bluuebunny/crossref_metadata_2025 huggingface dataset:
Age‐dependent differences in morphine‐induced taste aversions
Authors: Hurwitz Zachary E. , Merluzzi Andrew P. , Riley Anthony L.
Published: May 2012

Adolescence is a developmental period of particular importance given the host of neurobiological changes that occur during this stage of development. Drug use and abuse is said to be a function of the balance of its rewarding and aversive effects, and any age‐dependent differences in morphine's aversive effects could impact drug intake. The present experiments examined the ability of morphine sulfate (0, 3.2, 10, and 18 mg/kg) to induce taste aversions in adolescent and adult rats under high (20‐min fluid access each day; Experiment 1A/B) and low (50% of ad libitum access; Experiment 2A/B) deprivation conditions. In both studies, adolescent and adult rats were given a novel saccharin solution to drink and were subsequently injected with morphine. Independent of the deprivation condition, adults acquired stronger aversions than adolescents and did so at a faster rate. On a subsequent two‐bottle aversion test, all morphine‐injected subjects drank a significantly lower percentage of saccharin than vehicle‐injected controls with adults exhibiting stronger aversions than adolescents. These age‐dependent differences in morphine‐induced CTAs extend the findings with other drugs of abuse for which adolescents exhibit weaker aversions. The possible basis for and implications of these differences were discussed. © 2012 Wiley Periodicals, Inc. Dev Psychobiol 55: 415–428, 2013
Intraspecific variability in the response of bloom‐forming marine microalgae to changed climate conditions
Authors: Kremp Anke , Godhe Anna , Egardt Jenny , Dupont Sam , Suikkanen Sanna , Casabianca Silvia , Penna Antonella
Published: May 2012

Phytoplankton populations can display high levels of genetic diversity that, when reflected by phenotypic variability, may stabilize a species response to environmental changes. We studied the effects of increased temperature and CO2 availability as predicted consequences of global change, on 16 genetically different isolates of the diatom Skeletonema marinoi from the Adriatic Sea and the Skagerrak (North Sea), and on eight strains of the PST (paralytic shellfish toxin)‐producing dinoflagellate Alexandrium ostenfeldii from the Baltic Sea. Maximum growth rates were estimated in batch cultures of acclimated isolates grown for five to 10 generations in a factorial design at 20 and 24°C, and present day and next century applied atmospheric pCO2, respectively. In both species, individual strains were affected in different ways by increased temperature and pCO2. The strongest response variability, buffering overall effects, was detected among Adriatic S. marinoi strains. Skagerrak strains showed a more uniform response, particularly to increased temperature, with an overall positive effect on growth. Increased temperature also caused a general growth stimulation in A. ostenfeldii, despite notable variability in strain‐specific response patterns. Our data revealed a significant relationship between strain‐specific growth rates and the impact of pCO2 on growth—slow growing cultures were generally positively affected, while fast growing cultures showed no or negative responses to increased pCO2. Toxin composition of A. ostenfeldii was consistently altered by elevated temperature and increased CO2 supply in the tested strains, resulting in overall promotion of saxitoxin production by both treatments. Our findings suggest that phenotypic variability within populations plays an important role in the adaptation of phytoplankton to changing environments, potentially attenuating short‐term effects and forming the basis for selection. In particular, A. ostenfeldii blooms may expand and increase in toxicity under increased water temperature and atmospheric pCO2 conditions, with potentially severe consequences for the coastal ecosystem.
Invariant natural killer T cells are not affected by lysosomal storage in patients with Niemann‐Pick disease type C
Authors: Speak Anneliese O. , Platt Nicholas , Salio Mariolina , te Vruchte Danielle , Smith David A. , Shepherd Dawn , Veerapen Natacha , Besra Gurdyal S. , Yanjanin Nicole M. , Simmons Louise , Imrie Jackie , Wraith James E. , Lachmann Robin H. , Hartung Ralf , Runz Heiko , Mengel Eugen , Beck Michael , Hendriksz Christian J. , Porter Forbes D. , Cerundolo Vincenzo , Platt Frances M.
Published: May 2012

Invariant natural killer T (iNKT) cells are a specialised subset of T cells that are restricted to the MHC class I like molecule, CD1d. The ligands for iNKT cells are lipids, with the canonical superagonist being α‐galactosylceramide, a non‐mammalian glycosphingolipid. Trafficking of CD1d through the lysosome is required for the development of murine iNKT cells. Niemann‐Pick type C (NPC) disease is a lysosomal storage disorder caused by dysfunction in either of two lysosomal proteins, NPC1 or NPC2, resulting in the storage of multiple lipids, including glycosphingolipids. In the NPC1 mouse model, iNKT cells are virtually undetectable, which is likely due to the inability of CD1d to be loaded with the selecting ligand due to defective lysosomal function and/or CD1d trafficking. However, in this study we have found that in NPC1 patients iNKT cells are present at normal frequencies, with no phenotypic or functional differences. In addi‐tion, antigen‐presenting cells derived from NPC1 patients are functionally competent to present several different CD1d/iNKT‐cell ligands. This further supports the hypothesis that there are different trafficking requirements for the development of murine and human iNKT cells, and a functional lysosomal/late‐endosomal compartment is not required for human iNKT‐cell development.
Plasma‐derived MHC class II+ exosomes from tumor‐bearing mice suppress tumor antigen‐specific immune responses
Authors: Yang Chenjie , Ruffner Melanie A. , Kim Seon‐Hee , Robbins Paul D.
Published: May 2012

Tumor‐specific immunosuppression is frequently observed in tumor‐bearing hosts. Exosomes are nano‐sized, endosomal‐derived membrane vesicles secreted by most tumor and hematopoietic cells and have been shown to actively participate in immune regulation. We previously demonstrated that antigen‐specific immunosuppressive exosomes could be isolated from the blood plasma of antigen‐immunized mice. Here, we demonstrate that plasma‐derived exosomes isolated from mice bearing OVA‐expressing tumors were able to suppress OVA‐specific immune responses in a mouse delayed‐type hypersensitivity model. Enrichment of tumor‐derived exosomes in the plasma of mice bearing subcutaneous melanoma was not detected using an exosome‐tagging approach. Instead, depletion of MHC class II+ vesicles from plasma‐derived exosomes or using plasma‐derived exosomes isolated from MHC class II‐deficient mice resulted in significant abrogation of the suppressive effect. These results demonstrate that circulating host‐derived, MHC class II+ exosomes in tumor‐bearing hosts are able to suppress the immune response specific to tumor antigens.
Evidence for BCR‐ABL‐dependent dysfunctions of iNKT cells from chronic myeloid leukemia patients
Authors: Rossignol Alexis , Levescot Anaïs , Jacomet Florence , Robin Aurélie , Basbous Sara , Giraud Christine , Roy Lydia , Guilhot François , Turhan Ali G. , Barra Anne , Herbelin André , Gombert Jean‐Marc
Published: May 2012

Chronic myeloid leukemia (CML) is a clonal hematopoietic stem‐cell malignancy characterized by the presence of the chimeric BCR‐ABL oncoprotein with deregulated tyrosine‐kinase (TK) activity. Although conventional T cells are acknowledged as important players in the control of CML, a possible modification of invariant NKT (iNKT) cells, known for their antitumoral activity, has not been established as yet. Here, we showed that the expression of perforin, CD95L, and promyelocytic leukemia zinc finger, a transcription factor required for maintenance of iNKT cell functions, was reduced or suppressed in CML patients at diagnosis, as compared with healthy individuals. The proliferation rate of blood iNKT cells in response to their cognate ligand was likewise diminished. These functional deficiencies were corrected in patients having achieved complete cytogenetic remission following TK inhibitor or IFN‐α therapy. iNKT cells from CML patients in the chronic phase did not display increased TK activity, which argued against a direct autonomous action of BCR‐ABL. Instead, we found that their anergic status originated from both intrinsic and APC‐dependent dysfunctions. Our data demonstrate that chronic phase CML is associated with functional deficiencies of iNKT cells that are restored upon remission. These results suggest a possible contribution to disease control by TK inhibitor therapies.
NK cells are strongly activated by Lassa and Mopeia virus‐infected human macrophages in vitro but do not mediate virus suppression
Authors: Russier Marion , Reynard Stéphanie , Tordo Noël , Baize Sylvain
Published: May 2012

Lassa virus (LASV) and Mopeia virus (MOPV) are closely related Arenaviruses. LASV causes hemorrhagic fever, whereas MOPV is not pathogenic. Both viruses display tropism for APCs such as DCs and macrophages. During viral infections, NK cells are involved in the clearance of infected cells and promote optimal immune responses by interacting with APCs. We used an in vitro model of human NK and APC coculture to study the role of NK cells and to characterize their interactions with APCs during LASV and MOPV infections. As expected, NK cells alone were neither infected nor activated by LASV and MOPV, and infected DCs did not activate NK cells. By contrast, LASV‐ and MOPV‐infected macrophages activated NK cells, as shown by the upregulation of CD69, NKp30, and NKp44, the downregulation of CXCR3, and an increase in NK‐cell proliferation. NK cells acquired enhanced cytotoxicity, as illustrated by the increase in granzyme B (GrzB) expression and killing of K562 targets, but did not produce IFN‐γ. Contact between NK cells and infected macrophages and type I IFNs were essential for activation; however, NK cells could not kill infected cells and control infection. Overall, these findings show that MOPV‐ as well as pathogenic LASV‐infected macrophages mediate NK‐cell activation.
Avidity determines T‐cell reactivity in abacavir hypersensitivity
Authors: Adam Jacqueline , Eriksson Klara K. , Schnyder Benno , Fontana Stefano , Pichler Werner J. , Yerly Daniel
Published: May 2012

The antiretroviral drug abacavir (abc) elicits severe drug hypersensitivity reactions in HLA‐B*5701+ individuals. To understand the abc‐specific activation of CD8+ T cells, we generated abc‐specific T‐cell clones (abc‐TCCs). Abc reactivity could not be linked to the metabolism and/or processing of the drug, since abc metabolizing enzymes were not expressed in immune cells and inhibition of the proteasome in APCs did not affect TCC reactivity. Ca2+ influx assays revealed different reactivity patterns of abc‐TCCs. While all TCCs reacted to abc presented on HLA‐B*5701 molecules, a minority also reacted immediately to abc in solution. Titration experiments showed that the ability to react immediately to abc correlated significantly with the TCR avidity of the T cells. Modifications of soluble abc concentrations revealed that the reactivity patterns of abc‐TCCs were not fixed but dynamic. When TCCs with an intermediate TCR avidity were stimulated with increasing abc concentrations, they showed an accelerated activation kinetic. Thus, they reacted immediately to the drug, similar to the reaction of TCCs of high avidity. The observed immediate activation and the noninvolvement of the proteasome suggest that, in contrast to haptens, abc‐specific T‐cell stimulation does not require the formation of covalent bonds to produce a neo‐antigenic determinant.
Freeze‐thaw lysates of Plasmodium falciparum‐infected red blood cells induce differentiation of functionally competent regulatory T cells from memory T cells
Authors: Finney Olivia C. , Lawrence Emma , Gray Alice P. , Njie Madi , Riley Eleanor M. , Walther Michael
Published: May 2012

In addition to naturally occurring regulatory T (nTreg) cells derived from the thymus, functionally competent Treg cells can be induced in vitro from peripheral blood lymphocytes in response to TCR stimulation with cytokine costimulation. Using these artificial stimulation conditions, both naïve as well as memory CD4+ T cells can be converted into induced Treg (iTreg) cells, but the cellular origin of such iTreg cells in vivo or in response to more physiologic stimulation with pathogen‐derived antigens is less clear. Here, we demonstrate that a freeze/thaw lysate of Plasmodium falciparum schizont extract (PfSE) can induce functionally competent Treg cells from peripheral lymphocytes in a time‐ and dose‐dependent manner without the addition of exogenous costimulatory factors. The PfSE‐mediated induction of Treg cells required the presence of nTreg cells in the starting culture. Further experiments mixing either memory or naïve T cells with antigen presenting cells and CFSE‐labeled Treg cells identified CD4+CD45RO+CD25− memory T cells rather than Treg cells as the primary source of PfSE‐induced Treg cells. Taken together, these data suggest that in the presence of nTreg cells, PfSE induces memory T cells to convert into iTreg cells that subsequently expand alongside PfSE‐induced effector T cells.
RNAi screen for kinases and phosphatases that play a role in antigen presentation by dendritic cells
Authors: Moita Catarina F. , Chora Ângelo , Hacohen Nir , Moita Luis F.
Published: May 2012

Effective CD8+ T‐cell responses against tumor or microbial antigens that are not directly expressed in antigen‐presenting cells (APCs) depend on the cross‐presentation of these antigens on MHC class I in APCs. To identify signaling molecules that regulate cross‐presentation, we used lentiviral‐based RNA interference to test the roles of hundreds of kinases and phosphatases in this process. Our study uncovered eight previously unknown genes, consisting of one positive and seven negative regulators of antigen cross‐presentation. Depletion of Acvr1c, a type I receptor for TGF‐β family of signaling molecules, led to an increase in CD80 and CD86 co‐stimulator surface expression and secreted IL‐12 in mouse bone marrow‐derived DCs, as well as antigen‐specific T‐cell proliferation.
Retinoic acid alleviates Con A‐induced hepatitis and differentially regulates effector production in NKT cells
Authors: Lee Kyoo‐A , Song You Chan , Kim Ga‐Young , Choi Gyeyoung , Lee Yoon‐Sook , Lee Jung‐Mi , Kang Chang‐Yuil
Published: May 2012

Retinoic acid (RA) is a diverse regulator of immune responses. Although RA promotes natural killer T (NKT) cell activation in vitro by increasing CD1d expression on antigen‐presenting cells (APCs), the direct effects of RA on NKT‐cell responses in vivo are not known. In the present study, we demonstrated the effect of RA on the severity of Con A‐induced hepatitis and molecular changes of NKT cells. First, we demonstrated that Con A‐induced liver damage was ameliorated by RA. In correlation with cytokine levels in serum, RA regulated the production of IFN‐γ and IL‐4 but not TNF‐α by NKT cells without influencing the NKT‐cell activation status. However, RA did not alleviate α‐GalCer‐induced liver injury, even though it reduced IFN‐γ and IL‐4 but not TNF‐α levels in serum. This regulation was also detected when liver mononuclear cells (MNCs) or NKT hybridoma cells were treated with RA in vitro. The regulatory effect of RA on NKT cells was mediated by RAR‐α, and RA reduced the phosphorylation of MAPK. These results suggest that RA differentially modulates the production of effector cytokines by NKT cells in hepatitis, and the suppressive effect of RA on hepatitis varies with the pathogenic mechanism of liver injury.
Anti‐inflammatory effects of high‐dose IgG on TNF‐α‐activated human coronary artery endothelial cells
Authors: Matsuda Akio , Morita Hideaki , Unno Hirotoshi , Saito Hirohisa , Matsumoto Kenji , Hirao Yutaka , Munechika Koji , Abe Jun
Published: May 2012

High‐dose infusion of IgG (IVIG) is used to treat autoimmune and inflammatory diseases, including Kawasaki disease (KD). Although the immunomodulatory effects of IVIG on blood cells such as macrophages have been well studied, its effects on tissue cells remain unclear. Here, we show that high‐dose IgG specifically and completely inhibited TNF‐α‐induced, but not IL‐1β‐induced, secretion of proinflammatory cytokines such as G‐CSF and IL‐6 by cultured human coronary artery endothelial cells (HCAECs). High‐dose IgG did not inhibit TNF‐α‐mediated early signaling events of the NF‐κB and MAPK pathways but it potently inhibited gene expression of G‐CSF and IL‐6 12 h after TNF‐α‐stimulation. Interestingly, suppression of the G‐CSF and IL‐6 gene expression correlated closely with functional inhibition of a transcription factor, C/EBPδ, whose binding sites in the promoters of G‐CSF and IL‐6 have been shown to be critical for their transcriptional activation. Furthermore, the inhibitory effect of intact IgG on HCAECs was exerted mainly via its F(ab’)2 fragment, and not its Fc fragment. These findings suggest that the clinical effects of IVIG on KD patients are at least in part due to its direct anti‐inflammatory effects on the coronary endothelium, which is a major lesion site in the pathogenesis of KD.
Intra‐islet proliferation of cytotoxic T lymphocytes contributes to insulitis progression
Authors: Graham Kate L. , Krishnamurthy Balasubramanian , Fynch Stacey , Ayala‐Perez Rochelle , Slattery Robyn M. , Santamaria Pere , Thomas Helen E. , Kay Thomas W. H.
Published: May 2012

Infiltration of pancreatic islets by immune cells, termed insulitis, increases progressively once it begins and leads to clinical type 1 diabetes. But even after diagnosis some islets remain unaffected and infiltration is patchy rather than uniform. Traffic of autoreactive T cells into the pancreas is likely to contribute to insulitis progression but it could also depend on T‐cell proliferation within islets. This study utilizes transgenic NOD mice to assess the relative contributions of these two mechanisms. Progression of insulitis in NOD8.3 TCR transgenic mice was mildly reduced by inhibition of T‐cell migration with the drug FTY720. In FTY720‐treated mice, reduced beta cell MHC class I expression prevented progression of insulitis both within affected islets and to previously unaffected islets. CTL proliferation was significantly reduced in islets with reduced or absent beta cell expression of MHC class I protein. This indicates that intra‐islet proliferation, apparently dependent on beta cell antigen presentation, in addition to recruitment, is a significant factor in progression of insulitis.
Hybrid Cage Compounds with Organic and Inorganic Building Blocks
Authors: Kracke Andreas , von Hänisch Carsten , Kramer Nina
Published: May 2012

Two new hybrid ligands that exhibit organic as well as siloxane chains between four phosphorus atoms in bridge‐head positions were synthesized. These species show a very different ability with regard to the formation of coordination compounds. Whereas compound 1 with the short (C2H4)2O ether units shows no ability to act as a ligand, the compound with the longer (C2H4O)2C2H4 chains between the siloxane fragments could be obtained as the free ligand and with incorporated Li2I2 and Ag2I2 units. The observed coordination modi of the lithium and silver ions in these complexes corresponds to the HSAB‐ or Pearson concept. The silver ions prefer the soft phosphorus atoms as a bonding partner, while, for lithium, coordination by the hard oxygen atoms is favoured.
Decalactone Derivatives from Corynespora cassiicola, an Endophytic Fungus of the Mangrove Plant Laguncularia racemosa
Authors: Ebrahim Weaam , Aly Amal H. , Mándi Attila , Totzke Frank , Kubbutat Michael H. G. , Wray Victor , Lin Wen‐Han , Dai Haofu , Proksch Peter , Kurtán Tibor , Debbab Abdessamad
Published: May 2012

Chemical investigation of the ethyl acetate extract of Corynespora cassiicola, isolated from leaf tissues of the Chinese mangrove medicinal plant Laguncularia racemosa, yielded four new secondary metabolites, including three decalactones, xestodecalactones D–F (1–3) as well as corynesidone C (4), in addition to four known compounds. The structures of the new compounds were determined on the basis of one‐ and two‐dimensional NMR spectroscopy as well as by high‐resolution mass spectrometry. Absolute configurations of the optically active compounds 1–3 were determined by TDDFT ECD calculations of their solution conformers, proving that they belong to the (11S) series of xestodecalactones, opposite to the (11R) configuration of the known xestodecalactones A–C. All compounds were tested against a panel of human protein kinases. Among the isolated compounds, two inhibited several kinases such as IGF1‐R and VEGF‐R2 with IC50 values mostly in the low micromolar range.
Influence of the Acetylenic Substituent on the Intramolecular Carbolithiation of Alkynes (Eur. J. Org. Chem. 15/2012)
Authors: Girard Anne‐Lise , Lhermet Rudy , Fressigné Catherine , Durandetti Muriel , Maddaluno Jacques
Published: May 2012

The cover picture shows a crane operating in the harbour of Rouen to unload goods from the ships that sail up the Seine river from the English Channel. In the article by M. Durandetti, J. Maddaluno et al. on p. 2895 ff, the influence of the R terminal substituent of the acetylenic appendage on the carbolithiation of the triple bond is described. The results obtained suggest that, in some cases, the interaction between R and the Li cation can explain the surprizing anti selectivity of this reaction. Thus, Li+ first acts as a Lewis acid to activate the triple bond and promote the cyclization. It is then “carried” from one side of the newly created exocyclic double bond to the other, as if it were hooked on a crane rotating around its axis. We wish to thank Mr. Jonathan Rangapanaiken for his kind help in preparing the final version of the picture.

magnified image
Quantitative SNP genotyping by affinity capillary electrophoresis using PEG‐oligodeoxyribonucleotide block copolymers with electroosmotic flow
Authors: Tsukada Harumi , Watanabe Takashi , Kanayama Naoki , Takarada Tohru , Maeda Mizuo
Published: May 2012

Quantitative SNP detection was demonstrated with an ACE using a PEG‐oligodeoxyribonucleotide block copolymer (PEG‐b‐ODN) as a probe in the presence of an EOF. The probe's PEG segment with large molecular weight and small polydispersity yielded a high resolution in the separation of a chemically synthesized 60‐base ssDNA (WT) and its single‐base‐substituted mutant (MT). A mixture of WT and MT was clearly separated within 10 min by simultaneously using two types of PEG‐b‐ODN probes whose ODN segments were complementary to WT and MT and whose PEG segments were of different lengths. The peak area ratio between WT and MT was in good agreement with the feed ratio. The averaged difference between the feed and observed ratio of MT was determined to be 0.23%, which is lower than that of any other methods. The ACE using the PEG‐b‐ODN probes in the presence of EOF could be utilized as a facile method for estimating SNP allele frequency in various research fields.
Hurricane Lifespan Modeling through a Semi‐Markov Parametric Approach
Authors: Masala Giovanni
Published: May 2012

The estimation of hurricane intensity evolution in some tropical and subtropical areas is a challenging problem. Indeed, the prevention and the quantification of possible damage provoked by destructive hurricanes are directly linked to this kind of prevision. For this purpose, hurricane derivatives have been recently issued by the Chicago Mercantile Exchange, based on the so‐called Carvill hurricane index.

In our paper, we adopt a parametric homogeneous semi‐Markov approach. This model assumes that the lifespan of a hurricane can be described as a semi‐Markov process and also it allows the more realistic assumption of time event dependence to be taken into consideration. The elapsed time between two consecutive events (waiting time distributions) is modeled through a best‐fitting procedure on empirical data. We then determine the transition probabilities and so‐called crossing states probabilities. We conclude with a Monte Carlo simulation and the model is validated through a large database containing real data coming from HURDAT. Copyright © 2012 John Wiley & Sons, Ltd.
Amplification and overexpression of the ABCC3 (MRP3) gene in primary breast cancer
Authors: Partanen Laura , Staaf Johan , Tanner Minna , Tuominen Vilppu J , Borg Åke , Isola Jorma
Published: May 2012

The ATP‐binding cassette (ABC) of active transporters comprises a group of proteins that which facilitate efflux of anticancer drugs from cancer cells. We focused on the gene amplification and protein expression of ABCC3 (also known as MRP3) in breast cancer cell lines and clinical tumor samples. Fluorescence and chromogenic in situ hybridization, using an ABCC3‐specific probe, was used to analyze 11 breast cancer cell lines and 112 clinical tumor samples. The results of ABCC3 were correlated with the amplification status of HER2 and topoisomerase II alpha (TOP2A), which are located close to ABCC3 at 17q12‐q21. Immunohistochemistry was used to assess ABCC3 protein overexpression. Of the cell lines studied 6 HER2‐positive lines and 1 HER2‐negative line exhibited amplification of ABCC3. In the HER‐2‐negative clinical tumor samples, only 4/55 (7.3%) exhibited ABCC3 amplification. In the HER2‐positive tumors, ABCC3 was amplified in 16/57 tumors (28.1%, P = 0.0059). TOP2A did not exhibit any consistent coamplification pattern. ABCC3 (MRP3) protein overexpression was more common in tumors with gene amplification (P = 0.069). In silico analysis of 804 breast cancers with matched gene expression and copy number microarray data revealed significant differences ABCC3 across the molecular subtypes. Specifically, increased ABCC3 mRNA and gene copy numbers were most prominent in HER2 amplified and/or HER2‐enriched classified tumors. Moreover, differential ABCC3 mRNA levels were found within the HER‐2 amplified subset when stratified by the estrogen receptor status. We conclude that ABCC3 is frequently amplified and overexpressed in HER2‐positive breast cancer, and something that warrants further studies correlating the results with therapeutic outcome. © 2012 Wiley Periodicals, Inc.
Differential expression of RON in small and non–small cell lung cancers
Authors: Kanteti Rajani , Krishnaswamy Soundararajan , Catenacci Daniel , Tan Yi‐Hung Carol , EL‐Hashani Essam , Cervantes Gustavo , Husain Aliya N. , Tretiakova Maria , Vokes Everett E. , Huet Heather , Salgia Ravi
Published: May 2012

RON is a MET related receptor tyrosine kinase (RTK) and its natural ligand is macrophage stimulating protein (MSP). RON plays a very important role in the regulation of inflammation. Several studies have previously reported overexpression of RON in a variety of cancers including lung and identified numerous RON alternate splice forms that very likely contribute to tumor growth and metastasis. Here, we have analyzed the expression of total RON protein as well as its kinase‐active form (phospho‐RON) in 175 archival lung tumor FFPE (formalin fixed paraffin embedded) samples that included non–small‐cell lung cancer (NSCLC) and small cell lung cancer (SCLC), and their metastatic forms. The frequency and intensity of RON protein expression was much higher in lung tumors of neuroendocrine origin such as SCLC and in secondary tumors that metastasized to brain. In addition, the majority of the expressed RON protein was phospho‐RON. We also identified 62, and 30 kDa isoforms of RON (GenBank accession numbers are JN689381 and JN689382) using RNA isolated from pooled lung cancer cell lines and RT‐PCR. A majority of the NSCLC cell lines expressed a 150 kDa band that corresponded to the RON β chain and 120 kDa band in the panel of SCLC cell lines tested. RON was expressed on the cell surface in NSCLC cell lines. Finally, knock down of RON expression resulted in a significant loss in viability as well as motility in lung cancer cells suggesting that RON is a potential therapeutic target. © 2012 Wiley Periodicals, Inc.
RoboBee and Friends
Authors: Fuhr Eckhard
Published: May 2012

A columnist's view of the DFG exhibition “Von der Idee zur Erkenntnis” — an outsider's insight into the originality and playful spirit of basic research
Wanderers in a Settled World
Authors: Unterstell Rembert
Published: May 2012

Nomads past and present: The “Brisante Begegnungen” exhibition at Hamburg's Museum of Ethnology opens windows on a wide variety of lifestyles. This thought‐provoking exhibition showcases the findings of a DFG Collaborative Research Centre.
Reborn from the Spirit of Europe
Authors: Kreft Wolfgang
Published: May 2012

Moving map: The first volume of the historical‐topographical atlas of Silesian towns looks at the border town of Görlitz/Zgorzelec. The project is intended to create a basis for comparative city research.
From an Idea to Knowledge: Making Science Visible
Authors: Kleiner Matthias
Published: May 2012

Discussing research often comes down to talking about funding and organisation. It's easy to lose sight of what matters most: the research itself. That is why science promotion also involves showcasing scientific potential and successes to the public.
The Secret Life of the Commuter
Authors: Holz‐Rau Christian , Guth Dennis , Scheiner Joachim
Published: May 2012

From home to work: Commuting has become an established part of city life. From a scientific perspective, it's a highly complex phenomenon which is only now being explored.
A Demonstration of Solidarity
Authors: Wieczorek Iris
Published: May 2012

One year after Fukushima: German‐Japanese scientific cooperation shows the way forward
ALDH1 immunohistochemical expression and its significance in salivary adenoid cystic carcinoma
Authors: Zhou Jane H. , Hanna Ehab Y. , Roberts Dianna , Weber Randal S. , Bell Diana
Published: May 2012

Background

Adenoid cystic carcinoma (ACC) cells with a high level of ALDH1, a known cancer stem cell (CSC) marker, had higher tumorigenic, invasive, and metastatic abilities. We examined the immunohistochemical expression of ALDH1 in ACC and its correlation with survival.

Methods

Archival paraffin blocks of ACC were analyzed. A tissue microarray was constructed and immunohistochemical expression of ALDH1 was analyzed using anti‐ALDH1 monoclonal antibody. Correlations between ALDH1 expression and clinical and histological parameters were assessed by chi‐square tests. Survival was assessed by the Kaplan–Meier method and log‐rank test.

Results

Most of the tumors (63%) showed stromal staining only, 11% of the tumors showed both epithelial and stromal expression, and 26% of the tumors did not show either epithelial or stromal staining. Statistical analyses did not show any correlation between the pattern of ALDH1 expression and tumor histology, tumor size, or perineural invasion. There were no significant differences in survival among the 3 patterns of ALDH1 expression.

Conclusion

Other factors, besides CSCs, may play important roles in tumorigenesis, cell differentiation, and tumor progression in these tumors. © 2012 Wiley Periodicals, Inc. Head Neck, 2013
Ipsilateral neck nodal status as predictor of contralateral nodal metastasis in carcinoma of tongue crossing the midline
Authors: Singh Bikramjit , Nair Sudhir , Nair Deepa , Patil Asawari , Chaturvedi Pankaj , D'Cruz Anil K.
Published: May 2012

Background

In squamous cell carcinoma of the tongue, when lesions reach or cross the midline, there is a higher risk of contralateral nodal metastasis. Identifying factors that are associated with higher risk of nodal metastasis may help in optimizing the treatment.

Methods

A retrospective analysis was conducted of all patients with squamous cell carcinoma of the tongue who had undergone bilateral neck dissection at Tata Memorial Hospital between January 2007 and June 2010 for a lesion crossing or reaching the midline.

Results

Contralateral nodal metastases were present in 71 of 243 patients (29%) who underwent bilateral neck dissection. Of these 71 patients, 69 patients (97%) had ipsilateral nodal metastasis.

Conclusion

In carcinoma of the tongue, where lesions reach or cross the midline, the chance of contralateral nodal metastases without ipsilateral nodal metastasis is extremely rare. Frozen section of ipsilateral neck dissection can be a pointer for addressing the contralateral neck. © 2012 Wiley Periodicals, Inc. Head Neck, 2013
Dermal metastases in squamous cell carcinomas of the head and neck
Authors: Sesterhenn Andreas M. , Albers Max B. , Timmesfeld Nina , Werner Jochen A. , Wiegand Susanne
Published: May 2012

Background

Dermal metastases in squamous cell carcinomas of the head and neck are rare. The purpose of this study was to evaluate incidence, site, prognostic significance, and treatment modalities of dermal metastases of squamous cell carcinoma of the head and neck.

Methods

Medical records were retrospectively analyzed. Statistical analysis was performed using Fisher exact test, Cox regression, and Kaplan–Meier curves.

Results

Fifty‐one patients with dermal metastases were evaluated. Dermal metastases were located in the neck, face, chest wall, and upper extremities. The median time from diagnosis of the primary tumor to the occurrence of dermal metastases was 16 months. Survival after manifestation of dermal metastases ranged from 1 to 65 weeks. Localization and treatment of dermal metastases did not significantly correlate with survival.

Conclusion

Dermal metastases indicate the terminal phase of disease. No positive effect of certain therapy modalities could be validated. Therefore, invasive therapies should be abandoned in favor of best supportive care. © 2012 Wiley Periodicals, Inc. Head Neck, 2012
Overview of Human Factors and Ergonomics in the OR, with an Emphasis on Minimally Invasive Surgeries
Authors: Lowndes Bethany R. , Hallbeck M. Susan
Published: May 2012

Operating rooms (OR) are where medical teams work to improve the health of a patient. However, because of the complexity of the procedures, errors and unsafe situations are likely to occur. These complications can lead to harm to the patient or medical professionals. Human factors and ergonomic professionals have been working to improve these unsafe conditions in the OR for over a century. However, with advances in technology, increased surgical complexity, as well as an increase in medical team members in the OR, there are still numerous improvements yet to be accomplished. Minimally invasive surgeries require an even more advanced approach to prevent errors due to technology, fatigue, and miscommunication. Human factors and ergonomic techniques provide the ability to greatly improve conditions for patients and surgeons alike. It is imperative that human factors and ergonomics continue to grow and facilitate technological advancements in healthcare. © 2012 Wiley Periodicals, Inc.
Fuzzy modeling of the forced convection heat transfer from a V‐shaped plate exposed to an air slot jet
Authors: Yousefi Tooraj , Karami Alimohammad , Rezaei Ehsan , Ebrahimi Saeid
Published: May 2012

This paper focuses on the application of fuzzy logic (FL) to predict the forced convection heat transfer from V‐shaped plate internal surfaces exposed to an air impingement slot jet. The aim of the present paper is to consider the effects of the angle of a V‐shaped plate (Φ), slot‐to‐plate spacing ratio (Z/W), and Reynolds number (Re) variation on average heat transfer from the V‐shaped plate internal surfaces. The data used for developing the FL structure was obtained experimentally by a Mach‐Zehnder interferometer. The proposed FL was developed using MATLAB functions. It was observed that the average Nusselt number will be decreased with an increase in jet spacing and be increased with an increase in Reynolds number and angle of V‐shaped plate. Moreover, it is also shown that fuzzy logic is a powerful technique to use for predicting heat transfer due to its low error rate. The average error of the fuzzy predictions compared with experimental data was found to be 0.33% for this study. © 2012 Wiley Periodicals, Inc. Heat Trans Asian Res; Published online in Wiley Online Library (wileyonlinelibrary.com/journal/htj). DOI 10.1002/htj.21009
Transient heat transfer in a heat‐generating fin with radiation and convection with temperature‐dependent heat transfer coefficient
Authors: Khan Waqar A. , Aziz A.
Published: May 2012

The transient heat transfer in a heat‐generating fin with simultaneous surface convection and radiation is studied numerically for a step change in base temperature. The convection heat transfer coefficient is assumed to be a power law function of the local temperature difference between the fin and its surrounding fluid. The values of the power exponent n are chosen to include simulation of natural convection (laminar and turbulent) and nucleate boiling among other convective heat transfer modes. The fin is assumed to have uniform internal heat generation. The transient response of the fin depends on the convection‐conduction parameter, radiation‐conduction parameter, heat generation parameter, power exponent, and the dimensionless sink temperature. The instantaneous heat transfer characteristics such as the base heat transfer, surface heat loss, and energy stored are reported for a range of values of these parameters. When the internal heat generation exceeds a threshold the fin acts as a heat sink instead of a heat source. © 2012 Wiley Periodicals, Inc. Heat Trans Asian Res; Published online in Wiley Online Library (wileyonlinelibrary.com/journal/htj). DOI 10.1002/htj.21012
Accuracy of concurrent visual and cytology screening in detecting cervical cancer precursors in rural India
Authors: Deodhar Kedar , Sankaranarayanan Rengaswamy , Jayant Kasturi , Jeronimo Jose , Thorat Ranjit , Hingmire Sanjay , Muwonge Richard , Chiwate Aruna , Deshpande Rutha , Ajit Dulhan , Kelkar Rohini , Rekhi Bharat , Ruben Irene , Malvi Sylla G. , Chinoy Roshni , Jambhekar Nirmala , Nene Bhagwan M.
Published: May 2012

The high burden of cervical cancer and inadequate/suboptimal cytology screening in developing countries led to the evaluation of visual screening tests, like visual inspection with acetic acid (VIA) and Lugol's iodine (VILI). We describe the performance of VIA, VILI and cytology, carried out in a multinational project called “Screening Technologies to Advance Rapid Testing” in 5,519 women aged 30–49 years, in detecting cervical intraepithelial neoplasia (CIN). VIA, VILI and cytology were positive in 16.9%, 15.6% and 6.1% women, respectively. We found 57 cases of CIN2, 55 of CIN3 and 12 of cervical cancer; 90% of CIN3 and 43% CIN2 cases were positive for p16 overexpression and high‐risk HPV infection, indicating a high validity of histological diagnosis. The sensitivity of VIA, VILI and cytology to detect high‐grade CIN were 64.5%, 64.5% and 67.7%, respectively; specificities were 84.2%, 85.5% and 95.4%. A high proportion of p16 positive CIN 3 (93.8%) and 2 (76.9%) were positive on cytology compared with visual tests (68.8% and 53.8%, respectively) indicating a higher sensitivity of cytology to detect p16 positive high‐grade CIN. However, the immediate availability of the results from the visual tests permits diagnosis and/or treatment to be performed in the same sitting, which can potentially reduce loss to follow‐up when women must be recalled following positive cytology. Organizing visual screening services in low‐resource countries may facilitate the gradual building of an infrastructure committed to screening allowing the eventual introduction of more sensitive, highly objective, reproducible and affordable human papillomavirus screening tests in future.
Diesel and biodiesels induce hepatic palmitoyl‐coa oxidase enzymatic activity through different molecular mechanisms in rats
Authors: Pelletier Guillaume , Rigden Marc , Poon Raymond
Published: May 2012

Induction of palmitoyl‐CoA oxidase enzymatic activity in rat liver suggests that ingestion of diesel and biodiesels can cause mild hepatic peroxisomal proliferation. Surprisingly, quantification by immunochemistry of the enzyme itself (ACOX1) revealed that palmitoyl‐CoA oxidase enzymatic activity correlates with ACOX1 protein level following exposure to diesel, but not following exposure to biodiesels. Quantification of CYP4A1, another biomarker of peroxisomal proliferation, further indicates that contrary to diesel, the effects of biodiesels appear to be independent of this pathway. There are two ACOX1 protein isoforms that exhibit different enzymatic activities depending on the substrate. The results of our enzymatic assays performed on substrates presenting different carbon chain lengths (octanoyl‐CoA and palmitoyl‐CoA) are compatible with the hypothesis of a differential regulation of the ACOX1 isoforms by diesel and biodiesels. Further studies will be required to precisely determine the molecular mechanisms by which diesel and biodiesels induce palmitoyl‐CoA oxidase activity in rat liver. © 2012 Wiley Periodicals, Inc. J Biochem Mol Toxicol 26:235–240, 2012; View this article online at wileyonlinelibrary.com. DOI 10.1002/jbt.21412
Use of 1‐hexyl‐3‐methylimidazolium bromide ionic liquid in the recovery of lactic acid from wine
Authors: Lateef Huma , Gooding Anna , Grimes Sue
Published: May 2012

BACKGROUND: Lactic acid has many different applications in a variety of industries including the food, cosmetics, packaging, leather and chemical industries. Current methodologies for lactic acid production are lengthy and complicated and more efficient methods are being sought. Some organic wastes contain lactic acid and our work investigates the use of ionic liquids (ILs) in the efficient and selective extraction of lactic acid from organic waste using wine as a model system. The ionic liquid was chosen based on its ability to selectively solvate and separate lactic acid from the remaining bulk waste material.

RESULTS: Several ILs including 1‐hexyl‐3‐methylimidazolium chloride (hmimCl), 1‐hexyl‐3‐methylimidazolium bromide (hmimBr), 1‐hexyl‐3‐methylimidazolium iodide (hmimI) and N‐hexylpyridinium iodide (hpyrI) have been synthesized in high yield (68‐95%) using microwave technology. Lactic acid is soluble in each of the ILs synthesized with optimum results achieved with hmimBr where lactic acid is miscible in all proportions. HmimBr has been used to successfully separate and extract lactic acid from wine as confirmed by FTIR spectroscopy. Furthermore, it has been possible to recover the IL for recycle in subsequent extraction cycles where the efficiency for the extraction process increases with each recycle.

CONCLUSION: HmimBr has been used for the first time in a novel process for the separation and recovery of lactic acid from wine, as confirmed by FTIR spectroscopy. This work demonstrates a novel process which can be applied to the recovery of lactic acid from organic waste. Copyright © 2012 Society of Chemical Industry
Sinusoidal echo‐planar imaging with parallel acquisition technique for reduced acoustic noise in auditory fMRI
Authors: Zapp Jascha , Schmitter Sebastian , Schad Lothar R.
Published: May 2012

Purpose:

To extend the parameter restrictions of a silent echo‐planar imaging (sEPI) sequence using sinusoidal readout (RO) gradients, in particular with increased spatial resolution. The sound pressure level (SPL) of the most feasible configurations is compared to conventional EPI having trapezoidal RO gradients.

Materials and Methods:

We enhanced the sEPI sequence by integrating a parallel acquisition technique (PAT) on a 3 T magnetic resonance imaging (MRI) system. The SPL was measured for matrix sizes of 64 × 64 and 128 × 128 pixels, without and with PAT (R = 2). The signal‐to‐noise ratio (SNR) was examined for both sinusoidal and trapezoidal RO gradients.

Results:

Compared to EPI PAT, the SPL could be reduced by up to 11.1 dB and 5.1 dB for matrix sizes of 64 × 64 and 128 × 128 pixels, respectively. The SNR of sinusoidal RO gradients is lower by a factor of 0.96 on average compared to trapezoidal RO gradients.

Conclusion:

The sEPI PAT sequence allows for 1) increased resolution, 2) expanded RO frequency range toward lower frequencies, which is in general beneficial for SPL, or 3) shortened TE, TR, and RO train length. At the same time, it generates lower SPL compared to conventional EPI for a wide range of RO frequencies while having the same imaging parameters. J. Magn. Reson. Imaging 2012;36:581–588. © 2012 Wiley Periodicals, Inc.
Molecular characterization of hepatitis E virus in patients with acute hepatitis in Venezuela
Authors: García Cristina Gutiérrez , Sánchez Doneyla , Villalba Maria Caridad Montalvo , Pujol Flor Helene , de los Ángeles Rodríguez Lay Licel , Pinto Belquis , Chacón Elsa Patricia , Guzmán Maria Guadalupe
Published: May 2012

Hepatitis E virus (HEV) causes a common infection in developing countries. HEV infection occurs as outbreaks, as sporadic clinical cases and as large epidemics in endemic areas. The objective of this study was to determine the presence of HEV infection in patients with clinical suspicion of hepatitis A virus (HAV) infection, referred to the Instituto Nacional de Higiene “Rafael Rangel” in Venezuela. Seventy‐four sera were tested for anti‐HAV and anti‐HEV IgM antibodies. HEV‐RNA was amplified from anti‐HEV IgM positive sera using nested reverse transcription polymerase chain reaction for ORF1 (RNA dependent RNA polymerase region) and the amplicons sequenced for phylogenetic analysis. The frequency of anti‐HEV IgM was 22/74 (30%) in the samples tested. Dual infection with HAV and HEV was found in 31% (12/39) of anti‐HAV IgM positive patients. Viremia was detected in 3/22 (14%) of sera positive for anti‐HEV IgM. Two HEV strains were classified as genotype 1 and one as genotype 3, which were closely related to Yam 67 (north of India) and US1 isolates from the USA, respectively. These findings suggest that HEV is an important cause of acute viral hepatitis in Venezuela as a single infection or co‐infection with HAV, with high morbidity in children and young adults suggesting that this infection is endemic in Venezuela. J. Med. Virol. 84: 1025–1029, 2012. © 2012 Wiley Periodicals, Inc.
Hepatitis C virus related hepatocellular carcinoma: A case control study from India
Authors: Sarma Manash Pratim , Asim Mohammad , Medhi Subhash , Bharathi Thayumanavan , Kar Premashis
Published: May 2012

Infection with hepatitis C virus (HCV) is a major risk factor for hepatocellular carcinoma (HCC) in India. The study was designed to investigate the clinical and molecular profiles of HCV related HCC cases in Indian patients. In a prospective study, 68 HCV related HCC, 55 HCV related chronic hepatitis, and 68 HCV related patients with cirrhosis were included. Glutathione S‐transferase gene polymorphism was analyzed in all the cases. The sex ratios were 5.18:1, 1.39:1, and 0.83:1 with mean age of 50.57 ± 12.47, 39.41 ± 13.34, and 46.08 ± 15.06 years, respectively, in three groups. Amongst the HCV related HCC cases seen in India, 49.2% (30 out of 68) were with Okuda stage I while 34.4% (21 out of 68) cases were classified as stage II. Older age, poor standards of living, HCV genotype 4, smoking, and null genotypes of GST were the risk factors associated significantly with the development of HCC. In 55.9% cases (38 out of 68) the size of the tumor was ≥5 cm while in 38.2% cases (26 out of 68) the size was between 2 and 5 cm, indicating an advanced stage of the disease at presentation. J. Med. Virol. 84: 1009–1017, 2012. © 2012 Wiley Periodicals, Inc.