bluuebunny/crossref_metadata_2025 huggingface dataset:
The interaction potential of herbal medicinal products: a luminescence-based screening platform assessing effects on cytochrome P450 and its use with devil's claw (Harpagophyti radix) preparations
Authors: Modarai Maryam , Suter Andy , Kortenkamp Andreas , Heinrich Michael
Published: February 2011

Objectives

Potential interactions between herbal medicinal products and the cytochrome (CYP) P450 system are an important safety concern. We set out to develop a screening panel for assessing such interactions and use it to evaluate the interaction potential of devil's claw.

Methods

The panel consisted of luminescence-based inhibition assays for CYP1A2, 2C9, 2C19, 2D6 and 3A4, and a reporter gene (luciferase) assay for pregnane X receptor (PXR) activation and CYP3A4 induction. Caftaric acid and chlorogenic acid, two compounds with strong fluorescence quenching properties, were used to demonstrate the assay's resistance to interference. We tested 10 commercial devil's claw preparations as well as harpagoside and harpagide, two important constituents of devil's claw.

Key findings

Five preparations were found to weakly inhibit CYP3A4 (IC50 124.2–327.6 µg/ml) and five were found to weakly activate PXR (EC50 10.21–169.3 µg/ml). Harpagoside and harpagide did not inhibit CYP3A4. In agreement with published data, bergamottin, a natural product known to interact with CYP3A4, was shown to inhibit CYP3A4 with an IC50 of 13.63 µm and activate PXR with an EC50 of 6.7 µm.

Conclusions

Devil's claw preparations are unlikely to have a clinically relevant effect on CYP function. The assay panel proved effective in screening devil's claw preparations, demonstrating its suitability for use with plant extracts. It showed superior sensitivity and resistance to interference.
Leadership in context: A review and research agenda for sub‐Saharan Africa
Authors: Muchiri Michael K.
Published: February 2011

In today's fast‐paced dynamic work environment, organizations are recognizing the important role played by leadership in attaining and sustaining individual, unit, and organizational effectiveness. This paper briefly reviews extant literature and builds a logical framework depicting the interrelationships between leadership and the contextual factors of societal culture and patrimonial behaviours in sub‐Saharan Africa. The article concludes by outlining a future research agenda for leadership in sub‐Saharan Africa.
Altered electroretinograms in patients with KCNJ10 mutations and EAST syndrome
Authors: Thompson Dorothy A. , Feather Sally , Stanescu Horia C. , Freudenthal Bernard , Zdebik Anselm A. , Warth Richard , Ognjanovic Milos , Hulton Sally A. , Wassmer Evangeline , van't Hoff William , Russell‐Eggitt Isabelle , Dobbie Angus , Sheridan Eamonn , Kleta Robert , Bockenhauer Detlef
Published: February 2011

Non‐technical summary  Light stimulates ion flow through the retina. This generates a potential change at the cornea which is recorded as an electroretinogram (ERG). Our understanding of the role of potassium ions in generating the ERG is based on animal models. The KCJN10 gene constitutes Kir4.1, the principle potassium channel expressed on the retinal Muller cell. We have been able to study the impact of this potassium channel on the human retina for the first time by recording the ERGs of patients with EAST syndrome who have known mutations of KCJN10. Our data show a reduction in the amplitude of the photopic negative response of the light‐adapted ERG and a decrease in the sensitivity of the dark‐adapted ERG. These data increase our understanding of how the ERG is generated and why these ERG parameters may be affected in disease.
Acute and chronic effects of hypercalcaemia on cortical excitability as studied by 5 Hz repetitive transcranial magnetic stimulation
Authors: Iacovelli Elisa , Gilio Francesca , Mascia Maria Lucia , Scillitani Alfredo , Romagnoli Elisabetta , Pichiorri Floriana , Fucile Sergio , Minisola Salvatore , Inghilleri Maurizio
Published: February 2011

Non‐technical summary  Calcium ions play crucial roles in many forms of synaptic plasticity at central nervous system level. We studied the effects of chronic and acute hypercalcaemia on synaptic plasticity in patients with primary hyperparathyroidism and healthy controls by applying over the primary motor cortex a non‐invasive neurophysiological technique named repetitive transcranial magnetic stimulation (rTMS). Our results showed that conditions of hypercalcaemia decreased synaptic plasticity as tested by rTMS. Our results may help to understand the mechanisms underlying neuronal dysfunctions during hypercalcaemia and to evaluate asymptomatic patients.
Is connexin36 critical for GABAergic hypersynchronization in the hippocampus?
Authors: Beaumont Michael , Maccaferri Gianmaria
Published: February 2011

Non‐technical summary  In some forms of incurable epilepsies, GABAergic interneurons, which physiologically mediate inhibition in the brain, are thought to mediate excitation. The presence of a specific form of electrical communication between these cells, which is mediated by structures called gap junctions, has been proposed to be involved in the generation of synchronized epileptiform discharges. In support of this hypothesis is the repeated finding in the literature that the drug carbenoxolone, which is an effective blocker of gap junction function, decreases epileptiform activity in models of epilepsy both in vivo and in vitro. Our work challenges this view and highlights additional side‐effects of carbenoxolone, which are unrelated to gap junctions, but seem to contribute to its reported antiepileptic activity. A full knowledge of these additional mechanisms is important for the rational development of new molecules to be used in the therapy of epilepsy.
Fracture Toughness of Composite Joints With Carbon Nanotube Reinforcement
Authors: Faulkner S. D. , Kwon Y. W.
Published: February 2011

Fracture toughness tests were conducted for carbon composite scarf joints with and without carbon nanotube (CNT) reinforcement in order to study the effect of CNT on enhancing the fracture toughness of the scarf joint interface. Both mode I (i.e., opening mode) and mode II (i.e., shear mode) fracture tests were undertaken with and without CNT applied locally at the joint interface. During the study, the image correlation technique was used to examine the fracture mechanisms altered by the introduction of CNT. The experimental study showed that CNT increased the fracture toughness of the composite interface significantly, especially for the mode II fracture, with altering the fracture mechanism. On the other hand, there was no significant change on mode I fracture caused by CNT reinforcement. The enhancement of mode II fracture toughness was considered to result from the mechanical interlocking between polymers and CNT at the scarf joint interface.
Probabilistic Framework for Uncertainty Propagation With Both Probabilistic and Interval Variables
Authors: Zaman Kais , McDonald Mark , Mahadevan Sankaran
Published: February 2011

This paper develops and illustrates a probabilistic approach for uncertainty representation and propagation in system analysis, when the information on the uncertain input variables and/or their distribution parameters may be available as either probability distributions or simply intervals (single or multiple). A unique aggregation technique is used to combine multiple interval data and to compute rigorous bounds on the system response cumulative distribution function. The uncertainty described by interval data is represented through a flexible family of probability distributions. Conversion of interval data to a probabilistic format enables the use of computationally efficient methods for probabilistic uncertainty propagation. Two methods are explored for the implementation of the proposed approach, based on (1) sampling and (2) optimization. The sampling-based strategy is more expensive and tends to underestimate the output bounds. The optimization-based methodology improves both aspects. The proposed methods are used to develop new solutions to challenge problems posed by the Sandia epistemic uncertainty workshop (Oberkampf et al., 2004, “Challenge Problems: Uncertainty in System Response Given Uncertain Parameters,” Reliab. Eng. Syst. Saf., 85, pp. 11–19). Results for the challenge problems are compared with earlier solutions.
An Improved Scaling Model of Buffeting Lift Forces in Air-Water Flows
Authors: Pascal-Ribot Sylviane , Blanchet Yves
Published: February 2011

This paper presents the results of a series of experiments to study the influence of diameter on the loading of a single rigid cylinder subjected to air-water cross-flow. Five rigid cylinders of same length and different diameters (12.15×10−3 m to 31.9×10−3 m) were tested over void fractions ranging from 10% to 80%. The fluctuating lift forces on the cylinder are measured and represented in the form of power spectral density. A scaling model of these forces previously developed from one series of experiments with one tube diameter (12.15×10−3 m) is tested on these new results by investigating the effect of tube diameter D. Unlike single phase results where the force spectra vary as D3, it is shown that for two-phase flows, the force spectra vary as D2. The experimental data collapse remarkably well. Both local void fraction and flow regime appear to be sensitive parameters. It confirms the importance of a precise knowledge of the local characteristics of two-phase flows in the study of buffeting forces mechanisms.
An Integrative Methodology for Product and Supply Chain Design Decisions at the Product Design Stage
Authors: Chiu Ming-Chuan , Okudan Gül
Published: February 2011

Supplier selection is one of the key decisions in supply chain management. Companies need not only to make the “make” or “buy” decisions but also differentiate across potential suppliers in order to improve operational performance. Product design is an engineering based activity that realizes the customer requirements into functions of a new product. Many studies have pointed out that the integration of product and supply chain is a key factor for profitability and efficiency. However, most studies address supply chain performance after freezing the design of the product; only a few studies discuss when and how to incorporate supply chain decisions during product design. This paper presents a graph theory based optimization methodology to tackle this problem. The supplier selection issue is considered by evaluating its impact on both internal (e.g., ease of assembly) and external (e.g., transportation time) enterprise performances, which are aggregated as supply chain performance at the conceptual design stage. A case study in the bicycle industry demonstrates the advantages of this methodology. The presented mathematical programming formulation enables simultaneous optimization of both product design and supply chain design during the early design stages.
Development of a Numerical Optimization Method for Blowing Glass Parison Shapes
Authors: Groot J. A. W. M. , Giannopapa C. G. , Mattheij R. M. M.
Published: February 2011

Industrial glass blowing is an essential stage of manufacturing glass containers, i.e., bottles or jars. An initial glass preform is brought into a mold and subsequently blown into the mold shape. Over the past few decades, a wide range of numerical models for forward glass blow process simulation has been developed. A considerable challenge is the inverse problem: to determine an optimal preform from the desired container shape. A simulation model for blowing glass containers based on finite element methods has previously been developed (Giannopapa, 2008, “Development of a Computer Simulation Model for Blowing Glass Containers,” ASME J. Manuf. Sci. Eng., 130, p. 041003; Giannopapa and Groot, 2007, “A Computer Simulation Model for the Blow-Blow Forming Process of Glass Containers,” 2007 ASME Pressure Vessels and Piping Conference and 8th International Conference on CREEP and Fatigue at Elevated Temperature). This model uses level set methods to track the glass-air interfaces. The model described in a previous paper of the authors showed how to perform the forward computation of a final bottle from the given initial preform without using optimization. This paper introduces a method to optimize the shape of the preform combined with the existing simulation model. In particular, the new optimization method presented aims at minimizing the error in the level set representing the glass-air interfaces of the desired container. The number of parameters used for the optimization is restricted to a number of control points for describing the interfaces of the preform by parametric curves, from which the preform level set function can be reconstructed. Numerical applications used for the preform optimization method presented are the blowing of an axisymmetrical ellipsoidal container and an axisymmetrical jar.
Reinventing the Wheel
Authors: Zuo Zhi Hao , Xie Yi Min , Huang Xiaodong
Published: February 2011

A rational approach to the mechanical design of wheel rims as a typical periodic structure is presented in the current work. With novel application of the latest bidirectional evolutionary structural optimization method, a procedure is presented for the optimal topological design of wheel rims. Design applications are studied with realistic loads on a general vehicle in various scenarios, where the results not only demonstrate originalities of wheel patterns, but also provide insights into existing wheel designs. The simplicity and generic nature imply the general applicability of the proposed approach to a wide range of wheel designs.
The Crystal Structure of a Self-Activating G Protein α Subunit Reveals Its Distinct Mechanism of Signal Initiation
Authors: Jones Janice C. , Duffy Jeffrey W. , Machius Mischa , Temple Brenda R. S. , Dohlman Henrik G. , Jones Alan M.
Published: February 2011

The
Arabidopsis
G protein α subunit exhibits properties necessary and sufficient for receptor-independent activation.
How Cells Use Pseudopods for Persistent Movement and Navigation
Authors: Van Haastert Peter J. M.
Published: February 2011

A model of pseudopod formation, splitting, and persistence describes how cells migrate.
Repair and Protect
Authors: Gough Nancy R.
Published: February 2011

By stimulating metabolic flux through the pentose phosphate pathway, ATM promotes the production of nucleotides for DNA repair and limits production of reactive oxygen species.
USE During Stress
Authors: Wong Wei
Published: February 2011

Stress-induced activation of p38 promotes more efficient processing of USE-containing mRNAs, including that encoding thrombin.
A Tale of Two Stomata
Authors: Hines Pamela J.
Published: February 2011

The transition from passive to active metabolic control of stomata and plant water balance occurred about 360 million years ago.
Trioxaquine PA1259 Alkylates Heme in the Blood-Feeding Parasite Schistosoma mansoni
Authors: Pradines Vincent , Portela Julien , Boissier Jérôme , Coslédan Frédéric , Meunier Bernard , Robert Anne
Published: February 2011

Trioxaquine PA1259 is an efficient drug on larval- and adult-stage schistosomes, able to alkylate heme inside worms treated with it, leading to the formation of covalent heme-drug adducts. Such a mechanism, similar to one reported for other trioxaquines in
Plasmodium
, indicates that heme may be a common target of these trioxane-based drugs in different blood-feeding parasites.
Population Pharmacokinetics and Pharmacodynamics of Caspofungin in Pediatric Patients
Authors: Li Chi-Chung , Sun Peng , Dong Yingwen , Bi Sheng , Desai Rajesh , Dockendorf Marissa Fallon , Kartsonis Nicholas A. , Ngai Angela L. , Bradshaw Susan , Stone Julie A.
Published: February 2011

We describe the pharmacokinetics (PKs) of caspofungin, an echinocandin antifungal, administered once daily as a 1-hour intravenous infusion in children and adolescents (ages, 3 months to 17 years), based on pooled data from four prospective pediatric studies. Caspofungin dosing was body-surface-area (BSA) based (50 mg/m
2
daily after 70 mg/m
2
on day 1). The area under the concentration-time curve from time zero to 24 h (AUC
0–24
), the concentration at the end of infusion (1 h after the start of infusion;
C
1
), and the trough concentration (24 h after the start of infusion;
C
24
) were obtained for 32 pediatric patients with invasive candidiasis, 10 with invasive aspergillosis, and 82 in the setting of empirical therapy with fever and neutropenia. Exposures were modestly higher (93 to 134% for
C
1
, 45 to 78% for
C
24
, ∼40% for AUC
0–24
) in pediatric patients than in adults receiving the standard 50-mg daily dose. The potential for covariates (age, gender, weight, race, renal status, serum albumin level, and disease state) to alter PKs was evaluated with a multiple-linear-regression model. Weight and disease state had statistically significant (
P
< 0.05) yet small effects on caspofungin PKs in pediatric patients. Concomitant use of dexamethasone (a cytochrome p450 inducer) was associated with a statistically significant reduction (44%) in
C
24
in a limited number of patients (
n
= 4). Odds ratios were estimated for the association between log-transformed PKs and treatment outcome or adverse events. No PK parameter or hybrid parameter (AUC/MIC,
C
1
/MIC, and
C
24
/MIC) was significantly correlated with treatment outcome or adverse events in the setting of similar response levels as adults, which suggests that the concentrations examined fall within the therapeutic window for caspofungin in pediatric patients. These results support a 50-mg/m
2
daily dosing regimen (after a 70-mg/m
2
loading dose) in children ages 3 months to 17 years.
Bioactivity and the First Transmission Electron Microscopy Immunogold Studies of Short
De Novo
-Designed Antimicrobial Peptides
Authors: Azad Marisa Ann , Huttunen-Hennelly Heidi Esther Katrina , Ross Friedman Cynthia
Published: February 2011

In light of the era of microbial drug resistance, the current study aimed to better understand the relationships between sequence, higher-order structure, and mechanism of action for five designed peptides against multidrug-resistant (MDR) pathogens. All peptides studied were 15 residues long, were polycationic, adopted alpha-helical structures within hydrophobic environments (excluding the
d
-amino acid-substituted peptide MA-d), and contained N-terminal glycine residues, a novel antimicrobial peptide (AMP) design principle. Increasing hydrophobicity enhanced MICs (≤500 μg/ml to ≤7.4 μg/ml) without significantly increasing hemolytic activity (18% maximum hemolysis at 3,400 μg/ml). To the best of our knowledge, this is the first study to have successfully adapted and used a transmission electron microscopy (TEM) immunogold method to investigate the mechanism of action of short (∼15 residues long) AMPs within bacteria. We propose a “floodgate” mechanism to possibly explain membrane deformation and the relative absence of membrane-associated peptides 10 h into incubation.
Penetration of Meropenem into Epithelial Lining Fluid of Patients with Ventilator-Associated Pneumonia
Authors: Lodise T. P. , Sorgel F. , Melnick D. , Mason B. , Kinzig M. , Drusano G. L.
Published: February 2011

Antibiotic penetration to the infection site is critical for obtaining a good clinical outcome in patients with ventilator-associated pneumonia (VAP). Surprisingly few studies have quantified the penetration of β-lactam agents into the lung, as measured by the ratio of area under the concentration-time curve (AUC) in epithelial lining fluid (ELF) to AUC in plasma (AUC
ELF
/AUC
plasma
ratio). These have typically involved noninfected patients. This study examines the penetration and pharmacodynamics of meropenem in the ELF among patients with VAP. Meropenem plasma and ELF concentration-time data were obtained from patients in a multicenter clinical trial. Concentration-time profiles in plasma and ELF were simultaneously modeled using a three-compartment model with zero-order infusion and first-order elimination and transfer (big nonparametric adaptive grid [BigNPAG]). A Monte Carlo simulation was performed to estimate the range of ELF/plasma penetration ratios one would expect to observe in patients with VAP, as measured by the AUC
ELF
/AUC
plasma
ratio. The range of AUC
ELF
/AUC
plasma
penetration ratios predicted by the Monte Carlo simulation was large. The 10th percentile of lung penetration was 3.7%, while the 90th percentile of penetration was 178%. The variability of ELF penetration is such that if relatively high ELF exposure targets are required to attain multilog kill or resistance suppression for bacteria like
Pseudomonas aeruginosa
, then even receiving the largest licensed dose of meropenem with an optimal prolonged infusion may not result in target attainment for a substantial fraction of the population.
Use of Pharmacokinetic-Pharmacodynamic Analyses To Optimize Therapy with the Systemic Antifungal Micafungin for Invasive Candidiasis or Candidemia
Authors: Andes David , Ambrose Paul G. , Hammel Jeffrey P. , Van Wart Scott A. , Iyer Varsha , Reynolds Daniel K. , Buell Donald N. , Kovanda Laura L. , Bhavnani Sujata M.
Published: February 2011

Echinocandins have become a first-line therapy for invasive candidiasis (IC). Using phase 3 trial data for patients with IC, pharmacokinetic-pharmacodynamic (PK-PD) relationships for efficacy for micafungin were examined. Micafungin exposures were estimated using a population pharmacokinetic model, and univariable and multivariable logistic regressions were used to identify factors associated with outcome, including the micafungin area under the concentration-time curve (AUC)/MIC ratio. Monte Carlo simulation was used to evaluate the probability of achieving AUC/MIC ratios associated with efficacy. Mycological and clinical success rates for evaluable cases were 89.4 and 90.9, respectively. MIC
50
s and MIC
90
s for
Candida
species inhibition were 0.008 and 0.5 mg/liter, respectively. The median AUC/MIC ratio was 15,511 (range, 41.28 to 98,716). Univariable analyses revealed a significant relationship between the AUC/MIC ratio and mycological response, with the worst response being among patients with lower (≤3,000) AUC/MIC ratios (
P
= 0.005). For patients with
Candida parapsilosis
, AUC/MIC ratios of ≥285 were predictive of a higher mycological response (
P
= 0.11). Multivariable logistic regression demonstrated the AUC/MIC ratio, APACHE II score, and history of corticosteroid use to be significant independent predictors of a favorable response. PK-PD target attainment analyses suggested that 76.7% and 100% of patients would achieve an AUC/MIC ratio of ≥3,000 for an MIC of 0.03 mg/liter and an AUC/MIC ratio of ≥285 for an MIC of <0.5 mg/liter, respectively. The identification of a lower AUC/MIC ratio target for
C. parapsilosis
than other
Candida
species suggests consideration of species-specific echinocandin susceptibility breakpoints and values that are lower than those currently approved by regulatory agencies.
Anthelmintics Are Substrates and Activators of Nematode P Glycoprotein
Authors: Kerboeuf Dominique , Guégnard Fabrice
Published: February 2011

P glycoproteins (Pgp), members of the ABC transporter superfamily, play a major role in chemoresistance. In nematodes, Pgp are responsible for resistance to anthelmintics, suggesting that they are Pgp substrates, as they are in mammalian cells. However, their binding to nematode Pgp and the functional consequences of this interaction have not been investigated. Our study showed that levamisole and most of the macrocyclic lactones (MLs) are Pgp substrates in nematodes. Ivermectin, although a very good substrate in mammalian cells, is poorly transported. In contrast to their inhibitory effect on mammalian Pgp, these drugs had a stimulatory effect on the transport activity of the reference Pgp substrate rhodamine 123 (R123) in the nematode. This may be due to a specific sequence of nematode Pgp, which shares only 44% identity with mammalian Pgp. Other factors, such as the affinity of anthelmintics for Pgp and their concentration in the Pgp microenvironment, could also differ in nematodes, as suggested by the specific relationship observed between the octanol-water partition coefficient (log P) of MLs and R123 efflux. Nevertheless, some similarities were also observed in the functional activities of the mammalian and nematode Pgp. As in mammalian cells, substrates known to bind the H site (Hoechst 33342 and colchicine) activated the R site, resulting in an increased R123 efflux. Our findings thus show that ML anthelmintics, which inhibit Pgp-mediated efflux in mammals, activate transport activity in nematodes and suggest that several substituents in the ML structure are involved in modulating the stimulatory effect.
Vibrio cholerae Triggers SOS and Mutagenesis in Response to a Wide Range of Antibiotics: a Route towards Multiresistance
Authors: Baharoglu Zeynep , Mazel Didier
Published: February 2011

Antibiotic resistance development has been linked to the bacterial SOS stress response. In
Escherichia coli
, fluoroquinolones are known to induce SOS, whereas other antibiotics, such as aminoglycosides, tetracycline, and chloramphenicol, do not. Here we address whether various antibiotics induce SOS in
Vibrio cholerae
. Reporter green fluorescent protein (GFP) fusions were used to measure the response of SOS-regulated promoters to subinhibitory concentrations of antibiotics. We show that unlike the situation with
E. coli
, all these antibiotics induce SOS in
V. cholerae
.
An Improved Model of the Aspergillus fumigatus CYP51A Protein
Authors: Fraczek M. G. , Bromley M. , Bowyer P.
Published: February 2011

Azole resistance is an increasing clinical problem for
Aspergillus fumigatus
, with the majority of published resistance arising from mutations in the azole target gene CYP51A. Previous structural studies of this protein have suffered from a nonorthologous, low-homology template for homology modeling. Here we present a new model based on the human CYP51A orthologue that provides a higher-quality model for
A. fumigatus
CYP51A.
Putative ATP-Binding Cassette Transporter Is Essential for
Brucella ovis
Pathogenesis in Mice
Authors: Silva Teane M. A. , Paixão Tatiane A. , Costa Érica A. , Xavier Mariana N. , Sá Joicy Cortez , Moustacas Valéria S. , den Hartigh Andreas B. , Carvalho Neta Alcina V. , Oliveira Sérgio C. , Tsolis Renée , Santos Renato L.
Published: February 2011

Brucella ovis
is a major cause of reproductive failure in sheep, which is associated with epididymitis and infertility in rams. Importantly,
B. ovis
is one of the few
Brucella
species that is not zoonotic. Due to the scarcity of studies on
B. ovis
infection, a murine model of infection was developed. The roles of
B. ovis
genes encoding a putative hemagglutinin and an ABC transporter were investigated in the mouse model. The kinetics of
B. ovis
infection were similar in BALB/c and C57BL/6 mice, and both strains of mice developed multifocal microgranulomas in the liver and spleen, but only minimal colonization and histopathological changes were observed in the genital tract. Therefore, the mouse was considered a suitable infection model for
B. ovis
but not for
B. ovis
-induced genital disease. Two mutant strains were generated in this study (the Δ
abcAB
and Δ
hmg
strains). The
B. ovis
Δ
abcAB
strain was attenuated in the spleens and livers of BALB/c mice compared to the wild-type (WT) strain (
P
< 0.001). Conversely, the Δ
hmg
strain infected mice at the same level as WT
B. ovis
, suggesting that a putative hemagglutinin is not required for
B. ovis
pathogenesis. Additionally, the Δ
abcAB
strain did not survive in peritoneal macrophages, extracellularly in the peritoneal cavity, or in RAW 264.7 macrophages. Moreover, infection with the Δ
abcAB
strain was not lethal for male regulatory factor 1-knockout mice, whereas infection with the
B. ovis
WT strain was 100% lethal within 14 days postinfection. These results confirm that the predicted ABC transporter is required for the full virulence and survival of
B. ovis in vivo
.
The Cluster 1 Type VI Secretion System Is a Major Virulence Determinant in
Burkholderia pseudomallei
Authors: Burtnick Mary N. , Brett Paul J. , Harding Sarah V. , Ngugi Sarah A. , Ribot Wilson J. , Chantratita Narisara , Scorpio Angelo , Milne Timothy S. , Dean Rachel E. , Fritz David L. , Peacock Sharon J. , Prior Joanne L. , Atkins Timothy P. , DeShazer David
Published: February 2011

The
Burkholderia pseudomallei
K96243
genome encodes six type VI secretion systems (T6SSs), but little is known about the role of these systems in the biology of
B. pseudomallei
. In this study, we purified recombinant Hcp proteins from each T6SS and tested them as vaccine candidates in the BALB/c mouse model of melioidosis. Recombinant Hcp2 protected 80% of mice against a lethal challenge with
K96243
, while recombinant Hcp1, Hcp3, and Hcp6 protected 50% of mice against challenge. Hcp6 was the only Hcp constitutively produced by
B. pseudomallei in vitro
; however, it was not exported to the extracellular milieu. Hcp1, on the other hand, was produced and exported
in vitro
when the VirAG two-component regulatory system was overexpressed in
trans
. We also constructed six
hcp
deletion mutants (
Δhcp1
through
Δhcp6
) and tested them for virulence in the Syrian hamster model of infection. The 50% lethal doses (LD
50
s) for the
Δhcp2
through
Δhcp6
mutants were indistinguishable from
K96243
(<10 bacteria), but the LD
50
for the
Δhcp1
mutant was >10
3
bacteria. The
hcp1
deletion mutant also exhibited a growth defect in RAW 264.7 macrophages and was unable to form multinucleated giant cells in this cell line. Unlike
K96243
, the
Δhcp1
mutant was only weakly cytotoxic to RAW 264.7 macrophages 18 h after infection. The results suggest that the cluster 1 T6SS is essential for virulence and plays an important role in the intracellular lifestyle of
B. pseudomallei
.
Extensive Polymorphism and Evidence of Immune Selection in a Highly Dominant Antigen Recognized by Bovine CD8 T Cells Specific for Theileria annulata
Authors: MacHugh Niall D. , Weir William , Burrells Alison , Lizundia Regina , Graham Simon P. , Taracha Evans L. , Shiels Brian R. , Langsley Gordon , Morrison W. Ivan
Published: February 2011

Although parasite strain-restricted CD8 T cell responses have been described for several protozoa, the precise role of antigenic variability in immunity is poorly understood. The tick-borne protozoan parasiteTheileria annulatainfects leukocytes and causes an acute, often fatal lymphoproliferative disease in cattle. Building on previous evidence of strain-restricted CD8 T cell responses toT. annulata, this study set out to identify and characterize the variability of the target antigens. Three antigens were identified by screening expressed parasite cDNAs with specific CD8 T cell lines. In cattle expressing the A10 class I major histocompatibility complex haplotype, A10-restricted CD8 T cell responses were shown to be focused entirely on a single dominant epitope in one of these antigens (Ta9). Sequencing of the Ta9 gene from field isolates ofT. annulatademonstrated extensive sequence divergence, resulting in amino acid polymorphism within the A10-restricted epitope and a second A14-restricted epitope. Statistical analysis of the allelic sequences revealed evidence of positive selection for amino acid substitutions within the region encoding the CD8 T cell epitopes. Sequence differences in the A10-restricted epitope were shown to result in differential recognition by individual CD8 T cell clones, while clones also differed in their ability to recognize different alleles. Moreover, the representation of these clonal specificities within the responding CD8 T cell populations differed between animals. As well as providing an explanation for incomplete protection observed after heterologous parasite challenge of vaccinated cattle, these results have important implications for the choice of antigens for the development of novel subunit vaccines.
Adsorptive cathodic stripping voltammetric determination of curcumin in turmeric and human serum
Authors: Gholivand Mohammad Bagher , Ahmadi Farhad , Pourhossein Alireza
Published: February 2011

A simple, rapid, reliable and fully validated differential pulse adsorptive cathodic stripping voltammetric procedure has been developed for determination of the curcumin in human serum and turmeric, based on its electrochemical reduction at a hanging mercury drop electrode. The Britton–Robinson (BR) buffer of pH 9.5 was found to be reasonable as a supporting electrolyte for the assay of the compound. The effect of different parameters, such as pH, accumulation potential and accumulation time, on the sensitivity of method was evaluated. Under the optimized conditions (accumulation potential –0.3 V, accumulation time 50 s, BR buffer pH 9.5), curcumin was generated one irreversible cathodic peak. This cathodic peak showed a linear dependence on the concentration of curcumin over the range of 5.0 × 10–9–2.8 × 10–7 mol l–1. The obtained detection limit under the optimal experimental conditions is 1.5 × 10–9 mol l–1 after 50 s of the accumulation time. The relative standard deviation of 1.12% for concentration of 5.0 × 10–8 mol l–1 with 50 s accumulation time was obtained. The procedure was used successfully to the assay of the curcumin in turmeric and spiked human serum, and a good agreement was obtained between the results of the proposed method and high performance liquid chromatography (HPLC) analysis.
Attitudes towards exercise in patients with chronic disease: the influence of comorbid factors on motivation and ability to exercise
Authors: Murphy Claire-Louise , Sheane Barry J , Cunnane Gaye
Published: February 2011

Background

Exercise is an integral part of a healthy lifestyle. It has a well defined role in maintaining health in chronic illness. This study was undertaken to determine attitudes towards exercise in patients admitted to hospital with medical illnesses.

Methods

A questionnaire on attitudes to and extent of exercise was devised and administered to patients admitted to an acute medical unit of a large university teaching hospital in 2008. Data were analysed using SPSS.

Results

107 patients participated, mean age 57 years (range 20–92): 79% had at least one chronic disease, 60% were overweight, 42% did little or no exercise, while 81% did not achieve moderate physical activity. Factors associated with reduced activity included increasing age, alcohol excess, lower education level, and unemployment. Approximately 50% of the patients blamed health problems while the other half cited lack of time or motivation as reasons for not exercising. Only 3% were aware of national or international exercise recommendations.

Conclusions

Much greater awareness of the importance of exercise and its impact on health and longevity is needed. Healthcare providers have an important role in exercise education in patients with acute and chronic disease.
Seroprevalence of Histomonas meleagridis in pullets and laying hens determined by ELISA
Authors: Grafl B. , Liebhart D. , Windisch M. , Ibesich C. , Hess M.
Published: February 2011

Serum samples from 1120 layers from 56 flocks and 400 pullets from 20 flocks were tested by an indirect sandwich ELISA to investigate the prevalence of antibodies to Histomonas meleagridis in chickens kept in alternative husbandry systems. The overall prevalence of antibodies to H meleagridis in layers was 37.3 per cent, and positive birds were identified in 50 flocks. This was significantly higher than in pullets, where only 8.3 per cent of the birds tested positive. Optical density (OD) values obtained from pullet sera were much lower than the OD values from layers; however, positive birds were detected in half of the pullet flocks. In particular, all birds from an organic pullet flock were found to be positive, with high OD values. Overall, the highest prevalence of positive sera was obtained from birds kept in free‐range flocks. Attempts to reisolate live histomonads from birds in 18 layer flocks were unsuccessful.
Evolutionary ecology at the extremes of species’ ranges
Authors: Hardie David C. , Hutchings Jeffrey A.
Published: February 2011

The nature of species at the extremes of their ranges impinges fundamentally on diverse biological issues, including species’ range dynamics, population variability, speciation and conservation biology. We review the literature concerning genetic and ecological variation at species’ range edges, and discuss historical and contemporary forces that may generate observed trends, as well as their current and future implications. We discuss literature which shows how environmental, ecological and evolutionary factors act to limit species’ ranges, and how these factors impose selection for adaptation or dispersal in peripheral populations exposed to extreme and stochastic biotic and abiotic stressors. When conditions are sufficiently harsh such that local extinction is certain, peripheral populations may represent temporary offshoots from stable core populations. However, in cases where peripheral populations persist at the range edge under divergent or extreme conditions, biologically significant differences can arise from historical and contemporary ecological and evolutionary forces. In many such cases reviewed herein, peripheral populations tended to diverge from the species’ core, and to display lower genetic diversity or greater stress-adaptation. We conclude that while such populations may be of particular conservation value as significant components of intraspecific biodiversity or sources of evolutionary innovation and persistence during environmental change, small and greatly variable population size, especially combined with low genetic variability, can result in elevated extinction risk in harsh and stochastic peripheral environments. As a result, while peripheral populations should not be dismissed as evolutionary dead-ends destined for local extinction, neither should they be uncritically granted inherently superior significance based only on their peripheral position alone.
Overview of the current status of sediment chemical analysis: trends in analytical techniques
Authors: Parkinson Don-Roger , Dust Julian M.
Published: February 2011

This article reviews selected techniques and current trends in the analysis of contaminants in sediments since the year 2000. Because of the variety of anthropogenic target analytes encountered in sediments, the monograph is separated into inorganic and organic subsections. Practical aspects, including advances in: analysis of standards, biological methods, instrumental methods, modeling aspects, sample preparation and extraction methods, and speciation techniques are discussed. The sediment matrices are complex and require an integrated approach encompassing sampling, preparation, extraction, and analysis steps to reach the detection levels required. Often hyphenated techniques are employed to utilize the multi-resolving and isolation powers of the combined instrumentation. The review mainly focuses on the ability of developing techniques and their approaches and applications not only to solve new problems but also to push detection limits on historically well known inorganic and organic contaminants, while highlighting emerging persistent organic pollutants. The impetus of such research is to obtain a more factual understanding of an ecosystem and overall condition of its habitant in the context of sediments that may act as reservoirs for anthropogenic pollutants. The review is not comprehensive but rather provides an overview of the status of sediment chemical analysis and focuses on the trends in analytical approaches towards analytes of anthropogenic contaminants in sediments.
Seasonal reproductive patterns and recommended sampling times for sentinel fish species used in environmental effects monitoring programs in Canada
Authors: Barrett Timothy J. , Munkittrick Kelly R.
Published: February 2011

Canada’s environmental effects monitoring (EEM) program is currently in its fifth cycle of monitoring for the pulp and paper industry and second cycle of monitoring for the metal mining industry. More than 60 different sentinel fish species have been used in the EEM fish population surveys and reproductive impacts have been identified as an issue of concern in the pulp and paper program. A review of the literature was conducted to obtain details of the reproductive biology of each fish species that has been used in EEM studies in Canada. Using available data on seasonal changes in gonadosomatic indices, the seasonal reproductive patterns of Canadian fish species were divided into categories based on reproductive strategy and the timing of initiation of gonadal recrudescence. Recommended sampling times were developed for each reproductive pattern based on periods of temporal stability, minimum variability, and maximum value in gonadosomatic indices within a reproductive cycle. The reproductive strategy, spawning time, spawning temperature, and recommended sampling time were provided for the each sentinel fish species as well as life history characteristics including longevity, age and size at maturity, and mobility. Examination of the fish surveys using small bodied forage species from the EEM pulp and paper program revealed that approximately 72% of these studies were not conducted at the developed recommended sampling times and the magnitude of impacts may be underestimated by failing to sample at the recommended time.
A review of the interaction between forest birds and eastern spruce budworm
Authors: Venier L.A. , Holmes S.B.
Published: February 2011

The eastern spruce budworm, Choristoneura fumiferana Clem., (hereafter budworm) is responsible for the largest areas of insect-caused disturbance in North America, and as such, is an important part of spruce–fir forest change and succession. The insectivorous forest bird community shows large and rapid responses to budworm outbreaks. There is good evidence that there are budworm-linked species (bay-breasted, Cape May, and Tennessee warblers) that respond to budworm outbreak much more strongly and consistently than other species, probably through increased productivity of local populations when budworm are abundant. There also appears to be a more widespread positive bird community response to budworm outbreak that involves many more species. The response is evident in local and regional scale studies, but individual species’ responses across studies are not always consistent, probably because of the relatively small number of studies conducted in a wide variety of contexts. Budworm outbreaks provide a short-term increase in food supply for birds, but also result in longer-term habitat change due to budworm-induced defoliation and tree mortality. Birds appear to influence budworm cycles, mostly at endemic population levels, through predation of large larvae and pupae. There are good arguments suggesting that bird predation is not the primary cause of budworm oscillations, but may play a role in determining the mean level of oscillations. Climate change is expected to change the bird–budworm relationship through changes in fire regimes, spruce–fir distributions, bird distributions, and budworm and bird phenology.
A review on sources of brominated flame retardants and routes of human exposure with emphasis on polybrominated diphenyl ethers
Authors: Daso Adegbenro P. , Fatoki Olalekan S. , Odendaal James P. , Okonkwo Jonathan O.
Published: February 2011

The presence of brominated flame retardants (BFRs) in various environmental matrices, including humans, has been well documented. Increasing levels of these emerging contaminants in various environmental compartments suggest the wide application of these chemicals in products of everyday use. The release of BFRs from treated products is generally believed to be the major source of these contaminants into the environment, particularly in indoor environments. The sources and pathways through which BFRs enter the human system are evaluated in this paper. Human exposure via consumption of contaminated food and water, inhalation and ingestion of dust, as well as dermal absorption, are important pathways for these contaminants. Consumption of fatty foods especially fish, meat, dairy products as well as human milk constitute important routes for human exposure to these contaminants. Although brominated diphenyl ether (BDE) 209 has been found to be less bioaccumulative due to its high molecular weight, its dominance in indoor dust samples could be responsible for its detection in most human tissues investigated. BDE 47 is the most dominant polybrominated diphenyl ether (PBDE) congener found in human tissues. Regional differences in BFR levels in various environmental and biological matrices reflect their consumption patterns with higher levels mostly reported in the North American environments than in other regions of the world.
A review on arsenic concentrations in Canadian drinking water
Authors: McGuigan Claire F. , Hamula Camille L.A. , Huang Sarah , Gabos Stephan , Le X. Chris
Published: February 2011

Recent events have increased public awareness of drinking water quality in Canada. The goal of this review was to examine how much information about arsenic (As) in Canadian drinking water is available. Provincial, territorial, and federal Web sites were searched for information about As in drinking water. Major scientific databases (PubMed, Web of Science) were searched for drinking water As information for all provinces and territories. Resulting information was examined for availability, accessibility, quality, and timeliness. Most provinces provided at least basic fact sheets about As, and several provinces provided comprehensive databases containing actual test results. The vast majority of Canadian municipal drinking water systems with As data show a concentration below 10 μg/L, the current guideline level. Several locations in Alberta, British Columbia, Manitoba, New Brunswick, Newfoundland and Labrador, Nova Scotia, Québec, and Saskatchewan have localized elevations of As (“hotspots”, >10 μg/L As); this information is available at the provincial level, but may not include exact locations nor the degree by which they exceed the current guideline limit of 10 μg/L. For other locations, however, little information is available. The lack of a centralized information source represents a significant obstacle to obtaining drinking water quality data. Although difficult to implement, a centralized and standardized source of national drinking water quality data is urgently needed to determine the effects of As and other contaminants on Canadians.
Toward dynamic global vegetation models for simulating vegetation–climate interactions and feedbacks: recent developments, limitations, and future challenges
Authors: Quillet Anne , Peng Changhui , Garneau Michelle
Published: February 2011

There is a lack in representation of biosphere–atmosphere interactions in current climate models. To fill this gap, one may introduce vegetation dynamics in surface transfer schemes or couple global climate models (GCMs) with vegetation dynamics models. As these vegetation dynamics models were not designed to be included in GCMs, how are the latest generation dynamic global vegetation models (DGVMs) suitable for use in global climate studies? This paper reviews the latest developments in DGVM modelling as well as the development of DGVM–GCM coupling in the framework of global climate studies. Limitations of DGVM and coupling are shown and the challenges of these methods are highlighted. During the last decade, DGVMs underwent major changes in the representation of physical and biogeochemical mechanisms such as photosynthesis and respiration processes as well as in the representation of regional properties of vegetation. However, several limitations such as carbon and nitrogen cycles, competition, land-use and land-use changes, and disturbances have been identified. In addition, recent advances in model coupling techniques allow the simulation of the vegetation–atmosphere interactions in GCMs with the help of DGVMs. Though DGVMs represent a good alternative to investigate vegetation–atmosphere interactions at a large scale, some weaknesses in evaluation methodology and model design need to be further investigated to improve the results.