bluuebunny/crossref_metadata_2025 huggingface dataset:
Long non-coding RNA ZFAS1 is a major regulator of epithelial-mesenchymal transition through miR-200/ZEB1/E-cadherin, vimentin signaling in colon adenocarcinoma
Authors: O’Brien Stephen J. , Fiechter Casey , Burton James , Hallion Jacob , Paas Mason , Patel Ankur , Patel Ajay , Rochet Andre , Scheurlen Katharina , Gardner Sarah , Eichenberger Maurice , Sarojini Harshini , Srivastava Sudhir , Rai Shesh , Kalbfleisch Theodore , Polk Hiram C. , Galandiuk Susan
Published: March 2021

Colon adenocarcinoma is a common cause of cancer-related deaths worldwide. Epithelial-mesenchymal transition is a major regulator of cancer metastasis, and increased understanding of this process is essential to improve patient outcomes. Long non-coding RNA (lncRNA) are important regulators of carcinogenesis. To identify lncRNAs associated with colon carcinogenesis, we performed an exploratory differential gene expression analysis comparing paired colon adenocarcinoma and normal colon epithelium using an RNA-sequencing data set. This analysis identified lncRNA ZFAS1 as significantly increased in colon cancer compared to normal colon epithelium. This finding was validated in an institutional cohort using laser capture microdissection. ZFAS1 was also found to be principally located in the cellular cytoplasm. ZFAS1 knockdown was associated with decreased cellular proliferation, migration, and invasion in two colon cancer cell lines (HT29 and SW480). MicroRNA-200b and microRNA-200c (miR-200b and miR-200c) are experimentally validated targets of ZFAS1, and this interaction was confirmed using reciprocal gene knockdown. ZFAS1 knockdown regulated ZEB1 gene expression and downstream targets E-cadherin and vimentin. Knockdown of miR-200b or miR-200c reversed the effect of ZFAS1 knockdown in the ZEB1/E-cadherin, vimentin signaling cascade, and the effects of cellular migration and invasion, but not cellular proliferation. ZFAS1 knockdown was also associated with decreased tumor growth in an in vivo mouse model. These results demonstrate the critical importance of ZFAS1 as a regulator of the miR-200/ZEB1/E-cadherin, vimentin signaling cascade.
Active carpets drive non-equilibrium diffusion and enhanced molecular fluxes
Authors: Guzmán-Lastra Francisca , Löwen Hartmut , Mathijssen Arnold J. T. M.
Published: March 2021

Biological activity is often highly concentrated on surfaces, across the scales from molecular motors and ciliary arrays to sessile and motile organisms. These ‘active carpets’ locally inject energy into their surrounding fluid. Whereas Fick’s laws of diffusion are established near equilibrium, it is unclear how to solve non-equilibrium transport driven by such boundary-actuated fluctuations. Here, we derive the enhanced diffusivity of molecules or passive particles as a function of distance from an active carpet. Following Schnitzer’s telegraph model, we then cast these results into generalised Fick’s laws. Two archetypal problems are solved using these laws: First, considering sedimentation towards an active carpet, we find a self-cleaning effect where surface-driven fluctuations can repel particles. Second, considering diffusion from a source to an active sink, say nutrient capture by suspension feeders, we find a large molecular flux compared to thermal diffusion. Hence, our results could elucidate certain non-equilibrium properties of active coating materials and life at interfaces.
N-protein presents early in blood, dried blood and saliva during asymptomatic and symptomatic SARS-CoV-2 infection
Authors: Shan Dandan , Johnson Joseph M. , Fernandes Syrena C. , Suib Hannah , Hwang Soyoon , Wuelfing Danica , Mendes Muriel , Holdridge Marcella , Burke Elaine M. , Beauregard Katie , Zhang Ying , Cleary Megan , Xu Samantha , Yao Xiao , Patel Purvish P. , Plavina Tatiana , Wilson David H. , Chang Lei , Kaiser Kim M. , Nattermann Jacob , Schmidt Susanne V. , Latz Eicke , Hrusovsky Kevin , Mattoon Dawn , Ball Andrew J.
Published: March 2021

The COVID-19 pandemic continues to have an unprecedented impact on societies and economies worldwide. There remains an ongoing need for high-performance SARS-CoV-2 tests which may be broadly deployed for infection monitoring. Here we report a highly sensitive single molecule array (Simoa) immunoassay in development for detection of SARS-CoV-2 nucleocapsid protein (N-protein) in venous and capillary blood and saliva. In all matrices in the studies conducted to date we observe >98% negative percent agreement and >90% positive percent agreement with molecular testing for days 1–7 in symptomatic, asymptomatic, and pre-symptomatic PCR+ individuals. N-protein load decreases as anti-SARS-CoV-2 spike-IgG increases, and N-protein levels correlate with RT-PCR Ct-values in saliva, and between matched saliva and capillary blood samples. This Simoa SARS-CoV-2 N-protein assay effectively detects SARS-CoV-2 infection via measurement of antigen levels in blood or saliva, using non-invasive, swab-independent collection methods, offering potential for at home and point of care sample collection.
Defective metabolic programming impairs early neuronal morphogenesis in neural cultures and an organoid model of Leigh syndrome
Authors: Inak Gizem , Rybak-Wolf Agnieszka , Lisowski Pawel , Pentimalli Tancredi M. , Jüttner René , Glažar Petar , Uppal Karan , Bottani Emanuela , Brunetti Dario , Secker Christopher , Zink Annika , Meierhofer David , Henke Marie-Thérèse , Dey Monishita , Ciptasari Ummi , Mlody Barbara , Hahn Tobias , Berruezo-Llacuna Maria , Karaiskos Nikos , Di Virgilio Michela , Mayr Johannes A. , Wortmann Saskia B. , Priller Josef , Gotthardt Michael , Jones Dean P. , Mayatepek Ertan , Stenzel Werner , Diecke Sebastian , Kühn Ralf , Wanker Erich E. , Rajewsky Nikolaus , Schuelke Markus , Prigione Alessandro
Published: March 2021

Leigh syndrome (LS) is a severe manifestation of mitochondrial disease in children and is currently incurable. The lack of effective models hampers our understanding of the mechanisms underlying the neuronal pathology of LS. Using patient-derived induced pluripotent stem cells and CRISPR/Cas9 engineering, we developed a human model of LS caused by mutations in the complex IV assembly gene SURF1. Single-cell RNA-sequencing and multi-omics analysis revealed compromised neuronal morphogenesis in mutant neural cultures and brain organoids. The defects emerged at the level of neural progenitor cells (NPCs), which retained a glycolytic proliferative state that failed to instruct neuronal morphogenesis. LS NPCs carrying mutations in the complex I gene NDUFS4 recapitulated morphogenesis defects. SURF1 gene augmentation and PGC1A induction via bezafibrate treatment supported the metabolic programming of LS NPCs, leading to restored neuronal morphogenesis. Our findings provide mechanistic insights and suggest potential interventional strategies for a rare mitochondrial disease.
Loss of bone morphogenetic protein-binding endothelial regulator causes insulin resistance
Authors: Mao Hua , Li Luge , Fan Qiying , Angelini Aude , Saha Pradip K. , Wu Huaizhu , Ballantyne Christie M. , Hartig Sean M. , Xie Liang , Pi Xinchun
Published: March 2021

Accumulating evidence suggests that chronic inflammation of metabolic tissues plays a causal role in obesity-induced insulin resistance. Yet, how specific endothelial factors impact metabolic tissues remains undefined. Bone morphogenetic protein (BMP)–binding endothelial regulator (BMPER) adapts endothelial cells to inflammatory stress in diverse organ microenvironments. Here, we demonstrate that BMPER is a driver of insulin sensitivity. Both global and endothelial cell-specific inducible knockout of BMPER cause hyperinsulinemia, glucose intolerance and insulin resistance without increasing inflammation in metabolic tissues in mice. BMPER can directly activate insulin signaling, which requires its internalization and interaction with Niemann-Pick C1 (NPC1), an integral membrane protein that transports intracellular cholesterol. These results suggest that the endocrine function of the vascular endothelium maintains glucose homeostasis. Of potential translational significance, the delivery of BMPER recombinant protein or its overexpression alleviates insulin resistance and hyperglycemia in high-fat diet-fed mice and Leprdb/db (db/db) diabetic mice. We conclude that BMPER exhibits therapeutic potential for the treatment of diabetes.
Nonlinear machine learning pattern recognition and bacteria-metabolite multilayer network analysis of perturbed gastric microbiome
Authors: Durán Claudio , Ciucci Sara , Palladini Alessandra , Ijaz Umer Z. , Zippo Antonio G. , Sterbini Francesco Paroni , Masucci Luca , Cammarota Giovanni , Ianiro Gianluca , Spuul Pirjo , Schroeder Michael , Grill Stephan W. , Parsons Bryony N. , Pritchard D. Mark , Posteraro Brunella , Sanguinetti Maurizio , Gasbarrini Giovanni , Gasbarrini Antonio , Cannistraci Carlo Vittorio
Published: March 2021

The stomach is inhabited by diverse microbial communities, co-existing in a dynamic balance. Long-term use of drugs such as proton pump inhibitors (PPIs), or bacterial infection such as Helicobacter pylori, cause significant microbial alterations. Yet, studies revealing how the commensal bacteria re-organize, due to these perturbations of the gastric environment, are in early phase and rely principally on linear techniques for multivariate analysis. Here we disclose the importance of complementing linear dimensionality reduction techniques with nonlinear ones to unveil hidden patterns that remain unseen by linear embedding. Then, we prove the advantages to complete multivariate pattern analysis with differential network analysis, to reveal mechanisms of bacterial network re-organizations which emerge from perturbations induced by a medical treatment (PPIs) or an infectious state (H. pylori). Finally, we show how to build bacteria-metabolite multilayer networks that can deepen our understanding of the metabolite pathways significantly associated to the perturbed microbial communities.
TDP-43 and PINK1 mediate CHCHD10S59L mutation–induced defects in Drosophila and in vitro
Authors: Baek Minwoo , Choe Yun-Jeong , Bannwarth Sylvie , Kim JiHye , Maitra Swati , Dorn Gerald W. , Taylor J. Paul , Paquis-Flucklinger Veronique , Kim Nam Chul
Published: March 2021

Mutations in coiled-coil-helix-coiled-coil-helix domain containing 10 (CHCHD10) can cause amyotrophic lateral sclerosis and frontotemporal dementia (ALS-FTD). However, the underlying mechanisms are unclear. Here, we generateCHCH10S59L-mutantDrosophila melanogasterand HeLa cell lines to modelCHCHD10-associated ALS-FTD. TheCHCHD10S59Lmutation results in cell toxicity in several tissues and mitochondrial defects.CHCHD10S59Lindependently affects the TDP-43 and PINK1 pathways.CHCHD10S59Lexpression increases TDP-43 insolubility and mitochondrial translocation. Blocking TDP-43 mitochondrial translocation with a peptide inhibitor reducedCHCHD10S59L-mediated toxicity. While genetic and pharmacological modulation ofPINK1expression and activity of its substrates rescues and mitigates theCHCHD10S59L-induced phenotypes and mitochondrial defects, respectively, in bothDrosophilaand HeLa cells. Our findings suggest thatCHCHD10S59L-induced TDP-43 mitochondrial translocation and chronic activation of PINK1-mediated pathways result in dominant toxicity, providing a mechanistic insight into theCHCHD10mutations associated with ALS-FTD.
The Burkholderia pseudomallei intracellular ‘TRANSITome’
Authors: Heacock-Kang Yun , McMillan Ian A. , Norris Michael H. , Sun Zhenxin , Zarzycki-Siek Jan , Bluhm Andrew P. , Cabanas Darlene , Norton Robert E. , Ketheesan Natkunam , Miller Jeff F. , Schweizer Herbert P. , Hoang Tung T.
Published: March 2021

Prokaryotic cell transcriptomics has been limited to mixed or sub-population dynamics and individual cells within heterogeneous populations, which has hampered further understanding of spatiotemporal and stage-specific processes of prokaryotic cells within complex environments. Here we develop a ‘TRANSITomic’ approach to profile transcriptomes of single Burkholderia pseudomallei cells as they transit through host cell infection at defined stages, yielding pathophysiological insights. We find that B. pseudomallei transits through host cells during infection in three observable stages: vacuole entry; cytoplasmic escape and replication; and membrane protrusion, promoting cell-to-cell spread. The B. pseudomallei ‘TRANSITome’ reveals dynamic gene-expression flux during transit in host cells and identifies genes that are required for pathogenesis. We find several hypothetical proteins and assign them to virulence mechanisms, including attachment, cytoskeletal modulation, and autophagy evasion. The B. pseudomallei ‘TRANSITome’ provides prokaryotic single-cell transcriptomics information enabling high-resolution understanding of host-pathogen interactions.
Formation of large low shear velocity provinces through the decomposition of oxidized mantle
Authors: Wang Wenzhong , Liu Jiachao , Zhu Feng , Li Mingming , Dorfman Susannah M. , Li Jie , Wu Zhongqing
Published: March 2021

Large Low Shear Velocity Provinces (LLSVPs) in the lowermost mantle are key to understanding the chemical composition and thermal structure of the deep Earth, but their origins have long been debated. Bridgmanite, the most abundant lower-mantle mineral, can incorporate extensive amounts of iron (Fe) with effects on various geophysical properties. Here our high-pressure experiments and ab initio calculations reveal that a ferric-iron-rich bridgmanite coexists with an Fe-poor bridgmanite in the 90 mol% MgSiO3–10 mol% Fe2O3 system, rather than forming a homogeneous single phase. The Fe3+-rich bridgmanite has substantially lower velocities and a higher VP/VS ratio than MgSiO3 bridgmanite under lowermost-mantle conditions. Our modeling shows that the enrichment of Fe3+-rich bridgmanite in a pyrolitic composition can explain the observed features of the LLSVPs. The presence of Fe3+-rich materials within LLSVPs may have profound effects on the deep reservoirs of redox-sensitive elements and their isotopes.
Evaluating the economic impact of water scarcity in a changing world
Authors: Dolan Flannery , Lamontagne Jonathan , Link Robert , Hejazi Mohamad , Reed Patrick , Edmonds Jae
Published: March 2021

Water scarcity is dynamic and complex, emerging from the combined influences of climate change, basin-level water resources, and managed systems’ adaptive capacities. Beyond geophysical stressors and responses, it is critical to also consider how multi-sector, multi-scale economic teleconnections mitigate or exacerbate water shortages. Here, we contribute a global-to-basin-scale exploratory analysis of potential water scarcity impacts by linking a global human-Earth system model, a global hydrologic model, and a metric for the loss of economic surplus due to resource shortages. We find that, dependent on scenario assumptions, major hydrologic basins can experience strongly positive or strongly negative economic impacts due to global trade dynamics and market adaptations to regional scarcity. In many cases, market adaptation profoundly magnifies economic uncertainty relative to hydrologic uncertainty. Our analysis finds that impactful scenarios are often combinations of standard scenarios, showcasing that planners cannot presume drivers of uncertainty in complex adaptive systems.
Neural alignment predicts learning outcomes in students taking an introduction to computer science course
Authors: Meshulam Meir , Hasenfratz Liat , Hillman Hanna , Liu Yun-Fei , Nguyen Mai , Norman Kenneth A. , Hasson Uri
Published: March 2021

Despite major advances in measuring human brain activity during and after educational experiences, it is unclear how learners internalize new content, especially in real-life and online settings. In this work, we introduce a neural approach to predicting and assessing learning outcomes in a real-life setting. Our approach hinges on the idea that successful learning involves forming the right set of neural representations, which are captured in canonical activity patterns shared across individuals. Specifically, we hypothesized that learning is mirrored in neural alignment: the degree to which an individual learner’s neural representations match those of experts, as well as those of other learners. We tested this hypothesis in a longitudinal functional MRI study that regularly scanned college students enrolled in an introduction to computer science course. We additionally scanned graduate student experts in computer science. We show that alignment among students successfully predicts overall performance in a final exam. Furthermore, within individual students, we find better learning outcomes for concepts that evoke better alignment with experts and with other students, revealing neural patterns associated with specific learned concepts in individuals.
Microwave resonances of magnetic skyrmions in thin film multilayers
Authors: Satywali Bhartendu , Kravchuk Volodymyr P. , Pan Liqing , Raju M. , He Shikun , Ma Fusheng , Petrović A. P. , Garst Markus , Panagopoulos Christos
Published: March 2021

Non-collinear magnets exhibit a rich array of dynamic properties at microwave frequencies. They can host nanometre-scale topological textures known as skyrmions, whose spin resonances are expected to be highly sensitive to their local magnetic environment. Here, we report a magnetic resonance study of an [Ir/Fe/Co/Pt] multilayer hosting Néel skyrmions at room temperature. Experiments reveal two distinct resonances of the skyrmion phase during in-plane ac excitation, with frequencies between 6–12 GHz. Complementary micromagnetic simulations indicate that the net magnetic dipole moment rotates counterclockwise (CCW) during both resonances. The magnon probability distribution for the lower-frequency resonance is localised within isolated skyrmions, unlike the higher-frequency mode which principally originates from areas between skyrmions. However, the properties of both modes depend sensitively on the out-of-plane dipolar coupling, which is controlled via the ferromagnetic layer spacing in our heterostructures. The gyrations of stable isolated skyrmions reported in this room temperature study encourage the development of new material platforms and applications based on skyrmion resonances. Moreover, our material architecture enables the resonance spectra to be tuned, thus extending the functionality of such applications over a broadband frequency range.
Brown and beige adipose tissue regulate systemic metabolism through a metabolite interorgan signaling axis
Authors: Whitehead Anna , Krause Fynn N. , Moran Amy , MacCannell Amanda D. V. , Scragg Jason L. , McNally Ben D. , Boateng Edward , Murfitt Steven A. , Virtue Samuel , Wright John , Garnham Jack , Davies Graeme R. , Dodgson James , Schneider Jurgen E. , Murray Andrew J. , Church Christopher , Vidal-Puig Antonio , Witte Klaus K. , Griffin Julian L. , Roberts Lee D.
Published: March 2021

Brown and beige adipose tissue are emerging as distinct endocrine organs. These tissues are functionally associated with skeletal muscle, adipose tissue metabolism and systemic energy expenditure, suggesting an interorgan signaling network. Using metabolomics, we identify 3-methyl-2-oxovaleric acid, 5-oxoproline, and β-hydroxyisobutyric acid as small molecule metabokines synthesized in browning adipocytes and secreted via monocarboxylate transporters. 3-methyl-2-oxovaleric acid, 5-oxoproline and β-hydroxyisobutyric acid induce a brown adipocyte-specific phenotype in white adipocytes and mitochondrial oxidative energy metabolism in skeletal myocytes both in vitro and in vivo. 3-methyl-2-oxovaleric acid and 5-oxoproline signal through cAMP-PKA-p38 MAPK and β-hydroxyisobutyric acid via mTOR. In humans, plasma and adipose tissue 3-methyl-2-oxovaleric acid, 5-oxoproline and β-hydroxyisobutyric acid concentrations correlate with markers of adipose browning and inversely associate with body mass index. These metabolites reduce adiposity, increase energy expenditure and improve glucose and insulin homeostasis in mouse models of obesity and diabetes. Our findings identify beige adipose-brown adipose-muscle physiological metabokine crosstalk.
Author Correction: AdipoR1/AdipoR2 dual agonist recovers nonalcoholic steatohepatitis and related fibrosis via endoplasmic reticulum-mitochondria axis
Authors: Xu Hongjiao , Zhao Qian , Song Nazi , Yan Zhibin , Lin Runfeng , Wu Shuohan , Jiang Lili , Hong Sihua , Xie Junqiu , Zhou Huihao , Wang Rui , Jiang Xianxing
Published: March 2021

A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-22414-7
The inherent uncertainty of temporal networks is a true challenge for control
Authors: De Lellis Pietro , Di Meglio Anna , Garofalo Franco , Lo Iudice Francesco
Published: March 2021

Recently, it has been suggested that network temporality can be exploited to substantially reduce the energy required to control complex networks. This somewhat counterintuitive finding was explained through an evocative example of the advantage of temporal networks: when navigating a sailboat, we raise the sails when the wind helps us while lowering them when it works against us. Unfortunately, controlling complex networks inherits a further analogy with navigating a sailboat: having to face the inherent uncertainty of future winds. We rarely, if ever, have deterministic knowledge of the evolution of the network we want to control. Here, our challenge is to exploit the potential advantages of temporality when only a probabilistic description of the future is available. We prove that, in this more realistic setting, exploiting temporality is no more a panacea for network control, but rather an asset of a wider toolbox made available by the scientific community. One that can indeed turn out useful, provided that the temporality of the network structure matches the intrinsic time scales of the nodes we want to control.
Microsurgical resection of fronto-temporo-insular gliomas in the non-dominant hemisphere, under general anesthesia using adjunct intraoperative MRI and no cortical and subcortical mapping: a series of 20 consecutive patients
Authors: Leroy Henri-Arthur , Strachowksi Ondine , Tuleasca Constantin , Vannod-Michel Quentin , Le Rhun Emilie , Derre Benoit , Lejeune Jean-Paul , Reyns Nicolas
Published: March 2021

Fronto-temporo-insular (FTI) gliomas continue to represent a surgical challenge despite numerous technical advances. Some authors advocate for surgery in awake condition even for non-dominant hemisphere FTI, due to risk of sociocognitive impairment. Here, we report outcomes in a series of patients operated using intraoperative magnetic resonance imaging (IoMRI) guided surgery under general anesthesia, using no cortical or subcortical mapping. We evaluated the extent of resection, functional and neuropsychological outcomes after IoMRI guided surgery under general anesthesia of FTI gliomas located in the non-dominant hemisphere. Twenty patients underwent FTI glioma resection using IoMRI in asleep condition. Seventeen tumors were de novo, three were recurrences. Tumor WHO grades were II:12, III:4, IV:4. Patients were evaluated before and after microsurgical resection, clinically, neuropsychologically (i.e., social cognition) and by volumetric MR measures (T1G+ for enhancing tumors, FLAIR for non-enhancing). Fourteen (70%) patients benefited from a second IoMRI. The median age was 33.5 years (range 24–56). Seizure was the inaugural symptom in 71% of patients. The median preoperative volume was 64.5 cm3 (min 9.9, max 211). Fourteen (70%) patients underwent two IoMRI. The final median EOR was 92% (range 69–100). The median postoperative residual tumor volume (RTV) was 4.3 cm3 (range 0–38.2). A vast majority of residual tumors were located in the posterior part of the insula. Early postoperative clinical events (during hospital stay) were three transient left hemiparesis (which lasted less than 48 h) and one prolonged left brachio-facial hemiparesis. Sixty percent of patients were free of any symptom at discharge. The median Karnofsky Performance Score was of 90 both at discharge and at 3 months. No significant neuropsychological impairment was reported, excepting empathy distinction in less than 40% of patients. After surgery, 45% of patients could go back to work. In our experience and using IoMRI as an adjunct, microsurgical resection of non-dominant FTI gliomas under general anesthesia is safe. Final median EOR was 92%, with a vast majority of residual tumors located in the posterior insular part. Patients experienced minor neurological and neuropsychological morbidity. Moreover, neuropsychological evaluation reported a high preservation of sociocognitive abilities. Solely empathy seemed to be impaired in some patients.
RETRACTED ARTICLE: Noninvasive thrombectomy of graft by nano-magnetic ablating particles
Authors: Moghanizadeh Abbas , Ashrafizadeh Fakhreddin , Varshosaz Jaleh , Kharaziha Mahshid , Ferreira Antoine
Published: March 2021

Artificial vascular treatment is an emerging interdisciplinary subject of medicine. Although the use of artificial vessels has led to many successful advancements, blood clotting remains a major challenge, especially in terms of mural clots created along the vessel wall that do not completely block the vessel. The main objective of this study is to present a method for declotting artificial vessels. This research introduces a novel thrombectomy technique in artificial vessels by employing nano-magnetic particles under a rotating magnetic field to remove mural clots in artificial vessels. A mathematical model describes the relationship between process parameters. In vitro tests confirm the feasibility of nano-magnetic thrombectomy in cleaning and declotting artificial vessels. The results show that the clot fragments are nano-sized, which eliminates the risk of distal emboli as a concern of using current atherectomy techniques. Meanwhile, no damage to the artificial vessels is observed. The results show that the frequency of rotating the magnetic field has the greatest effect on clot removal. The conceptual principles stated in this study also have the potential to be used in other vascular depositions, such as the accumulation of lipids, and calcification atherosclerosis.
Glutathione ethyl ester reverses the deleterious effects of fentanyl on ventilation and arterial blood-gas chemistry while prolonging fentanyl-induced analgesia
Authors: Jenkins Michael W. , Khalid Faiza , Baby Santhosh M. , May Walter J. , Young Alex P. , Bates James N. , Cheng Feixiong , Seckler James M. , Lewis Stephen J.
Published: March 2021

There is an urgent need to develop novel compounds that prevent the deleterious effects of opioids such as fentanyl on minute ventilation while, if possible, preserving the analgesic actions of the opioids. We report that L-glutathione ethyl ester (GSHee) may be such a novel compound. In this study, we measured tail flick latency (TFL), arterial blood gas (ABG) chemistry, Alveolar-arterial gradient, and ventilatory parameters by whole body plethysmography to determine the responses elicited by bolus injections of fentanyl (75 μg/kg, IV) in male adult Sprague–Dawley rats that had received a bolus injection of GSHee (100 μmol/kg, IV) 15 min previously. GSHee given alone had minimal effects on TFL, ABG chemistry and A-a gradient whereas it elicited changes in some ventilatory parameters such as an increase in breathing frequency. In vehicle-treated rats, fentanyl elicited (1) an increase in TFL, (2) decreases in pH, pO2and sO2and increases in pCO2(all indicative of ventilatory depression), (3) an increase in Alveolar-arterial gradient (indicative of a mismatch in ventilation-perfusion in the lungs), and (4) changes in ventilatory parameters such as a reduction in tidal volume, that were indicative of pronounced ventilatory depression. In GSHee-pretreated rats, fentanyl elicited a more prolonged analgesia, relatively minor changes in ABG chemistry and Alveolar-arterial gradient, and a substantially milder depression of ventilation. GSHee may represent an effective member of a novel class of thiolester drugs that are able to prevent the ventilatory depressant effects elicited by powerful opioids such as fentanyl and their deleterious effects on gas-exchange in the lungs without compromising opioid analgesia.
Extracellular vesicles are associated with C-reactive protein in sepsis
Authors: Fendl Birgit , Weiss René , Eichhorn Tanja , Linsberger Ingrid , Afonyushkin Taras , Puhm Florian , Binder Christoph J. , Fischer Michael B. , Weber Viktoria
Published: March 2021

There is increasing evidence that C-reactive protein (CRP) can mediate inflammatory reactions following the transformation of functionally inert pentameric CRP (pCRP) into its structural isoform pCRP* and into monomeric CRP (mCRP). This conversion can occur on the membranes of apoptotic or activated cells or on extracellular vesicles (EVs) shed from the cell surface. Here, we characterized the association of CRP with EVs in plasma from sepsis patients using flow cytometry, and found highly elevated levels of total EV counts and CRP+ EVs as compared to healthy individuals. We further assessed the ability of PentraSorb CRP, an extracorporeal device for the adsorption of CRP, to deplete free CRP and CRP+ EVs. Treatment of septic plasma with the adsorbent in vitro resulted in almost complete removal of both, free CRP and CRP+ EVs, while total EV counts remained largely unaffected, indicating the detachment of CRP from the EV surface. EVs from septic plasma elicited a release of interleukin-8 from cultured human monocytes, which was significantly reduced by adsorbent treatment prior to EV isolation. Our findings provide evidence that CRP+ EVs exhibit pro-inflammatory characteristics and can contribute to the spreading of inflammation throughout the circulation on top of their pro-coagulant activity.
Author Correction: UV induced resistive switching in hybrid polymer metal oxide memristors
Authors: Stathopoulos Spyros , Tzouvadaki Ioulia , Prodromakis Themis
Published: March 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Controlling properties of thermogels by tuning critical solution behaviour of ternary copolymers
Authors: Smith Anton A. A. , Maikawa Caitlin L. , Lopez Hernandez Hector , Appel Eric A.
Published: March 2021

Thermogelling tri-block terpolymers were made from a bifunctional PEG RAFT agent. The critical solution behavior was tunable by alteration of the terpolymer composition, enabling modulation of gelation temperatures and hydrogel viscoelasticity.
Rational strategies toward efficient and stable lead-free tin halide perovskite solar cells
Authors: He Dongxu , Shen Liang , Bai Yang , Wang Lianzhou
Published: March 2021

We summarized the recent reported strategies for overcoming the challenges for lead-free tin halide perovskite solar cells (THPSCs), expecting to give a perspective outlining the possible future direction for THPSCs.
Inhibiting quinolone biosynthesis of Burkholderia
Authors: Prothiwa Michaela , Filz Verena , Oehler Sebastian , Böttcher Thomas
Published: March 2021

Competitive profiling with a chemical probe against the central quinolone biosynthesis enzyme HmqD results in inhibitors that quantitatively block quinolone production in Burkholderia.
Stepwise collapse of a giant pore metal–organic framework
Authors: Sapnik Adam F. , Johnstone Duncan N. , Collins Sean M. , Divitini Giorgio , Bumstead Alice M. , Ashling Christopher W. , Chater Philip A. , Keeble Dean S. , Johnson Timothy , Keen David A. , Bennett Thomas D.
Published: March 2021

Defect engineering is used to augment the porosity of MIL-100. Incorporation of defects leads to structural collapse and ultimately causes amorphisation. Pair distribution function analysis reveals a stepwise collapse of the hierarchical structure.
Docosahexaenoic acid-enriched phospholipids and eicosapentaenoic acid-enriched phospholipids inhibit tumor necrosis factor-alpha-induced lipolysis in 3T3-L1 adipocytes by activating sirtuin 1 pathways
Authors: Yang Yu-Hong , Hao Yi-Ming , Liu Xiao-Fang , Gao Xiang , Wang Bao-Zhen , Takahashi Koretaro , Du Lei
Published: March 2021

DHA-PL and EPA-PL have potential benefits for the treatment of cancer-associated cachexia and obesity-related metabolic disorders.
Evolution of cocoa flavanol analytics: impact on reporting and cross-study comparison
Authors: Bussy Ugo , Ottaviani Javier I. , Kwik-Uribe Catherine
Published: March 2021

Cocoa flavanols (CF) are a group of dietary bioactives that have been studied for over two decades. In this time, methods for CF testing have evolved, introducing the potential for differences in reported CF content.
Facile preparation of a phenyl-reinforced flexible silica aerogel with excellent thermal stability and fire resistance
Authors: Zhang Yu , Shen Qianqian , Li Xuesha , Wang Lili , Nie Chaoyin
Published: March 2021

A phenyl-reinforced flexible silica aerogel was synthesized using PTES as a reinforcer; the membrane-like structure derived from PTES improved the mechanical and thermal properties of the flexible silica aerogel.
Kinetic resolution of 2-aryl-2,3-dihydroquinolin-4(1H)-one derivatives by rhodium-catalysed asymmetric transfer hydrogenation
Authors: He Bin , Phansavath Phannarath , Ratovelomanana-Vidal Virginie
Published: March 2021

An efficient rhodium-catalysed kinetic resolution of 2-aryl-2,3-dihydroquinolin-4(1H)-one derivatives through asymmetric transfer hydrogenation.
Difluorination of α-(bromomethyl)styrenes via I(I)/I(III) catalysis: facile access to electrophilic linchpins for drug discovery
Authors: Häfliger Joel , Livingstone Keith , Daniliuc Constantin G. , Gilmour Ryan
Published: March 2021

Simple α-(bromomethyl)styrenes can be processed to a variety of 1,1-difluorinated electrophilic building blocks via I(I)/I(III) catalysis.
The way to the heart of diabetes is through your gut
Authors: Bewick Gavin , Jacobs Margot
Published: March 2021

The gut is famously known for its function in food digestion and absorption, but what if we told you that it is also involved in diseases like diabetes? Diabetes is a metabolic disease, which affects over 460 million adults worldwide, where the body struggles to regulate blood glucose levels. The gut releases hormones that help control glucose levels and, when severely obese patients with type 2 diabetes undergo a bypass surgery that rearranges their gut, they see independent weight loss and glucose improvements. Although various treatments are available for patients who suffer from diabetes, there are still many unresolved questions concerning its pathology which means we are yet to find a cure. This article explores how organoids, a 3D stem cell-derived model also known as a mini-organ, might be employed to study the gut’s role in diabetes. Intestinal organoids serve as an effective new model to better understand the disease, thanks to its ability in enabling the cells to arrange in a way that closely resembles the human gut. Using intestinal organoids in diabetes research could lead to new treatment options which are necessary in order to improve the lives of those whose are affected by diabetes every day.
Adaptive blind equalization of fast time‐varying channel with frequency estimation in impulsive noise environment
Authors: Zhang Yijiao , Tian Shulin , Pan Huiqing , Zhou Yi
Published: March 2021

In this paper, a novel source signal recovery method for fast time‐varying channels described by complex exponential‐basis expansion model (CE‐BEM) in the impulsive noise environment is proposed. This method consists of two phases. The first phase is the equalization of fast time‐varying channels, in this phase, a novel algorithm FSE‐FLOS‐CMA is proposed. The convergence performance of this newly proposed algorithm is much better than that of existing fractionally spaced equalizer‐constant modulus algorithm (FSE‐CMA) in impulsive noise environment. In the second phase, a novel frequency estimation method is proposed. The estimated frequency in impulsive noise environment is obtained by calculating a specific p‐order fractional low‐order cyclic moment of the equalized signal. Simulation results show that the proposed FSE‐FLOS‐CMA and frequency estimation method can effectively estimate the source signals transmitted through the fast time‐varying channels in impulsive noise environment.
Low latency group‐sorted QR decomposition algorithm for larger‐scale MIMO systems
Authors: Chen Lirui , Wang Yu , Xing Zuocheng , Qiu Shikai , Wang Qinglin , Li Yongzhong
Published: March 2021

Sorted QR decomposition (SQRD) has been extensively adopted for various multiple‐input‐multiple‐output (MIMO) detectors, in which the sorting process incurs severe latency when it comes to larger‐scale MIMO situations. This paper proposes a group‐SQRD (GSQRD) algorithm to alleviate the latency problem of general SQRD architectures for larger‐scale MIMO systems. Via predictively sorting a group of 4 columns at one stage, the GSQRD could eliminate the processing latency by 41% for decomposing 1616 complex‐valued matrices. Additionally, this percentage even rises up to 68% for decomposing 128128 matrices. To analyse the side effects, the GSQRD is applied in various MIMO detectors in a simulation link, which exhibits a negligible performance degradation for MIMO detection. Moreover, GSQRD is a hardware‐friendly algorithm because the division and square root operations in GSQRD are converted to multiplications for simplifying the hardware implementation. Based on this algorithm, two corresponding hardware architectures, which contains 2 and 4 columns respectively in a sorting group, are also implemented with 65‐nm CMOS technology. These architectures can work at 513 MHz to decompose 1616 complex‐valued matrices. The processing latencies are respectively 0.32 and 0.26 s, superior to the state‐of‐art designs.
Innovative system services for facilitating the integration of high levels of renewable generation in Ireland and Northern Ireland
Authors: Delaney Niamh , Deegan Joseph , Val Escudero Marta , O'Sullivan Jonathan
Published: March 2021

Variable renewable generation technologies such as wind and solar photovoltaic have introduced new challenges in power system management. Grid operators have traditionally used ancillary services such as reserve and reactive power to help to maintain a secure and reliable power system. In addition, conventional synchronous generators have inherent characteristics such as inertial response, which help the power system to recover after an event. In Ireland and Northern Ireland, a weakly‐interconnected island system with a high penetration of wind, new ancillary or ‘system’ services have been devised to address the technical scarcities arising from the displacement of synchronous generation. Twelve system services addressing the frequency and voltage control needs have been procured to date, allowing the power system to be operated with up to 65% instantaneous non‐synchronous renewable power on the system. This study outlines the implementation of the innovative system services framework. It includes an overview of the services procured and examples of the changed behaviour of existing units in response to financial incentives. It also examines how new technologies have responded to the signals provided, questions how aspects of the arrangements may be further improved and details the challenges of integrating the use of these innovative services into operational policy.
Differences in phosphorus acquisition and critical phosphorus requirements among nine
Authors: McLachlan Jonathan W. , Guppy Chris N. , Flavel Richard J.
Published: March 2021

The extensive grazing systems of northern Australia are dominated by C4 grasses and are established in N- and P-responsive soils that receive minimal nutrient input. Under these conditions, tropical pasture legumes are expected to improve the quality of grazing forage and fix atmospheric N2. However, legume persistence is relatively poor, which may be due to a presumed disparity in P requirements among tropical pasture species. This disparity suggests that P-efficient legumes may improve legume persistence, yet the P requirements of many tropical pasture legumes remain unquantified. Nine Desmanthus spp. genotypes were grown in pots to determine differences in shoot yield and root morphology in response to soil P supply (0–100 mg applied P kg–1 soil; 5–63 mg Colwell P kg–1 soil). The shoot yield of each genotype increased in response to increased P supply. When P supply was adequate for maximum plant growth, the shoot yield of the best genotype (3.5 g DM pot–1; JCU 9) was 1.7-fold larger than that of the next most productive genotype. There were also substantial differences in the critical external P requirements of the genotypes (29.4–64.0 mg P kg–1 soil), although these differences did not always reflect the efficiency of dry matter production per unit of applied P fertiliser. Differences in shoot yield and P acquisition were positively associated with differences in the development of root length. The results indicated that P-efficient genotypes of Desmanthus spp. can be identified for improved growth in the P-responsive pastures of northern Australia. These genotypes may compete more effectively with C4 grasses and form resilient pasture swards as climate patterns change.
Genome-wide phylogenetic study of Percomorpha providing robust support for previous molecular classification
Authors: Shou Chenyan , Han Zhiqiang
Published: March 2021

Percomorpha is the major branch of Actinopteri, comprising most of the acanthopterygian fishes. The relationships among different Percomorpha groups remain uncertain because of high species diversity, thereby creating challenges for phylogenetic studies on teleosts. The phylogenetic problems of Percomorpha have not been solved using mitochondrial genes and a few nuclear genes. In this study, genomes from 34 representative species from the 7 major taxa of Percomorpha were selected to solve this problem. In all, 29 592 conserved amino acid sites from 206 single-copy orthologous genes were chosen for the reconstruction of phylogenetic trees. The results showed that Gobiaria, whose position is different from that in previous studies, was the earliest branching lineage. The phylogenetic groups in this study were consistent with previous results using mitochondrial DNA and nuclear genes. Thus, this study provides a new perspective and directions for further research on the Percomorpha branch and other higher-order meta-taxonomic relationships of fish. The genome data obtained may be essential for future investigations of phylogeny and molecular evolution.
Centaurea iberica (Iberian starthistle).
Authors: Roché Cindy
Published: March 2021

C. iberica appears to be somewhat weedy in its native environment, but is less aggressively invasive elsewhere than other Centaurea species. The only South American country where it appears to have established as an invasive alien is Argentina. It has been introduced in Europe and North America, but has either failed to persist or eradication efforts have been successful to some degree. Only in California has eradication not been achieved. Introductions in Wyoming and Oregon have not expanded rapidly. In its native range, various uses in folk medicine are proving to have a scientific basis. C. iberica is on prohibited weed lists in Chile and Australia; and is a Class A noxious weed in California and Oregon, and a prohibited noxious weed in Arizona, Nevada and Wyoming.
Digitaria insularis (sourgrass).
Authors: Parker Chris
Published: March 2021

D. insularis is an aggressive perennial grass causing major weed problems in its native area, especially in Brazil, Paraquay and Bolivia. It was classed as a principal weed in Venezuela by Holm et al. (1979). It is a major weed where introduced to pastures in Hawaii, USA (Kuswata Kartawinata and Mueller-Dombois, 1972); also in Papua New Guinea (Chadhokar, 1978). In Hawaii, a weed risk assessment based on the Australia/New Zealand model rated the species at 20, i.e. high risk (PIER, 2012).
Eragrostis unioloides (Chinese lovegrass).
Authors: Duenas-Lopez Manuel Angel
Published: March 2021

Eragrostis unioloides is an annual grass or sometimes perennial, erect herb, rooting at nodes. Terrestrial, it grows in many dry as well as moist habitats. It is distributed in temperate and tropical Asia from southern Asia to Malesia and northeast Australia. It has been introduced in the southeast USA, Mesoamerica, the Caribbean, the Pacific Islands and in tropical West Africa. It is a common weedy grass mainly in rice crops in its native range and in some crops in the Caribbean region. It is found principally in disturbed sites, such as roadsides and in damp places in its distribution range. It is cited as invasive in Fiji, the Hawaiian Islands and Mexico, but no further information is available about its impacts in natural habitats or on biodiversity in its non-native range.
Sida acuta (sida).
Authors: Rojas-Sandoval Julissa , Acevedo-Rodríguez Pedro , Clements David
Published: March 2021

Originating in central America, the small perennial shrub, S. acuta has successfully invaded the tropics worldwide, largely as a contaminant in pasture seed. Its tolerance of a wide range of growing conditions has enabled S. acuta to become established in these diverse habitats. It infests various crops and habitats, but has been most problematic in pastures and rangelands, particularly in savannah-type biomes with pronounced wet and dry seasons. It can form dense monospecific stands in these regions, and has had a pronounced economic impact in northern Australia, Papua New Guinea and many Pacific Islands. Since the late 1980s, the foliage-feeding chrysomelid beetle Calligrapha pantherina has been introduced into many areas as a biological control agent specific to S. acuta and related Sida species. Introductions of C. pantherina have led to successes in control of S. acuta infestations, reducing seed production, and resulting in restoration of native vegetation in many cases.
Is musculoskeletal pain related to locomotive syndrome even in young and middle-aged adults?
Authors: Kato Toshihiro , Nishimura Akinobu , Ohtsuki Makoto , Wakasugi Yusuke , Nagao-Nishiwaki Rie , Fukuda Aki , Kato Ko , Sudo Akihiro
Published: March 2021

Objectives

Locomotive syndrome (LS) is the leading cause of persons needing long-term care in old age and is characterized by locomotive organ impairment including musculoskeletal pain. The aim was to examine the association between musculoskeletal pain and LS in young and middle-aged persons.

Methods

A total of 836 participants (male 667, female 169; mean age 44.4 years) were examined in this cross-sectional study. The LS was evaluated by three screening tools: the two-step test, the stand-up test, and the 25-question Geriatric Locomotive Function Scale. Musculoskeletal pain, exercise habits, physical function (walkability and muscle strength), and physical activity were also assessed.

Results

The LS was found in 22.8% of participants. The number with musculoskeletal pain was significantly higher in those with the LS. A significant correlation was found between the degree of musculoskeletal pain and exercise habits. Less regular exercise was significantly associated with higher LS prevalence. Physical activity and function were greater in participants with more regular exercise.

Conclusion

Musculoskeletal pain was significantly related to LS even in young and middle-aged persons. The present results suggest that control of musculoskeletal pain and improvement of exercise habits in young and middle-aged persons might help prevent the LS.