bluuebunny/crossref_metadata_2025 huggingface dataset:
Harnessing the Electrophilicity of Keteniminium Ions: A Simple and Straightforward Entry to Tetrahydropyridines and Piperidines from Ynamides
Authors: Lecomte Morgan , Evano Gwilherm
Published: March 2016

An efficient, modular and straightforward entry to tetrahydropyridines and piperidines is reported. This reaction is based on a formal intramolecular hydroalkylation of readily available, properly substituted ynamides which, upon simple activation under acidic conditions, generate highly reactive activated keteniminium ions whose reactivity can be finely controlled to induce a remarkably efficient [1,5]‐hydride shift from unactivated C−H bonds and trigger a cationic cyclization which is complete within minutes.
Transition‐Metal‐Free Borylation of Allylic and Propargylic Alcohols
Authors: Miralles Núria , Alam Rauful , Szabó Kálmán J. , Fernández Elena
Published: March 2016

The base‐catalyzed allylic borylation of tertiary allylic alcohols allows the synthesis of 1,1‐disubstituted allyl boronates, in moderate to high yield. The unexpected tandem performance of the Lewis acid–base adduct, [Hbase]+[MeO‐B2pin2]− favored the formation of 1,2,3‐triborylated species from the tertiary allylic alcohols and 1‐propargylic cyclohexanol at 90 °C.
Highly Enantioselective Rhodium‐Catalyzed Addition of Arylboroxines to Simple Aryl Ketones: Efficient Synthesis of Escitalopram
Authors: Huang Linwei , Zhu Jinbin , Jiao Guangjun , Wang Zheng , Yu Xingxin , Deng Wei‐Ping , Tang Wenjun
Published: March 2016

Highly enantioselective additions of arylboroxines to simple aryl ketones have been achieved for the first time with a Rh/(R,R,R,R)‐WingPhos catalyst, thus providing a range of chiral diaryl alkyl carbinols with excellent ee values and yields. (R,R,R,R)‐WingPhos has been proven to be crucial for the high reactivity and enantioselectivity. The method has enabled a new, concise, and enantioselective synthesis of the antidepressant drug escitalopram.
Photooxygenation of Furylalkylamines: Easy Access to Pyrrolizidine and Indolizidine Scaffolds
Authors: Kalaitzakis Dimitris , Triantafyllakis Myron , Sofiadis Manolis , Noutsias Dimitris , Vassilikogiannakis Georgios
Published: March 2016

A highly adaptable method targeting the ubiquitous and very important pyrrolizidine and indolizidine scaffolds is presented. The general synthetic utility of the method is underscored by its application to the rapid and easy synthesis of five natural products starting from readily accessible alkylfuran precursors. These unprotected primary furylalkylamines are subjected to photooxygenation conditions, which initiate a complex cascade reaction sequence concluding with the production of high value motifs. This sequence can be tailored to need by varying the choice of both photosensitizer and base additive.
Carborane Substituents Promote Direct Electrophilic Insertion over Reduction–Metalation Reactions
Authors: Man Wing Y. , Ellis David , Rosair Georgina M. , Welch Alan J.
Published: March 2016

Two‐electron reduction of 1,1′‐bis(o‐carborane) followed by reaction with [Ru(η‐mes)Cl2]2 affords [8‐(1′‐1′,2′‐closo‐C2B10H11)‐4‐(η‐mes)‐4,1,8‐closo‐RuC2B10H11]. Subsequent two‐electron reduction of this species and treatment with [Ru(η‐arene)Cl2]2 results in the 14‐vertex/12‐vertex species [1‐(η‐mes)‐9‐(1′‐1′,2′‐closo‐C2B10H11)‐13‐(η‐arene)‐1,13,2,9‐closo‐Ru2C2B10H11] by direct electrophilic insertion, promoted by the carborane substituent in the 13‐vertex/12‐vertex precursor. When arene=mesitylene (mes), the diruthenium species is fluxional in solution at room temperature in a process that makes the metal–ligand fragments equivalent. A unique mechanism for this fluxionality is proposed and is shown to be fully consistent with the observed fluxionality or nonfluxionality of a series of previously reported 14‐vertex dicobaltacarboranes.
Design and Development of Novel 4‐(4‐(1H‐Tetrazol‐5‐yl)‐1H‐pyrazol‐1‐yl)‐6‐morpholino‐N‐(4‐nitrophenyl)‐1,3,5‐triazin‐2‐amine as Cardiotonic Agent via Inhibition of PDE3
Authors: Mao Zhi‐Wei , Li Qiao‐Ling , Wang Ping , Sun Yang‐Li , Liu Yu
Published: March 2016

The classical phosphodiesterase 3A (PDE3A) inhibitors provide relaxation of the vasculature system via increasing the cellular level of cyclic adenosine monophosphate (cAMP) and proved to be useful in the management of congestive heart failure. Consequently, the present paper deals with the development of novel pyrazole derivatives tethered with substituted 1,3,5‐triazine derivatives in search for novel PDE3 inhibitors. The synthesis of designed inhibitors was realized in a multi‐step reaction and the structures were ascertained with the help of various spectroscopic techniques. Subsequently, these analogs were tested for their inhibitory activities against PDE3 enzymes, where they exhibited considerable inhibition, revealing 9g as the most promising inhibitor of the class. In a docking study, the morpholine fragment of compound 9g was efficiently engulfed in the small pocket of the active site lined by Gly940 and Pro941. The substituted aromatic ring of the core scaffold was found to be positioned deep in the cavity bordered by Tyr829, Asn830, Leu850, Glu851, and Thr893. Moreover, it considerably improved the contractility of cardiac muscles without altering the heart beat frequency in experimental subjects.
Time‐based tags for fiction movies: comparing experts to novices using a video labeling game
Authors: Estrada Liliana Melgar , Hildebrand Michiel , de Boer Victor , van Ossenbruggen Jacco
Published: March 2016

The cultural heritage sector has embraced social tagging as a way to increase both access to online content and to engage users with their digital collections. In this article, we build on two current lines of research. (a) We use Waisda?, an existing labeling game, to add time‐based annotations to content. (b) In this context, we investigate the role of experts in human‐based computation (nichesourcing). We report on a small‐scale experiment in which we applied Waisda? to content from film archives. We study the differences in the type of time‐based tags between experts and novices for film clips in a crowdsourcing setting. The findings show high similarity in the number and type of tags (mostly factual). In the less frequent tags, however, experts used more domain‐specific terms. We conclude that competitive games are not suited to elicit real expert‐level descriptions. We also confirm that providing guidelines, based on conceptual frameworks that are more suited to moving images in a time‐based fashion, could result in increasing the quality of the tags, thus allowing for creating more tag‐based innovative services for online audiovisual heritage.
Confined blood chimerism in a monochorionic dizygotic sex discordant twin pregnancy conceived after induced ovulation
Authors: Mayeur Le Bras Anne , Petit François , Benachi Alexandra , Bedel Bettina , Oucherif Salima , Martinovic Jelena , Armanet Narjes , Tosca Lucie , Gautier Valérie , Parisot Frédéric , Labrune Philippe , Tachdjian Gérard , Brisset Sophie
Published: March 2016

Background

Monochorionic twins are generally considered as a monozygotic twin pregnancy. However, several cases of monochorial dizygotic twin pregnancies have been reported. Case Report: We report on a rare case of monochorionic dizygotic twin pregnancy conceived after induced ovulation in a 32‐year‐old woman. The diagnosis was made on morphological ultrasound examination at 18+4 weeks of gestation, showing two fetuses with discordant sex. The amniocentesis was declined by the patient.

Results

The monochorionic status was confirmed after a histopathalogical study of the placenta. At delivery, both a phenotypically normal boy and a phenotypically normal girl without sexual abnormality were observed. This analysis also revealed the presence of vascular anastomoses between both fetal circulations. Postnatal cytogenetic analyses indicated the presence of a chimerism in peripheral blood lymphocytes. This chimerism was not observed in cells obtained from a buccal swab. Molecular determination of zygosity confirmed the existence of the confined peripheral blood chimerism with the presence of four parental alleles.

Conclusion

We report on a case of monochorionic dizygotic twin pregnancy. This observation underlies the need to carefully assess twin pregnancies, especially when obtained after assisted reproductive technology. Birth Defects Research (Part A) 106:298–303, 2016. © 2016 Wiley Periodicals, Inc.
X‐ray crystal structure of anhydrous chitosan at atomic resolution
Authors: Naito Philip‐Kunio , Ogawa Yu , Sawada Daisuke , Nishiyama Yoshiharu , Iwata Tadahisa , Wada Masahisa
Published: March 2016

We determined the crystal structure of anhydrous chitosan at atomic resolution, using X‐ray fiber diffraction data extending to 1.17 Å resolution. The unit cell [a = 8.129(7) Å, b = 8.347(6) Å, c = 10.311(7) Å, space group P212121] of anhydrous chitosan contains two chains having one glucosamine residue in the asymmetric unit with the primary hydroxyl group in the gt conformation, that could be directly located in the Fourier omit map. The molecular arrangement of chitosan is very similar to the corner chains of cellulose II implying similar intermolecular hydrogen bonding between O6 and the amine nitrogen atom, and an intramolecular bifurcated hydrogen bond from O3 to O5 and O6. In addition to the classical hydrogen bonds, all the aliphatic hydrogens were involved in one or two weak hydrogen bonds, mostly helping to stabilize cohesion between antiparallel chains. © 2016 Wiley Periodicals, Inc. Biopolymers 105: 361–368, 2016.
The first case of POEMS syndrome with synchronous breast cancer: What are the associated diagnostic challenges?
Authors: Hiyama Kazuhiro , Terashima Hideo , Kuroda Akihiro , Harada Kyoichi , Shibagaki Yasuro , Hosaka Ai , Hayashi Taichi , Horiguchi Hisashi
Published: March 2016

Key Clinical Message

Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, Skin changes (POEMS) syndrome is a rare plasma cell disorder that causes a paraneoplastic syndrome. We report the first case of POEMS syndrome with synchronous breast cancer. The patient was at risk of being misdiagnosed with metastatic cancer, and it is important to emphasize that physical examinations provided vital diagnostic clues.
Self‐Assembly and Compartmentalization of Nanozymes in Mesoporous Silica‐Based Nanoreactors
Authors: Huang Yanyan , Lin Youhui , Ran Xiang , Ren Jinsong , Qu Xiaogang
Published: March 2016

Herein, to mimic complex natural system, polyelectrolyte multilayer (PEM)‐coated mesoporous silica nanoreactors were used to compartmentalize two different artificial enzymes. PEMs coated on the surface of mesoporous silica could serve as a permeable membrane to control the flow of molecules. When assembling hemin on the surface of mesoporous silica, the hemin‐based mesoporous silica system possessed remarkable peroxidase‐like activity, especially at physiological pH, and could be recycled more easily than traditional graphene–hemin nanocompounds. The hope is that these new findings may pave the way for exploring novel nanoreactors to achieve compartmentalization of nanozymes and applying artificial cascade catalytic systems to mimic cell organelles or important biochemical transformations
Single‐Point Remote Control of Flapping Motion in Clothespin‐Shaped Bimetallic Palladium Complexes Based on the N(sp2)–N(sp3) Interconversion in Amide Functionalities
Authors: Inoue Ryo , Kawamorita Soichiro , Naota Takeshi
Published: March 2016

The synthesis, structure, and flapping motion of clothespin‐shaped binuclear trans‐bis(salicylaldiminato)palladium(II) complexes (anti‐1) with 4‐azaheptamethylene linkers bearing amide (a–g), urethane (h), or urea (i) functionalities are described in this report. Various 2D 1H NMR experiments and XRD analyses indicate that the amide‐ and urethane‐linked anti‐1 a,b,d–h complexes exist as equilibrated mixtures of major and minor conformers I and II in CDCl3, whereas the complexes anti‐1 c and i were observed as a single species. The mapping of NOESY cross‐peaks between conformers I and II revealed that the equilibration of the major and minor conformers of anti‐1 a,b,d–h proceeds by two pathways, namely a nonrotatory flapping motion of the coordinated blades and a nonflapping rotation of C−N bonds, whereas the equilibration of anti‐1 c proceeds by simultaneous flapping and rotation motions. Kinetic studies carried out by means of 1H–1H EXSY experiments revealed that 1) the ΔG≠298K values for the flapping motion are controlled remotely by the steric and electronic effects of the RCON functionalities and 2) the activation parameters for the nonrotatory flapping process are identical to those for the nonflapping peptide rotation in the complexes anti‐1 a,b,d–h, which indicates that the present multistep conformational transformation induced by the flapping motion is controlled by the rate‐determining pyramidalization/depyramidalization (i.e., sp2/sp3 interconversion) of the nitrogen atoms of the functionalities. The static and controllable molecular mobility of anti‐1 bearing peptide linkers has been discussed by comparison with the dynamic behavior of its analogues anti‐2–4 with flexible polymethylene linkers.
Structure‐Dependent Anchoring of Organic Molecules to Atomically Defined Oxide Surfaces: Phthalic Acid on Co3O4(111), CoO(100), and CoO(111)
Authors: Xu Tao , Schwarz Matthias , Werner Kristin , Mohr Susanne , Amende Max , Libuda Jörg
Published: March 2016

We have performed a model study to explore the influence of surface structure on the anchoring of organic molecules on oxide materials. Specifically, we have investigated the adsorption of phthalic acid (PA) on three different, well‐ordered, and atomically defined cobalt oxide surfaces, namely 1) Co3O4(111), 2) CoO(111), and 3) CoO(100) on Ir(100). PA was deposited by physical vapor deposition (PVD). The formation of the PA films and interfacial reactions were monitored in situ during growth by isothermal time‐resolved IR reflection absorption spectroscopy (TR‐IRAS) under ultrahigh vacuum (UHV) conditions. We observed a pronounced structure dependence on the three surfaces with three distinctively different binding geometries and characteristic differences depending on the temperature and coverage. 1) PA initially binds to Co3O4(111) through the formation of a chelating bis‐carboxylate with the molecular plane oriented perpendicularly to the surface. Similar species were observed both at low temperature (130 K) and at room temperature (300 K). With increasing exposure, chelating mono‐carboxylates became more abundant and partially replaced the bis‐carboxylate. 2) PA binds to CoO(100) in the form of a bridging bis‐carboxylate for low coverage. Upon prolonged deposition of PA at low temperature, the bis‐carboxylates were converted into mono‐carboxylate species. In contrast, the bis‐carboxylate layer was very stable at 300 K. 3) For CoO(111) we observed a temperature‐dependent change in the adsorption mechanism. Although PA binds as a mono‐carboxylate in a bridging bidentate fashion at low temperature (130 K), a strongly distorted bis‐carboxylate was formed at 300 K, possibly as a result of temperature‐dependent restructuring of the surface. The results show that the adsorption geometry of PA depends on the atomic structure of the oxide surface. The structure dependence can be rationalized by the different arrangements of cobalt ions at the three surfaces.
Magnetic N‐Enriched Fe3C/Graphitic Carbon instead of Pt as an Electrocatalyst for the Oxygen Reduction Reaction
Authors: Wang Xiaobai , Zhang Peng , Wang Wei , Lei Xiang , Yang Hua
Published: March 2016

A series of Fe3C/C‐Nx nanoparticles (NPs) with different nitrogen content are prepared by a simple one‐pot route. In the synthetic procedure, aniline and acetonitrile are simultaneously used as the carbon and nitrogen source. The effect of calcination temperature on the structural and functional properties of the materials is investigated. Magnetic measurement shows that the sample prepared at 800 °C (Fe3C/C‐N800 NPs) possesses the highest Ms value of 77.2 emu g−1. On testing as oxygen reduction reaction (ORR) catalysts, the sample prepared at 750 °C (Fe3C/C‐N750 NPs) shows the best ORR performance among the series, with a more positive onset potential (+0.99 V vs. RHE), higher selectivity (number of electron transfer n≈3.93), longer durability, and stronger tolerance against methanol crossover than commercial Pt/C catalysts in a 0.1 m KOH solution. Moreover, in acidic solution, the excellent ORR activity and stability are also exhibited.
Catalase‐Modified Carbon Electrodes: Persuading Oxygen To Accept Four Electrons Rather Than Two
Authors: Sepunaru Lior , Laborda Eduardo , Compton Richard G.
Published: March 2016

We successfully exploited the natural highly efficient activity of an enzyme (catalase) together with carbon electrodes to produce a hybrid electrode for oxygen reduction, very appropriate for energy transformation. Carbon electrodes, in principle, are cheap but poor oxygen reduction materials, because only two‐electron reduction of oxygen occurs at low potentials, whereas four‐electron reduction is key for energy‐transformation technology. With the immobilization of catalase on the surface, the hydrogen peroxide produced electrochemically is decomposed back to oxygen by the enzyme; the enzyme natural activity on the surface regenerates oxygen, which is further reduced by the carbon electrode with no direct electron transfer between the enzyme and the electrode. Near full four‐electron reduction of oxygen is realised on a carbon electrode, which is modified with ease by a commercially available enzyme. The value of such enzyme‐modified electrode for energy‐transformation devices is evident.
Problematik der Übertragbarkeit bestehender Verfahren zur Kunststoff‐Charakterisierung auf Kunststoffgemische
Authors: Forberger Jens , Becker Robert W.
Published: March 2016

Die Rückgewinnung von Stoffmengen aus Verbundwerkstoffen im Sinne von Molecular Sorting ist ökonomisch attraktiv, wenn möglichst viele Stoffgruppen identifiziert, separiert und in den Stoffkreislauf zurückgeführt werden können. Durch Recycling von Thermoplast‐Matrix oder neue Entwicklungen zur werkstofflichen Verwertung von Verbundwerkstoffen werden neue Stoffstrome zurück in den Primärmarkt generiert. Jedoch bereits bei der Materialanalyse sind bestehende Verfahren beispielsweise für die Unternehmen wenig praxistauglich und stehen daher nur eingeschränkt zur Verfügung. Auch hochwertige Lösungen zur Erfassung, Charakterisierung und Verarbeitung von Verbundsystemen verschiedenster Kunststofftypen können nur eingeschränkt eingesetzt werden.
N‐Benzyl‐4‐((heteroaryl)methyl)benzamides: A New Class of Direct NADH‐Dependent 2‐trans Enoyl–Acyl Carrier Protein Reductase (InhA) Inhibitors with Antitubercular Activity
Authors: Guardia Ana , Gulten Gulcin , Fernandez Raquel , Gómez Jesus , Wang Feng , Convery Maire , Blanco Delia , Martínez María , Pérez‐Herrán Esther , Alonso Marta , Ortega Fátima , Rullás Joaquín , Calvo David , Mata Lydia , Young Robert , Sacchettini James C. , Mendoza‐Losana Alfonso , Remuiñán Modesto , Ballell Pages Lluís , Castro‐Pichel Julia
Published: March 2016

Isoniazid (INH) remains one of the cornerstones of antitubercular chemotherapy for drug‐sensitive strains of M. tuberculosis bacteria. However, the increasing prevalence of multidrug‐resistant (MDR) and extensively drug‐resistant (XDR) strains containing mutations in the KatG enzyme, which is responsible for the activation of INH into its antitubercular form, have rendered this drug of little or no use in many cases of drug‐resistant tuberculosis. Presented herein is a novel family of antitubercular direct NADH‐dependent 2‐trans enoyl–acyl carrier protein reductase (InhA) inhibitors based on an N‐benzyl‐4‐((heteroaryl)methyl)benzamide template; unlike INH, these do not require prior activation by KatG. Given their direct InhA target engagement, these compounds should be able to circumvent KatG‐related resistance in the clinic. The lead molecules were shown to be potent inhibitors of InhA and showed activity against M. tuberculosis bacteria. This new family of inhibitors was found to be chemically tractable, as exemplified by the facile synthesis of analogues and the establishment of structure–activity relationships. Furthermore, a co‐crystal structure of the initial hit with the enzyme is disclosed, providing valuable information toward the design of new InhA inhibitors for the treatment of MDR/XDR tuberculosis.
Quantitative Detection of Nucleoside Analogues by Multi‐enzyme Biosensors using Time‐Resolved Kinetic Measurements
Authors: Muthu Pravin , Lutz Stefan
Published: March 2016

Fast, simple and cost‐effective methods for detecting and quantifying pharmaceutical agents in patients are highly sought after to replace equipment and labor‐intensive analytical procedures. The development of new diagnostic technology including portable detection devices also enables point‐of‐care by non‐specialists in resource‐limited environments. We have focused on the detection and dose monitoring of nucleoside analogues used in viral and cancer therapies. Using deoxyribonucleoside kinases (dNKs) as biosensors, our chemometric model compares observed time‐resolved kinetics of unknown analytes to known substrate interactions across multiple enzymes. The resulting dataset can simultaneously identify and quantify multiple nucleosides and nucleoside analogues in complex sample mixtures.
Syntheses and preliminary evaluation of [18F]AlF‐NOTA‐G‐TMTP1 for PET imaging of high aggressive hepatocellular carcinoma
Authors: Li Yesen , Zhang Deliang , Shi Ying , Guo Zhide , Wu Xinying , Ren Jian‐Lin , Zhang Xianzhong , Wu Hua
Published: March 2016

The goal of this study is to evaluate a new 18F‐labeled imaging agent for diagnosing high metastatic (aggressive) hepatocellular carcinoma using positron emission tomography (PET). The new 18F‐labeled imaging agent [18F]AlF‐NOTA‐G‐TMTP1 was synthesized and radiolabeled with 18F using NOTA‐AlF chelation method. The tumor‐targeting characteristics of [18F]AlF‐NOTA‐G‐TMTP1 was assessed in HepG2, SMCC‐7721, HCC97L and HCCLM3 xenografts. The total synthesis time was about 20 min with radiochemical yield of 25 ± 6%. The specific activity was about 11.1–14.8 GBq/µmol at the end of synthesis based on the amount of peptide used and the amount of radioactivity trapped on the C18 column. The log P value of [18F]AlF‐NOTA‐G‐TMTP1 was ‐3.166 ± 0.022. [18F]AlF‐NOTA‐G‐TMTP1 accumulated in SMCC‐7721 and HCCLM3 tumors (high metastatic potential) in vivo and result in tumor/muscle (T/M) ratios of 4.5 ± 0.3 and 4.7 ± 0.2 (n = 4) as measured by PET at 40 min post‐injection (p.i.). Meanwhile, the tumor/muscle (T/M) ratios of HepG2 and HCC97L tumors (low metastatic potential) were1.6 ± 0.3 and 1.8 ± 0.4. The tumor uptake of [18F]AlF‐NOTA‐G‐TMTP1 could be inhibited 61.9% and 57.6% by unlabeled G‐TMTP1 in SMCC‐7721 and HCCLM3 xenografts at 40 min p.i., respectively. Furthermore, [18F]AlF‐NOTA‐G‐TMTP1 showed pretty low activity in the liver and intestines in all tumor bearing mice, such in vivo distribution pattern would be advantageous for the detection of hepatic carcinoma. Overall, [18F]AlF‐NOTA‐G‐TMTP1 may specifically target high metastatic or/and aggressive hepatocellular carcinoma with low background activity and, therefore, holds the potential to be used as an imaging agent for detecting tumor lesions within the liver area. Copyright © 2016 John Wiley & Sons, Ltd.
Current international flow cytometric practices for the detection and monitoring of paroxysmal nocturnal haemoglobinuria clones: A UK NEQAS survey
Authors: Fletcher Matthew , Whitby Liam , Whitby Alison , Barnett David
Published: March 2016

Background

Paroxysmal nocturnal haemoglobinuria (PNH) is a rare acquired genetic disorder, with an incidence of approximately 1.3 new cases per million population per year. Evidence from the UK National External Quality Assessment Service for Leucocyte Immunophenotyping (UK NEQAS LI) programme suggested major discrepancies on how PNH testing is undertaken. To investigate this we surveyed laboratories in the UK NEQAS LI PNH programme and report here the findings.

Methods

A questionnaire was distributed to all centres registered in UK NEQAS LI flow cytometry programmes (n = 1587). Comprising several subsections, it covered the majority of clinical flow cytometric practices. Participants completed a general section and then the subsections relevant to their laboratory repertoire. One subsection contained 34 questions regarding practices in PNH clone detection.

Results

A total of 105 laboratories returned results for the PNH section; the results demonstrated lack of consensus in all areas of PNH testing. Variation was seen in gating and testing strategies, sensitivity levels and final reporting of test results. Several incorrect practices were highlighted such as inappropriate antibody selection and failure to wash the red blood cells (RBCs) prior to analysis.

Conclusion

Despite the availability of consensus guidelines there appears to be no agreement in the detection and monitoring of PNH. We found only fourteen centres using methods compatible with the International Clinical Cytometry Society guidelines. Of specific note we found that no two laboratories used the same method. This technical variation could lead to incorrect diagnoses, highlighting the need for better adoption and understanding of consensus practices. © 2016 International Clinical Cytometry Society
Metastatic ductal carcinoma of the breast to the thyroid gland diagnosed with fine needle aspiration: A case report with emphasis on morphologic and immunophenotypic features
Authors: Magers Martin J. , Dueber Julie C. , Lew Madelyn , Pang Judy C. , Davenport Robertson D.
Published: March 2016

Metastases to the thyroid are uncommon [<0.2% of thyroid fine needle aspirations (FNA)]. Of metastases to the thyroid, breast carcinoma is relatively common. The diagnosis of metastasis to the thyroid has important therapeutic and prognostic implications. To our knowledge, a morphologic and immunophenotypic comparison of metastatic ductal carcinoma of the breast and primary thyroid carcinomas has not been reported. Here, we report the case of a 37‐year‐old female with a history of metastatic ductal carcinoma of the breast (modified Bloom‐Richardson grade 2; ER+, PgR+, HER2+) diagnosed 6 years prior. She developed hoarseness, prompting a CT scan. Multiple thyroid nodules were found, including a 1.5 cm hypoechoic, solid, irregularly‐shaped nodule. On FNA, cells were arranged singly and in crowded groups, varied in size and degree of pleomorphism, and exhibited rare nuclear grooves, inconspicuous nucleoli, and rare intracytoplasmic lumina with no nuclear pseudoinclusions or colloid (Figs. 1A and B). These findings raised the differential of papillary thyroid carcinoma (Fig. 1C), follicular neoplasm (Fig. 1D), medullary carcinoma (Fig. 1E), parathyroid (Fig. 1F), and metastatic breast carcinoma. Immunostaining for GATA‐3 (+), ER (+), PAX‐8 (−), and TTF‐1 (−) was consistent with metastatic breast carcinoma (Fig. 2). We conclude that metastatic breast carcinoma to the thyroid may morphologically mimic primary thyroid carcinoma on FNA; a panel of immunomarkers, such as GATA‐3, hormonal marker(s), PAX‐8, and TTF‐1, may be useful in some cases. GATA‐3 immunostaining for metastatic breast carcinoma was helpful in our case and has not been previously reported in a thyroid metastasis sampled by FNA. Diagn. Cytopathol. 2016;44:530–534. © 2016 Wiley Periodicals, Inc.
Acute heat shock leads to cortical domain internalization and polarity loss in the C. elegans embryo
Authors: Singh Deepika , Odedra Devang , Lehmann Christina , Pohl Christian
Published: March 2016

Many developmental processes are inherently robust due to network organization of the participating factors and functional redundancy. The heterogeneity of the factors involved and their connectivity puts these processes at risk of abrupt system collapse under stress. The polarization of the one‐cell C. elegans embryo constitutes such an inherently robust process with functional redundancy. However, how polarization is affected by acute stress has not been thoroughly investigated. Here, we report that heat shock (34°C, 1 h) triggers a highly reproducible loss of the anterior and collapse of the posterior polarity domains. Temperature‐dependent loss of cortical non‐muscle myosin II drastically reduces cortical tension and leads to internalization of large plasma membrane domains including the membrane‐associated polarity factor PAR‐2. After internalization, plasma membrane vesicles and associated factors cluster around centrosomes and are thereby withdrawn from the polarization process. Transient formation of the posterior polarity domain suggests that microtubule‐induced self‐organization of this domain is not compromised after heat shock. Hence, our data uncover that the polarization system undergoes a temperature‐dependent collapse under acute stress. genesis, 2016. © 2016 Wiley Periodicals, Inc. genesis 54:220–228, 2016. © 2016 Wiley Periodicals, Inc.
The Caenorhabditis elegans Q neuroblasts: A powerful system to study cell migration at single‐cell resolution in vivo
Authors: Rella Lorenzo , Fernandes Póvoa Euclides E. , Korswagen Hendrik C.
Published: March 2016

During development, cell migration plays a central role in the formation of tissues and organs. Understanding the molecular mechanisms that drive and control these migrations is a key challenge in developmental biology that will provide important insights into disease processes, including cancer cell metastasis. In this article, we discuss the Caenorhabditis elegans Q neuroblasts and their descendants as a tool to study cell migration at single‐cell resolution in vivo. The highly stereotypical migration of these cells provides a powerful system to study the dynamic cytoskeletal processes that drive migration as well as the evolutionarily conserved signaling pathways (including different Wnt signaling cascades) that guide the cells along their specific trajectories. Here, we provide an overview of what is currently known about Q neuroblast migration and highlight the live‐cell imaging, genome editing, and quantitative gene expression techniques that have been developed to study this process. genesis, 2016. © 2016 Wiley Periodicals, Inc. genesis 54:198–211, 2016. © 2016 Wiley Periodicals, Inc.
Automated proximity sensing in small vertebrates: design of miniaturized sensor nodes and first field tests in bats
Authors: Ripperger Simon , Josic Darija , Hierold Martin , Koelpin Alexander , Weigel Robert , Hartmann Markus , Page Rachel , Mayer Frieder
Published: March 2016

Social evolution has led to a stunning diversity of complex social behavior, in particular in vertebrate taxa. Thorough documentation of social interactions is crucial to study the causes and consequences of sociality in gregarious animals. Wireless digital transceivers represent a promising tool to revolutionize data collection for the study of social interactions in terms of the degree of automation, data quantity, and quality. Unfortunately, devices for automated proximity sensing via direct communication among animal‐borne sensors are usually heavy and do not allow for the investigation of small animal species, which represent the majority of avian and mammalian taxa. We present a lightweight animal‐borne sensor node that is built from commercially available components and uses a sophisticated scheme for energy‐efficient communication, with high sampling rates at relatively low power consumption. We demonstrate the basic functionality of the sensor node under laboratory conditions and its applicability for the study of social interactions among free‐ranging animals. The first field tests were performed on two species of bats in temperate and tropical ecosystems. At <2 g, this sensor node is light enough to observe a broad spectrum of taxa including small vertebrates. Given our specifications, the system was especially sensitive to changes in distance within the short range (up to a distance of 4 m between tags). High spatial resolution at short distances enables the evaluation of interactions among individuals at a fine scale and the investigation of close contacts. This technology opens new avenues of research, allowing detailed investigation of events associated with social contact, such as mating behavior, pathogen transmission, social learning, and resource sharing. Social behavior that is not easily observed becomes observable, for example, in animals living in burrows or in nocturnal animals. A switch from traditional methods to the application of digital transceiver chips in proximity sensing offers numerous advantages in addition to an enormous increase in data quality and quantity. For future applications, the platform allows for the integration of additional sensors that may collect physiological or environmental data. Such information complements social network studies and may allow for a deeper understanding of animal ecology and social behavior.
Tooth wear patterns in black rats (Rattus rattus) of Madagascar differ more in relation to human impact than to differences in natural habitats
Authors: Winkler Daniela E. , Andrianasolo Tolona H. , Andriamandimbiarisoa Laza , Ganzhorn Jörg U. , Rakotondranary S. Jacques , Kaiser Thomas M. , Schulz‐Kornas Ellen
Published: March 2016

Dietary characteristics and environmental variables are important selective factors directing ecological diversification in rodents. On Madagascar, the introductions and spread of the commensal black rat (Rattus rattus) can be seen as example cases to study dietary niche occupation and dietary adaptation in an insular environment. We investigate how tooth wear as a measure of dietary adaptation of black rats differs between four distinct habitats (village, manioc fields, spiny forest, and rainforest) with different dietary resources. We use the 3D surface texture analysis (3DST, using 30 parameters according to ISO 25178) as a measure of dietary abrasiveness. 3DST is applied on the occlusal surface of the upper first molar of 37 black rat specimens. The rainforest sample displays less rough and less voluminous surface textures compared to the village samples as indicated by smaller values for height parameters (Sa, Sp, Sq), inverse areal material ratio (Smc), and volume parameters (Vm, Vmc, Vmp, Vv, and Vvc). We therefore rank sampling areas from highest to lowest abrasiveness (village>manioc fields/spiny forest>rainforest). The rats from villages and rainforest differ to such an extent that one could have interpreted them to belong to different species. This indicates a high degree of variability in terms of ingesta abrasiveness. Furthermore, the pronounced difference between rats from human habitations compared to rats from associated fields or natural vegetation is interpreted to clearly indicate shifts in dietary niche occupation in relation to human impact.
The temporal scale of diet and dietary proxies
Authors: Davis Matt , Pineda‐Munoz Silvia
Published: March 2016

Diets estimated from different proxies such as stable isotopes, stomach contents, and dental microwear often disagree, leading to nominally well‐supported but greatly differing estimates of diet for both extinct and extant species that complicate our understanding of ecology. We show that these perceived incongruences can be caused by proxies recording diet over vastly different timescales. Field observations reveal a diet averaged over minutes or hours, whereas dental morphology may reflect the diet of a lineage over millions of years of evolution. Failing to explicitly consider the scale of proxies and the potentially large temporal variability in diet can cause erroneous predictions in any downstream analyses such as conservation planning or paleohabitat reconstructions. We propose a cross‐scale framework for conceptualizing diet suitable for both modern ecologists and paleontologists and provide recommendations for any studies involving dietary data. Treating diet in this temporally explicit framework and matching the scale of our questions with the scale of our data will lead to a much richer and clearer understanding of ecological and evolutionary processes.
Fasciola hepatica tegumental antigens induce anergic‐like T cells via dendritic cells in a mannose receptor‐dependent manner
Authors: Aldridge Allison , O'Neill Sandra M.
Published: March 2016

FoxP3+ Treg cells and anergic T cells are the two regulatory phenotypes of T‐cell responses associated with helminth infection. Here, we examine the T‐cell responses in mice during Fasciola hepatica infection, and to its tegumental coat antigens (FhTeg) that are shed from the fluke every 2–3 h. FhTeg comprises a rich source of glycoproteins, mainly oligomannose N‐glycans that bind to mannose receptor. This study demonstrated a novel mechanism for the T‐cell unresponsiveness observed during F. hepatica infection and after injection with FhTeg. Markers of T‐cell anergy, such as GRAIL, EGR2, ICOS, and ITCH, are enhanced amongst CD4+ T‐cell populations during infection and following FhTeg injection. This is characterized by a lack of cytokine responses and reduced proliferative activity, which can be reversed with the addition of IL‐2. FhTeg‐activated dendritic cells (DCs) suppress T cells in vitro as measured by enhanced GRAIL and CTLA4 by RNA and suppressed cytokine expression in anti‐CD3 stimulated CD4+ T cells. FhTeg‐treated DCs have enhanced MR expression, which is critical for DC‐CD4+ T‐cell communication. Taken together, this study presents markers of anergy in a mouse model of F. hepatica infection, and improves our understanding of host–pathogen interactions and how helminths modulate host immunity.
Organotemplate‐Free Synthesis of a High‐Silica Zeolite with a TON Structure in the Absence of Zeolite Seeds
Authors: Yeqing Wang  , Zhu Chenqi , Qiu Jing , Jiang Fan , Meng Xiangju , Wang Xiong , Lei Chi , Jin Yinying , Pan Shuxiang , Xiao Feng‐Shou
Published: March 2016

A high‐silica zeolite with a TON structure designated as ZJM‐4 was successfully synthesized in the absence of any organic templates and zeolite seeds. Many factors such as the SiO2/K2O ratio, Si/Al ratio, SiO2/H2O in the starting aluminosilicate gels, crystallization temperature, and crystallization time strongly influence the formation of the ZJM‐4 zeolite. Interestingly, this synthesis shows very efficient silica utilization in the starting gels (>80 %). Catalytic tests on the isomerization of m‐xylene to p‐xylene show that the ZJM‐4 catalyst has high selectivity to p‐xylene (ca. 80 %), which could be potentially important for industrial applications for the ZJM‐4 zeolite as a candidate catalyst in the future.
Selective Elaboration of Aminodiols towards Small Ring α‐ and β‐Amino Acid Derivatives that Incorporate an Aziridine, Azetidine, or Epoxide Scaffold
Authors: Semina Elena , Žukauskaitė Asta , Šačkus Algirdas , De Kimpe Norbert , Mangelinckx Sven
Published: March 2016

The osmium‐catalyzed dihydroxylation of N‐substituted alkyl 2‐(aminomethyl)acrylates resulted in the efficient synthesis of 2‐(aminomethyl)‐2,3‐dihydroxypropanoates in good yields (82–89 %). The resulting aminodiols were elaborated in a selective diversity‐oriented synthesis to produce the corresponding 2‐(aminomethyl)oxirane‐2‐carboxylates, functionalized aziridine‐2‐carboxylates, and azetidine‐3‐carboxylates by using straightforward reactions.
Implementation of an analytical microfluidic device for the quantification of protein concentrations in high‐throughput format
Authors: Radtke Carsten Philipp , Schermeyer Marie‐Therese , Zhai Yün Claudia , Göpper Jacqueline , Hubbuch Jürgen
Published: March 2016

Nowadays, the performance of experiments in automated microliter scale format is common practice in the biopharmaceutical process development. The increased number of experiments, reduced sample volumes, and usage of robotic platforms require the adjustment of photometric measurements to determine the protein concentration. This work presents the qualification and usage of a disposable measurement device that can be used with conventional microplate photometers. The application of the microfluidic device (μF‐device) allows absorption measurements of protein concentrations from around 0.1 to 100 mg/mL with an accuracy of 99.2% dependent on given protein extinction coefficients. The integrated four measurement chambers of increasing height (100–1500 μm) allow the direct calculation of calibration curves and the determination of protein concentrations independent of used optical path lengths with a sample volume of 36 μL. This study contains the validation of the analytical μF‐device according to ICH Guidelines as well as a representative case study. A salt gradient screening with chromatography columns in microliter scale performed on a liquid handling station presents the usability of the μF‐device. It is shown that an improvement of the repeatability and accuracy of the chromatograms could be achieved by μF‐device implementation in comparison to photometric measurements performed in microtiter plates.
Tissue explant coculture model of the hypothalamic–pituitary–gonadal–liver axis of the fathead minnow (Pimephales promelas) as a predictive tool for endocrine disruption
Authors: Johnston Theresa K. , Perkins Edward , Ferguson Duncan C. , Cropek Donald M.
Published: March 2016

Endocrine-disrupting compounds (EDCs) can impact the reproductive system by interfering with the hypothalamic–pituitary–gonadal (HPG) axis. Although in vitro testing methods have been developed to screen chemicals for endocrine disruption, extrapolation of in vitro responses to in vivo action shows inconsistent accuracy. The authors describe a tissue coculture of the fathead minnow (Pimephales promelas) HPG axis and liver (HPG-L) as a tissue explant model that mimics in vivo results. Brain (hypothalamus), pituitary, gonad, and liver tissue explants from adult fish were examined for function both individually and in coculture to determine combinations and conditions that could replicate in vivo behavior. Only cocultures had the ability to respond to an EDC, trenbolone, similarly to in vivo studies, based on estradiol, testosterone, and vitellogenin production trends, where lower exposure doses suppressed hormone production but higher doses increased production, resulting in distinctive U-shaped curves. These data suggest that a coculture system with all components of the HPG-L axis can be used as a link between in vitro and in vivo studies to predict endocrine system disruption in whole organisms. This tissue-based HPG-L system acts as a flexible deconstructed version of the in vivo system for better control and examination of the minute changes in system operation and response on EDC exposure with options to isolate, interrogate, and recombine desired components. Environ Toxicol Chem 2016;35:2530–2541. Published 2016 Wiley Periodicals Inc. on behalf of SETAC. This article is a US Government work and, as such, is in the public domain in the United States of America.
Halogenated carbazoles induce cardiotoxicity in developing zebrafish (Danio rerio) embryos
Authors: Fang Mingliang , Guo Jiehong , Chen Da , Li An , Hinton David E. , Dong Wu
Published: March 2016

Halogenated carbazoles are increasingly identified as a novel class of environmental contaminants. However, no in vivo acute toxicity information on those compounds was available. In the present study, an in vivo zebrafish embryonic model (Danio rerio) was used to investigate the developmental toxicity of those halogenated carbazoles. The results suggested that acute toxicity was structure-dependent. Two of the 6 tested carbazoles, 2,7-dibromocarbazole (27-DBCZ) and 2,3,6,7-tetrachlorocarbazole, showed obvious developmental toxicity at nanomolar levels. The typical phenotypes were similar to dioxin-induced cardiotoxicity, including swollen yolk sac, pericardial sac edema, elongated and unlooped heart, and lower jaw shortening. During embryonic development 27-DBCZ also induced a unique pigmentation decrease. Gene expression and protein staining of cytochrome P4501A (CYP1A) showed that both halogenated carbazoles could induce CYP1A expression at the micromolar level and primarily in the heart area, which was similar to dioxin activity. Further, aryl hydrocarbon receptor-(AhR)2 gene knockdown with morpholino confirmed that the acute cardiotoxicity is AhR–dependent. In conclusion, the results demonstrate that halogenated carbazoles represent yet another class of persistent organic pollutants with dioxin-like activity in an in vivo animal model. Environ Toxicol Chem 2016;35:2523–2529. © 2016 SETAC
Bounds and approximations on the ergodic mutual information of spatially correlated Nakagami‐m MIMO channels
Authors: Guimarães Antonio Alisson P. , Kountouris Marios , Cavalcante Charles Casimiro
Published: March 2016

In this paper, the ergodic mutual information of point‐to‐point multi‐antenna systems with spatially correlated Nakagami‐m fading channel is studied. We consider that no channel knowledge is available at the transmitter side, while the receiver has perfect channel state information. Using the unitary‐independent‐unitary framework, tools from majorisation theory, and recent results on the sum of independent Gamma random variables with different parameters, we derive new analytical closed‐form bounds and tight approximations to the ergodic mutual information in spatially correlated multi‐antenna channels. Our analytical expressions are verified through Monte Carlo simulations, and their effectiveness is compared with prior results in the literature. Copyright © 2016 John Wiley & Sons, Ltd.
Optimization of Shea (Vitellaria paradoxa) butter quality using screw expeller extraction
Authors: Gezahegn Yonas A. , Emire Shimelis A. , Asfaw Sisay F.
Published: March 2016

The quality of Shea butter is highly affected by processing factors. Hence, the aim of this work was to evaluate the effects of conditioning duration (CD), moisture content (MC), and die temperature (DT) of screw expeller on Shea butter quality. A combination of 33 full factorial design and response surface methodology was used for this investigation. Response variables were refractive index, acid value, and peroxide value. The model enabled to identify the optimum operating settings (CD = 28–30 min, MC = 3–5 g/100 g, and DT = 65–70°C) for maximize refractive index and minimum acid value. For minimum peroxide value 0 min CD, 10 g/100 g MC, and 30°C were discovered. In all‐over optimization, optimal values of 30 min CD, 9.7 g/100 g MC, and 70°C DT were found. Hence, the processing factors must be at their optimal values to achieve high butter quality and consistence.