bluuebunny/crossref_metadata_2025 huggingface dataset:
Insulin glycation by methylglyoxal results in native-like aggregation and inhibition of fibril formation
Authors: Oliveira Luis MA , Lages Ana , Gomes Ricardo A , Neves Henrique , Família Carlos , Coelho Ana V , Quintas Alexandre
Published: August 2011

Background

Insulin is a hormone that regulates blood glucose homeostasis and is a central protein in a medical condition termed insulin injection amyloidosis. It is intimately associated with glycaemia and is vulnerable to glycation by glucose and other highly reactive carbonyls like methylglyoxal, especially in diabetic conditions. Protein glycation is involved in structure and stability changes that impair protein functionality, and is associated with several human diseases, such as diabetes and neurodegenerative diseases like Alzheimer's disease, Parkinson's disease and Familiar Amyloidotic Polyneuropathy. In the present work, methylglyoxal was investigated for their effects on the structure, stability and fibril formation of insulin.

Results

Methylglyoxal was found to induce the formation of insulin native-like aggregates and reduce protein fibrillation by blocking the formation of the seedingnuclei. Equilibrium-unfolding experiments using chaotropic agents showed that glycated insulin has a small conformational stability and a weaker dependence on denaturant concentration (smaller m-value). Our observations suggest that methylglyoxal modification of insulin leads to a less compact and less stable structure that may be associated to an increased protein dynamics.

Conclusions

We propose that higher dynamics in glycated insulin could prevent the formation of the rigid cross-β core structure found in amyloid fibrils, thereby contributing to the reduction in the ability to form fibrils and to the population of different aggregation pathways like the formation of native-like aggregates.
Promoting ranking diversity for genomics search with relevance-novelty combined model
Authors: Yin Xiaoshi , Li Zhoujun , Huang Jimmy Xiangji , Hu Xiaohua
Published: August 2011

Background

In the biomedical domain, the desired information of a question (query) asked by biologists usually is a list of a certain type of entities covering different aspects that are related to the question, such as genes, proteins, diseases, mutations, etc. Hence it is important for a biomedical information retrieval system to be able to provide comprehensive and diverse answers to fulfill biologists’ information needs. However, traditional retrieval models assume that the relevance of a document is independent of the relevance of other documents. This assumption may result in high redundancy and low diversity in the retrieval ranked lists.

Results

In this paper, we propose a relevance-novelty combined model, named RelNov model, based on the framework of an undirected graphical model. It consists of two component models, namely the aspect-term relevance model and the aspect-term novelty model. They model the relevance of a document and the novelty of a document respectively. We show that our approach can achieve 16. 4% improvement over the highest aspect level MAP reported in the TREC 2007 Genomics track, and 9. 8% improvement over the highest passage level MAP reported in the TREC 2007 Genomics track.

Conclusions

The proposed combination model which models aspects, terms, topic relevance and document novelty as potential functions is demonstrated to be effective in promoting ranking diversity as well as in improving relevance of ranked lists for genomics search. We also show that the use of aspect plays an important role in the model. Moreover, the proposed model can integrate various different relevance and novelty measures easily.
Lipid-lowering drugs in ischaemic heart disease: A quasi-experimental uncontrolled before-and-after study of the effectiveness of clinical practice guidelines
Authors: Dalmau Rosa , Boira Miriam , Aguilar Carina , López Carlos , Rodríguez Dolors , Gentille Delicia , Bofill Domingo , Diogene Eduard , Pepió Josep M
Published: August 2011

Background

Cardiovascular diseases(CVD), specifically ischaemic heart disease(IHD), are the main causes of death in industrialized countries. Statins are not usually prescribed in the most appropriate way. To ensure the correct prescription of these drugs, it is necessary to develop, disseminate and implement clinical practice guidelines(CPGs), and subsequently evaluate them.

The main objective of this study is to evaluate the effectiveness of the implementation of consensual Lipid-lowering drugs (LLD) prescription guidelines in hospital and primary care settings, to improve the control of Low-Density Lipoprotein Cholesterol (LDL-C) levels in patients with IHD in the Terres de l'Ebre region covered by the Catalonian Health Institute. Secondary objectives are to assess the improvement of the prescription profile of these LLDs, to assess cardiovascular morbimortality and the professional profile and participant centre characteristics that govern the control of LDL-C.

Methods/Design

Design: Quasi-experimental uncontrolled before and after study. The intervention consists of the delivery of training strategies for guideline implementation (classroom clinical sessions and on-line courses) aimed at primary care and hospital physicians. The improvement in the control of LDL-C levels in the 3,402 patients with IHD in our territory is then assessed.

Scope: Primary care physicians from 11 basic health areas(BHAs) and two hospital services (internal medicine and cardiology).

Sample: 3,402 patients registered with IHD in the database of the Catalan Institute of Health(E-cap) before December 2008 and patients newly diagnosed during 2009-2010.

Variables: Percentage of patients achieving good control of LDL-C, measured in milligrams per decilitre. The aim of the intervention is to achieve levels of LDL-C < 100 mg/dl in patients with IHD. Secondary variables measure type and time of diagnosis of IHD, type and dose of prescribed cholesterol-lowering drugs, level of physician participation in training activities and their professional profile.

Discussion

The development of prescription guidelines previously agreed by various medical specialists involved in treating IHD patients have usually improved drug prescription. The guideline presented in this study aims to improve the control of LDL-C by training physicians through presential and on-line courses on the dissemination of this guideline, and by providing feedback on their personal results a year after this training intervention.
Kinetic Targeting of pegylated liposomal Doxorubicin: a new Approach to Reduce Toxicity during Chemotherapy (CARL-trial)
Authors: Eckes Jürgen , Schmah Oliver , Siebers Jan W , Groh Ursula , Zschiedrich Stefan , Rautenberg Beate , Hasenburg Annette , Jansen Martin , Hug Martin J , Winkler Karl , Pütz Gerhard
Published: August 2011

Background

The therapeutic success of chemotherapeutic agents is often limited by severe adverse effects. To reduce toxicity of these drugs, nanoscale particle-based drug delivery systems (DDS) are used. DDS accumulate to some extent in tumor tissues, but only a very small portion of a given dose reaches this target. Accumulation of DDS in tumor tissues is supposed to be much faster than in certain other tissues in which side effects occur ("Kinetic Targeting"). Once saturation in tumor tissue is achieved, most of the administered DDS still circulate in the plasma. The extracorporeal elimination of these circulating nanoparticles would probably reduce toxicity.

Methods

For the CARL-trial (Controlled Application and Removal of Liposomal chemotherapeutics), pegylated liposomal doxorubicin (PLD) was used as chemotherapeutic agent and double filtration plasmapheresis (DFPP) was performed for extracorporeal elimination of liposomes. PLD was given as 40 mg/m2 every 3 weeks in combination with vinorelbine 2 × 25 mg/m2 (neoadjuvant treatment of breast cancer, 12 patients), or as 40 mg/m2 every 4 weeks (recurrent ovarian cancer, 3 patients). Primary endpoints were the efficiency and safety profile of DFPP, and secondary endpoints were side effects and tumor response.

Results

DFPP eliminated ~62% of circulating PLD, corresponding to ~45% of the total dose (n = 57 cycles). AUC of doxorubicin was reduced by 50%. No leakage of doxorubicin was detected during elimination, and no relevant DFPP-related side effects occurred. Reduction in tumor size > 30% occurred in 10/12 (neoadjuvant) and in 1/3 patients (recurrent). Only five grade 2 events and one grade 3 event (mucositis, neutropenia or leucopenia) and a single palmar-plantar erythrodysesthesia grade 2 were reported.

Conclusion

Extracorporeal elimination of PLD by DFPP is safe and efficient. CARL can diminish the main dose-limiting side effects of PLD, and probably many different DDS alike.

Trial registration

DRKS00000163
A novel inhibitor of hypoxia-inducible factor-1α P3155 also modulates PI3K pathway and inhibits growth of prostate cancer cells
Authors: Manohar Sonal M , Padgaonkar Amol A , Jalota-Badhwar Archana , Sonawane Vinay , Rathos Maggie J , Kumar Sanjay , Joshi Kalpana S
Published: August 2011

Background

Hypoxia-inducible factor-1 (HIF-1) is a master regulator of the transcriptional response to hypoxia. It is essential for angiogenesis and is associated with tumor progression and overexpression of HIF-1α has been demonstrated in many common human cancers. Therefore, HIF-1α is one of the most compelling anticancer targets.

Methods

To identify HIF-1α inhibitors, luciferase reporter gene assay under hypoxia and normoxia was used. Detailed studies such as western blotting, RT-PCR, immunofluorescence were carried out to elucidate its mechanism of action. Antiangiogenic activity of P3155 was demonstrated by migration assay and tube formation assay. Efficacy study of P3155 was performed on PC-3 xenograft model.

Results

P3155 showed specific HIF-1α inhibition with IC50of 1.4 μM under hypoxia. It suppressed HIF-1α expression as well as PI3K/Akt pathway and abrogated expression of HIF-1-inducible gene viz. vascular endothelial growth factor (VEGF). P3155 in combination with HIF-1α siRNA showed significant synergistic effect. In addition, it demonstrated significantin vivoefficacy and antiangiogenic potential in prostate cancer cell lines.

Conclusion

We have identified a novel HIF-1α inhibitor P3155 that also modulates PI3K/Akt pathway, which may contribute to its significantin vitroandin vivoantitumor activity.
Influence of in vitro supplementation with lipids from conventional and Alpine milk on fatty acid distribution and cell growth of HT-29 cells
Authors: Degen Christian , Lochner Alfred , Keller Sylvia , Kuhnt Katrin , Dänicke Sven , Jahreis Gerhard
Published: August 2011

Background

To date, the influence of milk and dairy products on carcinogenesis remains controversial. However, lipids of ruminant origin such as conjugated linoleic acids (CLA) are known to exhibit beneficial effectsin vitroandin vivo. The aim of the present study was to determine the influence of milk lipids of different origin and varying quality presenting as free fatty acid (FFA) solutions on cellular fatty acid distribution, cellular viability, and growth of human colon adenocarcinoma cells (HT-29).

Methods

FAME of conventional and Alpine milk lipids (MLcon, MLalp) and cells treated with FFA derivatives of milk lipids were analyzed by means of GC-FID and Ag+-HPLC. Cellular viability and growth of the cells were determined by means of CellTiter-Blue®-assay and DAPI-assay (4',6-diamidino-2-phenylindole dihydrochloride), respectively.

Results

Supplementation with milk lipids significantly decreased viability and growth of HT-29 cells in a dose- and time-dependent manner. MLalpshowed a lower SFA/MUFA ratio, a 8 fold increased CLA content, and different CLA profile compared to MLconbut did not demonstrate additional growth-inhibitory effects. In addition, total concentration and fatty acid distribution of cellular lipids were altered. In particular, treatment of the cells yielded highest amounts of two types of milk specific major fatty acids (μg FA/mg cellular protein) after 8 h of incubation compared to 24 h; 200 μM of MLcon(C16:0, 206 ± 43), 200 μM of MLalp(C18:1c9, (223 ± 19). Vaccenic acid (C18:1t11) contained in milk lipids was converted toc9,t11-CLA in HT-29 cells. Notably, the ratio oft11,c13-CLA/t7,c9-CLA, a criterion for pasture feeding of the cows, was significantly changed after incubation for 8 h with lipids from MLalp(3.6 - 4.8), compared to lipids from MLcon(0.3 - 0.6).

Conclusions

Natural lipids from conventional and Alpine milk showed similar growth inhibitory effects. However, different changes in cellular lipid composition suggested a milk lipid-depending influence on cell sensitivity. It is expected that similar changes may also be evident in other cell lines. To our knowledge, this is the first study showing a varied impact of complex milk lipids on fatty acid distribution in a colon cancer cell line.
Phosphoproteins regulated by heat stress in rice leaves
Authors: Chen Xinhai , Zhang Wenfeng , Zhang Baoqian , Zhou Jiechao , Wang Yongfei , Yang Qiaobin , Ke Yuqin , He Huaqin
Published: August 2011

Background

High temperature is a critical abiotic stress that reduces crop yield and quality. Rice (Oryza sativa L.) plants remodel their proteomes in response to high temperature stress. Moreover, phosphorylation is the most common form of protein post-translational modification (PTM). However, the differential expression of phosphoproteins induced by heat in rice remains unexplored.

Methods

Phosphoprotein in the leaves of rice under heat stress were displayed using two-dimensional electrophoresis (2-DE) and Pro-Q Diamond dye. Differentially expressed phosphoproteins were identified by MALDI-TOF-TOF-MS/MS and confirmed by Western blotting.

Results

Ten heat-phosphoproteins were identified from twelve protein spots, including ribulose bisphos-phate carboxylase large chain, 2-Cys peroxiredoxin BAS1, putative mRNA binding protein, Os01g0791600 protein, OSJNBa0076N16.12 protein, putative H(+)-transporting ATP synthase, ATP synthase subunit beta and three putative uncharacterized proteins. The identification of ATP synthase subunit beta was further validated by Western-blotting. Four phosphorylation site predictors were also used to predict the phosphorylation sites and the specific kinases for these 10 phosphoproteins.

Conclusion

Heat stress induced the dephosphorylation of RuBisCo and the phosphorylation of ATP-β, which decreased the activities of RuBisCo and ATP synthase. The observed dephosphorylation of the mRNA binding protein and 2-Cys peroxiredoxin may be involved in the transduction of heat-stress signaling, but the functional importance of other phosphoproteins, such as H+-ATPase, remains unknown.
Reliability and validity of the Spanish version of the 10-item Connor-Davidson Resilience Scale (10-item CD-RISC) in young adults
Authors: Notario-Pacheco Blanca , Solera-Martínez Montserrat , Serrano-Parra María D , Bartolomé-Gutiérrez Raquel , García-Campayo Javier , Martínez-Vizcaíno Vicente
Published: August 2011

Background

The 10-item Connor-Davidson Resilience Scale (10-item CD-RISC) is an instrument for measuring resilience that has shown good psychometric properties in its original version in English. The aim of this study was to evaluate the validity and reliability of the Spanish version of the 10-item CD-RISC in young adults and to verify whether it is structured in a single dimension as in the original English version.

Findings

Cross-sectional observational study including 681 university students ranging in age from 18 to 30 years. The number of latent factors in the 10 items of the scale was analyzed by exploratory factor analysis. Confirmatory factor analysis was used to verify whether a single factor underlies the 10 items of the scale as in the original version in English. The convergent validity was analyzed by testing whether the mean of the scores of the mental component of SF-12 (MCS) and the quality of sleep as measured with the Pittsburgh Sleep Index (PSQI) were higher in subjects with better levels of resilience. The internal consistency of the 10-item CD-RISC was estimated using the Cronbach α test and test-retest reliability was estimated with the intraclass correlation coefficient.

The Cronbach α coefficient was 0.85 and the test-retest intraclass correlation coefficient was 0.71. The mean MCS score and the level of quality of sleep in both men and women were significantly worse in subjects with lower resilience scores.

Conclusions

The Spanish version of the 10-item CD-RISC showed good psychometric properties in young adults and thus can be used as a reliable and valid instrument for measuring resilience. Our study confirmed that a single factor underlies the resilience construct, as was the case of the original scale in English.
Evaluation of a TDMA-based energy efficient MAC protocol for multiple capsule networks
Authors: Lin Lin , Wong Kai-Juan , Kumar Arun , Lu Zongqing , Tan Su-Lim , Phee Soo Jay
Published: August 2011

Wireless capsule endoscopy is a new kind of medical device, which monitors the gastrointestinal tract of the human body. It can be envisaged that in the future more than one capsule could be ingested by the patient and they operate collaboratively in the gastrointestinal (GI) tract to perform certain diagnostic and therapeutic tasks. These mobile capsules and the coordinator node, which is attached to the abdomen of the patient, form a wireless network. The capsule devices are typically powered by batteries, therefore, energy efficient medium access control (MAC) protocols for multiple capsule networks are necessary. This article proposes a novel energy efficient MAC protocol for multiple capsule networks based on time division multiple access (TDMA). An asymmetric up/down link network architecture is introduced. A novel TDMA slot assignment scheme is proposed and simulation results using Qualnet show that the proposed MAC protocol achieves lower energy consumption than B-MAC and star topology TDMA.
Common fixed point and invariant approximation in hyperbolic ordered metric spaces
Authors: Abbas Mujahid , Khamsi Mohamed Amine , Khan Abdul Rahim
Published: August 2011

We prove a common fixed point theorem for four mappings defined on an ordered metric space and apply it to find new common fixed point results. The existence of common fixed points is established for two or three noncommuting mappings where T is either ordered S-contraction or ordered asymptotically S-nonexpansive on a nonempty ordered starshaped subset of a hyperbolic ordered metric space. As applications, related invariant approximation results are derived. Our results unify, generalize, and complement various known comparable results from the current literature.

2010 Mathematics Subject Classification:

47H09, 47H10, 47H19, 54H25.
Opportunistic illnesses in Brazilian children with AIDS: results from two national cohort studies, 1983-2007
Authors: Ramos Alberto N , Matida Luiza H , Hearst Norman , Heukelbach Jorg
Published: August 2011

Background

HAART has significantly reduced AIDS-related morbidity in children. However, limited evidence is available from developing countries regarding patterns of opportunistic illnesses. We describe these events and their associated factors in children with AIDS in Brazil.

Methods

This study is based on two representative retrospective multi-center cohorts including a total 1,859 children with AIDS, infected via mother-to-child transmission (MTCT), between 1983-2002. Opportunistic illnesses were described and analyzed over time. The association of demographic, clinical and operational data with the occurrence of opportunistic diseases was assessed.

Results

In total, 1,218 (65.5%) had at least one event of an opportunistic disease. Variables significantly associated with occurrence of these events included: region of residence (OR 2.68-11.33, as compared to the Northern region), age < 1 year at diagnosis (OR 2.56, 95% CI 1.81-3.61, p < 0.001), and non-performance of MTCT prevention measures (OR 1.58, 95% CI 1.21-2.07, p < 0.001). Protective factors included year of HIV diagnosis in the HAART era (OR 0.34, 95% CI 0.15-0.76, p = 0.009) and ART use (OR 0.58, 95% CI 0.44-0.77, p < 0.001). In both periods bacterial infections represented the most common opportunistic events (58.6 vs. 34.7%; p < 0.001), followed byPneumocystis jiroveciipneumonia (21.9 vs. 13.2%; p < 0.001), and bacterial meningitis/sepsis (16.8 vs. 7.4%; p < 0.001).

Conclusions

Despite the significant reduction in recent years, opportunistic illnesses are still common in Brazilian children with AIDS in the HAART era, especially bacterial diseases. The data reinforce the need for scaling up prevention of MTCT, early diagnosis of infection, and improvement of comprehensive pediatric care.
Sequence analysis reveals mosaic genome of Aichi virus
Authors: Han Xiaohong , Zhang Wen , Xue Yanjun , Shao Shihe
Published: August 2011

Aichi virus is a positive-sense and single-stranded RNA virus, which demonstrated to be related to diarrhea of Children. In the present study, phylogenetic and recombination analysis based on the Aichi virus complete genomes available in GenBank reveal a mosaic genome sequence [GenBank: FJ890523], of which the nt 261-852 region (the nt position was based on the aligned sequence file) shows close relationship with AB010145/Japan with 97.9% sequence identity, while the other genomic regions show close relationship with AY747174/German with 90.1% sequence identity. Our results will provide valuable hints for future research on Aichi virus diversity.

Aichi virus is a member of the Kobuvirus genus of the Picornaviridae family [1, 2] and belongs to a positive-sense and single-stranded RNA virus. Its presence in fecal specimens of children suffering from diarrhea has been demonstrated in several Asian countries [3–6], in Brazil and German [7], in France [8] and in Tunisia [9]. Some reports showed the high level of seroprevalence in adults [7, 10], suggesting the widespread exposure to Aichi virus during childhood.

The genome of Aichi virus contains 8,280 nucleotides and a poly(A) tail. The single large open reading frame (nt 713-8014 according to the strain AB010145) encodes a polyprotein of 2,432 amino acids that is cleaved into the typical picornavirus structural proteins VP0, VP3, VP1, and nonstructural proteins 2A, 2B, 2C, 3A, 3B, 3C and 3D [2, 11]. Based on the phylogenetic analysis of 519-bp sequences at the 3C-3D (3CD) junction, Aichi viruses can be divided into two genotypes A and B with approximately 90% sequence homology [12]. Although only six complete genomes of Aichi virus were deposited in GenBank at present, mosaic genomes can be found in strains from different countries.
Prestimulus vigilance predicts response speed in an easy visual discrimination task
Authors: Minkwitz Juliane , Trenner Maja U , Sander Christian , Olbrich Sebastian , Sheldrick Abigail J , Schönknecht Peter , Hegerl Ulrich , Himmerich Hubertus
Published: August 2011

Background

Healthy adults show considerable within-subject variation of reaction time (RT) when performing cognitive tests. So far, the neurophysiological correlates of these inconsistencies have not yet been investigated sufficiently. In particular, studies rarely have focused on alterations of prestimulus EEG-vigilance as a factor which possibly influences the outcome of cognitive tests. We hypothesised that a low EEG-vigilance state immediately before a reaction task would entail a longer RT. Shorter RTs were expected for a high EEG-vigilance state.

Methods

24 female students performed an easy visual discrimination task while an electroencephalogram (EEG) was recorded. The vigilance stages of 1-sec-EEG-segments before stimulus presentation were classified automatically using the computer-based Vigilance Algorithm Leipzig (VIGALL). The mean RTs of each EEG-vigilance stage were calculated for each subject. A paired t-test for the EEG-vigilance main stage analysis (A vs. B) and a variance analysis for repeated measures for the EEG-vigilance sub-stage analysis (A1, A2, A3, B1, B2/3) were calculated.

Results

Individual mean RT was significantly shorter for events following the high EEG-vigilance stage A compared to the lower EEG-vigilance stage B. The main effect of the sub-stage analysis was marginal significant. A trend of gradually increasing RT was observable within the EEG-vigilance stage A.

Conclusion

We conclude that an automatically classified low EEG-vigilance level is associated with an increased RT. Thus, intra-individual variances in cognitive test might be explainable in parts by the individual state of EEG-vigilance. Therefore, the accuracy of neuro-cognitive investigations might be improvable by simultaneously controlling for vigilance shifts using the EEG and VIGALL.
Two-stage flux balance analysis of metabolic networks for drug target identification
Authors: Li Zhenping , Wang Rui-Sheng , Zhang Xiang-Sun
Published: August 2011

Background

Efficient identification of drug targets is one of major challenges for drug discovery and drug development. Traditional approaches to drug target identification include literature search-based target prioritization and in vitro binding assays which are both time-consuming and labor intensive. Computational integration of different knowledge sources is a more effective alternative. Wealth of omics data generated from genomic, proteomic and metabolomic techniques changes the way researchers view drug targets and provides unprecedent opportunities for drug target identification.

Results

In this paper, we develop a method based on flux balance analysis (FBA) of metabolic networks to identify potential drug targets. This method consists of two linear programming (LP) models, which first finds the steady optimal fluxes of reactions and the mass flows of metabolites in the pathologic state and then determines the fluxes and mass flows in the medication state with the minimal side effect caused by the medication. Drug targets are identified by comparing the fluxes of reactions in both states and examining the change of reaction fluxes. We give an illustrative example to show that the drug target identification problem can be solved effectively by our method, then apply it to a hyperuricemia-related purine metabolic pathway. Known drug targets for hyperuricemia are correctly identified by our two-stage FBA method, and the side effects of these targets are also taken into account. A number of other promising drug targets are found to be both effective and safe.

Conclusions

Our method is an efficient procedure for drug target identification through flux balance analysis of large-scale metabolic networks. It can generate testable predictions, provide insights into drug action mechanisms and guide experimental design of drug discovery.
Bioprospecting metagenomics of decaying wood: mining for new glycoside hydrolases
Authors: Li Luen-Luen , Taghavi Safiyh , McCorkle Sean M , Zhang Yian-Biao , Blewitt Michael G , Brunecky Roman , Adney William S , Himmel Michael E , Brumm Phillip , Drinkwater Colleen , Mead David A , Tringe Susannah G , Lelie Daniel van der
Published: August 2011

Background

To efficiently deconstruct recalcitrant plant biomass to fermentable sugars in industrial processes, biocatalysts of higher performance and lower cost are required. The genetic diversity found in the metagenomes of natural microbial biomass decay communities may harbor such enzymes. Our goal was to discover and characterize new glycoside hydrolases (GHases) from microbial biomass decay communities, especially those from unknown or never previously cultivated microorganisms.

Results

From the metagenome sequences of an anaerobic microbial community actively decaying poplar biomass, we identified approximately 4,000 GHase homologs. Based on homology to GHase families/activities of interest and the quality of the sequences, candidates were selected for full-length cloning and subsequent expression. As an alternative strategy, a metagenome expression library was constructed and screened for GHase activities. These combined efforts resulted in the cloning of four novel GHases that could be successfully expressed in Escherichia coli. Further characterization showed that two enzymes showed significant activity on p-nitrophenyl-α-L-arabinofuranoside, one enzyme had significant activity against p-nitrophenyl-β-D-glucopyranoside, and one enzyme showed significant activity against p-nitrophenyl-β-D-xylopyranoside. Enzymes were also tested in the presence of ionic liquids.

Conclusions

Metagenomics provides a good resource for mining novel biomass degrading enzymes and for screening of cellulolytic enzyme activities. The four GHases that were cloned may have potential application for deconstruction of biomass pretreated with ionic liquids, as they remain active in the presence of up to 20% ionic liquid (except for 1-ethyl-3-methylimidazolium diethyl phosphate). Alternatively, ionic liquids might be used to immobilize or stabilize these enzymes for minimal solvent processing of biomass.
Proteomic analysis of an Aedes albopictus cell line infected with Dengue serotypes 1 and 3 viruses
Authors: Patramool Sirilaksana , Surasombatpattana Pornapat , Luplertlop Natthanej , Sévéno Martial , Choumet Valérie , Thomas Frédéric , Missé Dorothée
Published: August 2011

Background

Proteomic analysis was performed to identify proteins regulated during infection by Dengue serotypes 1 and 3 in an Aedes albopictus cell line. The potential of these viruses to cause severe disease at primary infection is of interest although few studies have been performed with these two Dengue serotypes.

Results

The most relevant observation of our study is the significant overexpression of proteins involved in the cellular stress response and the glycolysis pathway after 48 hours of infection. Viral infection activates the translation of some host genes, which may result in stress due to responses involving unfolded proteins.

Conclusions

Therefore, the oxidation reduction and glycolytic mechanisms could participate in the antiviral response against Dengue virus. The results of our study should help to improve our knowledge of the virus-mosquito interaction at a cellular level with the aim of designing efficient strategies for the control of Dengue virus.
Histone H1 interphase phosphorylation becomes largely established in G1 or early S phase and differs in G1 between T-lymphoblastoid cells and normal T cells
Authors: Gréen Anna , Sarg Bettina , Gréen Henrik , Lönn Anita , Lindner Herbert H , Rundquist Ingemar
Published: August 2011

Background

Histone H1 is an important constituent of chromatin, and is involved in regulation of its structure. During the cell cycle, chromatin becomes locally decondensed in S phase, highly condensed during metaphase, and again decondensed before re-entry into G1. This has been connected to increasing phosphorylation of H1 histones through the cell cycle. However, many of these experiments have been performed using cell-synchronization techniques and cell cycle-arresting drugs. In this study, we investigated the H1 subtype composition and phosphorylation pattern in the cell cycle of normal human activated T cells and Jurkat T-lymphoblastoid cells by capillary electrophoresis after sorting of exponentially growing cells into G1, S and G2/M populations.

Results

We found that the relative amount of H1.5 protein increased significantly after T-cell activation. Serine phosphorylation of H1 subtypes occurred to a large extent in late G1 or early S phase in both activated T cells and Jurkat cells. Furthermore, our data confirm that the H1 molecules newly synthesized during S phase achieve a similar phosphorylation pattern to the previous ones. Jurkat cells had more extended H1.5 phosphorylation in G1 compared with T cells, a difference that can be explained by faster cell growth and/or the presence of enhanced H1 kinase activity in G1 in Jurkat cells.

Conclusion

Our data are consistent with a model in which a major part of interphase H1 phosphorylation takes place in G1 or early S phase. This implies that H1 serine phosphorylation may be coupled to changes in chromatin structure necessary for DNA replication. In addition, the increased H1 phosphorylation of malignant cells in G1 may be affecting the G1/S transition control and enabling facilitated S-phase entry as a result of relaxed chromatin condensation. Furthermore, increased H1.5 expression may be coupled to the proliferative capacity of growth-stimulated T cells.
Innegligible musculoskeletal disorders caused by zoledronic acid in adjuvant breast cancer treatment: a meta-analysis
Authors: Zhou Wen-Bin , Zhang Peng-Ling , Liu Xiao-An , Yang Tao , He Wei
Published: August 2011

Background

Zoledronic acid (ZOL) is widely used for preventing bone loss in early breast cancer patients. However, the adverse effects caused by ZOL itself should not be neglected. Musculoskeletal disorders were common after ZOL administration and distressing to the patients. Up to now, no precise estimation of musculoskeletal disorders has been made.

Methods

Relevant randomized clinical trials were selected by searching the electronic database PubMed, and a meta-analysis was conducted.

Results

Four trials reported musculoskeletal disorders of ZOL treatment versus no ZOL, including 2684 patients treated with ZOL and 2712 patients without ZOL treatment. Compared to patients without ZOL treatment, patients treated with ZOL had a significantly higher risk of arthralgia (risk ratio (RR): 1.162, 95% confidence interval (CI): 1.096-1.232, P = 0.466 for heterogeneity) and bone pain (RR: 1.257, 95% CI: 1.149-1.376, P = 0.193 for heterogeneity). Three clinical trials reported the complications of upfront versus delayed ZOL treatment, including 1091 patients with upfront ZOL and 1110 patients with delayed ZOL. The rate of bone pain in upfront group (119/824) was significantly higher than that in delayed group (74/836) (RR: 1.284, 95% CI: 1.135-1.453, P = 0.460 for heterogeneity).

Conclusions

Our meta-analysis suggested that treatment with ZOL was significantly associated to the occurrence of arthralgia and bone pain. Moreover, higher rate of bone pain was observed in patients treated with upfront ZOL compared with delayed ZOL treatment. More attentions should be paid to patients treated with ZOL, especially for immediate ZOL. For patients with low risk of osteoporosis, immediate ZOL may be not needed due to additional musculoskeletal disorders and little benefit. Or it can be stopped after the occurrence of these adverse events.
Urine hepcidin has additive value in ruling out cardiopulmonary bypass-associated acute kidney injury: an observational cohort study
Authors: Haase-Fielitz Anja , Mertens Peter R , Plaß Michael , Kuppe Hermann , Hetzer Roland , Westerman Mark , Ostland Vaughn , Prowle John R , Bellomo Rinaldo , Haase Michael
Published: August 2011

Introduction

Conventional markers of acute kidney injury (AKI) lack diagnostic accuracy and are expressed only late after cardiac surgery with cardiopulmonary bypass (CPB). Recently, interest has focused on hepcidin, a regulator of iron homeostasis, as a unique renal biomarker.

Methods

We studied 100 adult patients in the control arm of a randomized, controlled trial http://www.clinicaltrials.gov/NCT00672334 who were identified as being at increased risk of AKI after cardiac surgery with CPB. AKI was defined according to the Risk, Injury, Failure, Loss, End-stage renal disease classification of AKI classification stage. Samples of plasma and urine were obtained simultaneously (1) before CPB (2) six hours after the start of CPB and (3) twenty-four hours after CPB. Plasma and urine hepcidin 25-isoforms were quantified by competitive enzyme-linked immunoassay.

Results

In AKI-free patients (N = 91), urine hepcidin concentrations had largely increased at six and twenty-four hours after CPB, and they were three to seven times higher compared to patients with subsequent AKI (N = 9) in whom postoperative urine hepcidin remained at preoperative levels (P = 0.004, P = 0.002). Furthermore, higher urine hepcidin and, even more so, urine hepcidin adjusted to urine creatinine at six hours after CPB discriminated patients who did not develop AKI (area under the curve (AUC) receiver operating characteristic curve 0.80 [95% confidence interval (95% CI) 0.71 to 0.87] and 0.88 [95% CI 0.78 to 0.97]) or did not need renal replacement therapy initiation (AUC 0.81 [95% CI 0.72 to 0.88] 0.88 [95% CI 0.70 to 0.99]) from those who did. At six hours, urine hepcidin adjusted to urine creatinine was an independent predictor of ruling out AKI (P = 0.011). Plasma hepcidin did not predict no development of AKI. The study findings remained essentially unchanged after excluding patients with preoperative chronic kidney disease.

Conclusions

Our findings suggest that urine hepcidin is an early predictive biomarker of ruling out AKI after CPB, thereby contributing to early patient risk stratification.
Single cell transcriptomics of neighboring hyphae of Aspergillus niger
Authors: de Bekker Charissa , Bruning Oskar , Jonker Martijs J , Breit Timo M , Wösten Han AB
Published: August 2011

Single cell profiling was performed to assess differences in RNA accumulation in neighboring hyphae of the fungus Aspergillus niger. A protocol was developed to isolate and amplify RNA from single hyphae or parts thereof. Microarray analysis resulted in a present call for 4 to 7% of the A. niger genes, of which 12% showed heterogeneous RNA levels. These genes belonged to a wide range of gene categories.
Safety of antipsychotics in people with intellectual disability
Authors: Frighi Valeria , Stephenson Matthew T. , Morovat Alireza , Jolley Iain E. , Trivella Marialena , Dudley Christina A. , Anand Ezhil , White Sarah J. , Hammond Christina V. , Hockney Rena A. , Barrow Beryl , Shakir Rehana , Goodwin Guy M.
Published: August 2011

Background

Despite frequent use, little is known about the metabolic and endocrine side-effects of antipsychotics in individuals with intellectual disability.

Aims

To compare indices of obesity, glucose, lipids and prolactin between antipsychotic-treated and antipsychotic-naive individuals with intellectual disability and also between participants with intellectual disability and controls from the general population.

Method

Observational study comparing 138 antipsychotic-treated and 64 antipsychotic-naive participants with intellectual disability in one National Health Service trust with general population controls.

Results

Antipsychotic treatment comprised: risperidone 48%, olanzapine 18%, thioxanthenes 10%, other 24%; monotherapy 95% of participants; mean treatment duration 8 years; median daily chlorpromazine equivalent dose 108mg (range 16–667). Metabolic indices were the same or more favourable in the intellectual disability group than the general population control group but overweight/obesity and type 2 diabetes were more prevalent in the women in the intellectual disability group than the control group. Metabolic indices were similar, statistically or clinically, between the antipsychotic-treated and the antipsychotic-naive groups but there was a non-significant trend towards a higher rate of type 2 diabetes in the antipsychotic group. A total of 100% and 70% of participants on amisulpride/sulpiride and risperidone respectively had hyperprolactinaemia, with secondary hypogonadism in 77% and 4% of affected women and men.

Conclusions

Antipsychotics, on average, did not increase metabolic risk, although the existence of a susceptible subgroup at risk of diabetes cannot be excluded. Some antipsychotics induced hyperprolactinaemic hypogonadism, requiring active management. However, our findings suggest that antipsychotics at the low doses routinely prescribed for people with intellectual disability are generally safe in relation to metabolic adverse effects, even if efficacy remains poorly defined.
Pituitary Stem Cell Update and Potential Implications for Treating Hypopituitarism
Authors: Castinetti Frederic , Davis Shannon W. , Brue Thierry , Camper Sally A.
Published: August 2011

Stem cells have been identified in organs with both low and high cell turnover rates. They are characterized by the expression of key marker genes for undifferentiated cells, the ability to self-renew, and the ability to regenerate tissue after cell loss. Several recent reports present evidence for the presence of pituitary stem cells. Here we offer a critical review of the field and suggest additional studies that could resolve points of debate. Recent reports have relied on different markers, including SOX2, nestin, GFRa2, and SCA1, to identify pituitary stem cells and progenitors. Future studies will be needed to resolve the relationships between cells expressing these markers. Members of the Sox family of transcription factors are likely involved in the earliest steps of pituitary stem cell proliferation and the earliest transitions to differentiation. The transcription factor PROP1 and the NOTCH signaling pathway may regulate the transition to differentiation. Identification of the stem cell niche is an important step in understanding organ development. The niche may be the marginal zone around the lumen of Rathke's pouch, between the anterior and intermediate lobes of mouse pituitary, because cells in this region apparently give birth to all six pituitary hormone cell lineages. Stem cells have been shown to play a role in recurrent malignancies in some tissues, and their role in pituitary hyperplasia, pituitary adenomas, and tumors is an important area for future investigation. From a therapeutic viewpoint, the ability to cultivate and grow stem cells in a pituitary predifferentiation state might also be helpful for the long-term treatment of pituitary deficiencies.
Onyx Embolization of Extradural Spinal Arteriovenous Malformations With Intradural Venous Drainage
Authors: Lanzino Giuseppe , D'Urso Pietro Ivo , Kallmes David F. , Cloft Harry J.
Published: August 2011

BACKGROUND:

Extradural arteriovenous malformations (AVMs) are uncommon vascular malformations of the spine. They are characterized by an arteriovenous communication (localized in the paraspinal soft tissues and the epidural venous plexus) that may have retrograde intradural venous drainage. Surgical treatment of extradural AVMs can be challenging because of the common location ventral to the dural sac and the presence of arterialized venous lakes.

OBJECTIVE:

To assess the effectiveness of embolization with a liquid embolic material (Onyx; ev3 Inc, Irvine, California) in 7 consecutive patients with extradural spinal AVMs and intradural venous drainage.

METHODS:

We retrospectively collected information regarding patient characteristics, clinical presentation, symptom duration, diagnostic imaging, treatment, complications, and clinical and radiological follow-up.

RESULTS:

Patients were 5 men and 2 women (mean age, 66 years; range, 45-76 years). Symptom duration varied from 2 months to 6 years. Six patients underwent embolization of the AVM as the primary treatment; 1 patient was treated after attempted surgery. Complete obliteration was demonstrated in each patient on completion angiography and was confirmed during follow-up in 6. Three patients had resolution of their preembolization symptoms. Three patients had improvement but not complete resolution of their motor deficits. In 1 patient, the AVM was an incidental finding during an investigation for chronic low-back pain; symptoms were not thought to be related to the AVM, and symptoms were not ameliorated by successful embolization.

CONCLUSION:

Our early experience with these uncommon lesions suggests that Onyx embolization is a valuable and effective strategy for extradural spinal AVMs and intradural venous drainage.
The Natural History of Cranial Dural Arteriovenous Fistulae With Cortical Venous Reflux—The Significance of Venous Ectasia
Authors: Bulters Diederik O. , Mathad Nijaguna , Culliford David , Millar John , Sparrow Owen C.
Published: August 2011

BACKGROUND:

The quoted risk of hemorrhage from dural arteriovenous fistulae with cortical venous reflux varies widely, and the influence of angiographic grade on clinical course has not previously been reported.

OBJECTIVE:

To assess the risk of hemorrhage and the influence of angiographic grade on this risk, compared with known predictors of hemorrhage such as presentation.

METHODS:

Seventy-five fistulae with cortical venous reflux identified in our arteriovenous malformations clinic between 1992 and 2007 were followed up clinically, and their angiograms were reviewed.

RESULTS:

There were 8 hemorrhages in 90 years of follow-up. The annual incidence of hemorrhage before any treatment was 13%, and 4.7% after partial treatment, giving an overall incidence of 8.9% before definitive treatment. Borden and Cognard grades were poor discriminators of risk for lesions with the exception of Cognard type IV lesions. These lesions, characterized by venous ectasia, had a 7-fold increase in the incidence of hemorrhage (3.5% no ectasia vs 27% with ectasia). Patients presenting with hemorrhage (20%) or nonhemorrhagic neurological deficit (22%) had a higher incidence of hemorrhage than those with a benign presentation (4.3%), but this may be directly linked to the presence of venous ectasia.

CONCLUSION:

In this series untreated dural arteriovenous fistulae with cortical venous reflux had a 13% annual incidence of hemorrhage after diagnosis. There was a significant difference between those with and without venous ectasia. This should be confirmed by further studies, but probably defines a high-risk subgroup of patients that requires rapid intervention.
The use of mouse models to understand and improve cognitive deficits in Down syndrome
Authors: Das Ishita , Reeves Roger H.
Published: August 2011

Remarkable advances have been made in recent years towards therapeutics for cognitive impairment in individuals with Down syndrome (DS) by using mouse models. In this review, we briefly describe the phenotypes of mouse models that represent outcome targets for drug testing, the behavioral tests used to assess impairments in cognition and the known mechanisms of action of several drugs that are being used in preclinical studies or are likely to be tested in clinical trials. Overlaps in the distribution of targets and in the pathways that are affected by these diverse drugs in the trisomic brain suggest new avenues for DS research and drug development.
Consistency Among Elicitation Techniques for Intertemporal Choice: A Within-Subjects Investigation of the Anomalies
Authors: Guyse Jeffery L. , Simon Jay
Published: August 2011

The equivalence of two elicitation methods (sequences and matching) has been assumed when empirically testing the traditional discounting model even though the respective literature has revealed results that are dependent on the procedure used. Three common anomalies revealed (gain/loss asymmetry, short/long asymmetry, and the absolute magnitude effect) are investigated using the two different methods in a within-subjects experiment. In both procedures, it appears that the participants in this study evaluate monetary outcomes over time differently than the discounting model predicts. Patterns consistent with two of the anomalies (gain/loss and absolute magnitude effect) surface and interact in both elicitation techniques. Finally, a systematic inconsistency exists between the two methods. We observe significantly more consistency between the two elicitation techniques when the outcome is a gain in the relatively far future than when it is a future loss. This may be due to the participants' inability to display a preference for spreading losses, which they revealed in the sequences task, in the matching task.