Taken together, our findings highlight a critical role of BNIP3-mediated mitophagy in the induction and maintenance of pluripotency.
Silencing of lncRNA MALAT1 facilitates erastin-induced ferroptosis in endometriosis through miR-145-5p/MUC1 signaling
Authors: Liang Zongwen , Wu Qiong , Wang Honglin , Tan Jiahuan , Wang Han , Gou Yanling , Cao Yingying , Li Zhi , Zhang Zongfeng 
Published: April 2022

AbstractEndometriosis is a chronic disorder characterized by the implantation of endometrial glands and stroma outside the uterus. However, the pathogenesis of endometriosis is still unclear. To date, there is no fully effective treatment without trauma because of various side effects. Recent data suggest that ferroptosis is a novel recognized form of nonapoptosis-regulated cell death characterized by iron-dependent and lethal lipid peroxidation accumulation, showing great promise in the treatment of many diseases. In the present study, we verified that erastin induced ferroptosis in ectopic endometrial stromal cells (EESCs). Furthermore, we found that the expression of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was decreased during erastin-induced ferroptosis. Knockdown of MALAT1 significantly aggravated the inhibition of cell viability and increased intracellular iron, Liperfluo, and MDA levels in EESCs upon erastin treatment. Mechanistically, we demonstrated that MALAT1 served as a competing endogenous RNA of miR-145-5p to regulate the expression of MUC1, a suppressor of ferroptosis. MALAT1 knockdown-mediated ferroptotic cell death and MUC1 downregulation could be abrogated by inhibition of miR-145-5p. In addition, miR-145-5p inhibition-mediated ferroptotic cell death could be abolished by MUC1 knockdown. Furthermore, erastin-induced ferroptosis shrunk endometriotic lesions via the MALAT1/miR-145-5p/MUC1 axis in vivo. Taken together, our data indicate that knockdown of MALAT1 facilitates ferroptosis upon erastin treatment via miR-145-5p/MUC1 signaling. The synergistic effect of MALAT1 knockdown and erastin induction in ferroptosis may be a new therapeutic strategy for endometriosis.
NAMPT-dependent NAD+ salvage is crucial for the decision between apoptotic and necrotic cell death under oxidative stress
Authors: Nishida Takuto , Naguro Isao , Ichijo Hidenori 
Published: April 2022

AbstractOxidative stress is a state in which the accumulation of reactive oxygen species exceeds the capacity of cellular antioxidant systems. Both apoptosis and necrosis are observed under oxidative stress, and we have reported that these two forms of cell death are induced in H2O2-stimulated HeLa cells depending on the concentration of H2O2. Weak H2O2stimulation induces apoptosis, while strong H2O2stimulation induces necrosis. However, the detailed mechanisms controlling the switching between these forms of cell death depending on the level of oxidative stress remain elusive. Here, we found that NAD+metabolism is a key factor in determining the form of cell death in H2O2-stimulated HeLa cells. Under both weak and strong H2O2stimulation, intracellular nicotinamide adenine dinucleotide (NAD+) was depleted to a similar extent by poly (ADP-ribose) (PAR) polymerase 1 (PARP1)-dependent consumption. However, the intracellular NAD+concentration recovered under weak H2O2stimulation but not under strong H2O2stimulation. NAD+recovery was mediated by nicotinamide (NAM) phosphoribosyltransferase (NAMPT)-dependent synthesis via the NAD+salvage pathway, which was suggested to be impaired only under strong H2O2stimulation. Furthermore, downstream of NAD+, the dynamics of the intracellular ATP concentration paralleled those of NAD+, and ATP-dependent caspase-9 activation via apoptosome formation was thus impaired under strong H2O2stimulation. Collectively, these findings suggest that NAD+dynamics balanced by PARP1-dependent consumption and NAMPT-dependent production are important to determine the form of cell death activated under oxidative stress.
3D nanoprinting via spatially controlled assembly and polymerization
Authors: Pattison Thomas G. , Wang Shuo , Miller Robert D. , Liu Gang-yu , Qiao Greg G. 
Published: April 2022

AbstractMacroscale additive manufacturing has seen significant advances recently, but these advances are not yet realized for the bottom-up formation of nanoscale polymeric features. We describe a platform technology for creating crosslinked polymer features using rapid surface-initiated crosslinking and versatile macrocrosslinkers, delivered by a microfluidic-coupled atomic force microscope known as FluidFM. A crosslinkable polymer containing norbornene moieties is delivered to a catalyzed substrate where polymerization occurs, resulting in extremely rapid chemical curing of the delivered material. Due to the living crosslinking reaction, construction of lines and patterns with multiple layers is possible, showing quantitative material addition from each deposition in a method analogous to fused filament fabrication, but at the nanoscale. Print parameters influenced printed line dimensions, with the smallest lines being 450 nm across with a vertical layer resolution of 2 nm. This nanoscale 3D printing platform of reactive polymer materials has applications for device fabrication, optical systems and biotechnology.
Ubiquitin-like protein 3 (UBL3) is required for MARCH ubiquitination of major histocompatibility complex class II and CD86
Authors: Liu Haiyin , Wilson Kayla R. , Firth Ashley M. , Macri Christophe , Schriek Patrick , Blum Annabelle B. , Villar Javiera , Wormald Samuel , Shambrook Mitch , Xu Bangyan , Lim Hui Jing , McWilliam Hamish E. G. , Hill Andrew F. , Edgington-Mitchell Laura E. , Caminschi Irina , Lahoud Mireille H. , Segura Elodie , Herold Marco J. , Villadangos Jose A. , Mintern Justine D. 
Published: April 2022

AbstractThe MARCH E3 ubiquitin (Ub) ligase MARCH1 regulates trafficking of major histocompatibility complex class II (MHC II) and CD86, molecules of critical importance to immunity. Here we show, using a genome-wide CRISPR knockout screen, that ubiquitin-like protein 3 (UBL3) is a necessary component of ubiquitination-mediated trafficking of these molecules in mice and in humans. Ubl3-deficient mice have elevated MHC II and CD86 expression on the surface of professional and atypical antigen presenting cells. UBL3 also regulates MHC II and CD86 in human dendritic cells (DCs) and macrophages. UBL3 impacts ubiquitination of MARCH1 substrates, a mechanism that requires UBL3 plasma membrane anchoring via prenylation. Loss of UBL3 alters adaptive immunity with impaired development of thymic regulatory T cells, loss of conventional type 1 DCs, increased number of trogocytic marginal zone B cells, and defective in vivo MHC II and MHC I antigen presentation. In summary, we identify UBL3 as a conserved, critical factor in MARCH1-mediated ubiquitination with important roles in immune responses.
Predicting the future of excitation energy transfer in light-harvesting complex with artificial intelligence-based quantum dynamics
Authors: Ullah Arif , Dral Pavlo O. 
Published: April 2022

AbstractExploring excitation energy transfer (EET) in light-harvesting complexes (LHCs) is essential for understanding the natural processes and design of highly-efficient photovoltaic devices. LHCs are open systems, where quantum effects may play a crucial role for almost perfect utilization of solar energy. Simulation of energy transfer with inclusion of quantum effects can be done within the framework of dissipative quantum dynamics (QD), which are computationally expensive. Thus, artificial intelligence (AI) offers itself as a tool for reducing the computational cost. Here we suggest AI-QD approach using AI to directly predict QD as a function of time and other parameters such as temperature, reorganization energy, etc., completely circumventing the need of recursive step-wise dynamics propagation in contrast to the traditional QD and alternative, recursive AI-based QD approaches. Our trajectory-learning AI-QD approach is able to predict the correct asymptotic behavior of QD at infinite time. We demonstrate AI-QD on seven-sites Fenna–Matthews–Olson (FMO) complex.
Spectral analysis of product formulas for quantum simulation
Authors: Yi Changhao , Crosson Elizabeth 
Published: April 2022

AbstractWe consider the time-independent Hamiltonian simulation using the first order Lie–Trotter–Suzuki product formula under the assumption that the initial state is supported on a low-dimension subspace. By comparing the spectral decomposition of the original Hamiltonian and the effective Hamiltonian, we obtain better upper bounds for various conditions. Especially, we show that the Trotter step size needed to estimate an energy eigenvalue within precision ϵ using quantum phase estimation can be improved in scaling from ϵ to ϵ1/2 for a large class of systems. Our results also depend on the gap condition of the simulated Hamiltonian.
Mycobacterium avium-intracellulare complex promote release of pro-inflammatory enzymes matrix metalloproteinases by inducing neutrophil extracellular trap formation
Authors: Nakamura Kota , Nakayama Hitoshi , Sasaki Shinichi , Takahashi Kazuhisa , Iwabuchi Kazuhisa 
Published: April 2022

AbstractThe prevalence of and mortality from non-tuberculous mycobacteria (NTM) infections have been steadily increasing worldwide. Most NTM infections are caused byMycobacterium avium-intracellularecomplex (MAC). MAC can escape from killing by neutrophils, which are professional phagocytes. However, the involvement of neutrophils in the pathogenesis of MAC infection is poorly understood. The present study assessed the roles of neutrophil extracellular trap (NET) formation in neutrophil defense mechanisms against infection with MAC strains, includingM. aviumisolated from patients with severe or mild lung tissue destruction. Although all MAC induced NET formation, non-pathogenic mycobacteria (M. gordonaeandM. smegmatis) slightly but not significantly induced NET formation. Peptidylarginine deiminase 4 (PAD4) inhibitor reduced MAC-induced NET formation but did not affect MAC escape from neutrophils. PAD4 inhibition attenuated the MAC-induced matrix metalloproteinase (MMP)-8 and 9 release to the levels of MMPs from non-pathogenic mycobacteria. MAC also induced interleukin (IL)-8 release by neutrophils, a process independent of MAC-induced NET formation. Taken together, these findings suggest that MAC induce NET formation, IL-8 release and NETs-dependent release of MMP-8 and -9 from neutrophils, leading to neutrophil accumulation and further inflammation, thereby enhancing the progression of infection in the lungs.
Socioeconomic status impacts cognitive and socioemotional processes in healthy ageing
Authors: Migeot Joaquín , Calivar Mariela , Granchetti Hugo , Ibáñez Agustín , Fittipaldi Sol 
Published: April 2022

AbstractSocioeconomic status (SES) negatively impacts cognitive and executive functioning in older adults, yet its effects on socioemotional abilities have not been studied in this population. Also, evidence on neurocognitive processes associated with ageing primarily comes from Western, educated, industrialized, rich, and democratic (WEIRD) populations, hindering the generalization of findings to persons from upper-middle- and low‐middle‐income countries, such as those of Latin America. Here, we compared the performance of low- and high-SES older adults from Argentina in cognitive state, executive functions, social cognition (emotion recognition and theory of mind), and counter-empathic social emotions (envy and Schadenfreude; displeasure at others’ fortune and pleasure at others’ misfortune, respectively). Subsequently, we developed a path analysis to test the relationship among those variables in a theoretically plausible model and tested the main paths via multiple regression analyses. Relative to the high-SES group, low-SES older adults showed poorer performance on all assessed domains. Convergent evidence from covariance analysis, path analysis, and linear regressions suggested that low-SES impact on socioemotional processes was not primary but mediated by cognitive and executive impairment. These findings offer the first characterization of SES impacts on cognitive and socioemotional processes in a non-WEIRD population and have relevant equity-related implications for brain health.
Learning-based cable coupling effect modeling for robotic manipulation of heavy industrial cables
Authors: Mou Fangli , Wang Bin , Wu Dan 
Published: April 2022

AbstractThe robotic manipulation of a heavy industrial cable is challenging to model and control because of the high number of degrees of freedom and the rigid-flexible coupling dynamics. In this paper, we report the development of modeling the cable effect and control methodology for robotic cable manipulation. Our cable effect model is based on the 2D convolutional neural network, which is a deep learning-based method uses the effective cable representation method to achieve the accurate, generalizable, and efficient estimation of the cable coupling forces and torques. Practical problems such as the measurement limits and time efficiency are considered in our method for real applications. With these approaches, we are the first to solve the problem of dynamic payload effect caused by heavy industrial cables in experimental cases. The used control methodology combines the active disturbance rejection control framework with the sliding mode control method, which can acquire promising tracking performance. We integrate our cable effect model into the control scheme, and demonstrate it satisfies the high-quality robotic manipulation of heavy cables. The performance of the proposed method is assessed with both a simulated system and real robot system. The results show that our method can estimate the cable coupling effect with over 85% accuracy and accomplish manipulation with a positioning error less than 0.01 mm. This reveals that our method is promising for robotic manipulation of heavy industrial cables and can accomplish the challenging cable insertion task.
Life cycle assessment of biocemented sands using enzyme induced carbonate precipitation (EICP) for soil stabilization applications
Authors: Alotaibi Emran , Arab Mohamed G. , Abdallah Mohamed , Nassif Nadia , Omar Maher 
Published: April 2022

AbstractIntegrating sustainability goals into the selection of suitable soil stabilization techniques is a global trend. Several bio-inspired and bio-mediated soil stabilization techniques have been recently investigated as sustainable alternatives for traditional techniques known for their high carbon footprint. Enzyme Induced Carbonate Precipitation (EICP) is an emerging bio-inspired soil stabilization technology that is based on the hydrolysis of urea to precipitate carbonates that cement sand particles. A life cycle assessment (LCA) study was conducted to compare the use of traditional soil stabilization using Portland cement (PC) with bio-cementation via EICP over a range of environmental impacts. The LCA results revealed that EICP soil treatment has nearly 90% less abiotic depletion potential and 3% less global warming potential compared to PC in soil stabilization. In contrast, EICP in soil stabilization has higher acidification and eutrophication potentials compared to PC due to byproducts during the hydrolysis process. The sensitivity analysis of EICP emissions showed that reducing and controlling the EICP process emissions and using waste non-fate milk has resulted in significantly fewer impacts compared to the EICP baseline scenario. Moreover, a comparative analysis was conducted between EICP, PC, and Microbial Induced Carbonate Precipitation (MICP) to study the effect of treated soil compressive strength on the LCA findings. The analysis suggested that EICP is potentially a better environmental option, in terms of its carbon footprint, at lower compressive strength of the treated soils.
Identification of lamprey variable lymphocyte receptors that target the brain vasculature
Authors: Lajoie Jason M. , Katt Moriah E. , Waters Elizabeth A. , Herrin Brantley R. , Shusta Eric V. 
Published: April 2022

AbstractThe blood–brain barrier (BBB) represents a significant bottleneck for the delivery of therapeutics to the central nervous system. In recent years, the promise of coopting BBB receptor-mediated transport systems for brain drug delivery has increased in large part due to the discovery and engineering of BBB-targeting antibodies. Here we describe an innovative screening platform for identification of new BBB targeting molecules from a class of lamprey antigen recognition proteins known as variable lymphocyte receptors (VLRs). Lamprey were immunized with murine brain microvessel plasma membranes, and the resultant repertoire cloned into the yeast surface display system. The library was screened via a unique workflow that identified 16 VLR clones that target extracellular epitopes of in vivo-relevant BBB membrane proteins. Of these, three lead VLR candidates, VLR-Fc-11, VLR-Fc-30, and VLR-Fc-46 selectively target the brain vasculature and traffic within brain microvascular endothelial cells after intravenous administration in mice, with VLR-Fc-30 being confirmed as trafficking into the brain parenchyma. Epitope characterization indicates that the VLRs, in part, recognize sialylated glycostructures. These promising new targeting molecules have the potential for brain targeting and drug delivery with improved brain vascular specificity.
Selection of a novel strain of Christensenella minuta as a future biotherapy for Crohn’s disease
Authors: Relizani Karima , Le Corf Katy , Kropp Camille , Martin-Rosique Rebeca , Kissi Déborah , Déjean Guillaume , Bruno Lisa , Martinez Ccori , Rawadi Georges , Elustondo Frédéric , Mazier Wilfrid , Claus Sandrine P. 
Published: April 2022

AbstractMicrobiome-based therapies for inflammatory bowel diseases offer a novel and promising therapeutic approach. The human commensal bacteria of the species Christensenella minuta (C. minuta) have been reported consistently missing in patients affected by Crohn’s disease (CD) and have been documented to induce anti-inflammatory effects in human epithelial cells, supporting their potential as a novel biotherapy. This work aimed at selecting the most promising strain of C. minuta for future development as a clinical candidate for CD therapy. Here, we describe a complete screening process combining in vitro and in vivo assays to conduct a rational selection of a live strain of C. minuta with strong immunomodulatory properties. Starting from a collection of 32 strains, a panel of in vitro screening assays was used to narrow it down to five preclinical candidates that were further screened in vivo in an acute TNBS-induced rat colitis model. The most promising candidate was validated in vivo in two mouse models of colitis. The validated clinical candidate strain, C. minuta DSM 33715, was then fully characterized. Hence, applying a rationally designed screening algorithm, a novel strain of C. minuta was successfully identified as the most promising clinical candidate for CD.