bluuebunny/crossref_metadata_2025 huggingface dataset:
Liberation of acrylates from nickelalactones via Ni─O ring opening with alkyl iodides
Authors: Zhang Zhizhi , Guo Fangjie , Kühn Fritz E. , Sun Jing , Zhou Mingdong , Fang Xiangchen
Published: August 2016

The utilization of carbon dioxide as a feedstock for the production of raw chemicals is of high current industrial interest. One attractive reaction is the transformation of carbon dioxide into acrylic acid or acrylates. The cleavage of the Ni─O bond of nickelalactones may result in the formation of acrylates. In this work, C2H5I, CF3CH2I and CF3I are studied as alkylation reagents for the Ni─O ring opening of nickelalactones. The results indicate that both C2H5I and CF3CH2I are able to release acrylates from nickelalactones. Based on the experimental evidence and literature precedents, a mechanism – proceeding via Ni─O ring opening of nickelalactone, β‐H elimination to release the acrylate and reductive elimination for recovery of the Ni(0) species – is proposed.
Mexico, Indonesia, South Korea, Turkey, and Australia (MIKTA): Middle, Regional, and Constructive Powers Providing Global Governance
Authors: Schiavon Jorge A. , Domínguez Diego
Published: August 2016

This paper argues that MIKTA (Mexico, Indonesia, South Korea, Turkey, and Australia) are middle, regional, and constructive powers that can serve as providers of global governance in the international system. In order to support this idea, the paper first reviews the literature on these concepts, arguing that they can be complementary. Then, it explains why the MIKTA countries can be defined as middle, regional and constructive powers. To do so, it describes what MIKTA is, as well the common characteristics, objectives, and strategies that the countries that compose this mechanism share. Finally, it argues that in order for MIKTA countries to serve as middle, regional, and constructive powers, they need to consolidate the support of all relevant State and non‐State actors in their countries, allowing MIKTA to become a relevant mechanism to promote and generate public goods in the international system, specially global governance.
Synthesis of Trifluoromethylthiolated Alkenes and Ketones by Decarboxylative Functionalization of Cinnamic Acids
Authors: Pan Shen , Huang Yangen , Qing Feng‐Ling
Published: August 2016

A tunable decarboxylative trifluoromethylthiolation of cinnamic acids with AgSCF3 was developed to afford trifluoromethylthiolated alkenes or ketones by using transition metal‐mediated conditions.
Optimization of organic acid pretreatment of wheat straw
Authors: Barisik Gizem , Isci Asli , Kutlu Naciye , Bagder Elmaci Simel , Akay Bulent
Published: August 2016

The objective of this study was to determine the effectiveness of different organic acids (maleic, succinic, and oxalic acid) on enzymatic hydrolysis and fermentation yields of wheat straw. It was also aimed to optimize the process conditions (temperature, acid concentration, and pretreatment time) by using response surface methodology (RSM). In line with this objective, the wheat straw samples were pretreated at three different temperatures (170, 190, and 210°C), acid concentrations (1%, 3%, and 5%) and pretreatment time (10, 20, and 30 min). The findings show that at extreme pretreatment conditions, xylose was solubilized in liquid phase, causing an increase in cellulose and lignin content of biomass. Enzymatic hydrolysis experiments revealed that maleic and oxalic acids were quite effective at achieving high sugar yields (>90%) from wheat straw. In contrast, the highest sugar yields were 50–60%, when the samples were pretreated with succinic acid, indicating that succinic acid was not as effective. The optimum process conditions for maleic acid were, 210°C, 1.08% acid concentration, and 19.8 min; for succinic acid 210°C, 5% acid concentration, and 30 min; for oxalic acid 210°C, 3.6% acid concentration, and 16.3 min. The ethanol yields obtained at optimum conditions were 80, 79, and 59% for maleic, oxalic and succinic acid, respectively. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1487–1493, 2016
Five common clinical presentations in the elderly: An anatomical review
Authors: Collin Peter G. , Oskouian Rod J. , Loukas Marios , D'Antoni Anthony V. , Tubbs R. Shane
Published: August 2016

Elderly patients face distinct health challenges and have an increased demand for specific medical procedures. As the aging population continues to increase, age‐associated conditions such as congestive heart failure, hip fractures, spine degeneration, dementia, and airway compromise will increase in prevalence and procedures to correct these conditions will be increasingly performed. A clear understanding of the clinical anatomy of these diseases and procedures is imperative for anatomists and clinicians alike in order to best treat patients and continue to advance aging research and better teach future medical practitioners about the specific anatomy often involved in this group. The aging process mirrors in a variety of ways the common pathologies of the elderly, but it is key to draw the distinction between normal aging and pathology, particularly for congestive heart failure and dementia, in the clinical setting. This article aims to review the common presentations or procedures of the elderly and how the normal aging process is associated with the anatomy of these conditions or complications. Clin. Anat. 30:168–174, 2017. © 2017 Wiley Periodicals, Inc.
Patients with ROS1 rearrangement‐positive non‐small‐cell lung cancer benefit from pemetrexed‐based chemotherapy
Authors: Song Zhengbo , Su Haiyan , Zhang Yiping
Published: August 2016

ROS1 gene‐rearrangement in non‐small‐cell lung cancer (NSCLC) patients has recently been identified as a driver gene and benefited from crizotinib treatment. However, no data are available for ROS1‐positive NSCLC about chemotherapeutic options and prognostic data. We investigated pemetrexed‐based treatment efficacy in ROS1 translocation NSCLC patients and determined the expression of thymidylate synthetase (TS) to provide a rationale for the efficacy results. We determined the ROS1 status of 1750 patients with lung adenocarcinoma. Patients' clinical and therapeutic profiles were assessed. In positive cases, thymidylate synthetase (TS) mRNA level was performed by RT‐PCR. For comparison, we evaluated the TS mRNA status and pemetrexed‐based treatment efficacy from 170 NSCLC patients with anaplastic lymphoma kinase (ALK) translocation (n = 46), EGFR mutation (n = 50), KRAS mutation (n = 32), and wild‐type of EGFR/ALK/ROS1/KRAS (n = 42). Thirty‐four ROS1 translocation patients were identified at two institutions. Among the 34 patients, 12 with advanced stage or recurrence were treated with pemetrexed‐based first‐line chemotherapy. The median progression‐free survivals of pemetrexed‐based first‐line chemotherapy in ROS1 translocation, ALK translocation, EGFR mutation, KRAS mutation, and EGFR/ALK/ROS1/KRAS wild‐type patients were 6.8, 6.7, 5.2, 4.2, and 4.5 months, respectively (P = 0.003). The TS mRNA level was lower in patients with ROS1‐positive than ROS1‐negative patients (264 ± 469 × 10−4 vs. 469 ± 615 × 10−4, P = 0.03), but similar with ALK‐positive patients (264 ± 469 × 10−4 vs. 317 ± 524 × 10−4, P = 0.64). Patients diagnosed with ROS1 translocation lung adenocarcinoma may benefit from pemetrexed‐based chemotherapy. TS mRNA level enables the selection of therapeutic options for ROS1 translocation patients.
MicroRNA signatures predict dysregulated vitamin D receptor and calcium pathways status in limb girdle muscle dystrophies (LGMD) 2A/2B
Authors: Aguennouz M. , Lo Giudice C. , Licata N. , Rodolico C. , Musumeci O. , Fanin M. , Migliorato A. , Ragusa M. , Macaione V. , Di Giorgio R. M. , Angelini C. , Toscano A.
Published: August 2016

miRNA expression profile and predicted pathways involved in selected limb‐girdle muscular dystrophy (LGMD)2A/2B patients were investigated. A total of 187 miRNAs were dysregulated in all patients, with six miRNAs showing opposite regulation in LGMD2A versus LGMD2B patients. Silico analysis evidence: (1) a cluster of the dysregulated miRNAs resulted primarily involved in inflammation and calcium metabolism, and (2) two genes predicted as controlled by calcium‐assigned miRNAs (Vitamin D Receptor gene and Guanine Nucleotide Binding protein beta polypeptide 1gene) showed an evident upregulation in LGMD2B patients, in accordance with miRNA levels. Our data support alterations in calcium pathway status in LGMD 2A/B, suggesting myofibre calcium imbalance as a potential therapeutic target. Copyright © 2016 John Wiley & Sons, Ltd.
Preventive effect of Desferal on sperm motility and morphology
Authors: Nenkova Galina , Stefanov Rossen , Chervenkov Mihail , Alexandrova Albena
Published: August 2016

Transition metal ions, mainly iron, are involved in the generation of highly reactive hydroxyl radicals, which are the most powerful inducers of oxidative damage to all biomolecules. The lipids in sperm membranes are highly susceptible to oxidation. Sperm lipid peroxidation (LPO) leads to decrease of motility and reduction of likelihood for sperm‐oocyte fusion. The excess radical production may affect also the spermatozoa morphology. The aim of the present study was to investigate the effect of Desferal on the LPO, motility, and morphology of boar sperm subjected to oxidative stress. After collection, the ejaculates were equally separated and diluted in a commercial semen extender (experiment 1) or in physiological saline (experiment 2). The ejaculates of the 2 experiments were divided into aliquots, which were incubated with one of the following agents: FeSO4(0.1mM), H2O2(0.5mM), or FeSO4 + H2O2(Fenton system), in the presence or absence of Desferal. The application of Desferal in the incubation medium had a protective effect against FeSO4 + H2O2‐induced sperm damage, namely, decrease of LPO; decrease the quantity of immotile spermatozoa and decrease the number of morphological abnormalities, regardless of the used medium. In experiment 2, the presence of FeSO4in the incubation medium induced LPO in the same range as the combination FeSO4 + H2O2, in which the effect was reduced by Desferal. Thus, the supplement of Desferal to media used for sperm storage and processing could be a useful tool for diminishing oxidative injury and improving the quality of the semen.
Chemical Probes to Directly Profile Palmitoleoylation of Proteins
Authors: Zheng Baohui , Jarugumilli Gopala K. , Chen Baoen , Wu Xu
Published: August 2016

Palmitoleoylation is a unique fatty acylation of proteins in which a monounsaturated fatty acid, palmitoleic acid (C16:1), is covalently attached to a protein. Wnt proteins are known to be palmitoleoylated by cis‐Δ9 palmitoleate at conserved serine residues. O‐palmitoleoylation plays a critical role in regulating Wnt secretion, binding to the receptors, and in the dynamics of Wnt signaling. Therefore, protein palmitoleoylation is important in tissue homeostasis and tumorigenesis. Chemical probes based on saturated fatty acids, such as ω‐alkynyl palmitic acid (Alk‐14 or Alk‐C16), have been used to study Wnt palmitoleoylation. However, such probes require prior conversion to the unsaturated fatty acid by stearoyl‐CoA desaturase (SCD) in cells, significantly decreasing their selectivity and efficiency for studying protein palmitoleoylation. We synthesized and characterized ω‐alkynyl cis‐ and trans‐palmitoleic acids (cis‐ and trans‐Alk‐14:1) as chemical probes to directly study protein palmitoleoylation. We found that cis‐Alk‐14:1 could more efficiently label Wnt proteins in cells. Interestingly, the DHHC family of palmitoyl acyltransferases can charge both saturated and unsaturated fatty acids, potentially using both as acyl donors in protein palmitoylation and palmitoleoylation. Furthermore, proteomic analysis of targets labeled by these probes revealed new cis‐ and trans‐palmitoleoylated proteins. Our studies provided new chemical tools and revealed new insights into palmitoleoylation in cell signaling.
Opportunities of Immobilized Homogeneous Metathesis Complexes as Prominent Heterogeneous Catalysts
Authors: Dewaele Annelies , Verpoort Francis , Sels Bert
Published: August 2016

A plethora of strategies for immobilizing well‐defined metathesis catalysts on solid supports have been developed over the past decades. Whereas most reviews on classical heterogeneous metathesis catalyst designs mainly discuss covalent binding approaches, we here extended this topic with non‐covalent surface science methods, a research area that gained interest recently. Within this context, the main focus was set on the immobilization of ruthenium alkylidenes or so‐called Grubbs complexes, as these catalysts are known for their high activity, stability and commercial viability. Besides giving an overview of different immobilization strategies, the wide diversity of supported Grubbs catalysts also allows for discussing implications of attaching Grubbs catalysts that go beyond the traditional benefits of heterogeneous catalysis, such as easy catalyst separation. More specifically, this Review will summarize several unique opportunities of immobilized homogeneous catalysts in liquid‐phase metathesis transformations in terms of impact on activity, stability, and product selectivity, as to highlight the economic potential, but without ignoring possible shortcomings and limitations.
Synthesis, Characterization, and Electronic Structures of Porphyrins Fused with Polycyclic Aromatic Ring Systems
Authors: Okujima Tetsuo , Mack John , Nakamura Jun , Kubheka Gugu , Nyokong Tebello , Zhu Hua , Komobuchi Naoki , Ono Noboru , Yamada Hiroko , Uno Hidemitsu , Kobayashi Nagao
Published: August 2016

A series of porphyrins fused with acenaphthylene, phenanthroline, and benzofluoranthene polycyclic aromatic rings were prepared by means of a 3+1 porphyrin synthesis approach and subsequent retro‐Diels–Alder reaction of bicyclo[2.2.2]octadiene‐fused precursors. Analysis of the magnetic circular dichroism spectra and the results of time‐dependent DFT calculations are used to identify the reasons for the trends observed in the wavelengths and relative intensities of the Q bands of the products. Michl's perimeter model is used as a conceptual framework to explain the changes in the relative energies of the frontier π‐molecular orbitals.
A Ligand That Targets CUG Trinucleotide Repeats
Authors: Li Jinxing , Matsumoto Jun , Bai Li‐Ping , Murata Asako , Dohno Chikara , Nakatani Kazuhiko
Published: August 2016

Invited for the cover of this issue is the group of Kazuhiko Nakatani at the Osaka University. The image depicts the novel molecule DAP (2,9‐diaminoalkyl substituted 1,10‐phenanthroline), which binds to the r(CUG)n repeat. Read the full text of the article at 10.1002/chem.201602741.
ChemInform Abstract: Molecular Iodine‐Catalyzed Aerobic α,β‐Diamination of Cyclohexanones with 2‐Aminopyrimidine and 2‐Aminopyridines.
Authors: Nguyen Thanh Binh , Ermolenko Ludmila , Retailleau Pascal , Al‐Mourabit Ali
Published: August 2016

The diamination reaction provides fused heterocycles with a regiochemistry depending on the starting 2‐aminoazine.
ChemInform Abstract: Cp*CoIII‐Catalyzed Dehydrative C—H Allylation of 6‐Arylpurines and Aromatic Amides Using Allyl Alcohols in Fluorinated Alcohols.
Authors: Bunno Youka , Murakami Nanami , Suzuki Yudai , Kanai Motomu , Yoshino Tatsuhiko , Matsunaga Shigeki
Published: August 2016

The first example of Weinreb amide directed C—H bond functionalization under high‐valent cobalt catalysis is also presented.
ChemInform Abstract: Asymmetric Retro‐Claisen Reaction by Chiral Primary Amine Catalysis.
Authors: Zhu Yunbo , Zhang Long , Luo Sanzhong
Published: August 2016

An unprecedented enamine‐based enantioselective retro‐Claisen reaction of β‐diketones with ortho‐quinone methides is presented.
ChemInform Abstract: Synthesis of Benzofuranyl and Indolyl Methyl Azides by Tandem Silver‐Catalyzed Cyclization and Azidation.
Authors: Ranjith Kumar Gadi , Kiran Kumar Yalla , Kant Ruchir , Sridhar Reddy Maddi
Published: August 2016

An efficient route for the synthesis of the title 2‐azidomethyl heterocycles (IV) and (II), resp., based on Ag(I)‐catalyzed intramolecular cyclization and γ‐allylic azidation of readily available propargyl alcohols is developed.
ChemInform Abstract: Transition‐Metal‐Free Thiolation Annulation of 2‐Fluorophenylacetylene Derivatives: Expedient Synthesis of Benzo[b]thiophenes Using Na2S·9H2O.
Authors: Li Yibiao , Cheng Liang , Li Bin , Jiang Shaohua , Chen Lu , Shao Yan
Published: August 2016

Surprisingly, diyne (V) is converted into the thiophene (VI) instead of an expected 2,2′‐bisbenzothiophene derivative.
ChemInform Abstract: Copper/Guanidine‐Catalyzed Asymmetric Alkynylation of Isatins.
Authors: Chen Quangang , Tang Yu , Huang Tianyu , Liu Xiaohua , Lin Lili , Feng Xiaoming
Published: August 2016

The enantioselective alkynylation of isatins catalyzed by a bifunctional guanidine/CuI catalyst under mild reaction conditions is described.
ChemInform Abstract: An Unusual Grob‐Type C—C/C—O Bond Cleavage of 5‐Acyl‐2,3‐dihydro‐4H‐pyran‐4‐one Derivatives.
Authors: Ilangovan Andivelu , Sakthivel Palaniappan , Zipse Hendrik
Published: August 2016

Treatment of aryl‐substituted dihydropyrazinones with hydrazine hydrate provides pyrazoles via an unusual tandem nucleophilic 1,2‐addition/Grob‐type fragmentation reaction.
ChemInform Abstract: Metal‐ and Protection‐Free [4 + 2] Cycloadditions of Alkynes with Azadienes: Assembly of Functionalized Quinolines.
Authors: Saunthwal Rakesh K. , Patel Monika , Verma Akhilesh K.
Published: August 2016

Azadienes, generated in situ from o‐aminobenzyl alcohols, undergo [4 + 2] cycloaddition reactions with a wide variety of alkynes to produce quinoline derivatives.
ChemInform Abstract: Gold(I)‐Catalyzed Cascade Hydroarylation/Cycloaromatization to Indolizines via Pyridine Ring Construction.
Authors: Li Xiangdong , Xie Xin , Liu Yuanhong
Published: August 2016

The scalable reaction procedure provides multisubstituted indolizines which may contain a broad range of functional groups.
ChemInform Abstract: One‐Step Synthesis of Diverse Pyridine‐Containing Heterocycles with 3‐Ethoxycyclobutanones at Room Temperature.
Authors: Lin Yun , Yang Xinglin , Pan Weidong , Rao Yu
Published: August 2016

A general, concise, one‐pot method for a diversity‐oriented synthesis of bioactive pyridine‐containing fused heterocycles from easily available starting materials at ambient temperature is developed.
ChemInform Abstract: Quinazoline Synthesis via Rh(III)‐Catalyzed Intermolecular C—H Functionalization of Benzimidates with Dioxazolones.
Authors: Wang Jie , Zha Shanke , Chen Kehao , Zhang Feifei , Song Chao , Zhu Jin
Published: August 2016

The reaction tolerates various functional groups.
ChemInform Abstract: Synthesis of Functionalized 1,3,2‐Benzodiazaborole Cores Using Bench‐Stable Components.
Authors: Davies Geraint H. M. , Molander Gary A.
Published: August 2016

The reaction between 2‐phenylenediamines and diverse aryl, hetaryl, alkenyl or alkyl trifluoroborates tolerates various functional groups.
ChemInform Abstract: Diterpenoids and Phenanthrenones from the Leaves and Stems of Strophioblachia fimbricalyx.
Authors: Xu You‐kai , et al.
Published: August 2016

Five new compounds, namely fimbricalyxoid A, fimbricalyxoid B (II), fimbricalyxoid C (III), fimbricalyxoid D (IV), and 13‐O‐methylfimbricalyx B (V), together with five known compounds are isolated from the leaves and stems of Strophioblachia fimbricalyx.
ChemInform Abstract: Racemic Alkaloids from Macleaya cordata: Structural Elucidation, Chiral Resolution, and Cytotoxic, Antibacterial Activities.
Authors: Sai Chun‐Mei , Li Da‐Hong , Li Sheng‐Ge , Han Tong , Guo Yong‐Zhi , Pei Yue‐Hu , Bai Jiao , Jing Yong‐Kui , Li Zhan‐Lin , Hua Hui‐Ming
Published: August 2016

Macleayins C‐E are isolated as racemic mixtures and separated by chiral‐phase HPLC to give the pure enantiomers.
ChemInform Abstract: Three New Pyrrolizidine Alkaloids Derivatives from Liparis nervosa
Authors: Huang Shuai , Zhong De‐Xin , Shan Lian‐Hai , Zheng Ye‐Zi , Zhang Zhi‐Kuan , Bu Ya‐Heng , Ma Hong‐Wen , Zhou Xian‐Li
Published: August 2016

isolation, structure elucidation and cytotoxic activity of three new pyrrolizidine alkaloids named nervosine VII, VIII, and IX
ChemInform Abstract: New Alkaloids from Daphniphyllum himalense.
Authors: Zhang Hua , Zhang Dong‐Dong , Li Jing‐Ya , Shyaula Sajan L. , Li Jia , Yue Jian‐Min
Published: August 2016

Nine new alkaloids and sixteen biosynthetically related compounds are isolated.
ChemInform Abstract: A New Polyketide Synthase—Nonribosomal Peptide Synthetase Hybrid Metabolite from Plant Endophytic Fungus Periconia sp.
Authors: Zhang De‐Wu , Tao Xiao‐Yu , Liu Ji‐Mei , Chen Ri‐Dao , Zhang Min , Fang Xiao‐Mei , Yu Li‐Yan , Dai Jun‐Gui
Published: August 2016

isolation, structural elucidation and biological activity of a new polyketide (I) named pericoannosin B
ChemInform Abstract: Palladium‐Catalyzed Construction of Quaternary Carbon Centers with Propargylic Electrophiles
Authors: Franckevicius Vilius
Published: August 2016

Review: [43 refs.
ChemInform Abstract: Total Synthesis of Marine Natural Products: Cephalosporolides
Authors: Halle Mahesh B. , Fernandes Rodney A.
Published: August 2016

Review: [67 refs.
Vielfalt organischer Arsenverbindungen
Authors: Hille‐Rehfeld Annelle
Published: August 2016

Arsen, berüchtigt als Mordgift, ist im biogeochemischen Kreislauf allgegenwärtig. Seine Oxidationsstufen V, III, 0 und ‐III erlauben eine Vielfalt von Redox‐Reaktionen im Zellstoffwechsel, vor allem bei Mikroorganismen. Eine bislang unbekannte Vielfalt an organischen Arsenverbindungen mit Ähnlichkeiten zu Stickstoff‐ oder Phosphor‐haltigen Metaboliten stellt die toxikologische Forschung vor neue Herausforderungen.
Insights into the in vitro Anticancer Effects of Diruthenium‐1
Authors: Koceva‐Chyła Aneta , Matczak Karolina , Hikisz Msc. Paweł , Durka Msc. Kamil , Kochel Msc. Krzysztof , Süss‐Fink Georg , Furrer Julien , Kowalski Konrad
Published: August 2016

The in vitro anticancer activity of the dinuclear trithiolato‐bridged arene ruthenium complex diruthenium‐1 (DiRu‐1) was evaluated against a panel of human cancer cell lines used as in vitro models for hepatocellular carcinoma (HepG2 cells), estrogen‐responsive breast adenocarcinoma (MCF‐7 cells), and triple‐negative breast adenocarcinoma (MDA‐MB‐231 cells). DiRu‐1 is highly cytotoxic to these cell lines, demonstrating half‐maximal inhibitory concentrations (IC50) in the low‐nanomolar range (77±1.4 to 268.2±4.4 nm). The main molecular mechanisms responsible for the high cytotoxicity of DiRu‐1 against the most responsive MCF‐7 cell line (IC50=77±1.4 nm)were investigated on the basis of the capacity of DiRu‐1 to induce oxidative stress, apoptosis, and DNA damage, and to inhibit the cell cycle and proliferation. The results show that DiRu‐1 triggers caspase‐dependent apoptosis in MCF‐7 cells on both the intrinsic and extrinsic pathways. Moreover, the Ru complex also causes necrosis, mitotic catastrophe, and autophagy. DiRu‐1 increases the intracellular levels of reactive oxygen species (ROS), which play a significant role in its cytotoxicity and pro‐apoptotic activity. An important mechanism of the anticancer activity of DiRu‐1 appears to be the induction of DNA lesions, mainly due to apoptotic DNA fragmentation and cell‐cycle arrest at the G2/M checkpoint. These changes are correlated with the concentration of DiRu‐1, the duration of the cell treatment, and the post‐treatment time.
Ionotropic glutamate receptors: Which ones, when, and where in the mammalian neocortex
Authors: Hadzic Minela , Jack Alexander , Wahle Petra
Published: August 2016

A multitude of 18 iGluR receptor subunits, many of which are diversified by splicing and RNA editing, localize to >20 excitatory and inhibitory neocortical neuron types defined by physiology, morphology, and transcriptome in addition to various types of glial, endothelial, and blood cells. Here we have compiled the published expression of iGluR subunits in the areas and cell types of developing and adult cortex of rat, mouse, carnivore, bovine, monkey, and human as determined with antibody‐ and mRNA‐based techniques. iGluRs are differentially expressed in the cortical areas and in the species, and all have a unique developmental pattern. Differences are quantitative rather than a mere absence/presence of expression. iGluR are too ubiquitously expressed and of limited use as markers for areas or layers. A focus has been the iGluR profile of cortical interneuron types. For instance, GluK1 and GluN3A are enriched in, but not specific for, interneurons; moreover, the interneurons expressing these subunits belong to different types. Adressing the types is still a major hurdle because type‐specific markers are lacking, and the frequently used neuropeptide/CaBP signatures are subject to regulation by age and activity and vary as well between species and areas. RNA‐seq reveals almost all subunits in the two morphofunctionally characterized interneuron types of adult cortical layer I, suggesting a fairly broad expression at the RNA level. It remains to be determined whether all proteins are synthesized, to which pre‐ or postsynaptic subdomains in a given neuron type they localize, and whether all are involved in synaptic transmission. J. Comp. Neurol. 525:976–1033, 2017. © 2016 Wiley Periodicals, Inc.
Stem and progenitor cells of the mammalian olfactory epithelium: Taking poietic license
Authors: Schwob James E. , Jang Woochan , Holbrook Eric H. , Lin Brian , Herrick Daniel B. , Peterson Jesse N. , Hewitt Coleman Julie
Published: August 2016

The capacity of the olfactory epithelium (OE) for lifelong neurogenesis and regeneration depends on the persistence of neurocompetent stem cells, which self‐renew as well as generating all of the cell types found within the nasal epithelium. This Review focuses on the types of stem and progenitor cells in the epithelium and their regulation. Both horizontal basal cells (HBCs) and some among the population of globose basal cells (GBCs) are stem cells, but the two types plays vastly different roles. The GBC population includes the basal cells that proliferate in the uninjured OE and is heterogeneous with respect to transcription factor expression. From upstream in the hierarchy to downstream, GBCs encompass 1) Sox2+/Pax6+ stem‐like cells that are totipotent and self‐renew over the long term, 2) Ascl1+ transit‐amplifying progenitors with a limited capacity for expansive proliferation, and 3) Neurog1+/NeuroD1+ immediate precursor cells that make neurons directly. In contrast, the normally quiescent HBCs are activated to multipotency and proliferate when sustentacular cells are killed, but not when only OSNs die, indicating that HBCs are reserve stem cells that respond to severe epithelial injury. The master regulator of HBC activation is the ΔN isoform of the transcription factor p63; eliminating ΔNp63 unleashes HBC multipotency. Notch signaling, via Jagged1 ligand on Sus cells and Notch1 and Notch2 receptors on HBCs, is likely to play a major role in setting the level of p63 expression. Thus, ΔNp63 becomes a potential therapeutic target for reversing the neurogenic exhaustion characteristic of the aged OE. J. Comp. Neurol. 525:1034–1054, 2017. © 2016 Wiley Periodicals, Inc.
Anatomical characterization of subcortical descending projections to the inferior colliculus in mouse
Authors: Patel Mili B. , Sons Stacy , Yudintsev Georgiy , Lesicko Alexandria M.H. , Yang Luye , Taha Gehad A. , Pierce Scott M. , Llano Daniel A.
Published: August 2016

Descending projections from the thalamus and related structures to the midbrain are evolutionarily highly conserved. However, the basic organization of this auditory thalamotectal pathway has not yet been characterized. The purpose of this study was to obtain a better understanding of the anatomical and neurochemical features of this pathway. Analysis of the distributions of retrogradely labeled cells after focal injections of retrograde tracer into the inferior colliculus (IC) of the mouse revealed that most of the subcortical descending projections originated in the brachium of the IC and the paralaminar portions of the auditory thalamus. In addition, the vast majority of thalamotectal cells were found to be negative for the calcium‐binding proteins calbindin, parvalbumin, or calretinin. Using two different strains of GAD‐GFP mice, as well as immunostaining for GABA, we found that a subset of neurons in the brachium of the IC is GABAergic, suggesting that part of this descending pathway is inhibitory. Finally, dual retrograde injections into the IC and amygdala plus corpus striatum as well into the IC and auditory cortex did not reveal any double labeling. These data suggest that the thalamocollicular pathway comprises a unique population of thalamic neurons that do not contain typical calcium‐binding proteins and do not project to other paralaminar thalamic forebrain targets, and that a previously undescribed descending GABAergic pathway emanates from the brachium of the IC. J. Comp. Neurol. 525:885–900, 2017. © 2016 Wiley Periodicals, Inc.
Copper‐Based Metal–Organic Porous Materials for CO2 Electrocatalytic Reduction to Alcohols
Authors: Albo Jonathan , Vallejo Daniel , Beobide Garikoitz , Castillo Oscar , Castaño Pedro , Irabien Angel
Published: August 2016

The electrocatalytic reduction of CO2 has been investigated using four Cu‐based metal–organic porous materials supported on gas diffusion electrodes, namely, (1) HKUST‐1 metal–organic framework (MOF), [Cu3(μ6‐C9H3O6)2]n; (2) CuAdeAce MOF, [Cu3(μ3‐C5H4N5)2]n; (3) CuDTA mesoporous metal–organic aerogel (MOA), [Cu(μ‐C2H2N2S2)]n; and (4) CuZnDTA MOA, [Cu0.6Zn0.4(μ‐C2H2N2S2)]n. The electrodes show relatively high surface areas, accessibilities, and exposure of the Cu catalytic centers as well as favorable electrocatalytic CO2 reduction performance, that is, they have a high efficiency for the production of methanol and ethanol in the liquid phase. The maximum cumulative Faradaic efficiencies for CO2 conversion at HKUST‐1‐, CuAdeAce‐, CuDTA‐, and CuZnDTA‐based electrodes are 15.9, 1.2, 6, and 9.9 %, respectively, at a current density of 10 mA cm−2, an electrolyte‐flow/area ratio of 3 mL min cm−2, and a gas‐flow/area ratio of 20 mL min cm−2. We can correlate these observations with the structural features of the electrodes. Furthermore, HKUST‐1‐ and CuZnDTA‐based electrodes show stable electrocatalytic performance for 17 and 12 h, respectively.
Dopant‐Free Donor (D)–π–D–π–D Conjugated Hole‐Transport Materials for Efficient and Stable Perovskite Solar Cells
Authors: Zhang Fei , Liu Xicheng , Yi Chenyi , Bi Dongqin , Luo Jingshan , Wang Shirong , Li Xianggao , Xiao Yin , Zakeeruddin Shaik Mohammed , Grätzel Michael
Published: August 2016

Three novel hole‐transporting materials (HTMs) using the 4‐methoxytriphenylamine (MeOTPA) core were designed and synthesized. The energy levels of the HTMs were tuned to match the perovskite energy levels by introducing symmetrical electron‐donating groups linked with olefinic bonds as the π bridge. The methylammonium lead triiodide (MAPbI3) perovskite solar cells based on the new HTM Z34 (see main text for structure) exhibited a remarkable overall power conversion efficiency (PCE) of 16.1 % without any dopants or additives, which is comparable to 16.7 % obtained by a p‐doped 2,2′,7,7′‐tetrakis‐(N,N‐di‐4‐methoxyphenylamino)‐9,9′‐spirobifluorene (spiro‐OMeTAD)‐based device fabricated under the same conditions. Importantly, the devices based on the three new HTMs show relatively improved stability compared to devices based on spiro‐OMeTAD when aged under ambient air containing 30 % relative humidity in the dark.
Contrasting the hydrologic response due to land cover and climate change in a mountain headwaters system
Authors: Pribulick Christine E. , Foster Lauren M. , Bearup Lindsay A. , Navarre‐Sitchler Alexis K. , Williams Kenneth H. , Carroll Rosemary W.H. , Maxwell Reed M.
Published: August 2016

Land cover change due to drought and insect‐induced tree mortality or altered vegetation succession is one of the many consequences of anthropogenic climate change. While the hydrologic response to land cover change and increases in temperature have been explored independently, few studies have compared these two impacts in a systematic manner. These changes are particularly important in snow‐dominated, headwaters systems that provide streamflow for continental river systems. Here we study the hydrologic impacts of both vegetation change and climate warming along three transects in a mountain headwaters watershed using an integrated hydrologic model. Results show that while impacts due to warming generally outweigh those resulting from vegetation change, the inherent variability within the transects provides varying degrees of response. The combination of both vegetation change and warming results in greater changes to streamflow amount and timing than either impact individually, indicating a nonlinear response from these systems to multiple perturbations. The complexity of response underscores the need to integrate observational data and the challenge of deciphering hydrologic impacts from proxy studies.
Central sensitization as a determinant of patients’ benefit from total hip and knee replacement
Authors: Wylde V. , Sayers A. , Odutola A. , Gooberman‐Hill R. , Dieppe P. , Blom A.W.
Published: August 2016

Background

Discrepancies exist between osteoarthritic joint changes and pain severity before and after total hip (THR) and knee (TKR) replacement. This study investigated whether the interaction between pre‐operative widespread hyperalgesia and severity of radiographic osteoarthritis (OA) was associated with pain severity before and after joint replacement.

Methods

Data were analysed from 232 patients receiving THR and 241 receiving TKR. Pain was assessed pre‐operatively and at 12 months post‐operatively using the WOMAC Pain Scale. Widespread hyperalgesia was assessed through forearm pressure pain thresholds (PPTs). Radiographic OA was evaluated using the Kellgren and Lawrence scheme. Statistical analysis was conducted using multilevel models, and adjusted for confounding variables.

Results

Pre‐operative: In knee patients, there was weak evidence that the effect of PPTs on pain severity was greater in patients with more severe OA (Grade 3 OA: ß = 0.96 vs. Grade 4: ß = 4.03), indicating that in these patients higher PPTs (less widespread hyperalgesia) was associated with less severe pain. In hip patients, the effect of PPTs on pain did not differ with radiographic OA (Grade 3 OA: ß = 3.95 vs. Grade 4: ß = 3.67).

Post‐operative: There was weak evidence that knee patients with less severe OA who had greater widespread hyperalgesia benefitted less from surgery (Grade 3 OA: ß = 2.28; 95% CI −1.69 to 6.25). Conversely, there was weak evidence that hip patients with more severe OA who had greater widespread hyperalgesia benefitted more from surgery (Grade 4 OA: ß = −2.92; 95% CI −6.58 to 0.74).

Conclusions

Widespread sensitization may be a determinant of how much patients benefit from joint replacement, but the effect varies by joint and severity of structural joint changes.

Significance

Pre‐operative widespread hyperalgesia and radiographic osteoarthritis (OA) severity may influence how much patients benefit from joint replacement. Patients undergoing knee replacement with less severe OA and greater widespread hyperalgesia benefitted less from surgery than patients with less hyperalgesia. Patients undergoing hip replacement with more severe OA and greater widespread hyperalgesia benefitted more than patients with less hyperalgesia.
A Novel Solid‐state Electrochemiluminescent Enantioselective Sensor for Ascorbic Acid and Isoascorbic Acid
Authors: Zhu Shu , Lin Xia , Wang Qinghong , Xia Qiao , Ran Peiyao , Fu Yingzi
Published: August 2016

A novel, stable, solid‐state and stereoselective electrochemiluminescence (ECL) sensor has been designed to enantioselectively discriminate ascorbic acid (AA) and isoascorbic acid (IAA) by immobilizing Ru(bpy)32+ (Ru), thiolated β‐cyclodextrin (β‐CD‐SH) and gold/platinum hybrid nanoparticles supported on multiwalled carbon nanotube/silica coaxial nanocables (GP‐CSCN) on glassy carbon electrode. All chemical compounds could be immobilized on the surface of electrode stably through nafion film, and high stereoselectivity could be introduced to the sensor via the synergistic effects of the β‐CD‐SH and GP‐CSCN nanomaterials. When the developed sensor interacted with AA and IAA, obvious difference of ECL intensities was observed, and a larger intensity was obtained from AA, which indicated that this strategy could be employed to enantioselectively recognize AA and IAA. As a result, ECL technique might act as a promising method for recognition of chiral compounds.
A Novel Hybrid Nano‐composite Grafted Electrochemically Reduced Graphene Oxide Based Sensor for Sensitive Determination of Efavirenz
Authors: Raj Mamta , Gupta Pankaj , Thapliyal Neeta , Goyal Rajendra N.
Published: August 2016

A novel, facile fabrication, based on electrochemically reduced graphene oxide (ErGO), grafted with Pt nanoparticles and Nafion hybrid nano‐composite (ErGO‐Pt/Nafion) on the surface of edge plane pyrolytic graphite (EPPG) has been reported. The fabricated sensor has been used for the sensitive and selective determination of efavirenz (EFZ), a well‐known drug for HIV infections. The ErGO‐Pt/Nafion film was characterized by Field Emission Scanning Electron Microscopy (FE‐SEM), Energy‐dispersive X‐ray spectrometry (EDS) and Electrochemical Impedance Spectroscopy (EIS). The experimental results reveal that the modified sensor displays an excellent electrocatalytic activity towards the oxidation of EFZ and exhibits a large linear dynamic relationship in the range of 0.05 μM to 150 μM, with a detection limit of 1.8 nM. Practical utility of the developed sensor has been demonstrated by determining the EFZ in biological fluids and pharmaceutical samples and a low detection limit with high sensitivity observed makes it valuable for the clinical diagnosis.
Contactless conductivity detection for analytical techniques— Developments from 2014 to 2016
Authors: Kubáň Pavel , Hauser Peter C.
Published: August 2016

The development of capacitively coupled contactless conductivity detection for the two‐year period from mid‐2014 to mid‐2016 is covered in this review. This includes a survey of fundamental studies and further developments of the measuring technique reported as well as a discussion of new applications. These mostly concern capillary electrophoresis carried out in conventional capillaries as well as on microchip electrophoresis devices. The main focus is on the determination of small non‐UV‐absorbing organic ions and inorganic ions in different types of samples of clinical, nutritional or environmental interest. Outside of electrophoresis contactless conductivity detection is finding uses in detection in column chromatography, flow‐injection analysis and industrial applications.
Convenience Yields in Electricity Prices: Evidence from the Natural Gas Market
Authors: Milonas Nikolaos , Paratsiokas Nikolaos
Published: August 2016

This study develops a model in which changes in the electricity basis are directly related to changes in the fuel's storage level and the fuel's convenience yield. The model is tested with data from the US electricity and natural gas markets during the period 2004–2014. Empirical results show a negative relationship between the electricity basis and the fuel's convenience yield giving support to the argument that non‐storable commodities embody convenience yields. © 2016 Wiley Periodicals, Inc. Jrl Fut Mark 37:522–538, 2017
Allometric scaling of brain regions to intra‐cranial volume: An epidemiological MRI study
Authors: de Jong Laura W. , Vidal Jean‐Sébastien , Forsberg Lars E. , Zijdenbos Alex P. , Haight Thaddeus ,   Alzheimer's Disease Neuroimaging Initiative, Sigurdsson Sigurdur , Gudnason Vilmundur , van Buchem Mark A. , Launer Lenore J.
Published: August 2016

There is growing evidence that sub‐structures of the brain scale allometrically to total brain size, that is, in a non‐proportional and non‐linear way. Here, scaling of different volumes of interest (VOI) to intra‐cranial volume (ICV) was examined. It was assessed whether scaling was allometric or isometric and whether scaling coefficients significantly differed from each other. We also tested to what extent allometric scaling of VOI was introduced by the automated segmentation technique. Furthermore, reproducibility of allometric scaling was studied different age groups and study populations. Study samples included samples of cognitively healthy adults from the community‐based Age Gene/Environment Susceptibility‐Reykjavik Study (AGES‐Reykjavik Study) (N = 3,883), the Coronary Artery Risk Development in Young Adults Study (CARDIA) (N =709), and the Alzheimer's Disease Neuroimaging Initiative (ADNI) (N = 180). Data encompassed participants with different age, ethnicity, risk factor profile, and ICV and VOI obtained with different automated MRI segmentation techniques. Our analysis showed that (1) allometric scaling is a trait of all parts of the brain, (2) scaling of neo‐cortical white matter, neo‐cortical gray matter, and deep gray matter structures including the cerebellum are significantly different from each other, and (3) allometric scaling of brain structures cannot solely be explained by age‐associated atrophy, sex, ethnicity, or a systematic bias from study‐specific segmentation algorithm, but appears to be a true feature of brain geometry. Hum Brain Mapp 38:151–164, 2017. © 2016 Wiley Periodicals, Inc.
Association between duration and type of androgen deprivation therapy and risk of diabetes in men with prostate cancer
Authors: Crawley Danielle , Garmo Hans , Rudman Sarah , Stattin Pär , Häggström Christel , Zethelius Björn , Holmberg Lars , Adolfsson Jan , Van Hemelrijck Mieke
Published: August 2016

Androgen deprivation therapy (ADT) for prostate cancer (PCa) increases risk of type 2 diabetes (T2DM); however the association between types and duration of ADT has not been fully elucidated. We examined how type and duration of ADT affects risk of T2DM. Using data from Prostate Cancer database Sweden (PCBaSe) we investigated risk of T2DM in a cohort of 34,031 men with PCa on ADT; i.e., anti‐androgens (AA), orchiectomy, or gonadotropin‐releasing hormone (GnRH) agonists compared to an age‐matched, PCa‐free comparison cohort (n = 167,205) using multivariate Cox proportional hazard regression. T2DM was defined as a newly filled prescription for metformin, sulphonylurea, or insulin in the Prescribed Drug Register. A total of 21,874 men with PCa received GnRH agonists, 9,143 AA and 3,014 underwent orchiectomy. Risk of T2DM was increased in men in the GnRH agonists/orchiectomy group during the first 3 years of ADT [i.e., 1 − 1.5 years HR: 1.61 (95%CI: 1.36 − 1.91)], compared to PCa‐free men. The risk decreased thereafter (e.g., 3 − 4 years HR: 1.17 (95% CI: 0.98 − 1.40)). Conversely, no increased risk was seen in men on AA (HR: 0.74 (95%CI: 0.65 − 0.84). The incidence of T2DM per 1,000 person‐years was 10 for PCa‐free men, 8 for men on AA, and 13 for men on GnRH agonists/orchiectomy. Duration of ADT has a significant impact on risk of T2DM. With the peak after three years of treatment, our data indicates that men on ADT, even for a limited period of time, such as adjuvant to radiotherapy, are at increased risk of T2DM.
Alternating electric fields (TTFields) in combination with paclitaxel are therapeutically effective against ovarian cancer cells in vitro and in vivo
Authors: Voloshin Tali , Munster Mijal , Blatt Roni , Shteingauz Anna , Roberts Paul C. , Schmelz Eva M. , Giladi Moshe , Schneiderman Rosa S. , Zeevi Einav , Porat Yaara , Bomzon Ze'ev , Urman Noa , Itzhaki Aviran , Cahal Shay , Kirson Eilon D. , Weinberg Uri , Palti Yoram
Published: August 2016

Long‐term survival rates for advanced ovarian cancer patients have not changed appreciably over the past four decades; therefore, development of new, effective treatment modalities remains a high priority. Tumor Treating Fields (TTFields), a clinically active anticancer modality utilize low‐intensity, intermediate frequency, alternating electric fields. The goal of this study was to evaluate the efficacy of combining TTFields with paclitaxel against ovarian cancer cells in vitro and in vivo. In vitro application of TTFields on human ovarian cancer cell lines led to a significant reduction in cell counts as compared to untreated cells. The effect was found to be frequency and intensity dependent. Further reduction in the number of viable cells was achieved when TTFields treatment was combined with paclitaxel. The in vivo effect of the combined treatment was tested in mice orthotopically implanted with MOSE‐LTICv cells. In this model, combined treatment led to a significant reduction in tumor luminescence and in tumor weight as compared to untreated mice. The feasibility of effective local delivery of TTFields to the human abdomen was examined using finite element mesh simulations performed using the Sim4life software. These simulations demonstrated that electric fields intensities inside and in the vicinity of the ovaries of a realistic human computational phantom are about 1 and 2 V/cm pk‐pk, respectively, which is within the range of intensities required for TTFields effect. These results suggest that prospective clinical investigation of the combination of TTFields and paclitaxel is warranted.
Evaluation of Immunogenicity of Nivolumab Monotherapy and Its Clinical Relevance in Patients With Metastatic Solid Tumors
Authors: Agrawal Shruti , Statkevich Paul , Bajaj Gaurav , Feng Yan , Saeger Sally , Desai Dharmesh D. , Park Jong‐Soon , Waxman Ian M. , Roy Amit , Gupta Manish
Published: August 2016

Nivolumab is a fully human IgG4 monoclonal antibody targeting the programmed death‐1 (PD‐1) receptor that blocks interactions between PD‐1 and its ligands on tumor cells to prevent T‐cell exhaustion in patients with cancer. It has demonstrated efficacy in multiple tumor types, including melanoma, non‐small‐cell lung cancer, and renal cell carcinoma. This analysis assessed the immunogenicity of nivolumab and its impact on pharmacokinetics, safety, and efficacy in patients with solid tumors enrolled in 6 clinical studies. The incidence and prevalence of antidrug antibodies (ADAs) were determined by validated electrochemiluminescence assays in samples collected during nivolumab treatment and up to 100 days after the last dose. Confirmed positive samples from the 6 studies were also tested for presence of neutralizing antibodies (NAbs). Among 1086 nivolumab‐treated patients, 138 patients (12.7%) were ADA positive (relative to baseline), only 3 (0.3%) of whom were persistently positive for ADA, and 9 (0.8%) were NAb positive at 1 time point. The presence of ADAs was not associated with hypersensitivity, infusion reactions, or loss of efficacy and had minimal impact on nivolumab clearance. Additionally, the presence of NAbs was not associated with loss of efficacy. In conclusion, immunogenicity of nivolumab is not clinically meaningful.