bluuebunny/crossref_metadata_2025 huggingface dataset:
Flashing light signaling circuit in sponges: Endogenous light generation after tissue ablation in Suberites domuncula
Authors: Wiens Matthias , Wang Xiaohong , Unger Andreas , Schröder Heinz C. , Grebenjuk Vladislav A. , Pisignano Dario , Jochum Klaus P. , Müller Werner E.G.
Published: September 2010

The skeleton of siliceous sponges (phylum Porifera: classes Demospongiae and Hexactinellida), composed of tightly interacting spicules that assemble to a genetically fixed scaffold, is formed of bio‐silica. This inorganic framework with the quality of quartz glass has been shown to operate as light waveguide in vitro and very likely has a similar function in vivo. Furthermore, the molecular toolkit for endogenous light generation (luciferase) and light/photon harvesting (cryptochrome) has been identified in the demosponge Suberites domuncula. These three components of a light signaling system, spicules—luciferase—cryptochrome, are concentrated in the surface layers (cortex) of the poriferan body. Specimens from which this cortex has been removed/ablated do not emit light. However, with regeneration and reconstitution of the cortex the animals re‐gain the capacity to flash light. This newly discovered characteristic of sponges to generate light prompted us to investigate the genetic basis for the endogenous light signaling system. As a potential transcription factor involved in the expression of luciferase and cryptochrome, a SOX‐related protein has been identified. In dark‐adapted animals or in tissue from below the cortex region, the medulla, no gene or protein expression of SOX‐related protein, luciferase, and cryptochrome could be detected. However, during the regeneration of the cortex, a stage‐specific expression pattern was recorded: SOX‐related protein > luciferase > cryptochrome. We conclude that a flashing light signaling circuit exists, which might control the retinoic acid‐induced differentiation of stem cells into pulsating and contracting sponge cells, that is, pinacocytes and myocytes. J. Cell. Biochem. 111: 1377–1389, 2010. © 2010 Wiley‐Liss, Inc.
PTEN suppression promotes neurite development exclusively in differentiating PC12 cells via PI3‐kinase and MAP kinase signaling
Authors: Jia Lintao , Ji Shaoping , Maillet Jean‐Christian , Zhang Xia
Published: September 2010

As a dual‐specificity phosphatase catalyzing the dephosphorylation of phosphatidylinositols and protein substrates, PTEN is critically involved in the nervous system development. However, the regulatory role of PTEN in neurite outgrowth is still controversial, and the downstream signaling events remain elusive. Here, we show that PTEN knockdown promoted the proliferation and survival but not the neurite outgrowth of rat pheochromocytoma PC12 cells when exposed to nerve growth factor (NGF). In contrast, selective PTEN silencing in differentiating PC12 cells that express nestin significantly facilitated neurite elongation. Elevated Akt and Erk1/2 phosphorylation was involved in accelerated NGF‐induced neurite development of PC12 cells following PTEN knockdown. Discriminated roles of the lipid phosphatase and protein phosphatase activities of PTEN in neurite development, as well as the detailed molecular profiles affected by these phosphatase activities, were defined by restored expression of a lipid phosphatase‐deficient PTEN mutant following endogenous PTEN silencing in PC12 cells. Our study suggests an overall inhibitory effect of PTEN in neurite development reconciled by a probably indispensable role of this phosphatase in the initiation of PC12 cell differentiation. J. Cell. Biochem. 111: 1390–1400, 2010. © 2010 Wiley‐Liss, Inc.
Changes in cell adhesivity and cytoskeleton‐related proteins during imatinib‐induced apoptosis of leukemic JURL‐MK1 cells
Authors: Kuželová K. , Pluskalová M. , Grebeňová D. , Pavlásková K. , Halada P. , Hrkal Z.
Published: September 2010

The fusion protein Bcr–Abl, which is the molecular cause of chronic myelogenous leukemia (CML) interacts in multiple points with signaling pathways regulating the cellular adhesivity and cytoskeleton architecture and dynamics. We explored the effects of imatinib mesylate, an inhibitor of Bcr–Abl protein used in front‐line CML therapy, on the adhesivity of JURL‐MK1 cells to fibronectin and searched for underlying changes in the cell proteome. As imatinib induces apoptosis of JURL‐MK1 cells, we used three different caspase inhibitors to discriminate between direct consequences of Bcr–Abl inhibition and secondary changes related to the apoptosis. Imatinib treatment caused a transient increase in JURL‐MK1 cell adhesivity to fibronectin, possibly due to the switch off of Bcr–Abl activity. Subsequently, we observed a number of changes including a decrease in cell adhesivity, F‐actin decomposition, reduction of integrin β1, CD44, and paxillin expression levels and a marked increase in cofilin phophorylation at Ser3. These events were generally related to the proceeding apoptosis but they differed in their sensitivity to the individual caspase inhibitors. J. Cell. Biochem. 111: 1413–1425, 2010. © 2010 Wiley‐Liss, Inc.
Identification of new modulators and protein alterations in non‐apoptotic programmed cell death
Authors: Sperandio Sabina , Poksay Karen S. , Schilling Birgit , Crippen Danielle , Gibson Bradford W. , Bredesen Dale E.
Published: September 2010

This study describes the first proteomic analysis of paraptosis—a non‐apoptotic form of programmed cell death. As with apoptosis, the first description of paraptosis was based on morphological criteria. Since there are no known markers for paraptosis, the purpose of this study was to dissect changes in the proteome profile occurring during paraptosis. Using one‐ and two‐dimensional SDS–PAGE, Western analysis, and mass spectrometry, we show that during paraptosis, alterations occur mainly in cytoskeletal proteins, signal transduction proteins, mitochondrial proteins, and some metabolic proteins. We also report the identification of: (1) a paraptosis inhibitor, phosphatidylethanolamine binding protein (PEBP‐1), and (2) a candidate mediator of paraptosis, prohibitin. Identification of specific paraptotic changes will ultimately lead to tools to detect this type of programmed cell death in in vivo systems and allow for its further characterization. J. Cell. Biochem. 111: 1401–1412, 2010. © 2010 Wiley‐Liss, Inc.
Low‐level laser irradiation enhances BMP‐induced osteoblast differentiation by stimulating the BMP/Smad signaling pathway
Authors: Hirata Shizu , Kitamura Chiaki , Fukushima Hidefumi , Nakamichi Ikuo , Abiko Yoshimitsu , Terashita Masamichi , Jimi Eijiro
Published: September 2010

Low‐level laser irradiation (LLLI) has been shown to induce bone formation and osteoblast differentiation both in vivo and in vitro. However, the molecular mechanism by which LLLI stimulates osteoblast differentiation is still unclear. The aim of the present study was to examine whether Ga‐Al‐As laser irradiation could enhance BMP2‐induced alkaline phosphatase (ALP) activity in C2C12 cells. Laser irradiation at 0.5 W for 20 min enhanced BMP2‐induced ALP activity. Laser treatment alone did not affect ALP activity. To exclude the effect of pH or temperature changes during irradiation, we shortened the exposure time to 2 min, with various levels of laser power. At 2.5 W, irradiation stimulated BMP2‐induced ALP activity but not cell proliferation, whereas 1 or 5 W laser power did not induce any significant effects. Irradiation stimulated BMP2‐induced phosphorylation of Smad1/5/8 and BMP2 expression, but had no effect on the expression of inhibitory Smads 6 and 7, BMP4, or insulin‐like growth factor 1. Laser irradiation enhanced Smad‐induced Id1 reporter activity as well as expression of bone morphogenetic protein (BMP)‐induced transcription factors such as Id1, Osterix, and Runx2. Laser irradiation also stimulated BMP‐induced expressions of type I collagen, osteonectin, and osteocalcin mRNA, markers of osteoblasts. This enhancement of BMP2‐induced ALP activity and Smad phosphorylation by laser irradiation was also observed in primary osteoblasts. These results suggest that LLLI accelerates the differentiation of BMP‐induced osteoblasts by stimulating the BMP/Smad signaling pathway. J. Cell. Biochem. 111: 1445–1452, 2010. © 2010 Wiley‐Liss, Inc.
Anti‐fibrotic effect of chorionic plate‐derived mesenchymal stem cells isolated from human placenta in a rat model of CCl4‐injured liver: Potential application to the treatment of hepatic diseases
Authors: Lee Min‐Jae , Jung Jieun , Na Kyu‐Hwan , Moon Ji Suk , Lee Hey‐Jin , Kim Jae‐Hwan , Kim Gwang Il , Kwon Sung‐Won , Hwang Seong‐Gyu , Kim Gi Jin
Published: September 2010

Translational studies have explored the therapeutic effects of stem cells, raising hopes for the treatment of numerous diseases. Here, we evaluated the therapeutic effect of chorionic plate‐derived mesenchymal stem cells (CP‐MSCs) isolated from human placenta and transplanted into rats with carbon tetrachloride (CCl4)‐injured livers. CP‐MSCs were analyzed for hepatocyte‐specific gene expression, indocyanine green (ICG) uptake, glycogen storage, and urea production following hepatogenic differentiation. PKH26‐labeled CP‐MSCs were directly transplanted into the livers of rats that had been exposed to CCl4 (1.6 g/kg, twice per week for 9 weeks). Blood and liver tissue were analyzed at 1, 2, and 3 weeks post‐transplantation. The expression of type I collagen (Col I) and matrix metalloproteinases (MMPs) was analyzed in rat T‐HSC/Cl‐6 hepatic stellate cells co‐cultured with CP‐MSCs following exposure to TGF‐β. The expression levels of α‐smooth muscle actin (α‐SMA) and Col I were lower in transplanted (TP) rats than in non‐transplanted (Non‐TP) animals (P < 0.05), whereas the expression levels of albumin and MMP‐9 were increased. TP rats exhibited significantly higher uptake/excretion of ICG than non‐TP rats (P < 0.005). In addition, collagen synthesis in T‐HSC/Cl‐6 cells exposed to TGF‐β was decreased by co‐culture with CP‐MSCs, which triggered the activation of MMP‐2 and MMP‐9. These results contribute to our understanding of the potential pathophysiological roles of CP‐MSCs, including anti‐fibrotic effects in liver disease, and provide a foundation for the development of new cell therapy‐based strategies for the treatment of difficult‐to‐treat liver diseases. J. Cell. Biochem. 111: 1453–1463, 2010. © 2010 Wiley‐Liss, Inc.
Sorting nexin 6 interacts with breast cancer metastasis suppressor‐1 and promotes transcriptional repression
Authors: Rivera José , Megías Diego , Bravo Jerónimo
Published: September 2010

Sorting nexin 6 (SNX6), a predominantly cytoplasmic protein involved in intracellular trafficking of membrane receptors, was identified as a TGF‐β family interactor. However, apart from being a component of the Retromer, little is known about SNX6 cellular functions. Pim‐1‐dependent SNX6 nuclear translocation has been reported suggesting a putative nuclear role for SNX6. Here, we describe a previously non‐reported association of SNX6 with breast cancer metastasis suppressor 1 (BRMS1) protein detected by a yeast two‐hybrid screening. The interaction can be reconstituted in vitro and further FRET analysis confirmed the novel interaction. Additionally, we identified their coiled‐coil domains as the minimal binding motives required for interaction. Since BRMS1 has been shown to repress transcription, we sought the ability of SNX6 to interfere with this nuclear activity. Using a standard gene reporter assay, we observed that SNX6 increases BRMS1‐dependent transcriptional repression. Moreover, over‐expression of SNX6 was capable of diminishing trans‐activation in a dose‐dependent manner. J. Cell. Biochem. 111: 1464–1472, 2010. © 2010 Wiley‐Liss, Inc.
Ionic liquid enables simple and rapid sample preparation of human culturing cells for scanning electron microscope analysis
Authors: Ishigaki Yasuhito , Nakamura Yuka , Takehara Teruaki , Nemoto Noriko , Kurihara Takayuki , Koga Hironori , Nakagawa Hideaki , Takegami Tsutomu , Tomosugi Naohisa , Miyazawa Shichiro , Kuwabata Susumu
Published: September 2010

Ionic liquid is a kind of salt that stays in a molten state even at room temperature. It does not vaporize at all in vacuum and facilitates electrical conductivity to the sample surfaces for observations with a scanning electron microscope (SEM). In this study, we used an ionic liquid in SEM for the first time to observe fixed human culture cells. The condition for the cell culture using wrapping sheets and SEM settings were varied to elucidate the optimized protocol. Compared to samples prepared by the conventional way, the ionic liquid‐treatment of samples gave SEM images of the cellular ultra structures in more detail, enabling observation of microvilli that made bridges between separated cells. In addition, the ionic liquid treatment is less time consuming as well as less laborious compared with the conventional way that includes dehydration, drying, and conductivity treatments. Totally, we concluded the ionic liquid is a useful reagent for SEM sample preparation. Microsc. Res. Tech., 2011. © 2010 Wiley‐Liss, Inc.
Freeze substitution followed by low melting point wax embedding preserves histomorphology and allows protein and mRNA localization techniques
Authors: Durán Iván , Marí‐Beffa Manuel , Santamaría Jesús A. , Becerra José , Santos‐Ruiz Leonor
Published: September 2010

Fixation and embedding are major steps in tissue preservation for histological analysis. However, conventional fixatives like aldehyde‐based solutions usually mask tissular epitopes preventing their immunolocalization. Alternative fixation methods used to avoid this drawback, such as cryopreservation, alcohol‐ or zinc salts‐based fixatives do not efficiently preserve tissue and cell morphology. Likewise, paraffin and resin embedding, commonly used for thin sectioning, frequently damage epitopes due to the clearing agents and high temperatures needed along the embedding procedure. Alternatives like cryosectioning avoid the embedding steps but yield sections of poorer quality and are not suitable for all kinds of samples. To overcome these handicaps, we have developed a method that preserves histoarchitecture as well as tissue antigenic properties. This method, which we have named CryoWax, involves freeze substitution of the samples in isopentane and methanol, followed by embedding in low melting point polyester wax. CryoWax has proven efficient in obtaining thin sections of embryos and adult tissues from different species, including amphioxus, zebrafish, and mouse. CryoWax sections displayed optimal preservation of tissue morphology and were successfully immunostained for fixation‐ and temperature‐sensitive antigens. Furthermore, CryoWax has been tested for in situ hybridization application, obtaining positive results. Microsc. Res. Tech., 2011. © 2010 Wiley‐Liss, Inc.
A selective synthesis of enamines versus aziridines
Authors: Belei Dalila , Bicu Elena , Jones Peter G. , Birsa M. Lucian
Published: September 2010

The reaction of 10‐azidoacetyl‐10H‐phenothiazine with olefinic dipolarophiles depends on the reaction temperature. In refluxing toluene, a mixture of enamine and aziridine is formed in 3:1 ratio. The reaction mechanism appears to involve a Michael‐type addition of the nucleophilic N1 azide atom to the olefinic double bond. In chloroform, a cycloaddition reaction takes place with the formation of a 4,5‐dihydro‐1,2,3‐triazole. The heating of dihydrotriazoles in toluene is accompanied by nitrogen elimination leading to a mixture of enamine and aziridine in 1:3 ratio. J. Heterocyclic Chem., 2011.
Comparison of patellar bone strain in the natural and implanted knee during simulated deep flexion
Authors: Fitzpatrick Clare K. , Baldwin Mark A. , Ali Azhar A. , Laz Peter J. , Rullkoetter Paul J.
Published: September 2010

Instances of anterior knee pain and patellar fracture are significant complications following total knee replacement (TKR). Bone strain measured in the patella can provide an indication of patellar fracture risk and may also be related to anterior knee pain. The objective of this study was to develop subject‐specific finite element models of the patellofemoral (PF) joint including density‐mapped material properties to gain insight into the patellar bone strain distribution in the natural and implanted knee. In eight subjects, the volume of bone experiencing strains >0.5% in the implanted condition was ∼200% larger, on average, than the natural condition. An inverse relationship with a correlation of −0.74 was established between postoperative bone volume and strain in the implanted specimens, suggesting that patellar geometry may be a useful indicator of postoperative strain. Comparing strains between regions (superior, inferior, medial, and lateral), it was found that although highly strained bone was evenly distributed between medial and lateral regions in the natural case, the implanted specimens demonstrated significantly larger volumes of highly strained bone medially as a result of substantially lower modulus bone in the medial compartment. Understanding distributions of PF strain may aid in preoperative identification of those patients at risk for patellar fracture or anterior knee pain, guidance regarding altered component placement for at‐risk patients, and design of components considering the implications of PF load transfer and patellar strain distribution. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:232–239, 2011
Effects of smoking on taste: Assessment with contact endoscopy and taste strips
Authors: Konstantinidis Iordanis , Chatziavramidis Angelos , Printza Athanasia , Metaxas Spyros , Constantinidis Jannis
Published: September 2010

Objectives:

This study aims to compare the taste function between smokers and nonsmokers with clinical testing, subjective ratings, and contact endoscopy of the tongue.

Study Design:

Cross‐sectional survey.

Methods:

Data were collected from 38 smokers (mean age 37 years; 25 female, 23 male) and 34 nonsmokers (mean age 33.5 years; 18 female, 16 male). The parameters assessed were the number of fungiform papillae per square centimeter in a noncontact way and their morphology (surface, capillary vessels) by contact endoscopy. The morphology of the filiform papillae has also been assessed. In addition, clinical testing of gustatory function was performed by means of taste strips and subjective intensity ratings of natural taste stimuli.

Results:

No significant difference was found in clinical testing and intensity ratings between the two study groups. A trend toward significance was found in taste strip results for decreased bitter taste in heavy smokers (P = .06). The number and the size of fungiform papillae did not significantly differ between the study groups. No sex‐related differences were observed. Smokers exhibited significantly more keratin structures on the fungiform papillae surface, less tortuous capillary vessels, and a significant distortion of their filiform papillae.

Conclusions:

Taste function presents significant resistance to smoking, although changes in morphology of fungiform and filiform papillae have been observed especially in heavy smokers. Laryngoscope, 2010
Laser stimulation of single auditory nerve fibers
Authors: Littlefield Philip D. , Vujanovic Irena , Mundi Jagmeet , Matic Agnella Izzo , Richter Claus‐Peter
Published: September 2010

Objectives/Hypothesis:

One limitation with cochlear implants is the difficulty stimulating spatially discrete spiral ganglion cell groups because of electrode interactions. Multipolar electrodes have improved on this some, but also at the cost of much higher device power consumption. Recently, it has been shown that spatially selective stimulation of the auditory nerve is possible with a mid‐infrared laser aimed at the spiral ganglion via the round window. However, these neurons must be driven at adequate rates for optical radiation to be useful in cochlear implants. We herein use single‐fiber recordings to characterize the responses of auditory neurons to optical radiation.

Study Design:

In vivo study using normal‐hearing adult gerbils.

Methods:

Two diode lasers were used for stimulation of the auditory nerve. They operated between 1.844 μm and 1.873 μm, with pulse durations of 35 μs to 1,000 μs, and at repetition rates up to 1,000 pulses per second (pps). The laser outputs were coupled to a 200‐μm‐diameter optical fiber placed against the round window membrane and oriented toward the spiral ganglion. The auditory nerve was exposed through a craniotomy, and recordings were taken from single fibers during acoustic and laser stimulation.

Results:

Action potentials occurred 2.5 ms to 4.0 ms after the laser pulse. The latency jitter was up to 3 ms. Maximum rates of discharge averaged 97 ± 52.5 action potentials per second. The neurons did not strictly respond to the laser at stimulation rates over 100 pps.

Conclusions:

Auditory neurons can be stimulated by a laser beam passing through the round window membrane and driven at rates sufficient for useful auditory information. Optical stimulation and electrical stimulation have different characteristics; which could be selectively exploited in future cochlear implants. Laryngoscope, 2010
A Nanosegregant Approach to Superwettable and Water‐Attracting Surfaces
Authors: Xie Xian Ning , Lim Sharon Xiaodai , Wang Yuzhan , Gao Xingyu , Lee Kian Keat , Sow Chorng Haur , Chen Xiaohong , Loh Kian Ping , Wee Andrew Thye Shen
Published: September 2010

A simple and economical approach to the preparation of superhydrophilic and water‐capturing surfaces is reported. In this method, a common polymer aqueous blend is drop‐cast onto a substrate, and the natural drying of the aqueous drop allows for the formation of phase‐segregated nanosegregants between the bulk film and substrate surface. The nanosegregant is then exposed by dissolving the bulk film using water. The nanosegregant is stable, water‐insoluble and optically transparent, and exhibits superhydrophilicity with a minimum contact angle below 10°. It also displays strong water‐attracting ability. The mechanism of superwettability and water‐capturing behavior is discussed in terms of the self‐organization and functional group of the nanosegregant.

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Enhanced in vivo Magnetic Resonance Imaging of Tumors by PEGylated Iron‐Oxide–Gold Core–Shell Nanoparticles with Prolonged Blood Circulation Properties
Authors: Kumagai Michiaki , Sarma Tridib Kumar , Cabral Horacio , Kaida Sachiko , Sekino Masaki , Herlambang Nicholas , Osada Kensuke , Kano Mitsunobu R. , Nishiyama Nobuhiro , Kataoka Kazunori
Published: September 2010

High‐density poly(ethylene glycol) (PEG)‐coated iron‐oxide–gold core–shell nanoparticles (AuIONs) were developed as T2‐weighted magnetic resonance imaging (MRI) contrast agents for cancer imaging. The PEG‐coated iron‐oxide–gold core–shell nanoparticles (PEG‐AuIONs) were approximately 25 nm in diameter with a narrow distribution. Biodistribution experiments in mice bearing a subcutaneous colon cancer model prepared with C26 murine colon adenocarcinoma cells showed high accumulation of the PEG‐AuIONs within the tumor mass and low nonspecific accumulation in the liver and spleen, resulting in high specificity to solid tumors. T2‐weighted MR images following intravenous injection of PEG‐AuIONs showed selective negative enhancement of tumor tissue in an orthotopic pancreatic cancer model prepared with MiaPaCa‐2 human pancreatic adenocarcinoma cells. These results indicate that PEG‐AuIONs are a promising MRI contrast agent for diagnosis of malignant tumors, including pancreatic cancer.

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Role of AMPK throughout meiotic maturation in the mouse oocyte: Evidence for promotion of polar body formation and suppression of premature activation
Authors: Downs Stephen M. , Ya Ru , Davis Christopher C.
Published: September 2010

This study was conducted to assess the role of AMPK in regulating meiosis in mouse oocytes from the germinal vesicle stage to metaphase II. Exposure of mouse cumulus cell‐enclosed oocytes (CEO) and denuded oocytes (DO) during spontaneous maturation in vitro to AMPK‐activating agents resulted in augmentation of the rate and frequency of polar body formation. Inhibitors of AMPK had an opposite, inhibitory effect. In addition, the AMPK inhibitor, compound C (Cmpd C) increased the frequency of oocyte activation. The stimulatory action of the AMPK‐activating agent, AICAR, and the inhibitory action of Cmpd C were diminished if exposure was delayed, indicating an early action of AMPK on polar body formation. The frequency of spontaneous and Cmpd C‐induced activation in CEO was reduced as the period of hormonal priming was increased, and AMPK stimulation eliminated the activation response. Immunostaining of oocytes with antibody to active AMPK revealed an association of active kinase with chromatin, spindle poles, and midbody during maturation. Immunolocalization of the α1 catalytic subunit of AMPK showed an association with condensed chromatin and the meiotic spindle but not in the spindle poles or midbody; α2 stained only diffusely throughout the oocyte. These data suggest that AMPK is involved in a regulatory capacity throughout maturation and helps promote the completion of meiosis while suppressing premature activation. Mol. Reprod. Dev. 77:888–899, 2010. © 2010 Wiley‐Liss, Inc.
Genetic modifiers of HbF and response to hydroxyurea in sickle cell disease
Authors: Green Nancy S. , Barral Sandra
Published: September 2010

Fetal hemoglobin (HbF) levels are generally inversely proportional to severity of sickle cell disease (SCD) for given sickle phenotypes. Molecular regulation of HbF occurs through complex interactions cis and trans to the beta globin gene locus. Novel insights made through population‐based genetic epidemiologic studies of non‐anemic populations were replicated in SCD groups, despite large differences in HbF levels. Identification of the lymphoid transcription factor BCL11A as a key suppressor of HbF expression validates approaches using population genetics to study HbF expression. We review these methods and findings, and speculate on applying pharmaco‐genetics to optimize hydroxyurea therapy aimed at increasing HbF. Pediatr Blood Cancer 2011;56:177–181. © 2010 Wiley‐Liss, Inc.
Isolated extracranial recurrence of anaplastic ependymoma
Authors: Chao Mwe Mwe , Packer Roger J. , Myseros John S. , Rood Brian R.
Published: September 2010

Anaplastic ependymoma is a malignant glial tumor thought to arise from radial glial cells of the ventricular zone. Because ependymoma is frequently encountered within ventricular spaces, they are prone to leptomeningeal dissemination. Metastatic extracranial ependymoma has been reported, but in the context of progressive intracranial disease. We report on a boy who developed isolated extracranial recurrence of his anaplastic ependymoma, initially at the scalp and later metastases to cervical lymph nodes. The location of tumor recurrence proximate to the surgical site suggested surgical seeding. This case demonstrates an unusual site of recurrence of anaplastic ependymoma and highlights a previously underappreciated surgical complication. Pediatr Blood Cancer 2011;56:317–318. © 2010 Wiley‐Liss, Inc.
Thyroid and hepatic function after high‐dose 131I‐metaiodobenzylguanidine (131I‐MIBG) therapy for neuroblastoma
Authors: Quach Alekist , Ji Lingyun , Mishra Vikash , Sznewajs Aimee , Veatch Janet , Huberty John , Franc Benjamin , Sposto Richard , Groshen Susan , Wei Denice , Fitzgerald Paul , Maris John M. , Yanik Gregory , Hawkins Randall A. , Villablanca Judith G. , Matthay Katherine K.
Published: September 2010

Background

131I‐Metaiodobenzylguanidine (131I‐MIBG) provides targeted radiotherapy for children with neuroblastoma, a malignancy of the sympathetic nervous system. Dissociated radioactive iodide may concentrate in the thyroid, and 131I‐MIBG is concentrated in the liver after 131I‐MIBG therapy. The aim of our study was to analyze the effects of 131I‐MIBG therapy on thyroid and liver function.

Procedure

Pre‐ and post‐therapy thyroid and liver functions were reviewed in a total of 194 neuroblastoma patients treated with 131I‐MIBG therapy. The cumulative incidence over time was estimated for both thyroid and liver toxicities. The relationship to cumulative dose/kg, number of treatments, time from treatment to follow‐up, sex, and patient age was examined.

Results

In patients who presented with Grade 0 or 1 thyroid toxicity at baseline, 12 ± 4% experienced onset of or worsening to Grade 2 hypothyroidism and one patient developed Grade 2 hyperthyroidism by 2 years after 131I‐MIBG therapy. At 2 years post‐131I‐MIBG therapy, 76 ± 4% patients experienced onset or worsening of hepatic toxicity to any grade, and 23 ± 5% experienced onset of or worsening to Grade 3 or 4 liver toxicity. Liver toxicity was usually transient asymptomatic transaminase elevation, frequently confounded by disease progression and other therapies.

Conclusion

The prophylactic regimen of potassium iodide and potassium perchlorate with 131I‐MIBG therapy resulted in a low rate of significant hypothyroidism. Liver abnormalities following 131I‐MIBG therapy were primarily reversible and did not result in late toxicity. 131I‐MIBG therapy is a promising treatment for children with relapsed neuroblastoma with a relatively low rate of symptomatic thyroid or hepatic dysfunction. Pediatr Blood Cancer 2011;56:191–201. © 2010 Wiley‐Liss, Inc.
Increasing prevalence of nasal and rectal colonization with methicillin‐resistant Staphylococcus aureus in children with cancer
Authors: Srinivasan Ashok , Seifried Steven E. , Zhu Liang , Srivastava Deo K. , Perkins Rosalie , Shenep Jerry L. , Bankowski Matthew J. , Hayden Randall T.
Published: September 2010

Background

Infections with methicillin‐resistant Staphylococcus aureus (MRSA), in community‐settings, especially with strains carrying the Panton‐Valentine Leukocidin (PVL) genes, have increased markedly in recent years. Colonization with S. aureus is a risk factor for infection. However, there are few studies that examine colonization and infection with PVL‐positive strains of MRSA in cancer patients.

Procedure

The epidemiology of colonization and infection with MRSA was studied in children with cancer during two time periods: 2000/2001 and 2006/2007. PVL genes were screened and spa typing performed on the isolates.

Results

The prevalence of colonization with MRSA increased from 0.6% in 2000/2001 to 2.9% in 2006/2007 (P = 0.0003). MRSA colonization at admission was associated with infection (P < 0.0001; RR 38.32; 95% CI: 23.36–62.84). The prevalence of infection increased from 0.99% in 2000/2001 to 3.78% in 2006–2007 (P = 0.0002). Of the 32 colonized patients, 18 (56%) had infection. None of the 14 colonized but non‐infected patients had dual colonization of nares and rectum, while 8 of the 18 infected patients had colonization of both of these sites (P = 0.004). Ten patients (31%) were colonized with PVL‐positive strains. Patients colonized with PVL‐positive strains were more likely to be colonized both in the nares and rectum (P = 0.005), and more likely to have infection (P = 0.001). Recurrent MRSA infections were seen in 22% of patients.

Conclusion

An increasing prevalence of colonization with MRSA was observed in children with cancer at our institution. Colonization with MRSA especially with PVL‐positive strains was associated with infection. Pediatr Blood Cancer. 2010;55:1317–1322. © 2010 Wiley‐Liss, Inc.
Contactless measurement of minority carrier lifetime in silicon ingots and bricks
Authors: Swirhun James S. , Sinton Ronald A. , Forsyth M. Keith , Mankad Tanaya
Published: September 2010

Measuring the bulk lifetime of unpassivated blocks and ingots is of great interest to the solar cell industry. The eddy‐current photoconductance method is a common choice for such measurements, employing the quasi‐steady‐state (QSS) mode for lower lifetime samples, and the transient photoconductance decay (PCD) mode for higher lifetime samples. Due to the high surface recombination velocity in unpassivated bulk samples, the lifetime measured with this method consists of components of recombination at both the surface and in the bulk. In order to determine the bulk lifetime from the measurement data, simulations of both transient and QSS mode measurements were conducted. Copyright © 2010 John Wiley & Sons, Ltd.
Identification of Leishmania‐specific protein phosphorylation sites by LC‐ESI‐MS/MS and comparative genomics analyses
Authors: Hem Sonia , Gherardini Pier Federico , Fortéa José Osorio y , Hourdel Veronique , Morales Miguel A. , Watanabe Reiko , Pescher Pascale , Kuzyk Michael A. , Smith Derek , Borchers Christoph H. , Zilberstein Dan , Helmer‐Citterich Manuela , Namane Abdelkader , Späth Gerald F.
Published: September 2010

Human pathogenic protozoa of the genus Leishmania undergo various developmental transitions during the infectious cycle that are triggered by changes in the host environment. How these parasites sense, transduce, and respond to these signals is only poorly understood. Here we used phosphoproteomic approaches to monitor signaling events in L. donovani axenic amastigotes, which may be important for intracellular parasite survival. LC‐ESI‐MS/MS analysis of IMAC‐enriched phosphoprotein extracts identified 445 putative phosphoproteins in two independent biological experiments. Functional enrichment analysis allowed us to gain insight into parasite pathways that are regulated by protein phosphorylation and revealed significant enrichment in our data set of proteins whose biological functions are associated with protein turn‐over, stress response, and signal transduction. LC‐ESI‐MS/MS analysis of TiO2‐enriched phosphopeptides confirmed these results and identified 157 unique phosphopeptides covering 181 unique phosphorylation sites in 126 distinct proteins. Investigation of phosphorylation site conservation across related trypanosomatids and higher eukaryotes by multiple sequence alignment and cluster analysis revealed L. donovani‐specific phosphoresidues in highly conserved proteins that share significant sequence homology to orthologs of the human host. These unique phosphorylation sites reveal important differences between host and parasite biology and post‐translational protein regulation, which may be exploited for the design of novel anti‐parasitic interventions.
Characterization of multiple alternative forms of heterogeneous nuclear ribonucleoprotein K by phosphate‐affinity electrophoresis
Authors: Kimura Yayoi , Nagata Kayoko , Suzuki Nobutake , Yokoyama Ryo , Yamanaka Yuko , Kitamura Hiroshi , Hirano Hisashi , Ohara Osamu
Published: September 2010

The phosphorylation of heterogeneous nuclear ribonucleoprotein K (hnRNP K) is thought to play an important role in cell regulation and signal transduction. However, the relationship between hnRNP K phosphorylation and cellular events has only been indirectly examined, and the phosphorylated forms of endogenous hnRNP K have not been biochemically characterized in detail. In this study, we extensively examined the phosphorylated forms of endogenous hnRNP K by direct protein–chemical characterization using phosphate‐affinity electrophoresis followed by immunoblotting and MS. Phosphate‐affinity electrophoresis enabled us to sensitively detect and separate the phosphorylated forms of hnRNP K. When we used 2‐DE with phosphate‐affinity SDS‐PAGE in the second dimension, the nuclear fraction contained more than 20 spots of endogenous hnRNP K on the 2‐D map. We determined that the multiple forms of hnRNP K were produced mainly by alternative splicing of the single hnRNP K gene and phosphorylation of Ser116 and/or Ser284. Furthermore, the subcellular localization of these proteins revealed by the 2‐D gel correlated with their phosphorylation states and alternative splicing patterns. The results also indicated that the multiple forms of hnRNP K were differentially modulated in response to external stimulation with bacterial lipopolysaccharide or serum.
Molecular characterization of a trafficking organelle: Dissecting the axonal paths of calsyntenin‐1 transport vesicles
Authors: Steuble Martin , Gerrits Bertran , Ludwig Alexander , Mateos José María , Diep Tu‐My , Tagaya Mitsuo , Stephan Alexander , Schätzle Philipp , Kunz Beat , Streit Peter , Sonderegger Peter
Published: September 2010

Kinesin motors play crucial roles in the delivery of membranous cargo to its destination and thus for the establishment and maintenance of cellular polarization. Recently, calsyntenin‐1 was identified as a cargo‐docking protein for Kinesin‐1‐mediated axonal transport of tubulovesicular organelles along axons of central nervous system neurons. To further define the function of calsyntenin‐1, we immunoisolated calsyntenin‐1 organelles from murine brain homogenates and determined their proteome by MS. We found that calsyntenin‐1 organelles are endowed with components of the endosomal trafficking machinery and contained the β‐amyloid precursor protein (APP). Detailed biochemical analyses of calsyntenin‐1 immunoisolates in conjunction with immunocytochemical colocalization studies with cultured hippocampal neurons, using endosomal marker proteins for distinct subcompartments of the endosomal pathways, indicated that neuronal axons contain at least two distinct, nonoverlapping calsyntenin‐1‐containing transport packages: one characterized as early‐endosomal, APP positive, the other as recycling‐endosomal, APP negative. We postulate that calsyntenin‐1 acts as a general mediator of anterograde axonal transportation of endosomal vesicles. In this role, calsyntenin‐1 may actively contribute to axonal growth and pathfinding in the developing as well as to the maintenance of neuronal polarity in the adult nervous system; further, it may actively contribute to the stabilization of APP during its anterograde axonal trajectory.
Computational studies of colicin insertion into membranes: The closed state
Authors: Prieto Lidia , Lazaridis Themis
Published: September 2010

Colicins are water‐soluble toxins that, upon interaction with membranes, undergo a conformational change, insert, and form pores in them. Pore formation activity is localized in a bundle of 10 α‐helices named the pore‐forming domain (PFD). There is evidence that colicins attach to the membrane via a hydrophobic hairpin embedded in the core of the PFD. Two main models have been suggested for the membrane‐bound state: penknife and umbrella, differing in regard to the orientation of the hydrophobic hairpin with respect to the membrane. The arrangement of the amphipathic helices has been described as either a compact three‐dimensional structure or a two‐dimensional array of loosely interacting helices on the membrane surface. Using molecular dynamics simulations with an implicit membrane model, we studied the structure and stability of the conformations proposed earlier for four colicins. We find that colicins are initially driven towards the membrane by electrostatic interactions between basic residues and the negatively charged membrane surface. They do not have a unique binding orientation, but in the predominant orientations the central hydrophobic hairpin is parallel to the membrane. In the inserted state, the estimated free energy tends to be lower for the compact arrangements of the amphipathic helix, but the more expanded ones are in better agreement with experimental distance distributions. The difference in energy between penknife and umbrella conformations is small enough for equilibrium to exist between them. Elongation of the hydrophobic hairpin helices and membrane thinning were found unable to produce stabilization of the transmembrane configuration of the hydrophobic hairpin. Proteins 2010. © 2010 Wiley‐Liss, Inc.
A computational tool for identifying minimotifs in protein–protein interactions and improving the accuracy of minimotif predictions
Authors: Rajasekaran Sanguthevar , Merlin Jerlin Camilus , Kundeti Vamsi , Mi Tian , Oommen Aaron , Vyas Jay , Alaniz Izua , Chung Keith , Chowdhury Farah , Deverasatty Sandeep , Irvey Tenisha M. , Lacambacal David , Lara Darlene , Panchangam Subhasree , Rathnayake Viraj , Watts Paula , Schiller Martin R.
Published: September 2010

Protein–protein interactions are important to understanding cell functions; however, our theoretical understanding is limited. There is a general discontinuity between the well‐accepted physical and chemical forces that drive protein–protein interactions and the large collections of identified protein–protein interactions in various databases. Minimotifs are short functional peptide sequences that provide a basis to bridge this gap in knowledge. However, there is no systematic way to study minimotifs in the context of protein–protein interactions or vice versa. Here we have engineered a set of algorithms that can be used to identify minimotifs in known protein–protein interactions and implemented this for use by scientists in Minimotif Miner. By globally testing these algorithms on verified data and on 100 individual proteins as test cases, we demonstrate the utility of these new computation tools. This tool also can be used to reduce false‐positive predictions in the discovery of novel minimotifs. The statistical significance of these algorithms is demonstrated by an ROC analysis (P = 0.001). Proteins 2010. © 2010 Wiley‐Liss, Inc.
Intanza: first vaccine given intradermally for influenza
Authors: Chaplin Steve , Donati Matthew
Published: September 2010

Intanza is the first seasonal flu vaccine given by intradermal injection and offers an improved immune response in older people. In our New products review Steve Chaplin presents the clinical data relating to its efficacy and side‐effects compared with intramuscular flu vaccines, and Dr Matthew Donati discusses its place in flu vaccination.
Managing the high cost of newer oral agents in type 2 diabetes
Authors: Gadsby Roger , Patel Vinod , Riley Andrew
Published: September 2010

Over recent years there has been a significant number of new drugs launched for the management of diabetes. While this is good news for patients with the condition it has the potential to put significant pressure on the drugs bill. In this Expert Panel Discussion the participants discuss the rising cost of diabetes management and the impact of new drugs. In particular they discuss the NICE estimates for the cost of implementation of recent guidance on use of new drugs and how this guidance can be implemented most cost‐effectively.
Fullerene‐induced magnetization training effect in single molecular magnet
Authors: Makarova Tatiana L. , Zagaynova Valeria S. , Spitsina Natalia G.
Published: September 2010

Fullerene‐containing complexes of Mn12‐based single molecular magnets have been studied. It is confirmed that fullerenes have strong influence on the relaxation processes inside single molecular magnets. Notably, the hysteresis curves are found not to return to the initial point after 1 T to −1 T to1 T measurement cycle, but the magnetization progressively increases with each cycle. The effect is reproducible, and we call it “magnetization training” drawing an analogy with the “magnetic training” in exchange‐biased multilayers, but emphasizing that magnetization rather than coercivity is trained in our system. The effect is presumably due to magnetic ordering linked to orientational ordering of incorporated C60 molecules in magnetic field.

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Al‐doped ZnO nanofilms: Synthesis and characterization
Authors: Huczko A. , Dąbrowska A. , Madhup D. K. , Subedi D. P. , Chimouriya S. P.
Published: September 2010

Al‐doped and un‐doped ZnO nanofilms on quartz substrate were obtained by ultrasonic spray pyrolysis of salt solutions (mole concentration of Al within 0–10%). The films were characterized by Scanning electron microscopy (SEM), X‐ray diffraction (XRD), Atomic force microscopy (AFM) and UV spectroscopy to study the morphology and optical properties. The optical studies showed that the increase in Al within ZnO thin layer increases its band gap energy. The obtained value of band gap energy is very close to the determined oscillation energy. However, the dispersion energy is nearly half of band gap energy value.
Encapsulation of electrical contacts for suspended single‐walled carbon nanotubes by atomic layer deposition
Authors: Muoth Matthias , Lee Shih‐Wei , Chikkadi Kiran , Mattmann Moritz , Helbling Thomas , Intlekofer Alexander , Hierold Christofer
Published: September 2010

We show encapsulation of electrical contacts to freestanding single‐walled carbon nanotubes (SWNTs) by selective nucleation of Al2O3 from atomic layer deposition (ALD). Passivating electrical contacts is often required to prevent degradation of devices, and for chemical sensing it can separate sensing mechanisms either dedicated to metal contact regions or to SWNT channels. As ALD Al2O3 does not grow on defect‐free SWNTs, Al2O3 is selectively deposited on contacts to suspended SWNTs. TEM imaging on micromachined structures enables to investigate the mask‐less fabricated encapsulation.

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Surface selective nucleation of Al2O3 during ALD encapsulates electrical contacts to suspended SWNTs while leaving pristine sections unaffected.
Evolution of the Raman intensity and the transport properties of SWNTs in various electrochemical doping stages – Exciton effects and functionalization‐induced DOS changes
Authors: Rafailov Peter M. , Monev Milko , Bretzler Rita , Evtimova Svetla , Arnaudov Boris , Thomsen Christian , Dettlaff‐Weglikowska Urszula , Roth Siegmar
Published: September 2010

We monitored the full sequence of electrochemical doping of a single‐walled carbon nanotube‐bundle sample (mean tube diameter 1.35 nm) in a NH4Cl solution from double‐layer charging to intercalation and functionalization with Raman spectroscopy, scanning electron microscopy, and transport measurements. The different doping dependences of the Raman intensity of metallic and semiconducting tubes are explained with the excitonic nature of the Raman effect in SWNTs. Temperature‐dependent conductivity measurements indicate a decreasing metallicity of the sample in the non‐covalent functionalization region where the conductivity still increases with doping level. We attribute this phenomenon to changes in the density of states of metallic SWNTs.
Interaction of NH3 with the reduced surface of graphite fluoride C2F
Authors: Okotrub A. V. , Babin K. S. , Gusel'nikov A. V. , Asanov I. P. , Bulusheva L. G.
Published: September 2010

A treatment of graphite fluoride C2F with hydrazine vapor resulted in development of conductive surface layer. Exposure of the reduced C2F sample to gaseous NH3 (∼5% in ambient air) was shown to lead to rapid increase in layer resistance. Relative change of resistance averaged over three cycles is ∼14%. Only air purging at room temperature is required to recover the sensor. Quantum chemical calculations showed that NH3 molecules should interact more readily with partially fluorinated graphitic layer than with graphene.

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Side view of NH3 molecule on the top of reduced surface of fluorinated graphene.
Investigation of the Jahn–Teller effect in the ${\rm C}_{60}^{{-} } $ monoanion under high pressure
Authors: Francis E. A. , Scharinger S. , Németh K. , Kamarás K. , Kuntscher C. A.
Published: September 2010

We report the Jahn–Teller (JT) dynamics of the ${\rm C}_{60}^{{-} } $ monoanion under pressure in (Ph4P)2IC60. (Ph4P)2IC60 was synthesized by electrochemical crystallization and investigated by infrared transmission measurements up to 5 GPa. The behavior of two T1u vibrational modes of ${\rm C}_{60}^{{-} } $, which exhibit signatures of the dynamic JT effect at ambient conditions, was followed under pressure. The pressure‐induced transition from the dynamic to the static JT state was observed at ∼2 GPa. Due to symmetry lowering related to the dynamic JT effect, the G1u mode is activated and shows a splitting at the pressure‐induced dynamic‐to‐static JT distortion.