bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discovery of a Mosaic‐Like Biosynthetic Assembly Line with a Decarboxylative Off‐Loading Mechanism through a Combination of Genome Mining and Imaging
Authors: Mir Mohseni Mahsa , Höver Thomas , Barra Lena , Kaiser Marcel , Dorrestein Pieter C. , Dickschat Jeroen S. , Schäberle Till F. 
Published: September 2016

AbstractThe biosynthetic gene cluster for the antiplasmodial natural product siphonazole was identified by using a combination of genome mining, imaging, and expression studies in the natural producer Herpetosiphon sp. B060. The siphonazole backbone is assembled from an unusual starter unit from the shikimate pathway that is extended by the action of polyketide synthases and non‐ribosomal peptide synthetases with unusual domain structures, including several split modules and a large number of duplicated domains and domains predicted to be inactive. Product release proceeds through decarboxylation and dehydration independent of the thioesterase SphJ and yields the diene terminus of siphonazole. High variation in terms of codon‐usage within the gene cluster, together with the dislocated domain organization, suggest a recent emergence in evolutionary terms.
Electrophilic RNA for Peptidyl‐RNA Synthesis and Site‐Specific Cross‐Linking with tRNA‐Binding Enzymes
Authors: Fonvielle Matthieu , Sakkas Nicolas , Iannazzo Laura , Le Fournis Chloé , Patin Delphine , Mengin‐Lecreulx Dominique , El‐Sagheer Afaf , Braud Emmanuelle , Cardon Sébastien , Brown Tom , Arthur Michel , Etheve‐Quelquejeu Mélanie 
Published: September 2016

AbstractRNA functionalization is challenging due to the instability of RNA and the limited range of available enzymatic reactions. We developed a strategy based on solid phase synthesis and post‐functionalization to introduce an electrophilic site at the 3′ end of tRNA analogues. The squarate diester used as an electrophile enabled sequential amidation and provided asymmetric squaramides with high selectivity. The squaramate‐RNAs specifically reacted with the lysine of UDP‐MurNAc‐pentapeptide, a peptidoglycan precursor used by the aminoacyl‐transferase FemXWv for synthesis of the bacterial cell wall. The peptidyl‐RNA obtained with squaramate‐RNA and unprotected UDP‐MurNAc‐pentapeptide efficiently inhibited FemXWv. The squaramate unit also promoted specific cross‐linking of RNA to the catalytic Lys of FemXWv but not to related transferases recognizing different aminoacyl‐tRNAs. Thus, squaramate‐RNAs provide specificity for cross‐linking with defined groups in complex biomolecules due to its unique reactivity.
One‐Step Microfluidic Fabrication of Polyelectrolyte Microcapsules in Aqueous Conditions for Protein Release
Authors: Zhang Liyuan , Cai Li‐Heng , Lienemann Philipp S. , Rossow Torsten , Polenz Ingmar , Vallmajo‐Martin Queralt , Ehrbar Martin , Na Hui , Mooney David J. , Weitz David A. 
Published: September 2016

AbstractWe report a microfluidic approach for one‐step fabrication of polyelectrolyte microcapsules in aqueous conditions. Using two immiscible aqueous polymer solutions, we generate transient water‐in‐water‐in‐water double emulsion droplets and use them as templates to fabricate polyelectrolyte microcapsules. The capsule shell is formed by the complexation of oppositely charged polyelectrolytes at the immiscible interface. We find that attractive electrostatic interactions can significantly prolong the release of charged molecules. Moreover, we demonstrate the application of these microcapsules in encapsulation and release of proteins without impairing their biological activities. Our platform should benefit a wide range of applications that require encapsulation and sustained release of molecules in aqueous environments.
Mirror‐Image Packing Provides a Molecular Basis for the Nanomolar Equipotency of Enantiomers of an Experimental Herbicide
Authors: Bisson Claudine , Britton K. Linda , Sedelnikova Svetlana E. , Rodgers H. Fiona , Eadsforth Thomas C. , Viner Russell C. , Hawkes Tim R. , Baker Patrick J. , Rice David W. 
Published: September 2016

AbstractPrograms of drug discovery generally exploit one enantiomer of a chiral compound for lead development following the principle that enantiomer recognition is central to biological specificity. However, chiral promiscuity has been identified for a number of enzyme families, which have shown that mirror‐image packing can enable opposite enantiomers to be accommodated in an enzyme's active site. Reported here is a series of crystallographic studies of complexes between an enzyme and a potent experimental herbicide whose chiral center forms an essential part of the inhibitor pharmacophore. Initial studies with a racemate at 1.85 Å resolution failed to identify the chirality of the bound inhibitor, however, by extending the resolution to 1.1 Å and by analyzing high‐resolution complexes with the enantiopure compounds, we determined that both enantiomers make equivalent pseudosymmetric interactions in the active site, thus mimicking an achiral reaction intermediate.
Lessons from 1,3‐Hydride Shifts in Sesquiterpene Cyclizations
Authors: Rinkel Jan , Rabe Patrick , Garbeva Paolina , Dickschat Jeroen S. 
Published: September 2016

AbstractStereospecifically labelled precursors were subjected to conversion by seven bacterial sesquiterpene cyclases to investigate the stereochemistry of their initial 1,10‐cyclisation‐1,3‐hydride shift cascades. Enzymes with products of known absolute configuration showed a coherent stereochemical course, except for (−)‐α‐amorphene synthase, for which the obtained results are better explained by an initial 1,6‐cyclisation. The link between the absolute configuration of the product and the stereochemical course of the 1,3‐hydride shifts enabled assignment of the absolute configurations of three enzyme products, which were confirmed independently through the absolute configuration of the common byproduct germacrene D‐4‐ol.
A Macrocyclic Ruthenium(III) Complex Inhibits Angiogenesis with Down‐Regulation of Vascular Endothelial Growth Factor Receptor‐2 and Suppresses Tumor Growth In Vivo
Authors: Kwong Wai‐Lun , Lam Kar‐Yee , Lok Chun‐Nam , Lai Yau‐Tsz , Lee Pui‐Yan , Che Chi‐Ming 
Published: September 2016

AbstractA macrocyclic ruthenium(III) complex [RuIII(N2O2)Cl2]Cl (Ru‐1) is reported as an inhibitor of angiogenesis and an anti‐tumor compound. The complex is relatively non‐cytotoxic towards endothelial and cancer cell lines in vitro, but specifically inhibited the processes of angiogenic endothelial cell tube formation and cancer cell invasion. Moreover, compared with known anti‐cancer ruthenium complexes, Ru‐1 is distinct in that it suppressed the expression of vascular endothelial growth factor receptor‐2 (VEGFR2), and the associated downstream signaling that is crucial to tumor angiogenesis. In addition, in vivo studies showed that Ru‐1 inhibited angiogenesis in a zebrafish model and suppressed tumor growth in nude mice bearing cancer xenografts.
Enantioselective Pd‐Catalyzed Allylic Alkylation Reactions of Dihydropyrido[1,2‐a]indolone Substrates: Efficient Syntheses of (−)‐Goniomitine, (+)‐Aspidospermidine, and (−)‐Quebrachamine
Authors: Pritchett Beau P. , Kikuchi Jun , Numajiri Yoshitaka , Stoltz Brian M. 
Published: September 2016

AbstractThe successful application of dihydropyrido[1,2‐a]indolone (DHPI) substrates in Pd‐catalyzed asymmetric allylic alkylation chemistry facilitates rapid access to multiple alkaloid frameworks in an enantioselective fashion. Strategic bromination at the indole C3 position greatly improved the allylic alkylation chemistry and enabled a highly efficient Negishi cross‐coupling downstream. The first catalytic enantioselective total synthesis of (−)‐goniomitine, along with divergent formal syntheses of (+)‐aspidospermidine and (−)‐quebrachamine, are reported herein.
Preparation and characterization of cellulose triacetate membranes via thermally induced phase separation
Authors: Yu Yuan , Wu Qing‐Yun , Liang Hong‐Qing , Gu Lin , Xu Zhi‐Kang 
Published: September 2016

ABSTRACTA series of cellulose triacetate (CTA) membranes were prepared via thermally induced phase separation (TIPS) process with dimethyl sulfone (DMSO2) and polyethylene glycol (PEG400) as a crystallizable diluent and an additive, respectively. The phase separation behavior of CTA/DMSO2/PEG400 ternary system was investigated in detail by optical microscopy, differential scanning calorimetry and wide angle X‐ray diffraction. This ternary system dynamically undergoes solid‐solid phase separation and thus the CTA membranes possess cellular, lacy, plate‐, or even ellipse‐shaped pores. However, we can modulate the pore structure, porosity, water flux, and mechanical properties of the membranes by varying polymer concentration, composition of the mixed diluent, and cooling condition. Due to the intrinsic hydrophilicity, the prepared CTA membranes have better antifouling property than polysulfone membranes. These porous membranes were used as supports to fabricate thin‐film composite forward osmosis (FO) membranes, which show good water permeability and selectivity. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci.2017,134, 44454.
Metal/Graphitic Carbon Nitride Composites: Synthesis, Structures, and Applications
Authors: Wang Luona , Wang Chengyin , Hu Xiaoya , Xue Huaiguo , Pang Huan 
Published: September 2016

AbstractGraphitic carbon nitride (g‐C3N4) has been widely used in fields related to energy and materials science. However, nanostructured g‐C3N4 photocatalysts synthesized by traditional thermal polycondensation methods have the disadvantage of small specific surface areas and wide band gaps; these limit the catalytic activity and application range of g‐C3N4. Based on the unique nanostructure of g‐C3N4, it is a feasible method to modify g‐C3N4 with metals to design novel metal–semiconductor composites. Metals alter the photochemical properties of g‐C3N4, in particular, narrow the band gap and expand photoabsorption into the visible range, which improves the photocatalytic performance. This review covers recent progress in metal/g‐C3N4 nanocomposites for photocatalysts, organic systems, biosensors, and so on. The aim is to summarize the synthetic methods, nanostructures, and applications of metal/g‐C3N4 nanocomposite materials, as well as discuss future research directions in these areas.
Acid‐Base Switchable [2]‐ and [3]Rotaxane Molecular Shuttles with Benzimidazolium and Bis(pyridinium) Recognition Sites
Authors: Zhu Kelong , Vukotic V. Nicholas , Loeb Stephen J. 
Published: September 2016

AbstractFor the purpose of developing higher level mechanically interlocked molecules (MIMs), such as molecular switches and machines, a new rotaxane system was designed in which both the 1,2‐bis(pyridinium)ethane and benzimidazolium recognition templating motifs were combined. These two very different recognition sites were successfully incorporated into [2]rotaxane and [3]rotaxane molecular shuttles which were fully characterized by 1H NMR, 2D EXSY, single‐crystal X‐ray diffraction and VT NMR analysis. By utilizing benzimidazolium as both a recognition site and stoppering group it was possible to create not only an acid/base switchable [2]rotaxane molecular shuttle (energy barrier 20.9 kcal⋅mol−1) but also a [3]rotaxane molecular shuttle that displays unique dynamic behavior involving the simultaneous motion of two macrocyclic wheels on a single dumbbell. This study provides new insights into the design of switchable molecular shuttles. Due to the unique properties of benzimidazoles, such as fluorescence and metal coordination, this new type of molecular shuttle may find further applications in developing functional molecular machines and materials.
A GIS‐based model to estimate citrus pulp availability for biogas production: an application to a region of the Mediterranean Basin
Authors: Valenti Francesca , Porto Simona MC , Chinnici Gaetano , Cascone Giovanni , Arcidiacono Claudia 
Published: September 2016

AbstractIn recent years, biogas from biomasses has increasingly been considered a feasible alternative to energy from fossil fuel. The utilization of biomasses obtained from citrus processing for juice extraction is being investigated for energy purposes, as a biofuel or organic matrix for bioethanol or biogas extraction, besides for the extraction of high added‐value by‐products and animal feed. In citrus producing areas, uncertainty often exists as to the amount of processed product and, therefore, correct planning of the use of ‘citrus pulp’ for energy purposes has not yet been carried out.The objective of this study was to analyze the spatial distribution of the citrus fruit production area and the amount of processed citrus in order to quantify the citrus pulp available for biogas production. It could contribute to build an information base suitable for multi‐criteria analysis aimed at finding optimal locations for biogas plants and increasing their number in a territory. The GIS‐based methodology, which was applied to the case study of citrus pulp production in Sicily, included official statistics data and information derived from specific surveys and the computation of indicators regarding citrus‐producing areas, citrus production, processed production, and the amount of citrus pulp obtained. The results showed that the index that describes the level of availability of citrus pulp for biogas production is suitable to provide information on the potential production of citrus pulp in the different areas of the whole territory analyzed. Furthermore, the total amount of available citrus pulp corresponded theoretically to 15,204,775.8 Nm3 biogas. © 2016 Society of Chemical Industry and John Wiley & Sons, Ltd
Down‐regulation of hepatic CYP3A1 expression in a rat model of indomethacin‐induced small intestinal ulcers
Authors: Kawauchi Shoji , Nakamura Tsutomu , Horibe Sayo , Tanahashi Toshihito , Mizuno Shigeto , Hamaguchi Tsuneo , Rikitake Yoshiyuki 
Published: September 2016

AbstractThe liver and the small intestine are closely related in the processes of drug absorption, metabolism and excretion via the enterohepatic circulation. Small intestinal ulcers are a serious adverse effect commonly occurring in patients taking nonsteroidal anti‐inflammatory drugs. However, the influence of small intestinal ulcers on drug metabolism has not been established. This study examined the expressional changes of cytochrome P450 (CYP) in the liver using an indomethacin‐induced small intestinal ulcer rat model and in cultured cells. After the administration of indomethacin to rats, ulcers were observed in the small intestine and expression of CYP3A1, the major isoform of hepatic CYP, was significantly down‐regulated in the liver, accompanied by increased expression of inducible nitric oxide synthase, tumor necrosis factor α, interleukin (IL)‐1β and IL‐6, in the small intestine and the liver. The indomethacin‐induced small intestinal ulceration, the increase in inflammatory mediators in the small intestine and the liver, and the down‐regulation of CYP3A1 expression in the liver were inhibited by co‐administration of ampicillin, an antibacterial agent. In the human hepatic HepG2 cell line, IL‐1β, IL‐6 and NOC‐18, an NO donor, caused down‐regulation of CYP3A4, the major isoform of human CYP3A. Thus, this study suggests that after indomethacin treatment small intestinal ulcers cause the down‐regulation of CYP3A1 in the rat liver through an increase in ulcer‐derived inflammatory mediators. Copyright © 2016 John Wiley & Sons, Ltd.
Identification of key genes involved in polysaccharide bioflocculant synthesis in Bacillus licheniformis
Authors: Chen Zhen , Liu Peize , Li Zhipeng , Yu Wencheng , Wang Zhi , Yao Haosheng , Wang Yuanpeng , Li Qingbiao , Deng Xu , He Ning 
Published: September 2016

ABSTRACTThe present study reports the sequenced genome of Bacillus licheniformis CGMCC 2876, which is composed of a 4,284,461 bp chromosome that contains 4,188 protein‐coding genes, 72 tRNA genes, and 21 rRNA genes. Additional analysis revealed an eps gene cluster with 16 open reading frames. Conserved Domains Database analysis combined with qPCR experiments indicated that all genes in this cluster were involved in polysaccharide bioflocculant synthesis. Phosphoglucomutase and UDP‐glucose pyrophosphorylase were supposed to be key enzymes in polysaccharide secretion in B. licheniformis. A biosynthesis pathway for the production of polysaccharide bioflocculant involving the integration of individual genes was proposed based on functional analysis. Overexpression of epsDEF from the eps gene cluster in B. licheniformis CGMCC 2876 increased the flocculating activity of the recombinant strain by 90% compared to the original strain. Similarly, the crude yield of polysaccharide bioflocculant was enhanced by 27.8%. Overexpression of the UDP‐glucose pyrophosphorylase gene not only increased the flocculating activity by 71% but also increased bioflocculant yield by 13.3%. Independent of UDP‐N‐acetyl‐D‐mannosamine dehydrogenase gene, flocculating activity, and polysaccharide yield were negatively impacted by overexpression of the UDP‐N‐acetylglucosamine 2‐epimerase gene. Overall, epsDEF and gtaB2 were identified as key genes for polysaccharide bioflocculant synthesis in B. licheniformis. These results will be useful for further engineering of B. licheniformis for industrial bioflocculant production. Biotechnol. Bioeng. 2017;114: 645–655. © 2016 Wiley Periodicals, Inc.
Development of in situ product removal strategies in biocatalysis applying scaled‐down unit operations
Authors: Heintz Søren , Börner Tim , Ringborg Rolf H. , Rehn Gustav , Grey Carl , Nordblad Mathias , Krühne Ulrich , Gernaey Krist V. , Adlercreutz Patrick , Woodley John M. 
Published: September 2016

ABSTRACTAn experimental platform based on scaled‐down unit operations combined in a plug‐and‐play manner enables easy and highly flexible testing of advanced biocatalytic process options such as in situ product removal (ISPR) process strategies. In such a platform, it is possible to compartmentalize different process steps while operating it as a combined system, giving the possibility to test and characterize the performance of novel process concepts and biocatalysts with minimal influence of inhibitory products. Here the capabilities of performing process development by applying scaled‐down unit operations are highlighted through a case study investigating the asymmetric synthesis of 1‐methyl‐3‐phenylpropylamine (MPPA) using ω‐transaminase, an enzyme in the sub‐family of amino transferases (ATAs). An on‐line HPLC system was applied to avoid manual sample handling and to semi‐automatically characterize ω‐transaminases in a scaled‐down packed‐bed reactor (PBR) module, showing MPPA as a strong inhibitor. To overcome the inhibition, a two‐step liquid–liquid extraction (LLE) ISPR concept was tested using scaled‐down unit operations combined in a plug‐and‐play manner. Through the tested ISPR concept, it was possible to continuously feed the main substrate benzylacetone (BA) and extract the main product MPPA throughout the reaction, thereby overcoming the challenges of low substrate solubility and product inhibition. The tested ISPR concept achieved a product concentration of 26.5 gMPPA · L−1, a purity up to 70% gMPPA · gtot−1 and a recovery in the range of 80% mol · mol−1 of MPPA in 20 h, with the possibility to increase the concentration, purity, and recovery further. Biotechnol. Bioeng. 2017;114: 600–609. © 2016 Wiley Periodicals, Inc.
Simultaneous analysis of 35 specific antihypertensive adulterants in dietary supplements using LC/MS/MS
Authors: Heo Seok , Choi Ji Yeon , Yoo Geum Joo , Park Sung‐Kwan , Baek Sun Young 
Published: September 2016

AbstractA sensitive and specific LC/MS/MS method was developed for the simultaneous analysis of 35 compounds used for treating hypertension as adulterants in dietary supplements. The method was validated for specificity, linearity, accuracy, precision, limit of detection, limit of quantitation, stability and recovery. The limit of detection and limit of quantitation ranged from 0.20 to 20.0 and 0.50 to 60.0 ng/g, respectively. The linearity was good (r2 > 0.999), with intra‐ and interday precision levels of 0.43–7.87% and 0.65–9.95% and the intra‐ and interday accuracies of 84.36–115.82% and 83.78–118.69%, respectively. The stability (relative standard deviation) was <14.75%. The mean recovery was 80.81–117.86% (relative standard deviation <10.00%). Ninety‐seven commercial dietary supplements available in South Korea were analyzed. While none contained detectable amounts of the 35 antihypertensive compounds, the developed LC/MS/MS procedure can be used for routine analysis to monitor illegal adulteration in various forms of dietary supplements.
Primary cutaneous B‐cell lymphoma other than marginal zone: clinicopathologic analysis of 161 cases: Comparison with current classification and definition of prognostic markers
Authors: Lucioni Marco , Berti Emilio , Arcaini Luca , Croci Giorgio A. , Maffi Aldo , Klersy Catherine , Goteri Gaia , Tomasini Carlo , Quaglino Pietro , Riboni Roberta , Arra Mariarosa , Dallera Elena , Grandi Vieri , Alaibac Mauro , Ramponi Antonio , Rattotti Sara , Cabras Maria Giuseppina , Franceschetti Silvia , Fraternali‐Orcioni Giulio , Zerbinati Nicola , Onida Francesco , Ascani Stefano , Fierro Maria Teresa , Rupoli Serena , Gambacorta Marcello , Zinzani Pier Luigi , Pimpinelli Nicola , Santucci Marco , Paulli Marco 
Published: September 2016

AbstractCategorization of primary cutaneous B‐cell lymphomas (PCBCL) other than marginal zone (MZL) represents a diagnostic challenge with relevant prognostic implications. The 2008 WHO lymphoma classification recognizes only primary cutaneous follicular center cell lymphoma (PCFCCL) and primary cutaneous diffuse large B‐cell lymphoma, leg type (PCDLBCL‐LT), whereas the previous 2005 WHO/EORTC classification also included an intermediate form, namely PCDLBCL, other. We conducted a retrospective, multicentric, consensus‐based revision of the clinicopathologic characteristics of 161 cases of PCBCL other than MZL. Upon the histologic features that are listed in the WHO classification, 96 cases were classified as PCFCCL and 25 as PCDLBCL‐LT; 40 further cases did not fit in the former subgroups in terms of cytology and/or architecture, thus were classified as PCDLBCL, not otherwise specified (PCDLBCL‐NOS). We assigned all the cases a histogenetic profile, based on the immunohistochemical detection of CD10, BCL6, and MUM1, and a “double hit score” upon positivity for BCL2 and MYC. PCDLBCL‐NOS had a clinical presentation more similar to PCFCCL, whereas the histology was more consistent with the picture of a diffuse large B‐cell lymphoma, as predominantly composed of centroblasts but with intermixed a reactive infiltrate of small lymphocytes. Its behavior was intermediate between the other two forms, particularly when considering only cases with a “non‐germinal B‐cell” profile, whereas “germinal center” cases resembled PCFCCL. Our data confirmed the aggressive behavior of PCDLBC‐LT, which often coexpressed MYC and BCL2. The impact of single factors on 5‐year survival was documented, particularly histogenetic profile in PCDLBCL and BCL2 translocation in PCFCCL. Our study confirms that a further group—PCDLBCL‐NOS—exists, which can be recognized through a careful combination of histopathologic criteria coupled with adequate clinical information.