bluuebunny/crossref_metadata_2025_split huggingface dataset:
The biosynthetic pathway of potato solanidanes diverged from that of spirosolanes due to evolution of a dioxygenase
Authors: Akiyama Ryota , Watanabe Bunta , Nakayasu Masaru , Lee Hyoung Jae , Kato Junpei , Umemoto Naoyuki , Muranaka Toshiya , Saito Kazuki , Sugimoto Yukihiro , Mizutani Masaharu 
Published: February 2021

AbstractPotato (Solanum tuberosum), a worldwide major food crop, produces the toxic, bitter tasting solanidane glycoalkaloids α-solanine and α-chaconine. Controlling levels of glycoalkaloids is an important focus on potato breeding. Tomato (Solanum lycopersicum) contains a bitter spirosolane glycoalkaloid, α-tomatine. These glycoalkaloids are biosynthesized from cholesterol via a partly common pathway, although the mechanisms giving rise to the structural differences between solanidane and spirosolane remained elusive. Here we identify a 2-oxoglutarate dependent dioxygenase, designated as DPS (Dioxygenase for Potato Solanidane synthesis), that is a key enzyme for solanidane glycoalkaloid biosynthesis in potato. DPS catalyzes the ring-rearrangement from spirosolane to solanidane via C-16 hydroxylation. Evolutionary divergence of spirosolane-metabolizing dioxygenases contributes to the emergence of toxic solanidane glycoalkaloids in potato and the chemical diversity in Solanaceae.
Association between antecedent statin use and decreased mortality in hospitalized patients with COVID-19
Authors: Gupta Aakriti , Madhavan Mahesh V. , Poterucha Timothy J. , DeFilippis Ersilia M. , Hennessey Jessica A. , Redfors Bjorn , Eckhardt Christina , Bikdeli Behnood , Platt Jonathan , Nalbandian Ani , Elias Pierre , Cummings Matthew J. , Nouri Shayan N. , Lawlor Matthew , Ranard Lauren S. , Li Jianhua , Boyle Claudia , Givens Raymond , Brodie Daniel , Krumholz Harlan M. , Stone Gregg W. , Sethi Sanjum S. , Burkhoff Daniel , Uriel Nir , Schwartz Allan , Leon Martin B. , Kirtane Ajay J. , Wan Elaine Y. , Parikh Sahil A. 
Published: February 2021

AbstractThe coronavirus disease 2019 (COVID-19) can result in a hyperinflammatory state, leading to acute respiratory distress syndrome (ARDS), myocardial injury, and thrombotic complications, among other sequelae. Statins, which are known to have anti-inflammatory and antithrombotic properties, have been studied in the setting of other viral infections, but their benefit has not been assessed in COVID-19. This is a retrospective analysis of patients admitted with COVID-19 from February 1st through May 12th, 2020 with study period ending on June 11th, 2020. Antecedent statin use was assessed using medication information available in the electronic medical record. We constructed a multivariable logistic regression model to predict the propensity of receiving statins, adjusting for baseline sociodemographic and clinical characteristics, and outpatient medications. The primary endpoint includes in-hospital mortality within 30 days. A total of 2626 patients were admitted during the study period, of whom 951 (36.2%) were antecedent statin users. Among 1296 patients (648 statin users, 648 non-statin users) identified with 1:1 propensity-score matching, statin use is significantly associated with lower odds of the primary endpoint in the propensity-matched cohort (OR 0.47, 95% CI 0.36–0.62, p < 0.001). We conclude that antecedent statin use in patients hospitalized with COVID-19 is associated with lower inpatient mortality.
The fate of volcanic ash: premature or delayed sedimentation?
Authors: Rossi Eduardo , Bagheri Gholamhossein , Beckett Frances , Bonadonna Costanza 
Published: February 2021

AbstractA large amount of volcanic ash produced during explosive volcanic eruptions has been found to sediment as aggregates of various types that typically reduce the associated residence time in the atmosphere (i.e., premature sedimentation). Nonetheless, speculations exist in the literature that aggregation has the potential to also delay particle sedimentation (rafting effect) even though it has been considered unlikely so far. Here, we present the first theoretical description of rafting that demonstrates how delayed sedimentation may not only occur but is probably more common than previously thought. The fate of volcanic ash is here quantified for all kind of observed aggregates. As an application to the case study of the 2010 eruption of Eyjafjallajökull volcano (Iceland), we also show how rafting can theoretically increase the travel distances of particles between 138–710 μm. These findings have fundamental implications for hazard assessment of volcanic ash dispersal as well as for weather modeling.
The Campylobacter jejuni CiaD effector co-opts the host cell protein IQGAP1 to promote cell entry
Authors: Negretti Nicholas M. , Gourley Christopher R. , Talukdar Prabhat K. , Clair Geremy , Klappenbach Courtney M. , Lauritsen Cody J. , Adkins Joshua N. , Konkel Michael E. 
Published: February 2021

AbstractCampylobacter jejuniis a foodborne pathogen that binds to and invades the epithelial cells lining the human intestinal tract. Maximal invasion of host cells byC. jejunirequires cell binding as well as delivery of the Cia proteins (Campylobacterinvasion antigens) to the host cell cytosol via the flagellum. Here, we show that CiaD binds to the host cell protein IQGAP1 (a Ras GTPase-activating-like protein), thus displacing RacGAP1 from the IQGAP1 complex. This, in turn, leads to the unconstrained activity of the small GTPase Rac1, which is known to have roles in actin reorganization and internalization ofC. jejuni. Our results represent the identification of a host cell protein targeted by a flagellar secreted effector protein and demonstrate thatC. jejuni-stimulated Rac signaling is dependent on IQGAP1.
Orchestrating performance of healthcare networks subjected to the compound events of natural disasters and pandemic
Authors: Hassan Emad M. , Mahmoud Hussam N. 
Published: February 2021

AbstractThe current COVID-19 pandemic has demonstrated the vulnerability of healthcare systems worldwide. When combined with natural disasters, pandemics can further strain an already exhausted healthcare system. To date, frameworks for quantifying the collective effect of the two events on hospitals are nonexistent. Moreover, analytical methods for capturing the dynamic spatiotemporal variability in capacity and demand of the healthcare system posed by different stressors are lacking. Here, we investigate the combined impact of wildfire and pandemic on a network of hospitals. We combine wildfire data with varying courses of the spread of COVID-19 to evaluate the effectiveness of different strategies for managing patient demand. We show that losing access to medical care is a function of the relative occurrence time between the two events and is substantial in some cases. By applying viable mitigation strategies and optimizing resource allocation, patient outcomes could be substantially improved under the combined hazards.
Distinct genetic pathways define pre-malignant versus compensatory clonal hematopoiesis in Shwachman-Diamond syndrome
Authors: Kennedy Alyssa L. , Myers Kasiani C. , Bowman James , Gibson Christopher J. , Camarda Nicholas D. , Furutani Elissa , Muscato Gwen M. , Klein Robert H. , Ballotti Kaitlyn , Liu Shanshan , Harris Chad E. , Galvin Ashley , Malsch Maggie , Dale David , Gansner John M. , Nakano Taizo A. , Bertuch Alison , Vlachos Adrianna , Lipton Jeffrey M. , Castillo Paul , Connelly James , Churpek Jane , Edwards John R. , Hijiya Nobuko , Ho Richard H. , Hofmann Inga , Huang James N. , Keel Siobán , Lamble Adam , Lau Bonnie W. , Norkin Maxim , Stieglitz Elliot , Stock Wendy , Walkovich Kelly , Boettcher Steffen , Brendel Christian , Fleming Mark D. , Davies Stella M. , Weller Edie A. , Bahl Christopher , Carter Scott L. , Shimamura Akiko , Lindsley R. Coleman 
Published: February 2021

AbstractTo understand the mechanisms that mediate germline genetic leukemia predisposition, we studied the inherited ribosomopathy Shwachman-Diamond syndrome (SDS), a bone marrow failure disorder with high risk of myeloid malignancies at an early age. To define the mechanistic basis of clonal hematopoiesis in SDS, we investigate somatic mutations acquired by patients with SDS followed longitudinally. Here we report that multiple independent somatic hematopoietic clones arise early in life, most commonly harboring heterozygous mutations in EIF6 or TP53. We show that germline SBDS deficiency establishes a fitness constraint that drives selection of somatic clones via two distinct mechanisms with different clinical consequences. EIF6 inactivation mediates a compensatory pathway with limited leukemic potential by ameliorating the underlying SDS ribosome defect and enhancing clone fitness. TP53 mutations define a maladaptive pathway with enhanced leukemic potential by inactivating tumor suppressor checkpoints without correcting the ribosome defect. Subsequent development of leukemia was associated with acquisition of biallelic TP53 alterations. These results mechanistically link leukemia predisposition to germline genetic constraints on cellular fitness, and provide a rational framework for clinical surveillance strategies.
A family of ionic supersalts with covalent-like directionality and unconventional multiferroicity
Authors: Gao Yaxin , Wu Menghao , Jena Puru 
Published: February 2021

AbstractIonic crystals composed of elemental ions such as NaCl are non-polar due to directionless ionic bonding interactions. Here, we show that these can develop polarity by changing their building blocks from elemental ions to superalkali and superhalogen cluster-ions, which mimic the chemistry of alkali and halogen atoms, respectively. Due to the non-spherical geometries of these cluster ions, corresponding supersalts form anisotropic polar structures with ionic bonding, yet covalent-like directionality, akin to sp3 hybridized systems. Using density functional theory and extensive structure searches, we predict a series of stable ferroelectric/ferroelastic supersalts, PnH4MX4 (Pn = N, P; M = B, Al, Fe; X = Cl, Br) composed of superalkali PnH4 and superhalogen MX4 ions. Unlike traditional ferroelectric/ferroelastic materials, the cluster-ion based supersalts possess ultra-low switching barrier and can endure large ion displacements and reversible strain. In particular, PH4FeBr4 exhibits triferroic coupling of ferroelectricity, ferroelasticity, and antiferromagnetism with controllable spin directions via either ferroelastic or 90-degree ferroelectric switching.
Electrical switching of high-performance bioinspired nanocellulose nanocomposites
Authors: Jiao Dejin , Lossada Francisco , Guo Jiaqi , Skarsetz Oliver , Hoenders Daniel , Liu Jin , Walther Andreas 
Published: February 2021

AbstractNature fascinates with living organisms showing mechanically adaptive behavior. In contrast to gels or elastomers, it is profoundly challenging to switch mechanical properties in stiff bioinspired nanocomposites as they contain high fractions of immobile reinforcements. Here, we introduce facile electrical switching to the field of bioinspired nanocomposites, and show how the mechanical properties adapt to low direct current (DC). This is realized for renewable cellulose nanofibrils/polymer nanopapers with tailor-made interactions by deposition of thin single-walled carbon nanotube electrode layers for Joule heating. Application of DC at specific voltages translates into significant electrothermal softening via dynamization and breakage of the thermo-reversible supramolecular bonds. The altered mechanical properties are reversibly switchable in power on/power off cycles. Furthermore, we showcase electricity-adaptive patterns and reconfiguration of deformation patterns using electrode patterning techniques. The simple and generic approach opens avenues for bioinspired nanocomposites for facile application in adaptive damping and structural materials, and soft robotics.
Catalytic asymmetric reductive hydroalkylation of enamides and enecarbamates to chiral aliphatic amines
Authors: Wang Jia-Wang , Li Yan , Nie Wan , Chang Zhe , Yu Zi-An , Zhao Yi-Fan , Lu Xi , Fu Yao 
Published: February 2021

AbstractTo increase the reliability and success rate of drug discovery, efforts have been made to increase the C(sp3) fraction and avoid flat molecules. sp3-Rich enantiopure amines are most frequently encountered as chiral auxiliaries, synthetic intermediates for pharmaceutical agents and bioactive natural products. Streamlined construction of chiral aliphatic amines has long been regarded as a paramount challenge. Mainstream approaches, including hydrogenation of enamines and imines, C–H amination, and alkylation of imines, were applied for the synthesis of chiral amines with circumscribed skeleton structures; typically, the chiral carbon centre was adjacent to an auxiliary aryl or ester group. Herein, we report a mild and general nickel-catalysed asymmetric reductive hydroalkylation to effectively convert enamides and enecarbamates into drug-like α-branched chiral amines and derivatives. This reaction involves the regio- and stereoselective hydrometallation of an enamide or enecarbamate to generate a catalytic amount of enantioenriched alkylnickel intermediate, followed by C–C bond formation via alkyl electrophiles.
Cavity frequency-dependent theory for vibrational polariton chemistry
Authors: Li Xinyang , Mandal Arkajit , Huo Pengfei 
Published: February 2021

AbstractRecent experiments demonstrate the control of chemical reactivities by coupling molecules inside an optical microcavity. In contrast, transition state theory predicts no change of the reaction barrier height during this process. Here, we present a theoretical explanation of the cavity modification of the ground state reactivity in the vibrational strong coupling (VSC) regime in polariton chemistry. Our theoretical results suggest that the VSC kinetics modification is originated from the non-Markovian dynamics of the cavity radiation mode that couples to the molecule, leading to the dynamical caging effect of the reaction coordinate and the suppression of reaction rate constant for a specific range of photon frequency close to the barrier frequency. We use a simple analytical non-Markovian rate theory to describe a single molecular system coupled to a cavity mode. We demonstrate the accuracy of the rate theory by performing direct numerical calculations of the transmission coefficients with the same model of the molecule-cavity hybrid system. Our simulations and analytical theory provide a plausible explanation of the photon frequency dependent modification of the chemical reactivities in the VSC polariton chemistry.
Maintenance of type 2 glycolytic myofibers with age by Mib1-Actn3 axis
Authors: Seo Ji-Yun , Kang Jong-Seol , Kim Ye Lynne , Jo Young-Woo , Kim Ji-Hoon , Hann Sang-Hyeon , Park Jieon , Park Inkuk , Park Hyerim , Yoo Kyusang , Rhee Joonwoo , Park Jung-Wee , Ha Yong Chan , Kong Young-Yun 
Published: February 2021

AbstractAge-associated muscle atrophy is a debilitating condition associated with loss of muscle mass and function with age that contributes to limitation of mobility and locomotion. However, the underlying mechanisms of how intrinsic muscle changes with age are largely unknown. Here we report that, with age, Mind bomb-1 (Mib1) plays important role in skeletal muscle maintenance via proteasomal degradation-dependent regulation of α-actinin 3 (Actn3). The disruption of Mib1 in myofibers (Mib1ΔMF) results in alteration of type 2 glycolytic myofibers, muscle atrophy, impaired muscle function, and Actn3 accumulation. After chronic exercise, Mib1ΔMF mice show muscle atrophy even at young age. However, when Actn3 level is downregulated, chronic exercise-induced muscle atrophy is ameliorated. Importantly, the Mib1 and Actn3 levels show clinical relevance in human skeletal muscles accompanied by decrease in skeletal muscle function with age. Together, these findings reveal the significance of the Mib1-Actn3 axis in skeletal muscle maintenance with age and suggest the therapeutic potential for the treatment or amelioration of age-related muscle atrophy.
A tris-spiro metalla-aromatic system featuring Craig-Möbius aromaticity
Authors: Huang Zhe , Zhang Yongliang , Zhang Wen-Xiong , Wei Junnian , Ye Shengfa , Xi Zhenfeng 
Published: February 2021

AbstractAs aromaticity is one of the most fundamental concepts in chemistry, the construction of aromatic systems has long been an important subject. Herein, we report the synthesis and characterization of a tris-spiroaromatic complex, hexalithio spiro vanadacycle 2. The delocalization of the four electrons within the two V 3d orbitals and the π* orbitals of the three biphenyl ligands leads to a 40π Craig-Möbius aromatic system with three metalla-aromatic rings, as revealed by both experimental measurements and theoretical analyses. For comparison, if Cr is used instead of V, a similar Craig-Möbius aromatic system can not be generated. In this case, pentalithio spiro chromacycle 3 is obtained, and the Cr center uses its two 3d orbitals to form two independent metalla-aromatic rings. This work presents a type of aromatic systems that will contribute to both aromaticity theory and organometallic chemistry.
Nanoscale redox mapping at the MoS2-liquid interface
Authors: Du He-Yun , Huang Yi-Fan , Wong Deniz , Tseng Mao-Feng , Lee Yi-Hsin , Wang Chen-Hao , Lin Cheng-Lan , Hoffmann Germar , Chen Kuei-Hsien , Chen Li-Chyong 
Published: February 2021

AbstractLayered MoS2 is considered as one of the most promising two-dimensional photocatalytic materials for hydrogen evolution and water splitting; however, the electronic structure at the MoS2-liquid interface is so far insufficiently resolved. Measuring and understanding the band offset at the surfaces of MoS2 are crucial for understanding catalytic reactions and to achieve further improvements in performance. Herein, the heterogeneous charge transfer behavior of MoS2 flakes of various layer numbers and sizes is addressed with high spatial resolution in organic solutions using the ferrocene/ferrocenium (Fc/Fc+) redox pair as a probe in near-field scanning electrochemical microscopy, i.e. in close nm probe-sample proximity. Redox mapping reveals an area and layer dependent reactivity for MoS2 with a detailed insight into the local processes as band offset and confinement of the faradaic current obtained. In combination with additional characterization methods, we deduce a band alignment occurring at the liquid-solid interface.
Cell polarisation in a bulk-surface model can be driven by both classic and non-classic Turing instability
Authors: Borgqvist Johannes , Malik Adam , Lundholm Carl , Logg Anders , Gerlee Philip , Cvijovic Marija 
Published: February 2021

AbstractThe GTPase Cdc42 is the master regulator of eukaryotic cell polarisation. During this process, the active form of Cdc42 is accumulated at a particular site on the cell membrane called the pole. It is believed that the accumulation of the active Cdc42 resulting in a pole is driven by a combination of activation–inactivation reactions and diffusion. It has been proposed using mathematical modelling that this is the result of diffusion-driven instability, originally proposed by Alan Turing. In this study, we developed, analysed and validated a 3D bulk-surface model of the dynamics of Cdc42. We show that the model can undergo both classic and non-classic Turing instability by deriving necessary conditions for which this occurs and conclude that the non-classic case can be viewed as a limit case of the classic case of diffusion-driven instability. Using three-dimensional Spatio-temporal simulation we predicted pole size and time to polarisation, suggesting that cell polarisation is mainly driven by the reaction strength parameter and that the size of the pole is determined by the relative diffusion.
A SARS-CoV-2 cytopathicity dataset generated by high-content screening of a large drug repurposing collection
Authors: Ellinger Bernhard , Bojkova Denisa , Zaliani Andrea , Cinatl Jindrich , Claussen Carsten , Westhaus Sandra , Keminer Oliver , Reinshagen Jeanette , Kuzikov Maria , Wolf Markus , Geisslinger Gerd , Gribbon Philip , Ciesek Sandra 
Published: February 2021

AbstractSARS-CoV-2 is a novel coronavirus responsible for the COVID-19 pandemic, in which acute respiratory infections are associated with high socio-economic burden. We applied high-content screening to a well-defined collection of 5632 compounds including 3488 that have undergone previous clinical investigations across 600 indications. The compounds were screened by microscopy for their ability to inhibit SARS-CoV-2 cytopathicity in the human epithelial colorectal adenocarcinoma cell line, Caco-2. The primary screen identified 258 hits that inhibited cytopathicity by more than 75%, most of which were not previously known to be active against SARS-CoV-2 in vitro. These compounds were tested in an eight-point dose response screen using the same image-based cytopathicity readout. For the 67 most active molecules, cytotoxicity data were generated to confirm activity against SARS-CoV-2. We verified the ability of known inhibitors camostat, nafamostat, lopinavir, mefloquine, papaverine and cetylpyridinium to reduce the cytopathic effects of SARS-CoV-2, providing confidence in the validity of the assay. The high-content screening data are suitable for reanalysis across numerous drug classes and indications and may yield additional insights into SARS-CoV-2 mechanisms and potential therapeutic strategies.
Hospitalization and mortality associated with SARS-CoV-2 viral clades in COVID-19
Authors: Nakamichi Kenji , Shen Jolie Z. , Lee Cecilia S. , Lee Aaron , Roberts Emma A. , Simonson Paul D. , Roychoudhury Pavitra , Andriesen Jessica , Randhawa April K. , Mathias Patrick C. , Greninger Alex L. , Jerome Keith R. , Van Gelder Russell N. 
Published: February 2021

AbstractThe COVID-19 epidemic of 2019–20 is due to the novel coronavirus SARS-CoV-2. Following first case description in December, 2019 this virus has infected over 10 million individuals and resulted in at least 500,000 deaths world-wide. The virus is undergoing rapid mutation, with two major clades of sequence variants emerging. This study sought to determine whether SARS-CoV-2 sequence variants are associated with differing outcomes among COVID-19 patients in a single medical system. Whole genome SARS-CoV-2 RNA sequence was obtained from isolates collected from patients registered in the University of Washington Medicine health system between March 1 and April 15, 2020. Demographic and baseline clinical characteristics of patients and their outcome data including their hospitalization and death were collected. Statistical and machine learning models were applied to determine if viral genetic variants were associated with specific outcomes of hospitalization or death. Full length SARS-CoV-2 sequence was obtained 190 subjects with clinical outcome data. 35 (18.4%) were hospitalized and 14 (7.4%) died from complications of infection. A total of 289 single nucleotide variants were identified. Clustering methods demonstrated two major viral clades, which could be readily distinguished by 12 polymorphisms in 5 genes. A trend toward higher rates of hospitalization of patients with Clade 2 infections was observed (p = 0.06, Fisher’s exact). Machine learning models utilizing patient demographics and co-morbidities achieved area-under-the-curve (AUC) values of 0.93 for predicting hospitalization. Addition of viral clade or sequence information did not significantly improve models for outcome prediction. In summary, SARS-CoV-2 shows substantial sequence diversity in a community-based sample. Two dominant clades of virus are in circulation. Among patients sufficiently ill to warrant testing for virus, no significant difference in outcomes of hospitalization or death could be discerned between clades in this sample. Major risk factors for hospitalization and death for either major clade of virus include patient age and comorbid conditions.