bluuebunny/crossref_metadata_2025_split huggingface dataset:
Two-stage flux balance analysis of metabolic networks for drug target identification
Authors: Li Zhenping , Wang Rui-Sheng , Zhang Xiang-Sun 
Published: August 2011

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract
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

AbstractSingle 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

BackgroundDespite frequent use, little is known about the metabolic and endocrine side-effects of antipsychotics in individuals with intellectual disability.AimsTo 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.MethodObservational study comparing 138 antipsychotic-treated and 64 antipsychotic-naive participants with intellectual disability in one National Health Service trust with general population controls.ResultsAntipsychotic 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.ConclusionsAntipsychotics, 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.
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

Abstract

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

Abstract

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.
Simple Economics of the Price-Setting Newsvendor Problem
Authors: Salinger Michael , Ampudia Miguel 
Published: August 2011

The Lerner relationship linking the profit-maximizing price to marginal cost and the elasticity of demand generalizes to the price-setting newsvendor, and the result resolves the puzzle over the different effects of additive and multiplicative uncertainty on the solution. Multiplicative uncertainty increases the optimal price because it increases the marginal cost of a unit sold and does not affect the markup factor. Additive uncertainty has no effect on the marginal cost of a unit sold and lowers the markup factor because it increases the elasticity of the average quantity sold with respect to price. This paper was accepted by Martin Lariviere, operations management.
Durable Products, Time Inconsistency, and Lock-in
Authors: Gilbert Stephen M. , Jonnalagedda Sreelata 
Published: August 2011

Many durable products cannot be used without a contingent consumable product, e.g., printers require ink, iPods require songs, razors require blades, etc. For such products, manufacturers may be able to lock in consumers by making their products incompatible with consumables that are produced by other firms. We examine the effectiveness of such a strategy in the presence of strategic consumers who anticipate the future prices of both the durable product and the contingent consumable. Under a lock-in strategy, the manufacturer has pricing power over the contingent consumable, which she can use to extract additional rents from higher valuation consumers, but such pricing power may also reduce consumers' willingness to pay for the durable because it subjects them to being held up with higher consumables prices in the future. Restricting our attention to linear pricing policies, we find that if the manufacturer can commit to shutting down production of her durable after an initial one-time sale, then competition from another consumable of an appropriately degraded level of quality can benefit the manufacturer by mitigating consumers' fears of being held up. On the other hand, when the manufacturer cannot commit to shutting down production of her durable, then her own output of additional durables gives her an incentive to keep consumables prices low, and competition in the consumables market is less beneficial. This paper was accepted by Pradeep Chintagunta and Preyas Desai, special issue editors. This paper was accepted by Pradeep Chintagunta and Preyas Desai, special issue editors.
Label Confusion: The Groucho Effect of Uncertain Standards
Authors: Harbaugh Rick , Maxwell John W. , Roussillon Beatrice 
Published: August 2011

Labels certify that a product meets some standard for quality, but often consumers are unsure of the exact standard that the label represents. Focusing on the case of ecolabels for environmental quality, we show how even small amounts of uncertainty can create consumer confusion that reduces or eliminates the value to firms of adopting voluntary labels. First, consumers are most suspicious of a label when a product with a bad reputation has it, so labels are often unpersuasive at showing that a seemingly bad product is actually good. Second, label proliferation aggravates the effect of uncertainty, causing the informativeness of labels to decrease rather than increase. Third, uncertainty makes labeling and nonlabeling equilibria more likely to coexist as the number of labels increases, so consumers face greater strategic uncertainty over how to interpret the presence or absence of a label. Finally, a label can be legitimitized or spoiled for other products when a product with a good or bad reputation displays it, so firms may adopt labels strategically to manipulate such information spillovers, which further exacerbates label confusion. Managers can reduce label confusion by supporting mandatory labeling or by undertaking investments to make certain labels “focal.” This paper was accepted by Pradeep Chintagunta and Preyas Desai, special issue editors. This paper was accepted by Pradeep Chintagunta and Preyas Desai, special issue editors.
The (Exponential) Bipartitional Polynomials and Polynomial Sequences of Trinomial Type: Part II
Authors: Belbachir Hacène , Mihoubi Miloud 
Published: August 2011

AbstractIn a previous paper we investigated the (exponential) bipartitional polynomials involving polynomial sequences of trinomial type. Our aim is to give properties of bipartitional polynomials related to the derivatives of polynomial sequences of trinomial type. Furthermore, we deduce identities involving Bell polynomials.