bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pathological features of COVID-19-associated lung injury: a preliminary proteomics report based on clinical samples
Authors: Leng Ling , Cao Ruiyuan , Ma Jie , Mou Danlei , Zhu Yunping , Li Wei , Lv Luye , Gao Dunqin , Zhang Shikun , Gong Feng , Zhao Lei , Qiu Bintao , Xiang Haiping , Hu Zhongjie , Feng Yingmei , Dai Yan , Zhao Jiang , Wu Zhihong , Li Hongjun , Zhong Wu 
Published: October 2020

AbstractThe COVID-19 pandemic has emerged as a global health emergency due to its association with severe pneumonia and relative high mortality. However, the molecular characteristics and pathological features underlying COVID-19 pneumonia remain largely unknown. To characterize molecular mechanisms underlying COVID-19 pathogenesis in the lung tissue using a proteomic approach, fresh lung tissues were obtained from newly deceased patients with COVID-19 pneumonia. After virus inactivation, a quantitative proteomic approach combined with bioinformatics analysis was used to detect proteomic changes in the SARS-CoV-2-infected lung tissues. We identified significant differentially expressed proteins involved in a variety of fundamental biological processes including cellular metabolism, blood coagulation, immune response, angiogenesis, and cell microenvironment regulation. Several inflammatory factors were upregulated, which was possibly caused by the activation of NF-κB signaling. Extensive dysregulation of the lung proteome in response to SARS-CoV-2 infection was discovered. Our results systematically outlined the molecular pathological features in terms of the lung response to SARS-CoV-2 infection, and provided the scientific basis for the therapeutic target that is urgently needed to control the COVID-19 pandemic.
Experimentally-validated correlation analysis reveals new anaerobic methane oxidation partnerships with consortium-level heterogeneity in diazotrophy
Authors: Metcalfe Kyle S , Murali Ranjani , Mullin Sean W , Connon Stephanie A , Orphan Victoria J 
Published: October 2020

Abstract
Archaeal anaerobic methanotrophs (“ANME”) and sulfate-reducing Deltaproteobacteria (“SRB”) form symbiotic multicellular consortia capable of anaerobic methane oxidation (AOM), and in so doing modulate methane flux from marine sediments. The specificity with which ANME associate with particular SRB partners in situ, however, is poorly understood. To characterize partnership specificity in ANME-SRB consortia, we applied the correlation inference technique SparCC to 310 16S rRNA amplicon libraries prepared from Costa Rica seep sediment samples, uncovering a strong positive correlation between ANME-2b and members of a clade of Deltaproteobacteria we termed SEEP-SRB1g. We confirmed this association by examining 16S rRNA diversity in individual ANME-SRB consortia sorted using flow cytometry and by imaging ANME-SRB consortia with fluorescence in situ hybridization (FISH) microscopy using newly-designed probes targeting the SEEP-SRB1g clade. Analysis of genome bins belonging to SEEP-SRB1g revealed the presence of a complete nifHDK operon required for diazotrophy, unusual in published genomes of ANME-associated SRB. Active expression of nifH in SEEP-SRB1g within ANME-2b—SEEP-SRB1g consortia was then demonstrated by microscopy using hybridization chain reaction (HCR-) FISH targeting nifH transcripts and diazotrophic activity was documented by FISH-nanoSIMS experiments. NanoSIMS analysis of ANME-2b—SEEP-SRB1g consortia incubated with a headspace containing CH4 and 15N2 revealed differences in cellular 15N-enrichment between the two partners that varied between individual consortia, with SEEP-SRB1g cells enriched in 15N relative to ANME-2b in one consortium and the opposite pattern observed in others, indicating both ANME-2b and SEEP-SRB1g are capable of nitrogen fixation, but with consortium-specific variation in whether the archaea or bacterial partner is the dominant diazotroph.
Exploring the use of mouth guards in Muay Thai: a questionnaire survey
Authors: Pickering Kimberley , Bissett Susan M. , Holliday Richard , Vernazza Christopher , Preshaw Philip M. 
Published: October 2020

AbstractObjectiveTo identify Muay Thai participants’ attitudes towards use of mouth guards and their experiences of dental trauma.Materials and methodsAn online cross-sectional survey was used to record Muay Thai participants’ experiences and opinions regarding use of mouth guards. Participants were recruited from a Muay Thai gym in the north east of England.Results92 respondents took part in the survey. 3% reported having never worn a mouth guard, whereas 61% reported routinely wearing mouth guards during a fight. Significantly more (73%) younger participants (18–29 years) reported wearing mouth guards during fights compared to those aged 30 years and older (50%) (p < 0.05). Mouth-formed (‘boil and bite’) were the most frequently used type of mouth guard (60% of users), followed by custom-made mouth guards provided by a dentist (32%). Factors such as protection, breathing, good fit and comfort were all considered important in the choice of mouth guard. 14% of respondents had experienced dental injuries, with chipped/broken teeth being the most common.ConclusionGiven the risk for dental trauma in Muay Thai, it is important that participants are advised regarding mouth guard use, particularly those that do not routinely wear them.
Mesenchymal stem cells reverse EMT process through blocking the activation of NF-κB and Hedgehog pathways in LPS-induced acute lung injury
Authors: Xiao Kun , He Wanxue , Guan Wei , Hou Fei , Yan Peng , Xu Jianqiao , Zhou Ting , Liu Yuhong , Xie Lixin 
Published: October 2020

AbstractAcute lung injury (ALI) is a pulmonary disorder, which can result in fibrosis of the lung tissues. Recently, mesenchymal stem cell (MSC) has become a novel therapeutic method for ALI. However, the potential mechanism by which MSC regulates the progression of ALI remains blurry. The present study focused on investigating the mechanism underneath MSC-reversed lung injury and fibrosis. At first, we determined that coculture with MSC led to the inactivation of NF-κB signaling and therefore suppressed hedgehog pathway in LPS-treated MLE-12 cells. Besides, we confirmed that MSC-exosomes were responsible for the inhibition of EMT process in LPS-treated MLE-12 cells through transmitting miRNAs. Mechanism investigation revealed that MSC-exosome transmitted miR-182-5p and miR-23a-3p into LPS-treated MLE-12 cells to, respectively, target Ikbkb and Usp5. Of note, Usp5 interacted with IKKβ to hamper IKKβ ubiquitination. Moreover, co-inhibition of miR-182-5p and miR-23a-3p offset the suppression of MSC on EMT process in LPS-treated MLE-12 cells as well as in LPS-injured lungs of mice. Besides, the retarding effect of MSC on p65 nuclear translocation was also counteracted after co-inhibiting miR-182-5p and miR-23a-3p, both in vitro and in vivo. In summary, MSC-exosome transmitted miR-23a-3p and miR-182-5p reversed the progression of LPS-induced lung injury and fibrosis through inhibiting NF-κB and hedgehog pathways via silencing Ikbkb and destabilizing IKKβ.
PRMT5/Wnt4 axis promotes lymph-node metastasis and proliferation of laryngeal carcinoma
Authors: Wang Nan , Yan Honghong , Wu Di , Zhao Zheng , Chen Xiaoqi , Long Qian , Zhang Changlin , Wang Xiaohao , Deng Wuguo , Liu Xuekui 
Published: October 2020

AbstractMetastasis is the main cause of laryngeal cancer-related death; its molecular mechanism remains unknown. Here we identify protein arginine methyltransferase 5 (PRMT5) as a new metastasis-promoting factor in laryngeal carcinoma, and explore its underlying mechanism of action in regulating laryngeal cancer progression. We illustrated that PRMT5 expression was positively correlated with tumor stages, lymphatic metastasis, and unfavorable outcome. Functional assays revealed that PRMT5 promoted laryngeal carcinoma cell proliferation, migration, and invasive capacity in vitro, as well as lymph-node metastasis in vivo. The ectopic expression of PRMT5 induced EMT with downregulation of E-cadherin and upregulation of N-cadherin, snail, and MMP9. Mechanistic results revealed that the metastatic effects could be attributed to PRMT5-mediated activation of Wnt signaling, and Wnt4 is an important driver of Wnt/β-catenin signaling pathway. Wnt4 silencing could reverse PRMT5-induced cell proliferation, migration, and invasion capacities. Furthermore, inhibition of the Wnt/β-catenin signaling pathway abolished the effect of PRMT5-induced proliferation, whereas activation of the pathway enhanced the effect of PRMT5 overexpression on cell proliferation. These results demonstrated that the oncogenic role of PRMT5 could be attributed to PRMT5/Wnt4 axis-mediated activation of the Wnt/β-catenin signaling pathway. PRMT5 may serve as a novel prognostic marker and a therapeutic target for lymphatic metastasis of laryngeal carcinoma.
Unique immunological profile in patients with COVID-19
Authors: Varchetta Stefania , Mele Dalila , Oliviero Barbara , Mantovani Stefania , Ludovisi Serena , Cerino Antonella , Bruno Raffaele , Castelli Alberto , Mosconi Mario , Vecchia Marco , Roda Silvia , Sachs Michele , Klersy Catherine , Mondelli Mario U. 
Published: October 2020

AbstractThe relationship between severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and host immunity is poorly understood. We performed an extensive analysis of immune responses in 32 patients with severe COVID-19, some of whom succumbed. A control population of healthy subjects was included. Patients with COVID-19 had an altered distribution of peripheral blood lymphocytes, with an increased proportion of mature natural killer (NK) cells and low T-cell numbers. NK cells and CD8+T cells overexpressed T-cell immunoglobulin and mucin domain-3 (TIM-3) and CD69. NK cell exhaustion was attested by increased frequencies of programmed cell death protein 1 (PD-1) positive cells and reduced frequencies of natural killer group 2 member D (NKG2D)-, DNAX accessory molecule-1 (DNAM-1)- and sialic acid-binding Ig-like lectin 7 (Siglec-7)-expressing NK cells, associated with a reduced ability to secrete interferon (IFN)γ. Patients with poor outcome showed a contraction of immature CD56brightand an expansion of mature CD57+FcεRIγnegadaptive NK cells compared to survivors. Increased serum levels of IL-6 were also more frequently identified in deceased patients compared to survivors. Of note, monocytes secreted abundant quantities of IL-6, IL-8, and IL-1β which persisted at lower levels several weeks after recovery with concomitant normalization of CD69, PD-1 and TIM-3 expression and restoration of CD8+T cell numbers. A hyperactivated/exhausted immune response dominate in severe SARS-CoV-2 infection, probably driven by an uncontrolled secretion of inflammatory cytokines by monocytes. These findings unveil a unique immunological profile in COVID-19 patients that will help to design effective stage-specific treatments for this potentially deadly disease.
Cardio-centric hemodynamic management improves spinal cord oxygenation and mitigates hemorrhage in acute spinal cord injury
Authors: Williams Alexandra M. , Manouchehri Neda , Erskine Erin , Tauh Keerit , So Kitty , Shortt Katelyn , Webster Megan , Fisk Shera , Billingsley Avril , Munro Alex , Tigchelaar Seth , Streijger Femke , Kim Kyoung-Tae , Kwon Brian K. , West Christopher R. 
Published: October 2020

AbstractChronic high-thoracic and cervical spinal cord injury (SCI) results in a complex phenotype of cardiovascular consequences, including impaired left ventricular (LV) contractility. Here, we aim to determine whether such dysfunction manifests immediately post-injury, and if so, whether correcting impaired contractility can improve spinal cord oxygenation (SCO2), blood flow (SCBF) and metabolism. Using a porcine model of T2 SCI, we assess LV end-systolic elastance (contractility) via invasive pressure-volume catheterization, monitor intraparenchymal SCO2 and SCBF with fiberoptic oxygen sensors and laser-Doppler flowmetry, respectively, and quantify spinal cord metabolites with microdialysis. We demonstrate that high-thoracic SCI acutely impairs cardiac contractility and substantially reduces SCO2 and SCBF within the first hours post-injury. Utilizing the same model, we next show that augmenting LV contractility with the β-agonist dobutamine increases SCO2 and SCBF more effectively than vasopressor therapy, whilst also mitigating increased anaerobic metabolism and hemorrhage in the injured cord. Finally, in pigs with T2 SCI survived for 12 weeks post-injury, we confirm that acute hemodynamic management with dobutamine appears to preserve cardiac function and improve hemodynamic outcomes in the chronic setting. Our data support that cardio-centric hemodynamic management represents an advantageous alternative to the current clinical standard of vasopressor therapy for acute traumatic SCI.
Engineering Af1521 improves ADP-ribose binding and identification of ADP-ribosylated proteins
Authors: Nowak Kathrin , Rosenthal Florian , Karlberg Tobias , Bütepage Mareike , Thorsell Ann-Gerd , Dreier Birgit , Grossmann Jonas , Sobek Jens , Imhof Ralph , Lüscher Bernhard , Schüler Herwig , Plückthun Andreas , Leslie Pedrioli Deena M. , Hottiger Michael O. 
Published: October 2020

AbstractProtein ADP-ribosylation is a reversible post-translational modification that regulates important cellular functions. The identification of modified proteins has proven challenging and has mainly been achieved via enrichment methodologies. Random mutagenesis was used here to develop an engineered Af1521 ADP-ribose binding macro domain protein with 1000-fold increased affinity towards ADP-ribose. The crystal structure reveals that two point mutations K35E and Y145R form a salt bridge within the ADP-ribose binding domain. This forces the proximal ribose to rotate within the binding pocket and, as a consequence, improves engineered Af1521 ADPr-binding affinity. Its use in our proteomic ADP-ribosylome workflow increases the ADP-ribosylated protein identification rates and yields greater ADP-ribosylome coverage. Furthermore, generation of an engineered Af1521 Fc fusion protein confirms the improved detection of cellular ADP-ribosylation by immunoblot and immunofluorescence. Thus, this engineered isoform of Af1521 can also serve as a valuable tool for the analysis of cellular ADP-ribosylation under in vivo conditions.
DOT1L-mediated murine neuronal differentiation associates with H3K79me2 accumulation and preserves SOX2-enhancer accessibility
Authors: Ferrari Francesco , Arrigoni Laura , Franz Henriette , Izzo Annalisa , Butenko Ludmila , Trompouki Eirini , Vogel Tanja , Manke Thomas 
Published: October 2020

AbstractDuring neuronal differentiation, the transcriptional profile and the epigenetic context of neural committed cells is subject to significant rearrangements, but a systematic quantification of global histone modification changes is still missing. Here, we show that H3K79me2 increases and H3K27ac decreases globally during in-vitro neuronal differentiation of murine embryonic stem cells. DOT1L mediates all three degrees of methylation of H3K79 and its enzymatic activity is critical to modulate cellular differentiation and reprogramming. In this context, we find that inhibition of DOT1L in neural progenitor cells biases the transcriptional state towards neuronal differentiation, resulting in transcriptional upregulation of genes marked with H3K27me3 on the promoter region. We further show that DOT1L inhibition affects accessibility of SOX2-bound enhancers and impairs SOX2 binding in neural progenitors. Our work provides evidence that DOT1L activity gates differentiation of progenitors by allowing SOX2-dependent transcription of stemness programs.
Enabling “lithium-free” manufacturing of pure lithium metal solid-state batteries through in situ plating
Authors: Wang Michael J. , Carmona Eric , Gupta Arushi , Albertus Paul , Sakamoto Jeff 
Published: October 2020

AbstractThe coupling of solid-state electrolytes with a Li-metal anode and state-of-the-art (SOA) cathode materials is a promising path to develop inherently safe batteries with high energy density (>1000 Wh L−1). However, integrating metallic Li with solid-electrolytes using scalable processes is not only challenging, but also adds extraneous volume since SOA cathodes are fully lithiated. Here we show the potential for “Li-free” battery manufacturing using the Li7La3Zr2O12 (LLZO) electrolyte. We demonstrate that Li-metal anodes >20 μm can be electroplated onto a current collector in situ without LLZO degradation and we propose a model to relate electrochemical and nucleation behavior. A full cell consisting of in situ formed Li, LLZO, and NCA is demonstrated, which exhibits stable cycling over 50 cycles with high Coulombic efficiencies. These findings demonstrate the viability of “Li-free” configurations using LLZO which may guide the design and manufacturing of high energy density solid-state batteries.
Multiplying the efficiency and impact of biofortification through metabolic engineering
Authors: Van Der Straeten Dominique , Bhullar Navreet K. , De Steur Hans , Gruissem Wilhelm , MacKenzie Donald , Pfeiffer Wolfgang , Qaim Matin , Slamet-Loedin Inez , Strobbe Simon , Tohme Joe , Trijatmiko Kurniawan Rudi , Vanderschuren Hervé , Van Montagu Marc , Zhang Chunyi , Bouis Howarth 
Published: October 2020

AbstractEnding all forms of hunger by 2030, as set forward in the UN-Sustainable Development Goal 2 (UN-SDG2), is a daunting but essential task, given the limited timeline ahead and the negative global health and socio-economic impact of hunger. Malnutrition or hidden hunger due to micronutrient deficiencies affects about one third of the world population and severely jeopardizes economic development. Staple crop biofortification through gene stacking, using a rational combination of conventional breeding and metabolic engineering strategies, should enable a leap forward within the coming decade. A number of specific actions and policy interventions are proposed to reach this goal.
SUSA2 is an F-box protein required for autoimmunity mediated by paired NLRs SOC3-CHS1 and SOC3-TN2
Authors: Liang Wanwan , Tong Meixuezi , Li Xin 
Published: October 2020

AbstractBoth higher plants and mammals rely on nucleotide-binding leucine-rich repeat (NLR) immune receptors to detect pathogens and initiate immunity. Upon effector recognition, plant NLRs oligomerize for defense activation, the mechanism of which is poorly understood. We previously showed that disruption of the E3 ligase, Senescence-Associated E3 Ubiquitin Ligase 1 (SAUL1) leads to the activation of the NLR SOC3. Here, we report the identification of suppressor of saul1 2 (susa2) and susa3 from the saul1-1 suppressor screen. Pairwise interaction analysis suggests that both SUSA proteins interact with components of an SCFSUSA2 E3 ligase complex as well as CHS1 or TN2, truncated NLRs that pair with SOC3. susa2-2 only suppresses the autoimmunity mediated by either CHS1 or TN2, suggesting its specific involvement in SOC3-mediated immunity. In summary, our study indicates links between plant NLRs and an SCF complex that may enable ubiquitination and degradation of unknown downstream components to activate defense.
Dimer rattling mode induced low thermal conductivity in an excellent acoustic conductor
Authors: Qi Ji , Dong Baojuan , Zhang Zhe , Zhang Zhao , Chen Yanna , Zhang Qiang , Danilkin Sergey , Chen Xi , He Jiaming , Fu Liangwei , Jiang Xiaoming , Chai Guozhi , Hiroi Satoshi , Ohara Koji , Zhang Zongteng , Ren Weijun , Yang Teng , Zhou Jianshi , Osami Sakata , He Jiaqing , Yu Dehong , Li Bing , Zhang Zhidong 
Published: October 2020

AbstractA solid with larger sound speeds usually exhibits higher lattice thermal conductivity. Here, we report an exception that CuP2 has a quite large mean sound speed of 4155 m s−1, comparable to GaAs, but single crystals show very low lattice thermal conductivity of about 4 W m−1 K−1 at room temperature, one order of magnitude smaller than GaAs. To understand such a puzzling thermal transport behavior, we have thoroughly investigated the atomic structures and lattice dynamics by combining neutron scattering techniques with first-principles simulations. This compound crystallizes in a layered structure where Cu atoms forming dimers are sandwiched in between P atomic networks. In this work, we reveal that Cu atomic dimers vibrate as a rattling mode with frequency around 11 meV, which is manifested to be remarkably anharmonic and strongly scatters acoustic phonons to achieve the low lattice thermal conductivity.
A nanoluciferase SARS-CoV-2 for rapid neutralization testing and screening of anti-infective drugs for COVID-19
Authors: Xie Xuping , Muruato Antonio E. , Zhang Xianwen , Lokugamage Kumari G. , Fontes-Garfias Camila R. , Zou Jing , Liu Jianying , Ren Ping , Balakrishnan Mini , Cihlar Tomas , Tseng Chien-Te K. , Makino Shinji , Menachery Vineet D. , Bilello John P. , Shi Pei-Yong 
Published: October 2020

AbstractA high-throughput platform would greatly facilitate coronavirus disease 2019 (COVID-19) serological testing and antiviral screening. Here we present a high-throughput nanoluciferase severe respiratory syndrome coronavirus 2 (SARS-CoV-2-Nluc) that is genetically stable and replicates similarly to the wild-type virus in cell culture. SARS-CoV-2-Nluc can be used to measure neutralizing antibody activity in patient sera within 5 hours, and it produces results in concordance with a plaque reduction neutralization test (PRNT). Additionally, using SARS-CoV-2-Nluc infection of A549 cells expressing human ACE2 receptor (A549-hACE2), we show that the assay can be used for antiviral screening. Using the optimized SARS-CoV-2-Nluc assay, we evaluate a panel of antivirals and other anti-infective drugs, and we identify nelfinavir, rupintrivir, and cobicistat as the most selective inhibitors of SARS-CoV-2-Nluc (EC500.77 to 2.74 µM). In contrast, most of the clinically approved antivirals, including tenofovir alafenamide, emtricitabine, sofosbuvir, ledipasvir, and velpatasvir were inactive at concentrations up to 10 µM. Collectively, this high-throughput platform represents a reliable tool for rapid neutralization testing and antiviral screening for SARS-CoV-2.
Dual redox mediators accelerate the electrochemical kinetics of lithium-sulfur batteries
Authors: Liu Fang , Sun Geng , Wu Hao Bin , Chen Gen , Xu Duo , Mo Runwei , Shen Li , Li Xianyang , Ma Shengxiang , Tao Ran , Li Xinru , Tan Xinyi , Xu Bin , Wang Ge , Dunn Bruce S. , Sautet Philippe , Lu Yunfeng 
Published: October 2020

AbstractThe sluggish electrochemical kinetics of sulfur species has impeded the wide adoption of lithium-sulfur battery, which is one of the most promising candidates for next-generation energy storage system. Here, we present the electronic and geometric structures of all possible sulfur species and construct an electronic energy diagram to unveil their reaction pathways in batteries, as well as the molecular origin of their sluggish kinetics. By decoupling the contradictory requirements of accelerating charging and discharging processes, we select two pseudocapacitive oxides as electron-ion source and drain to enable the efficient transport of electron/Li+ to and from sulfur intermediates respectively. After incorporating dual oxides, the electrochemical kinetics of sulfur cathode is significantly accelerated. This strategy, which couples a fast-electrochemical reaction with a spontaneous chemical reaction to bypass a slow-electrochemical reaction pathway, offers a solution to accelerate an electrochemical reaction, providing new perspectives for the development of high-energy battery systems.