bluuebunny/crossref_metadata_2025 huggingface dataset:
Ectomycorrhizal fungi of whitebark pine (a tree in peril) revealed by sporocarps and molecular analysis of mycorrhizae from treeline forests in the Greater Yellowstone Ecosystem
Authors: Mohatt Katherine R. , Cripps Cathy L. , Lavin Matt
Published: April 2008

Whitebark pine ( Pinus albicaulis Engelm.) is unique as the only stone pine in North America. This species has declined 40%–90% throughout its range owing to blister rust infection, mountain pine beetle, fire suppression, and global climate change. However, intact mature and old growth forests still exist in the Greater Yellowstone Ecosystem (GYE) at high timberline elevations. This study addresses the urgent need to discover the ectomycorrhizal (ECM) fungi critical to this tree species before forests are further reduced. A study of mature whitebark pine forests across five mountain ranges in the Northern GYE confirmed 32 ECM species of fungi with the pine by sporocarp occurrence in pure stands or by identification of mycorrhizae with ITS-matching. Boletales and Cortinariales ( Cortinarius ) comprise 50% of the species diversity discovered. In Boletales, Suillus subalpinus M.M. Moser (with stone pines), Suillus sibericus Singer (stone pines), Rhizopogon evadens A.H. Sm. (five-needle pines), Rhizopogon spp. (pines) and a semi-secotioid Chroogomphus sp. (pines) are restricted to the hosts listed and are not likely to occur with other high elevation conifers in the GYE. The ascomycete generalist, Cenococcum geophilum Fr., was the most frequent (64%) and abundant (51%) ECM fungus on seedling roots, as previously reported for high elevation spruce-fir and lower elevation lodgepole pine forests in the GYE. The relative importance of the basidiomycete specialists and the ascomycete generalist to whitebark pine (and for seedling establishment) is not known, however this study is the first step in delineating the ECM fungi associated with this pine in peril.
Vertical migration of rays leads to the development of a double-storied phenotype in the cambium ofAesculus turbinata
Authors: Myśkow Elżbieta , Zagórska-Marek Beata
Published: April 2008

In the vascular cambium of Aesculus turbinata (Blume) the double-storied structure develops slowly. Initially, the arrangement of primary rays is nonstoried. New secondary rays are initiated during cambial expansion. Rays grow by addition of new initials at both ray margins and then split by the intrusive elongation of adjacent fusiform cells. The repetitive splits give rise to groups of several rays of common descent. Initially, the secondary rays are also nonstoried. Later, they become organized into horizontal tiers. This results from the vertical migration of ray initials in the vascular cambium. Controlled polar additions and eliminations of ray-cell initials at the opposite margins of the ray continue until it reaches the appropriate position within the storey of fusiform initials. We postulate that there are at least two mechanisms for the formation and maintenance of ray tiers in cambium. They are unrelated to cell inclination changes, which as described earlier, are known to sometimes induce a double-storied phenotype. The first of these mechanisms, involves initiation of secondary rays exactly within the storeys of fusiform initials, as in Hippophaë rhamnoides L. The second mechanism, present in A. turbinata, is based on the dynamic, controlled migration of rays.
Comparing the effect of habitat on the magnitude of inbreeding depression in the Mediterranean native Senecio malacitanus and the alien S. inaequidens: consequences for invasive ability
Authors: Garcia-Serrano Hèctor , Escarré Josep , Caño Lidia , Sans F. Xavier
Published: April 2008

We studied the effects of inbreeding depression and the level of self-compatibility on overall fitness parameters in the invasive species Senecio inaequidens DC. and the native Senecio malacitanus Huter, in plots with and without interspecific competition by natural vegetation. Competition had a stronger effect on fitness parmeters for both species, but it mostly affected the survival of S. malacitanus during the first year, and particularly the survival of individuals issued from inbred crosses. Inbreeding depression decreased the seed production in both species. Summer drought in the second year reduced the fitness of all inbreeding levels, masking the effect of inbreeding.The alien species had a shorter pre-reproductive time, a greater head production, and greater resistance to competition from established vegetation. In addition, a negative relationship was found between inbreeding coefficient and herbivory in the native species only. All these factors may help to explain the invasive ability of S. inaequidens. The magnitude of inbreeding depression and the environmental conditions can thus determine the success or failure of an invasion.
SYMPLECTIC GEOMETRIES ON SUPERMANIFOLDS
Authors: LAVROV P. M. , RADCHENKO O. V.
Published: April 2008

Extension of symplectic geometry on manifolds to the supersymmetric case is considered. In the even case it leads to the even symplectic geometry (or, equivalently, to the geometry on supermanifolds endowed with a nondegenerate Poisson bracket) or to the geometry on an even Fedosov supermanifolds. It is proven that in the odd case there are two different scalar structures (namely, an odd closed differential 2-form and the antibracket) which can be used for construction of two different types of odd geometries on supermanifolds.
INTERACTING BOSE AND FERMI GASES IN LOW DIMENSIONS AND THE RIEMANN HYPOTHESIS
Authors: LECLAIR ANDRÉ
Published: April 2008

We apply the S-matrix based finite temperature formalism to nonrelativistic Bose and Fermi gases in 1+1 and 2+1 dimensions. For the (2+1)-dimensional case in the constant scattering length approximation, the free energy is given in terms of Roger's dilogarithm in a way analagous to the thermodynamic Bethe ansatz for the relativistic (1+1)-dimensional case. The 1d fermionic case with a quasiperiodic two-body potential is closely connected with the Riemann hypothesis.
DIRAC–COULOMB SCATTERING WITH PLANE WAVE ENERGY EIGENSPINORS ON DE SITTER EXPANDING UNIVERSE
Authors: COTĂESCU ION I. , CRUCEAN COSMIN
Published: April 2008

The lowest order contribution of the amplitude of Dirac–Coulomb scattering in de Sitter space–time is calculated assuming that the initial and final states of the Dirac field are described by exact solutions of the free Dirac equation on de Sitter space–time with a given energy and helicity. We find that the total energy is conserved in the scattering process.
ASYMPTOTIC ITERATION METHOD FOR SINGULAR POTENTIALS
Authors: CHAMPION BRODIE , HALL RICHARD L. , SAAD NASSER
Published: April 2008

The asymptotic iteration method (AIM) is applied to obtain highly accurate eigenvalues of the radial Schrödinger equation with the singular potential V(r) = r2+λ/rα(α,λ>0) in arbitrary dimensions. Certain fundamental conditions for the application of AIM, such as a suitable asymptotic form for the wave function, and the termination condition for the iteration process, are discussed. Several suggestions are introduced to improve the rate of convergence and to stabilize the computation. AIM offers a simple, accurate, and efficient method for the treatment of singular potentials, such as V(r), valid for all ranges of coupling λ.
INTERACTING QUANTUM TOPOLOGIES AND THE QUANTUM HALL EFFECT
Authors: BALACHANDRAN A. P. , GUPTA KUMAR S. , KÜRKÇÜOǦLU SEÇKIN
Published: April 2008

The algebra of observables of planar electrons subject to a constant background magnetic field B is given by [Formula: see text], the product of two mutually commuting Moyal algebras. It describes the free Hamiltonian and the guiding center coordinates. We argue that [Formula: see text] itself furnishes a representation space for the actions of these two Moyal algebras, and suggest physical arguments for this choice of the representation space. We give the proper setup to couple the matter fields based on [Formula: see text] to electromagnetic fields which are described by the Abelian commutative gauge group [Formula: see text], i.e. gauge fields based on [Formula: see text]. This enables us to give a manifestly gauge covariant formulation of integer quantum Hall effect (IQHE). Thus, we can view IQHE as an elementary example of interacting quantum topologies, where matter and gauge fields based on algebras [Formula: see text] with different θ′ appear. Two-particle wave functions in this approach are based on [Formula: see text]. We find that the full symmetry group in IQHE, which is the semidirect product [Formula: see text] acts on this tensor product using the twisted coproduct Δθ. Consequently, as we show, many particle sectors of each Landau level have twisted statistics. As an example, we find the twisted two particle Laughlin wave functions.
Role of Stomata in Plant Innate Immunity and Foliar Bacterial Diseases
Authors: Melotto Maeli , Underwood William , He Sheng Yang
Published: April 2008

Pathogen entry into host tissue is a critical first step in causing infection. For foliar bacterial plant pathogens, natural surface openings, such as stomata, are important entry sites. Historically, these surface openings have been considered as passive portals of entry for plant pathogenic bacteria. However, recent studies have shown that stomata can play an active role in limiting bacterial invasion as part of the plant innate immune system. As a counter-defense, the plant pathogen Pseudomonas syringae pv. tomato DC3000 uses the virulence factor coronatine to actively open stomata. In nature, many foliar bacterial disease outbreaks require high humidity, rain, or storms, which could favor stomatal opening and/or bypass stomatal defense by creating wounds as alternative entry sites. Further studies on microbial and environmental regulation of stomatal closure and opening could fill gaps in our understanding of bacterial pathogenesis, disease epidemiology, and microbiology of the phyllosphere.
Yeast as a Model Host to Explore Plant Virus-Host Interactions
Authors: Nagy Peter D.
Published: April 2008

The yeast Saccharomyces cerevisiae is invaluable for understanding fundamental cellular processes and disease states of relevance to higher eukaryotes. Plant viruses are intracellular parasites that take advantage of resources of the host cell, and a simple eukaryotic cell, such as yeast, can provide all or most of the functions for successful plant virus replication. Thus, yeast has been used as a model to unravel the interactions of plant viruses with their hosts. Indeed, genome-wide and proteomics studies using yeast as a model host with bromoviruses and tombusviruses have facilitated the identification of replication-associated factors that affect host-virus interactions, virus pathology, virus evolution, and host range. Many of the host genes that affect the replication of the two viruses, which belong to two dissimilar virus families, are distinct, suggesting that plant viruses have developed different ways to utilize the resources of host cells. In addition, a surprisingly large number of yeast genes have been shown to affect RNA-RNA recombination in tombusviruses; this opens an opportunity to study the role of the host in virus evolution. The knowledge gained about host-virus interactions likely will lead to the development of new antiviral methods and applications in biotechnology and nanotechnology, as well as new insights into cellular functions of individual genes and the basic biology of the host cell.
Inosine and equilibrative nucleoside transporter 2 contribute to hypoxic preconditioning in the murine cardiomyocyte HL-1 cell line
Authors: Naydenova Zlatina , Rose Jennifer B. , Coe Imogen R.
Published: April 2008

The purine nucleoside adenosine is a physiologically important molecule in the heart. Brief exposure of cardiomyocytes to hypoxic challenge results in the production of extracellular adenosine, which then interacts with adenosine receptors to activate compensatory signaling pathways that lead to cellular resistance to subsequence hypoxic challenge. This phenomenon is known as preconditioning (PC), and, while adenosine is clearly involved, other components of the response are less well understood. Flux of nucleosides, such as adenosine and inosine, across cardiomyocyte membranes is dependent on equilibrative nucleoside transporters 1 and 2 (ENT1 and ENT2). We have previously shown in the murine cardiomyocyte HL-1 cell line that hypoxic challenge leads to an increase in intracellular adenosine, which exits the cell via ENT1 and preconditions via A1 and A3 adenosine receptor-dependent mechanisms. However, the role and contribution of inosine and ENT2 are unclear. In this study, we confirmed that ENT1 and ENT2 are both capable of transporting inosine. Moreover, we found that hypoxic challenge leads to a significant increase in levels of intracellular inosine, which exits the cell via both ENT1 and ENT2. Exogenously added inosine (5 μM) preconditions cardiomyocytes in an A1 adenosine receptor-dependent manner since preconditioning can be blocked by the A1 adenosine receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (1 μM) but not the A3 adenosine receptor antagonist MRS-1220 (200 nM). These data suggest that cardiomyocyte responses to hypoxic PC are more complex than previously thought, involving both adenosine and inosine and differing, but overlapping, contributions of the two ENT isoforms.
Prostacyclin analogs stimulate VEGF production from human lung fibroblasts in culture
Authors: Kamio Koichiro , Sato Tadashi , Liu Xiangde , Sugiura Hisatoshi , Togo Shinsaku , Kobayashi Tetsu , Kawasaki Shin , Wang Xingqi , Mao Lijun , Ahn Youngsoo , Holz Olaf , Magnussen Helgo , Rennard Stephen I.
Published: April 2008

Prostacyclin is a short-lived metabolite of arachidonic acid that is produced by several cells in the lung and prominently by endothelial cells. It increases intracellular cAMP levels activating downstream signaling thus regulating vascular mesenchymal cell functions. The alveolar wall contains a rich capillary network as well as a population of mesenchymal cells, i.e., fibroblasts. The current study evaluated the hypothesis that prostacyclin may mediate signaling between endothelial and mesenchymal cells in the alveolar wall by assessing the ability of prostacyclin analogs to modulate fibroblast release of VEGF. To accomplish this study, human lung fibroblasts were cultured in routine culture on plastic support and in three-dimensional collagen gels with or without three prostacyclin analogs, carbaprostacyclin, iloprost, and beraprost, and the production of VEGF was evaluated by ELISA and quantitative real-time PCR. Iloprost and beraprost significantly stimulated VEGF mRNA levels and protein release in a concentration-dependent manner. These effects were blocked by the adenylate cyclase inhibitor SQ-22536 and by the protein kinase A (PKA) inhibitor KT-5720 and were reproduced by a direct PKA activator but not by an activator of exchange protein directly activated by cAMP (Epac), indicating that cAMP-activated PKA signaling mediated the effect. Since VEGF serves to maintain the pulmonary microvasculature, the current study suggests that prostacyclin is part of a bidirectional signaling network between the mesenchymal and vascular cells of the alveolar wall. Prostacyclin analogs, therefore, have the potential to modulate the maintenance of the pulmonary microcirculation by driving the production of VEGF from lung fibroblasts.
Peripheral oxygen transport and utilization in rats following continued selective breeding for endurance running capacity
Authors: Howlett Richard A. , Kirkton Scott D. , Gonzalez Norberto C. , Wagner Harrieth E. , Britton Steven L. , Koch Lauren G. , Wagner Peter D.
Published: April 2008

Untrained rats selectively bred for either high (HCR) or low (LCR) treadmill running capacity previously demonstrated divergent physiological traits as early as the seventh generation (G7). We asked whether continued selective breeding to generation 15 (G15) would further increase the divergence in skeletal muscle capillarity, morphometry, and oxidative capacity seen previously at G7. At G15, mean body weight was significantly lower ( P < 0.001) in the HCR rats ( n = 11; 194 ± 3 g) than in LCR ( n = 12; 259 ± 9 g) while relative medial gastrocnemius muscle mass was not different (0.23 ± 0.01 vs. 0.22 ± 0.01% total body weight). Normoxic (FiO2= 0.21) V̇o2maxwas 50% greater ( P < 0.001) in HCR despite the lower absolute muscle mass, and skeletal muscle O2conductance (measured in hypoxia; FiO2= 0.10) was 49% higher in HCR ( P < 0.001). Muscle oxidative enzyme activities were significantly higher in HCR (citrate synthase: 16.4 ± 0.4 vs. 14.0 ± 0.6; β-hydroxyacyl-CoA dehydrogenase: 5.2 ± 0.2 vs. 4.2 ± 0.2 mmol·kg−1·min−1). HCR rats had ∼36% more total muscle fibers and also 36% more capillaries in the medial gastrocnemius. Because average muscle fiber area was 35% smaller, capillary density was 36% higher in HCR, but capillary-to-fiber ratio was the same. Compared with G7, G15 HCR animals showed 38% greater total fiber number with an additional 25% decrease in mean fiber area. These data suggest that many of the skeletal muscle structural and functional adaptations enabling greater O2utilization in HCR at G7 continue to progress following additional selective breeding for endurance capacity. However, the largest changes at G15 relate to O2delivery to skeletal muscle and not to the capacity of skeletal muscle to use O2.
Lipid-Bloated Subretinal Microglial Cells Are at the Origin of Drusen Appearance in CX3CR1-Deficient Mice
Authors: Raoul W. , Feumi C. , Keller N. , Lavalette S. , Houssier M. , Behar-Cohen F. , Combadière C. , Sennlaub F.
Published: April 2008

Drusen, the white yellowish deposits that can be seen in funduscopy, are a hallmark of age-related macular degeneration. Histologically, drusen are believed to be dome-shaped or more confluent lipid accumulations between the retinal pigment epithelium and the choriocapillaries. Recent advances in mouse funduscopy have revealed the presence of drusen-like structures in chemokine knockout animals in the absence of sizeable dome-shaped material below the retinal pigment epithelium. We show that aged CX3CR1–/– mice present with drusen-like appearance in funduscopy that is associated with a progressive age-related microglial cell accumulation in the subretinal space. We demonstrate that the anatomical equivalent of the drusen-like appearance in these mice are lipid-bloated subretinal microglial cells rather than subretinal pigment epithelium deposits [Combadière C, et al: J Clin Invest 2007;117:2920–2928].
Animal Models of Vogt-Koyanagi-Harada Disease (Sympathetic Ophthalmia)
Authors: Yamaki Kunihiko , Ohono Shigeaki
Published: April 2008

Background/Aims: We aimed to establish the animal model of Vogt-Koyanagi-Harada disease (VKH). Methods: Rats, Akita dogs and monkeys were immunized with the peptides derived from tyrosinase-related protein 1. Each experimental animal was examined clinically and histologically. Results and Conclusion: The rats developed ocular and extraocular inflammation homologous to human VKH by immunization of tyrosinase-related protein 1. The Akita dogs also developed the autoimmune disease almost similar to the spontaneously emerging dog VKH equivalent to human VKH. The monkeys developed similar clinical findings as human VKH. These models may serve as human VKH models.
Experimental Melanin-Induced Uveitis: Experimental Model of Human Acute Anterior Uveitis
Authors: Smith Justine R. , Rosenbaum James T. , Williams Keryn A.
Published: April 2008

Experimental melanin-protein-induced uveitis (EMIU), which is also known as experimental autoimmune anterior uveitis, was first described in 1993 by Broekhuyse et al. This experimental uveitis may be induced in certain inbred and outbred rat strains by immunization with bovine ocular melanin. The inflammation shares clinical features with human acute anterior uveitis. The duration of the first episode is approximately 1 month. Spontaneous recovery to a near normal clinical state is the rule, but multiple recurrences are common. Slit-lamp biomicroscopic examination reveals a florid anterior-chamber reaction, with formation of a retro-iridal empyema, fibrin clots and posterior synechiae. At a microscopic level, leukocytic infiltration is first observed in the anterior uvea. Although this tissue remains the site of maximum inflammation throughout an attack, in severe cases, limbitis, vitritis and choroiditis are also observed. Abrogation of EMIU occurs after treatment with anti-CD4 antibody, indicating that the uveitis is controlled by CD4-positive T cells. Several research groups have used EMIU to investigate various aspects of the pathogenesis of acute anterior uveal inflammation, including the participation of different leukocyte subsets, the expression of cell adhesion molecules, cytokines, chemokines and nitric oxide, the role of complement and the impact of apoptosis. In addition, EMIU has also been used to evaluate various biologic interventions with potential implications for the treatment of human disease.
Evidence for Extrathymic Generation of Regulatory T Cells Specific for a Retinal Antigen
Authors: Gregerson Dale S. , Heuss Neal D. , Lehmann Ute , McPherson Scott W.
Published: April 2008

Background: Thymic expression of a photoreceptor cell antigen, interphotoreceptor retinoid-binding protein, is known to generate regulatory T cells (Treg) that prevent spontaneous autoimmune disease of the retina. However, the contribution of other endogenous, tissue-specific antigens (Ags) expressed in the retina to the generation of Treg is uncertain. Methods: Transgenic mice that express β-galactosidase (β-gal) in photoreceptor cells, together with β-gal-specific T cell receptor transgenic mice, were used to study the induction of Treg in vivo. Results: Transgenic expression of β-gal on the arrestin promoter led to a spontaneous immunoregulatory response that inhibited the development of immune responses to β-gal. The regulation was transferred by CD3+4+25+ Treg. Several strategies were then used to show that β-gal expressed in the retina supported spontaneous, thymus-independent Treg development. The endogenous Treg also differed from the Treg induced by Ag inoculation into the anterior chamber of the eye. Conclusion: These results demonstrate that retinal expression of very small amounts of a tissue-specific Ag can generate Treg in the periphery.
Uveitis Secondary to Bacterial Products
Authors: Rosenbaum James T. , Rosenzweig Holly L. , Smith Justine R. , Martin Tammy M. , Planck Stephen R.
Published: April 2008

Bacteria are suspected contributors to several forms of immune-mediated, noninfectious forms of uveitis including that associated with ankylosing spondylitis, sarcoidosis, Behçet’s disease and inflammatory bowel disease. Endotoxin (lipopolysaccharide)-induced uveitis has been a widely used model for more than 2 decades. Both rats and mice develop a transient, bilateral anterior uveitis after a systemic injection of endotoxin. Inflammation posterior to the lens is generally milder than anterior segment inflammation. The uveitis is severer if the lipopolysaccharides are injected intraocularly. The model has been invaluable in helping to identify mediators induced in the inflamed eye and in testing pharmacologic approaches to reduce eye inflammation. Muramyl dipeptide is another bacterial cell component that can induce uveitis in laboratory animals. Muramyl dipeptide is especially intriguing as a cause of uveitis because it activates the intracellular protein, Nod2, and mutations in the NOD2 gene are the cause of the autosomal dominant form of uveitis that is characteristic of Blau syndrome. Since a mutation in a gene that codes for a protein which senses a bacterial product consistently results in uveitis, it is critical to understand more fully the mechanisms by which bacterial products cause uveitis in laboratory animals.
Mouse Models of Experimental Autoimmune Uveitis
Authors: Caspi Rachel R. , Silver Phyllis B. , Luger Dror , Tang Jun , Cortes Lizette M. , Pennesi Giuseppina , Mattapallil Mary J. , Chan Chi-Chao
Published: April 2008

The mouse model of experimental autoimmune uveitis, induced by immunization of mice with the retinal protein IRBP, was developed in our laboratory 20 years ago and published in 1988. Since that time it has been adopted by many investigators and has given rise to many studies that helped elucidate genetic influences, dissect the basic mechanisms of pathogenesis and test novel immunotherapeutic paradigms. The current overview will summarize the salient features of the experimental autoimmune uveitis model and discuss its mechanisms.
Anterior Uveitis Accompanies Joint Disease in a Murine Model Resembling Ankylosing Spondylitis
Authors: Rosenzweig H.L. , Martin T.M. , Planck S.R. , Jann M.M. , Smith J.R. , Glant T.T. , van Eden W. , Davey M.P. , Rosenbaum J.T.
Published: April 2008

Background: Uveitis is often associated with a systemic inflammatory disease such as ankylosing spondylitis. Our understanding of the eye’s susceptibility to immune-mediated uveitis as in the apparent absence of infection has been limited by a relative lack of experimental models. Here we sought to assess whether ocular inflammation occurs in a previously described murine model of proteoglycan-induced spondylitis, wherein mice develop progressive spondylitis, sacroiliitis and peripheral arthritis – features common to the clinical presentations of ankylosing spondylitis. Methods: Using intravital microscopy we examined the ocular inflammatory response after the onset of arthritis in mice that overexpressed the T cell receptor (TCR) specific for a dominant arthritogenic epitope of cartilage proteoglycan [TCR-Tg (transgenic) mice] or BALB/c controls. Results: Immunized TCR-Tg mice showed a significant increase in the number of rolling and adhering cells within the iris vasculature compared to adjuvant control mice. Cellular infiltration within the iris tissue, as assessed by intravital microscopy and histology, was also increased. Our initial temporal analysis has revealed that immunized TCR-Tg mice show a significant increase in intravascular inflammation by 2 weeks after immunization, but it diminishes at 4 weeks after immunization. Conclusions: Although these data are preliminary, this model has the potential to clarify the mechanisms accounting for the coexistence of eye and sacroiliac inflammation as occurs in patients with ankylosing spondylitis.
Animal Models of Intraocular Lymphomas
Authors: Touitou Valérie , Bodaghi Bahram , de Kozak Yvonne , LeHoang Phuc , Sautès-Fridman Catherine , Fisson Sylvain
Published: April 2008

Primary intraocular lymphoma is a high-grade non-Hodgkin lymphoma whose pathogenesis is still unclear. Few animal models exist in order to study this condition. Although intraocular lymphomas in humans are usually B cell lymphomas, most of these models are T cell lymphomas. Recently, a major step forward has been realized with the development of new models of intraocular B cell lymphoma. New therapeutic tools are being evaluated in these models of B cell lymphoma. We evaluate the contribution of the different animal models available to study intraocular lymphomas, and we discuss the new therapeutic strategies and their various targets in the tumor as well as in the environment, which are currently investigated through the development of these models.
Optic Nerve Degeneration in Experimental Autoimmune Encephalomyelitis
Authors: Guy John
Published: April 2008

The mechanisms of axonal and neuronal degeneration causing disability in optic neuritis and multiple sclerosis are poorly understood. Here we describe the role of mitochondria, oxidative stress and the effects of modulating antioxidant gene expression in the optic nerves of mice induced with experimental autoimmune encephalomyelitis, with a focus on long-term neuroprotection. Oxidative injury to the mitochondrion began prior to inflammatory cell infiltration and continued. It affected subunits of the respiratory chain, glycolysis and a chaperone critical to the stabilization and import of proteins. Oxidative products were associated with loss of membrane potential, mitochondrial degeneration and severe axonal loss. Reductions in ATP synthesis were even greater than those associated with mitochondrial diseases. Increasing SOD2 levels by viral mediated gene transfer rescued ATP synthesis, suppressed myelin fiber injury and increased retinal ganglion cell survival 1 year later.
First and Second Language Tongue Movements in Spanish and Korean Bilingual Speakers
Authors: Nissen Shawn L. , Dromey Christopher , Wheeler Cynthia
Published: April 2008

A number of previous studies have relied on perceptual judgments or acoustic analysis to examine second language (L2) production. However, few researchers have studied L2 performance by directly tracking the physical movements of the articulators. The purpose of the present study was to investigate intraspeaker differences in native (Korean or Spanish) and L2 (English) production through kinematic indices of tongue activity. This involved measurement of the speed, duration, and distance of tongue movements or strokes during speech. Findings indicated that the speakers had significantly slower stroke speeds and longer movement durations for L2 when compared to their native language (L1), yet no significant differences in stroke distance. The bilingual speakers were found to pause more and speak proportionally less of the time in their L2. Interestingly, those speakers who exhibited greater relative kinematic changes from L1 to L2 were also rated as having a stronger perceived accent.
Phonetic Applications of the Time-Corrected Instantaneous Frequency Spectrogram
Authors: Fulop Sean A.
Published: April 2008

A reassigned or time-corrected instantaneous frequency spectrogram has been developed in the work of a number of practitioners. Here we present a general description of this imaging technique and explore its manifold applications to acoustic phonetics. The TCIF spectrogram shows the locations of signal components with unrivalled precision, eliminating the blurring and smearing of components that hamper the readability of the conventional spectrogram. Formants of vowels and other resonants are shown with great accuracy by observing glottal pulsations at very short time scales with a wideband analysis. A further post-processing technique is also described, by which signal components such as formants, as well as impulsive events, can be effectively isolated to the exclusion of other signal information. When the phonation process is examined this closely, a variety of evidence surfaces which supports recent developments in the theory and computational simulation of aeroacoustic phenomena in speech. Narrowband analysis is also demonstrated to permit pitch tracking with relative ease.
Dipole Source Analysis of Temporal Slow Waves in the Elderly
Authors: Motomura Eishi , Inui Koji , Ogawa Hiroyuki , Nakase Shinji , Hamanaka Kenji , Honda Tomoyuki , Shiroyama Takashi , Matsumoto Takuya , Komori Teruhisa , Okada Motohiro , Kakigi Ryusuke
Published: April 2008

Background: Temporal low-voltage irregular δ-waves (TLID) are often found in elderly subjects. The physiological significance of TLID has not been clarified; however, our previous studies suggest that TLID are associated with mild cerebrovascular dysfunction. Objective: The present study aimed to reveal the origin of TLID and their neural mechanisms by dipole source modeling. Methods: From electroencephalography records taken from 21 scalp electrodes, clear and typical TLID of 6 elderly subjects (mean age, 69 ± 6.2 years) were selected. Among these, we selected and averaged 7–12 clear TLID on the left side in each subject, and estimated a single equivalent current dipole for the averaged TLID. Results: The best equivalent current dipoles were estimated to be located in the medial part of the temporal lobe in or near the parahippocampal gyrus in the hemisphere ipsilateral to the TLID, with a high reliability in all subjects. Conclusions: Considering the source localization of TLID, TLID seem to indicate certain dysfunctions of the hippocampus or adjacent regions. This is the first study to report the cerebral origin of TLID and suggest its physiological significance.
Genes and Environmental Exposures in Veterans with Amyotrophic Lateral Sclerosis: The GENEVA Study
Authors: Schmidt Silke , Allen Kelli D. , Loiacono Valerie T. , Norman Barbara , Stanwyck Catherine L. , Nord Kristina M. , Williams Christina D. , Kasarskis Edward J. , Kamel Freya , McGuire Valerie , Nelson Lorene M. , Oddone Eugene Z.
Published: April 2008

Recent reports of a potentially increased risk of amyotrophic lateral sclerosis (ALS) for veterans deployed to the 1990–1991 Persian Gulf War prompted the Department of Veterans Affairs to establish a National Registry of Veterans with ALS, charged with the goal of enrolling all US veterans with a neurologist-confirmed diagnosis of ALS. The Genes and Environmental Exposures in Veterans with ALS study (GENEVA) is a case-control study presently enrolling cases from the Department of Veterans Affairs registry and a representative sample of veteran controls to evaluate the joint contributions of genetic susceptibility and environmental exposures to the risk of sporadic ALS. The GENEVA study design, recruitment strategies, methods of collecting DNA samples and environmental risk factor information are described here, along with a summary of demographic characteristics of the participants (537 cases, 292 controls) enrolled to date.
Homocysteine, Folate and Cognition in a Large Community-Based Sample of Elderly People – The 3C Dijon Study
Authors: Vidal Jean-Sébastien , Dufouil Carole , Ducros Véronique , Tzourio Christophe
Published: April 2008

Background: Hyperhomocysteinemia is associated with an increased risk of cognitive impairment in the elderly. Recent studies suggest that folate level may also influence the course of cognitive decline. Objective: We performed the cross-sectional analysis of the relationship between homocysteine and folate levels and cognitive performances in a population-based study including 3,914 subjects aged 65 years and older. Method: Subjects had an evaluation of their cognitive level using five neuropsychological tests. A Cognitive Summary Score was computed as the sum of each of the 5 cognitive tests score standardized. Relations of folate and homocysteine levels with cognition were first studied separately in a covariance analysis. Stratified analyses were also performed because of interaction between folate and homocysteine in relation to cognition. Results: Subjects in the higher quartile of homocysteine (high homocysteine group) and subjects in the lower quartile of folate (low folate group) had consistently lower cognitive performances in all tests. When stratified on folate level, high homocysteinemia was associated with lower cognitive performances only in subjects with a low folate level. Conclusion: In this large population-based sample of elderly people, the association between high homocysteinemia and decreased cognition was only seen in participants with low folate levels.
Creutzfeldt-Jakob Disease in Austria: An Autopsy-Controlled Study
Authors: Gelpi Ellen , Heinzl Harald , Höftberger Romana , Unterberger Ursula , Ströbel Thomas , Voigtländer Till , Drobna Edita , Jarius Christa , Lang Susanna , Waldhör Thomas , Bernheimer Hanno , Budka Herbert
Published: April 2008

Background: Definite diagnosis of prion diseases or transmissible spongiform encephalopathies (TSEs) requires neuropathology, usually at autopsy. Epidemiology of human TSEs has relied on definite as well as ‘probable’ cases in which neuropathological confirmation is lacking, usually because of low autopsy rates in most countries. Methods: In Austria, an active surveillance program for human prion diseases was established in 1996. Since then, more than 900 referrals were analyzed. Postmortem investigation of brain tissue is mandatory in every suspect case of TSE. Thus, epidemiological data on TSEs from Austria may serve as autopsy-controlled reference for countries with lower autopsy rates. Results: The total number of TSE cases in Austria since 1969 is 206. The average yearly mortality for the active surveillance period from 1996 to 30 June 2006 is 1.39 per million, with the highest rates for Vienna (2.37) compared with other provinces. Eighty-five percent of definite TSEs were classified as sporadic Creutzfeldt-Jakob disease (sCJD). We observed a significant linear increase in the mean age at death of 0.6 years per calendar year. Clinical diagnostic surveillance criteria had a sensitivity and specificity of 82.7 and 80.0% for probable CJD, respectively, and a positive predictive value of 80.5% for probable and 38.9% for ‘possible’ CJD. Alternative neuropathological diagnoses in suspect cases included Alzheimer’s disease with or without Lewy body pathology, vascular encephalopathy, metabolic encephalopathies and viral or limbic encephalitis. Conclusion: The steady increase in mortality rates, especially in old age groups, most likely reflects improved case ascertainment due to active surveillance causing higher awareness of the medical community. In comparison with other European countries, it is reassuring to note that the overall death rate of TSEs does not differ from the Austrian autopsy-controlled data, thus confirming the value of clinical surveillance criteria.
New Insights into the Biology of Peritoneal Mesothelial Cells: The Roles of Epithelial-to-Mesenchymal Transition and Cellular Senescence
Authors: Witowski Janusz , Książek Krzysztof , Jörres Achim
Published: April 2008

Ultrafiltration failure due to dysfunction of the peritoneum as a dialyzing organ is a major clinical limitation of peritoneal dialysis. It is increasingly clear that mesothelial cells play an important role in fibrogenesis and vasculopathy that underlie peritoneal membrane dysfunction. New and extensively studied aspects of peritoneal mesothelial cell biology include epithelial-to-mesenchymal transition and cellular senescence. We discuss the potential significance of these processes for the peritoneal membrane function.
The Utility of Two Daytime Icodextrin Exchanges to Reduce Dextrose Exposure in Automated Peritoneal Dialysis Patients: A Pilot Study of Nine Patients
Authors: Gobin Jaya , Fernando Sanjay , Santacroce Sally , Finkelstein Fredric O.
Published: April 2008

Background: The use of dextrose-containing solutions in peritoneal dialysis (PD) is thought to be associated with glucose-related toxicity both to the peritoneal membrane and systemically. There has, therefore, been considerable interest in minimizing the use of dextrose exposure during PD. The present study was designed to explore the use of icodextrin in patients with high/high-average transporter characteristics for two exchanges per day to minimize glucose exposure. Methods: We performed a 6-month prospective cohort study using two icodextrin exchanges per day in a group of high/high-average transporters maintained on automated PD. Icodextrin levels, serum sodium levels, and glucose exposure were measured at baseline, 3 and 6 months. Results: Nine patients completed the study protocol. While the total volume of PD solution remained the same, there was a reduction in mean glucose exposure from a baseline mean value of 410 ± 75 to 275 ± 57 g/day at 3 months and 300 ± 75 g/day at 6 months. Serum icodextrin levels rose from a baseline mean of 345 ± 145 to 615 ± 120 mg/dl at 3 months and 620 ± 108 mg/dl at 6 months. Serum sodium levels remained stable. Conclusion: The use of two (double) icodextrin exchanges in high/high-average transporters on PD can contribute to reduction in glucose exposure for patients maintained on automated PD and appears to be safe.
Does Dopamine Still Have a Leading Role in Advanced Parkinson’s Disease after Subthalamic Stimulation?
Authors: Jabre Mazen , Nohra George , Damier Philippe , Bejjani Boulos-Paul
Published: April 2008

The role of endogenous dopamine in severe Parkinson’s disease is often underestimated. We report on a case of acute general motor worsening induced by the ingestion of fluphenazine in a parkinsonian patient successfully treated with STN DBS. Other etiologies were ruled out. Clinical improvement was gradual and fully reversible 4 days after discontinuation of the antidopaminergic drug. We suggest that residual striatal and extrastriatal dopaminergic pathways still play a paramount role in mediating central neurotrasmissions that may take part in STN DBS’s mechanism of action.
Distension of the Carotid Artery and Risk of Coronary Events
Authors: Leone Nathalie , Ducimetière Pierre , Gariépy Jerôme , Courbon Dominique , Tzourio Christophe , Dartigues Jean-François , Ritchie Karen , Alpérovitch Annick , Amouyel Philippe , Safar Michel E. , Zureik Mahmoud
Published: April 2008

Objective—

Arterial mechanical properties are of growing interest in the understanding of cardiovascular disease development. We aimed to determine the predictive value of carotid wall mechanics on coronary heart disease (CHD) in the Three-City study.

Methods and Results—

At baseline, 3337 participants aged ≥65 years underwent a carotid B-mode ultrasonography. During a median follow-up of 43.4 months, 128 CHD occurred. Increased carotid distension (relative stroke change in lumen diameter) was significantly associated with CHD risk. Comparison of subjects in tertile 3 versus those in tertile 1 (reference) showed a hazard ratio (HR) of 1.80 (95% CI, 1.17 to 2.75). Controlling for various confounders including age, heart rate, brachial (or carotid) pulse pressure, and common carotid intima-media thickness did not alter the association between carotid distension and CHD with a HR of 1.79 (95% CI, 1.12 to 2.86; tertile 3 versus tertile 1). Brachial and carotid pulse pressures were also independently associated with CHD. No association was found between CHD and carotid distensibility coefficient, cross-sectional compliance coefficient, Young’s elastic modulus, or β stiffness index.

Conclusions—

In the elderly, increased carotid distension was independently predictive of CHD. This simple and noninvasive parameter might be of particular interest for cardiovascular risk assessment.
Acute Elevation of Plasma PLTP Activity Strongly Increases Pre-existing Atherosclerosis
Authors: Moerland Matthijs , Samyn Hannelore , van Gent Teus , van Haperen Rien , Dallinga-Thie Geesje , Grosveld Frank , van Tol Arie , de Crom Rini
Published: April 2008

Objective—

A transgenic mouse model was generated that allows conditional expression of human PLTP, based on the tetracycline-responsive gene system, to study the effects of an acute increase in plasma PLTP activity as may occur in inflammation.

Methods and Results—

The effects of an acute elevation of plasma PLTP activity on the metabolism of apolipoprotein B–containing lipoproteins and on diet-induced pre-existing atherosclerosis were determined in mice displaying a humanized lipoprotein profile (low-density lipoprotein receptor knockout background). Induced expression of PLTP strongly increases plasma VLDL levels in LDL receptor knockout mice, whereas VLDL secretion is not affected. The elevation in plasma triglyceride levels is explained by a PLTP-dependent inhibition of VLDL catabolism, which is caused, at least partly, by a decreased lipoprotein lipase activity. Together with the decreased plasma HDL levels, the acutely increased PLTP expression results in a highly atherogenic lipoprotein profile. Induction of PLTP expression leads to a further increase in size of pre-existing atherosclerotic lesions, even on a chow diet. In addition, the lesions contain more macrophages and less collagen relative to controls, suggesting a less stable lesion phenotype.

Conclusion—

In conclusion, acute elevation of PLTP activity destabilizes atherosclerotic lesions and aggravates pre-existing atherosclerosis.
T-lymphocyte Infiltration in Visceral Adipose Tissue
Authors: Kintscher Ulrich , Hartge Martin , Hess Katharina , Foryst-Ludwig Anna , Clemenz Markus , Wabitsch Martin , Fischer-Posovszky Pamela , Barth Thomas F.E. , Dragun Duska , Skurk Thomas , Hauner Hans , Blüher Matthias , Unger Thomas , Wolf Anna-Maria , Knippschild Uwe , Hombach Vinzenz , Marx Nikolaus
Published: April 2008

Background—

Adipose tissue inflammation may play a critical role in the pathogenesis of insulin resistance (IR). The present study examined the role of lymphocytes in adipose tissue inflammation and IR.

Methods and Results—

In a mouse model of obesity-mediated IR, high-fat diet (HFD) induced IR already after 5 weeks, which was associated with a marked T-lymphocyte infiltration in visceral adipose tissue. In contrast, recruitment of macrophages was delayed with an increase of MAC3-positive staining and F4/80 mRNA expression after 10 weeks of HFD, suggesting a dissociation of macrophage invasion into adipose tissue and IR initiation. In patients with type 2 diabetes, lymphocyte content in adipose tissue biopsies significantly correlated with waist circumference, a marker of IR. Immunohistochemical staining of human adipose tissue revealed the presence of mainly CD4-positive lymphocytes as well as macrophage infiltration. Most macrophages were HLA-DR–positive, reflecting activation through IFNγ, a cytokine released from CD4-positive lymphocytes.

Conclusions—

Proinflammatory T-lymphocytes are present in visceral adipose tissue and may contribute to local inflammatory cell activation before the appearance of macrophages, suggesting that these cells could play an important role in the initiation and perpetuation of adipose tissue inflammation as well as the development of IR.
Temporally Expressed PDGF and FGF-2 Regulate Embryonic Coronary Artery Formation and Growth
Authors: Tomanek Robert J. , Hansen Heidi K. , Christensen Lance P.
Published: April 2008

Objective—

PDGF and FGF-2 are important regulators of vascular wall assembly. We tested the hypothesis that their embryonic temporal expression facilitates 2 specific events: (1) the endothelial invasion of the aortic root to form the coronary artery stems and (2) the subsequent growth and development of the arterial tree.

Methods and Results—

Addition of FGF-2 and PDGF-BB proteins to embryonic quail heart explants stimulated a 3- and 7-fold increase, respectively, in tubulogenesis, whereas neutralizing antibodies to these growth factors attenuated tubulogenesis by 40%. Anti–FGF-2 and anti-PDGF neutralizing antibodies were then introduced in ovo via the vitelline vein at various embryonic (E) days. When injections occurred before coronary ostial formation, the embryos usually developed only 1 coronary artery or lacked coronary arteries. When 1 or both major coronary arteries formed: (1) their branches had a thinner tunica media, and (2) smooth muscle investment did not progress as far distally as in shams. Other anomalies included smaller diameter coronary artery stems in some hearts. Inhibition of VEGF via injections of aflibercept (VEGF-Trap, a VEGFR-1 and -2 chimera), previously shown to be essential for coronary stem formation, limited development of the coronary arteries even though introduced after formation of coronary ostia (at E9 or EI0).

Conclusions—

Our data (1) document a role for FGF-2 and PDGF in the temporal regulation of coronary artery stem formation and growth of the coronary arterial tree and (2) reveal that VEGF expression is required for normal artery/arterial formation, even after coronary artery stem formation.