bluuebunny/crossref_metadata_2025 huggingface dataset:
Arctic Clouds and Precipitation in the Community Earth System Model Version 2
Authors: McIlhattan Elin A. , Kay Jennifer E. , L'Ecuyer Tristan S.
Published: October 2020

The Arctic climate is changing rapidly, warming at about twice the rate of the planet. Global climate models (GCMs) are invaluable tools both for understanding the drivers of these changes and predicting future Arctic climate evolution. While GCMs are continually improving, there remain difficulties in representing cloud processes which occur on scales smaller than GCM resolution. Since clouds influence the Arctic energy and water cycles, their accurate representation in models is critical for robust future projections. In this work, we examine the representation of Arctic clouds and precipitation in the Community Earth System Model (CESM) with the Community Atmosphere Model (CAM), comparing the newly released version (CESM2 with CAM6) with its predecessor (CESM1 with CAM5). To isolate changes in the Arctic mean state, we compare preindustrial control runs. Arctic cloud ice has decreased slightly, while cloud water has increased dramatically in CESM2. Annual mean liquid‐containing cloud (LCC) frequency has increased from 19% in CESM1 to 51% in CESM2. Since LCCs strongly modulate downwelling radiation at the surface, their increase has led to an increase in mean downwelling longwave (+22 W m−2) and corresponding decrease in downwelling shortwave (−23 W m−2) radiation. The mean Arctic surface temperature increased from 257 K in CESM1 to 260 K in CESM2, with the largest seasonal difference in winter (+6 K). Annual average snowfall has decreased slightly (−1 mm month−1), while rainfall has increased (+5 mm month−1).
Sediment Connectivity: A Framework for Analyzing Coastal Sediment Transport Pathways
Authors: Pearson Stuart G. , van Prooijen Bram C. , Elias Edwin P. L. , Vitousek Sean , Wang Zheng Bing
Published: October 2020

Connectivity provides a framework for analyzing coastal sediment transport pathways, building on conceptual advances in graph theory from other scientific disciplines. Connectivity schematizes sediment pathways as a directed graph (i.e., a set of nodes and links). This study presents a novel application of graph theory and connectivity metrics like modularity and centrality to coastal sediment dynamics, exemplified here using Ameland Inlet in the Netherlands. We divide the study site into geomorphic cells (i.e., nodes) and then quantify sediment transport between these cells (i.e., links) using a numerical model. The system of cells and fluxes between them is then schematized in a network described by an adjacency matrix. Network metrics like link density, asymmetry, and modularity quantify system‐wide connectivity. The degree, strength, and centrality of individual nodes identify key locations and pathways throughout the system. For instance, these metrics indicate that under strictly tidal forcing, sand originating near shore predominantly bypasses Ameland Inlet via the inlet channels, whereas sand on the deeper foreshore mainly bypasses the inlet via the outer delta shoals. Connectivity analysis can also inform practical management decisions about where to place sand nourishments, the fate of nourishment sand, or how to monitor locations vulnerable to perturbations. There are still open challenges associated with quantifying connectivity at varying space and time scales and the development of connectivity metrics specific to coastal systems. Nonetheless, connectivity provides a promising technique for predicting the response of our coasts to climate change and the human adaptations it provokes.
Getting to the Root of Plant‐Mediated Methane Emissions and Oxidation in a Thermokarst Bog
Authors: Turner Jesse C. , Moorberg Colby J. , Wong Andrea , Shea Kathleen , Waldrop Mark P. , Turetsky Merritt R. , Neumann Rebecca B.
Published: October 2020

Vascular plants are important in the wetland methane cycle, but their effect on production, oxidation, and transport has high uncertainty, limiting our ability to predict emissions. In a permafrost‐thaw bog in Interior Alaska, we used plant manipulation treatments, field‐deployed planar optical oxygen sensors, direct measurements of methane oxidation, and microbial DNA analyses to disentangle mechanisms by which vascular vegetation affect methane emissions. Vegetation operated on top of baseline methane emissions, which varied with proximity to the thawing permafrost margin. Emissions from vegetated plots increased over the season, resulting in cumulative seasonal methane emissions that were 4.1–5.2 g m−2 season−1 greater than unvegetated plots. Mass balance calculations signify these greater emissions were due to increased methane production (3.0–3.5 g m−2 season−1) and decreased methane oxidation (1.1–1.6 g m−2 season−1). Minimal oxidation occurred along the plant‐transport pathway, and oxidation was suppressed outside the plant pathway. Our data indicate suppression of methane oxidation was stimulated by root exudates fueling competition among microbes for electron acceptors. This contention is supported by the fact that methane oxidation and relative abundance of methanotrophs decreased over the season in the presence of vegetation, but methane oxidation remained steady in unvegetated treatments; oxygen was not detected around plant roots but was detected around silicone tubes mimicking aerenchyma; and oxygen injection experiments suggested that oxygen consumption was faster in the presence of vascular vegetation. Root exudates are known to fuel methane production, and our work provides evidence they also decrease methane oxidation.
Impact of a New Sea Ice Thermodynamic Formulation in the CESM2 Sea Ice Component
Authors: Bailey David A. , Holland Marika M. , DuVivier Alice K. , Hunke Elizabeth C. , Turner Adrian K.
Published: October 2020

The sea ice component of the Community Earth System Model version 2 (CESM2) contains new “mushy‐layer” physics that simulates prognostic salinity in the sea ice, with consequent modifications to sea ice thermodynamics and the treatment of melt ponds. The changes to the sea ice model and their influence on coupled model simulations are described here. Two simulations were performed to assess the changes in the vertical thermodynamics formulation with prognostic salinity compared to a constant salinity profile. Inclusion of the mushy layer thermodynamics of Turner et al. (2013, https://doi.org/10.1002/jgrc.20171) in a fully coupled Earth system model produces thicker and more extensive sea ice in the Arctic, with relatively unchanged sea ice in the Antarctic compared to simulations using a constant salinity profile. While this is consistent with the findings of uncoupled ice‐ocean model studies, the role of the frazil and congelation growth is more important in fully coupled simulations. Melt pond drainage is also an important contribution to simulated ice thickness differences as also found in the uncoupled simulations of Turner and Hunke (2015; https://doi.org/10.1002/2014JC010358). However, it is an interaction of the ponds and the snow fraction that impacts the surface albedo and hence the top melt. The changes in the thermodynamics and resulting ice state modify the ice‐ocean‐atmosphere fluxes with impacts on the atmosphere and ocean states, particularly temperature.
Modeling Soil Erosion With Evolving Rills on Hillslopes
Authors: Wu Songbai , Chen Li
Published: October 2020

Whereas current erosion models are successful in quantitative estimates of soil erosion by water flow, modeling the coevolution of geomorphological features, particularly rill network properties and soil erosion on hillslopes, is still a major challenge. In this study, we propose a rill evolution modeling approach and combine it with a rainfall‐runoff and soil erosion model to simulate the feedback loop of hillslope geomorphic development and soil erosion processes. Rill evolution is mainly characterized by three rill network attributes, rill density, orientation angle, and rill width, all modeled with physical equations. The entire rainfall‐runoff‐erosion and rill evolution model is tested against a set of rill network evolution and soil erosion data from an experimental hillslope subjected to successive rainfall events. The simulated spatial and temporal variations of rill network characteristics and soil erosion agree well with the measured data. The results demonstrate that the three rill network characteristics continually alter the partitioning of interrill and rill flows and affect the interrill and rill flow erosivity and soil erosion, which in turn modify the rill geometry and rill network planform. Comparatively, existing approaches such as Water Erosion Prediction Project (WEPP) that ignore the rill evolution processes largely underestimate the hillslope soil erosion when using time independent model parameters. Moreover, a sensitivity analysis indicates that both the rill evolution and soil erosion processes are sensitive to the rill evolution parameters, rainfall intensity, and slope angle. These results can inform the development of general geomorphic evolution and soil erosion models on evolving rilled hillslopes.
How Probable Is Widespread Flooding in the United States?
Authors: Brunner Manuela I. , Papalexiou Simon , Clark Martyn P. , Gilleland Eric
Published: October 2020

Widespread flooding can cause major damages and substantial recovery costs. Still, estimates of how susceptible a region is to widespread flooding are largely missing mainly because of the sparseness of widespread flood events in records. The aim of this study is to assess the seasonal susceptibility of regions in the United States to widespread flooding using a stochastic streamflow generator, which enables simulating a large number of spatially consistent flood events. Furthermore, we ask which factors influence the strength of regional flood susceptibilities. We show that susceptibilities to widespread flooding vary regionally and seasonally. They are highest in regions where catchments show regimes with a strong seasonality, that is, the Pacific Northwest, the Rocky Mountains, and the Northeast. In contrast, they are low in regions where catchments are characterized by a weak seasonality and intermittent regimes such as the Great Plains. Furthermore, susceptibility is found to be the highest in winter and spring when spatial flood dependencies are strongest because of snowmelt contributions and high soil moisture availability. We conclude that regional flood susceptibilities emerge in river basins with catchments sharing similar streamflow and climatic regimes.
Acute dose-dependent effects of lysergic acid diethylamide in a double-blind placebo-controlled study in healthy subjects
Authors: Holze Friederike , Vizeli Patrick , Ley Laura , Müller Felix , Dolder Patrick , Stocker Melanie , Duthaler Urs , Varghese Nimmy , Eckert Anne , Borgwardt Stefan , Liechti Matthias E.
Published: October 2020

Growing interest has been seen in using lysergic acid diethylamide (LSD) in psychiatric research and therapy. However, no modern studies have evaluated subjective and autonomic effects of different and pharmaceutically well-defined doses of LSD. We used a double-blind, randomized, placebo-controlled, crossover design in 16 healthy subjects (eight women, eight men) who underwent six 25 h sessions and received placebo, LSD (25, 50, 100, and 200 µg), and 200 µg LSD 1 h after administration of the serotonin 5-hydroxytryptamine-2A (5-HT2A) receptor antagonist ketanserin (40 mg). Test days were separated by at least 10 days. Outcome measures included self-rating scales that evaluated subjective effects, autonomic effects, adverse effects, plasma brain-derived neurotrophic factor levels, and pharmacokinetics up to 24 h. The pharmacokinetic-subjective response relationship was evaluated. LSD showed dose-proportional pharmacokinetics and first-order elimination and dose-dependently induced subjective responses starting at the 25 µg dose. A ceiling effect was observed for good drug effects at 100 µg. The 200 µg dose of LSD induced greater ego dissolution than the 100 µg dose and induced significant anxiety. The average duration of subjective effects increased from 6.7 to 11 h with increasing doses of 25–200 µg. LSD moderately increased blood pressure and heart rate. Ketanserin effectively prevented the response to 200 µg LSD. The LSD dose–response curve showed a ceiling effect for subjective good effects, and ego dissolution and anxiety increased further at a dose above 100 µg. These results may assist with dose finding for future LSD research. The full psychedelic effects of LSD are primarily mediated by serotonin 5-HT2A receptor activation.
LncRNA SNHG11 facilitates tumor metastasis by interacting with and stabilizing HIF-1α
Authors: Xu Linguo , Huan Lin , Guo Tianan , Wu Yangjun , Liu Yanfang , Wang Qifeng , Huang Shenglin , Xu Ye , Liang Linhui , He Xianghuo
Published: October 2020

Epigenetic alteration is one of the hallmarks of colorectal cancer (CRC). Many driver genes are regulated by DNA methylation in CRC. However, the role of DNA methylation regulating lncRNAs remain elusive. Here, we identify that SNHG11 (small nucleolar RNA host gene 11) is upregulated by promotor hypomethylation in CRC and is associated with poor prognosis in CRC patients. SNHG11 can promote CRC cell migration and metastasis under hypoxia. Interestingly, the DNA-binding motif of SNHG11 is similar to that of HIF-1α. In addition, SNHG11-associated genes are enriched with members of the HIF-1 signaling pathway in CRC. Mechanistically, SNHG11 binds to the pVHLrecognition sites on HIF-1α, thus blocking the interaction of pVHL with HIF-1α and preventing its ubiquitination and degradation. Moreover, SNHG11 upregulates the expression of HIF-1α target genes, i.e., AK4, ENO1, HK2, and Twist1. Notably, SNHG11 can bind to the HRE sites in the promoter of these genes and increase their transcription. In summary, these results identify a SNHG11/ HIF-1α axis that plays a pivotal role in tumor invasion and metastasis.
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

The 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

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

Objective

To identify Muay Thai participants’ attitudes towards use of mouth guards and their experiences of dental trauma.

Materials and methods

An 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.

Results

92 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.

Conclusion

Given 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

Acute 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

Metastasis 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

The 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

Chronic 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

Protein 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

During 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

The 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

Ending 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

Both 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

A 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

A 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

The 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.
Author Correction: Leptin receptor-expressing neuron Sh2b1 supports sympathetic nervous system and protects against obesity and metabolic disease
Authors: Jiang Lin , Su Haoran , Wu Xiaoyin , Shen Hong , Kim Min-Hyun , Li Yuan , Myers Martin G. , Owyang Chung , Rui Liangyou
Published: October 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Patient outcomes following GPs’ educations about COPD: a cluster randomized controlled trial
Authors: Sandelowsky Hanna , Krakau Ingvar , Modin Sonja , Ställberg Björn , Johansson Sven-Erik , Nager Anna
Published: October 2020

This study aimed to compare patient outcomes following case method learning and traditional lectures as methods for continuing medical education (CME) about chronic obstructive pulmonary disease (COPD) for general practitioners (GPs) in Sweden. In a pragmatic cluster randomized controlled trial, COPD patients (n = 425; case method group n = 209, traditional lectures group n = 216) from 24 primary health care centers replied to questionnaires prior to and 18 months after a 2 × 2-h CME was given to GPs (n = 255). We measured changes in the scores of the Clinical COPD Questionnaire (CCQ), symptoms, needs for disease information, exacerbations, smoking, and use of pulmonary rehabilitation. The changes over time were similar for both CME methods. Patients who had used pulmonary rehabilitation increased from 13.2 to 17.8% (P = 0.04), and prevalence of smoking decreased from 28.9 to 25.1% (P = 0.003). In conclusion, neither of the used CME methods was superior than the other regarding patient outcomes. CME’s primary value may lay in improving GPs’ adherence to guidelines, which should lead to long-term positive changes in patient health.
COVID-19-associated acute kidney injury: consensus report of the 25th Acute Disease Quality Initiative (ADQI) Workgroup
Authors: Nadim Mitra K. , Forni Lui G. , Mehta Ravindra L. , Connor Michael J. , Liu Kathleen D. , Ostermann Marlies , Rimmelé Thomas , Zarbock Alexander , Bell Samira , Bihorac Azra , Cantaluppi Vincenzo , Hoste Eric , Husain-Syed Faeq , Germain Michael J. , Goldstein Stuart L. , Gupta Shruti , Joannidis Michael , Kashani Kianoush , Koyner Jay L. , Legrand Matthieu , Lumlertgul Nuttha , Mohan Sumit , Pannu Neesh , Peng Zhiyong , Perez-Fernandez Xose L. , Pickkers Peter , Prowle John , Reis Thiago , Srisawat Nattachai , Tolwani Ashita , Vijayan Anitha , Villa Gianluca , Yang Li , Ronco Claudio , Kellum John A.
Published: October 2020

Kidney involvement in patients with coronavirus disease 2019 (COVID-19) is common, and can range from the presence of proteinuria and haematuria to acute kidney injury (AKI) requiring renal replacement therapy (RRT; also known as kidney replacement therapy). COVID-19-associated AKI (COVID-19 AKI) is associated with high mortality and serves as an independent risk factor for all-cause in-hospital death in patients with COVID-19. The pathophysiology and mechanisms of AKI in patients with COVID-19 have not been fully elucidated and seem to be multifactorial, in keeping with the pathophysiology of AKI in other patients who are critically ill. Little is known about the prevention and management of COVID-19 AKI. The emergence of regional ‘surges’ in COVID-19 cases can limit hospital resources, including dialysis availability and supplies; thus, careful daily assessment of available resources is needed. In this Consensus Statement, the Acute Disease Quality Initiative provides recommendations for the diagnosis, prevention and management of COVID-19 AKI based on current literature. We also make recommendations for areas of future research, which are aimed at improving understanding of the underlying processes and improving outcomes for patients with COVID-19 AKI.
Timing anticipation in adults and children with Developmental Dyslexia: evidence of an inefficient mechanism
Authors: Pagliarini Elena , Scocchia Lisa , Granocchio Elisa , Sarti Daniela , Stucchi Natale , Guasti Maria Teresa
Published: October 2020

Developmental Dyslexia (DD) is a learning disorder characterized by specific difficulties in learning to read accurately and fluently, which has been generally explained in terms of phonological deficits. Recent research has shown that individuals with DD experience timing difficulties in the domains of language, music perception and motor control, probably due to impaired rhythmic perception, suggesting that timing deficit might be a key underlying factor to explain such a variety of difficulties. The present work presents two experiments aimed at assessing the anticipatory ability on a given rhythm of 9-year old Italian children and Italian adults with and without DD. Both adults and children with DD displayed a greater timing error and were more variable than controls in high predictable stimuli. No difference between participants with and without DD was found in the control condition, in which the uncertain timing of the beat did not permit the extraction of regularities. These results suggest that both children and adults with DD are unable to exploit temporal regularities to efficiently anticipate the next sensory event whereas control participants easily are. By showing that the anticipatory timing system of individuals with Developmental Dyslexia appears affected, this study adds another piece of evidence to the multifaceted reality of Developmental Dyslexia.
Different conformations of the German shepherd dog breed affect its posture and movement
Authors: Humphries A. , Shaheen A. F. , Gómez Álvarez C. B.
Published: October 2020

The conformation of the German shepherd dog (GSD) varies considerably within the breed. These differences may result in large variation in the movement and limb loading and undesirable consequences to their musculoskeletal health. This study aimed to investigate the relationship between conformation and biomechanical measures in 60 GSDs. Full body kinematic and kinetic measures were computed from 3D motion capture and pressure data. The dogs were divided into groups based on their back slope and curvature. Correlation analysis and statistical differences between groups showed that GSDs with a greater back slope have a greater contact area in their forelimbs and place them closer together when standing (n = 60). During trot, the dogs with sloped back showed a greater vertical force in the forelimbs and a greater mid-thoracic flexion (n = 60). Unilateral differences were found in the stifle flexion, hock flexion and hock adduction, suggesting greater movement asymmetry with an increase in the back slope (n = 30). In conclusion, several biomechanical parameters are affected by the GSD’s slope of the back and not by its curvature. Further studies are required to determine whether the variation in movement, posture and conformation within the breed relates to an increased susceptibility to musculoskeletal disorders.
A new class of antimicrobial molecules derived from kefir, effective against Pseudomonas aeruginosa and methicillin resistant Staphylococcus aureus (MRSA) strains
Authors: Marques Vaniky Duarte , Franzolin Marcia Regina , Sanabani Sabri Saeed , Vigerelli Hugo , Piazza Roxane Maria Fontes , Pimenta Daniel Carvalho , Venâncio Tiago , Neves Irys Viana , de Sousa Silva Herbert Guimarães , dos Santos Courrol Daniella , Mendonça-Previato Lucia , Previato José Osvaldo , Jorge Soraia Attie Calil , de Oliveira Domingos Marta
Published: October 2020

Many studies have linked the antimicrobial properties of kefir with the presence of bacteriocins and organic acids. In the present work, results obtained from bacteriostatic and bactericidal studies, and from RP-HPLC, Mass Spectrometry and proton NMR analysis, show that a sample of milk kefir grains is able to produce an antimicrobial fraction, denoted FK-1000, composed of sugars and amino acids, predominantly polymers of alanine, doublets of tyrosine and phenylalanine. Since this fraction is a lyophilized product whose molecular profile is different from bacteriocins and simple carboxylic acids, its antimicrobial effect cannot be attributed to these molecules, or to alcohols or hydrogen peroxide. The fraction is bactericidal against weak-acid-resistant MRSA and weak-acid resistant P. aeruginosa at pH 5, and is bacteriostatic against both pathogens at pH 7. In combination formulation, the FK-1000 fraction is able to increase fivefold the effect of streptomycin against P. aeruginosa and it is not toxic to human epithelial cells at antimicrobial concentrations. 16 S rRNA microbiota analysis of antimicrobial-producing and non-producing kefir grains demonstrated that they are distinct. In summary, the results indicate that milk kefir grains can produce different classes of molecules with potent antibiotic activity against resistant bacteria.
Synthesis and characterization of WS2/graphene/SiC van der Waals heterostructures via WO3−x thin film sulfurization
Authors: Bradford Jonathan , Shafiei Mahnaz , MacLeod Jennifer , Motta Nunzio
Published: October 2020

Van der Waals heterostructures of monolayer transition metal dichalcogenides (TMDs) and graphene have attracted keen scientific interest due to the complementary properties of the materials, which have wide reaching technological applications. Direct growth of uniform, large area TMDs on graphene substrates by chemical vapor deposition (CVD) is limited by slow lateral growth rates, which result in a tendency for non-uniform multilayer growth. In this work, monolayer and few-layer WS2 was grown on epitaxial graphene on SiC by sulfurization of WO3−x thin films deposited directly onto the substrate. Using this method, WS2 growth was achieved at temperatures as low as 700 °C – significantly less than the temperature required for conventional CVD. Achieving long-range uniformity remains a challenge, but this process could provide a route to synthesize a broad range of TMD/graphene van der Waals heterostructures with novel properties and functionality not accessible by conventional CVD growth.