bluuebunny/crossref_metadata_2025 huggingface dataset:
Marine genomics: at the interface of marine microbial ecology and biodiscovery
Authors: Heidelberg Karla B. , Gilbert Jack A. , Joint Ian
Published: July 2010

The composition and activities of microbes from diverse habitats have been the focus of intense research during the past decade with this research being spurred on largely by advances in molecular biology and genomic technologies. In recent years environmental microbiology has entered very firmly into the age of the ‘omics’– (meta)genomics, proteomics, metabolomics, transcriptomics – with probably others on the rise. Microbes are essential participants in all biogeochemical processes on our planet, and the practical applications of what we are learning from the use of molecular approaches has altered how we view biological systems. In addition, there is considerable potential to use information about uncultured microbes in biodiscovery research as microbes provide a rich source of discovery for novel genes, enzymes and metabolic pathways. This review explores the brief history of genomic and metagenomic approaches to study environmental microbial assemblages and describes some of the future challenges involved in broadening our approaches – leading to new insights for understanding environmental problems and enabling biodiscovery research.
A novel family of functional operons encoding methane/ammonia monooxygenase‐related proteins in gammaproteobacterial methanotrophs
Authors: Tavormina Patricia L. , Orphan Victoria J. , Kalyuzhnaya Marina G. , Jetten Mike S. M. , Klotz Martin G.
Published: July 2010

Genomes of alphaproteobacterial and verrucomicrobial methane‐oxidizing bacteria (MOB) encode sequence‐divergent copies of particulate methane monooxygenase [pMMO = (PmoABC); pmoCAB]. In contrast, sequenced gammaproteobacterial MOB (Gamma‐MOB) genomes contain single or multiple near‐identical copies of pmoCAB operons. In betaproteobacterial ammonia‐oxidizing bacteria (Beta‐AOB), near‐identical amoCAB operons encode ammonia monooxygenase (AMO), a homologue of pMMO. Here, we report that Gamma‐MOB in the genera Methylomonas, Methylobacter and Methylomicrobium also encode a sequence‐divergent particulate monooxygenase (pXMO). Whereas all known genes encoding pMMO or AMO cluster in the order ‘CAB’, the genes encoding pXMO are uniquely organized in the non‐canonical form ‘pxmABC.’ Steady state pxm mRNA was detected in cultures of Methylomonas sp. as well as in freshwater creek sediment samples, demonstrating that pxm genes are expressed in culture and in situ. Inclusion of PxmA and PxmB proteins in phylogenetic analyses of the Pmo/Amo protein superfamilies created trifurcated trees with three major clades: (i) Pmo of Alpha‐ and Gamma‐MOB and Amo of Gamma‐AOB; (ii) Amo of Beta‐AOB, Pmo of putative ethane‐oxidizing Gamma‐MOB and Pxm of Gamma‐MOB; and (iii) verrucomicrobial Pmo and Amo of ammonia‐oxidizing Archaea. These data support but do not prove the hypothesis that oxygen‐dependent methane and ammonia monooxygenases evolved from a substrate‐promiscuous ancestor after horizontal transfer while being integrated into the catabolic contexts of their extant hosts.
Use of an external fixator to correct a wry nose in a yearling
Authors: Cousty M. , Haudiquet P. , Geffroy O.
Published: July 2010

Wry nose is a rare condition. The resultant deviation of the nasal septum and maxilla/premaxilla often complicates deglutition and respiration. Traditional treatment consists of internal fixation with pins after an osteotomy and a rib graft. A 17‐month‐old Arab yearling was presented for evaluation of deviation of the maxilla and nasal septum. This deviation was managed using an external fixation device after bilateral osteotomy of the maxilla/premaxilla and reduction of the deviation. Partial resection of the nasal septum by a dorsal approach was also performed. The dental malocclusion and respiratory noise were corrected.
Equine embryonic stem‐like cells and mesenchymal stromal cells have different survival rates and migration patterns following their injection into damaged superficial digital flexor tendon
Authors: GUEST D. J. , SMITH M. R. W. , ALLEN W. R.
Published: July 2010

Reasons for performing study: Injury to the superficial digital flexor tendon (SDFT) is common in racing and sport horses and poor tendon regeneration leads to high reinjury rates. Autologous mesenchymal stromal cells (MSCs) are being used clinically to improve tendon regeneration but they have some practical limitations. Embryonic stem cells (ESCs) may overcome these limitations but their fate following injection into the damaged SDFT is unknown.

Objective: To inject MSCs and ESCs into distinct areas of damage in the SDFT and monitor their survival over a 3 month period.

Methods: MSCs and ESCs expressing different reporter genes were injected into separate sites of mechanically induced damage in SDFTs. Cell survival and distribution were examined post mortem after 10, 30, 60 and 90 days and host immune responses determined.

Results: Neither MSCs nor ESCs produced signs of cell‐mediated immune response or tumour formation. ESC survival was high and numbers were maintained at a constant level over 90 days. ESCs were present at all sites of damage. In contrast, MSCs showed <5% survival at 10 days and numbers declined over the course of the experiment. MSCs were detected only at the site into which they were injected.

Conclusions: ESCs survived in greater numbers than MSCs in the damaged tendon and did not induce an immune response, or form tumours at the injection sites in the 90 day time period studied. ESCs also demonstrated an ability to migrate to other areas of damage within the same tendon, whereas MSCs did not.

Potential relevance: ESCs can be used allogeneically, therefore providing a possible ‘off the shelf’ source of cells for therapeutic use which overcomes the practical limitations of autologous MSCs. Furthermore, MSCs and ESCs have different survival rates and migration patterns in the damaged tendon, suggesting that they may produce different functional effects. This may have clinical relevance to treating tendon injuries in the horse.
Comparative physical, mechanical and crystallographic properties of a series of gemfibrozil salts
Authors: David Sarah E , Ramirez Miren , Timmins Peter , Conway Barbara R
Published: July 2010

Objectives

Understanding the impact of the counterion on the properties of an acidic or basic drug may influence the choice of salt form, especially for less potent drugs with a high drug load per unit dose. The aim of this work was to determine the influence of the hydrogen bonding potential of the counterion on the crystal structure of salts of the poorly soluble, poorly compressible, acidic drug gemfibrozil and to correlate these with mechanical properties.

Methods

Compacts of the parent drug and the salts were used to determine Young's modulus of elasticity using beam bending tests. Crystal structures were determined previously from X-ray powder diffraction data.

Key findings

The free acid, tert-butylamine, 2-amino-2-methylpropan-1-ol and 2-amino-2-methylpropan-1,3-diol salts had a common crystal packing motif of infinite hydrogen-bonded chains with cross-linking between pairs of adjacent chains. The tromethamine (trsi) salt, with different mechanical properties, had a two-dimensional sheet-like network of hydrogen bonds, with slip planes, forming a stiffer compact.

Conclusions

The type of counter ion is important in determining mechanical properties and could be selected to afford slip and plastic deformation.
Solubilisation of drugs within liposomal bilayers: alternatives to cholesterol as a membrane stabilising agent
Authors: Ali M Habib , Kirby Daniel J , Mohammed Afzal R , Perrie Yvonne
Published: July 2010

Objectives

The aim of this work was to investigate the effect of cholesterol on the bilayer loading of drugs and their subsequent release and to investigate fatty alcohols as an alternative bilayer stabiliser to cholesterol.

Methods

The loading and release rates of four low solubility drugs (diazepam, ibuprofen, midazolam and propofol) incorporated within the bilayer of multilamellar liposomes which contained a range of cholesterol (0–33 mol/mol%) or a fatty alcohol (tetradecanol, hexadecanol and octadecanol) were investigated. The molecular packing of these various systems was also investigated in Langmuir monolayer studies.

Key findings

Loading and release of drugs within the liposome bilayer was shown to be influenced by their cholesterol content: increasing cholesterol content was shown to reduce drug incorporation and inclusion of cholesterol in the bilayer changed the release profile of propofol from zero-order, for phosphatidyl choline only liposomes, to a first-order model when 11 to 33 total molar % of cholesterol was present in the formulation. At higher bilayer concentrations substitution of cholesterol with tetradecanol was shown to have less of a detrimental impact on bilayer drug loading. However, the presence of cholesterol within the liposome bilayer was shown to reduce drug release compared with fatty alcohols. Monolayer studies undertaken showed that effective mean area per molecule for a 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) : cholesterol mixture deviated by 9% from the predicted area compared with 5% with a similar DSPC : tetradecanol mixture. This evidence, combined with cholesterol being a much more bulky structure, indicated that the condensing influence of tetradecanol was less compared with cholesterol, thus supporting the reduced impact of tetradecanol on drug loading and drug retention.

Conclusions

Liposomes can be effectively formulated using fatty alcohols as an alternative bilayer stabiliser to cholesterol. The general similarities in the characteristics of liposomes containing fatty alcohols or cholesterol suggest a common behavioural influence for both compounds within the bilayer.
New perspectives on lipid and surfactant based drug delivery systems for oral delivery of poorly soluble drugs
Authors: Müllertz Anette , Ogbonna Anayo , Ren Shan , Rades Thomas
Published: July 2010

Objectives

The aim of this review is to highlight relevant considerations when implementing a rational strategy for the development of lipid and surfactant based drug delivery system and to discuss shortcomings and challenges to the current classification of these delivery systems. We also aim to offer suggestions for an improved classification system that will accommodate lipid based formulations that are not currently accommodated in the lipid formulation classification system.

Key findings

When categorising lipid and surfactant based drug delivery systems, the current Lipid Formulations Classifications System is a useful tool. However, it does not apply to all marketed lipid and surfactant systems or those reported in research papers. A more profound understanding of the functionalities of lipids and surfactants and their role in emulsion formation will enable a rational development strategy and will create the basis for a revised classification system encompassing all employed lipid and surfactant drug delivery systems.

The ever-increasing number of poorly soluble compounds in drug discovery and development calls for the serious need for effective and affordable drug delivery strategies that will enhance bioavailability and decrease variability. Lipid and surfactant based drug delivery systems offer these advantages; however, the development of these systems requires proper understanding of the physicochemical nature of the compound as well as the lipid excipients and gastrointestinal digestion. One major challenge of lipid excipients and delivery systems is the varying range of compounds they contain. This has contributed to the challenge of proper characterisation and evaluation of these delivery systems, their stability, classification and regulatory issues, which consequently have affected the number of these formulations that eventually reach the market. Suggestions as to proper classification of these delivery systems based on their main lipid component and recommended use are put forward. The prospect of these delivery systems looks promising.
Patients' perceptions and illness severity at start of antidepressant treatment in general practice
Authors: Van Geffen Erica C G , Heerdink Eiebert R , Hugtenburg Jacqueline G , Siero Frans W , Egberts Antoine C G , Van Hulten Rolf
Published: July 2010

Objectives

Patients' perceptions are important to consider when trying to understand why patients often do not follow prescriptions for antidepressant treatment. This study aimed to investigate the influence of patients' perceptions and illness severity at the start on antidepressant-medication-taking behaviour.

Methods

Eighteen community pharmacies in the Netherlands participated in this 6-month follow-up study. One hundred and ten patients presenting a first antidepressant prescription, prescribed by a general practitioner (GP), were included. A questionnaire was completed at inclusion, after 6 and 26 weeks.

Key findings

Of all 110 patients, eight (7.3%) did not initiate drug taking, 32 (29.1%) discontinued use, six (5.5%) switched to different antidepressant medication, and 64 (58.2%) continued on the same antidepressant during follow-up. Compared to continuers, non-initiators had lower belief scores for impact of illness (P = 0.044), perceived norm GP (P < 0.001), intention to take medication (P < 0.001), and attitude towards medication (P = 0.004). Furthermore, non-initiators were less severely depressed (P = 0.024). Discontinuers and continuers did not differ in illness severity at inclusion. However, discontinuers more often reported a non-specific reason for use, such as fatigue and sleeping problems (P = 0.014). Compared to continuers, switchers had higher illness severity scores at inclusion (depression, P = 0.041; anxiety, P = 0.050). During follow-up depression and anxiety severity improved for all treatment groups and reached the same level of severity at 6 months.

Conclusions

Patients' illness and treatment perceptions and illness severity influence their decisions about antidepressant drug taking. Patients' care could be improved by eliciting patients' beliefs about illness and treatment and assessing illness severity before prescribing.
Adverse reactions to complementary medicines: the Australian pharmacy experience
Authors: Braun Lesley A , Tiralongo Evilin , Wilkinson Jenny M , Poole Susan , Spitzer Ondine , Bailey Michael , Dooley Michael
Published: July 2010

Objectives

The primary aim was to determine the prevalence of adverse reactions to over-the-counter complementary medicines and their severity, as described by consumers. Secondary aims were to identify consumers' reporting behaviours and understanding of the AUST L designation on product labels.

Methods

An anonymous, self-administered survey was completed by randomly selected pharmacy customers at 60 community pharmacy locations between August 2008 and February 2009.

Key findings

Of the 1121 survey participants (response rate 62%), 72% had used a complementary medicine product in the previous 12 months, and 7% of this group (n = 55) reported having experienced an adverse reaction at some time. Of these, 71% described the reaction as mild and not requiring treatment, 22% as moderate and/or requiring advice from a healthcare professional and 7% (n = 4) described it as severe and requiring hospitalisation. If they were to report the reaction, it was most commonly to a medical practitioner. Most (88%) of complementary medicine consumers had never noticed the term ‘AUST L’.

Conclusions

Complementary medicines are widely used by pharmacy customers. Adverse reactions to these products are under-reported to healthcare authorities. Most adverse reactions are mild and serious reactions are rare. Customers have little awareness of the designation AUST L.
The DoTS classification is a useful way to classify adverse drug reactions: a preliminary study in hospitalized patients
Authors: Calderón-Ospina Carlos , Bustamante-Rojas Carlos
Published: July 2010

Objective

The aim was to determine the prevalence of adverse drug reactions (ADRs) in hospitalized patients in a university hospital.

Methods

ADRs were identified by two evaluators, who reviewed the clinical histories of all patients admitted between 24 April and 24 May 2006. Patients with suspected ADRs were contacted. Three different investigators evaluated causality, the degree of preventability, and the mechanism producing the ADR. Causality was assessed using the scale proposed by the World Health Organization (WHO), and preventability was assessed using the modified Schumock and Thornton criteria.

Key findings

There were 32 ADRs in 104 hospitalized patients. Effects on the autonomic nervous system were the most common (13%) and the drugs most frequently implicated were systemic antimicrobial drugs (19%). Fifty-four per cent of the ADRs were classified as possible. Using the Dose, Time and Susceptibility (DoTS) classification, 77% of the ADRs were classified as being of collateral dose-responsiveness (i.e. they occurred within the range of therapeutic doses), and 65% were classified as intermediate reactions. The susceptibility factors associated most frequently with ADRs were comorbidities (i.e. the presence of diseases that were considered as risk factors to developing an ADR; 36%), age (26%) and exogenous factors (i.e. the presence of drug interactions that were involved in the occurrence of ADRs; 17%). Fifty per cent of the ADRs could have been prevented.

Conclusions

ADRs are very frequent in hospitalized patients and a significant proportion of them is preventable. The DoTS classification allowed complete evaluation of the types of ADR encountered. We are currently carrying out a much larger prospective study.
Eco-Friendly Screen-Printing Inks of Gadolinia Doped Ceria
Authors: Sanson Alessandra , Roncari Edoardo , Boldrini Stefano , Mangifesta Patrizia , Doubova Lioudmila
Published: July 2010

Gadolina doped ceria (GDC) is a promising electrolyte for intermediate temperature solid oxide fuel cells (IT-SOFC). Dense layers of this material can be economically deposited by screen printing. However, the inks for this technique generally use organic compounds that can raise health and safety issues, as well as economical issues. In order to obtain a low-cost alternative to the generally accepted organic-based ink, four different blends of binders were considered to prepare water-based GDC inks. The systems were deposited onto green NiO/GDC anodes produced by tape casting and treated at 1673 K for 4 h. By choosing the right combination of solvents and binders, it was possible to obtain a dense crack-free film of GDC from a water-based system.
Computational and Experimental Studies on the Effect of Flow-Distributors on the Performance of PEMFC
Authors: Bansode A. S. , Sundararajan T. , Das Sarit K.
Published: July 2010

Effective supply of reactants and product-water removal are the key issues in proton exchange membrane fuel cell (PEMFC) from the performance view point. Reactant distribution pattern can be one of the potential solutions for the well known water management problem in PEMFC. To study the effect of different flow configurations on the cell performance, three different flow-distributors, namely, parallel, serpentine, and mixed are analyzed numerically. A three-dimensional, numerical study was carried out in the three distributors for the identical reaction area. The effect of operating parameters such as flow rate and temperature was studied. The mixed flow-distributor is found to exhibit the best electrochemical performance as well as moderate pressure drop compared with the parallel and serpentine flow-distributors. The observation was confirmed by appropriate experimental study involving similar distributor geometries. Better reactant accessibility to the catalyst layer and moderate product-water removal from the cathode without diluting the reactant is argued to be the reason behind the better performance for the mixed-distributor.
Effects of Electrode Microstructure on Intermediate Temperature Solid Oxide Fuel Cell Performance
Authors: Naimaster Edward J. , Sleiti A. K.
Published: July 2010

In this study, the effects of electrode microstructure and electrolyte parameters on intermediate temperature solid oxide fuel cell (ITSOFC) performance were investigated using a one-dimensional solid oxide fuel cell model from the Pacific Northwest National Laboratory (PNNL). The activation overpotential was investigated through the exchange current density term, which is dependent on the cathode activation energy, the cathode porosity, and the pore size and grain size at the cathode triple phase boundary. The cathode pore size, grain size, and porosity were not integrated in the PNNL model, therefore, an analytical solution for exchange current density from Deng and Petric (2005, “Geometric Modeling of the Triple-Phase Boundary in Solid Oxide Fuel Cells,” J. Power Sources, 140, pp. 297–303) was utilized to optimize their effects on performance. Through parametric evaluation and optimization of the electrode microstructure parameters, the activation overpotential was decreased by 29% and the overall ITSOFC maximum power density was increased by almost 400% from the benchmark PNNL case. The effects and importance of electrode microstructure parameters on ITSOFC performance were defined. Optimization of such parameters will be the key in creating viable ITSOFC systems. Although this was deemed successful for this project, future research should be focused on numerically quantifying and modeling the electrode microstructure in two- and three-dimensions for more accurate results, as the electrode microstructure may be highly multidimensional in nature.
Channel Geometry Effect for Proton Exchange Membrane Fuel Cell With Serpentine Flow Field Using a Three-Dimensional Two-Phase Model
Authors: Wang Xiao-Dong , Zhang Xin-Xin , Liu Tao , Duan Yuan-Yuan , Yan Wei-Mon , Lee Duu-Jong
Published: July 2010

This study presents a complete three-dimensional, two-phase transport model for proton exchange membrane fuel cells based on the two-fluid method, which couples the mass, momentum, species, and electrical potential equations. The different liquid water transport mechanisms in the flow channels, gas diffusion layers, catalyst layers, and membrane are modeled using two different liquid water transport equations. In the flow channels, gas diffusion layers, and catalyst layers, the generalized Richards equation is used to describe the liquid water transport including the effect of the pressure gradient, capillary diffusion, evaporation and condensation, and electro-osmotic, while in the membrane, the liquid water transport equation only takes into account the effect of back diffusion and electro-osmotic. Springer’s model is utilized on the catalyst layer-membrane interface to maintain continuum of the liquid water distribution. The model is used to investigate the effect of flow channel aspect ratio on the performance of fuel cells with single and triple serpentine flow fields. The predictions show that for both flow fields, the cell performance improves with decreasing aspect ratio. The aspect ratio has less effect on the cell performance for the triple serpentine flow field than for the single serpentine flow field due to the weaker under-rib convection.
Numerical Analysis of a Cell-Based Indirect Internal Reforming Tubular SOFC Operating With Biogas
Authors: Nishino Takafumi , Szmyd Janusz S.
Published: July 2010

A numerical study is performed on the thermal and electrochemical characteristics of a tubular solid oxide fuel cell (SOFC) employing the steam reforming of biogas in each individual cell unit but indirectly from the anode. The numerical model used in this study takes account of momentum, heat, and mass transfer in and around the cell, including the effects of radiation, internal reforming, and electrochemical reactions. The biogas, which is fed into the reformer with steam, is assumed to be composed of methane (CH4) and carbon dioxide (CO2). The results show that, under the conditions of a constant average current density of 400 mA/cm2 and a constant fuel utilization of 80%, the terminal voltage of the cell decreases but only moderately as the proportion of CH4 in the fuel supplied to the reformer is reduced. It is also shown that temperature gradients within the cell decrease as the proportion of CH4 in the supplied fuel is reduced. These results are promising for the future use of biogas for this type of indirect internal reforming SOFC system.
Economic Viability of a Molten Carbonate Fuel Cell Working With Biogas
Authors: Castell Albert , Margalef Pere , Medrano Marc , Cabeza Luisa F. , Samuelsen Scott
Published: July 2010

Catalonia (Spain) has a significant potential of biogas production from agricultural activities and municipal waste. In addition, there are plenty of industrial cogeneration plants, but most of them use conventional fuels, such as natural gas, and conventional energy conversion devices, such as internal combustion engines. Molten carbonate fuel cells are ultraclean and highly efficient power generator devices capable of converting biogas into electricity and heat. Located in Lleida (Catalonia), Nufri is a fruit processing company with a long tradition on biogas production and cogeneration, with an installed capacity bigger than 45 MW. This study analyzes the economic viability of a fuel cell operating on biogas in Spain, on a real case basis (Nufri). Different fuel cell capacities are analyzed (from 300 kW to 1200 kW). A parametric study of different fuel cell prices ($/kW installed) is performed. Additional biogas cleanup requirements are taken into account. The results are based on the Spanish legislation, which establishes a special legal framework that grants favorable, technology-dependent feed-in premiums for renewable energy and cogeneration. Results show that the payback period ranges from 5 years to 8 years depending on the fuel cell capacity and installation price.
Polymer Electrolyte Fuel Cell Transport Mechanisms: A Universal Approach to Multilayer Two-Phase Modeling Through the General Transport Equation
Authors: Rama Pratap , Chen Rui
Published: July 2010

A mathematical multilayer, multispecies two-phase model for polymer electrolyte fuel cells (PEFCs) is presented based on fundamental molecular theory using the general transport equation (GTE). The GTE was previously developed and applied to bridge the gap that exists between the benchmark modeling philosophies in the literature for transport across the PEFC. In the current work, the GTE is applied with Darcy’s law to describe water transport and water uptake through the porous and quasiporous layers of a PEFC under single- and two-phase operating conditions. The characteristic transport equations and available material properties from the literature are translated into a single-cell fuel cell model, which is implemented using the object modeling technique. The PEFC model is applied to predict and validate the net water transport ratio and water content under a range of operating conditions. The numerical model exhibits good agreement with experimental data under both vapor- and liquid-equilibrated conditions. The model is then applied in a water transport study to determine the effects of cell compression on local water content, liquid water intrusion, water transport, and Ohmic resistance across nonreinforced polymer electrolyte membranes (PEMs) under two-phase operating conditions. The modeling results suggest that the presence of liquid water at the cathodic boundary of the PEM and a well-established liquid water network can affect water uptake and water transport and can reduce the Ohmic resistance of the PEM.
Noncoding No More
Authors: VanHook Annalisa M.
Published: July 2010

A polycistronic RNA encodes multiple small peptides that regulate the activity of a transcription factor.
Inhibiting Adhesion
Authors: Gough Nancy R.
Published: July 2010

Interferon-γ inhibits cell spreading by increasing the abundance of an unusual guanosine triphosphatase, GBP-2, that inhibits phosphoinositide 3-kinase.
Science Signaling
Podcast: 20 July 2010
Authors: Fainzilber Mike , VanHook Annalisa M.
Published: July 2010

Network redundancies lend robustness to the neuronal injury response.
Efficacy of Daptomycin against
Bacillus anthracis
in a Murine Model of Anthrax Spore Inhalation
Authors: Heine Henry S. , Bassett Jennifer , Miller Lynda , Purcell Bret K. , Byrne W. Russell
Published: July 2010

Daptomycin demonstrated
in vitro
(MIC
90
, 4 μg/ml) and
in vivo
activities against
Bacillus anthracis
. Twice-daily treatment with a dose of 50 mg/kg of body weight was begun 24 h after challenge and continued for 14 or 21 days; results were compared to those for controls treated with phosphate-buffered saline or ciprofloxacin. Day 43 survival rates were 6/10 mice for the 14-day and 9/10 mice for the 21-day treatment groups, compared to survival with ciprofloxacin: 8/10 and 9/10 mice, respectively. Culture results from tissues removed at the termination of the experiment were negative.
ADS-J1 Inhibits HIV-1 Entry by Interacting with gp120 and Does Not Block Fusion-Active gp41 Core Formation
Authors: González-Ortega Emmanuel , Mena Maria-Pau , Permanyer Marc , Ballana Ester , Clotet Bonaventura , Esté José A.
Published: July 2010

We had shown that virus resistance to ADS-J1 was associated with amino acid changes in the envelope glycoprotein, mostly located in the gp120 coding region. Time-of-addition and endocytic virus transfer assays clearly demonstrated that ADS-J1 behaved as a gp120 inhibitor. ADS-J1-resistant virus was cross-resistant to the polyanion dextran sulfate, and recombination of gp120 recovered only the ADS-J1-resistant phenotype. In summary, ADS-J1 blocks an early step of virus entry that appears to be driven by gp120 alone.
Lysogenic Transfer of
mef
(A) and
tet
(O) Genes Carried by Φm46.1 among Group A Streptococci
Authors: Di Luca Maria Chiara , D'Ercole Stefania , Petrelli Dezemona , Prenna Manuela , Ripa Sandro , Vitali Luca A.
Published: July 2010

We report the ex vivo lysogenic transfer of erythromycin and tetracycline resistance genes among group A streptococci (GAS). Of 42 susceptible strains, 69% acquired erythromycin/tetracycline resistance when infected with purified supernatants from strain m46 culture containing the phage Φm46.1. A significant
emm
-type-dependent barrier to lysogenic transfer was not observed. The
emm
12 strains were the only strains susceptible to the lytic action of the bacteriophage preparation.
Developmental Expression of a
Trypanosoma cruzi
Phosphoinositide-Specific Phospholipase C in Amastigotes and Stimulation of Host Phosphoinositide Hydrolysis
Authors: de Paulo Martins Vicente , Galizzi Melina , Salto Maria Laura , Docampo Roberto , Moreno Silvia N. J.
Published: July 2010

Phosphoinositide phospholipase C (PI-PLC) plays an essential role in cell signaling. A unique
Trypanosoma cruzi
PI-PLC (
Tc
PI-PLC) is lipid modified in its N terminus and localizes to the outer surface of the plasma membrane of amastigotes. We show here that
Tc
PI-PLC is developmentally regulated in amastigotes and shows two peaks of surface expression during the developmental cycle of
T. cruzi
, the first immediately after differentiation of trypomastigotes into amastigotes and the second before differentiation of amastigotes into trypomastigotes. Surface expression of
Tc
PI-PLC coincides with phosphatidylinositol 4,5-bisphosphate (PIP
2
) depletion in the host cell membrane and with an increase in the levels of its product, inositol 1,4,5-trisphosphate. During extracellular differentiation, PI-PLC is secreted into the incubation medium. Maximal early expression of
Tc
PI-PLC on the surface of amastigotes and PIP
2
depletion coincide with host cytoskeletal changes, Ca
2+
signaling, and transcriptional responses described previously. The presence of
Tc
PI-PLC on the outer surface of the plasma membrane of the parasite and the capacity to be secreted and to alter host phospholipids are novel mechanisms of the host-parasite interaction.
Involvement of Regulatory T Cells in the Immunosuppression Characteristic of Patients with Paracoccidioidomycosis
Authors: Ferreira Maria Carolina , de Oliveira Rômulo Tadeu Dias , da Silva Rosiane Maria , Blotta Maria Heloisa Souza Lima , Mamoni Ronei Luciano
Published: July 2010

Patients with paracoccidioidomycosis (PCM) exhibit a suppression of the cellular immune response characterized by negative delayed-type hypersensitivity (DTH) to
Paracoccidioides brasiliensis
antigens, the apoptosis of lymphocytes, and high levels of expression of cytotoxic-T-lymphocyte-associated antigen 4 (CTLA-4), interleukin-10 (IL-10), and transforming growth factor β (TGF-β). The aim of this study was to investigate whether and how regulatory T cells (Treg cells) are involved in this immunosuppression by analyzing the number, phenotype, and activity of these cells in patients with active disease (AD group) and patients who had received treatment (TD group). Our results showed that the AD patients had more Treg cells than the TD patients or controls (C group) and also had elevated levels of expression of regulatory markers (glucocorticoid-induced tumor necrosis factor [TNF] receptor-related protein [GITR], CTLA-4, CD95L, LAP-1, and CD38). An analysis of regulatory activity showed that Treg cells from the AD group had greater activity than did cells from the other groups and that cell-cell contact is mandatory for this activity in the C group but was only partially involved in the regulatory activity of cells from AD patients. The addition of anti-IL-10 and anti-TGF-β neutralizing antibodies to the cultures showed that the production of cytokines may be another mechanism used by Treg cells. In conclusion, the elevated numbers of these cells with an increased regulatory phenotype and strong suppressive activity suggest a potential role for them in the immunosuppression characteristic of paracoccidioidomycosis. In addition, our results indicate that while Treg cells act by cell-cell contact, cytokine production also plays an important role.
Evaluating the Involvement of Alternative Sigma Factors SigF and SigG in
Clostridium perfringens
Sporulation and Enterotoxin Synthesis
Authors: Li Jihong , McClane Bruce A.
Published: July 2010

Clostridium perfringens
type A food poisoning is the second most commonly identified bacterial food-borne illness. Sporulation contributes to this disease in two ways: (i) most food-poisoning strains form exceptionally resistant spores to facilitate their survival of food-associated stresses, and (ii) the enterotoxin (CPE) responsible for the symptoms of this food poisoning is synthesized only during sporulation. In
Bacillus subtilis
, four alternative sigma factors mediate sporulation. The same four sigma factors are encoded by
C. perfringens
genomes, and two (SigE and SigK) have previously been shown to be necessary for sporulation and CPE production by SM101, a transformable derivative of a
C. perfringens
food-poisoning strain (K. H. Harry, R. Zhou, L. Kroos, and S. B. Melville, J. Bacteriol. 2009, 191:2728-2742). However, the importance of SigF and SigG for
C. perfringens
sporulation or CPE production had not yet been assessed. In the current study, after confirming that sporulating wild-type SM101 cultures produce SigF (from a tricistronic operon) and SigG, we prepared isogenic
sigF
- or
sigG
-null mutants. Whereas SM101 formed heat-resistant, phase-refractile spores, spore formation was blocked in the
sigF
- and
sigG
-null mutants. Complementation fully restored sporulation by both mutants. By use of these mutants and complementing strains, CPE production was shown to be SigF dependent but SigG independent. This finding apparently involved regulation of the production of SigE and SigK, which Harry et al. showed to be necessary for CPE synthesis, by SigF. By combining these findings with those previous results, it is now apparent that all four alternative sigma factors are necessary for
C. perfringens
sporulation, but only SigE, SigF, and SigK are needed for CPE synthesis.
The impact of reduced ignition propensity cigarette regulation on smoking behaviour in a cohort of Ontario smokers: Figure 1
Authors: O'Connor Richard J , Fix Brian V , Hammond David , Giovino Gary A , Hyland Andrew , Fong Geoffrey T , Cummings K Michael
Published: July 2010

This study examined the degree to which legislation intended to reduce the incidence of cigarette-caused fires influenced the behaviours of a cohort of smokers in Ontario. A random digit dialled telephone survey of adult smokers residing in Ontario was conducted in 2005, ending 1 month prior to the reduced ignition propensity (RIP) regulation's implementation date. A follow-up survey was conducted one year later. Of the baseline participants, 73.0% (n=435) completed the follow-up survey. The frequency of fire risk behaviours was similar across both surveys. At baseline, only 3.7% of smokers interviewed reported that their cigarettes went out on their own ‘often’ while smoking. Following the implementation of the reduced ignition propensity legislation, this increased significantly to 14.7%. Results suggest that the proportion of Ontario smokers who reported engaging in behaviour such as leaving a cigarette burning unattended and smoking in bed actually declined, although these declines were not statistically significant across all measures of fire risk.
Firearm possession among arrestees in Trinidad and Tobago
Authors: Wells William , Katz Charles M , Kim Jeonglim
Published: July 2010

Objectives

To describe the sources that active offenders in Trinidad and Tobago use to obtain firearms and report their motivations for obtaining them. To estimate relationships between gang involvement, drug selling, and firearm ownership (or possession).

Setting

Port of Spain (Republic of Trinidad and Tobago).

Methods

A cross-sectional research design was used to collect self-report data from 421 recently booked arrestees (within 72 h of their arrest) in the Port of Spain Police District Detention Center. A survey instrument was used to collect data on firearm acquisition, drug use, gang membership and other behaviours. The sample provides insights about guns in the lives of arrestees in Trinidad and Tobago.

Results

15% of respondents reported ever owning (or possessing) a firearm. Among the possessor group, 82% owned a gun primarily for defensive purposes, but approximately half reported using a gun in a crime. Nearly half of gun possessors stored their guns in outside locations. Firearm possession was greater among arrestees involved in gangs and those involved in drug selling.

Conclusions

A comprehensive approach of prevention, intervention, and suppression strategies that are intended to prevent gun-related incidents should be focused on gangs, drugs, and guns. Searches for high-risk firearms should focus on public areas where gang members live and socialise. The study shows the value of collecting data from offender-based populations in the region for the purpose of directing violence-prevention strategies.
Muscle weakness, palpitations and a small chin: the Andersen–Tawil syndrome
Authors: Rajakulendran S , Tan S V , Hanna M G
Published: July 2010

‘Ion channelopathies’ have emerged in the past decade as a new cause of several neurological diseases. These Mendelian disorders are caused by mutations in genes that encode ion channel subunits and are often characterised by paroxysmal attacks of brain or muscle dysfunction, interspersed with periods of clinical normality. Andersen–Tawil syndrome is one of the rarest and is characterised clinically by the triad of periodic paralysis, cardiac dysrhythmias and skeletal abnormalities. Mutations in a potassium channel gene,KCNJ2which encodes the potassium channel, Kir2.1, underlie the disorder. Here, the authors describe a patient and review the clinical spectrum and genetic features of the disorder.
When the first antiepileptic drug fails in a patient with juvenile myoclonic epilepsy
Authors: Nicolson Andrew , Marson Anthony G
Published: July 2010

Juvenile myoclonic epilepsy is one of the most common types of epilepsy seen in an adult epilepsy clinic. Most patients have a good prognosis, particularly when treated with valproate, but a significant minority are more difficult to treat. In this article, we will focus on a management strategy when the initial antiepileptic drug is unsuccessful and outline an approach that translates directly to the clinic.
Epilepsy: creative sparks
Authors: Thomas Rhys H , Mullins Jane M , Waddington Tracey , Nugent Kane , Smith Phil E M
Published: July 2010

“If you are exposed to radioactive toxic waste there are case reports of people developing super-powers; but lymphoma is more likely.”Naomi Thomas, paediatrician and philosopher

An epilepsy diagnosis is very verbal, relying on witness history, personal narrative and analysis of how people describe the experience. Occasionally however, non-verbal descriptions of seizures allow us to gain a fuller understanding of this complex disorder. Artists are often inspired by personal experience, so it should be no surprise to find people depicting images of ill health, both their own and people they have observed. Furthermore, an ailment or affliction may influence an artist's portfolio over their lifetime, such as de Kooning's Alzheimer's disease and Monet's glaucoma. Epilepsy (in contrast with cerebrovascular or neurodegenerative disease) may present not just with a loss of function but with unusual super-added experiences such as déjà vu, ecstatic auras or hallucinations. Here we describe some artists who were thought to have had epilepsy, and the way in which their seizures influenced their art. It appears that for some, they have succeeded despite, rather than because of, their epilepsy and that rather than be inspired by their symptoms they were ashamed of them. If there is a common theme, it is in the unwanted psychological harm of some seizures provoking dark, frustrated imagery.
Lung cancer risk and radon exposure in a cohort of iron ore miners in Malmberget, Sweden
Authors: Jonsson Håkan , Bergdahl Ingvar A , Åkerblom Gustav , Eriksson Kåre , Andersson Kurt , Kågström Leif , Järvholm Bengt , Damber Lena
Published: July 2010

Objectives

Lung cancer caused by radon in miners is a well-known risk. However, the risk estimates vary between studies and between mines. We have studied the dose response–relationship in a Swedish iron ore mine where two other studies have previously reached different risk estimates. As this mine has relatively low radon levels, the results are highly relevant for risk estimation in non-uranium underground mines.

Methods

A new cohort of 5486 male workers employed from 1923 to 1996 was established. Cumulative radon exposures were assessed based on a large number of measurements, including reconstructions of historical conditions. 122 lung cancer cases occurred during the follow-up period of 1958–2000.

Results

The average cumulative exposure in underground workers was 32 kBq year/m3(65 working level months (WLM)), experienced over 14.6 years. The excess RR (ERR) per kBq year/m3was 0.046 (95% CI 0.015 to 0.077; 0.022 ERR/WLM). Confounding by quartz may affect these results but appears to account only for 10–20% of the risk. The results for squamous cell and small cell lung cancer were 0.049 and 0.072, respectively. However, no increased risk was observed for adenocarcinoma (0.000 ERR per kBq year/m3, 95% CI −0.017 to 0.017).

Conclusion

Our overall risk estimate is about half of that found in the first Malmberget study but twice that found in the same cohort in the previously published pooled analysis. Radon did not increase the risk for adenocarcinoma in the lung.
Bladder cancer risk in painters: a meta-analysis
Authors: Guha Neela , Steenland Nelson Kyle , Merletti Franco , Altieri Andrea , Cogliano Vincent , Straif Kurt
Published: July 2010

The International Agency for Research on Cancer has classified occupational exposure as a painter as ‘carcinogenic to humans’, largely based on increased risks of bladder and lung cancer. A meta-analysis, including more than 2900 incident cases or deaths from bladder cancer among painters reported in 41 cohort (n=2), record linkage (n=9) and case–control (n=30) studies, was conducted to quantitatively compare the results of the different study designs and the potential confounding effect of smoking as well as other occupational exposures. The summary relative risk (meta-RR, random effects) for bladder cancer in painters was 1.25 (95% CI 1.16 to 1.34; 41 studies) overall and 1.28 (95% CI 1.15 to 1.43; 27 studies) when including only smoking adjusted risk estimates. The elevated risk persisted when restricted to studies that adjusted for other occupational exposures (meta-RR 1.27; 95% CI 0.99 to 1.63; 4 studies). The results remained robust when stratified by study design, gender and study location. Furthermore, exposure–response analyses suggested that the risk increased with duration of employment. There was no evidence of publication bias. Taken together, these results support the conclusion that occupational exposures in painters are causally associated with the risk of bladder cancer.
The incidence of medically reported work-related ill health in the UK construction industry: Table 1
Authors: Stocks S J , McNamee R , Carder M , Agius R M
Published: July 2010

Objective

Self-reported work-related ill health (SWI) data show a high incidence of occupational ill health and a high burden of cancer attributable to occupational factors in the UK construction industry. However, there is little information on the incidence of medically reported work-related ill health (WRI) within this industry. This study aims to examine the incidence of WRI within the UK construction industry.

Method

Standardised incidence rate ratios (SRRs) were used to compare incidence rates of reports of medically certified work-related ill health returned to The Health and Occupation Reporting network (THOR) within the UK construction industry with all other UK industries combined.

Results

Male UK construction industry workers aged under 65 years had significantly raised SRRs for respiratory (3.8, 95% CI 3.5 to 4.2), skin (1.6, 1.4 to 1.8) and musculoskeletal disorders (MSD; 1.9, 1.6 to 2.2). These SRRs were further raised for those working within a construction trade. The increased SRRs for skin disease within male construction industry workers were due to contact dermatitis (1.4, 1.2 to 1.6) and neoplasia (4.2, 3.3 to 5.3). For respiratory disease, the increased SRRs were due to non-malignant pleural disease (7.1, 6.3 to 8.1), mesothelioma (7.1, 6.0 to 8.3), lung cancer (5.4, 3.2 to 8.9) and pneumoconiosis (5.5, 3.7 to 8.0), but the SRRs for asthma (0.09, 0.06 to 0.11) and mental ill health (0.3, 0.1 to 0.4) were significantly reduced.

Conclusion

The significantly raised SRRs for medically reported MSD and significantly reduced SRRs for mental ill health in construction workers confirm self-reported UK data. These SRRs provide a baseline of the incidence of WRI in the UK construction industry from which to monitor the effects of changes in policy or exposures.