bluuebunny/crossref_metadata_2025 huggingface dataset:
Photoprotective behaviour and sunscreen use: impact on vitamin D levels in cutaneous lupus erythematosus
Authors: Cusack Caitriona , Danby Claire , Fallon Jason C. , Ho Wen Lyn , Murray Barbara , Brady Jennifer , O'Kelly Patrick , Ambrose Nicola , Kearns Grainne , Murphy Gillian M.
Published: September 2008

Background: Sun exposure of the skin, independent of dietary sources, may provide sufficient vitamin D in healthy individuals. A recent study of patients with cutaneous lupus erythematosus concluded that over 70% of them restrict their sun exposure.

Methods: We recruited 52 patients with biopsy‐proven cutaneous lupus erythematosus to establish whether they are deficient in 25‐hydroxyvitamin D [25(OH)D]. We measured their serum 25(OH)D levels during summer months, investigated the effects of several variables on 25(OH)D levels and assessed the role of vitamin D supplementation.

Results: An overall mean 25(OH)D level of 63.03 (±23.3) nmol/l was obtained. Significantly low values (<25 nmol/l) were recorded in two (3.8%) patients and concentrations below 75 nmol/l were found in 34 (65.4%) patients. 25(OH)D levels were significantly lower among sun avoiders and daily sunscreen users, while significantly higher values were found among those who took cholecalciferol (vitamin D3) supplements. Low values were recorded among those with renal disease despite supplementation with vitamin D3 in some cases.

Conclusions: We suggest that patients with cutaneous lupus erythematous have suboptimal 25(OH)D levels, which are significantly raised by the addition of at least 400 IU/day of cholecalciferol. We recommend supplementation with an active vitamin D analogue in collaboration with a consultant nephrologist, for the subgroup of patients with renal disease.
Actinic prurigo
Authors: Ross Gayle , Foley Peter , Baker Chris
Published: September 2008

Actinic Prurigo (AP), an uncommon idiopathic photodermatosis, presents a distinct clinical picture and can be severely debilitating. The clinical features, investigation and treatment of AP are reviewed. We report the experience of an Australian photobiology unit with this condition.
Effect of the brain‐derived neurotrophic factor and the apolipoprotein E polymorphisms on disease progression in preclinical Alzheimer’s disease
Authors: Hashimoto R. , Hirata Y. , Asada T. , Yamashita F. , Nemoto K. , Mori T. , Moriguchi Y. , Kunugi H. , Arima K. , Ohnishi T.
Published: September 2008

Genetic factors, such as apolipoprotein E (ApoE) polymorphisms, are thought to play an important role in the etiology of Alzheimer’s disease (AD). Recent association studies have suggested that the Val66Met polymorphism in the brain‐derived neurotrophic factor (BDNF) gene could play a role in the development of AD. To identify genotypic effects of the BDNF and the ApoE genes on disease progression in preclinical AD, we assessed morphological changes using serial magnetic resonance imaging during the preclinical period of AD in 35 individuals. When all subjects were analyzed as one group, progressive atrophy was noted in the limbic, paralimbic and neocortical areas. Individuals of the BDNF Val/Val genotype showed progressive atrophy in the left medial temporal areas, whereas the BDNF Met allele carriers showed additional changes in the anterior cingulate cortex (ACC), posterior cingulate cortex (PCC) and the precuneus. An interaction between the BDNF genotype and progressive morphological changes was found in the PCC. The noncarriers for the ApoE ɛ4 allele showed progressive atrophy in the bilateral medial temporal areas. In addition to changes in the medial temporal areas, ɛ4 carriers showed progressive atrophy in the PCC, ACC and precuneus. An interaction between the ApoE genotype and progressive morphological change was noted in the right medial temporal area. The present preliminary study indicates that polymorphisms of the ApoE and the BDNF genes could affect disease progression in preclinical AD and implies that the Met‐BDNF polymorphism could be an additional risk factor for rapid disease progression in preclinical AD.
Bovine Blood and Neuromuscular Paralysis as a Bridge to Recovery in a Patent with Severe Autoimmune Hemolytic Anemia
Authors: Pachinburavan Monvasi , Marik Paul E.
Published: September 2008

Hemoglobin solutions have several advantages as substitutes for erythrocyte transfusions. They have a prolonged shelf life, do not require cross‐matching, are associated with few transfusion reactions, and are effective in delivering oxygen to the tissues. Despite the potential clinical utility of these solutions, they have not achieved widespread use. HbOC‐201 (Hemopure, Biopure, Cambridge, MA, USA) is a bovine hemoglobin solution that has been FDA approved for compassionate use in Jehovah's witness patients requiring transfusions. Here we report a case of a patient with hemoglobin H disease who developed a severe life‐threatening mixed warm and cold antibody mediated autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP) who was successfully treated with HbOC‐201 as an adjunct to blood transfusion.
Effect of the Soluble TNF‐Antagonist Etanercept on Tumor Necrosis Factor Bioactivity and Stability
Authors: Mann Douglas L. , Bozkurt Biykem , Torre‐Amione Guillermo , Soran Ozlem Z. , Sivasubramanian Natarajan
Published: September 2008

Background: Targeted anti‐tumor necrosis factor (TNF) strategies in patients with rheumatoid arthritis have resulted in new and/or worsening heart failure in individuals who were free of cardiovascular disease.

Methods and Results: To determine the mechanism of new and/or worsening heart failure in patients who were receiving the soluble TNF‐antagonist etanercept, we analyzed frozen plasma samples from a previous clinical trial with etanercept in heart failure patients, and conducted complimentary mechanistic in vitro studies. Analysis of the clinical trial data showed that use of etanercept resulted in a significant 70‐fold increase in the level of immunoreactive TNF. Complimentary in vitro studies using an L929 bioassay showed that at low concentrations of etanercept relative to TNF there was an unexpected 1.5‐ to 1.75‐fold increase in the absolute level of TNF bioactivity. We also examined the effect of etanercept on TNF stability and the results showed that there was a two‐fold increase in the mass of bioactive homotrimeric TNF when the molar ratio of TNF to etanercept was approximately 200:1.

Conclusion: Etanercept increases the immunoreactive mass of TNF in heart failure patients, as well as augments TNF cytotoxicity in certain settings, thus suggesting one potential mechanism for the worsening heart failure in some patients who were receiving this agent.
Bioinformatic Primer for Clinical and Translational Science
Authors: Faustino Randolph S. , Chiriac Anca , Terzic Andre
Published: September 2008

The advent of high‐throughput technologies has accelerated generation and expansion of genomic, transcriptomic, and proteomic data. Acquisition of high‐dimensional datasets requires archival systems that permit efficiency of storage and retrieval, and so, multiple electronic repositories have been initiated and maintained to meet this demand. Bioinformatic science has evolved, from these intricate bodies of dynamically updated information and the tools to manage them, as a necessity to harness and decipher the inherent complexity of high‐volume data. Large datasets are associated with a variable degree of stochastic noise that contributes to the balance of an ordered, multistable state with the capacity to evolve in response to stimulus, thus exhibiting a hallmark feature of biological criticality. In this context, the network theory has become an invaluable tool to map relationships that integrate discrete elements that collectively direct global function within a particular –omic category, and indeed, the prioritized focus on the functional whole of the genomic, transcriptomic, or proteomic strata over single molecules is a primary tenet of systems biology analyses. This new biology perspective allows inspection and prediction of disease conditions, not limited to a monogenic challenge, but as a combination of individualized molecular permutations acting in concert to effect a phenotypic outcome. Bioinformatic integration of multidimensional data within and between biological layers thus harbors the potential to identify unique biological signatures, providing an enabling platform for advances in clinical and translational science.
The making of a melanocyte: the specification of melanoblasts from the neural crest
Authors: Thomas Aaron J. , Erickson Carol A.
Published: September 2008

Melanocytes differentiate from the neural crest (NC), which is a transient population of cells that delaminates from the neural tube and migrates extensively throughout the embryo during vertebrate development. Melanoblast specification from NC precursors is a progressive process during which initially pluripotent cells become restricted to the melanogenic lineage and adopt the gene expression profile and morphology of melanocytes. This specification process is governed primarily by Wnt and BMP signaling molecules, although other signaling pathways, such as those activated by Kit and Endothelin 3, can also stimulate melanogenesis. The transcriptional repressor FoxD3 occupies a central role in melanocyte fate determination by repressing melanogenesis in premigratory NC cells and in other NC lineages.
Diminishing return on investment for biodiversity data in conservation planning
Authors: Grantham Hedley S. , Moilanen Atte , Wilson Kerrie A. , Pressey Robert L. , Rebelo Tony G. , Possingham Hugh P.
Published: September 2008

It is generally assumed that gathering more data is a good investment for conservation planning. However, the benefits of additional data have seldom been evaluated by analyzing the return on investment. If there are diminishing returns in terms of improved planning, then resources might be better directed toward other actions, depending on their relative costs and benefits. Our aim was to determine the return on investment from spending different amounts on survey data before undertaking a program of implementing new protected areas. We estimated how much protea data is obtained as a function of dollars invested in surveying. We then simulated incremental protection and loss of habitat to determine the benefit of investment in that data on the protection of proteas. We found that, after an investment of only US$100,000 (∼780,000 South Africa Rand [ZAR]), there was little increase in the effectiveness of conservation prioritizations, despite the full data set costing at least 25 times that amount.
Immediate versus delayed sequential bilateral cataract surgery: an analysis of costs and patient value
Authors: Lundström Mats , Albrecht Susanne , Roos Pontus
Published: September 2008

Purpose:  To compare resource utilization of two different strategies for bilateral cataract surgery: immediate sequential cataract surgery (ISCS) versus delayed sequential cataract surgery (DSCS). The purpose was also to analyse the value for the patient of undergoing ISCS versus DSCS.

Methods:  Differences in routines and resource utilization between ISCS (n = 17) and DSCS (n = 80) were studied in a cohort of cataract surgery patients at our clinic in Karlskrona, Sweden. Costs were extracted from an earlier publication by the same clinic. The value for the patient was studied using the capability index, based on published data on the benefit to the patient of ISCS or DSCS using the Catquest questionnaire.

Results:  Operating both eyes of a patient was 1.14 times more expensive with DSCS than with ISCS including all surgical costs. The value to the patient of undergoing ISCS depended on the time between first‐ and second‐eye surgery in DSCS and the remaining lifetime after both‐eye surgery. A long waiting time for second‐eye surgery and a short remaining lifetime decreased the patient value of DSCS compared to ISCS.

Conclusion:  DSCS is 14% more expensive than ISCS. The value for the patient of ISCS compared to DSCS depends on how long the period will be between first‐ and second‐eye surgery in DSCS and also on the patient’s survival time after surgery.
Vernal keratoconjunctivitis: a major review
Authors: Kumar Sunil
Published: September 2008

Vernal keratoconjunctivitis (VKC) is a chronic, bilateral, at times asymmetrical, seasonally exacerbated, allergic inflammation of the ocular surface, involving tarsal and/or bulbar conjunctiva. Though the allergic nature of this entity has been accepted for a long time, the accumulation of a large amount of immunological data has proved that the pathogenesis of VKC is much more complex than a mere type 1 hypersensitivity reaction. In the past several years, many clinical and experimental studies about the cells and mediators involved in initiating and perpetuating the ocular allergic inflammation have shown that T helper type 2 cells and their cytokines, corneal fibroblasts and epithelium along with various growth factors play an important role in the pathogenesis of VKC. Based on this information about the pathogenesis of VKC newer, more selective drugs like anti‐chemokine receptor antibodies and leukotriene receptor antagonists are under evaluation. Cyclosporine has been shown to be effective in the treatment of VKC but further randomized control trials are required to establish the minimum effective concentration.
Antigen-Specific T-Cell Responses of Leprosy Patients
Authors: Duthie Malcolm S. , Goto Wakako , Ireton Greg C. , Reece Stephen T. , Sampaio Lucas H. , Grassi A. B. , Sousa Ana Lucia M. , Martelli Celina M. T. , Stefani Mariane M. A. , Reed Steven G.
Published: September 2008

The identification of human T-cell antigens of
Mycobacterium leprae
could improve treatment and help to disrupt the transmission of leprosy by directing diagnosis and vaccine programs. This study screened a panel of
M. leprae
recombinant proteins for T-cell recall responses, measured by gamma interferon (IFN-γ) production, among leprosy patients. After initial studies using peripheral blood mononuclear cells from leprosy patients, we transitioned our studies to simple whole-blood assays (WBA), which are more applicable in field or clinical settings. T-cell responses generated in WBA using blood from individuals in Goiânia, Brazil, demonstrated that several
M. leprae
antigens (ML0276, ML0840, ML1623, ML2044, and 46f) elicited >0.5 IU/ml IFN-γ, and these proteins were classified as immunogenic and leprosy specific. Several of these individual antigens were recognized by cells from >60% of Brazilian paucibacillary (PB) leprosy patients, and ML0276, ML0840, ML1623, and 46f complemented each other such that 82% of PB patients had strong (>1.25 IU/ml IFN-γ) responses to at least one of these proteins. These proteins were also recognized by cells from a significant proportion of the household contacts of multibacillary leprosy patients, but in contrast, few responses were observed in active tuberculosis patients or healthy control groups from areas of endemicity. Our results indicate several potential candidate antigens which may be useful for either leprosy diagnosis or vaccination and demonstrate the utility of leprosy WBA that can be applied broadly in clinical or field settings.
Comparison of Four Molecular Typing Methods for Characterization of
Corynebacterium diphtheriae
and Determination of Transcontinental Spread of
C. diphtheriae
Based on BstEII rRNA Gene Profiles
Authors: De Zoysa Aruni , Hawkey Peter , Charlett Andre , Efstratiou Androulla
Published: September 2008

The diphtheria epidemic in the Russian Federation in the 1990s made diphtheria a focus of global concern once again. The development of rapid and reproducible typing methods for the molecular characterization of
Corynebacterium diphtheriae
has become a priority in order to be able to monitor the spread of this important pathogen on a global scale. We report on a comparison of four molecular typing methods (ribotyping, pulsed-field gel electrophoresis [PFGE], random amplification of polymorphic DNA [RAPD], and amplified fragment length polymorphism [AFLP]) for the characterization of
C. diphtheriae
strains. Initially, 755 isolates originating from 26 countries were analyzed by ribotyping. One strain of each ribotype was then randomly chosen and characterized by PFGE, RAPD, and AFLP. In order to ascertain whether the Eastern European epidemic ribotype could be further discriminated, 10 strains of ribotype D1 (the epidemic ribotype) from different geographical regions were randomly chosen and subjected to analysis by PFGE, RAPD, and AFLP. The results revealed that ribotyping is highly discriminatory and reproducible and is currently the method of choice for typing
C. diphtheriae
. PFGE and AFLP were less discriminatory than ribotyping and RAPD. An assessment of the transcontinental spread of the organism showed that several genotypes of
C. diphtheriae
circulated on different continents of the world and that each outbreak was caused by a distinct clone. The ribotypes seen in Europe appeared to be distinct from those seen elsewhere, and certain ribotypes appeared to be unique to particular countries.
Identification of Coagulase-Negative Staphylococci by Using the BD Phoenix System in the Low-Inoculum Mode
Authors: Brigante Gioconda , Menozzi Maria Grazia , Pini Beatrice , Porta Rosaria , Somenzi Pietro , Sciacca Agata , Spanu Teresa , Stefani Stefania
Published: September 2008

The new “low-inoculum” mode of the Phoenix system was evaluated to identify clinical coagulase-negative staphylococci. API ID32 Staph panels were used as comparators, and discrepancies were resolved by 16S rRNA and
tuf
gene analysis. The system correctly identified 90.5% of isolates, with a mean time of 10.2 h. Accuracy was satisfactory for
Staphylococcus epidermidis, S. saprophyticus
, and
S. haemolyticus
.
Validation of an Automated Detection Platform for Use with the Roche Linear Array Human Papillomavirus Genotyping Test
Authors: Stevens Matthew P. , Garland Suzanne M. , Tabrizi Sepehr N.
Published: September 2008

An automated platform (BeeBlot) was evaluated in parallel with the recommended protocol for the hybridization and detection steps of the Roche Linear Array human papillomavirus (HPV) genotyping test using DNA from 143 cervical specimens. Genotyping profiles showed 100% concordance between the methods, suggesting that automation could complement the Roche Linear Array for enhanced speed and reproducibility.
Use of
Bordetella pertussis
BP3385 To Establish a Cutoff Value for an IS
481
-Targeted Real-Time PCR Assay
Authors: Guthrie J. L. , Seah C. , Brown S. , Tang P. , Jamieson F. , Drews S. J.
Published: September 2008

This study utilized the
Bordetella pertussis
single-copy PCR target BP3385 as a means of confirming IS
481
PCR-positive reactions with cycle threshold (

C
T

) values of >35. IS
481
PCRs with

C
T

values of >35 cycles may represent PCR conditions where there is <1 CFU of
B. pertussis
per PCR.
Progress in combating cigarette smuggling: controlling the supply chain
Authors: Joossens L , Raw M
Published: September 2008

Background:

The illicit tobacco trade results in huge losses of revenue to governments, estimated at $US40–50 billion in 2006, and in increased consumption and thus health problems because it makes tobacco available more cheaply. On 20 October 2008 the second meeting of the International Negotiating Body (INB2) on the illicit trade protocol of WHO’s Framework Convention on Tobacco Control (FCTC) will discuss measures to tackle the illicit trade in tobacco products.

Methods:

This paper presents the experience over the last decade of three countries, Italy, Spain and the United Kingdom, which shows that tobacco smuggling can be successfully tackled.

Conclusion:

The evidence strongly suggests that the key to controlling smuggling is controlling the supply chain, and that the supply chain is controlled to a great extent by the tobacco industry.
SIMPLIFIED FINITE DIFFERENCE THERMAL LATTICE BOLTZMANN METHOD
Authors: NOR AZWADI C. S. , TANAHASHI T.
Published: September 2008

In this paper, a well-known finite difference technique is combined with thermal lattice Boltzmann method to solve 2-dimensional incompressible thermal fluid flow problems. A small number of microvelocity components are applied for the calculation of temperature field. The combination of finite difference with lattice Boltzmann method is found to be an efficient and stable approach for the simulation at high Rayleigh number of natural convection in a square cavity.
TEMPERATURE-TUNED BAND GAP ENERGY AND OSCILLATOR PARAMETERS OF TlInSeS LAYERED SINGLE CRYSTALS
Authors: GASANLY N. M. , GULER I.
Published: September 2008

The parameters of monoclinic unit cell of TlInSeS layered crystals were determined from X-ray powder diffraction study. The optical properties of TlInSeS have been investigated by means of transmission and reflection measurements in the wavelength range of 500–1100 nm. The optical indirect transitions with band gap energy of 2.05 eV and direct transitions with band gap energy of 2.21 eV were found by means of the analysis of the absorption data at room temperature. Transmission measurements carried out in the temperature range of 10–300 K revealed that the rate of change of the indirect band gap with temperature is γ = -4.7 × 10-4 eV/K. The dispersion of the refractive index is discussed in terms of the single oscillator model. The refractive index dispersion parameters: oscillator wavelength and strength were found to be 2.78 × 10-7 m and 1.21 × 1014 m -2, respectively.
A FILTERING PROBLEM FOR A LINEAR STOCHASTIC EVOLUTION EQUATION DRIVEN BY A FRACTIONAL BROWNIAN MOTION
Authors: GRECKSCH WILFRIED , TUDOR CONSTANTIN
Published: September 2008

A linear unbiased and square mean optimal estimation is obtained for the mild solution process of a stochastic evolution equation with an infinite-dimensional fractional Brownian motion as noise and the noise in the observation process is a finite-dimensional Brownian motion. An innovation process is introduced and the estimation is obtained as a solution of a stochastic differential equation with a finite-dimensional noise. By using an approach based on the equivalence with a deterministic control problem, the estimation for the Fourier coefficients of the signal process is also determined.
A PROBLEM IN STOCHASTIC AVERAGING OF NONLINEAR FILTERS
Authors: PARK JUN H. , NAMACHCHIVAYA N. SRI , SOWERS RICHARD B.
Published: September 2008

We consider the stochastic averaging of a particular degenerate problem in nonlinear filtering. In particular, we consider a problem on the cylinder with fast angular diffusion and slow axial diffusion. The observation process depends only on the fast angle. We show that as the separation of scales (between fast and slow) grows, one can approximate the filter for the original problem by a much simpler one. Although our problem is similar to a number of others considered in the literature, the techniques required are different from the known ones.
OFFSHORE HYDROCARBON AND SYNTHETIC HYDROCARBON SPILLS IN EASTERN CANADA: THE ISSUE OF FOLLOW-UP AND EXPERIENCE
Authors: FRASER GAIL S. , ELLIS JOANNE
Published: September 2008

The Environmental Assessment (EA) process should involve the generation of testable predictions generated using clearly stated methods and followed by the collection of environmental monitoring data. Follow-up programs should aim to determine the accuracy of the initial predictions. We examined the follow-up process for six oil and gas extraction projects in eastern Canada with respect to assessing batch spill (< 50 barrels of hydrocarbons and synthetic hydrocarbons) predictions. For three projects we compared oil spill frequency predictions to observed data. All three projects exceeded their predicted frequencies and two projects by ratios (actual to predicted) greater than six. Spill histories from earlier projects, clearly exceeding predictions of future projects, are not provided in subsequent oil and gas EAs for the region, when there were opportunities to do so. We provide recommendations on how to strengthen the quality of EAs and increase protection of the marine environment in Canada.
Wake Up and Smell the Roses: The Ecology and Evolution of Floral Scent
Authors: Raguso Robert A.
Published: September 2008

Floral scent constitutes an ancient and important channel of communication between flowering plants, their pollinators, and enemies. Fragrance is a highly complex component of floral phenotype, with dynamic patterns of emission and chemical composition. The information content of specific volatile compounds is highly context dependent, and scent can function in direct and indirect ways from landscape to intrafloral scales. Floral scent promotes specialization in plant–pollinator relationships through private channels of unusual compounds, unique ratios of more widespread compounds, or through multicomponent floral filters. Floral scent also promotes outcrossing and reproductive isolation through floral constancy, via appetitive conditioning and discrimination on the basis of diverse mechanisms, including pheromone mimicry, odor intensity, complexity, composition, and synergy with visual stimuli. Finally, floral scent is a sexual signal and should be subject to the same selective pressures and modes of signal evolution as animal display, including signal honesty, sensory drive, and sensory exploitation.
Trait-Based Community Ecology of Phytoplankton
Authors: Litchman Elena , Klausmeier Christopher A.
Published: September 2008

Trait-based approaches are increasingly used in ecology. Phytoplankton communities, with a rich history as model systems in community ecology, are ideally suited for applying and further developing these concepts. Here we summarize the essential components of trait-based approaches and review their historical and potential application to illuminating phytoplankton community ecology. Major ecological axes relevant to phytoplankton include light and nutrient acquisition and use, natural enemy interactions, morphological variation, temperature sensitivity, and modes of reproduction. Trade-offs between these traits play key roles in determining community structure. Freshwater and marine environments may select for a different suite of traits owing to their different physical and chemical properties. We describe mathematical techniques for integrating traits into measures of growth and fitness and predicting how community structure varies along environmental gradients. Finally, we outline challenges and future directions for the application of trait-based approaches to phytoplankton ecology.
Fluid Mechanics in Disks Around Young Stars
Authors: Shariff Karim
Published: September 2008

This article reviews hydrodynamic and magnetohydrodynamic processes in disks around young stars, encompassing the epochs of molecular-cloud turbulence, dense core collapse, disk formation, disk evolution, and planetesimal formation.
The Oceanic Vertical Pump Induced by Mesoscale and Submesoscale Turbulence
Authors: Klein Patrice , Lapeyre Guillaume
Published: September 2008

The motivation to study the vertical exchanges of tracers associated with mesoscale eddies is that the mean concentration of most oceanic tracers changes rapidly with depth. Because mesoscale processes may transport these tracers vertically, biogeochemists hypothesized that these vertical exchanges may strongly affect global tracer budgets. This hypothesis has motivated a large number of biogeochemical studies that we review here by focusing on the significant advances that have been achieved and the remaining issues and uncertainties. The main question that emerges concerns the importance of the submesoscales (10 km in the horizontal) in these vertical exchanges. Independently, in the past decade, fluid dynamicists examined the three-dimensional properties of submesoscales generated by a mesoscale (100 km in the horizontal) turbulent eddy field. We review their results and discuss how the vertical exchanges associated with these submesoscales may answer the issues raised by biogeochemical studies and inspire future directions.
Evolution of Intracellular Pathogens
Authors: Casadevall Arturo
Published: September 2008

The evolution of intracellular pathogens is considered in the context of ambiguities in basic definitions and the diversity of host-microbe interactions. Intracellular pathogenesis is a subset of a larger world of host-microbe interactions that includes amoeboid predation and endosymbiotic existence. Intracellular pathogens often reveal genome reduction. Despite the uniqueness of each host-microbe interaction, there are only a few general solutions to the problem of intracellular survival, especially in phagocytic cells. Similarities in intracellular pathogenic strategies between phylogenetically distant microbes suggest convergent evolution. For discerning such patterns, it is useful to consider whether the microbe is acquired from another host or directly from the environment. For environmentally acquired microbes, biotic pressures, such as amoeboid predators, may select for the capacity for virulence. Although often viewed as a specialized adaptation, the capacity for intracellular survival may be widespread among microbes, thus questioning whether the intracellular lifestyle warrants a category of special distinctiveness.
Hijacking of Host Cellular Functions by the Apicomplexa
Authors: Plattner Fabienne , Soldati-Favre Dominique
Published: September 2008

Intracellular pathogens such as viruses and bacteria subvert all the major cellular functions of their hosts. Targeted host processes include protein synthesis, membrane trafficking, modulation of gene expression, antigen presentation, and apoptosis. In recent years, it has become evident that protozoan pathogens, including members of the phylum Apicomplexa, also hijack their host cell's functions to access nutrients and to escape cellular defenses and immune responses. These obligate intracellular parasites provide superb illustrations of the subversion of host cell processes such as the recruitment and reorganization of host cell compartments without fusion around the parasitophorous vacuole of Toxoplasma gondii; the export of Plasmodium falciparum proteins on the surface of infected erythrocytes; and the induced transformation of the lymphocytes infected by Theileria parva, which leads to clonal extension.
Molecular Mechanisms of the Cytotoxicity of ADP-Ribosylating Toxins
Authors: Deng Qing , Barbieri Joseph T.
Published: September 2008

Bacterial pathogens utilize toxins to modify or kill host cells. The bacterial ADP-ribosyltransferases are a family of protein toxins that covalently transfer the ADP-ribose portion of NAD to host proteins. Each bacterial ADP-ribosyltransferase toxin modifies a specific host protein(s) that yields a unique pathology. These toxins possess the capacity to enter a host cell or to use a bacterial Type III apparatus for delivery into the host cell. Advances in our understanding of bacterial toxin action parallel the development of biophysical and structural biology as well as our understanding of the mammalian cell. Bacterial toxins have been utilized as vaccines, as tools to dissect host cell physiology, and more recently for the development of novel therapies to treat human disease.
Study of hypothalamic leptin receptor expression in low-birth-weight piglets and effects of leptin supplementation on neonatal growth and development
Authors: Attig L. , Djiane J. , Gertler A. , Rampin O. , Larcher T. , Boukthir S. , Anton P. M. , Madec J. Y. , Gourdou I. , Abdennebi-Najar L.
Published: September 2008

Low birth weight resulting from intrauterine growth retardation (IUGR) is a risk factor for further development of metabolic diseases. The pig appears to reproduce nearly all of the phenotypic pathological consequences of human IUGR and is likely to be more relevant than rodents in studies of neonatal development. In the present work, we characterized the model of low-birth-weight piglets with particular attention to the hypothalamic leptin-sensitive system, and we tested whether postnatal leptin supplementation can reverse the precocious signs of adverse metabolic programming. Our results demonstrated that 1) IUGR piglets present altered postnatal growth and increased adiposity; 2) IUGR piglets exhibit abnormal hypothalamic distribution of leptin receptors that may be linked to further disturbance in food-intake behavior; and 3) postnatal leptin administration can partially reverse the IUGR phenotype by correcting growth rate, body composition, and development of several organs involved in metabolic regulation. We conclude that IUGR may be characterized by altered leptin receptor distribution within the hypothalamic structures involved in metabolic regulation and that leptin supplementation can partially reverse the IUGR phenotype. These results open interesting therapeutic perspectives in physiopathology for the correction of defects observed in IUGR.
Water deprivation increases Fos expression in hypothalamic corticotropin-releasing factor neurons induced by right atrial distension in awake rats
Authors: Benedetti Mauricio , Rorato Rodrigo , Castro Margaret , Machado Benedito H. , Antunes-Rodrigues Jose , Elias Lucila L. K.
Published: September 2008

Atrial mechanoreceptors, sensitive to stretch, contribute in regulating heart rate and intravascular volume. The information from those receptors reaches the nucleus tractus solitarius and then the paraventricular nucleus (PVN), known to have a crucial role in the regulation of cardiovascular function. Neurons in the PVN synthesize CRF, AVP, and oxytocin (OT). Stimulation of atrial mechanoreceptors was performed in awake rats implanted with a balloon at the junction of the superior vena cava and right atrium. Plasma ACTH, AVP, and OT concentrations and Fos, CRF, AVP, and OT immunolabeling in the PVN were determined after balloon inflation in hydrated and water-deprived rats. The distension of the balloon increased the plasma ACTH concentrations, which were higher in water-deprived than in hydrated rats ( P < 0.05). In addition, the distension in the water-deprived group decreased plasma AVP concentrations ( P < 0.05), compared with the respective control group. The distension increased the number of Fos- and double-labeled Fos/CRF neurons in the parvocellular PVN, which was higher in the water-deprived than in the hydrated group ( P < 0.01). There was no difference in the Fos expression in magnocellular PVN neurons after distension in hydrated and water-deprived groups, compared with respective controls. In conclusion, parvocellular CRF neurons showed an increase of Fos expression induced by stimulation of right atrial mechanoreceptors, suggesting that CRF participates in the cardiovascular reflex adjustments elicited by volume loading. Activation of CRF neurons in the PVN by cardiovascular reflex is affected by osmotic stimulation.
Exercise promotes α7 integrin gene transcription and protection of skeletal muscle
Authors: Boppart Marni D. , Volker Sonja E. , Alexander Nicole , Burkin Dean J. , Kaufman Stephen J.
Published: September 2008

The α7β1 integrin is increased in skeletal muscle in response to injury-producing exercise, and transgenic overexpression of this integrin in mice protects against exercise-induced muscle damage. The present study investigates whether the increase in the α7β1 integrin observed in wild-type mice in response to exercise is due to transcriptional regulation and examines whether mobilization of the integrin at the myotendinous junction (MTJ) is a key determinant in its protection against damage. A single bout of downhill running exercise selectively increased transcription of the α7 integrin gene in 5-wk-old wild-type mice 3 h postexercise, and an increased α7 chain was detected in muscle sarcolemma adjacent to tendinous tissue immediately following exercise. The α7B, but not α7A isoform, was found concentrated and colocalized with tenascin-C in muscle fibers lining the MTJ. To further validate the importance of the integrin in the protection against muscle damage following exercise, muscle injury was quantified in α7−/−mice. Muscle damage was extensive in α7−/−mice in response to both a single and repeated bouts of exercise and was largely restricted to areas of high MTJ concentration and high mechanical force near the Achilles tendon. These results suggest that exercise-induced muscle injury selectively increases transcription of the α7 integrin gene and promotes a rapid change in the α7β integrin at the MTJ. These combined molecular and cellular alterations are likely responsible for integrin-mediated attenuation of exercise-induced muscle damage.
Neutrophil-induced skeletal muscle damage: a calculated and controlled response following hindlimb unloading and reloading
Authors: Dumont Nicolas , Bouchard Patrice , Frenette Jérôme
Published: September 2008

Neutrophils phagocyte necrotic debris and release cytokines, enzymes, and oxidative factors. In the present study, we investigated the contribution of neutrophils to muscle injury, dysfunction, and recovery using an unloading and reloading model. Mice were submitted to 10 days of hindlimb unloading and were transiently depleted in neutrophils with anti-Ly6G/Ly6C antibody prior to reloading. Leukocyte accumulation and muscle function were assessed immunohistologically and functionally in vitro. In addition, soleus muscles submitted to unloading and reloading were incubated in vitro with LPS (100 μg/ml) to determine whether exogenous stimulus would activate neutrophil response and produce extensive muscle damage. Contractile properties were recorded every hour for 6 h, and muscles were subsequently incubated in procion orange to assess muscle damage. Neutrophil depletion affected neither the loss in muscle force nor the time of recovery in atrophied and reloaded soleus muscles. However, atrophied and reloaded soleus muscles that contained high concentration of neutrophils experienced a 20% greater loss in force than atrophied and reloaded soleus muscles depleted in neutrophils following in vitro incubation with LPS. Procion orange dye also confirmed that neutrophils induced a 2.5-fold increase in muscle membrane damage in the presence of LPS. These results show that neutrophil infiltration during modified mechanical loading is highly regulated and efficiently eliminated, with no significant muscle fiber injury unless the activation state of neutrophils is modified by the presence of LPS.
Rapid signaling by steroid receptors
Authors: Levin Ellis R.
Published: September 2008

Steroid receptors transcribe genes that lead to important biological processes, including normal organ development and function, tissue differentiation, and promotion of oncogenic transformation. These actions mainly result from nuclear steroid receptor action. However, for 50 years, it has been known that rapid effects of steroid hormones occur and could result from rapid signal transduction. Examples of these effects include stress responses to secreted glucocorticoids, rapid actions of thyroid hormones in the heart, and acute uterine/vaginal responses to injected estrogen. These types of responses have increasingly been attributed to rapid signaling by steroid hormones, upon engaging binding proteins most often at the cell surface of target organs. It is clear that rapid signal transduction serves an integrated role to modify existing proteins, altering their structure and activity, and to modulate gene transcription, often through collaboration with the nuclear pool of steroid receptors. The biological outcomes of steroid hormone actions thus reflect input from various cellular pools, cocoordinating the necessary events that are restrained in temporal and kinetic fashion. Here I describe the current understanding of rapid steroid signaling that is now appreciated to extend to virtually all members of this family of hormones and their receptors.
A novel cell-permeable antioxidant peptide decreases renal tubular apoptosis and damage in unilateral ureteral obstruction
Authors: Mizuguchi Yasunori , Chen Jie , Seshan Surya V. , Poppas Dix P. , Szeto Hazel H. , Felsen Diane
Published: September 2008

Unilateral ureteral obstruction (UUO) is characterized by decreases in renal function, increased interstitial fibrosis, tubular apoptosis, and cellular infiltration. It has been suggested that inhibition of tubular apoptosis may protect against renal damage in obstruction. We have recently developed a series of peptides which are concentrated in the inner mitochondrial membrane and prevent cell death. These peptides are also active in vivo, in myocardial infraction, ischemic brain injury, and amyotrophic lateral sclerosis models. We therefore used SS-31, a prototype of these peptides, and assessed its effects on renal damage and oxidative stress in a 14-day obstruction model. SS-31 (1 or 3 mg/kg) or saline was given 1 day before and throughout the 14 days of obstruction. Kidneys were harvested and assessed for apoptosis (terminal transferase-dUTP-nick-end labeling, caspase 3 expression), fibrosis (trichrome staining), macrophage infiltration, fibroblast expression (immunoperoxidase), and oxidative damage (8-OH deoxyguanosine and heme oxygenase-1 expression), cytokines, and signaling pathways (transforming growth factor-β, CCR-1, p38-MAPK, NF-κB). SS-31 significantly attenuated the effects of obstruction on all aspects of renal damage which were examined, with both the 1 and 3 mg/kg doses showing efficacy. We noted increased oxidative stress in obstruction, which was also attenuated by SS-31 treatment. Signaling via NF-κB and p38 MAPK pathways were both affected by SS-31 treatment. This study provides a proof of concept that peptides which protect mitochondria in vitro can provide protection from renal damage in a UUO model. The mechanism by which protection is afforded requires further studies both in vitro and in vivo.
Combined knockout of collecting duct endothelin A and B receptors causes hypertension and sodium retention
Authors: Ge Yuqiang , Bagnall Alan , Stricklett Peter K. , Webb David , Kotelevtsev Yuri , Kohan Donald E.
Published: September 2008

The collecting duct (CD) endothelin (ET) system regulates blood pressure (BP) and Na excretion. CD-specific knockout (KO) of ET-1 causes hypertension, CD-specific KO of the ETA receptor does not alter BP, while CD-specific KO of the ETB receptor increases BP to a lesser extent than CD ET-1 KO. These findings suggest a paracrine role for CD-derived ET-1; however, they do not exclude compensation for the loss of one ET receptor by the other. To examine this, mice with CD-specific KO of both ETA and ETB receptors were generated (CD ETA/B KO). CD ETA/B KO mice excreted less urinary Na than controls during acute or chronic Na loading. Urinary aldosterone excretion and plasma renin concentration were similar during Na intake and both fell comparably during Na loading. On a normal sodium diet, CD ETA/B KO mice had increased BP, which increased further with high salt intake. The degree of BP elevation during normal Na intake was similar to CD ET-1 KO mice and higher than CD ETB KO animals. During 1 wk of Na loading, CD ETA/B KO mice had higher BPs than CD ETB KO, while BP was less than CD ET-1 KOs until the latter days of Na loading. These studies suggest that 1) CD ETA/B deficiency causes salt-sensitive hypertension, 2) CD ETA/B KO-associated Na retention is associated with failure to suppress the renin-angiotensin-aldosterone system, and 3) CD ETA and ETB receptors exerts a combined hypotensive effect that exceeds that of either receptor alone.
Salt and acid-base metabolism in claudin-16 knockdown mice: impact for the pathophysiology of FHHNC patients
Authors: Himmerkus Nina , Shan Qixian , Goerke Boeren , Hou Jianghui , Goodenough Daniel A. , Bleich Markus
Published: September 2008

Claudin-16 is defective in familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC). Claudin-16 knockdown (CLDN16 KD) mice show reduced cation selectivity in the thick ascending limb. The defect leads to a collapse of the lumen-positive diffusion voltage, which drives Ca2+and Mg2+absorption. Because of the reduced tight junction permeability ratio for Na+over Cl−, we proposed a backleak of NaCl into the lumen. Systemic analysis had revealed lower blood pressure and a moderately increased plasma aldosterone concentration. In this study, we measured the amiloride-sensitive equivalent short-circuit current in isolated, perfused collecting ducts and found it increased by fivefold in CLDN16 KD mice compared with wild-type (WT) mice. Amiloride treatment unmasked renal Na+loss in the thick ascending limb of the nephron. Under amiloride treatment, CLDN16 KD mice developed hyponatremia and the renal fractional excretion of Na+was twofold higher in CLDN16 KD compared with WT mice. The loss of claudin-16 also resulted in increased urinary flow, reduced HCO3−excretion, and lower urine pH. We conclude that perturbation in salt and acid-base metabolism in CLDN16 KD mice has its origin in the defective cation permselectivity of the thick ascending limb of the nephron. This study has contributed to the still incomplete understanding of the symptoms of FHHNC patients.
Inducible rodent models of acquired podocyte diseases
Authors: Pippin Jeffrey W. , Brinkkoetter Paul T. , Cormack-Aboud Fionnualla C. , Durvasula Raghu V. , Hauser Peter V. , Kowalewska Jolanta , Krofft Ronald D. , Logar Christine M. , Marshall Caroline B. , Ohse Takamoto , Shankland Stuart J.
Published: September 2008

Glomerular diseases remain the leading cause of chronic and end-stage kidney disease. Significant advances in our understanding of human glomerular diseases have been enabled by the development and better characterization of animal models. Diseases of the glomerular epithelial cells (podocytes) account for the majority of proteinuric diseases. Rodents have been extensively used experimentally to better define mechanisms of disease induction and progression, as well as to identify potential targets and therapies. The development of podocyte-specific genetically modified mice has energized the research field to better understand which animal models are appropriate to study acquired podocyte diseases. In this review we discuss inducible experimental models of acquired nondiabetic podocyte diseases in rodents, namely, passive Heymann nephritis, puromycin aminonucleoside nephrosis, adriamycin nephrosis, liopolysaccharide, crescentic glomerulonephritis, and protein overload nephropathy models. Details are given on the model backgrounds, how to induce each model, the interpretations of the data, and the benefits and shortcomings of each. Genetic rodent models of podocyte injury are excluded.