bluuebunny/crossref_metadata_2025 huggingface dataset:
Expansion of the variable expression of Muenke syndrome: Hydrocephalus without craniosynostosis
Authors: González‐del Angel Ariadna , Estandía‐Ortega Bernardette , Alcántara‐Ortigoza Miguel Angel , Martínez‐Cruz Víctor , Gutiérrez‐Tinajero Diana Judith , Rasmussen Astrid , Gómez‐González Claudia Sofía
Published: August 2016

Muenke syndrome (MS) is an autosomal dominant coronal craniosynostosis syndrome with variable extracranial anomalies. We studied 56 unrelated patients with non‐syndromic uni‐ or bicoronal craniosynostosi to identify the frequency and clinical characteristics of MS in a cohort of Mexican childrens. The FGFR3 pathogenic variation p.Pro250Arg responsible for MS was characterized in all probands by PCR‐restriction assay; available first‐degree relatives (15 parents, 5 siblings) of the confirmed p.Pro250Arg carriers were also tested. All heterozygotes for p.Pro250Arg underwent clinical and audiologic assessment, as well as X‐ray evaluations of hands and feet. Eight of 56 probands (14%) were found to carry the p.Pro250Arg variant and half of them were familial cases. Four p.Pro250Arg heterozygous familial members had been considered unaffected before the molecular testing. In one MS family, hydrocephalus without craniosynostosis, was documented as the only clinical manifestation in a previously undetected heterozygous male sibling. Hydrocephalus without craniosynostosis in a patient with the p.Pro250Arg variant suggests that some patients with MS might present only this manifestation; to our knowledge, hydrocephalus has not been described as isolated feature in MS, so we propose to consider this feature as an expansion of the MS phenotype rather than an unrelated finding. Our data also reinforce the notion that molecular testing of FGFR3 must be included in the diagnostic approach of coronal craniosynostosis. This will allow accurate genetic counseling and optimal management of MS, which might otherwise go undiagnosed because of mild manifestations and wide variability of expression. © 2016 Wiley Periodicals, Inc.
Kabuki syndrome as a cause of non‐immune fetal hydrops/ascites
Authors: Long Ashleigh , Sinkovskaya Elena S. , Edmondson Andrew C. , Zackai Elaine , Schrier Vergano Samantha A.
Published: August 2016

Kabuki syndrome (MIM 147920) is a well‐described, multiple congenital anomaly syndrome characterized by growth and developmental delay, cardiac, renal, and vertebral anomalies, as well as persistent fetal finger pads and distinct facial features. Facies are characterized by long palpebral fissures with eversion of lateral third of the lower eyelid, resembling the “Kabuki make‐up” theatre genre after which the syndrome is named. Kabuki syndrome is estimated to affect 1/32,000 births, with 55–80% of patients showing nonsense or frameshift mutations in the KMT2D (MLL2) gene, which encodes a histone transferase located on chromosome 12q. Additionally, owing to the heterogeneous nature of Kabuki syndrome, a smaller number of diagnosed patients have been identified with mutations or deletions in KDM6A (a component of the same transcriptional complex as KMT2D) with no mutations in KMT2D, or as those diagnosed with Kabuki syndrome and without alterations in either KMT2D or KDM6A. Diagnosis of the syndrome in newborns and infants is difficult, as the facial features are not as evident as in toddler‐ or childhood. There are no known “tell‐tale” signs of Kabuki syndrome prenatally, and there are no reports of common, specific findings in fetuses that might suggest the diagnosis. We present here two infants who presented with prenatal hydrops/ascites, who were subsequently diagnosed with Kabuki syndrome. Although relatively non‐specific, we suggest that Kabuki syndrome be added to the list of genetic syndromes that are suspected in cases of prenatal hydrops, review the molecular etiology of Kabuki syndrome, and broaden the phenotype of this well‐described disorder. © 2016 Wiley Periodicals, Inc.
Wahrnehmung der chemischen Prozesse in einzelnen Organellen mit niedermolekularen Fluoreszenzsonden
Authors: Xu Wang , Zeng Zebing , Jiang Jian‐Hui , Chang Young‐Tae , Yuan Lin
Published: August 2016

Ohne genau durchdachte Fluoreszenzmarker/‐sonden kann auch das fortschrittlichste hochauflösende Mikroskopieverfahren keinen Einblick in subzelluläre Matrizes geben. Die Entwicklung der Biologie wurde in zunehmendem Maße durch Fortschritte im Bereich der Chemie vorangetrieben. Ein prominentes Beispiel hierfür sind niedermolekulare Fluoreszenzsonden, die nicht nur die Bildgebung auf zellulärer Ebene ermöglichen, sondern auch subzelluläre Abbildungen. Die meisten chemischen/biologischen Ereignisse finden innerhalb von Zellorganellen statt, sodass diese Substrukturen zunehmend mithilfe von Fluoreszenzverfahren untersucht wurden. Dieser Aufsatz fasst die vorhandenen Fluoreszenzsonden zusammen, die auf chemische/biologische Geschehnisse innerhalb einzelner Organellen zielen. Darüber hinaus werden Strategien zur Verankerung an den Organellen vorgestellt, um das Design neuer Fluoreszenzsonden anzuregen. Abschließend werden die Zukunftsaussichten für weitere Entwicklungen in der chemischen Biologie diskutiert.
Metal Transition in Sodium–Ammonia Nanodroplets
Authors: Hartweg Sebastian , West Adam H. C. , Yoder Bruce L. , Signorell Ruth
Published: August 2016

The famous nonmetal‐to‐metal transition in Na–ammonia solutions is investigated in nanoscale solution droplets by photoelectron spectroscopy. In agreement with the bulk solutions, a strong indication for a transition to the metallic state is found at an average metal concentration of 8.8±2.2 mole%. The smallest entity for the phase transition to be observed consists of approximately 100–200 solvent molecules. The quantification of this critical entity size is a stepping stone toward a deeper understanding of these quantum–classical solutions through direct modeling at the molecular level.
Application of a Palladium‐Catalyzed C−H Functionalization/Indolization Method to Syntheses of cis‐Trikentrin A and Herbindole B
Authors: Leal Raul A. , Bischof Caroline , Lee Youjin V. , Sawano Shota , McAtee Christopher C. , Latimer Luke N. , Russ Zachary N. , Dueber John E. , Yu Jin‐Quan , Sarpong Richmond
Published: August 2016

We describe herein formal syntheses of the indole alkaloids cis‐trikentrin A and herbindole B from a common meso‐hydroquinone intermediate prepared by a ruthenium‐catalyzed [2+2+1+1] cycloaddition that has not been used previously in natural product synthesis. Key steps include a sterically demanding Buchwald–Hartwig amination as well as a unique C(sp3)−H amination/indole formation. Studies toward a selective desymmetrization of the meso‐hydroquinone are also reported.
Discerning the Chemistry in Individual Organelles with Small‐Molecule Fluorescent Probes
Authors: Xu Wang , Zeng Zebing , Jiang Jian‐Hui , Chang Young‐Tae , Yuan Lin
Published: August 2016

Principle has it that even the most advanced super‐resolution microscope would be futile in providing biological insight into subcellular matrices without well‐designed fluorescent tags/probes. Developments in biology have increasingly been boosted by advances of chemistry, with one prominent example being small‐molecule fluorescent probes that not only allow cellular‐level imaging, but also subcellular imaging. A majority, if not all, of the chemical/biological events take place inside cellular organelles, and researchers have been shifting their attention towards these substructures with the help of fluorescence techniques. This Review summarizes the existing fluorescent probes that target chemical/biological events within a single organelle. More importantly, organelle‐anchoring strategies are described and emphasized to inspire the design of new generations of fluorescent probes, before concluding with future prospects on the possible further development of chemical biology.
Cyclometalated Palladium(II) N‐Heterocyclic Carbene Complexes: Anticancer Agents for Potent In Vitro Cytotoxicity and In Vivo Tumor Growth Suppression
Authors: Fong Tommy Tsz‐Him , Lok Chun‐Nam , Chung Clive Yik‐Sham , Fung Yi‐Man Eva , Chow Pui‐Keong , Wan Pui‐Ki , Che Chi‐Ming
Published: August 2016

Palladium(II) complexes are generally reactive toward substitution/reduction, and their biological applications are seldom explored. A new series of palladium(II) N‐heterocyclic carbene (NHC) complexes that are stable in the presence of biological thiols are reported. A representative complex, [Pd(C^N^N)(N,N′‐nBu2NHC)](CF3SO3) (Pd1 d, HC^N^N=6‐phenyl‐2,2′‐bipyridine, N,N′‐nBu2NHC=N,N′‐di‐n‐butylimidazolylidene), displays potent killing activity toward cancer cell lines (IC50=0.09–0.5 μm) but is less cytotoxic toward a normal human fibroblast cell line (CCD‐19Lu, IC50=11.8 μm). In vivo anticancer studies revealed that Pd1 d significantly inhibited tumor growth in a nude mice model. Proteomics data and in vitro biochemical assays reveal that Pd1 d exerts anticancer effects, including inhibition of an epidermal growth factor receptor pathway, induction of mitochondrial dysfunction, and antiangiogenic activity to endothelial cells.
Effect of block composition on the morphology, hydration, and transport properties of sulfonated PS‐b‐PEGPEM‐b‐PS
Authors: Pérez‐Pérez Maritza , Suleiman David
Published: August 2016

This work discusses the effect of block composition on the properties of proton conducting polymer membranes. A homopolymer and two block copolymers were synthesized using atom transfer radical polymerization. The homopolymer poly(ethylene glycol phenyl ether methacrylate) (PEGPEM) was used as a bifunctional macroinitiator. Polystyrene (PS), was added to both sides of PEGPEM (A) with two different percentages of PS (B) (i.e., 18 and 31%). These copolymers, BAB 18, BAB 31 and the homopolymer A, were completely sulfonated (SA, SBAB 18 and SBAB 31). The resulting polymers produced different water absorption values and transport properties for direct methanol fuel cell (DMFC) applications. The nanostructure and morphology of the casted membranes were studied using small‐angle X‐ray scattering and atomic force microscopy. The results revealed that all six membranes exhibited a disordered phase‐segregated morphology, which changed on sulfonation into small‐interconnected ionic domains. Normalized DMFC selectivities (proton conductivity over methanol permeability divided by the respective values for Nafion®) were calculated and ranged from 1.16 (SBAB 31) to 15.30 (BAB 18), indicating that the performance of these materials can be comparable or better than Nafion®. Transport property results also suggest that chemistry (block nature and composition), morphology and water content play a critical role in the transport mechanism of protons and methanol. For example, the percentage of B in BAB 18 provides shorter interstitial ionic distances and sufficient water content to produce high proton conductivity, while maintaining low methanol permeability in a multi‐ionic proton exchange membrane. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 44343.
Measurement of urine indolylacroylglycine is not useful in the diagnosis or dietary management of autism
Authors: Dalton Neil R. , Chandler Susie , Turner Charles , Charman Tony , Pickles Andrew , Simonoff Emily , Baird Gillian
Published: August 2016

To measure urine indolylacroylglycine (IAG) excretion using the IAG:creatinine ratio in children with autism spectrum disorder (ASD) compared with two groups of age matched controls, one with special needs but without ASD (SEN) and one typically developing (TD) and in subgroups with/without current gastrointestinal problems and ASD with and without regression. IAG:creatinine ratio was measured in the urine of 279 children aged 10–14 years: 129 children with ASD (28 with and 101 without regression), 62 SEN controls and 88 TD controls. The prevalence of gastro‐intestinal symptoms (GIS) was recorded. No differences were found in the urine IAG:creatinine ratio among groups ASD, TD and SEN; nor in the ASD groups with/without regression, nor in those with/without GIS. This study finds no evidence of increased urine IAG excretion in children with ASD, with or without GIS or with or without regression. Urinary IAG measurements in children with ASD offer no support for increased presence of neuroactive peptides proposed to result from increased gut permeability. We found measurement of urinary IAG to have no value in the diagnosis of autism or in the dietary management of children with ASD. Autism Res 2017, 10: 408–413. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
Discriminating typical and atypical cystic fibrosis‐related bacteria by multiplex PNA‐FISH
Authors: Lopes Susana P. , Carvalho Daniel T. , Pereira Maria O. , Azevedo Nuno F.
Published: August 2016

This study aims to report the development of peptide nucleic acid (PNA) probes to specifically detect the cystic fibrosis (CF)‐associated traditional and atypical species Pseudomonas aeruginosa and Inquilinus limosus, respectively. PNA probes were designed in silico, developed and tested in smears prepared in phosphate‐buffer saline (PBS), and in artificial sputum medium (ASM). A multiplex fluorescent in situ hybridization (FISH) approach using the designed probes was further validated in artificially contaminated clinical sputum samples and also applied in polymicrobial 24 h‐old biofilms involving P. aeruginosa, I. limosus, and other CF‐related bacteria. Both probes showed high predictive and experimental specificities and sensitivities. The multiplex PNA‐FISH assay, associated with non‐specific staining, was successfully adapted in the clinical samples and in biofilms of CF‐related bacteria, allowing differentiating the community members and inferring about microbial‐microbial interactions within the consortia. This study revealed the great potential of PNA‐FISH as a diagnostic tool to discriminate between classical and less common CF‐associated bacteria, being suitable to further describe species‐dependent prevention strategies and deliver more effective target control therapeutics. Biotechnol. Bioeng. 2017;114: 355–367. © 2016 Wiley Periodicals, Inc.
A pumpless multi‐organ‐on‐a‐chip (MOC) combined with a pharmacokinetic–pharmacodynamic (PK–PD) model
Authors: Lee Hyuna , Kim Dae Shik , Ha Sang Keun , Choi Inwook , Lee Jong Min , Sung Jong Hwan
Published: August 2016

A multi‐organ‐on‐a‐chip (MOC), also known as a human‐on‐a‐chip, aims to simulate whole body response to drugs by connecting microscale cell cultures of multiple tissue types via fluidic channels and reproducing the interaction between them. While several studies have demonstrated the usefulness of MOC at a proof‐of‐concept level, improvements are needed to enable wider acceptance of such systems; ease of use for general biological researchers, and a mathematical framework to design and interpret the MOC systems. Here, we introduce a pumpless, user‐friendly MOC which can be easily assembled and operated, and demonstrate the use of a PK–PD model for interpreting drug's action inside the MOC. The metabolism‐dependent anticancer activity of a flavonoid, luteolin, was evaluated in a two‐compartment MOC containing the liver (HepG2) and the tumor (HeLa) cells, and the observed anticancer activity was significantly weaker than that anticipated from a well plate study. Simulation of a PK–PD model revealed that simultaneous metabolism and tumor‐killing actions likely resulted in a decreased anti‐cancer effect. Our work demonstrates that the combined platform of mathematical PK–PD model and an experimental MOC can be a useful tool for gaining an insight into the mechanism of action of drugs with interactions between multiple organs. Biotechnol. Bioeng. 2017;114: 432–443. © 2016 Wiley Periodicals, Inc.
The role of host cell physiology in the productivity of the baculovirus‐insect cell system: Fluxome analysis of Trichoplusia ni and Spodoptera frugiperda cell lines
Authors: Monteiro Francisca , Bernal Vicente , Alves Paula M.
Published: August 2016

The Insect Cell‐Baculovirus Expression Vector System (IC‐BEVS) is broadly used for the production of recombinant proteins and vaccine manufacture, yet the host physiological aspects that contribute to productivity are to be disclosed. This work provides the first quantitative analysis of the metabolic fluxes of High Five cells. This analysis was conducted in comparison with Sf9 cells, another major host for biologicals production via BEVS. Moreover, herein is presented, for the first time, quantitative data of the relative contribution of sugars and amino acids catabolism to the activity of the TCA cycle in Sf9 and High Five cells. High Five cells metabolic activity was markedly influenced by the amino acids concentration in culture medium, which determine the rates of amino acid catabolism, carbon overflow and by‐product formation. This characteristic of High Five cells was reflected in the activities of anaplerotic metabolism and the TCA cycle, which may not work as a true cycle as a function of medium composition. This was not the case for Sf9 cells, in which the glucose carbon incorporation in the TCA cycle was significantly higher and lactate production minor. Following infection, the decrease in by‐product accumulation rates was accompanied by an increase in net ATP synthesis in Sf9 and High Five cells, although through distinct mechanisms cell‐line dependent. The impact of baculovirus infection on cellular metabolic status highlights the capacity of this virus to re‐direct the cellular fluxome toward ATP production to support replication and progeny generation. These results pave the way to deepen our knowledge on the relationship between a host cell and the virus, contributing to disclosing the metabolic determinants that contribute to productivity. Biotechnol. Bioeng. 2017;114: 674–684. © 2016 Wiley Periodicals, Inc.
The future of protein scaffolds as affinity reagents for purification
Authors: Dias Ana M.G.C. , Roque Ana C.A.
Published: August 2016

Affinity purification is one of the most powerful separation techniques extensively employed both at laboratory and production scales. While antibodies still represent the gold standard affinity reagents, others derived from non‐immunoglobulin scaffolds emerged as interesting alternatives in particular for affinity purification. The lower costs of production, fast ligand development, and high robustness are appealing advantages of non‐immunoglobulin scaffolds. These have successfully been used in the affinity purification of relevant targets as antibodies, human serum albumin, transferrin, and other biomarkers, as reviewed in this work. Furthermore, a critical assessment on the strengths, weaknesses, opportunities, and threats related with the implementation of non‐immunoglobulin scaffolds as ligands in affinity purification are discussed. Biotechnol. Bioeng. 2017;114: 481–491. © 2016 Wiley Periodicals, Inc.
A UPLC–MS/MS approach for simultaneous determination of eight flavonoids in rat plasma, and its application to pharmacokinetic studies of Fu‐Zhu‐Jiang‐Tang tablet in rats
Authors: Tao Yi , Chen Xi , Jiang Yanhui , Cai Baochang
Published: August 2016

The purpose of this study is to establish and validate a UPLC–MS/MS approach to determine eight flavonoids in biological samples and apply the method to pharmacokinetic study of Fu‐Zhu‐Jiang‐Tang tablet. A Waters BEH C18 UPLC column was employed with methanol/0.1% formic acid–water as mobile phases. The mass analysis was carried out in a triple quadrupole mass spectrometer using multiple reaction monitoring with negative scan mode. A one‐step protein precipitation by methanol was used to extract the analytes from blood. Eight major flavonoids were selected as markers. Our results showed that calibration curves for 3′‐hydroxypuerarin, mirificin, puerarin, 3′‐methoxypuerarin, daidzin, rutin, astragalin and daidzein displayed good linear regression (r2 > 0.9986). The intra‐day and inter‐day precisions (RSD) of the eight flavonoids at high, medium and low levels were <8.03% and the bias of the accuracies ranged from −5.20 to 6.75%.The extraction recoveries of the eight flavonoids were from 91.4 to 100.5% and the matrix effects ranged from 89.8 to 103.8%. The validated approach was successfully applied to a pharmacokinetic study in Sprague–Dawley rats after oral administration of FZJT tablet. Double peaks were emerged in curves of mean plasma concentration for 3′‐methoxypuerarin, which was reported for the first time.
Hemodynamics‐driven deposition of intraluminal thrombus in abdominal aortic aneurysms
Authors: Di Achille P. , Tellides G. , Humphrey J. D.
Published: August 2016

Accumulating evidence suggests that intraluminal thrombus plays many roles in the natural history of abdominal aortic aneurysms. There is, therefore, a pressing need for computational models that can describe and predict the initiation and progression of thrombus in aneurysms. In this paper, we introduce a phenomenological metric for thrombus deposition potential and use hemodynamic simulations based on medical images from 6 patients to identify best‐fit values of the 2 key model parameters. We then introduce a shape optimization method to predict the associated radial growth of the thrombus into the lumen based on the expectation that thrombus initiation will create a thrombogenic surface, which in turn will promote growth until increasing hemodynamically induced frictional forces prevent any further cell or protein deposition. Comparisons between predicted and actual intraluminal thrombus in the 6 patient‐specific aneurysms suggest that this phenomenological description provides a good first estimate of thrombus deposition. We submit further that, because the biologically active region of the thrombus appears to be confined to a thin luminal layer, predictions of morphology alone may be sufficient to inform fluid‐solid–growth models of aneurysmal growth and remodeling.
Consumption of a high‐fat meal was associated with an increase in monocyte adhesion molecules, scavenger receptors, and Propensity to Form Foam Cells
Authors: Henning A. L. , Venable A. S. , Vingren J. L. , Hill D. W. , McFarlin B. K.
Published: August 2016

Background

Macrophage‐derived foam cells are the predominant component of arterial plaques in the early stages of atherosclerosis. One factor that poses a major risk for plaque development is high levels of plasma low‐density lipoprotein (LDL) as a result of a high‐fat meal. In order to better understand how an individuals' diet affects arterial plaque deposition via the process of foam cell formation, we measured the acute circulating monocyte activity response after consuming a high‐fat meal (85% of daily fat allowance).

Materials and Methods

Venous blood samples from 17 participants were acquired on a FlowSight. Samples were analyzed to identify nonclassical (CD14+/16+) and classical (CD14+/16−) monocytes. We measured monocyte concentration, adhesion molecule expression, CD36 expression, and oxidized LDL (oxLDL) endocytosis for preprandial 1, 3, and 5 h postprandial.

Results

Consuming a high‐fat meal caused increases in oxLDL uptake, adhesion molecule expression, and CD36 expression in both classical and nonclassical monocytes, with the nonclassical monocytes responding with larger increases than the classical monocytes.

Conclusion

These results suggest that consumption of a high‐fat meal increased the potential of monocytes to become foam cells, and implicates nonclassical monocytes as having greater potential than classical monocytes to become foam cells. © 2016 International Clinical Cytometry Society
Neuroprotective effects of testosterone metabolites and dependency on receptor action on the morphology of somatic motoneurons following the death of neighboring motoneurons
Authors: Cai Yi , Chew Cory , Muñoz Fernando , Sengelaub Dale R.
Published: August 2016

Partial depletion of spinal motoneuron populations induces dendritic atrophy in neighboring motoneurons, and treatment with testosterone is neuroprotective, attenuating induced dendritic atrophy. In this study we examined whether the protective effects of testosterone could be mediated via its androgenic or estrogenic metabolites. Furthermore, to assess whether these neuroprotective effects were mediated through steroid hormone receptors, we used receptor antagonists to attempt to prevent the neuroprotective effects of hormones after partial motoneuron depletion. Motoneurons innervating the vastus medialis muscles of adult male rats were selectively killed by intramuscular injection of cholera toxin‐conjugated saporin. Simultaneously, some saporin‐injected rats were treated with either dihydrotestosterone or estradiol, alone or in combination with their respective receptor antagonists, or left untreated. Four weeks later, motoneurons innervating the ipsilateral vastus lateralis muscle were labeled with cholera toxin‐conjugated horseradish peroxidase, and dendritic arbors were reconstructed in three dimensions. Compared with intact normal animals, partial motoneuron depletion resulted in decreased dendritic length in remaining quadriceps motoneurons. Dendritic atrophy was attenuated with both dihydrotestosterone and estradiol treatment to a degree similar to that seen with testosterone, and attenuation of atrophy was prevented by receptor blockade. Together, these findings suggest that neuroprotective effects on motoneurons can be mediated by either androgenic or estrogenic hormones and require action via steroid hormone receptors, further supporting a role for hormones as neurotherapeutic agents in the injured nervous system. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 691–707, 2017
IL‐1R1–MyD88 axis elicits papain‐induced lung inflammation
Authors: Agoro Rafiou , Piotet‐Morin Julie , Palomo Jennifer , Michaudel Chloé , Vigne Solenne , Maillet Isabelle , Chenuet Pauline , Guillou Noëlline , Le Bérichel Jessica , Kisielow Malgorzata , Flodby Per , Borok Zea , Crandall Edward D. , Le Bert Marc , Quesniaux Valérie , Muller Matthias , Di Padova Franco , Ryffel Bernhard , Gabay Cem , Couturier‐Maillard Aurélie
Published: August 2016

Allergic asthma is characterized by a strong Th2 response with inflammatory cell recruitment and structural changes in the lung. Papain is a protease allergen disrupting the airway epithelium triggering a rapid inflammation with eosinophilia mediated by innate lymphoid cell activation (ILC2) and leading to a Th2 immune response. In this study, we focused on inflammatory responses to a single exposure to papain and showed that intranasal administration of papain results in the recruitment of inflammatory cells, including neutrophils and eosinophils with a rapid production of IL‐1α, IL‐1β, and IL‐33. The inflammatory response is abrogated in the absence of IL‐1R1 and MyD88. To decipher the cell type(s) involved in MyD88‐dependent IL‐1R1/MyD88 signaling, we used new cell‐specific MyD88‐deficient mice and found that the deletion of MyD88 signaling in single cell types such as T cells, epithelial cells, CD11c‐positive or myeloid cells leads to only a partial inhibition compared to complete absence of MyD88, suggesting that several cell types contribute to the response. Importantly, the inflammatory response is largely ST2 and IL‐36R independent. In conclusion, IL‐1R1 signaling via MyD88 is critical for the first step of inflammatory response to papain.
Protein phosphatase 1 abrogates IRF7‐mediated type I IFN response in antiviral immunity
Authors: Wang Ling , Zhao Juan , Ren Junping , Hall Kenton H. , Moorman Jonathan P. , Yao Zhi Q. , Ning Shunbin
Published: August 2016

Interferon (IFN) regulatory factor 7 (IRF7) plays a key role in the production of IFN‐α in response to viral infection, and phosphorylation at IRF7 C‐terminal serine sites is prelude to its function. However, phosphatases that negatively regulate IRF7 phosphorylation and activity have not been reported. In this study, we have identified a conserved protein phosphatase 1 (PP1)‐binding motif in human and mouse IRF7 proteins, and shown that PP1 physically interacts with IRF7. Exogenous expression of PP1 subunits (PP1α, β, or γ) ablates IKKε‐stimulated IRF7 phosphorylation and dramatically attenuates IRF7 transcriptional activity. Inhibition of PP1 activity significantly increases IRF7 phosphorylation and IRF7‐mediated IFN‐α production in response to Newcastle disease virus (NDV) infection or Toll‐like receptor 7 (TLR7) challenge, leading to impaired viral replication. In addition, IFN treatment, TLR challenges and viral infection induce PP1 expression. Our findings disclose for the first time a pivotal role for PP1 in impeding IRF7‐mediated IFN‐α production in host immune responses.
Diastereoselective Synthesis of Dialkylated Bis(phosphino)ferrocenes: Their Use in Promoting Silver‐Mediated Nucleophilic Fluorination of Chloroquinolines
Authors: Roger Julien , Royer Sylviane , Cattey Hélène , Savateev Aleksandr , Smaliy Radomyr V. , Kostyuk Aleksandr N. , Hierso Jean‐Cyrille
Published: August 2016

The diastereoselective synthesis of dialkylated ferrocenyl bis(phosphane)s bearing aryl, alkyl, and hetero‐ or polycyclic substituents on the phosphino groups is reported, together with their characterization in the solid state by X‐ray structure analysis and in solution by multinuclear NMR spectroscopy. Introduction of various alkyl groups on the ferrocene backbone, namely, tert‐butyl, isopropyl, and trimethylsilyl, has a significant influence on the stereoselectivity of the ensuing lithiation/phosphination reactions. Only the introduction of the tert‐butyl groups ensures both a high yield and perfect diastereoselectivity, which leads to the exclusive formation of the rac planar chiral tert‐butylated diphosphanes. The introduction of electron‐rich and ‐poor phosphorus‐based functional groups, namely, furyl‐, isopropyl‐, cyclohexyl‐, phenyl‐, mesityl‐phosphino, and benzophosphindole, is achieved and gives new alkylated ferrocenyl diphosphanes in moderate to high yields. Investigations are conducted to apply these robust alkylated diphosphanes as auxiliaries in the very challenging palladium‐catalyzed nucleophilic fluorination of chloroquinolines at the C–Cl bond. Unexpectedly, a significant favorable effect from the ferrocenyl phosphanes is evidenced by using the commercial AgF reagent for this fluorination that renders any palladium addition useless. This innovative nucleophilic fluorination thus avoids harsh conditions (strictly anhydrous) and highly specialized reagents.
Determination of the Solubility of Rhabdophanes LnPO4·0.667H2O (Ln = La to Dy)
Authors: Gausse Clémence , Szenknect Stéphanie , Qin Dan Wen , Mesbah Adel , Clavier Nicolas , Neumeier Stefan , Bosbach Dirk , Dacheux Nicolas
Published: August 2016

A systematic study of the solubility of the rhabdophanes LnPO4·0.667H2O (Ln = La–Dy) was performed through oversaturation and undersaturation experiments at different temperatures (298–363 K) to demonstrate the reversibility of the equilibria. The structure of the neoformed phase was controlled carefully over the entire temperature range to enable the unambiguous attribution of the solubility products and the derived thermodynamic data to the rhabdophane phases. The log K°s,0 (298 K) values for LnPO4·0.667H2O ranged from –25.6 ± 0.8 (Pr) to –24.9 ± 1.7 (Eu), and the minimum values were for Pr to Sm, whereas the ΔfG° values at 298 K varied between (–1984 ± 2) and (–2004 ± 2) kJ mol–1 whatever the lanthanide element considered, except for Eu‐rhabdophane, which presented the highest Gibbs energy of formation [(–1896 ± 2) kJ mol–1]. From the solubility data obtained at various temperatures, the enthalpies of formation of the rhabdophanes ΔfH° were found to be (–2151 ± 13) to (–2130 ± 12) kJ mol–1, excepted for that of Eu, which reached (–2057 ± 9) kJ mol–1.
Homo‐ and Heteroleptic Copper(I) Complexes with Diazabutadiene Ligands: Synthesis, Solution‐ and Solid‐State Structural Studies
Authors: Zelenay Benjamin , Frutos‐Pedreño Roberto , Markalain‐Barta Jordi , Vega‐Isa Esmeralda , White Andrew J. P. , Díez‐González Silvia
Published: August 2016

The preparation of novel copper(I) complexes of diazabutadiene (DAB) ligands with aliphatic backbones is reported. [Cu(DABR)2](BF4), [Cu(DABR)(NCMe)2](BF4) and [CuCl(DABR)] are easily synthesised and air‐stable. These complexes, which remain scarce in the literature, have been fully characterised, and their behaviour both in the solid state as well as in solution has been studied by means of X‐ray crystallography, NMR and UV/Vis spectroscopy.
Zintl Phases K4–xNaxSi4 (1 ≤ x ≤ 2.2) and K7NaSi8: Synthesis, Crystal Structures, and Solid‐State NMR Spectroscopic Investigations
Authors: Scherf Lavinia M. , Pecher Oliver , Griffith Kent J. , Haarmann Frank , Grey Clare P. , Fässler Thomas F.
Published: August 2016

The Zintl phases K4–xNaxSi4 (1 ≤ x ≤ 2.2) and K7NaSi8 are the first representatives of the K–Na–Si system, and both contain tetrahedral [Si4]4– clusters and a charge‐balancing number of K+ and Na+ cations. All phases of K4–xNaxSi4 (1 ≤ x ≤ 2.2) crystallize in a new structure type with space group P21/n, as determined by single‐crystal X‐ray diffraction analysis of the parent phase K3NaSi4. Rietveld refinement of the X‐ray diffraction data showed that the solid solutions follow Vegard's rule. K7NaSi8 can only be synthesized by diffusion‐controlled reaction of binary precursors and is isostructural with known A7A′T8 (A = Na–Cs; A′ = Li, Na; T = Si, Ge) phases. A combination of solid‐state NMR investigations and quantum mechanical calculations served to show the anisotropic chemical bonding behavior of all the atoms in K7NaSi8, which is additionally compared with the related phases A7NaSi8 (A = Rb, Cs).
Tin(IV) Chalcogenide Complexes: Single Source Precursors for SnS, SnSe and SnTe Nanoparticle Synthesis
Authors: Thompson Joseph R. , Ahmet Ibbi Y. , Johnson Andrew L. , Kociok‐Köhn Gabriele
Published: August 2016

A family of tin(IV) bis(hexamethylsilylamide) complexes 2–9 have been synthesized by reaction of [Sn{N(SiMe3)2}2] (1) with the diphenyl dichalcogenanes Ph2E2 (E = S, Se, Te), the radical species TEMPO, or the group 16 elements to form the complexes [(PhE)2Sn{N(SiMe3)2}2] (2–4) and [(TEMPO)2Sn{N(SiMe3)2}2] (5), and [{(Me3Si)2N}2Sn(µ2‐E)]2 (6–9) (E = S, 2 & 6; E = Se 3 & 7; E = Te, 4 & 9, E = O2, 9). The isolated tin complexes were characterized by elemental analysis, NMR spectroscopy, and the molecular structures of the complexes were determined by single crystal X‐ray diffraction. Thermogravimetric analysis showed complexes 2–4 and 6–8 all to have residual masses close to those expected for the formation of the corresponding “SnE” systems. Complexes 2–4 and 6–8 were also assessed for their utility in the formation of nanoparticles. The materials obtained were characterized by powder X‐ray diffraction (XRD), field emission scanning electron microscopy (FE‐SEM) and energy‐dispersive X‐ray analysis (EDX). Analysis showed formation of SnSe and SnTe from complexes 3–4 and 6–7, respectively.
Nickel Complexes of Pyridine‐Functionalized N‐Heterocyclic Carbenes: Syntheses, Structures, and Activity in Electrocatalytic Hydrogen Production
Authors: Luo Siyuan , Siegler Maxime A. , Bouwman Elisabeth
Published: August 2016

Two bis(benz)imidazolium salts alkylated with pyridyl side arms, H2L1Br2 (1,2‐bis{[1‐(2‐pyridylmethyl)benzimidazolium‐3‐yl]methyl}benzene bromide) and H2L2Br2 (1,2‐bis{[1‐(2‐pyridylmethyl)imidazolium‐3‐yl]methyl}benzene bromide) have been prepared and were used as precursors in the synthesis of novel nickel compounds of N‐heterocyclic carbenes (Ni‐NHCs). The four Ni‐NHC complexes [Ni(L1)Br]Br (1a), [Ni(L1)](PF6)2 (1b), [Ni(L2)]Br2 (2a) and [Ni(L2)](PF6)2 (2b) were isolated and characterized by various methods, and the X‐ray crystal structures of 1a, 2a and 2b are reported. The nickel ion in 1a is in a square‐pyramidal geometry with one of the bromide ions in the apical position, the nickel ions in 2a and 2b are in square‐planar geometries. The compounds of the ligand with an imidazole‐based carbene revealed much higher activity in electrocatalytic proton reduction and better acid tolerance, although their overpotentials are higher than those of the benzimidazole‐based compounds. The presence of bromide ions has an adverse effect on the redox potentials as well as the overpotentials for proton reduction. Complex 2b, having the most planar coordination geometry, appeared to have the highest catalytic efficiency for proton reduction in DMF (ic/ip = 50, kobs = 490 s–1 at 0.1 V/s) when using acetic acid as the proton source. To the best of our knowledge, this is the first report of Ni‐NHC complexes that are active in electrocatalytic proton reduction.
Iridium(III) Complexes Bearing Chelating Bis‐NHC Ligands and Their Application in the Catalytic Reduction of Imines
Authors: Aznarez Francisco , Iglesias Manuel , Hepp Alexander , Veit Benjamin , Sanz Miguel Pablo J. , Oro Luis A. , Jin Guo‐Xin , Hahn F. Ekkehardt
Published: August 2016

The IrIII complexes 4 and 5 bearing bis‐NHC ligands (NHC = N‐heterocyclic carbene) composed of one classical NR,NR NHC and one N,NR NHC donor were prepared by the reaction of the azolium/azole compounds 2I and 3Br, respectively, with [{Cp*IrCl(µ‐Cl)}2] (Cp*=η5‐C5Me5) in the presence of NaOAc as base. Most likely, the salts 2I and 3Br were first selectively deprotonated at the C2 position of the disubstituted (NR,NR) diazaheterocycle to generate an NHC donor, which then coordinated to the IrIII center. Subsequently, NaOAc promoted C–H bond activation at the pendant imidazole moiety of the intermediate IrIII mono‐NHC complexes led to the formation of the six‐membered iridacycles 4 and 5, which bear a chelating, doubly C‐metalated C(NHC)^C(NHC′) bis‐NHC ligand. The IrIII complexes 4 and 5 were tested as precatalysts for the reduction of imines with molecular hydrogen. Moderate to good activity was observed at a catalyst loading of 5 mol‐% and an H2 pressure of 3 bar in MeOH.
Organocatalytic Asymmetric Michael/Cyclization Cascade Reaction of 3‐Isothiocyanato Oxindoles with Maleimides for the Efficient Construction of Pyrrolidonyl Spirooxindoles
Authors: Liu Lei , Zhao Bo‐Liang , Du Da‐Ming
Published: August 2016

The development of a Michael/cyclization cascade reaction between 3‐isothiocyanato‐oxindoles and maleimide catalyzed by chrial squaramides is reported. This protocol provides a series of pyrrolidonyl spirooxindoles bearing three contiguous stereocenters in excellent yields (up to 99 %) with high diastereo‐ and enantioselectivities (up to >99:1 dr, 91 % ee).
Preparation of No‐Carrier‐Added 6‐[18F]Fluoro‐l‐tryptophan via Cu‐Mediated Radiofluorination
Authors: Schäfer Dominique , Weiß Philipp , Ermert Johannes , Castillo Meleán Johnny , Zarrad Fadi , Neumaier Bernd
Published: August 2016

18F‐Labeled aromatic amino acids exhibit great potential for diagnostic applications using positron emission tomography. However, the introduction of 18F into aromatic compounds remains challenging, and novel fluorination methods facilitating easy access to 18F‐labeled arenes are highly sought after. In recent years, novel metal‐mediated fluorination methods have been reported and transferred into radiochemistry. Based on Cu‐mediated radiofluorination, a two‐step synthesis of no‐carrier‐added (n.c.a.) 6‐[18F]fluoro‐l‐tryptophan was developed. 6‐[18F]Fluoro‐l‐tryptophan was synthesized with an overall radochemical yield of 16 ± 4% within 110 min and a specific activity of 280 GBq µmol–1. The radiochemical purity was more than 99 %. The developed method allowed access to radiofluorinated tryptophan derivatives in high radiochemical yields and opens new ways to provide radiofluorinated amino acids. Furthermore, the reaction conditions were optimized to facilitate automation.
Decarbonylation of Salicylaldehyde Activated byp‐Cymene Ruthenium(II) Dimer: Implication for Catalytic Alkyne Hydrothiolation
Authors: Modem Sarangapani , Kankala Shravankumar , Balaboina Ramesh , Thirukovela Narasimha Swamy , Jonnalagadda Sreekantha B. , Vadde Ravinder , Vasam Chandra Sekhar
Published: August 2016

A stoichiometric C–H activation/decarbonylation of salicylaldehyde by [(η6‐p‐cymene)RuCl2]2gave a carbonyl derivative [(η6‐p‐cymene)RuCl(CO)(Ph‐O)] (1) without the use of CO gas. A variety of polar phosphines were then incorporated into compound1to give new RuIIcationic catalysts, [(η6‐p‐cymene)Ru(CO)(Ph‐O)L]BF4(2–8). These were used to catalyse the hydrothiolation of alkynes with a range of thiols in aqueous THF to give anti‐MarkovnikovE‐linear vinyl sulfides in high yields.
Copper‐Catalyzed Cross‐Dehydrogenative Coupling of N‐Iminoquinolinium Ylides with Secondary Amines
Authors: Hua Zerui , Fang Lei , Wu Shengying , Wang Limin
Published: August 2016

The copper‐catalyzed cross‐dehydrogenative coupling of N‐iminoquinolinium ylides with secondary amines led to ortho‐amino‐substituted quinoline derivatives with high levels of regioselectivity in good yields. This direct C–H bond amination transformation employs CuI as the catalyst without the use of a ligand, external oxidant, or base. The reaction is operationally simple and can be conducted under mild conditions. The N‐benzoyl directing group can be removed without any additional steps.
Estimation of protein concentration at high sensitivity using SDS‐capillary gel electrophoresis‐laser induced fluorescence detection with 3‐(2‐furoyl)quinoline‐2‐carboxaldehyde protein labeling
Authors: Arrell Miriam S. , Kálmán Franka
Published: August 2016

3‐(2‐furoyl)quinoline‐2‐carboxaldehyde (FQ) is a sensitive fluorogenic dye, used for derivatization of proteins for SDS‐CGE with LIF detection (SDS‐CGE‐LIF) at silver staining sensitivity (ng/mL). FQ labels proteins at primary amines, found at lysines and N‐termini, which vary in number and accessibility for different proteins. This work investigates the accuracy of estimation of protein concentration with SDS‐CGE‐LIF in real biological samples, where a different protein must be used as a standard. Sixteen purified proteins varying in molecular weight, structure, and sequence were labeled with FQ at constant mass concentration applying a commonly used procedure for SDS‐CGE‐LIF. The fluorescence of these proteins was measured using a spectrofluorometer and found to vary with a RSD of 36%. This compares favorably with other less sensitive methods for estimation of protein concentration such as SDS‐CGE‐UV and SDS‐PAGE‐Coomassie and is vastly superior to the equivalently sensitive silver stain. Investigation into the number of labels bound with UHPLC‐ESI‐QTOF‐MS revealed large variations in the labeling efficiency (percentage of labels to the number of labeling sites given by the sequence) for different proteins (from 3 to 30%). This explains the observation that fluorescence per mole of protein was not proportional to the number of lysines in the sequence.
DNA fragment separations by on‐line combination of capillary isotachophoresis–capillary zone electrophoresis with UV detection
Authors: Fraňo Milan , Džuganová Katarína , Koiš Pavol , Masár Marián
Published: August 2016

A high‐speed DNA fragment separation system based on an on‐line combination of capillary ITP with CZE (CITP‐CZE) and using UV detection at 260 nm was developed. A novel CITP‐CZE buffer system of pH 6.1 was designed for the separation of ten DNA fragments with sizes ranging from 100 to 1000 bp. An effect of underivatized α‐, β‐ and γ‐cyclodextrins on the resolution of DNA fragments in the CZE step of the CITP‐CZE combination was systematically investigated. Methylhydroxyethylcellulose present in the BGE was used to eliminate the EOF. DNA ladder fragments were separated within 10 min with LODs in the range of 1–5 ng/μL (S/N = 3). The RSDs of the migration time and peak area of individual DNA fragments were in the range of 1–3 and 3–9%, respectively. The developed CITP‐CZE system was further applied to the analysis of digest plasmid DNA samples.
How to trigger periplasmic release in recombinant Escherichia coli: A comparative analysis
Authors: Wurm David J. , Slouka Christoph , Bosilj Tadej , Herwig Christoph , Spadiut Oliver
Published: August 2016

Recombinant protein production in Escherichia coli usually leads to accumulation of the product inside the cells. To capture the product, cells are harvested, resuspended, and lysed. However, in cases where the product is transported to the periplasm, selective disruption of the outer membrane leads to much purer crude extracts compared to complete cell lysis, as only 4–8% of the native E. coli host cell proteins are located in the periplasmic space. A variety of different strategies to enable selective release of the product from the periplasm is available. However, in most of these studies cells are harvested before they are resuspended in permeabilization agent and no differentiation between leakiness and lysis is made. Here, we tested and compared different strategies to trigger leakiness. In contrast to other studies, we performed these experiments during cultivation and quantified both leakiness and lysis. In summary, we recommend incubation with 350 mM TRIS at constant pH for several hours followed by a mild heat treatment up to 38°C to trigger leakiness with only minimal lysis. This study represents a comparative summary of different strategies to trigger E. coli leakiness and describes a solid basis for further experiments in this field.
Alterations in brain white matter contributing to age‐related slowing of task switching performance: The role of radial diffusivity and magnetization transfer ratio
Authors: Serbruyns Leen , Leunissen Inge , van Ruitenbeek Peter , Pauwels Lisa , Caeyenberghs Karen , Solesio‐Jofre Elena , Geurts Monique , Cuypers Koen , Meesen Raf L. , Sunaert Stefan , Leemans Alexander , Swinnen Stephan P.
Published: August 2016

Successfully switching between tasks is critical in many daily activities. Age‐related slowing of this switching behavior has been documented extensively, but the underlying neural mechanisms remain unclear. Here, we investigated the contribution of brain white matter changes associated with myelin alterations to age‐related slowing of switching performance. Diffusion tensor imaging derived radial diffusivity (RD) and magnetization transfer imaging derived magnetization transfer ratio (MTR) were selected as myelin sensitive measures. These metrics were studied in relation to mixing cost (i.e., the increase in reaction time during task blocks that require task switching) on a local‐global switching task in young (n = 24) and older (n = 22) adults. Results showed that higher age was associated with widespread increases in RD and decreases in MTR, indicative of white matter deterioration, possibly due to demyelination. Older adults also showed a higher mixing cost, implying slowing of switching performance. Finally, mediation analyses demonstrated that decreases in MTR of the bilateral superior corona radiata contributed to the observed slowing of switching performance with increasing age. These findings provide evidence for a role of cortico‐subcortical white matter changes in task switching performance deterioration with healthy aging. Hum Brain Mapp 37:4084–4098, 2016. © 2016 Wiley Periodicals, Inc.