bluuebunny/crossref_metadata_2025 huggingface dataset:
ZNF703 gene amplification at 8p12 specifies luminal B breast cancer
Authors: Sircoulomb Fabrice , Nicolas Nathalie , Ferrari Anthony , Finetti Pascal , Bekhouche Ismahane , Rousselet Estelle , Lonigro Aurélie , Adélaïde José , Baudelet Emilie , Esteyriès Séverine , Wicinski Julien , Audebert Stéphane , Charafe‐Jauffret Emmanuelle , Jacquemier Jocelyne , Lopez Marc , Borg Jean‐Paul , Sotiriou Christos , Popovici Cornel , Bertucci François , Birnbaum Daniel , Chaffanet Max , Ginestier Christophe
Published: February 2011

Luminal B breast cancers represent a fraction of oestrogen receptor (ER)‐positive tumours associated with poor recurrence‐free and disease‐specific survival in all adjuvant systemic treatment categories including hormone therapy alone. Identification of specific signalling pathways driving luminal B biology is paramount to improve treatment. We have studied 100 luminal breast tumours by combined analysis of genome copy number aberrations and gene expression. We show that amplification of the ZNF703 gene, located in chromosomal region 8p12, preferentially occurs in luminal B tumours. We explored the functional role of ZNF703 in luminal B tumours by overexpressing ZNF703 in the MCF7 luminal cell line. Using mass spectrometry, we identified ZNF703 as a co‐factor of a nuclear complex comprising DCAF7, PHB2 and NCOR2. ZNF703 expression results in the activation of stem cell‐related gene expression leading to an increase in cancer stem cells. Moreover, we show that ZNF703 is implicated in the regulation of ER and E2F1 transcription factor. These findings point out the prominent role of ZNF703 in transcription modulation, stem cell regulation and luminal B oncogenesis.

→See accompanying Closeup by Vessela Kristensen DOI 10.1002/emmm201100128
Does the EU sugar policy reform increase added sugar consumption? An empirical evidence on the soft drink market
Authors: Bonnet Céline , Requillart Vincent
Published: February 2011

Whereas National Health authorities recommend a decrease in the consumption of ‘added’ sugar, a reform on the sugar market will lead to a 36% decrease of the sugar price in the EU. Using French data on soft drinks purchases, this paper investigates the anticipated impact of this reform on the consumption of sugar‐sweetened beverages. The reform of the EU sugar policy leads to a decrease in regular soft drink prices by 3% and varies across brands. To assess substitution within this food category, we use a random‐coefficients logit model that takes into account a large number of differentiated products and heterogeneity in consumers' behavior. Results suggest that price changes would lead to an increase in market shares of regular products by 7.5% and to substitutions between brands to the benefit of products with the highest sugar content. On the whole, it would raise consumption of regular soft drinks by more than 1 litre per person per year and consumption of added sugar by 124 g per person per year, this increase being larger in households composed of overweight and obese individuals. Copyright © 2011 John Wiley & Sons, Ltd.
MicroRNA-221 regulates FAS-induced fulminant liver failure
Authors: Sharma Amar Deep , Narain Nidhi , Händel Eva-Maria , Iken Marcus , Singhal Nishant , Cathomen Toni , Manns Michael P. , Schöler Hans R. , Ott Michael , Cantz Tobias
Published: February 2011

Death receptor-mediated apoptosis of hepatocytes contributes to hepatitis and fulminant liver failure. MicroRNAs (miRNAs), 19–25 nucleotide-long noncoding RNAs, have been implicated in the posttranscriptional regulation of the various apoptotic pathways. Here we report that global loss of miRNAs in hepatic cells leads to increased cell death in a model of FAS/CD95 receptor-induced apoptosis. miRNA profiling of murine liver identified 11 conserved miRNAs, which were up-regulated in response to FAS-induced fulminant liver failure. We show that ectopic expression of miR-221, one of the highly up-regulated miRNAs in response to apoptosis, protects primary hepatocytes and hepatoma cells from apoptosis. Importantly,

in vivo

overexpression of miR-221 by adeno-associated virus serotype 8 (AAV8) delays FAS-induced fulminant liver failure in mice. We additionally demonstrate that miR-221 regulates hepatic expression of p53 up-regulated modulator of apoptosis (

Puma

), a well-known proapoptotic member of the Bcl2 protein family.

Conclusion:

We identified miR-221 as a potent posttranscriptional regulator of FAS-induced apoptosis. miR-221 may serve as a potential therapeutic target for the treatment of hepatitis and liver failure. (HEPATOLOGY 2011;)
High expression of indoleamine 2,3‐dioxygenase in the tumour is associated with medullary features and favourable outcome in basal‐like breast carcinoma
Authors: Jacquemier Jocelyne , Bertucci François , Finetti Pascal , Esterni Benjamin , Charafe‐Jauffret Emmanuelle , Thibult Marie‐Laure , Houvenaeghel Gilles , Van den Eynde Benoit , Birnbaum Daniel , Olive Daniel , Xerri Luc
Published: February 2011

Medullary breast cancer (MBC) is a basal‐like breast carcinoma (BLBC) with a favourable outcome, whereas nonmedullary BLBC has a poor prognosis. Tumour infiltrating lymphocytes (TILs) are present in both MBC and BLBC. We hypothesized that the immunosuppressive enzyme indoleamine 2,3‐dioxygenase (IDO) could modulate the TILs effects among these tumours and explain their different outcomes. The amount of TILs and IDO expression were analysed using immunohistochemistry (IHC) in 155 BC cases including MBC (n = 17), atypical MBC (n = 13) and non‐MBC (n = 125). Messenger RNA expression of the INDO gene, which encodes IDO, was measured in 262 cases from our institution. INDO mRNA expression and histoclinical data of 1,487 BC cases were collected from public databases. IDO immunostaining was present in both neoplastic and stromal cells in 100% of MBC and was associated with histological medullary features among non‐MBC cases. There was a significant correlation between IDO positivity and TIL amounts. In our series including mostly grade‐3 BC, IDO immunostaining was the most significant marker (p = 0.02) associated with better survival in multivariate analysis. Among our 262 analysed BC cases, INDO mRNA showed significant overexpression in BLBC as compared to luminal A tumours, and in MBC as compared to basal‐like non‐MBC. In the pooled series of 1,749 BC cases, INDO mRNA was overexpressed in BLBC and was the most significant predictor of better survival in this subtype using multivariate analysis (p = 0.0024). In conclusion, high IDO expression is associated with morphological medullary features and has an independent favourable prognostic value in BLBC.
A self‐consistent Hirshfeld method for the atom in the molecule based on minimization of information loss
Authors: Ghillemijn Dieter , Bultinck Patrick , Van Neck Dimitri , Ayers Paul W.
Published: February 2011

Based on the so‐called Hirshfeld atom in the molecule scheme, a new AIM method is presented. The method is similar to the Hirshfeld‐I scheme, with the AIM weight function being constructed by minimizing the information loss upon formation of the molecule, but now requiring explicitly that the promolecular densities integrate to the same number of electrons as the AIM densities. This new weight function leads to a new iterative AIM scheme, and the resulting operative scheme is examined and discussed. The final results indicate that the newly proposed method does not perform as well as the Hirshfeld‐I method.
The role of the membrane potential in chondrocyte volume regulation
Authors: Lewis Rebecca , Asplin Katie E. , Bruce Gareth , Dart Caroline , Mobasheri Ali , Barrett‐Jolley Richard
Published: February 2011

Many cell types have significant negative resting membrane potentials (RMPs) resulting from the activity of potassium‐selective and chloride‐selective ion channels. In excitable cells, such as neurones, rapid changes in membrane permeability underlie the generation of action potentials. Chondrocytes have less negative RMPs and the role of the RMP is not clear. Here we examine the basis of the chondrocyte RMP and possible physiological benefits. We demonstrate that maintenance of the chondrocyte RMP involves gadolinium‐sensitive cation channels. Pharmacological inhibition of these channels causes the RMP to become more negative (100 µM gadolinium: ΔVm = −30 ± 4 mV). Analysis of the gadolinium‐sensitive conductance reveals a high permeability to calcium ions (PCa/PNa ≈80) with little selectivity between monovalent ions; similar to that reported elsewhere for TRPV5. Detection of TRPV5 by PCR and immunohistochemistry and the sensitivity of the RMP to the TRPV5 inhibitor econazole (ΔVm = −18 ± 3 mV) suggests that the RMP may be, in part, controlled by TRPV5. We investigated the physiological advantage of the relatively positive RMP using a mathematical model in which membrane stretch activates potassium channels allowing potassium efflux to oppose osmotic water uptake. At very negative RMP potassium efflux is negligible, but at more positive RMP it is sufficient to limit volume increase. In support of our model, cells clamped at −80 mV and challenged with a reduced osmotic potential swelled approximately twice as much as cells at +10 mV. The positive RMP may be a protective adaptation that allows chondrocytes to respond to the dramatic osmotic changes, with minimal changes in cell volume. J. Cell. Physiol. 226: 2979–2986, 2011. © 2011 Wiley‐Liss, Inc.
Efficient mAb production in CHO cells incorporating PEI‐mediated transfection, mild hypothermia and the co‐expression of XBP‐1
Authors: Codamo Joe , Hou Jeff Jia Cheng , Hughes Benjamin S. , Gray Peter P. , Munro Trent P.
Published: February 2011

BACKGROUND: Transient gene expression (TGE) provides a rapid way to generate recombinant protein biologics for pre‐clinical assessment. Human embryonic kidney (HEK293) cells have traditionally been used for TGE; however, there is demand from industry for efficient, high‐producing TGE systems that utilize Chinese hamster ovary (CHO) cells. A polyethyleneimine (PEI) ‐based TGE process has been developed for CHO cells using an episomal expression system to generate enhanced recombinant protein titers.

RESULTS: A five‐fold improvement in monoclonal antibody (mAb) volumetric productivity was achieved by examining key parameters including transfection medium, cell density, transfection reagent, DNA:reagent ratio, the time of transfer to mild hypothermia and feeding strategy post‐transfection. The Epi‐CHO system allowed for a six‐fold expansion in culture volume post‐transfection without significantly affecting specific productivity. This system generates 400% more mAb per µg of plasmid DNA when compared with a non‐episomal system. In addition, the use of X‐box binding protein 1 to enhance secretion capacity and provide further improvements in mAb production with TGE was investigated.

CONCLUSION: Through optimization of key parameters, our results demonstrate the development of a low‐cost, high‐yielding, episomal TGE system that may be adopted during pre‐clinical biologic drug development. Copyright © 2011 Society of Chemical Industry
New frontiers in cell line development: challenges for biosimilars
Authors: Hou Jeff Jia Cheng , Codamo Joe , Pilbrough Warren , Hughes Benjamin , Gray Peter P , Munro Trent P
Published: February 2011

Worldwide sales of biologic drugs exceeded US$ 92 billion in 2009. With many biopharmaceutical patents expiring over the next decade, a wave of second‐generation or ‘follow‐on’ biologics will be vying for market share and regulatory approval. Patents cover not only the drugs, but also the molecular modalities that facilitate their high‐level expression. Companies have historically relied on gene amplification to create productive cell lines, yet this lengthy and imprecise process usually leads to extensive variation and unpredictable stability of expression. Biosimilar manufacturers must therefore decide whether traditional methods of cell line development will suffice or if emerging technologies can provide greater reproducibility and speed. Volumetric yields of 1–2 g L−1 are adequate for most production processes and the focus has shifted towards reliable and predicable product quality attributes over maximum possible titres. Recent advances in this area include cell lines with targeted genetic modifications, alternative production hosts such as PER.C6® or yeast, and engineered expression vectors, including the UCOE™ and Selexis platforms. Host cell engineering, single‐use technologies, and rapid transient gene expression are also likely to be enablers of biosimilars. Given the well‐known biologics industry mantra ‘the process defines the product’, it remains to be seen how novel cell line development strategies will affect product equivalence and regulatory approval in a biosimilars context. Some recent advances in the field and how they relate to biosimilars are explored. Copyright © 2011 Society of Chemical Industry
Infant lungs are preferentially infected by adenovirus and herpes simplex virus type 1 vectors: role of the tissue mesenchymal cells
Authors: Massler Anda , Kolodkin‐Gal Dror , Meir Karen , Khalaileh Abed , Falk Haya , Izhar Uzi , Shufaro Yoel , Panet Amos
Published: February 2011

Background

Adenovirus (AD) and herpes‐simplex‐virus‐1 (HSV‐1) have been extensively applied as vectors for gene and cancer therapy in clinical trials. AD5, from which the vector was constructed, is a common respiratory virus that infects mainly infants, yet the reasons for infant sensitivity to infection, other than immunity, are not clear. HSV‐1, usually a neurotropic virus, may also cause severe pneumonia or disseminated diseases in infants and immunocompromised patients.

Methods

The tropism of these viruses to different human and mouse lung tissues of newborn and adult was studied in an ex vivo organ culture and it was also applied in vivo using a murine model.

Results

The data obtained indicated preferential viral infection of young lung tissues versus adult tissues in organ culture. Further studies indicated that the preferential infection of young tissues was not related to differences in receptor expression or exposure but rather to the different distribution of cell types in these tissues. Murine and human young lungs consist of a relative abundance of mesenchymal cells and these cells were much more susceptible to viral infection compared to adjacent epithelial‐pneumocyte cells. These observations were further confirmed using an in vivo model of mouse infection.

Conclusions

The similarity of the human and mouse tissues, with respect to viral vector tropism, validates the mouse model in studies of gene transfer to the lung. Furthermore, the results should facilitate the improved design of gene therapy trials for lung‐related diseases in young and adults patients. Copyright © 2011 John Wiley & Sons, Ltd.
Nutrient composition of the marine snail (Hexaplex trunculus) from the Tunisian Mediterranean coasts
Authors: Zarai Zied , Frikha Fakher , Balti Rafik , Miled Nabil , Gargouri Youssef , Mejdoub Hafedh
Published: February 2011

BACKGROUND: Marine snail (Hexaplex trunculus) presents increasing nutritional, commercial and economical importance, being widely consumed in northern Africa, particularly in Mediterranean countries. From a nutritional point of view there is still limited information on the chemical composition of edible tissues (meat and hepatopancreas) of this species. Therefore, the aims of the present work were to study the proximate chemical composition, fatty acid and amino acid profiles of H. trunculus from the Tunisian Mediterranean coasts.

RESULTS: Fatty acid profiles showed that the polyunsaturated fatty acids (PUFA) content is higher than the saturated fatty acids (SFA). The yields of PUFA and SFA present in the meat fat were 68.2% and 33.4% of the total fatty acids, respectively. Similar values were obtained in the hepatopancreatic lipidic fraction. Snail tissues contain valuable concentrations of PUFA, especially n‐6 and n‐3 with chain lengths of 20 and 22 carbons. All edible tissues were valuable sources of essential amino acids. Aspartic acid is the major amino acids present in the meat and hepatopancreas. The concentrations of nutrients were also determined in the hepatopancreas and meat of H. trunculus. Significantly high concentrations of minerals and trace elements were found in these tissues.

CONCLUSION: This study suggests that H. trunculus is an important source of protein and essential amino acids. Furthermore, the snail lipidic fraction contains high proportions of polyunsaturated fatty acids benefical for human health. Copyright © 2011 Society of Chemical Industry
Synthesis of some novel antioxidant and anticorrosive additives for Egyptian gasoline motor oils
Authors: Hassan H. M. , Habib O. M. O. , Moawad Evelin B. , El‐Bana Ghada G. , El Defrawy A. M.
Published: February 2011

2‐Methyl‐benzo[d][1,3]oxazin‐4‐one (1) was used as a key intermediate for the synthesis of different benzoxazinone and quinazolinone derivatives. In order to evaluate the applicability of the synthesised benzoxazinones and quinazolinones as antioxidant additives for lube oil, these antioxidant additives decomposed the alkyl peroxide radicals and/or alkyl hydrogen peroxides to produce esters, ketone and hydroxy compounds rather than carboxylic acids. The compounds that showed antioxidant efficiency were tested as corrosion inhibitors using three types of metals: Cu, Al and Fe. Copyright © 2011 John Wiley & Sons, Ltd.
General Purpose Electronegativity Relaxation Charge Models Applied to CoMFA and CoMSIA Study of GSK‐3 Inhibitors
Authors: Tsareva Daria A. , Osolodkin Dmitry I. , Shulga Dmitry A. , Oliferenko Alexander A. , Pisarev Sergey A. , Palyulin Vladimir A. , Zefirov Nikolay S.
Published: February 2011

Two fast empirical charge models, Kirchhoff Charge Model (KCM) and Dynamic Electronegativity Relaxation (DENR), had been developed in our laboratory previously for widespread use in drug design research. Both models are based on the electronegativity relaxation principle (Adv. Quantum Chem.2006,51, 139–156) and parameterized against ab initio dipole/quadrupole moments and molecular electrostatic potentials, respectively. As 3D QSAR studies comprise one of the most important fields of applied molecular modeling, they naturally have become the first topic to test our charges and thus, indirectly, the assumptions laid down to the charge model theories in a case study. Here these charge models are used in CoMFA and CoMSIA methods and tested on five glycogen synthase kinase 3 (GSK‐3) inhibitor datasets, relevant to our current studies, and one steroid dataset. For comparison, eight other different charge models, ab initio through semiempirical and empirical, were tested on the same datasets. The complex analysis including correlation and cross‐validation, charges robustness and predictability, as well as visual interpretability of 3D contour maps generated was carried out. As a result, our new electronegativity relaxation‐based models both have shown stable results, which in conjunction with other benefits discussed render them suitable for building reliable 3D QSAR models.
Static modes switching for more efficient flexible multibody simulation
Authors: Heirman Gert H. K. , Tamarozzi Tommaso , Desmet Wim
Published: February 2011

Body flexibility is of ever‐increasing importance in multibody simulation. The current state‐of‐the‐art simulation techniques typically have difficulties with systems in which flexible bodies can be loaded in many degrees of freedom (DOFs). However, in many applications, loading is possible in many DOFs but only few are loaded simultaneously at any given moment, such that at any moment only a low‐dimensional part of the reduced body flexibility description contributes to the solution. Static Modes Switching, the methodology proposed in this paper, exploits this by judiciously choosing the body flexibility mode set and at any moment only including those modes that contribute to the solution. Static Modes Switching does not improve simulation accuracy; however, it can significantly reduce simulation times. In a numerical experiment, results using Static Modes Switching match results for a conventional model using the same mode set. The approximation errors are negligible compared to the accuracy loss encountered when using a mode set without compensation for the quasi‐static response of the high‐frequency dynamics, while both simulation results are obtained at a comparable computational cost. Static Modes Switching numerically introduces discontinuities when removing a mode from the mode set. This is overcome by time integration schemes exhibiting high‐frequency numerical damping. Copyright © 2011 John Wiley & Sons, Ltd.
Genetic assessment following increased nuchal translucency and normal karyotype
Authors: Pergament Eugene , Alamillo Christina , Sak Katrin , Fiddler Morris
Published: February 2011

Objective

The objective of this study was to assess the first formal approach for monitoring genetic/developmental syndromes associated with the presence of an increased nuchal translucency (NT) thickness (>3 mm) in the first trimester of pregnancy.

Methods

Multiple technologies—a DNA chip using the APEX technology, qPCR, microfluidic PCR, and sequencing—were applied to assay 310 mutations across five conditions—Noonan syndrome, congenital adrenal hyperplasia, spinal muscular atrophy (SMA), DiGeorge syndrome, and Smith‐Lemli Opitz syndrome.

Results

We report the results of assessing the first 120 patients in which 8 cases of Noonan syndrome were detected as well as an unusually high rate of heterozygosity for SMA.

Conclusion

While testing for Noonan syndrome in association with increased NT appears warranted, the reported association of the remaining four genetic syndromes is likely to be weak and possibly insignificant. Copyright © 2011 John Wiley & Sons, Ltd.
Tumorbehandlung mittels Partikeltherapie
Authors: Barfuss Heinz
Published: February 2011

Strahlentherapie wird schon seit Jahrzehnten zur Behandlung von bösartigen Tumoren eingesetzt. Der Ionenstrahl zerstört die Erbanlagen (DNA) der Krebszelle und verhindert die weitere Zellteilung, da die erforderlichen Informationen nicht mehr vorhanden sind. Folglich stirbt die Krebszelle ab. Die Strahlentherapie hat ihren Anwendungsbereich nur in der Behandlung von lokalen Tumoren. Metastasierende Tumore können damit nicht behandelt werden. Speziell Patienten mit komplizierten, tief im Körper liegenden Tumoren können im Gegensatz zur konventionellen Strahlentherapie erfolgreich behandelt werden. Kindliche Krebsarten können sehr schonend ohne negative Langzeiteffekte behandelt werden.

Die Partikel werden im Hochvakuum < 1*10‐8 mbar mittels Magnete in Vakuumröhren und einem Synchrotron auf bis zu 75 % der Lichtgeschwindigkeit beschleunigt, um ihre radioaktive Dosis gezielt abgeben zu können.
Posttranscriptional control of X‐chromosome dosage compensation
Authors: Graindorge Antoine , Militti Cristina , Gebauer Fátima
Published: February 2011

RNA regulation plays a major role in the generation of diversity at the molecular and cellular levels, and furnishes the cell with flexibility potential to adapt to changing environments. Often, the regulation by/of RNA dictates when, where, and how the information encoded in the nucleus is revealed. One example is the regulation of X‐chromosome dosage compensation. In Drosophila, differences in X‐linked gene dosage between males and females are compensated by the transcriptional upregulation of the single male X chromosome. Mechanisms of alternative splicing and translational control, among others, enforce dosage compensation in males while inhibiting this process in females. In this review, we discuss the posttranscriptional RNA regulatory mechanisms that ensure appropriate dosage compensation in Drosophila, drawing parallels with the mammalian system when appropriate. WIREs RNA 2011 2 534–545 DOI: 10.1002/wrna.75

This article is categorized under:

RNA Interactions with Proteins and Other Molecules > RNA–Protein Complexes

Translation > Translation Regulation

RNA Processing > Splicing Regulation/Alternative Splicing

RNA in Disease and Development > RNA in Development
Dynamic Light Scattering Studies on the Effect of 1‐Alkanols, Alkanediols and Alkoxyethanols on the Micelles of a Moderately Hydrophobic/Hydrophilic PEO‐PPO‐PEO Triblock Copolymer
Authors: Parekh Paresh , Bahadur Pratap
Published: February 2011

The results on changes in the apparent hydrodynamic diameter (Dh) of micelles in a solution containing 5% of a moderately hydrophobic/hydrophilic triblock PEO‐PPO‐PEO copolymer in the presence of several hydroxyl compounds at 23 °C from dynamic light scattering (DLS) are reported. Distribution plots show micelles with hydrodynamic diameter ∼17 nm and low polydispersity (<0.1) except at low concentrations where a unimer peak (∼ 4 nm) was also noticed. These additives increase/decrease the micelle size and show micellar transition depending upon their hydrophilicity/hydrophobicity. The results are discussed in terms of the effect of the additives on altering water structure and their partitioning in micelle. Short chain alcohols (C1–C3) increase solvation of PEO and thus increase micelle hydrodynamic size while higher alcohols, initially reduce Dh due shrinkage of PEO followed by micellar growth at higher concentrations. Among αω‐alkanediols, C2 and C4 diols increase micelle size by immobilizing water sphere around the micelles whereas higher diols form wicket like structures and reside in palisade layer. Isomeric hexanediols (1,2; 1,5; 2,5 and 1,6) alter micelle size in different ways depending on their hydrophobicity. In C6EOm (m = 0, 1, 2), as the number of EO group increases, it becomes more hydrophilic and increases Dh at higher concentration. Addition of a hydrophobic triblock copolymer leads to unfavorable mixing with a moderately hydrophobic/hydrophilic triblock copolymer which results in increase in size, while the addition of a hydrophilic counterpart increases the average hydrodynamic size and follows appearance of unimer peak.
Stabilization of Gas Bubbles Released from Water‐Soluble Carbohydrates Using Amphiphilic Compounds: Preparation of Formulations and Acoustic Monitoring of Bubble Lifetime
Authors: Hoff Lars , Foss Per A. , Dyrstad Knut , Klaveness Jo , Rongved Pål
Published: February 2011

The ultrasound contrast agents Echovist® and Levovist® (Bayer AG, Schering AG, Germany) are based on the release of gas bubbles from milled α‐d‐galactose. In diagnostic ultrasound, for this class of contrast agents, there is a need for prolonged contrast duration. To investigate if new carbohydrate compositions could prolong the lifetime of the gas bubbles, α‐d‐galactose was mixed with other carbohydrates or amphiphiles with varying log P. Acoustic attenuation vs. time (390 s) area under the curve (A390) and bubble half‐time (t½) were used as measures of prolonged lifetime of gas bubbles. The products, to which 0.1% of a lipophilic carboxylic acid (5β‐cholanic acid, behenic acid, and melissic acid) has been added, showed more than 5, 7 and 11 times enhancement of A390, respectively, compared with the reference compound 2 (RC2) corresponding to the commercial product Levovist®. The half‐time t ½ of the same compounds was prolonged more than 6 times compared with RC2. A partial least square (PLS) statistical analysis confirmed that, for additives, high log P carboxylic acids lead to the highest A390. The present results bear a promise of products with a more persistent in vivo ultrasound contrast effect than the commercially available agents.
Mild Testicular Hyperthermia Transiently Increases Lipid Droplet Accumulation and Modifies Sphingolipid and Glycerophospholipid Acyl Chains in the Rat Testis
Authors: Furland Natalia E. , Luquez Jessica M. , Oresti Gerardo M. , Aveldaño Marta I.
Published: February 2011

Spermatogenesis is known to be vulnerable to temperature. The aim of this study was to investigate the effects on testicular lipids of the transient germ cell loss that is induced by mild testicular hyperthermia. Adult rat testes were exposed once a day to 43 °C for 15 min for 5 days and the effects were followed for several weeks. Two week after the last heat exposure, spermatocytes and early spermatids had virtually disappeared and the seminiferous tubules were populated mostly by mature spermatids and spermatozoa. One week later, the latter were also absent and mostly Sertoli cells populated the tubules. During these 3 weeks, glycerophospholipids (Gpl) and triacylglycerols with long‐chain polyunsaturated fatty acids (PUFA) (e.g., 22:5n‐6) and species of sphingomyelin and ceramide with nonhydroxy and 2‐hydroxy very long‐chain (VLC) PUFA (e.g., 28:4n‐6, 2‐OH 30:5n‐6) decreased alongside the germ cells. Concomitantly, the amounts of cholesteryl esters and ether‐linked triglycerides increased, both lipids accumulating long‐chain and very‐long‐chain polyenes. This concurred with a considerable buildup of lipid droplets in Sertoli cells, evidently containing these neutral lipids, apparently formed during germ cell‐derived membrane lipid catabolism. Between week 4 and week 6, new cohorts of spermatocytes appeared, and by week 12 most cell changes were reversed. Accordingly, as germ cell differentiation proceeded, 22:5n‐6‐rich Gpl augmented and spermatocyte‐associated sphingolipids with nonhydroxy VLCPUFA appeared before their 2‐hydroxy counterparts. The unique fatty acids of rat testicular lipids after mild hyperthermia reveal lipid catabolic and biosynthetic reactions that occur in normal spermatogenesis.
Glucokinase Regulatory Protein (GCKR) Gene rs4425043 Polymorphism is Associated with Overweight and Obesity in Chinese Women
Authors: Cao Feifei , Wang Xiaofeng , Lu Ming , Yang Yajun , An Yu , Zhang Juan , Chen Xingdong , Li Lei , Li Shuyuan , Jiang Jie , Ye Weimin , Jin Li
Published: February 2011

The aim of this study was to investigate the effects of GCKR polymorphism on the prevalence of overweight and obesity in Chinese female subjects using a gene‐wide tagging‐ single nucleotide polymorphism (tSNP) strategy. We conducted a genetic association study in the Taizhou Retiree Women Cohort, a sub‐cohort of the Taizhou longitudinal study. We genotyped four tSNPs (rs4425043, rs780094, rs814295, and rs8179206) of the GCKR gene using the Taqman assay in 2,851 female subjects and investigated their associations with overweight and obesity. Odds ratios and their 95% confidence intervals (CIs) were derived from ordered logistic regression model. We observed significant association between rs4425043 and body‐mass‐index‐defined overweight and obesity. The frequencies of A allele of the rs4425043 exhibited a significant increasing trend from normal weight (13.20%), overweight (15.08%), to obese subjects (17.10%) (P = 0.006). Individuals with the GA or AA genotypes showed a 31% excessive risk to develop overweight or obesity (95% CI: 1.12–1.52, P = 0.001). In addition, we observed significantly increased levels of fasting plasma glucose associated with variations of both rs780094 and rs814295 (5.03, 5.09, and 5.15 mmol/L for rs780094 AA, GA and GG genotypes, respectively, and 5.03, 5.11, and 5.20 mmol/L for rs814295 AA, GA and GG genotypes, respectively). In conclusion, a novel polymorphism (rs4425043) in the GCKR gene increases the risk of overweight and obesity in Chinese women. Previous report that other polymorphisms in the GCKR gene are associated with glucose levels have also been confirmed.
Reprogramming of adult human testicular cells by four transcription factors (OCT4, SOX2, KLF4, and C‐MYC)
Authors: Kobayashi Hideyuki , Nakajima Koichi , Oka Yusuke , Tai Toshihiro , Nagao Koichi , Ishii Nobuhisa
Published: February 2011

Purpose

Induced pluripotent stem (iPS) cells have been generated from mouse and human fibroblasts by several groups; however, transplanted mouse iPS cells can cause teratomas, depending on their tissue of origin. Therefore, human iPS cells are preferable, and various tissues are being evaluated for their potential to generate human iPS cells.

Methods

We examined whether adult human testicular tissue had undergone reprogramming by introducing four transcription factors, OCT4, SOX2, KLF4, and C‐MYC, using lentiviral vectors.

Results

We obtained embryonic stem (ES)‐like cells derived from human testicular tissue by introducing four cDNAs, encoding the transcription factors OCT4, SOX2, KLF4, and C‐MYC, using lentiviral vectors. We showed that DAZL and VASA were expressed in testicular cells but down‐regulated in ES‐like cells, indicating that the cells had undergone reprogramming. ES‐like cells could develop tumors, which is a hallmark of pluripotency, when SCID mice were injected with these cells.

Conclusions

We induced iPS cells from adult human testicular tissue by introducing four transcription factors, OCT4, SOX2, KLF4, and C‐MYC, using lentiviral vectors. Future studies on these cells may elucidate the causes of male infertility, and eventually lead to treatments with autologous testicular tissue‐derived iPS cells.
Two soliton collision for nonlinear Schrödinger equations in dimension 1
Authors: Perelman Galina
Published: February 2011

We study the collision of two solitons for the nonlinear Schrödinger equation

i\psi _{t} = −\psi _{xx} + F(|\psi |^{2})\psi

,

F(\xi ) = −2\xi + O(\xi ^{2})

as

\xi \rightarrow 0

, in the case where one soliton is small with respect to the other. We show that in general, the two soliton structure is not preserved after the collision: while the large soliton survives, the small one splits into two outgoing waves that for sufficiently long times can be controlled by the cubic NLS:

i\psi _{t} = −\psi _{xx}−2|\psi |^{2}\psi

.
Representation of dynamic mechanical allodynia in the ventral medial prefrontal cortex of trigeminal neuropathic rats
Authors: Devoizel Laurent , Alvarezl Pédro , Monconduitl Lénaïc , Dallell Radhouane
Published: February 2011

Trigeminal neuropathic pain is due to lesion or dysfunction of the nervous system. Dynamic mechanical allodynia is a widespread symptom of neuropathic pain for which mechanisms are still poorly understood. Recent studies demonstrate that forebrain neurons, including neurons in the medial prefrontal cortex (mPFC) are important for the perception of acute and chronic pain. Using the phosphorylation of the extracellular‐signal regulated kinase (pERK‐1/2) as an anatomical marker of neuronal activation, the present study investigated how dynamic mechanical allodynia is processed in the rat ventral mPFC (prelimbic and infralimbic cortex) after chronic constriction injury to the infraorbital nerve (IoN‐CCI). Two weeks after unilateral IoN‐CCI, rats showed a dramatic bilateral trigeminal dynamic mechanical allodynia. Light, moving stroking of the infraorbital skin resulted in strong, bilateral upregulation of pERK‐1/2 in the ventral mPFC of IoN‐CCI animals. pERK‐1/2 was located in neuronal cells only. Stimulus‐evoked pERK‐1/2 immunopositive cell bodies displayed a rostrocaudal gradient and layer‐selective distribution in the ventral mPFC, being predominant in the rostral ventral mPFC and in layers II—III and V—VI of the ventral mPFC. In layers II—III, intense pERK‐1/2 also extended into distal dendrites, up to layer I. These results demonstrate that trigeminal nerve injury induces a significant alteration in the ventral mPFC processing of tactile stimuli and suggest that ERK phosphorylation contributes to the mechanisms underlying abnormal pain perception under this condition.
The menacing phantom: What pulls the trigger?
Authors: Giummarral Melita J. , Georgiou‐Karistianisl Nellie , Nichollsl Michael E.R. , Gibsonl Stephen J. , Choul Michael , Bradshawl John L.
Published: February 2011

Phantom phenomena are frequent following amputation, but how this often painful experience is modified or triggered by spontaneous events or sensations often puzzles amputees and clinicians alike. We explored triggers of phantom phenomena in a heterogeneous sample of 264 upper and lower limb adult amputees with phantom sensations. Participants completed a structured questionnaire to determine the prevalence and nature of the triggers of phantom phenomena. The four categories of triggers identified include: (a) a quarter of participants experiencing psychological, emotional or autonomic triggers; (b) half experiencing behavioral triggers, “forgetting” the limb's absence and attempting to use the phantom; (c) one‐fifth experiencing weather‐induced triggers; and (d) one‐third experiencing sensations referred from parts of the body. Upper limb amputees; and were more likely to experience weather‐induced phantom phenomena than lower limb amputees; and upper and lower limb amputees were equally likely to experience referred sensations from the genitals, contradicting the homuncular remapping hypothesis. Traumatic amputees were more likely to report emotional triggers. Further, while those with emotional triggers exhibited poorer acceptance of the limitations of amputation, they were more likely to employ adaptive coping mechanisms. Finally, habitual “forgetting” behaviors were most common soon after amputation, whereas other more adaptive schemata (e.g., self‐defense) were equally likely to be performed at any time following amputation. Various likely inter‐related mechanisms are discussed in relation to phantom triggers. Ultimately, optimizing stump and neuroma management, as well as restoring function of central networks for pain, limb movement, and amputation‐related memories, should help manage spontaneously triggered phantom phenomena.
Circadian clock gene Per3 variants influence the postpartum onset of bipolar disorder
Authors: Dallaspezia S. , Lorenzi C. , Pirovano A. , Colombo C. , Smeraldi E. , Benedetti F.
Published: February 2011

Postpartum depression can mark the onset of bipolar disorder. The coding region of Per3 gene contains a variable-number tandem-repeat polymorphism, which has been shown to influence bipolar disorder onset and to affect breast cancer risk. We showed a relationship between Per3 polymorphism and postpartum depressive onset in bipolar disorder.
Use of the Hypomania Checklist-32 and the Mood Disorder Questionnaire for detecting bipolarity in 1,051 patients with major depressive disorder
Authors: Rybakowski J.K. , Dudek D. , Pawlowski T. , Lojko D. , Siwek M. , Kiejna A.
Published: February 2011

Purpose

To use the Hypomania Checklist (HCL-32) and the Mood Disorder Questionnaire (MDQ), for detecting bipolarity in depressed patients.

Patients

One thousand and fifty-one patients fulfilling ICD-10 criteria for unipolar major depressive episode, single or recurrent, were studied. Patients were assessed using a structured demographic and clinical data interview, and by the Polish versions of the HCL-32 and MDQ questionnaires.

Results

Hypomanic symptoms exceeding cut-off criteria for bipolarity by HCL-32 were found in 37.5% of patients and, by MDQ, in 20% of patients. Patients with HCL-32 (+) or MDQ (+) differed significantly from patients with HCl-32 (−) and MDQ (−) respectively, by being less frequently married, having more family history of depression, bipolar disorder, alcoholism and suicide, earlier onset of illness, and more depressive episodes and psychiatric hospitalizations. The percentage of patients resistant to treatment with antidepressant drugs was significantly higher in HCL-32 (+) vs HCL-32 (−) and in MDQ (+) vs MDQ (−): 43.9% vs 30.0%, and 26.4% vs 12.4%, respectively.

Conclusions

The results confirm a substantial percentage of bipolarity in major depressive disorder. Such patients have a number of clinical characteristics pointing on a more severe form of the illness and their depression is more resistant to treatment with antidepressants.
Electrocardiographic signs of autonomic imbalance in medicated patients with first-episode schizophrenia spectrum disorders – relations to first treatment discontinuation and five-year remission status
Authors: Bodén Robert , Lindström Leif , Rautaharju Pentti , Sundström Johan
Published: February 2011

Purpose

To explore measures in electrocardiograms (ECG) influenced by autonomic balance in early schizophrenia spectrum disorders and to examine their relation to subsequent first antipsychotic pharmacotherapy discontinuation and five-year remission status.

Subjects and methods

Twelve-lead ECGs were recorded at baseline in 58 patients with first-episode schizophrenia spectrum disorders and in 47 healthy controls of similar age. Selected ECG variables included heart rate and measures of repolarization. Pharmacotherapy data were extracted from medical records. At a five-year follow-up the patients were interviewed and assessed with the Positive and Negative Syndrome Scale.

Results

Patients had higher heart rate and a different ST-T pattern than the controls. High T-wave amplitudes in the leads aVF and V5 and ST-elevations in V5 were associated both with higher risk of an earlier discontinuation of first antipsychotic pharmacotherapy and with non-remission five years later.

Discussion and conclusion

In this longitudinal cohort study, simple ECG measures influenced by autonomic balance in the early phase of schizophrenia spectrum disorders contained prognostic information. As this is the first report of this association and is based on a relatively small sample, the results should be interpreted with caution.
Death by request in Switzerland: Posttraumatic stress disorder and complicated grief after witnessing assisted suicide
Authors: Wagner B. , Müller J. , Maercker A.
Published: February 2011

Background

Despite continuing political, legal and moral debate on the subject, assisted suicide is permitted in only a few countries worldwide. However, few studies have examined the impact that witnessing assisted suicide has on the mental health of family members or close friends.

Methods

A cross-sectional survey of 85 family members or close friends who were present at an assisted suicide was conducted in December 2007. Full or partial Post-Traumatic Distress Disorder (PTSD; Impact of Event Scale–Revised), depression and anxiety symptoms (Brief Symptom Inventory) and complicated grief (Inventory of Complicated Grief) were assessed at 14 to 24 months post-loss.

Results

Of the 85 participants, 13% met the criteria for full PTSD (cut-off≥35), 6.5% met the criteria for subthreshold PTSD (cut-off≥25), and 4.9% met the criteria for complicated grief. The prevalence of depression was 16%; the prevalence of anxiety was 6%.

Conclusion

A higher prevalence of PTSD and depression was found in the present sample than has been reported for the Swiss population in general. However, the prevalence of complicated grief in the sample was comparable to that reported for the general Swiss population. Therefore, although there seemed to be no complications in the grief process, about 20% of respondents experienced full or subthreshold PTSD related to the loss of a close person through assisted suicide.
The relationship between renal functions and thrombolysis in myocardial infarction frame count in patients with slow coronary flow
Authors: Koc Fatih , Kalay Nihat , Kilci Hakan , Ceyhan Koksal , Celik Atac , Kadi Hasan , Calapkorur Bekir , Celik Ahmet , Onalan Orhan
Published: February 2011

We investigated the relationship between renal function and coronary thrombolysis in myocardial infarction frame count (TFC) in patients with slow coronary flow (SCF). The patient group was composed of 34 patients with SCF. The control group was made up of 34 well‐matched individuals who have normal SCF in their coronary arteries. The coronary flow rates of all subjects were documented by TFC. Glomerular filtration rate (GFR) and corrected GFR (cGFR) were calculated by creatinine clearance according to the Cockcroft‐Gault formula. There is no difference in the gender or age of the groups. Blood urea nitrogen and creatinine were significantly higher in the SCF group compared the control group (blood urea nitrogen: 17 ± 6 mg/dL vs. 14 ± 4 mg/dL, p = 0.04 and creatine: 0.9 ± 0.1 mg/dL vs. 0.7 ± 0.1 mg/dL, p = 0.01). GFR and cGFR were significantly different between the groups (GFR: 92 ± 28 mL/min vs. 112 ± 27 mL/min, p = 0.004 and cGFR: 77 ± 22 mL/min/1.73 m2 vs. 96 ± 24 mL/min/1.73 m2, p = 0.007). There was a negative correlation between GFR/cGFR and TFC in all coronary arteries. This study shows that impaired renal function is associated with SCF. Patients with SCF have worse renal function compared with patients without SCF.
The biology of cancer testis antigens: Putative function, regulation and therapeutic potential
Authors: Fratta Elisabetta , Coral Sandra , Covre Alessia , Parisi Giulia , Colizzi Francesca , Danielli Riccardo , Marie Nicolay Hugues Jean , Sigalotti Luca , Maio Michele
Published: February 2011

Cancer testis antigens (CTA) are a large family of tumor‐associated antigens expressed in human tumors of different histological origin, but not in normal tissues except for testis and placenta. This tumor‐restricted pattern of expression, together with their strong in vivo immunogenicity, identified CTA as ideal targets for tumor‐specific immunotherapeutic approaches, and prompted the development of several clinical trials of CTA‐based vaccine therapy. Driven by this practical clinical interest, a more detailed characterization of CTA biology has been recently undertaken. So far, at least 70 families of CTA, globally accounting for about 140 members, have been identified. Most of these CTA are expressed during spermatogenesis, but their function is still largely unknown. Epigenetic events, particularly DNA methylation, appear to be the primary mechanism regulating CTA expression in both normal and transformed cells, as well as in cancer stem cells. In view of the growing interest in CTA biology, the aim of this review is to provide the most recent information on their expression, regulation and function, together with a brief summary of the major clinical trials involving CTA as therapeutic agents. The pharmacologic modulation of CTA expression profiles on neoplastic cells by DNA hypomethylating drugs will also be discussed as a feasible approach to design new combination therapies potentially able to improve the clinical efficacy of currently adopted CTA‐based immunotherapeutic regimens in cancer patients.
The potential lateral growth of lithalsas
Authors: Pissart Albert , Calmels Fabrice , Wastiaux Cécile
Published: February 2011

The lithalsas in the Hudson Bay region of northern Québec, Canada, are the closest modern analogs of ancient features that collapsed to form conspicuous circular depressions (“viviers”) common in the Hautes-Fagnes, a region in Belgium. Observations made in both regions are complementary and suggest that these mounds formed by frost heaving displacing soil not only upward, as previously assumed, but also laterally. This lateral displacement is consistent with diverse observations and inferences, which include (1) the simple rounded outline, either circular or oval, typical of both active and relic lithalsas; (2) evidence of local lateral extension inferred from exposures of the relic forms; (3) the relative inefficiency of solifluction in accumulating surface material to form the peripheral ramparts of remnant lithalsas due to the very gentle slopes of the mounds; and (4) the dip of ice lenses within a lithalsa in the Hudson Bay region, perhaps indicating that the freezing front dipped outward along its periphery. The growth of segregation ice is the primary driver for the vertical growth and lateral enlargement of a lithalsa.