bluuebunny/crossref_metadata_2025 huggingface dataset:
An evaluation of the CYP2D6 and CYP3A4 inhibition potential of metoprolol metabolites and their contribution to drug–drug and drug–herb interaction by LC‐ESI/MS/MS
Authors: Borkar Roshan M. , Bhandi Murali Mohan , Dubey Ajay P. , Ganga Reddy V. , Komirishetty Prashanth , Nandekar Prajwal P. , Sangamwar Abhay T. , Kamal Ahmed , Banerjee Sanjay K. , Srinivas R.
Published: March 2016

The aim of the present study was to evaluate the contribution of metabolites to drug–drug interaction and drug–herb interaction using the inhibition of CYP2D6 and CYP3A4 by metoprolol (MET) and its metabolites. The peak concentrations of unbound plasma concentration of MET, α‐hydroxy metoprolol (HM), O‐desmethyl metoprolol (ODM) and N‐desisopropyl metoprolol (DIM) were 90.37 ± 2.69, 33.32 ± 1.92, 16.93 ± 1.70 and 7.96 ± 0.94 ng/mL, respectively. The metabolites identified, HM and ODM, had a ratio of metabolic area under the concentration–time curve (AUC) to parent AUC of ≥0.25 when either total or unbound concentration of metabolite was considered. In vitro CYP2D6 and CYP3A4 inhibition by MET, HM and ODM study revealed that MET, HM and ODM were not inhibitors of CYP3A4‐catalyzed midazolam metabolism and CYP2D6‐catalyzed dextromethorphan metabolism. However, DIM only met the criteria of >10% of the total drug related material and <25% of the parent using unbound concentrations. If CYP inhibition testing is solely based on metabolite exposure, DIM metabolite would probably not be considered. However, the present study has demonstrated that DIM contributes significantly to in vitro drug–drug interaction. Copyright © 2016 John Wiley & Sons, Ltd.
Surface functionalization of nanobiomaterials for application in stem cell culture, tissue engineering, and regenerative medicine
Authors: Rana Deepti , Ramasamy Keerthana , Leena Maria , Jiménez Constanza , Campos Javier , Ibarra Paula , Haidar Ziyad S. , Ramalingam Murugan
Published: March 2016

Stem cell‐based approaches offer great application potential in tissue engineering and regenerative medicine owing to their ability of sensing the microenvironment and respond accordingly (dynamic behavior). Recently, the combination of nanobiomaterials with stem cells has paved a great way for further exploration. Nanobiomaterials with engineered surfaces could mimic the native microenvironment to which the seeded stem cells could adhere and migrate. Surface functionalized nanobiomaterial‐based scaffolds could then be used to regulate or control the cellular functions to culture stem cells and regenerate damaged tissues or organs. Therefore, controlling the interactions between nanobiomaterials and stem cells is a critical factor. However, surface functionalization or modification techniques has provided an alternative approach for tailoring the nanobiomaterials surface in accordance to the physiological surrounding of a living cells; thereby, enhancing the structural and functional properties of the engineered tissues and organs. Currently, there are a variety of methods and technologies available to modify the surface of biomaterials according to the specific cell or tissue properties to be regenerated. This review highlights the trends in surface modification techniques for nanobiomaterials and the biological relevance in stem cell‐based tissue engineering and regenerative medicine. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:554–567, 2016
Dimethyloxalylglycine may be enhance the capacity of neural‐like cells in treatment of Alzheimer disease
Authors: Ghasemi Moravej Fahimeh , Vahabian Mehrangiz , Soleimani Asl Sara
Published: March 2016

Although using differentiated stem cells is the best proposed option for the treatment of Alzheimer disease (AD), an efficient differentiation and cell therapy require enhanced cell survival and homing and decreased apoptosis. It seems that hypoxia preconditioning via Dimethyloxalylglycine (DMOG) may increase the capacity of MSC to induce neural like stem cells (NSCs). Furthermore, it can likely improve the viability of NSCs when transplanted into the brain of AD rats.
A novel small molecule, Rosline, inhibits growth and induces caspase‐dependent apoptosis in human lung cancer cells A549 through a reactive oxygen species‐dependent mechanism
Authors: Zhao Ting , Feng Yang , Jin Wenling , Pan Hui , Li Haizhou , Zhao Yang
Published: March 2016

Chemical screening using synthetic small molecule libraries has provided a huge amount of novel active molecules. It generates lead compound for drug development and brings focus on molecules for mechanistic investigations on many otherwise intangible biological processes. In this study, using non‐small cell lung cancer cell A549 to screen against a structurally novel and diverse synthetic small molecule library of 2,400 compounds, we identified a molecule named rosline that has strong anti‐proliferation activity on A549 cells with a 50% cell growth inhibitory concentration (IC50) of 2.87 ± 0.39 µM. We showed that rosline treatment increased the number of Annexin V‐positive staining cell, as well as G2/M arrest in their cell cycle progression. Further, we have demonstrated that rosline induces a decrease of mitochondrial membrane potential (Δφm) and an increase of caspases 3/7 and 9 activities in A549 cells, although having no effect on the activity of caspase 8. Moreover, we found that rosline could induce the production of reactive oxygen species (ROS) and inhibit the phosphorylation of signaling molecule Akt in A549 cells. Alternatively, an antioxidant N‐acetyl‐L‐cysteine (NAC) significantly attenuated rosline's effects on the mitochondrial membrane potential, caspases 3/7 and 9 activities, cell viabilities and the phosphorylation of Akt. Our results demonstrated that ROS played an important role in the apoptosis of A549 cells induced by rosline.
Reactivity of 2,1‐Benzisoxazole in Palladium‐Catalyzed Direct Arylation with Aryl Bromides
Authors: Aidene Mohand , Belkessam Fatma , Soulé Jean‐François , Doucet Henri
Published: March 2016

The Pd‐catalyzed direct arylation of 2,1‐benzisoxazole with aryl bromides to access 3‐arylbenzoisoxazoles proceeds in moderate‐to‐high yields with 1 mol % Pd(OAc)2 or 2 mol % PdCl(C3H5)(dppb) (dppb=1,4‐bis(diphenylphosphino)butane) as the catalysts and KOAc as an inexpensive base. A wide variety of (hetero)aryl bromides have been employed successfully. Moreover, arylations followed by benzisoxazole ring opening allowed the preparation of 2‐aminobenzophenones in only two steps.
Base‐Catalyzed Condensation of Levulinic Acid: A New Biorefinery Upgrading Approach
Authors: Faba Laura , Díaz Eva , Ordóñez Salvador
Published: March 2016

The base‐catalyzed condensation of levulinic acid (LA) under mild conditions (0.1 MPa, 323 K, 0.45 mol L−1 aq solution of levulinic acid, catalyst/reactant=1:24 wt.) was proposed as a new approach for the upgrading of this molecule by using mixed oxides as catalysts. Three products were identified: α‐angelica lactone (AL) and two aldol condensation adducts, LA–LA and AL–LA. These last ones (obtained with selectivities higher than 90 % at 30 % conversion upon using MgZr) present high value as fuel and chemical precursors. The distribution of basic and acidic sites on the catalyst governs the performance and selectivity of the catalyst, whereas the stability of the catalyst in the reaction media determines the deactivation behavior. Bulk MgZr oxides present a good balance of these properties.
Beyond Clusters: Supramolecular Networks Self‐Assembled from Nanosized Silver Clusters and Inorganic Anions
Authors: Wang Zhi , Li Xiao‐Yu , Liu Li‐Wei , Yu Si‐Qi , Feng Zhen‐Yu , Tung Chen‐Ho , Sun Di
Published: March 2016

Assembly of small clusters into rigid bodies with precise shape and symmetry has been witnessed by the significant advances in cluster‐based metal–organic frameworks (MOFs), however, nanosized silver cluster based MOFs remain largely unexplored. Herein, two anion‐templated silver clusters, CO3@Ag20 and SO4@Ag22, were ingeniously incorporated into a 2D sql lattice (1, [CO3@Ag20(iPrS)10(NO3)8(DMF)2]n) and an unprecedented 3D two‐fold interpenetrated dia network (2, [SO4@Ag22(iPrS)12(NO3)6⋅2 NO3]n), respectively, under mild solvothermal conditions. Their atomically precise structures were confirmed by single‐crystal X‐ray diffraction analysis and further consolidated by IR spectroscopy, thermogravimetric analysis (TGA), and elemental analysis. Each drum‐like CO3@Ag20 cluster is extended by twelve NO3− ions to form the 2D sql lattice of 1, whereas each ball‐shaped SO4@Ag22 cluster with a twisted truncated tetrahedral geometry is pillared by four [Ag6(NO3)3] triangular prisms to form the 3D interpenetrated dia network of 2. Notably, 2 is the first interpenetrated 3D MOF constructed from silver clusters. These results demonstrate the dual role of the anions, which not only internally act as anion templates to induce the formation of silver thiolate clusters but also externally extend the cluster units into the rigid networks. The photoluminescent and electrochemical properties of 2 are discussed in detail.
Multichromophoric π‐Conjugation: Modular Design for Gated and Cascade Energy Transfer
Authors: Park Byung Gyu , Hong Dae Ho , Lee Ho Yong , Lee Milim , Lee Dongwhan
Published: March 2016

Multichromophore arrays allow for cascade energy transfer. As an isoelectronic analogue of indacenyl, bis(triazolo)benzene features a fused tricyclic skeleton that rigidly places two π‐extended triazoles in close proximity. Such triazole‐based fluorophores behave as electronically independent modules in the ground states, but become tightly coupled upon photoexcitation for highly efficient excitation energy transfer (EET) that can be gated by external stimuli. Taking this donor–acceptor fluorophore system a step further, we have designed and implemented a cascade EET. Here, the initial excitation takes part in a circular relay to arrive at the longest‐wavelength emitting site as the final destination. Modularly constructed triazoloarenes should serve as versatile platforms for chemically controlled optical signaling.
Emergent Catalytic Behavior of Self‐Assembled Low Molecular Weight Peptide‐Based Aggregates and Hydrogels
Authors: Tena‐Solsona Marta , Nanda Jayanta , Díaz‐Oltra Santiago , Chotera Agata , Ashkenasy Gonen , Escuder Beatriu
Published: March 2016

We report a series of short peptides possessing the sequence (FE)n or (EF)n and bearing l‐proline at their N‐terminus that self‐assemble into high aspect ratio aggregates and hydrogels. We show that these aggregates are able to catalyze the aldol reaction, whereas non‐aggregated analogues are catalytically inactive. We have undertaken an analysis of the results, considering the accessibility of catalytic sites, pKa value shifts, and the presence of hydrophobic pockets. We conclude that the presence of hydrophobic regions is indeed relevant for substrate solubilization, but that the active site accessibility is the key factor for the observed differences in reaction rates. The results presented here provide an example of the emergence of a new chemical property caused by self‐assembly, and support the relevant role played by self‐assembled peptides in prebiotic scenarios. In this sense, the reported systems can be seen as primitive aldolase I mimics, and have been successfully tested for the synthesis of simple carbohydrate precursors.
A Thermo‐ and Photo‐Switchable Ruthenium Initiator For Olefin Metathesis
Authors: Sashuk Volodymyr , Danylyuk Oksana
Published: March 2016

A ruthenium carbene complex bearing azobenzene functionality is reported. The complex exists in the form of two isomers differing by the size of the chelate ring. Both isomers were isolated by applying kinetic or thermodynamic control during the synthesis and characterized by X‐ray diffraction analysis. The isomerization of the complex was studied by UV/Vis spectroscopy. The stable isomer was tested as a catalyst in olefin metathesis. The complex was activated at about 100 °C to promote ring‐closing and ring‐opening polymerization metathesis reactions. The activation took place also at room temperature under middle ultraviolet radiation.
ChemInform Abstract: AVPO4F (A: Li, K): A 4 V Cathode Material for High‐Power Rechargeable Batteries.
Authors: Fedotov Stanislav S. , Khasanova Nellie R. , Samarin Aleksandr Sh. , Drozhzhin Oleg A. , Batuk Dmitry , Karakulina Olesia M. , Hadermann Joke , Abakumov Artem M. , Antipov Evgeny V.
Published: March 2016

Phase pure KVPO4F is prepared by firing equimolar amounts of VPO4 and KHF2 under Ar (600 °C, 1 h).
Entwicklungen und Trends in der industriellen Prozessanalytik für Life‐Science‐Anwendungen
Authors: Gerlach Martin , Gross Reinhard , Steckenreiter Thomas , Traenkle Jens , Tulke Albert
Published: March 2016

Prozessanalytik und die ihr zugrundeliegende Prozessanalysentechnik müssen auf die spezifischen Anforderungen an Prozesse in der Life‐Science‐Industrie eingehen, um dort künftig umfassend eingesetzt zu werden. Dies hängt einerseits mit den vielfältigen regulatorischen Anforderungen zusammen, aber auch mit der Komplexität und anderen Herausforderungen der einzelnen Mess‐ und Regelaufgaben. Beispiele für aktuell erzielte Ergebnisse werden im vorliegenden Beitrag vorgestellt. Echtzeitinformationen – gegebenenfalls auch stoffspezifisch – als Grundlage eines besseren Prozessverständnisses und einer überlegenen, automatisierten Prozessführung zu gewinnen, gehört dabei zu den wichtigsten Anforderungen.
Developments in slurry flow modelling in a historical perspective
Authors: Wilson Kenneth , Sellgren Anders
Published: March 2016

Durand's slurry flow model attempted to find a single formula for sand‐size particles and larger, but Babcock's data showed that a single formula could not apply. A subsequent group of models is based on Wilson's layered force‐balance analysis of slurry flows applied to friction losses and deposition limit. Models based on variants of this analysis include those by Shook and others at the Saskatchewan Research Council (SRC). Early versions of Wilson's model relied on particle fall velocity to find friction losses, but the classical iterative method of finding fall velocity has now been replaced by a direct method. This is based on the shear Reynolds number of the particle, which can be expressed in terms of the better known Archimedes number. Thus, calculations of slurry friction and limit of deposition involve two principal parameters: the Archimedes number and the diameter ratio d/D.
Concentration and velocity profiles of sediment‐water mixtures using the drift flux model
Authors: Goeree Joep C. , Keetels Geert H. , Munts Edwin A. , Bugdayci Hassan H. , van Rhee Cees
Published: March 2016

In this paper, the concentration and velocity profiles of sediment water mixtures for open‐channel flows are modelled numerically and validated with experimental results. A continuum approach, the drift flux model, is used. The mixture consists of volume fractions with different particle sizes. Hindered settling is taken into account with the closure relation of Richardson and Zaki. Transport equations are used for sediment transport. Turbulence is modelled with the LES (large eddy simulation) WALE model. The discretization of the transport and Navier‐Stokes equations is done with the finite volume method. The Navier‐Stokes equations are solved using a fractional step method. The numerical results are compared with experimental results concerning open‐channel flows.
Hierarchical Co3O4 Nanowires as Binder Free Electrodes for Reversible Lithium Storage
Authors: Zhang Zichao , Li Li , Ren Quan , Xu Qi , Cao Bingqiang
Published: March 2016

To develop a long cycle life and good rate capability electrode, tricobalt tetraoxide (Co3O4) nanowires with hierarchical structure composed of ultra‐small nanoparticles are directly grown on nickel foam current collector. The size of the nanoparticles is about 10 nm. They are synthesized via a facile hydrothermal route followed by calcination and evaluated as an anode of binder‐free lithium‐ion batteries. The concentration of reactant and duration of reaction are considered as important synthesis parameters. Co3O4 nanowires electrode exhibits excellent electrochemical performance including outstanding cycling performance, a high reversible discharge capacity and good rate capability, owing to the hierarchical architecture composed of micro‐/nanostructures. After rate capacity performance measurements, a capacity of 1060.1 mAh·g−1 is retained. At a rate of 500 mA·g−1, a reversible capacity remains stable as high as 957 mAh·g−1. The enhanced performance is owing to the hierarchical structure of the nanowires and good contact with the substrate which can make electrons efficiently transport from Co3O4 nanowires to the current collectors. The mesoporous structure may facilitate the lithium ion diffusion and mitigate the internal mechanical stress induced by volume variations of the electrode upon cycling, which lead to outstanding electrochemical performance.
Synthesis and Improved Properties of Hypergolic Boronium‐Based Ionic Liquids
Authors: Li Xingye , Lu Huijie , Wang Qi , Huang Jinglun , Nie Fude , Li Haibo , Chen Fu‐Xue
Published: March 2016

A series of asymmetric monoimidazolium dihydroboronium‐based ionic liquids (ILs) were synthesized from amine‐boranes. All the resulting ILs were fully characterized by 1H and 13C NMR, IR spectroscopy, elemental analysis or high resolution mass spectrum. Compared with the symmetric bisimidazolium dihydroboronium‐based ILs, these new ILs exhibited improved properties with shorter ignition delay times (IDs), higher densities, and lower phase transition temperature showing the promising application potential as green propellants.
Alkylation of Staurosporine to Derive a Kinase Probe for Fluorescence Applications
Authors: Disney Alexander J. M. , Kellam Barrie , Dekker Lodewijk V.
Published: March 2016

The natural product staurosporine is a high‐affinity inhibitor of nearly all mammalian protein kinases. The labelling of staurosporine has proven effective as a means of generating protein kinase research tools. Most tools have been generated by acylation of the 4′‐methylamine of the sugar moiety of staurosporine. Herein we describe the alkylation of this group as a first step to generate a fluorescently labelled staurosporine. Following alkylation, a polyethylene glycol linker was installed, allowing subsequent attachment of fluorescein. We report that this fluorescein–staurosporine conjugate binds to cAMP‐dependent protein kinase in the nanomolar range. Furthermore, its binding can be antagonised with unmodified staurosporine as well as ATP, indicating it targets the ATP binding site in a similar fashion to native staurosporine. This reagent has potential application as a screening tool for protein kinases of interest.
Synthesis and Biological Evaluation of New (−)‐Englerin Analogues
Authors: López‐Suárez Laura , Riesgo Lorena , Bravo Fernando , Ransom Tanya T. , Beutler John A. , Echavarren Antonio M.
Published: March 2016

We report the synthesis and biological evaluation of a series of (−)‐englerin A analogues obtained along our previously reported synthetic route based on a stereoselective gold(I) cycloaddition process. This synthetic route is a convenient platform to access analogues with broad structural diversity and has led us to the discovery of unprecedented and easier‐to‐synthesize derivatives with an unsaturation in the cyclopentyl ring between C4 and C5. We also introduce novel analogues in which the original isopropyl motif has been substituted with cyclohexyl, phenyl, and cyclopropyl moieties. The high selectivity and growth‐inhibitory activity shown by these new derivatives in renal cancer cell lines opens new ways toward the final goal of finding effective drugs for the treatment of renal cell carcinoma (RCC).
Detection of PIK3CA mutations, including a novel mutation of V344G in exon 4, in metastatic lung adenocarcinomas: A retrospective study of 115 FNA cases
Authors: Allison Derek B. , Lilo Mohammed T. , Geddes Susan , Pallavajjalla Aparna , Askin Frederic , Gabrielson Edward , Zheng Gang , Li Qing Kay
Published: March 2016

BACKGROUND

Phosphatidylinositol‐4,5‐bisphosphate 3‐kinase catalytic subunit alpha (PIK3CA) mutations and amplification are detected in 1% of primary lung adenocarcinomas (ADCs) and in 38% of primary lung squamous cell carcinomas. Alterations of PIK3CA in metastatic non–small cell lung carcinoma (NSCLC), however, are still not fully understood. This study investigated PIK3CA alterations in metastatic ADCs and correlated the findings with those for other commonly tested molecular abnormalities via fine‐needle aspiration (FNA) and small‐core biopsy materials.

METHODS

This study identified 115 FNA cases of metastatic lung ADC with standard lung cancer panel analysis by targeted next‐generation sequencing and fluorescence in situ hybridization at the Johns Hopkins Medical Institute over a 12‐month period. The panel included mutational analysis of PIK3CA, AKT, BRAF, EGFR, ERBB2, KRAS, and NRAS genes and tests of rearrangements for ALK and ROS1 genes.

RESULTS

A PIK3CA mutation was detected in 7 of 115 cases of metastatic ADC (6.1%). The majority of the mutations were located in exon 9 or exon 20; however, a mutation in exon 1 was seen in 1 case. Furthermore, p.V344G in exon 4 was detected in 2 cases. Among cases with PIK3CA mutations, 4 had coexisting EGFR mutations, whereas 2 had a coexisting BRAF or KRAS mutation.

CONCLUSIONS

Several common mutations as well as a novel mutation in the PIK3CA gene were observed in metastatic NSCLC (particularly ADC). The unique role, however, of PIK3CA mutations in metastatic NSCLC and the clinical implications need to be further investigated. Cancer Cytopathol 2016;124:485–92. © 2016 American Cancer Society.
Discover the person behind the administrator
Authors: Hodges Dawn Z.
Published: March 2016

When my college took a break between the fall and spring semesters, so did I. I took three weeks off. Now, I realize that's a luxury for most administrators. But every now and then, maybe even we deserve it. Or even if we don't deserve it, maybe we just need it. I know I did.
Prepare students for the future with education about diversity
Authors: Hope Joan
Published: March 2016

By the year 2050, the population of the United States will be less than 50 percent white. Our graduates will work in a very diverse world, said Tom Loper, Ed.D., associate provost and dean of the School of Science and Management at Bay Path University.
mTOR kinase is needed for the development and stabilization of dendritic arbors in newly born olfactory bulb neurons
Authors: Skalecka Agnieszka , Liszewska Ewa , Bilinski Robert , Gkogkas Christos , Khoutorsky Arkady , Malik Anna R. , Sonenberg Nahum , Jaworski Jacek
Published: March 2016

Neurogenesis is the process of neuron generation, which occurs not only during embryonic development but also in restricted niches postnatally. One such region is called the subventricular zone (SVZ), which gives rise to new neurons in the olfactory bulb (OB). Neurons that are born postnatally migrate through more complex territories and integrate into fully functional circuits. Therefore, differences in the differentiation of embryonic and postnatally born neurons may exist. Dendritogenesis is an important process for the proper formation of future neuronal circuits. Dendritogenesis in embryonic neurons culturedin vitrowas shown to depend on the mammalian target of rapamycin (mTOR). Still unknown, however, is whether mTOR could regulate the dendritic arbor morphology of SVZ‐derived postnatal OB neurons under physiological conditionsin vivo. The present study usedin vitrocultured and differentiated SVZ‐derived neural progenitors and found that both mTOR complex 1 and mTOR complex 2 were required for the dendritogenesis of SVZ‐derived neurons. Furthermore, using a combination ofin vivoelectroporation of neural stem cells in the SVZ and genetic and pharmacological inhibition of mTOR, it was found that mTOR was crucial for the growth of basal and apical dendrites in postnatally born OB neurons under physiological conditions and contributed to the stabilization of their basal dendrites. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1308–1327, 2016
Clustering and diagnostic modelling of slimming aids based on chromatographic and mass spectrometric fingerprints
Authors: Custers D. , Van Hoeck E. , Courselle P. , Apers S. , Deconinck E.
Published: March 2016

Herbal medicines and food supplements intended as slimming aids are increasingly gaining popularity worldwide, especially for treating obesity. In this study, an ultra‐performance liquid chromatography coupled to photodiode array detection (UPLC‐PDA) and an ultra‐performance liquid chromatography mass spectrometry (UPLC‐MS) method were developed to analyze 92 slimming aids (confiscated by customs), aimed at acquiring highly informative fingerprints. Three types of fingerprints were acquired (PDA, Total Ion Chromatograms (TIC), and MS fingerprints) which were used in the chemometric data analysis. Both unsupervised (i.e., Hierarchical Cluster Analysis (HCA)) and supervised techniques (i.e., Classification and Regression Tree (CART) and Partial Least Squares – Discriminant Analysis (PLS‐DA)) were applied. The aim was to perform an in‐depth study of the samples, thereby exploring potential patterns present in the data. HCA was able to generate a clustering which was mainly defined by chemical compounds detected in the samples, i.e., sibutramine, phenolphthalein and amfepramone. PLS‐DA generated the best diagnostic models for both PDA and TIC fingerprints, characterized by correct classification rates of external validation of 85% and 80%, respectively. For the MS fingerprints, the best model was obtained by CART (65% correct classification rate of external validation). Despite a lower correct classification rate, exploration of the concerned misclassifications revealed that the MS fingerprints proved to be superior since even very low concentrations of sibutramine could be detected. This study shows that reliable chemometric models can be obtained, based on the presence of prohibited chemical substances, which allow high‐throughput data analysis of such samples. Moreover, they generate a prime notion of potential threat to a patient's health posed by these kinds of slimming aids. Copyright © 2016 John Wiley & Sons, Ltd.
Capturing the ephemeral human pluripotent state
Authors: Ávila‐González Daniela , García‐López Guadalupe , García‐Castro Irma Lydia , Flores‐Herrera Héctor , Molina‐Hernández Anayansi , Portillo Wendy , Díaz Néstor Fabián
Published: March 2016

During human development, pluripotency is present only in early stages of development. This ephemeral cell potential can be captured in vitro by obtaining pluripotent stem cells (PSC) with self‐renewal properties, the human embryonic stem cells (hESC). However, diverse studies suggest the existence of a plethora of human PSC (hPSC) that can be derived from both embryonic and somatic sources, depending on defined culture conditions, their spatial origin, and the genetic engineering used for reprogramming. This review will focus on hPSC, covering the conventional primed hESC, naïve‐like hPSC that resemble the ground‐state of development, region‐selective PSC, and human induced PSC (hiPSC). We will analyze differences and similarities in their differentiation potential as well as in the molecular circuitry of pluripotency. Finally, we describe the need for human feeder cells to derive and maintain hPSC, because they could emulate the interaction of in vivo pluripotent cells with extraembryonic structures that support development. Developmental Dynamics 245:762–773, 2016. © 2016 Wiley Periodicals, Inc.
EGCG stabilizes growth cone filopodia and impairs retinal ganglion cell axon guidance
Authors: Atkinson‐Leadbeater Karen , Hehr Carrie L. , Johnston Jill , Bertolesi Gabriel , McFarlane Sarah
Published: March 2016

Background: Antioxidants such as the green tea polyphenol epigallocatechin gallate (EGCG) are neuroprotective under many conditions in mature nervous systems; however, their impact has rarely been explored in developing nervous systems, in which a critical step is the formation of connections between neurons. Axons emerge from newly formed neurons and are led by a dynamic structure found at their tip called a growth cone. Here we explore the impact of EGCG on the development of retinal ganglion cell (RGC) axons, which connect the eye to the brain. Results: EGCG acts directly on RGC axons to increase the number of growth cone filopodia, fingerlike projections that respond to extrinsic signals, in vitro and in vivo. Furthermore, EGCG exposure leads to a dramatic defect in the guided growth of RGC axons where the axons fail to make a key turn in the mid‐diencephalon required to reach their target. Intriguingly, at guidance points where RGCs do not show a change in direction, EGCG has no influence on RGC axon behavior. Conclusions: We propose that EGCG stabilizes filopodia and prevents normal filopodial dynamics required for axons to change their direction of outgrowth at guidance decision points. Developmental Dynamics 245:667–677, 2016. © 2016 Wiley Periodicals, Inc.
Selection of food patches by sympatric herbivores in response to concealment and distance from a refuge
Authors: Crowell Miranda M. , Shipley Lisa A. , Camp Meghan J. , Rachlow Janet L. , Forbey Jennifer S. , Johnson Timothy R.
Published: March 2016

Small herbivores face risks of predation while foraging and are often forced to trade off food quality for safety. Life history, behaviour, and habitat of predator and prey can influence these trade‐offs. We compared how two sympatric rabbits (pygmy rabbit, Brachylagus idahoensis; mountain cottontail, Sylvilagus nuttallii) that differ in size, use of burrows, and habitat specialization in the sagebrush‐steppe of western North America respond to amount and orientation of concealment cover and proximity to burrow refuges when selecting food patches. We predicted that both rabbit species would prefer food patches that offered greater concealment and food patches that were closer to burrow refuges. However, because pygmy rabbits are small, obligate burrowers that are restricted to sagebrush habitats, we predicted that they would show stronger preferences for greater cover, orientation of concealment, and patches closer to burrow refuges. We offered two food patches to individuals of each species during three experiments that either varied in the amount of concealment cover, orientation of concealment cover, or distance from a burrow refuge. Both species preferred food patches that offered greater concealment, but pygmy rabbits generally preferred terrestrial and mountain cottontails preferred aerial concealment. Only pygmy rabbits preferred food patches closer to their burrow refuge. Different responses to concealment and proximity to burrow refuges by the two species likely reflect differences in perceived predation risks. Because terrestrial predators are able to dig for prey in burrows, animals like pygmy rabbits that rely on burrow refuges might select food patches based more on terrestrial concealment. In contrast, larger habitat generalists that do not rely on burrow refuges, like mountain cottontails, might trade off terrestrial concealment for visibility to detect approaching terrestrial predators. This study suggests that body size and evolutionary adaptations for using habitat, even in closely related species, might influence anti‐predator behaviors in prey species.
Sperm use economy of honeybee (Apis mellifera) queens
Authors: Baer Boris , Collins Jason , Maalaps Kristiina , den Boer Susanne P. A.
Published: March 2016

The queens of eusocial ants, bees, and wasps only mate during a very brief period early in life to acquire and store a lifetime supply of sperm. As sperm cannot be replenished, queens have to be highly economic when using stored sperm to fertilize eggs, especially in species with large and long‐lived colonies. However, queen fertility has not been studied in detail, so that we have little understanding of how economic sperm use is in different species, and whether queens are able to influence their sperm use. This is surprising given that sperm use is a key factor of eusocial life, as it determines the fecundity and longevity of queens and therefore colony fitness. We quantified the number of sperm that honeybee (Apis mellifera) queens use to fertilize eggs. We examined sperm use in naturally mated queens of different ages and in queens artificially inseminated with different volumes of semen. We found that queens are remarkably efficient and only use a median of 2 sperm per egg fertilization, with decreasing sperm use in older queens. The number of sperm in storage was always a significant predictor for the number of sperm used per fertilization, indicating that queens use a constant ratio of spermathecal fluid relative to total spermathecal volume of 2.364 × 10−6 to fertilize eggs. This allowed us to calculate a lifetime fecundity for honeybee queens of around 1,500,000 fertilized eggs. Our data provide the first empirical evidence that honeybee queens do not manipulate sperm use, and fertilization failures in worker‐destined eggs are therefore honest signals that workers can use to time queen replacement, which is crucial for colony performance and fitness.
TRPM7 is down‐regulated in both left atria and left ventricle of ischaemic cardiomyopathy patients and highly related to changes in ventricular function
Authors: Ortega Ana , Roselló‐Lletí Esther , Tarazón Estefanía , Gil‐Cayuela Carolina , Lago Francisca , González‐Juanatey Jose‐Ramón , Martinez‐Dolz Luis , Portolés Manuel , Rivera Miguel
Published: March 2016

Aims

The kinase ion channel transient receptor potential melastatin 7 (TRPM7) is considered a modulator of cardiac fibrosis progression; nevertheless, we lack of studies analysing its role in human ischaemic cardiomyopathy (ICM). Our objective was to analyse the expression of genes encoding cardiac ion channels in human ICM, focusing on the alterations in mRNA levels of TRPM7 and its relationship with changes in the ventricular function.

Methods and results

RNA‐sequencing was carried out in 13 left ventricular (LV) samples of patients with ICM compared with a control group (n = 10). The analysis revealed a total of 25 ion channel genes differentially expressed. We performed an RTqPCR analysis of the TRPM7 mRNA in LV and left atrial samples and found that it was down‐regulated in both cavities (−1.43‐fold and −1.52‐fold, respectively). Atrial TRPM7 mRNA levels showed an excellent and inverse relationships with the depressed ejection fraction (r = −0.724, P = 0.042) and with the mitral A wave (r = −0.938, P = 0.006).

Conclusions

We report the down‐regulation of TRPM7 in tissue samples from both left atria and left ventricle in patients with ICM. We found an inverse relationship between both cardiac chambers mRNA levels with LV dysfunction, suggesting an important role of TRPM7 in the left atrial and LV functional depression found in this cardiomyopathy.
Global cardiac risk assessment in the Registry Of Pregnancy And Cardiac disease: results of a registry from the European Society of Cardiology
Authors: van Hagen Iris M. , Boersma Eric , Johnson Mark R. , Thorne Sara A. , Parsonage William A. , Escribano Subías Pilar , Leśniak‐Sobelga Agata , Irtyuga Olga , Sorour Khaled A. , Taha Nasser , Maggioni Aldo P. , Hall Roger , Roos‐Hesselink Jolien W. ,   on behalf of the ROPAC investigators and EORP team
Published: March 2016

Aims

To validate the modified World Health Organization (mWHO) risk classification in advanced and emerging countries, and to identify additional risk factors for cardiac events during pregnancy.

Methods and results

The ongoing prospective worldwide Registry Of Pregnancy And Cardiac disease (ROPAC) included 2742 pregnant women (mean age ± standard deviation, 29.2 ± 5.5 years) with established cardiac disease: 1827 from advanced countries and 915 from emerging countries. In patients from advanced countries, congenital heart disease was the most prevalent diagnosis (70%) while in emerging countries valvular heart disease was more common (55%). A cardiac event occurred in 566 patients (20.6%) during pregnancy: 234 (12.8%) in advanced countries and 332 (36.3%) in emerging countries. The mWHO classification had a moderate performance to discriminate between women with and without cardiac events (c‐statistic 0.711 and 95% confidence interval (CI) 0.686–0.735). However, its performance in advanced countries (0.726) was better than in emerging countries (0.633). The best performance was found in patients with acquired heart disease from developed countries (0.712). Pre‐pregnancy signs of heart failure and, in advanced countries, atrial fibrillation and no previous cardiac intervention added prognostic value to the mWHO classification, with a c‐statistic of 0.751 (95% CI 0.715–0.786) in advanced countries and of 0.724 (95% CI 0.691–0.758) in emerging countries.

Conclusion

The mWHO risk classification is a useful tool for predicting cardiac events during pregnancy in women with established cardiac disease in advanced countries, but seems less effective in emerging countries. Data on pre‐pregnancy cardiac condition including signs of heart failure and atrial fibrillation, may help to improve preconception counselling in advanced and emerging countries.
4‐Arylation of N‐Acylamino‐ and Aminopyrazoles by the Suzuki–Miyaura Cross‐Coupling Reaction
Authors: Jedinák Lukáš , Cankař Petr
Published: March 2016

Halogenated aminopyrazoles have rarely been utilized in metal‐catalysed cross‐coupling reactions mainly due to the complexation of the aminopyrazoles to the metal center, which deactivates the catalyst. In this paper we reveal that the appropriate combination of palladium source and ligand enables efficient Suzuki–Miyaura cross‐coupling reactions with even challenging substrates such as halogenated aminopyrazoles. The combination of Pd(OAc)2 and XPhos allowed efficient coupling of halogenated N‐acetylaminopyrazoles, whereas XPhos Pd G2 was needed when unprotected aminopyrazoles were used. Generally, the halogenated aminopyrazoles underwent facile cross‐coupling reactions with a range of aryl‐, heteroaryl‐, and styrylboronic acids and esters. The resulting biaryl, bisheteroaryl, or arylalkenyl derivatives were obtained in good‐to‐high isolated yields.
Restructure your office to better serve your students, Part II
Authors: Sutton Halley
Published: March 2016

ANAHEIM, CALIF. — When Rebecca Mathern of Oregon State University was given the task of restructuring her admissions office, she made it a priority to keep her focus on getting the right people in place to boost the success of students at her university. Before her attempts to restructure, Mathern found that, although nothing was really wrong in her office, her team lacked direction and had stopped feeling excited for what was coming next. “We had to stop feeling overwhelmed and start feeling empowered,” Mathern said. In a session at the recent Pacific Association of Collegiate Registrars and Admissions Officers annual conference, Mathern gave tips, tricks, best practices and anecdotes from her own experience transforming her office into a successful student‐serving team.
Impact of Daily Startup–Shutdown Conditions on the Production of Solar Methanol over a Commercial Cu–ZnO–Al2O3 Catalyst
Authors: Ash‐Kurlander Uri , Martin Oliver , Fontana Luca D. , Patil Vikas R. , Bernegger Men , Mondelli Cecilia , Pérez‐Ramírez Javier , Steinfeld Aldo
Published: March 2016

Methanol production with the use of syngas derived from solar‐driven splitting of CO2 and H2O is a promising route to sustainable liquid fuels. Herein, we investigated the effect of using a CO2‐rich syngas with the same composition as that obtained in a solar thermochemical reactor and of applying a daily startup–shutdown (DSS) routine matching the intermittent solar operation over a benchmark Cu–ZnO–Al2O3 catalyst. The catalyst reached fast equilibration (10 h) in the presence of this syngas mixture and reversibly responded to changes in the concentrations of CO and CO2 by mimicking fluctuations in the feed composition. Remarkably, its deactivation was even less pronounced over 27 cycles under a DSS regime than for a corresponding time on stream under uninterrupted operation if the reactor was purged with H2‐free syngas upon shutdown. Characterization and modeling indicated that this purging avoided the formation of inactive ZnCO3 and minimized the oxidation of the Cu surface atoms.
Policy analysis of greenhouse gases’ Mitigation in Iran Energy Sector Using System Dynamics Approach
Authors: Kazemi Aliyeh , Hosseinzadeh Mahnaz
Published: March 2016

The present study aims to shed new light in the energy supply planning in Iran by adopting a system dynamics (SD) model, so as to provide a quantitative assessment of each option of supply allocation policy, the long‐term greenhouse gases (GHG) emissions’ trends of the country as a whole. This paper thus presents the projections of future GHG emissions’ trend under various options of supply policies for a time span of 15 years. The GHG emissions are projected to reach 6,20,000 tonnes of carbon dioxide equivalent (TCO2e) by the year 2021 if the existing supply policy options are followed. 10 different scenarios considering the major variable of “economic sanctions” ‐which have recently affected Iran's economy‐ are developed. By running different scenarios, several fundamental dynamic behaviors can be seen explicitly. The results show that the more allocation of supply resources to the power plants will lessen the GHG emissions in the long run; however this option is quite sensitive to the economic sanctions, so that in case of more economic sanctions, it is not a good decision to be made. More gas injection into the oil reservoirs and less gas exports, is highly efficient in the short term, but its relative effectiveness in not substantial in the long run. Increasing the percentage of oil and gas allocated to the industrial sector, declines cumulative GHG in the long run. The GHG emissions from the power plants’ scenario are less in comparison to those from the injection and industry scenarios in the modeling period. However, combined scenarios in the both level of the sanctions are the ideal. © 2016 American Institute of Chemical Engineers Environ Prog, 35: 1221–1230, 2016
Determination of aroma compounds in pork broth produced by different processing methods
Authors: Wang Yao , Song Huanlu , Zhang Yu , Tang Jiani , Yu Donghai
Published: March 2016

The aroma‐active compounds in pork broth cooked by different processing methods were extracted by solid phase micro extraction (SPME) and solvent‐assisted flavour evaporation (SAFE) and analysed by gas chromatography‐olfactometry‐mass spectrometry (GC‐O‐MS). In total, 78 different aroma‐active compounds were tentatively identified in pork broth. Among them, 12 compounds such as ethyl acetate, 3‐(methylthio) propanal, hexanal, 2‐butanone, dimethyl disulfide and dimethyl trisulfide were tentatively identified as predominant aroma‐active compounds in pork broth, according to their high FD value. According to sensory evaluation, the main characteristic flavour of the four samples was the intensely meaty aroma. By investigating the four kinds of pork broth processed by different methods, the broth cooked at 96 °C with air circulation was found to possess stronger meaty aroma and best overall sensory. Copyright © 2016 John Wiley & Sons, Ltd.
Perceived Managerial and Leadership Effectiveness Within South Korean and British Private Companies: A Derived Etic Comparative Study
Authors: Hamlin Robert G. , Kim Sewon , Chai Dae Seok , Kim Junhee , Jeong Shinhee
Published: March 2016

This derived etic cross‐case/cross nation comparative study explored the extent to which behavioral indicators of perceived managerial and leadership effectiveness, as perceived and judged by managers and non‐managerial employees in South Korean private sector companies, are different (local/context‐specific) or similar (potentially global/context‐general) to behavioral indicators perceived by their counterparts within British private sector companies. The empirical data used for the study were obtained from emic replication studies previously carried out by the authors in South Korea and the United Kingdom respectively. High degrees of overlap and convergence were revealed, with the vast majority of managerial behaviors (87.75% South Korean and 90.53% British) that distinguish effective managers from ineffective managers being found to be the same, similar, or congruent in meaning. The most surprising result of the study is that only 1 out of 13 South Korean behavioral indicators found to be non‐convergent showed any evidence of being local/context‐general, and thus culturally embedded. Overall, the findings bring into question the validity of past claims in the cross‐cultural management literature which assert that particular types and styles of managerial and leadership behavior are contingent upon the cultural aspects of specific societies and countries. Our study is a rare example of Type 4 indigenous management research, and our findings are illustrative of what has become known as geocentric (emic‐and‐etic) knowledge.
RAS mutation is a prognostic biomarker in colorectal cancer patients with metastasectomy
Authors: Osumi Hiroki , Shinozaki Eiji , Suenaga Mitsukuni , Matsusaka Satoshi , Konishi Tsuyoshi , Akiyoshi Takashi , Fujimoto Yoshiya , Nagayama Satoshi , Fukunaga Yosuke , Ueno Masashi , Mise Yoshihiro , Ishizawa Takeaki , Inoue Yosuke , Takahashi Yu , Saiura Akio , Uehara Hirohumi , Mun Mingyon , Okumura Sakae , Mizunuma Nobuyuki , Miki Yoshio , Yamaguchi Toshiharu
Published: March 2016

Studies have demonstrated a relationship between clinical outcomes after curative resection for colorectal cancer (CRC) and gene mutations of the EGFR pathway; however, no studies have examined metastatic CRC (mCRC) patients with metastasectomy. The aim of this study was to evaluate the relationship between gene mutations of EGFR pathway and clinical outcomes after metastasectomy in mCRC patients. A total of 1,053 patients histopathologically confirmed CRC received a genotyping test for the EGFR pathway from February 2012 to October 2013. Detailed information was obtained through review of medical records. Gene mutations of EGFR pathway were analyzed by Luminex assay. Overall survival (OS) and recurrence free survival were estimated by the Kaplan‐Meier method and the log‐rank test was used to compare the survival outcomes by gene mutation status. A total of 132 patients received metastasectomy. The frequencies of KRAS exon 2, KRAS exon 3.4, NRAS, BRAF, and PIK3CA mutations were 38.6% (51/132), 3.6% (5/132), 5.1% (7/132), 5.1% (7/132), and 8.7% (12/132), respectively. With a median follow‐up of 84.1 months (57.2—NA) for a survivor, the 4‐year OS rate was 65.6% for mCRC with RAS mutation, and 81.3% for mCRC with wild‐type RAS (p < 0.05). We observed a statistically significant correlation for only the RAS mutation and OS. In multivariate analysis, RAS mutation and liver metastasis were independent factors for shorter OS. There were no significant differences between gene mutations of EGFR pathway and recurrence free survival. RAS mutation in mCRC metastasectomy patients was associated with shorter overall survival.