bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic Engineering in Combination with Semi‐Synthesis Leads to a New Route for Gram‐Scale Production of the Immunosuppressive Natural Product Brasilicardin A
Authors: Botas Alma , Eitel Michael , Schwarz Paul N. , Buchmann Anina , Costales Paula , Núñez Luz Elena , Cortés Jesús , Morís Francisco , Krawiec Michał , Wolański Marcin , Gust Bertolt , Rodriguez Mirna , Fischer Wolf‐Nicolas , Jandeleit Bernd , Zakrzewska‐Czerwińska Jolanta , Wohlleben Wolfgang , Stegmann Evi , Koch Pierre , Méndez Carmen , Gross Harald 
Published: March 2021

AbstractBrasilicardin A (1) consists of an unusual anti/syn/anti‐perhydrophenanthrene skeleton with a carbohydrate side chain and an amino acid moiety. It exhibits potent immunosuppressive activity, yet its mode of action differs from standard drugs that are currently in use. Further pre‐clinical evaluation of this promising, biologically active natural product is hampered by restricted access to the ready material, as its synthesis requires both a low‐yielding fermentation process using a pathogenic organism and an elaborate, multi‐step total synthesis. Our semi‐synthetic approach included a) the heterologous expression of the brasilicardin A gene cluster in different non‐pathogenic bacterial strains producing brasilicardin A aglycone (5) in excellent yield and b) the chemical transformation of the aglycone 5 into the trifluoroacetic acid salt of brasilicardin A (1 a) via a short and straightforward five‐steps synthetic route. Additionally, we report the first preclinical data for brasilicardin A.
Recombinant Spider Silk Gels Derived from Aqueous–Organic Solvents as Depots for Drugs
Authors: Neubauer Vanessa J. , Trossmann Vanessa T. , Jacobi Sofia , Döbl Annika , Scheibel Thomas 
Published: March 2021

AbstractHydrogels are widely used in various biomedical applications, as they cannot only serve as materials for biofabrication but also as depots for the administration of drugs. However, the possibilities of formulation of water‐insoluble drugs in hydrogels are rather limited. Herein, we assembled recombinant spider silk gels using a new processing route with aqueous–organic co‐solvents, and the properties of these gels could be controlled by the choice of the co‐solvent. The presence of the organic co‐solvent further enabled the incorporation of hydrophobic drugs as exemplarily shown for 6‐mercaptopurine. The developed gels showed shear‐thinning behaviour and could be easily injected to serve, for example, as drug depots, and they could even be 3D printed to serve as scaffolds for biofabrication. With this new processing route, the formulation of water‐insoluble drugs in spider silk‐based depots is possible, circumventing common pharmaceutical solubility issues.
Peroxopolyoxometalate nanoparticles blended PES membrane with improved hydrophilicity, anti‐fouling, permeability, and dye separation properties
Authors: Barzegar Hossein , Shahsavarifar Samaneh , Vatanpour Vahid , Masteri‐Farahani Majid 
Published: March 2021

AbstractPoly(ethersulfone) (PES) is one of the polymers most widely used for the fabrication of ultrafiltration or nanofiltration membranes in various applications, but its membrane suffers from fouling. In this study, preparation, characterization, and performance of PES nanocomposite membrane comprising peroxopolyoxometalate nanoparticles was studied to provide improved permeability and anti‐fouling properties. The high oxygen ratio of the PW4 nanoparticles could enhance the hydrophilicity of the membranes. The PW4 nanoparticles were characterized using Fourier transform infrared spectroscopy, scanning electron microscopy (SEM), energy dispersive X‐ray (EDX), and X‐ray diffraction analyses. The mixed matrix membranes were fabricated using a non‐solvent induced phase‐separation method. The fabricated membranes were characterized using atomic force microscopy, attenuated total reflection, SEM, EDX mapping, total average porosity, thermogravimetric analyze, and water contact angle experiments. The dye flux and rejection, pure water permeability and anti‐fouling properties of the membranes were investigated. All of the membranes blended by different contents of the PW4 nanoparticles presented better performance compared to the unmodified membrane. The filtration performance of the membranes in reactive green 19 (RG19) and reactive yellow 160 (RY160) dye separation showed that all of the PW4 blended membranes possessed dye rejection greater than 86% and 96% for RY160 and RG19, respectively. The reusability test using bovine serum albumin (BSA) protein and RG19 dye solutions in five cycle experiments presented good reproductivity of the PW4 blended membranes. The PES membrane containing 1 wt% of PW4 nanoparticles showed the highest flux recovery ratio (75%) as well as reduced irreversible fouling ratio (8%) through BSA protein filtration.
Sex differentiation of brain structures in autism: Findings from a gray matter asymmetry study
Authors: Deng Zhizhou , Wang Suiping 
Published: March 2021

AbstractAutism spectrum disorder (ASD) is diagnosed much more often in males than females. This male predominance has prompted a number of studies to examine how sex differences are related to the neural expression of ASD. Different theories, such as the “extreme male brain” theory, the “female protective effect” (FPE) theory, and the gender incoherence (GI) theory, provide different explanations for the mixed findings of sex‐related neural expression of ASD. This study sought to clarify whether either theory applies to the brain structure in individuals with ASD by analyzing a selective high‐quality data subset from an open data resource (Autism Brain Imaging Data Exchange I and II) including 35 males/35 females with ASD and 86 male/86 female typical‐controls (TCs). We examined the sex‐related changes in ASD in gray matter asymmetry measures (i.e., asymmetry index, AI) derived from voxel‐based morphometry using a 2 (diagnosis: ASD vs. TC) ×  2 (sex: female vs. male) factorial design. A diagnosis‐by‐sex interaction effect was identified in the planum temporale/Heschl's gyrus: (i) compared to females, males exhibited decreased AI (indicating more leftward brain asymmetry) in the TC group, whereas AI was greater (indicating less leftward brain asymmetry) for males than for females in the ASD group; and (ii) females with ASD showed reduced AI (indicating more leftward brain asymmetry) compared to female TCs, whereas there were no differences between ASDs and TCs in the male group. This interaction pattern supports the FPE theory in showing greater brain structure changes (masculinization) in females with ASD.Lay SummaryTo understand the neural mechanisms underlying male predominance in autism spectrum disorder (ASD), we investigated the sex differences in ASD‐related alterations in brain asymmetry. We found greater changes in females with ASD compared with males with ASD, revealing a female protective effect. These findings provide novel insights into the neurobiology of sex differences in ASD.
Enhancing erythrocyte–influenza virus specificity by glycan‐conjugated gold nanoparticle: Validation of hemagglutination by aptamer and neuraminidases
Authors: Ye Meiyi , Lin Lei , Yang Wei , Gopinath Subash C.B. 
Published: March 2021

ABSTRACTThis study demonstrated the terminated sialo‐sugar chains (Neu5Acα2,6Gal and Neu5Acα2,3Gal)‐mediated specificity enhancement of influenza virus and chicken red blood cell (RBC) by hemagglutination assay. These glycan chains were immobilized on the gold nanoparticle (GNP) to withhold the higher numbers. With the preliminary optimization, a clear button formation with 0.5% RBC was visualized. On the other hand, intact B/Tokio/53/99 with 750 nM hemagglutinin (HA) displayed a nice hemagglutination. The interference on the specificity of RBC and influenza virus was observed by anti‐influenza aptamer at the concentration 31 nM; however, there is no hemagglutination prevention was noticed in the presence of complementary aptamer sequences. Spiking GNP‐conjugated Neu5Acα2,6Gal or Neu5Acα2,3Gal or a mixture of these two to the reaction promoted the hemagglutination to 63‐folds higher with 12 nM virus, whereas under the same condition the heat‐inactivated viruses were lost the hemagglutination. Neuraminidases from Clostridium perfringens and Arthrobacter ureafaciens at 0.0025 neuraminidase units are able to abolish the hemagglutination. Other enzymes, Glycopeptidase F (Elizabethkingia meningoseptica) and Endoglycosidase H (Streptomyces plicatus) did not show the changes with agglutination. Obviously, sialyl‐Gal‐terminated glycan‐conjugated GNP amendment has enhanced the specificity of erythrocyte–influenza virus and able to be controlled by aptamer or neuraminidases.
Investigating antecedents of Islamophobia: The role of perceived control over terrorism, threat, meta‐dehumanization, and dehumanization
Authors: Pavetich Melissa , Stathi Sofia 
Published: March 2021

AbstractMeta‐dehumanization contributes to a vicious cycle of hostility. This study extends the literature by investigating antecedents and outcomes of meta‐dehumanization in the context of Muslim–non‐Muslim relations. Specifically, control over terrorism (COT) and threat were tested as predictors of meta‐dehumanization among non‐Muslim British nationals (N = 313). The results revealed that lower perceptions of COT predicted increased threat, which in turn predicted meta‐dehumanization. Meta‐dehumanization, consequently, predicted Islamophobia via increased dehumanization of Muslim people. The results were significant while controlling for political orientation and intergroup contact. This research highlights the unsettling cycle of meta‐dehumanization and intergroup hostility. Theoretical and practical implications of this research are discussed. Please refer to the Supplementary Material section to find this article's Community and Social Impact Statement.
Fluorinated Azobenzenes Switchable with Red Light
Authors: Leistner Anna‐Lena , Kirchner Susanne , Karcher Johannes , Bantle Tobias , Schulte Mariam L. , Gödtel Peter , Fengler Christian , Pianowski Zbigniew L. 
Published: March 2021

AbstractMolecular photoswitches triggered with red or NIR light are optimal for photomodulation of complex biological systems, including efficient penetration of the human body for therapeutic purposes (“therapeutic window”). Yet, they are rarely reported, and even more rarely functional under aqueous conditions. In this work, fluorinated azobenzenes are shown to exhibit efficient E→Z photoisomerization with red light (PSS660nm >75 % Z) upon conjugation with unsaturated substituents. Initially demonstrated for aldehyde groups, this effect was also observed in a more complex structure by incorporating the chromophore into a cyclic dipeptide with propensity for self‐assembly. Under physiological conditions, the latter molecule formed a supramolecular material that reversibly changed its viscosity upon irradiation with red light. Our observation can lead to design of new photopharmacology agents or phototriggered materials for in vivo use.
3D Uranyl Organic Frameworks Supported by Rigid Octadentate Carboxylate Ligand: Synthesis, Structure Diversity, and Luminescence Properties
Authors: Wu Dai , Mo Xiu‐Fang , He Piao , Li Hai‐Ru , Yi Xiao‐Yi , Liu Chao 
Published: March 2021

AbstractSeven three dimensional (3D) uranyl organic frameworks (UOFs), formulated as [NH4][(UO2)3(HTTDS)(H2O)] (1), [(UO2)4(HTTDS)2](HIM)6 (2, IM=imidazole), [(UO2)4(TTDS)(H2O)2(Phen)2] (3, Phen=1,10‐phenanthroline), [Zn(H2O)4]0.5[(UO2)3(HTTDS)(H2O)4] (4), and {(UO2)2[Zn(H2O)3]2(TTDS)} (5), {Zn(UO2)2(H2O)(Dib)0.5(HDib)(HTTDS)} (6, Dib=1,4‐di(1H‐imidazol‐1‐yl)benzene) and [Na]{(UO2)4[Cu3(u3‐OH)(H2O)7](TTDS)2} (7) have been hydrothermally prepared using a rigid octadentate carboxylate ligand, tetrakis(3,5‐dicarboxyphenyl)silicon(H8TTDS). These UOFs have different 3D self‐assembled structures as a function of co‐ligands, structure‐directing agents and transition metals. The structure of 1 has an infinite ribbon formed by the UO7 pentagonal bipyramid bridged by carboxylate groups. With further introduction of auxiliary N‐donor ligands, different structure of 2 and 3 are formed, in 2 the imidazole serves as space filler, while in 3 the Phen are bound to [UO2]2+ units as co‐ligands. The second metal centers were introduced in the syntheses of 4–7, and in all cases, they are part of the final structures, either as a counterion (4) or as a component of framework (5−7). Interesting, in 7, a rare polyoxometalate [Cu3(μ3‐OH)O7(O2CR)4] cluster was found in the structure. It acts as an inorganic building unit together with the dimer [(UO2)2(O2CR)4] unit. Those uranyl carboxylates were sufficiently determined by single crystal X‐ray diffraction, and their topological structures and luminescence properties were analyzed in detail.
Prediction and Validation of a Druggable Site on Virulence Factor of Drug Resistant Burkholderia cenocepacia**
Authors: Lal Kanhaya , Bermeo Rafael , Cramer Jonathan , Vasile Francesca , Ernst Beat , Imberty Anne , Bernardi Anna , Varrot Annabelle , Belvisi Laura 
Published: March 2021

AbstractBurkholderia cenocepacia is an opportunistic Gram‐negative bacterium that causes infections in patients suffering from chronic granulomatous diseases and cystic fibrosis. It displays significant morbidity and mortality due to extreme resistance to almost all clinically useful antibiotics. The bacterial lectin BC2L‐C expressed in B. cenocepacia is an interesting drug target involved in bacterial adhesion and subsequent deadly infection to the host. We solved the first high resolution crystal structure of the apo form of the lectin N‐terminal domain (BC2L‐C‐nt) and compared it with the ones complexed with carbohydrate ligands. Virtual screening of a small fragment library identified potential hits predicted to bind in the vicinity of the fucose binding site. A series of biophysical techniques and X‐ray crystallographic screening were employed to validate the interaction of the hits with the protein domain. The X‐ray structure of BC2L‐C‐nt complexed with one of the identified active fragments confirmed the ability of the site computationally identified to host drug‐like fragments. The fragment affinity could be determined by titration microcalorimetry. These structure‐based strategies further provide an opportunity to elaborate the fragments into high affinity anti‐adhesive glycomimetics, as therapeutic agents against B. cenocepacia.
Synthesis of Desepoxy‐Tedanolide C
Authors: Lücke Daniel , Kalesse Markus 
Published: March 2021

AbstractThe synthesis of desepoxy‐tedanolide C was accomplished and provided experimental evidence on the configuration of tedanolide C. The reported chemical shifts and coupling constants point to a configuration different from the published structure and analogous to the structures of the other members of this family of natural products. The key step is a Kiyooka aldol protocol for the stereoselective synthesis of the tertiary alcohol flanked by three additional oxygenated carbon atoms. Furthermore, two additional aldol reactions and a Julia–Kocienski olefination were used to assemble the carbon framework.
Copper‐Catalyzed Synthesis of Tetrasubstituted Alkenes via Regio‐ and anti‐Selective Addition of Silylboronates to Internal Alkynes
Authors: Moniwa Hirokazu , Shintani Ryo 
Published: March 2021

AbstractAs a new and complementary method for the synthesis of structurally defined tetrasubstituted alkenes, a copper‐catalyzed regio‐ and anti‐selective addition of silylboronates to unsymmetric internal alkynes has been developed. A variety of unactivated alkynes can be employed with high selectivity under simple and mild conditions, and the resulting products have been further functionalized by utilizing silyl and boryl groups on the alkene.
The impact of underweight and obesity on outcomes in anticoagulated patients with atrial fibrillation: A systematic review and meta‐analysis on the obesity paradox
Authors: Grymonprez Maxim , Capiau Andreas , De Backer Tine L. , Steurbaut Stephane , Boussery Koen , Lahousse Lies 
Published: March 2021

AbstractAlthough obesity is associated with the development and progression of atrial fibrillation (AF), an obesity paradox may be present, illustrated by seemingly protective effects of obesity on AF‐related outcomes. Body mass index (BMI) has an impact on outcomes in AF patients using oral anticoagulants. After searching Medline and Embase, meta‐analysis of results of four randomized and five observational studies demonstrated significantly lower risks of stroke or systemic embolism (RR 0.80, 95%CI [0.73–0.87]; RR 0.63, 95%CI [0.57–0.70]; and RR 0.42, 95%CI [0.31–0.57], respectively) and all‐cause mortality (RR 0.73, 95%CI [0.64–0.83]; RR 0.61, 95%CI [0.52–0.71]; and RR 0.56, 95%CI [0.47–0.66], respectively) in overweight, obese and morbidly obese anticoagulated AF patients (BMI 25 to <30, ≥30 and ≥40 kg/m2, respectively) compared to normal BMI anticoagulated AF patients (BMI 18.5 to <25 kg/m2). In contrast, thromboembolic (RR 1.92, 95%CI [1.28–2.90]) and mortality (RR 3.57, 95%CI [2.50–5.11]) risks were significantly increased in underweight anticoagulated AF patients (BMI <18.5 kg/m2). In overweight and obese anticoagulated AF patients, the risks of major bleeding (RR 0.86, 95%CI [0.76–0.99]; and RR 0.88, 95%CI [0.79–0.98], respectively) and intracranial bleeding (RR 0.75, 95%CI [0.58–0.97]; and RR 0.57, 95%CI [0.40–0.80], respectively) were also significantly lower compared to normal BMI patients, while similar risks were observed in underweight and morbidly obese patients. This meta‐analysis demonstrated lower thromboembolic and mortality risks with increasing BMI. However, as this paradox was driven by results from randomized studies, while observational studies rendered more conflicting results, these seemingly protective effects should still be interpreted with caution.
Halogen and Chalcogen Bonding Between the Triphenylphosphine Chalcogenides (Ph3P=E; E=O, S, Se) and Iodofluorobenzenes
Authors: Peloquin Andrew J. , McMillen Colin D. , Iacono Scott T. , Pennington William T. 
Published: March 2021

AbstractA series of cocrystals of Ph3P=E (E=O, S, Se) with organoiodines were studied to understand the roles of noncovalent interactions including chalcogen (ChB) and halogen (XB) bonding in their formation. The structure of the cocrystal of Ph3P=S and 1,2‐diiodotetrafluorobezene was determined, which demonstrates a similar chalcogen⋅⋅⋅iodine XB pattern to the previously reported isomorphic Ph3P=Se structure. The cocrystalline structures resulting from the combination of 1,3‐diiodotetrafluorobenzene (1,3‐F4DIB), as well as iodopentafluorobenzene, with all three triphenylphosphine chalcogenides, were also determined. The (Ph3P=Se) ⋅ (1,3‐F4DIB) cocrystal presents a rare example of a selenium⋅⋅⋅organoiodine ChB. The observed ChB and XB interactions have normalized distance parameters (RXB) ranging from 0.80 to 0.98. The strength of the XB and ChB interactions were analyzed using natural bond orbital (NBO) theory, with calculated energies falling between 3.14 kcal/mol and 12.81 kcal/mol.
Triple full‐sibs: A method for estimating components of genetic variance and progeny selection in plants
Authors: Chaves Lázaro José 
Published: March 2021

AbstractQuantifying the genetic variability present in plant populations is crucial for the success of selection plans. The partitioning of genetic variance into its components allows inferences about the inheritance of quantitative traits and prediction of the gain from selection. The present study aimed to present an alternative method to estimate components of genetic variance with applications in recurrent selection. The mating scheme is based on biparental cyclic crossing involving three parents in each chain, here called the triple full‐sibs (TFS) family, each of which is composed of three biparental progenies in which individuals are full‐sibs within each progeny and half‐sibs among progenies. The progenies are evaluated in experimental trials, and the total effect of progenies is hierarchically partitioned into the effects of TFS families and progenies within families. From the components of variance, additive and dominance variance, as well as the associated errors, can be estimated. Simulated data are used to illustrate the method of analysis and parameter estimation. The method combines the advantages of North Carolina Design I regarding estimation of variance components with the practicality of conventional full‐sib selection. The TFS method allows different selection strategies according to the selection unit and provides expected genetic gain equal to or greater than unrelated full‐sib selection. There is no further advantage to using more than three parents in each chain‐cross.
The evolution of hummock–depression micro‐topography in an alpine marshy wetland in Sanjiangyuan as inferred from vegetation and soil characteristics
Authors: Wu Guiling , Li Xilai , Gao Jay 
Published: March 2021

AbstractThe hummock–depression micro‐topography characteristics of the alpine marshy wetland in Sanjiangyuan are indicative of wetland degradation and the process by which healthy wetlands are transformed into flat grasslands. The aim of the present study was to examine changes in plant community structure and soil characteristics in a hummock–depression micro‐topography along a degradation gradient. We observed that: (a) the height and cover of dominant hydrophytes decreased gradually with an increase in degradation severity, leading to replacement by xerophytes; (b) with the transition from healthy to degraded wetlands, hummocks became sparser, shorter, and broader and became merged with nearby depressions; water reserves in the depressions shifted from perennial to seasonal, until they dried out completely; and (c) soil moisture content, porosity, hardness, and organic matter gradually decreased by 30.61%, 19.06%, 37.04%, and 73.27%, respectively, in hummocks and by 33.25%, 8.19%, 47.72%, and 76.79%, respectively, in depressions. Soil bulk density, soil electrical conductivity, and soil dry weight increased by 31%, 83.33%, and 105.44%, respectively, in hummocks, but by only 11.93%, 7.14%, and 97.72%, respectively, in depressions. The results show that hummock soils in healthy wetlands have strong water absorption properties, through which plant roots can penetrate easily. Wetland degradation reduces the water absorption capacity of hummock soil and soil saturation capacity of depressions, thus enhancing soil erosion potential and susceptibility to external factors. Soil moisture is a key environmental factor influencing wetland degradation, and grazing accelerates the process. Based on the changes observed in hummock morphology, vegetation, and soil properties along a degradation gradient, a conceptual model is proposed to illustrate the process of gradual degradation of marshy wetlands from healthy to transitional wetlands and finally to a degenerated state. Thus, our research provides insights into the degradation process of the alpine marshy wetland ecosystem in Sanjiangyuan.