bluuebunny/crossref_metadata_2025 huggingface dataset:
CD43 regulates the threshold for T cell activation by targeting Cbl functions
Authors: Pedraza‐Alva Gustavo , Mérida Lilia B. , del Rio Roxana , Fierro Nora A. , Cruz‐Muñoz Mario E. , Olivares Norma , Melchy Erika , Igras Vivian , Holländer Georg A. , Burakoff Steven J. , Rosenstein Yvonne
Published: September 2011

T cell (TC) activation requires the coordinated signaling of the T cell receptor (TCR) and coreceptor molecules, allowing TCs to respond to lower degrees of TCR occupancy. Coreceptor molecules set the threshold for TC activation by controlling different regulatory signaling loops. The Cbl family members prevent undesired activation of T cells by regulating TCR signals. In this report, we show that TC prestimulation by the CD43 coreceptor molecule before TCR engagement inhibits TCR‐dependent c‐Cbl tyrosine phosphorylation, c‐Cbl interaction with the adapter molecule Crk‐L and promotes Cbl‐b degradation in a PKCθ‐dependent manner. Consequently, the prolonged tyrosine phosphorylation and delayed degradation of ZAP‐70 and of the ζ chain lead to enhanced mitogen‐activated protein kinase activation and robust TC response. These data indicates that CD43‐mediated signals lower the threshold for TC activation by restricting the c‐Cbl and Cbl‐b inhibitory effects on TCR signaling. In addition to the strength and duration of intracellular signals, our data underscore temporality with which certain molecules are engaged as yet another mechanism to fine tune TC signal quality, and ultimately immune function. © 2011 IUBMB IUBMB Life, 2011
Signaling through Toll‐like receptor 4 and mast cell‐dependent innate immunity responses
Authors: Avila Martin , Gonzalez‐Espinosa Claudia
Published: September 2011

Signal transduction through Toll‐like receptors (TLRs) has been one of the main topics in immunology research in recent years. Because of their signaling particularities based on the homotypic recognition of protein domains in multiple adaptors and selective activation of protein kinases, TLRs have become a paradigm to study ligand recognition coupled to dynamic and highly specific transcriptional and secretory responses in immune cells. Particularly, deleterious effects of Gram‐negative bacteria‐associated immune reactions has promoted intense research in the field, leading to the description of a number of canonical molecules connecting lipopolysaccharide‐induced TLR4 activation with NFκB‐dependent transcription. However, the diversity of immune cell phenotypes and the activity of distinct immune receptors in the same cell, strongly suggest that a number of elements in TLR4 signaling cascade, such as novel coreceptors, tyrosine kinases, and molecules regulating the secretion of preformed mediators remain to be described. Recent investigations have placed the mast cells, widely known by their role on allergic responses, as important effectors of innate immunity reactions against Gram‐negative bacteria. Their remarkable capacity of cytokine storage, synthesis and release, and the large number of inflammatory reactions controlled by their activation, suggest the existence of new modulators of TLR4 signaling in this particular cell type. © 2011 IUBMB IUBMB Life, 2011
mTORC1‐ and mTORC2‐interacting proteins keep their multifunctional partners focused
Authors: Bracho‐Valdés Ismael , Moreno‐Alvarez Paola , Valencia‐Martínez Israel , Robles‐Molina Evelyn , Chávez‐Vargas Lydia , Vázquez‐Prado José
Published: September 2011

The mammalian target of rapamycin, best known as mTOR, is a phylogenetically conserved serine/threonine kinase that controls life‐defining cellular processes such as growth, metabolism, survival, and migration under the influence of multiple interacting proteins. Historically, the cellular activities blocked by rapamycin in mammalian cells were considered the only events controlled by mTOR. However, this paradigm changed with the discovery of two signaling complexes differentially sensitive to rapamycin, whose catalytic component is mTOR. The one sensitive to rapamycin, known as mTORC1, promotes protein synthesis in response to growth factors and nutrients via the phosphorylation of p70S6K and 4EBP1; while the other, known as mTORC2, promotes cell migration and survival via the activation of Rho GTPases and the phosphorylation of AKT, respectively. Although mTORC2 kinase activity is not inhibited by rapamycin, hours of incubation with this antibiotic can impede the assembly of this signaling complex. The direct mechanism by which mTORC2 leads to cell migration depends on its interaction with P‐Rex1, a Rac‐specific guanine nucleotide exchange factor, while additional indirect pathways involve the intervention of PKC or AKT, multifunctional ubiquitous serine/threonine kinases that activate effectors of cell migration upon being phosphorylated by mTORC2 in response to chemotactic signals. These mTORC2 effectors are altered in metastatic cancer. Numerous clinical trials are testing mTOR inhibitors as potential antineoplasic drugs. Here, we briefly review the actions of mTOR with emphasis on the controlling role of mTORC1 and mTORC2‐interacting proteins and highlight the mechanisms linked to cell migration. © 2011 IUBMB IUBMB Life, 2011
Protein kinase C in Wnt signaling: Implications in cancer initiation and progression
Authors: Luna‐Ulloa Luis Bernardo , Hernández‐Maqueda José G. , Castañeda‐Patlán M. Cristina , Robles‐Flores Martha
Published: September 2011

Although it is well known that Wnt and protein kinase C (PKC) signaling pathways are both involved in carcinogenesis and tumor progression, their synergistic contribution to these processes or the crosstalk between them has just recently been approached. The Wnt and PKC signaling are involved in many cellular functions including proliferation, differentiation, survival, apoptosis, cytoskeletal remodeling, and cell motility. Canonical Wnt signaling has been well characterized as one of the most important contributors to tumorigenesis, and it has been implicated in many types of solid tumors. PKC is one of the key targets of noncanonical Wnt signaling, particularly in the Wnt/Ca2+ pathway. Recently, data have implicated components of noncanonical Wnt/Ca2+ and Wnt/planar cell polarity signaling in directly promoting the invasiveness and malignant progression of diverse forms of human cancer. But, unlike the canonical pathway, defining the roles of noncanonical Wnt signaling in human cancer is in its infancy. In this review, we provide a concise description of the current knowledge of the interaction between PKC and Wnt pathways and discuss the role of this crosstalk in cancer initiation and progression. © 2011 IUBMB IUBMB Life, 2011
Blood thioredoxin reductase activity, oxidative stress and hematological parameters in painters and battery workers: relationship with lead and cadmium levels in blood
Authors: Conterato Greicy M. M. , Bulcão Rachel P. , Sobieski Rocheli , Moro Angela M. , Charão Mariele F. , de Freitas Fernando A. , de Almeida Fernanda L. , Moreira Ana P. L. , Roehrs Miguel , Tonello Raquel , Batista Bruno L. , Grotto Denise , Barbosa Fernando , Garcia Solange C. , Emanuelli Tatiana
Published: September 2011

Oxidative stress has been shown to be involved in lead and cadmium toxicity. We recently showed that the activity of the antioxidant enzyme thioredoxin reductase (TrxR) is increased in the kidneys of lead‐exposed rats. The present study evaluated the blood cadmium and blood lead levels (BLLs) and their relationship with hematological and oxidative stress parameters, including blood TrxR activity in 50 painters, 23 battery workers and 36 control subjects. Erythrocyte δ‐aminolevulinate dehydratase (δ‐ALA‐D) activity and its reactivation index were measured as biomarkers of lead effects. BLLs increased in painters, but were even higher in the battery workers group. In turn, blood cadmium levels increased only in the painters group, whose levels were higher than the recommended limit. δ‐ALA‐D activity was inhibited only in battery workers, whereas the δ‐ALA‐D reactivation index increased in both exposed groups; both parameters were correlated to BLLs (r = −0.59 and 0.84, P < 0.05), whereas the reactivation index was also correlated to blood cadmium levels (r = 0.27, P < 0.05). The changes in oxidative stress and hematological parameters were distinctively associated with either BLLs or blood cadmium levels, except glutathione‐S‐transferase activity, which was correlated with both lead (r = 0.34) and cadmium (r = 0.47; P < 0.05). However, TrxR activity did not correlate with any of the metals evaluated. In conclusion, blood TrxR activity does not seem to be a good parameter to evaluate oxidative stress in lead‐ and cadmium‐exposed populations. However, lead‐associated changes in biochemical and hematological parameters at low BLLs underlie the necessity of re‐evaluating the recommended health‐based limits in occupational exposure to this metal. Copyright © 2011 John Wiley & Sons, Ltd.
Deoxyactein stimulates osteoblast function and inhibits bone‐resorbing mediators in MC3T3‐E1 cells
Authors: Choi Eun Mi
Published: September 2011

Osteoporosis is a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. In order to improve the treatment of osteoporosis, identification of anabolic agents with minimal side effects is highly desirable. Cimicifuga racemosa has a long and diverse history of medicinal use and deoxyactein isolated from this species is one of the major constituents. In the present study, the effect of deoxyactein on the function of osteoblastic MC3T3‐E1 cells was studied. Deoxyactein caused a significant elevation of cell growth, alkaline phosphatase activity, collagen content, and mineralization in the cells (P < 0.05). Moreover, deoxyactein significantly (P < 0.05) decreased the production of reactive oxygen species (ROS) and osteoclast differentiation‐inducing factors such as TNF‐α, IL‐6 and receptor activator of nuclear factor‐κB ligand in the presence of antimycin A, which inhibits mitochondrial electron transport and has been used as an ROS generator. These results demonstrate that deoxyactein may have positive effects on skeletal structure. Copyright © 2011 John Wiley & Sons, Ltd.
Local protein backbone folds determined by calculated NMR chemical shifts
Authors: Czajlik András , Hudáky Ilona , Perczel András
Published: September 2011

NMR chemical shifts (CSs: δNNH, δCα, δCβ, δC′, δHNH, and δHα) were computed for the amino acid backbone conformers (αL, βL, γL, δL, εL, αD, γD, δD, and εD [Perczel et al., J Am Chem Soc 1991, 113, 6256]) modeled by oligoalanine structures. Topological differences of the extended fold were investigated on single β‐strands, hairpins with type I and II β‐turns, as well as double‐ and triple‐stranded β‐sheet models. The so‐called “capping effect” was analyzed: residues at the termini of a homoconformer sequence unit usually have different CSs than the central residues of an adequately long homoconformer model. In heteroconformer sequences capping effect ruins the direct applicability of several chemical shift types (δHNH, δC′, and δNNH) for backbone structure determination of the parent residue. Experimental δHα, δCα, and δCβ values retrieved from protein database are in good agreement with the relevant computed data in the case of the common backbone conformers (αL, βL, γL, and εL), even though neighboring residue effects were not accounted for. Experimental and computed ΔδHα‐ΔδCα, ΔδHα‐ΔδCβ, and ΔδCα‐ΔδCβ maps give qualitatively the same picture, that is, the positions of the backbone conformers relative to each other are very similar. This indicates that the Hα, Cα, and Cβ chemical shifts of alanine depend considerably on the backbone fold of the parent residue also in proteins. We provide tabulated CSs of the chiral amino acids that may predict the various structures of the residues. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011
A Novel Polymeric Chemosensor: Dual Colorimetric Detection of Metal Ions Through Click Synthesis
Authors: Li Yongrong , Ashizawa Minoru , Uchida Satoshi , Michinobu Tsuyoshi
Published: September 2011

A highly colored polystyrene derivative bearing side chain chromophores composed of dialkylanilino donor and cyano‐based acceptor groups, prepared by atom‐economic click postfunctionalization, displays the dual colorimetric detection behavior of several metal ions based on the specific interactions with different nitrogen atoms. Hard to borderline metal ions, such as Fe3+, Fe2+, and Sn2+, are always recognized by the dialkylanilino nitrogen atom, resulting in a decrease in the charge‐transfer (CT) band intensity of the donor–acceptor chromophores. On the other hand, the recognition site of a soft metal ion of Ag+ is the cyano nitrogen atom due to the readily formed multivalent coordination, which produces a bathochromic shift of the CT band.
An in vitro, short‐term culture method for mammalian haploid round spermatids amenable for molecular manipulation
Authors: Dehnugara Tushna , Dhar Surbhi , Rao M.R. Satyanarayana
Published: September 2011

Extensive chromatin remodeling is a characteristic feature of mammalian spermiogenesis. To date, methods for the molecular manipulation of haploid spermatids are not available as there is a lack of a well‐established culture system. Biochemical experiments and knockout studies reveal only the final outcome; studying the incremental details of the intricate mechanisms involved is still a challenge. We have established an in vitro culture system for pure haploid round spermatids isolated from rat testes that can be maintained with good viability for up to 72 hr. Changes in cell morphology and flagellar growth were also studied in the cultured spermatids. Further, we have demonstrated that upon treatment of cells with specific histone deacetylase inhibitors, sodium butyrate and trichostatin A, there is an increase in the hyperacetylation status of histone H4, mimicking an important event characteristic of histone replacement process that occurs during later stages of spermiogenesis. We have also tried various methods for introducing DNA and protein into these round spermatids in culture, and report that while DNA transfection is still a challenging task, protein transfection could be achieved using Chariot™ peptide as a transfection reagent. Thus, the method described here sets a stage to study the molecular roles of spermatid‐specific proteins and chromatin remodelers in the cellular context. Mol. Reprod. Dev. 79:19–30, 2012. © 2011 Wiley Periodicals, Inc.
Spinschaltung und intelligente Kontrastmittel in der MRT
Authors: Herges Rainer
Published: September 2011

Isolierte Atome und Moleküle existieren in zwei magnetischen Zuständen: dia‐ und para magnetisch. Bis vor kurzem war magnetische Bistabilität auf Festkörper beschränkt und Einzelmoleküle ließen sich bei Raumtemperatur nicht zwischen diesen Zuständen hin und her schalten. Die Entwicklung des ligandgetriebenen Spinwechsels erlaubt nun auch das Spinschalten ohne kooperative Effekte. Neue Anwendungen wie schaltbare Kontrastmittel für die Kernspintomographie sind so möglich.
Phosphor in der Elektronik
Authors: Schmetterer Clemens , Ipser Herbert
Published: September 2011

Den Verbraucher interessiert meist nur, dass ein elektronisches Gerät funktioniert, aber nicht wie. Gerade dies ist aber für die Hersteller von Bedeutung. Grundlagenforschung liefert dafür Basisdaten und zeigt, wie zum Beispiel Phosphor Materialeigenschaften beeinflusst.
Chemielehrer für die Zukunft
Authors: Bader Hans Joachim , Melle Insa
Published: September 2011

Neue Erkenntnisse und das Problem, aus der riesigen Menge an Informationen die relevanten heraus zufiltern, machen lebenslanges Lernen notwendig. Im letzten Jahr haben etwa 8000 Lehrer die 480 Kurse der Chemielehrerfortbildungszentren besucht.
Ausstieg oder Einstieg?
Authors: Schneider Bernd W. , Kuschel Matthias
Published: September 2011

Obwohl das Transaktionsvolumen der chemischen Industrie im zweiten Quartal sank, zeigt der Trend nach oben. Dabei beteiligen sich wieder mehr Finanzinvestoren. Ein lohnendes Feld scheint zurzeit die Spezialchemie.
Scientists as lobbyists? How science can make its voice heard in the South African policy‐making arena
Authors: Funke Nikki , Nienaber Shanna , Henwood Roland
Published: September 2011

This paper examines the complexity of the South African policy‐making context and its official and non‐official actors and investigates the challenges that scientists face when trying to exert their influence here in order to strengthen the science–policy interface. Based on this analysis, the paper makes preliminary recommendations on how scientists can venture to lobby policy‐makers in spite of the many obstacles they face. The main areas of interest in this paper are the science–policy interface, the policy‐making process and lobbying. Copyright © 2011 John Wiley & Sons, Ltd.
Efficacy of clay content and microstructure of curing agents on the structure–property relationship of new‐generation polyurethane nanocomposites
Authors: Maji Pradip K. , Bhowmick Anil K.
Published: September 2011

The physicomechanical properties of new polyurethanes (PUs) derived from toluene diisocyanate, poly(propylene glycol), and cured by third‐generation hyperbranched polyester polyol (HB3), trimethylolpropane (TMP), or glycerol and their nanocomposites have been investigated. An apparent microphase‐segregated morphology of PU nanocomposites cured by HB3 has been observed by transmission electron microscopy and atomic force microscopy. Morphological studies reveal regions of mostly exfoliated and some intercalated morphology in the case of the nanocomposites, which have been further ascertained by X‐ray diffraction analysis. The HB3‐cured PU nanocomposite containing 8 wt% of modified montmorillonite (Cloisite 30B) clay shows approximately 140% increase in tensile strength along with improvement in thermal and dynamic mechanical properties in comparison with the control hyperbranched PU. It has also been found from Fourier transform infrared spectroscopy analysis that the extent of tethering reactions between the polymer chains carrying residual –NCO groups and the reactive hydroxyl (−OH) groups of HB3 is significant, and the nanofiller has been found to preferentially react with the –NCO group of the prepolymer. Furthermore, the properties of HB3‐cured PU have been compared with the glycerol and TMP‐cured PUs and their nanocomposites. The physicomechanical and thermal properties for nanocomposites of HB3‐cured PUs are superior to those of the conventionally cured PUs. Copyright © 2011 John Wiley & Sons, Ltd.
Long‐term non‐cancer mortality in pediatric and young adult cancer survivors in Finland
Authors: Prasad Pinki K. , Signorello Lisa B. , Friedman Debra L. , Boice John D. , Pukkala Eero
Published: September 2011

Background

Excess late mortality has been reported among pediatric cancer survivors, but there is a need to further establish risk profiles for non‐cancer death and to examine cause‐specific mortality among survivors of young adult cancers.

Procedures

In a nationwide record linkage study in Finland, we identified 9,245 5‐year cancer survivors diagnosed before age 35 and treated between 1966 and 1999, and followed them for mortality endpoints from 1971 to 2008. Standardized mortality ratios (SMRs) and 95% confidence intervals (95% CIs) were calculated to compare the observed number of deaths with those expected in the general Finnish population. Primary endpoints included death from cardiovascular and respiratory diseases; death from malignant diseases was excluded.

Results

Non‐malignant disease mortality in the cohort was 90% higher (SMR = 1.9, 95% CI: 1.7–2.2) than expected, with SMRs for circulatory and respiratory disease similarly elevated (SMR = 1.9, 95% CI: 1.5–2.3 and SMR = 2.3, 95% CI: 1.3–3.8, respectively). Important differences were noted amongst patient subgroups, with risk greatest for survivors of central nervous system (CNS) cancer, Hodgkin lymphoma (HL), and non‐Hodgkin lymphoma (NHL). The SMR's for circulatory disease were 6.6 (95% CI: 4.8–8.9) for HL and 4.8 (95% CI: 2.6–8.1) for NHL for the entire population; but these risks remained elevated for survivors diagnosed between 15 and 34 years of age.

Conclusions

Previous studies have shown that there is an elevated risk of non‐cancer mortality in childhood cancer survivors; this is one of the first studies that show an increase in cardiovascular and respiratory mortality in long‐term survivors of adolescent and young adult cancers. Pediatr Blood Cancer 2012; 58: 421–427. © 2011 Wiley Periodicals, Inc.
Retinoblastoma in Central America: Report from the Central American Association of Pediatric Hematology Oncology (AHOPCA)
Authors: Luna‐Fineman Sandra , Barnoya Margarita , Bonilla Miguel , Fu Ligia , Baez Fulgencio , Rodríguez‐Galindo Carlos
Published: September 2011

Background

Retinoblastoma is highly curable in high income countries. Low income countries have poor results due to advanced disease and lack of resources. Central American Association of Pediatric Hematology Oncology (AHOPCA) aimed to standardize the approach and to improve outcomes of patients with retinoblastoma.

Procedure

One hundred seventy‐one patients, age <18 years newly diagnosed with retinoblastoma were treated according to laterality and stage. Therapeutic modalities were: surgery (enucleation), local control (laser therapy, cryotherapy), chemotherapy, and radiation therapy. Chemotherapy consisted of vincristine, etoposide, and carboplatin (6 cycles). Outcomes were measured by overall survival. Events were abandonment of therapy and death.

Results

One hundred seventy‐one patients (129 unilateral, 42 bilateral) were treated. Median age was 2 years 4 months; 112 (66%) were diagnosed before 3 years of age. 119 (92%) eyes in patients with unilateral disease were Reese–Ellsworth IV or V versus 52 (62%) eyes in patients with bilateral disease. Extraocular disease was more prevalent in unilateral disease (65% vs. 50%). Older age at diagnosis correlated with higher stage. Estimated overall survival at 60 months was 0.48 ± 0.04. Outcome of patients with bilateral disease was significantly better than unilateral (62% ± 0.09 vs. 42% ± 0.05, P = 0.0006). Thirty‐eight patients (22%) refused or abandoned therapy.

Conclusions

Protocol‐directed therapy for retinoblastoma in Central America is possible. Patients present with advanced disease and outcome is significantly worse than in middle and high‐income countries. Refusal and abandonment of therapy are societal events that affect outcome. Initiatives aimed at improving early diagnosis, while dedicated treatment centers are developed, are critical. Pediatr Blood Cancer 2012; 58: 545–550. © 2011 Wiley Periodicals, Inc.
Pilot study of the effect of romiplostim on child health‐related quality of life (HRQoL) and parental burden in immune thrombocytopenia (ITP)
Authors: Klaassen Robert J. , Mathias Susan D. , Buchanan George , Bussel James , Deuson Robert , Young Nancy L. , Collier Anderson , Bomgaars Lisa , Blanchette Victor
Published: September 2011

Background

Childhood ITP can have a negative impact on the child and his/her family even though it is typically a benign disorder with low risk of serious bleeding. In adults and now children, romiplostim increases the platelet count without significant adverse effects. In this study, the impact of romiplostim treatment on the HRQoL of children with chronic ITP was assessed using the Kid's ITP Tools (KIT).

Procedure

Subjects 1–18 years old, with chronic ITP (>6 months), were enrolled in a multi‐center, randomized, double‐blind, placebo‐controlled phase 1/2 treatment study with romiplostim (reported elsewhere). Subjects and/or proxies completed the KIT at baseline, week 5, and week 13. Scores were computed for child self‐report (children >7 years), proxy‐report, and parent impact. Changes in mean scores from baseline to week 13 were computed.

Results

Twenty‐two children (17 receiving romiplostim, 5 placebo) and/or their parents provided data. Change in mean scores demonstrated significant improvement in HRQoL for romiplostim versus placebo for parent impact (24 ± 17 vs. −6 ± 8; P = 0.008). Change scores for child self‐report trended toward improvement with romiplostim and decreased with placebo (5 ± 10 vs. −7 ± 17; P = 0.29). Romiplostim proxy‐report mean change scores were 6 points higher than placebo (8 ± 16 vs. 2 ± 12; P = 0.50).

Conclusions

Romiplostim significantly reduced parental burden in this study. Whether the same and/or additional improvements in HRQoL would be demonstrated by a larger, longer study of romiplostim‐treated children with ITP remains to be determined. Pediatr Blood Cancer 2012; 58: 395–398. © 2011 Wiley Periodicals, Inc.
Phase 2 clinical trial of intrathecal topotecan in children with refractory leptomeningeal leukemia: A Children's Oncology Group trial (P9962)
Authors: Potter Samara L. Poplack , Berg Stacey , Ingle Ashish Mark , Krailo Mark , Adamson Peter C. , Blaney Susan M.
Published: September 2011

Purpose

We performed a phase 2 study in children with recurrent or refractory leptomeningeal leukemia to determine the objective response rate after treatment with intrathecal (IT) topotecan.

Patients and Methods

Patients received age‐adjusted IT topotecan (0.4 mg/dose for patients >3 years of age) administered twice weekly (every 3–4 days) for 6 weeks during induction, weekly for 4 weeks during consolidation, and twice monthly for 4 months and then monthly thereafter during maintenance.

Results

Twenty‐two patients enrolled in the study, of whom 20 were eligible and assessable for toxicity and 16 were assessable for response. Of 16 patients, 6 (38%) had a complete response, 8 (50%) had stable disease, and 2 (13%) had progressive disease. The median event‐free survival time (95% CI) was 3.1 (1.6–10.3) months and the median overall survival time (95% CI) was 18.0 (7.3–38.3) months. Eight patients (40%) experienced grade 3 or 4 adverse events. There were no grade 4 neurological events (Table III). Four patients experienced a total of 6 grade 3 neurological events including an olfactory seizure, a headache, transient grade 3 speech impairment, muscle weakness, motor neuropathy, and ataxia. Headache was the most common grade ≤2 neurologic event and two patients developed grade ≤2 arachnoiditis.

Conclusion

IT administration of topotecan was tolerable on this dose and schedule. The majority of adverse events were mild to moderate, reversible side effects. Complete central nervous system remissions were achieved in a subset of children with recurrent or refractory central nervous system leukemia. Pediatr Blood Cancer 2012; 58: 362–365. © 2011 Wiley Periodicals, Inc.
Real‐time monitoring and parameter estimation of the emulsion polymerization of carboxylated styrene/butadiene latexes
Authors: Soares Matheus , Machado Fabricio , Guimarães Alessandro , Amaral Marcelo M. , Pinto José Carlos
Published: September 2011

This work presents a mathematical model for semibatch carboxylated styrene/butadiene (XSBR) emulsion polymerizations, intended for the online and real‐time data reconciliation and monitoring of the polymerization reactor. Proposed procedures assume that some parameters must be estimated in real time, for accommodation of the unavoidable fluctuations of industrial operation conditions. Pressure, temperature, and feed rate profiles are used for parameter estimation, allowing for real‐time prediction of important properties of XSBR latexes, including monomer conversions, solids contents, and copolymer compositions. The proposed scheme was validated with actual data obtained in Pilot‐plant and full‐scale reactors. In all cases, estimated n values ranged from 0.1 to 1.7, which agree with results reported previously. As observed at plant, heat transfer coefficients can change from batch‐to‐batch and experience large changes during the batch due to modification of the reactor volume and accumulation of polymer material on the heat transfer areas. POLYM. ENG. SCI., 2011. © 2011 Society of Plastics Engineers
Gel‐free proteomic identification of the Bacillus subtilis insoluble spore coat protein fraction
Authors: Abhyankar Wishwas , Beek Alex Ter , Dekker Henk , Kort Remco , Brul Stanley , de Koster Chris G.
Published: September 2011

Species from the genus Bacillus have the ability to form endospores, dormant cellular forms that are able to survive heat and acid preservation techniques commonly used in the food industry. Resistance characteristics of spores towards various environmental stresses are in part attributed to their coat proteins. Previously, 70 proteins have been assigned to the spore coat of Bacillus subtilis using SDS‐PAGE, 2‐DE gel approaches, protein localization studies and genome‐wide transcriptome studies. Here, we present a “gel‐free” protocol that is capable of comprehensive B. subtilis spore coat protein extraction and addresses the insoluble coat fraction. Using LC‐MS/MS we identified 55 proteins from the insoluble B. subtilis spore coat protein fraction, of which 21 are putative novel spore coat proteins not assigned to the spore coat until now. Identification of spore coat proteins from a B. subtilis food‐spoilage isolate corroborated a generic and “applied” use of our protocol. To develop specific and sensitive spore detection and/or purification systems from food stuff or patient material, suitable protein targets can be derived from our proteomic approach. Finally, the protocol can be extended to study cross‐linking among the spore coat proteins as well as for their quantification.
Increased expression of peroxiredoxin 1 and identification of a novel lipid‐metabolizing enzyme in the early phase of liver ischemia reperfusion injury
Authors: Wilson Claire H. , Zeile Susanne , Chataway Tim , Nieuwenhuijs Vincent B. , Padbury Robert T. A. , Barritt Greg J.
Published: September 2011

Warm ischemia reperfusion (IR) injury of the liver is associated with changes in the expression and/or post‐translational modification of numerous proteins. Only a few of these have been identified. We used 2‐D DIGE to identify cytosolic proteins altered in the early stage of IR in an established rat model of segmental hepatic ischemia. Proteins in 18 abundant spots altered by IR were identified by LC‐MS/MS and Western blot. Many identified proteins were enzymes involved in glucose and lipid metabolism. Isoamyl acetate‐hydrolysing esterase 1 homolog, not previously characterized in liver, was also identified. A threefold increase in peroxiredoxin 1 (Prx1) and its oxidized forms was observed as was an increase in Prx1 mRNA. Peroxiredoxins and their overoxidation have previously been associated with IR. In contrast to other studies, we did not detect typical overoxidation of Prx1 on the peroxidatic cysteine (Cys52). Instead, we identified novel overoxidation of the resolving cysteine (Cys173) residue by LC‐MS/MS. Our results show that a rapid increase in Prx1 expression is associated with the early phase of IR of the liver, likely contributing to mechanisms that protect the liver against IR damage. Additionally, we have revealed a potential role in liver for a novel lipid‐metabolizing enzyme.
A third of the yeast mitochondrial proteome is dual localized: A question of evolution
Authors: Ben‐Menachem Reut , Tal Merav , Shadur Tanya , Pines Ophry
Published: September 2011

There are a growing number of examples of identical or almost identical proteins, which are localized to two (or more) separate compartments, a phenomenon that is termed protein dual localization, dual distribution or dual targeting. We previously divided a reference set of known yeast mitochondrial proteins into two groups, suggested to be dual localized or exclusive mitochondrial proteins. Here we examined this evaluation by screening 320 mitochondrial gene products for dual targeting, using the α‐complementation assay. The analysis of the results of this experimentally independent screen supports our previous evaluation that dual localized mitochondrial proteins constitute a subgroup of mitochondrial proteins with distinctive properties. These proteins are characterized by a lower probability of mitochondrial localization (MitoProtII score), a lower net charge and are enriched for proteins with a weaker mitochondrial targeting sequence. Conversely, mRNAs of exclusive mitochondrial proteins are enriched in polysomes associated with mitochondria. Based on the discovery of more than 60 new gene products that are now assumed to be dual targeted, we have updated an annotation list of dual‐targeted proteins. We currently estimate that more than a third of the mitochondrial proteome is dual targeted, and suggest that this abundant dual targeting presents an evolutionary advantage.
Light‐driven and aggregation‐induced emission from side‐chain azoindazole polymers
Authors: Li Ying , Zhou Nianchen , Zhang Wei , Zhang Feng , Zhu Jian , Zhang Zhengbiao , Cheng Zhenping , Tu Yingfeng , Zhu Xiulin
Published: September 2011

The well‐defined azoindazole‐containing homopolymer, poly(6‐{6‐[(4‐dimethylamino) phenylazo]‐indazole}‐hexyl methacrylate) (PDHMA), and amphiphilic diblock copolymer, poly({6‐[6‐(4‐dimethylamino)phenylazo]‐indazole}‐hexyl methacrylate)‐b‐poly(2‐(dimethylamino)ethylmethacrylate) (PDHMAm‐b‐PDMAEMAn), were successfully prepared via reversible addition‐fragmentation chain transfer polymerization technique. The homopolymer and amphiphilic diblock copolymer in CH2Cl2 exhibited intense fluorescence emission accompanied by trans–cis photoisomerization of azoindazole group under UV irradiation. The experiment results indicated that the intense fluorescence emission may be attributed to an inhibition of photoinduced electron transfer of the cis form of azoindazole. On the other hand, the intense fluorescence emission of amphiphilic diblock copolymers in water‐tetrahydrofuran mixture was observed, which increased with the volume ratio of water in the mixed solvent. The self‐aggregation behaviors of three amphiphilic diblock copolymers were examined by transmission electron microscopy, laser light scattering, and UV–vis spectra. The restriction of intramolecular rotation of the azoindazole groups in aggregates was considered as the main cause of aggregation‐induced fluorescence emission. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011.
Photovoltaic response to structural modifications on a series of conjugated polymers based on 2‐aryl‐2H‐benzotriazoles
Authors: Pasker Felix M. , Klein Michael F. G. , Sanyal Monamie , Barrena Esther , Lemmer Uli , Colsmann Alexander , Höger Sigurd
Published: September 2011

The synthesis, characterization, and photovoltaic properties of a series of four conjugated polymers containing 2‐aryl‐2H‐benzotriazoles and “bis(thiopheno)dialkylfluorenes” is described. The polymers were obtained via Suzuki‐polycondensation and comprise alternating electron rich and electron poor building blocks. The impact of systematic structural changes on the electronic and morphological properties and device efficiencies were studied. Application of these polymers as light‐harvesting and electron‐donating materials in organic solar cells using PCBM derivatives as electron accepting materials resulted in power conversion efficiencies up to 1.8%. Both the properties of the pristine polymers and the device performance show that the impact of the substitution farther‐off the backbone is negligible while substitution directly on the backbone has a major impact. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011.
Formation of triblock copolymers via a tandem enhanced spin capturing—nitroxide‐mediated polymerization reaction sequence
Authors: Junker Tanja , Zang Lin , Wong Edgar H.H. , Dingenouts Nico , Barner‐Kowollik Christopher
Published: September 2011

The preparation of ABA‐type block copolymers via tandem enhanced spin capturing polymerization (ESCP) and nitroxide‐mediated polymerization (NMP) processes is explored in‐depth. Midchain alkoxyamine functional polystyrenes (Mn = 6200, 12,500 and 19,900 g mol−1) were chain extended with styrene as well as tert‐butyl acrylate at elevated temperature NMP conditions (T = 110 °C) generating a tandem ESCP‐NMP sequence. Although the chain extensions and thus the block copolymer formation processes function well (yielding in the case of the chain extension with styrene number average molecular weights of up to 20,800 g mol−1 (PDI = 1.22) when the 6200 g mol−1 precursor is used and up to 67,500 g mol−1 (PDI = 1.36) when the 19,900 g mol−1 precursor is used and 21,600 g mol−1 (PDI = 1.17) as well as 37,100 g mol−1 (PDI = 1.21) for the tert‐butyl acrylate chain extensions for the 6200 and 12,500 g mol−1 precursors, respectively), it is also evident that the efficiency of the block copolymer formation process decreases with an increasing chain length of the ESCP precursor macromolecules (i.e., for the 19,900 g mol−1 ESCP precursor no efficient chain extension with tert‐butyl acrylate can be observed). For the polystyrene‐block‐tert‐butyl acrylate‐block‐polystyrene polymers, the molecular weights were determined via triple detection SEC using light scattering and small‐angle X‐ray scattering. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011.
Use of psychotropic medications by US cancer survivors
Authors: Punekar Rajeshwari S. , Short Pamela Farley , Moran John R.
Published: September 2011

Objectives

This study aimed to describe national utilization of psychotropic medications by adult cancer survivors in the USA and to estimate the extra use of psychotropic medications that is attributable to cancer survivorship.

Methods

Prescription data for 2001–2006 from the Medical Expenditure Panel Survey (MEPS) were linked to the data identifying cancer survivors from the National Health Interview Survey, the MEPS sampling frame. The sample was limited to adults 25 years of age and older. Propensity score matching was used to estimate the effects of cancer survivorship on utilization of psychotropic medications by comparing cancer survivors and other adults in MEPS. Utilization was measured as any use during a calendar year and the number of prescriptions purchased (including refills). Analyses were stratified by gender and age, distinguishing adults younger than 65 years from those 65 years and older.

Results

Nineteen percent of cancer survivors under age 65 years and 16% of survivors age 65 years and older used psychotropic medications. Sixteen percent of younger survivors used antidepressants, 7% used antianxiety medications. For older survivors, utilization rates for these two drug types were 11% and 7%, respectively. The increase in any use attributable to cancer amounted to 4–5 percentage points for younger survivors (p < 0.05) and 2–3 percentage points for older survivors (p < 0.05), depending on gender.

Conclusion

Increased use of psychotropic medications by cancer survivors, compared with other adults, suggests that survivorship presents ongoing psychological challenges. Copyright © 2011 John Wiley & Sons, Ltd.
Perceptions of prostate cancer in Black African and Black Caribbean men: a systematic review of the literature
Authors: Pedersen Vibe Hjelholt , Armes Jo , Ream Emma
Published: September 2011

Background

Prostate cancer (PC) is common and affects Black African and Caribbean men disproportionately more than White men. It is known that PC awareness is low in these groups, but knowledge is lacking about other factors that may deter Black men from seeking information about, or getting tested for, PC. The aim of this review was to appraise research on knowledge and perceptions of PC among Black men.

Methods

Four medical and social science databases were systematically searched, and reference lists of relevant papers were hand searched. Non‐English publications were excluded. Qualitative findings were synthesised using comparative thematic analysis to which quantitative findings were integrated.

Results

Thirteen qualitative studies and 20 cross‐sectional surveys were included. All except two were conducted in the USA. The analysis identified individual, cultural and social factors likely to impact on Black men's awareness of, and willingness to be tested for, PC. Black men's awareness of personal risk of PC varied greatly between studies. Misunderstandings regarding methods of diagnosis and treatment were widespread. PC testing and treatment were perceived as a threat to men's sense of masculinity. Mistrust of the health‐care system, limited access to health care and lack of trusting relationships with health professionals were also prominent.

Conclusion

The factors impacting on Black men's awareness of PC may contribute to late PC diagnosis and should be taken into account when communicating with Black men seeking prostate care. Further, the review demonstrated a need for high‐quality studies in countries other than the USA to determine the relevance of the review findings for Black men in other nations and continents. Copyright © 2011 John Wiley & Sons, Ltd.
Getting back on track: evaluation of a brief group psychoeducation intervention for women completing primary treatment for breast cancer
Authors: Jones Jennifer M. , Cheng Terry , Jackman Maureen , Walton Tara , Haines Susan , Rodin Gary , Catton Pamela
Published: September 2011

Objective

Patients with breast cancer experience unmet informational and psychosocial needs at the end of treatment. A brief psychoeducational intervention delivered at this transition may help to address some of the challenges these women face. The purpose of this study was to test the effectiveness of a single‐session group psychoeducational intervention (GBOT group) compared with standard print material (usual care).

Methods

In this randomized controlled trial, 442 patients with breast cancer who were completing their adjuvant radiotherapy were recruited and randomized to receive either usual care, which includes standard print material (CRL group n = 226) or usual care and the GBOT group intervention (INT group n = 216). Participants completed measures at baseline and again at 3 and 6 months post‐intervention.

Results

The INT group showed significant improvement in their knowledge regarding the re‐entry transition period (d = 0.31) and in their feelings of preparedness for re‐entry (d = 0.37). There were no differences between the groups over time on health‐related distress or mood.

Conclusions

Results support the effectiveness of providing a single‐session group psychoeducational intervention as a first‐step approach to supportive care for women at the end of breast cancer treatment. Copyright © 2011 John Wiley & Sons, Ltd.
Molecular‐dynamics simulations of silicene nanoribbons under strain
Authors: İnce Alper , Erkoç Şakir
Published: September 2011

Structural properties of silicene nanoribbons (SiNRs) of varying width have been investigated under 5% and 10% uniaxial strain via classical Molecular‐Dynamics simulations at 1 and 300 K temperatures by the aid of atomistic many‐body potential energy functions (PEFs). It has been found that under strain, SiNRs show such material properties: they are very ductile, with considerable toughness and a very long plastic range before fragmentation.

magnified image

Behavior of silicene nanoribbon under uniaxial strain: 2D structure changes to 1D gradually. The figure shows the mid‐steps (steps #3–#5) of an eight‐step stain application.
A framework for quantifying net benefits of alternative prognostic models
Authors: Rapsomaniki Eleni , White Ian R. , Wood Angela M. , Thompson Simon G. ,   Emerging Risk Factors Collaboration
Published: September 2011

New prognostic models are traditionally evaluated using measures of discrimination and risk reclassification, but these do not take full account of the clinical and health economic context. We propose a framework for comparing prognostic models by quantifying the public health impact (net benefit) of the treatment decisions they support, assuming a set of predetermined clinical treatment guidelines. The change in net benefit is more clinically interpretable than changes in traditional measures and can be used in full health economic evaluations of prognostic models used for screening and allocating risk reduction interventions. We extend previous work in this area by quantifying net benefits in life years, thus linking prognostic performance to health economic measures; by taking full account of the occurrence of events over time; and by considering estimation and cross‐validation in a multiple‐study setting. The method is illustrated in the context of cardiovascular disease risk prediction using an individual participant data meta‐analysis. We estimate the number of cardiovascular‐disease‐free life years gained when statin treatment is allocated based on a risk prediction model with five established risk factors instead of a model with just age, gender and region. We explore methodological issues associated with the multistudy design and show that cost‐effectiveness comparisons based on the proposed methodology are robust against a range of modelling assumptions, including adjusting for competing risks. Copyright © 2011 John Wiley & Sons, Ltd.
The acute administration of the selective dopamine D3 receptor antagonist SB‐277011A reverses conditioned place aversion produced by naloxone precipitated withdrawal from acute morphine administration in rats
Authors: Rice Onarae V. , Gardner Eliot L. , Heidbreder Christian A. , Ashby Charles R.
Published: September 2011

We examined the effect of SB‐277011A, a selective D3 receptor antagonist, on the conditioned place aversion (CPA) response associated with naloxone‐induced withdrawal from acute morphine administration in male Sprague‐Dawley rats. Morphine (5.6 mg/kg i.p.) was given, followed 4 hrs later by naloxone (0.3 mg/kg i.p.) and prior to placing the animals in one specific chamber of the test apparatus. All animals were subjected to 2 of these trials. A significant CPA occurred in animals that received an i.p. injection of vehicle 30 minutes prior to the measurement of chamber preference. The pretreatment of animals (30 minutes prior to testing) with 3 mg/kg i.p. of SB‐277011A did not significantly alter the CPA compared to animals treated with vehicle (1 ml/kg i.p. of deionized distilled water). In contrast, the acute pretreatment of animals with 6, 12 or 24 mg/kg i.p. of SB‐277011A significantly decreased the CPA compared to vehicle‐treated animals. In fact, the 12 and 24 mg/kg doses of SB‐277011A significantly increased the time spent in the chamber where animals were paired with morphine and naloxone. These results suggest that the selective antagonism of D3 receptors attenuates the CPA produced by a model of naloxone‐induced withdrawal from acute morphine dependence. Synapse, 2012. © 2011 Wiley Periodicals, Inc.
Insights into the Sigma‐1 receptor Chaperone's cellular functions: A microarray report
Authors: Tsai Shang‐Yi , Rothman Richard Kyle , Su Tsung‐Ping
Published: September 2011

We previously demonstrated that Sig‐1Rs are critical regulators in neuronal morphogenesis and development via the regulation of oxidative stress and mitochondrial functions. In the present study, we sought to identify pathways and genes that are affected by Sig‐1R. Gene expression profiles were examined in rat hippocampal neurons that had been cultured for 18 days in vitro (DIV). The cells were transduced with AAV siRNA targeting Sig‐1R on DIV 10 for 7 days, followed by gene expression analysis using a rat genome cDNA array. The gene array results indicated that Sig‐1R knockdown hampered cellular functions including steroid biogenesis, protein ubiquitination, actin cytoskeleton network, and Nrf‐2 mediated oxidative stress. Many of the cellular components important for actin polymerization and synapse plasticity, including F‐actin capping protein and neurofilaments, were significantly changed in AAV‐siSig‐1R neurons. Further, cytochrome c was reduced in AAV‐Sig‐1R neurons whereas free‐radical generating enzymes including cytochrome p450 and cytochrome b‐245 were increased. The microarray results also suggest that Sig‐1Rs may regulate genes that are involved in the pathogenesis of many CNS diseases including Alzheimer's disease and Parkinson's disease. These data further confirmed that Sig‐1Rs play critical roles in the CNS and thus these findings may aid in future development of therapeutic treatments targeting neurodegenerative disorders. Synapse, 2012. © 2011 Wiley Periodicals, Inc.