bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

AbstractMedullary 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

AbstractBased 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

AbstractMany 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

AbstractBACKGROUND: 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

AbstractWorldwide 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

AbstractBackgroundAdenovirus (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.MethodsThe 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.ResultsThe 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.ConclusionsThe 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

AbstractBACKGROUND: 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

Abstract2‐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

AbstractTwo 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

AbstractBody 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

AbstractObjectiveThe 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.MethodsMultiple 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.ResultsWe 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.ConclusionWhile 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

AbstractStrahlentherapie 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

AbstractRNA 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.75This 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

AbstractThe 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.