bluuebunny/crossref_metadata_2025 huggingface dataset:
High‐Fidelity Protein Targeting into Membrane Lipid Microdomains in Living Cells
Authors: Beutel Oliver , Nikolaus Jörg , Birkholz Oliver , You Changjiang , Schmidt Thomas , Herrmann Andreas , Piehler Jacob
Published: December 2013

Lipid analogues carrying three nitrilotriacetic acid (tris‐NTA) head groups were developed for the selective targeting of His‐tagged proteins into liquid ordered (lo) or liquid disordered (ld) lipid phases. Strong partitioning into the lo phase of His‐tagged proteins bound to tris‐NTA conjugated to saturated alkyl chains (tris‐NTA DODA) was achieved, while tris‐NTA conjugated to an unsaturated alkyl chain (tris‐NTA SOA) predominantly resided in the ld phase. Interestingly, His‐tag‐mediated lipid crosslinking turned out to be required for efficient targeting into the lo phase by tris‐NTA DODA. Robust partitioning into lo phases was confirmed by using viral lipid mixtures and giant plasma membrane vesicles. Moreover, efficient protein targeting into lo and ld domains within the plasma membrane of living cells was demonstrated by single‐molecule tracking, thus establishing a highly generic approach for exploring lipid microdomains in situ.
Reply to Comments on “Synthesis, Characterization, and Structures of Persistent Aniline Radical Cation”
Authors: Chen Xiaoyu , Wang Xingyong , Sui Yunxia , Li Yizhi , Ma Jing , Zuo Jinglin , Wang Xinping
Published: December 2013

The identification of the aniline radical cation TBA.+ (TBA=2,4,6‐tBu3C6H2NH2) reported in 2012 was questioned in the preceeding Correspondence articles. The original authors have reexamined their UV/Vis absorption and EPR data and insist that TBA.+ radical cation is indeed persistent and stable. The possible cocrystallization of TBA.+ with TBAH+ makes crystal structures more complicated.
Full Functionalization of the Imidazole Scaffold by Selective Metalation and Sulfoxide/Magnesium Exchange
Authors: Sämann Christoph , Coya Estibaliz , Knochel Paul
Published: December 2013

A simple, flexible, and straightforward method for the functionalization of all the positions of the imidazole heterocycle through regioselective arylations, allylations, acylations, and additions to aldehydes is disclosed. Starting from the readily available key imidazole 1, highly functionalized imidazole derivatives have been synthesized in a regioselective manner from directed metalations and a sulfoxide/magnesium exchange. Moreover, the selective N3‐alkylation followed by deprotection of N1 (trans‐N‐alkylation) allows the regioselective N‐alkylation of complex imidazoles.
Preparation of anion exchange membrane based on homogeneous quaternization of bromomethylated poly(arylene ether sulfone)
Authors: Zhao Chengji , Ma Wenjia , Sun Wenmo , Na Hui
Published: December 2013

This article presented the synthetic and preparation route of quaternary ammonium functionalized anion exchange membranes (AEMs), which were derived from an engineering plastics polymer, poly(arylene ether sulfone) with 3,3′,5,5′‐tetramethyl‐4,4′‐dihydroxybipheny moiety (PAES‐TM). The benzylmethyl groups on the main‐chain of PAES‐TM were converted to the bromomethyl groups via a radical reaction, thereby avoiding complicated chloromethylation, which required carcinogenic reagents. The chemical structure of the bromomethylated PAES was characterized by 1H NMR spectrum. Following a homogeneous quaternization with trimethylamine in the solution, a series of flexible and tough membranes were obtained by a solution casting and anion exchange process. The ion exchange capacity values were ranging from 1.03 to 1.37 meq g−1. The properties of the membranes, including water uptake, hydroxide conductivity, and methanol permeability were evaluated in detail. The AEM showed a high conductivity above 10−2 S cm−1 at room temperature and extremely low methanol permeability of 4.16–4.94 × 10−8 cm2 s−1. The high hydroxide conductivity of TMPAES‐140‐NOH could be attributed to the nano‐scale phase‐separated morphology in the membrane, which was confirmed by their transmission electron microscopy images. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40256.
Beitrag zur Methodik der pauschalen Bestimmung von Wärmedurchgangskoeffizienten bei bestehenden Wohngebäuden
Authors: Kempf Heike
Published: December 2013

Aufgrund unzureichender oder fehlender Datengrundlagen im Wohngebäudebestand dürfen beim öffentlich‐rechtlichen Nachweis nach der Energieeinsparverordnung pauschale Kennwerte wie der Wärmedurchgangskoeffizient verwendet werden. Diese können aus einer Tabelle der Regeln zur vereinfachten Datenaufnahme des Bundesministeriums für Verkehr, Bau und Stadtentwicklung (BMVBS) entnommen werden. Die vorliegende Untersuchung zeigt, dass es sich bei den derzeitig pauschalen Wärmedurchgangkoeffizienten um einen zu vereinfachten Ansatz handelt. Diese Wärmedurchgangskoeffizienten nehmen einen nicht vernachlässigbaren Einfluss auf die Anforderungsgrößen, die zur Erstellung des Energiebedarfsausweises notwendig sind. Aus diesem Grund ist es sinnvoll, die derzeitige Tabelle um weitere Daten, wie beispielsweise die Dicke der Bauteile, zu ergänzen.

Contribution to the methodology of the general terms at coefficients of heat transfer in existing residential buildings. Due to an insufficient or missing data base concerning existing residential buildings it is permitted to use general values, e. g. for the heat transfer coefficient (U‐value) according to the German Energy Saving Ordinate. The values for simplified data acquisition are provided by the German Federal Ministry of Transport, Building and Urban Development. The present study shows that the current general heat transfer coefficient results from a too simplified approach, with considerable influence on the calculated energy demand. This is the reason to extend the existing data table with further data, e. g. thickness of building component.
Dämmstoffintegrierte Kanäle für zentrale Lüftungsanlagen mit Wärmerückgewinnung
Authors: Hauser Gerd , Kaiser Jan
Published: December 2013

Der energetischen Sanierung von Bestandsgebäuden kommt u. a. auch für die Erreichung der klimapolitischen Ziele der Bundesregierung bis zum Jahr 2050 eine Schlüsselrolle zu. Allerdings bleiben bis dato – insbesondere aufgrund hoher Investitionskosten – die hierfür notwendigen Sanierungsquoten deutlich hinter den Erwartungen zurück. Ziel muss es daher sein, den Wärmebedarf von Bestandsgebäuden möglichst einfach und kostengünstig zu senken.

In folgendem Beitrag wird ein innovatives Produkt vorgestellt, welches die Funktionen Gebäudedämmung und Luftführung in einem Bauteil vereint und somit den Einbau einer kontrollierten Wohnungslüftungsanlage mit Wärmerückgewinnung ermöglicht, ohne die üblichen Probleme bei einer Nachrüstung von Luftleitungen im Innenraum hervorzurufen. Es handelt sich dabei um Lüftungskanäle, welche direkt in handelsübliche Dämmplatten integriert sind.

Am Beispiel von Demonstrationsobjekten wird die Funktion und Verarbeitung des neuartigen Systems erläutert. Es werden sowohl die energetischen, thermo‐hygrischen und akustischen Eigenschaften des Systems beschrieben als auch brandschutztechnische und hygienische Aspekte beleuchtet.

Integrated ventilation ducts in thermal insulation panels for heat recovery. The energy‐efficient renovation of existing buildings will among other things also play a key‐role in achieving the climate‐policy goals of the Federal Government by the year 2050. So far, however, the required number of modernized buildings remains far behind expectations, especially because of the high investment costs involved. The aim must, therefore, be to reduce the heating requirement of existing buildings as simply and cost‐effectively as possible.

In the following an innovative product is presented which combines the functions of building insulation and ventilation in one component and thus allows the installation of controlled domestic ventilation systems with heat recovery without the usual problems of retrofitting air‐ducts inside the building. In this new product, ventilation ducts are integrated directly in the usual commercially available insulating panels.

The function and processing of this novel system are illustrated and exemplified by demonstration objects. Not only are the energy‐efficient, hygrothermal and acoustic characteristics of this system described in detail, but the fire protection and hygienic aspects are examined as well.
Conditionally unbiased and near unbiased estimation of the selected treatment mean for multistage drop‐the‐losers trials
Authors: Bowden Jack , Glimm Ekkehard
Published: December 2013

The two‐stage drop‐the‐loser design provides a framework for selecting the most promising of K experimental treatments in stage one, in order to test it against a control in a confirmatory analysis at stage two. The multistage drop‐the‐losers design is both a natural extension of the original two‐stage design, and a special case of the more general framework of Stallard & Friede () (Stat. Med. 27, 6209–6227). It may be a useful strategy if deselecting all but the best performing treatment after one interim analysis is thought to pose an unacceptable risk of dropping the truly best treatment. However, estimation has yet to be considered for this design. Building on the work of Cohen & Sackrowitz () (Stat. Prob. Lett. 8, 273–278), we derive unbiased and near‐unbiased estimates in the multistage setting. Complications caused by the multistage selection process are shown to hinder a simple identification of the multistage uniform minimum variance conditionally unbiased estimate (UMVCUE); two separate but related estimators are therefore proposed, each containing some of the UMVCUEs theoretical characteristics. For a specific example of a three‐stage drop‐the‐losers trial, we compare their performance against several alternative estimators in terms of bias, mean squared error, confidence interval width and coverage.
Representations of Poverty in British Newspapers: A Case of ‘Othering’ the Threat?
Authors: Chauhan Apurv , Foster Juliet
Published: December 2013

The meanings of social problems like poverty develop within the public sphere. This paper uses the theory of social representations to examine how poverty is represented in British newspapers. Poverty has been discussed and interpreted in numerous ways, and newspapers not only provide a platform for these elaborations but also contribute to shaping public understanding on the issue. The study sampled news coverage on poverty in four British newspapers during two randomly chosen one‐month periods in the years 2001 and 2011. The data set of news reports (n = 274) was thematically analysed to examine representations of poverty. The study found that in the domestic context, media represents poverty as a problem limited to vulnerable groups such as children and the elderly. With a lack of discussion on the wider socio‐economic causes and contributing factors, poverty within the UK appears as an ‘orphan phenomenon’ with an unknown genesis. In contrast, the representations of poverty outside the UK are vivid and elaborate, and the news reports hold the socio‐political inefficiency of countries responsible for poverty. The study also found that the media uses poverty to make sense of catastrophic events in society: the September 11, 2001 terrorist attacks in the United States and the London riots of 2011 were both anchored using poverty. This paper discusses the representational dynamics of these findings and argues that the media representations distance general society from poverty, representing it as a problem of the other. Copyright © 2013 John Wiley & Sons, Ltd.
What is ambiguous about ambiguous goods?
Authors: Ross Sandy L.
Published: December 2013

Ambiguous goods are not a category of things. No goods are ambiguous by default, not even digital virtual ones. Ambiguity may arise in many ways, but this article examines one specific process: ambiguity that occurs when entities appear as objects that blur category boundaries. Ambiguity is created around pre‐existing categories through socio‐material entanglements. This article explores how a central category in consumer capitalist societies—property—takes on ambiguous forms in distributions and recirculations of prestige items in the massively multi‐player online role‐playing game Final Fantasy XI. Prestige objects are powerful, sought‐after armour and weapons acquired in the game world by completing difficult battlefields or tasks, often in large groups. When discussing these items, respondents are not confused actors trying to make sense of slippery things. Instead, they produce ambiguities around property by blurring distinctions between gifts and commodities. Blurred boundaries help resolve tensions arising from different orderings of people, relations and things. Hybridised property forms allow selective alienation of goods, allowing participants to privilege some relations and connections over others.

With this article, I hope to spark further debate on building a conceptual toolkit to explore ambiguities, and contribute to increasing interest in non‐dyadic gift relations in consumer culture research. ‘Ambiguous goods’ is not a viable category for thinking about things, people and relations or digital virtual objects. But ambiguity can be a useful way to think about how people and things—whether they are digital, virtual or neither—are related. Copyright © 2014 John Wiley & Sons, Ltd.
Hedgehog signalling is dispensable in the proliferation of stem cells from human exfoliated deciduous teeth
Authors: Ejeian Fatemeh , Baharvand Hossein , Nasr‐Esfahani Mohammad Hossein
Published: December 2013

The hedgehog (Hh) signalling pathway is one of the key regulators in development with a dual role in cell fate specification, proliferation, and survival on different target cells. We have investigated the effect of recombinant sonic hedgehog (r‐SHH) on extracted multipotent stem cells from human exfoliated deciduous teeth (SHED), which represent a potential stem cell population for therapeutic applications. Cell proliferation and cycle assays shown that r‐SHH did not have a distinctive effect on cell cycle progression, nor did it increase cell number over a wide range of concentrations. Quantitative polymerase chain reaction (Q‐PCR) also suggests that r‐SHH treatment has no demonstrable influence on expression of proliferative genes (CCNE1 and KI67); in contrast, the anti‐proliferative gene (CDKN1A) is overexpressed in response to SHH. Our findings have suggested the possibility that SHEDs demonstrate a different potential from human bone marrow mesenchymal stem cells (h‐BMSCs) and dorsal neural progenitor in response to growth factors such as SHH.
How source cues impact consumer evaluations of direct and indirect persuasion attempts
Authors: Main Kelley J. , Aditya Sutapa , Dahl Darren W.
Published: December 2013

This research demonstrates how the directness of a persuasion attempt by a sales agent, in this case flattery, changes how source cues influence consumers’ evaluation of the shopping experience. When the persuasion attempt is direct, source cues do not influence consumer evaluations. However, when an indirect persuasion attempt is used, it is only effective when positive source cues are present. In particular, when the persuasion attempt is indirect, evaluations are more effective when the sales agent is attractive to or shares similar opinions with the consumer. Copyright © 2013 ASAC. Published by John Wiley & Sons, Ltd.
Baseline health perceptions, dysphagia, and survival in patients with head and neck cancer
Authors: Lango Miriam N. , Egleston Brian , Fang Carolyn , Burtness Barbara , Galloway Thomas , Liu Jeffrey , Mehra Ranee , Ebersole Barbara , Moran Kathleen , Ridge John A.
Published: December 2013

BACKGROUND

In head and neck cancer patients prior to treatment, dysphagia noted by patients is more common than aspiration on formal swallow studies. The authors hypothesized that patient‐reported dysphagia impacts multiple domains of quality of life (QOL) and predicts disease recurrence and disease‐related death.

METHODS

The Swal‐QOL, a dysphagia‐specific, swallowing‐related, QOL measure, and the EuroQOL‐5D‐3L were administered to 159 patients before treatment with curative intent in this prospective cohort study. Logistic regression analysis evaluated associations among clinical and subjective measures. Multivariable competing risk regression tested the impact of clinical, tumor, and patient‐reported measures on survival.

RESULTS

Baseline dysphagia, pain, and diminished patient‐reported health state were found to be closely associated with weight loss before treatment and advanced T classification. However, only 58% of patients (23 of 40 patients) reporting dysphagia experienced > 5% weight loss. Dysphagia was found to be associated with pain and/or diminished patient‐reported health state, independent of weight loss. Female patients were more likely to report pain and dysphagia, whereas male patients reported dysphagia alone. Dysphagia was found to be predictive of disease recurrence and disease‐related death, adjusting for T and N classifications, ECOG performance status, smoking status, and weight loss, and accounting for competing risks of death (recurrence‐free survival: hazards ratio, 3.8 [95% confidence interval, 1.7‐8.4; P = .001] and disease‐related death: hazards ratio, 4.2 [95% confidence interval, 1.04‐5; P = .004]).

CONCLUSIONS

Baseline dysphagia affects multiple domains of QOL and general health perceptions in patients with head and neck cancer prior to treatment. A dysphagia measure captures the effort of maintaining nutrition, and identifies patients predisposed to disease recurrence and disease‐related death. Cancer 2014;120:840–847. © 2013 American Cancer Society.
Activation of the Akt‐mTOR pathway and receptor tyrosine kinase in patients with solitary fibrous tumors
Authors: Yamada Yuichi , Kohashi Kenichi , Fushimi Fumiyoshi , Takahashi Yusuke , Setsu Nokitaka , Endo Makoto , Yamamoto Hidetaka , Tokunaga Shoji , Iwamoto Yukihide , Oda Yoshinao
Published: December 2013

BACKGROUND

Solitary fibrous tumors (SFTs) are soft tissue tumors of intermediate malignancy that rarely metastasize. Although unresectable SFTs are reported to have a poor prognosis, to the authors' knowledge there is currently no effective therapy. Molecular target therapy is a promising approach for patients with unresectable tumors, but knowledge of the molecular biology of SFTs is currently insufficient to support such therapy. The current study investigated the activation of receptor tyrosine kinases (RTKs) and the Akt‐mammalian target of rapamycin (Akt‐mTOR) pathway in SFTs as therapeutic targets.

METHODS

The phosphorylation statuses of Akt‐mTOR pathway proteins (p‐Akt, p‐mTOR, phosphorylated 4E‐binding protein [p‐4EBP1], and phosphorylated S6 ribosomal protein [p‐S6RP]) and RTKs (phosphorylated platelet‐derived growth factor receptor‐α [p‐PDGFRα], p‐PDGFRβ, p‐c‐met, and phosphorylated insulin‐like growth factor‐1 receptor‐β [p‐IGF‐1Rβ]) were assessed by immunohistochemistry in 66 samples of SFTs, and the data were compared with clinicopathological and histopathological findings. The expression of phosphorylated proteins was assessed by Western blot analysis in 6 frozen samples.

RESULTS

The immunohistochemical results were as follows: p‐Akt, 56.0% (nuclear and cytoplasmic staining); p‐mTOR, 69.6% (nuclear and cytoplasmic staining); p‐4EBP1, 80.3% (nuclear and cytoplasmic staining); p‐S6RP, 69.6% (cytoplasmic staining); p‐PDGFRα, 39.0% (cytoplasmic staining); p‐PDGFRβ, 52.0% (cytoplasmic staining); p‐c‐met, 37.8% (nuclear staining) and 19.6% (cytoplasmic staining); and p‐IGF‐1Rβ, 16.6% (nuclear staining). Phosphorylation of the Akt‐mTOR pathway proteins was correlated with one another except for p‐Akt with S6RP. p‐PDGFRβ and p‐IGF‐1Rβ were correlated with p‐Akt. Moreover, significant relationships were noted between disease‐free survival or overall survival and the presence of hypoglycemia, necrosis, cystic and myxoid degeneration, and atypical findings.

CONCLUSIONS

The Akt/mTOR pathway was activated in approximately 50% of the cases of SFTs and was associated with RTKs, which were phosphorylated at different rates. Thus, the Akt‐mTOR pathway may be involved in the tumorigenesis of SFTs. Cancer 2014;120:864–876. © 2013 American Cancer Society.
Set shifting in children and adolescents with anorexia nervosa: An exploratory systematic review and meta‐analysis
Authors: Lang Katie , Stahl Daniel , Espie Jonathan , Treasure Janet , Tchanturia Kate
Published: December 2013

Objective

Set shifting inefficiencies in adults with anorexia nervosa (AN) are established, however the neurocognitive profile of children and adolescents with AN is less clear. This study aimed to provide a review of the literature.

Method

Electronic databases were used to search for manuscripts.

Results

Meta‐analysis was performed on seven studies using two neuropsychological tests (Trail Making Task, TMT; Wisconsin Card Sorting Task, WCST). The mean difference in outcome between AN and healthy control (HC) groups was standardized by calculating Cohen's d. Meta‐analysis of TMT studies showed a nonsignificant negative, pooled standardized mean difference of −0.005 (95% C.I. −0.416 to 0.406, z = 0.02, p = .98). WCST studies revealed a nonsignificant pooled effect size of d = 0.196 (95% C.I. −0.091–0.483, z = 1.34, p = .18). Studies which did not allow for a calculation of effect size typically showed a nonsignificant, worse performance by the AN groups.

Discussion

The inefficiencies in set shifting that are apparent in the adult AN literature do not appear to be as pronounced in children. This may suggest that set shifting difficulties in adult AN are the result of starvation or indicative of longer duration of illness. Larger studies are needed to confirm these impressions. © 2013 Wiley Periodicals, Inc. (Int J Eat Disord 2014; 47:394–399)
EurJOC around the Clock
Authors: Ross Haymo
Published: December 2013

This editorial reflects on the past year in EurJOC, including the launch of the EurJOC app, and looks forward at the changes to come in 2014.
Gamers against science: The case of the violent video games debate
Authors: Nauroth Peter , Gollwitzer Mario , Bender Jens , Rothmund Tobias
Published: December 2013

This article explores the notion that scientific research programs and empirical findings are fundamentally devalued when they threaten a perceiver's social identity. Findings from three studies show the following: (1) identification with the group of “gamers” (i.e., people who play video games on a regular basis) influences the extent to which perceivers devalue research suggesting that playing violent video games has negative consequences; (2) this effect is mediated by the feeling that the group of gamers is being stigmatized by such research (Studies 1 and 2) as well as by anger about this research (Study 2); (3) the effect of in‐group identification on negative research evaluations cannot be explained by attitude or behavioral preference inconsistency (Studies 1 and 3); and (4) strongly identified gamers not only devalue a specific scientific study but also generalize their negative evaluations to the entire field of violent video games research (Study 3). The findings suggest that the influence of social identity processes on the evaluation of research is larger than it has previously been recognized. Implications of these findings for science communication are discussed. Copyright © 2013 John Wiley & Sons, Ltd.
An integrated proteomic and transcriptomic approach to understanding azathioprine‐ induced hepatotoxicity in rat primary hepatocytes
Authors: Cho Young‐Eun , Moon Pyong‐Gon , Baek Moon‐Chang
Published: December 2013

Azathioprine, an immunosuppressant, has gained a prominent position in the clinic for prevention of graft rejection in organ transplants, as well as dermatological autoimmune diseases. However, according to a number of research reports, hepatotoxicity, as one of the side effects, is a major obstacle in azathioprine therapy. In this study, an integrated toxicoproteomic and toxicotranscriptomic analysis was performed using rat primary hepatocytes, in order to gain insight into the in‐depth pathway map related to azathioprine‐induced hepatotoxicity. For proteomic and transcriptomic analysis, rat primary hepatocytes were exposed to azathioprine at IC20 concentration for 24 h. In particular, 2D LC‐MS/MS and informatics‐assisted label‐free strategy for proteomic analysis were applied in order to increase the number of identified proteins and to improve the confidence of the quantitation results. Among 119 differentially identified protein species, 69 were upregulated and 50 were downregulated in the azathioprine‐treated group. At the mRNA level, results of transcriptomic analysis showed increased transcription of 340 genes and decreased transcription of 63 genes in the azathioprine‐treated group. Based on the analysis of transcriptomic and proteomic results using the DAVID program, drug metabolism/oxidative stress enzymes, xenobiotic metabolism by cytochrome P450, fatty acid metabolism, primary bile acid biosynthesis, contraction, inflammation metabolism, and mitogen‐activated protein kinase (MAPK) kinase (ERK/JNK/p38 kinase) pathways were affected in azathioprine‐treated hepatotoxicity. The effects on genes and proteins related to several important pathways were confirmed by real‐time PCR and immunoblot analysis, respectively. This study is the first to report on relevant pathways related to azathioprine‐induced hepatotoxicity through performance of integrated transcriptomic and proteomic analyses.
Analysis of cerebrospinal fluid γ‐aminobutyric acid by capillary electrophoresis with laser‐induced fluorescence detection
Authors: Casado Mercedes , Molero Marta , Sierra Cristina , García‐Cazorla Angels , Ormazabal Aida , Artuch Rafael
Published: December 2013

The measurement of γ‐aminobutyric acid (GABA) is suitable for investigating various neurological disorders. In this study, a sensitive and selective method for free GABA quantification in cerebrospinal fluid (CSF) has been standardised. This method is based on CE with LIF detection using 4‐fluoro‐7‐nitrobenzo‐2‐oxa‐1,3‐diazole (NBD‐F) as a derivatisating agent. The reaction conditions (NBD‐F concentration, pH, temperature and reaction time) and the electrophoretic parameters (run buffer composition and pH and separation voltage) were optimised to obtain the maximum derivatisation efficiency and electrophoretic resolution. The best resolution was obtained using 200 mM sodium borate, 10 mM SDS, 8.5 mM β‐CD, pH 10 and 20 kV voltage. The method was linear in the concentration range of 2.5–1000 nM with good inter‐ and intra‐assay precision values. The effects of CSF handling on free GABA concentrations were also evaluated. Our results show that the time delay between CSF collection and freezing strongly increases the CSF GABA values. Age‐related reference values were established in 55 paediatric controls. The influence of antiepileptic therapy on free CSF GABA was studied in 38 neuropaediatric patients. Significantly, higher GABA values were obtained in patients taking valproic acid or vigabatrin therapy, which are antiepileptic drugs that modulate GABA metabolism.
Capillary electrophoresis separation of human milk neutral and acidic oligosaccharides derivatized with 2‐aminoacridone
Authors: Galeotti Fabio , Coppa Giovanni V. , Zampini Lucia , Maccari Francesca , Galeazzi Tiziana , Padella Lucia , Santoro Lucia , Gabrielli Orazio , Volpi Nicola
Published: December 2013

Human milk is a unique fluid in glycobiology due to the presence of many free structurally complex oligosaccharides emerging as important dietary factors during early life and having many biological and protective functions. Methods that allow accurate profiling of oligosaccharide mixtures in this complex biological fluid with quantification of the four known genetically determined groups are welcomed. A high‐voltage CE separation and detection at 254 nm of 17 neutral and acidic human milk oligosaccharide (HMO) standard along with lactose derivatized with 2‐aminoacridone, using a BGE containing 20% methanol as an organic modifier and borate, able to form on‐capillary anionic borate‐polyol complexes, is reported. This CE approach was able to separate both neutral HMOs and acidic HMOs, with the sialic acid residue, also in the presence of lactose in high content. This method was applied to the four secretory groups individually extracted by a rapid and simple preparative step. LODs were found ranging from ∼50 to 700 fmol. We were able to measure HMO content also in the presence of excess fluorophore, or interference from proteins, peptides, salts, and other impurities normally present in this complex biological fluid. Overall, CE equipped with a UV detector is a common analytical approach and this simple CE separation offers high resolution and sensitivity for the differentiation of human milk samples related to genetic groups and days of lactation by considering that important changes in HMO content are a reflection of the lactation day.
Horizontal comparative fluorescence two‐dimensional gel electrophoresis for improved spot coordinate detection
Authors: Hanneken Marina , König Simone
Published: December 2013

Vertical comparative 2D fluorescence gel electrophoresis (CoFGE) has recently been shown to increase the reproducibility of coordinate assignment for protein spots, in particular in singular experiments, which cannot be investigated using DIGE. The method applies a standardized marker grid formed by a set of purified proteins to the sample proteome in a conglomerate of 1DE, 2DE, and DIGE. Here, improvements are demonstrated by transferring CoFGE to horizontal 2DE. These include the elimination of the protein modification by residual acrylamide monomer unavoidable in vertical CoFGE, reduced buffer volumes, and highly efficient laboratory procedures. Spot patterns are well defined and can be easily analyzed using commercially available warping algorithms. With horizontal CoFGE also a correction for changes in pI was introduced using a third fluorescent dye. Horizontal CoFGE holds high promises in comparative proteomics.
Electrophoretic mobilities of neutral analytes and electroosmotic flow markers in aqueous solutions of Hofmeister salts
Authors: Křížek Tomáš , Kubíčková Anna , Hladílková Jana , Coufal Pavel , Heyda Jan , Jungwirth Pavel
Published: December 2013

Small neutral organic compounds have traditionally the role of EOF markers in electrophoresis, as they are expected to have zero electrophoretic mobility in external electric fields. The BGE contains, however, ions that have unequal affinities to the neutral molecules, which in turn results in their mobilization. In this study we focused on two EOF markers—thiourea and DMSO, as well as on N‐methyl acetamide (NMA) as a model of the peptide bond. By means of CE and all atom molecular dynamics simulations we explored mobilization of these neutral compounds in large set of Hofmeister salts. Employing a statistical mechanics approach, we were able to reproduce by simulations the experimental electrophoretic mobility coefficients. We also established the role of the chemical composition of marker and the BGE on the measured electrophoretic mobility coefficient. For NMA, we interpreted the results in terms of the relative affinities of cations versus anions to the peptide bond.
Higher taxa: Reply to cartmill
Authors: Tattersall Ian
Published: December 2013

Ian Tattersall is a curator emeritus at the American Museum of Natural History. He has worked on lemur systematics and ecology as well as paleoanthropology, where his special interest is in hominid diversity and cognitive evolution.
Relating genes in the biosynthesis of the polyphenol composition of Andean colored potato collection
Authors: Tejeda Leslie , Alvarado Juan Antonio , Dębiec Magdalena , Peñarrieta José Mauricio , Cárdenas Oscar , Alvarez Maria Teresa , Chawade Aakash , Nilsson Lars , Bergenståhl Björn
Published: December 2013

The objective of this study was to evaluate total antioxidant capacity (TAC), total phenolic content (TPH), and the identification of anthocyanidin and polyphenolic compounds in 13 colored potatoes collected from the Andean region of Bolivia, and understand how the chemical composition correlated with the botanical classification and molecular characterization of genes, ans (anthocyanidin synthase) and stan1 (Solanum tuberosum anthocyanidin synthase), associated with the synthesis of anthocyanidins. The results show the existence of a limited correlation between botanical classification, based on morphological identification and polyphenol composition. No association between genetic grouping of the ans and stan genes and botanical classification was found. However, it was possible to identify a correlation between the ans gene clades and the levels of anthocyanidins as well as of other polyphenols. Thus, this result confirms the concept that potato color can be used in the search for high polyphenol potato cultivars.
Survival outcomes of patients with temporal bone squamous cell carcinoma with different invasion patterns
Authors: Xie Bingbin , Zhang Ting , Dai Chunfu
Published: December 2013

Background

The correlation between the survival rate and various invasion patterns of patients with temporal bone squamous cell carcinoma (SCC) is unclear. This study was performed to compare the survival outcomes of these patients to disclose the correlation.

Methods

The cases of 39 patients with temporal bone SCC who underwent surgery between January 2004 and December 2012 were reviewed.

Results

The 2‐year overall survival rate was 56.9%, and it was 22.3% for patients with stage IV disease, and 100% for patients with stage I–III disease. Patients with parotid invasion (n = 11), temporomandibular joint (TMJ) involvement (n = 8), and middle ear surgery (n = 7) before temporal bone malignancies were diagnosed had poor survival with statistical difference.

Conclusion

Patients with parotid gland, TMJ involvement, and previous middle ear surgery for chronic otitis media had poor outcomes. © 2014 Wiley Periodicals, Inc. Head Neck 37: 188‐196, 2015
Analysis of 320 gastroenteropancreatic neuroendocrine tumors identifies TS expression as independent biomarker for survival
Authors: Lee Hye Seung , Chen Min , Kim Ji Hun , Kim Woo Ho , Ahn Soyeon , Maeng Kyungah , Allegra Carmen J. , Kaye Frederic J. , Hochwald Steven N. , Zajac‐Kaye Maria
Published: December 2013

Thymidylate synthase (TS), a critical enzyme for DNA synthesis and repair, is both a potential tumor prognostic biomarker as well as a tumorigenic oncogene in animal models. We have now studied the clinical implications of TS expression in gastroenteropancreatic (GEP) neuroendocrine tumors (NETs) and compared these results to other cell cycle biomarker genes. Protein tissue arrays were used to study TS, Ki‐67, Rb, pRb, E2F1, p18, p21, p27 and menin expression in 320 human GEP‐NETs samples. Immunohistochemical expression was correlated with univariate and multivariate predictors of survival utilizing Kaplan Meier and Cox proportional hazards models. Real time RT‐PCR was used to validate these findings. We found that 78 of 320 GEP‐NETs (24.4%) expressed TS. NETs arising in the colon, stomach and pancreas showed the highest expression of TS (47.4%, 42.6% and 37.3%, respectively), whereas NETs of the appendix, rectum and duodenum displayed low TS expression (3.3%, 12.9% and 15.4%, respectively). TS expression in GEP‐NETs was associated with poorly differentiated endocrine carcinoma, angiolymphatic invasion, lymph node metastasis and distant metastasis (p < 0.05). Patients with TS‐positive NETs had markedly worse outcomes than TS‐negative NETs as shown by univariate (p < 0.001) and multivariate (p = 0.01) survival analyses. Expression of p18 predicted survival in TS‐positive patients that received chemotherapy (p = 0.015). In conclusion, TS protein expression was an independent prognostic biomarker for GEP‐NETs. The strong association of increased TS expression with aggressive disease and early death supports the role of TS as a cancer promoting agent in these tumors.
The influence of intensity and duration of a painful conditioning stimulation on conditioned pain modulation in volunteers
Authors: Razavi M. , Hansson P.T. , Johansson B. , Leffler A.‐S.
Published: December 2013

Background and Method

The aim was to investigate influence from variations in intensity of a painful conditioning stimulation (CS) on early (0–6 min) and prolonged (6–12 min) conditioned pain modulation (CPM) in volunteers during concurrent exposure to test stimuli (TS). CS was applied to either forearm using painful heat with an intensity of 2/10 and 5/10, respectively, rated on a 0–10 numerical pain rating scale. At a second session, CS with an intensity of 7/10 was applied to the arm using a tourniquet. Threshold and suprathreshold painful heat and pressure as well as painful repeated monofilament pricking (RMP) were assessed as TS.

Results

Regardless of TS, there was no significant difference in the magnitude of CPM within the same stimulus modality during the various intensities and phases of the CS. Significant modulation of heat pain thresholds (HPTs) was found during the early phase at 5/10 and 7/10, but not at 2/10. Only at 5/10 the prolonged CS resulted in a significant additional increase in HPT. During the early CS phase, CPM of suprathreshold heat pain was found at 2/10 and 5/10. The prolonged CS resulted in a significant additional temperature increase at 5/10. Only during the early phase significant CPM of pressure pain thresholds were found for all three pain intensities in conjunction with a significant CPM of suprathreshold pressure pain at 5/10. There was no CPM of RMP.

Conclusion

The CS intensity and the duration of CPM modulated pain sensitivity differentially across TS modalities.
Poly‐cyclodextrin functionalized porous bioceramics for local chemotherapy and anticancer bone reconstruction
Authors: Chai Feng , Abdelkarim Mohamed , Laurent Thomas , Tabary Nicolas , Degoutin Stephanie , Simon Nicolas , Peters Fabian , Blanchemain Nicolas , Martel Bernard , Hildebrand Hartmut F.
Published: December 2013

The progress in bone cancer surgery and multimodal treatment concept achieve only modest improvement in the overall survival, due to failure in clearing out residual cancer cells at the surgical margin and extreme side‐effects of adjuvant postoperative treatments. Our study aims to propose a new method based on cyclodextrin polymer (polyCD) functionalized hydroxyapatite (HA) for achieving a high local drug concentration with a sustained release profile and a better control of residual malignant cells via local drug delivery and promotion of the reconstruction of bone defects. PolyCD, a versatile carrier for therapeutic molecules, can be incorporated into HA (bone regeneration scaffold) through thermal treatment. The parameters of polyCD treatment on the macroporous HA (porosity 65%) were characterized via thermogravimetric analysis. Good cytocompatibility of polyCD functionalized bioceramics was demonstrated on osteoblast cells by cell vitality assay. An antibiotic (gentamicin) and an anticancer agent (cisplatin) were respectively loaded on polyCD functionalized bioceramics for drug release test. The results show that polyCD functionalization leads to significantly improved drug loading quantity (30% more concerning gentamicin and twice more for cisplatin) and drug release duration (7 days longer concerning gentamicin and 3 days longer for cisplatin). Conclusively, this study offers a safe and reliable drug delivery system for bioceramic matrices, which can load anticancer agents (or/and antibiotics) to reduce local recurrence (or/and infection). © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 102B: 1130–1139, 2014.
MiR-335-5p Promotes Chondrogenesis in Mouse Mesenchymal Stem Cells and Is Regulated Through Two Positive Feedback Loops
Authors: Lin Xiao , Wu Li , Zhang Zhenming , Yang Ruohuan , Guan Qian , Hou Xinfeng , Wu Qiong
Published: December 2013

Chondrogenic differentiation of mesenchymal stem cells (MSCs) is regulated by many factors and signal pathways, including transcription factors such as Sox9 and microRNAs. MiR-335-5p has been previously reported to regulate osteogenic and adipogenic differentiations of MSCs, but its role in chondrogenic differentiation of MSC remains unknown. In this study, we found that miR-335-5p and its host gene Mest are co-expressed and greatly upregulated during mouse MSCs (mMSCs) chondrogenesis. Overexpression of miR-335-5p in mMSCs increased expression of chondrogenic marker genes. Molecular mechanism explorations revealed that miR-335-5p targets Daam1 and ROCK1, a set of negative regulators of Sox9; Sox9 downregulates the expression of miR-29a and 29b, both negative regulators of Mest expression, thus forming a positive loop from miR-335-5p to Sox9 to Mest/miR-335-5p. In addition, miR-335-5p targets DKK1 during mMSC chondrogenic differentiation to increase β-catenin/TCF activity, which leads to increased level of Mest transcription. These data showed miR-335-5p positively regulates MSC chondrogenesis, and two positive feedback loops are identified for the expression of miR-335-5p and its host gene Mest during the early phase of mMSC chondrogenic differentiation. © 2014 American Society for Bone and Mineral Research.
High‐valent technetium chemistry—new opportunities for radiopharmaceutical developments
Authors: Braband Henrik
Published: December 2013

The rich coordination chemistry of 99mTc distinguishes this radiometal from other radiolabels applied for single‐photon emission computed tomography (SPECT) or positron emission tomography (PET). This potential should be used to create novel opportunities for the development of effective imaging probes. In this context, the field of high‐valent technetium chemistry has received much interest. It has been shown that fac‐{99mTcO3}+ complexes are potential new synthons for radiopharmaceutical developments, due to their unique physicochemical properties and unprecedented reactivity. In this article, recent developments and the ‘state of the art’ in this field of technetium chemistry will be reviewed comprehensively. Copyright © 2013 John Wiley & Sons, Ltd.
Imaging COX‐2 expression in cancer using PET/SPECT radioligands: current status and future directions
Authors: Pacelli A. , Greenman J. , Cawthorne C. , Smith G.
Published: December 2013

The role of cyclooxygenase (COX)‐2 as a driving force in early tumourigenesis and the current interest in the combination of COX‐2 inhibitors with standard therapy in clinical trials creates an urgent need to establish clinically relevant diagnostic tests for COX‐2 expression. Molecular imaging using small‐molecule probes radiolabelled for both positron emission tomography (PET) and single photon emission computed tomography (SPECT) offers the potential to meet this need, providing a minimally invasive readout for the whole disease burden. This review summarises current approaches to the radiolabelling of small‐molecule COX‐2 inhibitors and their analogues for PET and SPECT imaging, and gives an overview of their biological evaluation and likely success of clinical application.
Dental patterning in the earliest sharks: Implications for tooth evolution
Authors: Maisey John G. , Turner Susan , Naylor Gavin J.P. , Miller Randall F.
Published: December 2013

Doliodus problematicusis the oldest known fossil shark‐like fish with an almost intact dentition (Emsian, Lower Devonian, c. 397Ma). We provide a detailed description of the teeth and dentition inD. problematicus, based on tomographic analysis of NBMG 10127 (New Brunswick Museum, Canada). Comparisons with modern shark dentitions suggest thatDolioduswas a ram‐feeding predator with a dentition adapted to seizing and disabling prey.Doliodusprovides several clues about the early evolution of the “shark‐like” dentition in chondrichthyans and also raises new questions about the evolution of oral teeth in jawed vertebrates. As in modern sharks, teeth inDolioduswere replaced in a linguo‐labial sequence within tooth families at fixed positions along the jaws (12–14 tooth families per jaw quadrant in NBMG 10127).Doliodusteeth were replaced much more slowly than in modern sharks. Nevertheless, its tooth formation was apparently as highly organized as in modern elasmobranchs, in which future tooth positions are indicated by synchronized expression ofshhat fixed loci within the dental epithelium. Comparable dental arrays are absent in osteichthyans, placoderms, and many “acanthodians”; a “shark‐like” dentition, therefore, may be a synapomorphy of chondrichthyans and gnathostomes such asPtomacanthus. The upper anterior teeth inDolioduswere not attached to the palatoquadrates, but were instead supported by the ethmoid region of the prechordal basicranium, as in some other Paleozoic taxa (e.g.,Triodus,Ptomacanthus). This suggests that the chondrichthyan dental lamina was originally associated with prechordal basicranial cartilage as well as jaw cartilage, and that the modern elasmobranch condition (in which the oral dentition is confined to the jaws) is phylogenetically advanced. Thus, oral tooth development in modern elasmobranchs does not provide a complete developmental model for chondrichthyans or gnathostomes. J. Morphol. 275:586–596, 2014. © 2013 Wiley Periodicals, Inc.
Design of 3D Hybrid Composite Scaffolds: Effect of Composition on Scaffold Structure and Cell Proliferation
Authors: Dorati R. , Colonna C. , Tomasi C. , Genta I. , Modena T. , Conti B.
Published: December 2013

The aim of this study was to develop multi‐phase composite 3D scaffolds and to investigate the in vitro degradation performance, the cell seeding capacity and cells proliferation onto/into the composite scaffolds. Multi‐phase composite scaffolds were formulated by solvent casting and particulate leaching technique, hydroxyapatite (HAP) was used to improve the mechanical properties of poly[(DL‐lactide)‐coglycolide] (PLGA) polymer scaffold, while chitosan (CTS) was added to the formulation for its bioactivity, osteoconductivity and bioadhesive properties. The in vitro degradation results demonstrated that the composite scaffold had a degradation rate correlating with their composition and structural features. Adult fibroblast cells were seeded on the surface of the composite scaffolds. Cell viability and long‐term proliferation onto/into composite scaffolds were evaluated. The results showed that viable cells attached on the surface of scaffolds gradually migrated into the porous scaffold. These results suggest that the two‐phase scaffold, namely PLGA/HAP and PLGA/CTS composite scaffolds, are promising grafts for bone tissue engineering. Further studies are in progress to design an improved three‐phase composite construct obtained combining PLGA, HAP and CTS in a wafer‐like scaffold.
Development and characterization of active nanocomposites with embedded shape memory alloy wires
Authors: Leal A. S. C. , de Araújo C. J. , Silva S. M. L. , de Lima A. G. B.
Published: December 2013

Active nanocomposites of epoxy resin containing bentonite clay and shape memory alloy (SMA) were made to evaluate the thermomechanical behavior in the range of phase transformation of shape memory alloy during heating. The epoxy resin system studied was prepared using bifunctional diglycidyl ether of bisphenol A (DGEBA), crosslinking agent diaminodiphenylsulfone (DDS), purified bentonite organoclay (APOC) and thin Ni‐Ti shape memory alloy wires. The evaluated ratio DGEBA/DDS was 100:40, for the epoxy resin/clay system was 100:1 and the shape memory alloy volumetric fraction of Ni‐Ti wires were 1.55%; 2.56%; 3.57% and 4.54%. The formation of nanocomposite was confirmed by X‐ray diffraction analysis. Phase transformation of the shape memory alloy wires were determined by differential scanning calorimetry (DSC). Specimens of the active nanocomposites were characterized mainly by dynamic mechanical analysis (DMA). According to the DMA results was evidenced a significant increase in glass transition temperature and storage modulus when 1 parts per hundred resin of clay is added to epoxy resin. A recover of storage modulus was observed in the active nanocomposite during heating in the range of the phase transformation of Ni‐Ti shape memory alloy wires when the volumetric fraction is above 3.5%.