bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficient Virus-Induced Gene Silencing in Roots Using a Modified Tobacco Rattle Virus Vector
Authors: Valentine Tracy , Shaw Jane , Blok Vivian C. , Phillips Mark S. , Oparka Karl J. , Lacomme Christophe
Published: December 2004

Due to their capability of eliciting a form of posttranscriptional gene silencing (termed virus-induced gene silencing or VIGS), plant viruses are increasingly used as reverse-genetics tools for functional characterization of plant genes. RNA viruses have been shown to trigger silencing in a variety of host plants, including members of Solanacae and Arabidopsis (Arabidopsis thaliana). Several factors affect the silencing response, including host range and viral tropism within the plant. The work presented here demonstrates that a modified tobacco rattle virus (TRV) vector retaining the helper protein 2b, required for transmission by a specific vector nematode, not only invades and replicates extensively in whole plants, including meristems, but also triggers a pervasive systemic VIGS response in the roots of Nicotiana benthamiana, Arabidopsis, and tomato (Lycopersicon esculentum). This sustained VIGS response was exemplified by the silencing of genes involved in root development (IRT1, TTG1 [transparent testa glabra], RHL1 [root hairless1], and β-tubulin), lateral root-meristem function (RML1 [root meristemless1]), and nematode resistance (Mi). Roots of silenced plants exhibit reduced levels of target mRNA and phenocopy previously described mutant alleles. The TRV-2b vector displays increased infectivity and meristem invasion, both key requirements for efficient VIGS-based functional characterization of genes in root tissues. Our data suggest that the TRV helper protein 2b may have an essential role in the host regulatory mechanisms that control TRV invasion.
In Vivo Dynamics and Differential Microtubule-Binding Activities of MAP65 Proteins
Authors: Van Damme Daniël , Van Poucke Kris , Boutant Emmanuel , Ritzenthaler Christophe , Inzé Dirk , Geelen Danny
Published: December 2004

Plant cells produce different microtubule arrays that are essential for cell division and morphogenesis without equivalent in other eukaryotes. Microtubule-associated proteins influence the behavior of microtubules that is presumed to culminate into transitions from one array to another. We analyzed the microtubule-binding properties of three Arabidopsis (Arabidopsis thaliana) members, AtMAP65-1, AtMAP65-4, and AtMAP65-5, in live cells using laser scanning confocal microscopy. Depending on the overall organization of the cortical array, AtMAP65-1-GFP (green fluorescent protein) and AtMAP65-5-GFP associated with a subset of microtubules. In cells containing both coaligned and oblique microtubules, AtMAP65-1-GFP and AtMAP65-5-GFP tended to be associated with the coaligned microtubules. Cortical microtubules labeled with AtMAP65-1-GFP and AtMAP65-5-GFP appeared as thick bundles and showed more resistance to microtubule-destabilizing drugs. The polymerization rates of AtMAP65-1-GFP and AtMAP65-5-GFP microtubules were similar to those of tubulin-GFP marked microtubules but were different from AtEB1a-GFP, a microtubule plus-end-binding EB1-like protein that stimulated polymerization. By contrast, depolymerization rates of AtMAP65-1-GFP- and AtMAP65-5-GFP-labeled microtubules were reduced. AtMAP65-1-GFP associated with polymerizing microtubules within a bundle, and with fixed microtubule termini, suggesting that AtMAP65-1's function is to bundle and stabilize adjacent microtubules of the cortex. Polymerization within a bundle took place in either direction so that bundling occurred between parallel or antiparallel aligned microtubules. AtMAP65-4-GFP did not label cortical microtubules or the preprophase band, despite continuous expression driven by the 35S promoter, and its subcellular localization was restricted to microtubules that rearranged to form a spindle and the polar sides of the spindle proper. The expression of AtMAP65-4 peaked at mitosis, in agreement with a function related to spindle formation, whereas AtMAP65-1 and AtMAP65-5 were expressed throughout the cell cycle.
Plant-Specific Microtubule-Associated Protein SPIRAL2 Is Required for Anisotropic Growth in Arabidopsis
Authors: Shoji Tsubasa , Narita Noriyuki N. , Hayashi Kazunori , Asada Junko , Hamada Takahiro , Sonobe Seiji , Nakajima Keiji , Hashimoto Takashi
Published: December 2004

In diffusely growing plant cells, cortical microtubules play an important role in regulating the direction of cell expansion. Arabidopsis (Arabidopsis thaliana) spiral2 (spr2) mutant is defective in directional cell elongation and exhibits right-handed helical growth in longitudinally expanding organs such as root, hypocotyl, stem, petiole, and petal. The growth of spr2 roots is more sensitive to microtubule-interacting drugs than is wild-type root growth. The SPR2 gene encodes a plant-specific 94-kD protein containing HEAT-repeat motifs that are implicated in protein-protein interaction. When expressed constitutively, SPR2-green fluorescent protein fusion protein complemented the spr2 mutant phenotype and was localized to cortical microtubules as well as other mitotic microtubule arrays in transgenic plants. Recombinant SPR2 protein directly bound to taxol-stabilized microtubules in vitro. Furthermore, SPR2-specific antibody and mass spectrometry identified a tobacco (Nicotiana tabacum) SPR2 homolog in highly purified microtubule-associated protein fractions from tobacco BY-2 cell cultures. These results suggest that SPR2 is a novel microtubule-associated protein and is required for proper microtubule function involved in anisotropic growth.
Analysis in Vitro of the Enzyme CRTISO Establishes a Poly-cis-Carotenoid Biosynthesis Pathway in Plants
Authors: Isaacson Tal , Ohad Itzhak , Beyer Peter , Hirschberg Joseph
Published: December 2004

Most enzymes in the central pathway of carotenoid biosynthesis in plants have been identified and studied at the molecular level. However, the specificity and role of cis-trans-isomerization of carotenoids, which occurs in vivo during carotene biosynthesis, remained unresolved. We have previously cloned from tomato (Solanum lycopersicum) the CrtISO gene, which encodes a carotene cis-trans-isomerase. To study the biochemical properties of the enzyme, we developed an enzymatic in vitro assay in which a purified tomato CRTISO polypeptide overexpressed in Escherichia coli cells is active in the presence of an E. coli lysate that includes membranes. We show that CRTISO is an authentic carotene isomerase. Its catalytic activity of cis-to-trans isomerization requires redox-active components, suggesting that isomerization is achieved by a reversible redox reaction acting at specific double bonds. Our data demonstrate that CRTISO isomerizes adjacent cis-double bonds at C7 and C9 pairwise into the trans-configuration, but is incapable of isomerizing single cis-double bonds at C9 and C9′. We conclude that CRTISO functions in the carotenoid biosynthesis pathway in parallel with ζ-carotene desaturation, by converting 7,9,9′-tri-cis-neurosporene to 9′-cis-neurosporene and 7′9′-di-cis-lycopene into all-trans-lycopene. These results establish that in plants carotene desaturation to lycopene proceeds via cis-carotene intermediates.
Characterization of Plastidial Thioredoxins from Arabidopsis Belonging to the New y-Type
Authors: Collin Valérie , Lamkemeyer Petra , Miginiac-Maslow Myroslawa , Hirasawa Masakazu , Knaff David B. , Dietz Karl-Josef , Issakidis-Bourguet Emmanuelle
Published: December 2004

The plant plastidial thioredoxins (Trx) are involved in the light-dependent regulation of many enzymatic activities, owing to their thiol-disulfide interchange activity. Three different types of plastidial Trx have been identified and characterized so far: the m-, f-, and x-types. Recently, a new putative plastidial type, the y-type, was found. In this work the two isoforms of Trx y encoded by the nuclear genome of Arabidopsis (Arabidopsis thaliana) were characterized. The plastidial targeting of Trx y has been established by the expression of a Trx∷GFP fusion protein. Then both isoforms were produced as recombinant proteins in their putative mature forms and purified to characterize them by a biochemical approach. Their ability to activate two plastidial light-regulated enzymes, NADP-malate dehydrogenase (NADP-MDH) and fructose-1,6-bisphosphatase, was tested. Both Trx y were poor activators of fructose-1,6-bisphosphatase and NADP-MDH; however, a detailed study of the activation of NADP-MDH using site-directed mutants of its regulatory cysteines suggested that Trx y was able to reduce the less negative regulatory disulfide but not the more negative regulatory disulfide. This property probably results from the fact that Trx y has a less negative redox midpoint potential (−337 mV at pH 7.9) than thioredoxins f and m. The y-type Trxs were also the best substrate for the plastidial peroxiredoxin Q. Gene expression analysis showed that Trx y2 was mainly expressed in leaves and induced by light, whereas Trx y1 was mainly expressed in nonphotosynthetic organs, especially in seeds at a stage of major accumulation of storage lipids.
The Role of Plastocyanin in the Adjustment of the Photosynthetic Electron Transport to the Carbon Metabolism in Tobacco
Authors: Schöttler Mark Aurel , Kirchhoff Helmut , Weis Engelbert
Published: December 2004

We investigated adaptive responses of the photosynthetic electron transport to a decline in the carbon assimilation capacity. Leaves of different ages from wild-type tobacco (Nicotiana tabacum) L. var Samsun NN and young mature leaves of tobacco transformants with impaired photoassimilate export were used. The assimilation rate decreased from 280 in young mature wild-type leaves to below 50 mmol electrons mol chlorophyll−1 s−1 in older wild-type leaves or in transformants. The electron transport capacity, measured in thylakoids isolated from the different leaves, closely matched the leaf assimilation rate. The numbers of cytochrome (cyt)-bf complexes and plastocyanin (PC) decreased with the electron transport and assimilation capacity, while the numbers of photosystem I (PSI), photosystem II, and plastoquinone remained constant. The PC to PSI ratio decreased from five in leaves with high assimilation rates, to values below one in leaves with low assimilation rates, and the PC versus flux correlation was strictly proportional. Redox kinetics of cyt-f, PC, and P700 suggest that in leaves with low electron fluxes, PC is out of the equilibrium with P700 and cyt-f and the cyt-f reoxidation rate is restricted. It is concluded that the electron flux is sensitive to variations in the number of PC, relative to PSI and cyt-bf, and PC, in concert with cyt-bf, is a key component that adjusts to control the electron transport rate. PC dependent flux control may serve to adjust the electron transport rate under conditions where the carbon assimilation is diminished and thereby protects PSI against over-reduction and reactive oxygen production.
A Plant-Specific Kinesin Binds to Actin Microfilaments and Interacts with Cortical Microtubules in Cotton Fibers
Authors: Preuss Mary L. , Kovar David R. , Lee Y.-R. Julie , Staiger Christopher J. , Delmer Deborah P. , Liu Bo
Published: December 2004

A novel kinesin, GhKCH1, has been identified from cotton (Gossypium hirsutum) fibers. GhKCH1 has a centrally located kinesin catalytic core, a signature neck peptide of minus end-directed kinesins, and a unique calponin homology (CH) domain at its N terminus. GhKCH1 and other CH domain-containing kinesins (KCHs) belong to a distinct branch of the minus end-directed kinesin subfamily. To date the KCH kinesins have been found only in higher plants. Because the CH domain is often found in actin-binding proteins, we proposed that GhKCH1 might play a role in mediating dynamic interaction between microtubules and actin microfilaments in cotton fibers. In an in vitro actin-binding assay, GhKCH1's N-terminal region including the CH domain interacted directly with actin microfilaments. In cotton fibers, GhKCH1 decorated cortical microtubules in a punctate manner. Occasionally GhKCH1 was found to be associated with transverse-cortical actin microfilaments, but never with axial actin cables in cotton fibers. Localization of GhKCH1 on cortical microtubules was independent of the integrity of actin microfilaments. Thus, GhKCH1 may play a role in organizing the actin network in coordination with the cortical microtubule array. These data also suggest that flowering plants may employ unique KCHs to coordinate actin microfilaments and microtubules during cell growth.
The Biosynthesis of UDP-Galacturonic Acid in Plants. Functional Cloning and Characterization of Arabidopsis UDP-d-Glucuronic Acid 4-Epimerase
Authors: Gu Xiaogang , Bar-Peled Maor
Published: December 2004

UDP-GlcA 4-epimerase (UGlcAE) catalyzes the epimerization of UDP-α-d-glucuronic acid (UDP-GlcA) to UDP-α-d-galacturonic acid (UDP-GalA). UDP-GalA is a precursor for the synthesis of numerous cell-surface polysaccharides in bacteria and plants. Using a biochemical screen, a gene encoding AtUGlcAE1 in Arabidopsis (Arabidopsis thaliana) was identified and the recombinant enzyme biochemically characterized. The gene belongs to a small gene family composed of six isoforms. All members of the UGlcAE gene family encode a putative type-II membrane protein and have two domains: a variable N-terminal region approximately 120 amino acids long composed of a predicted cytosolic, transmembrane, and stem domain, followed by a large conserved C-terminal catalytic region approximately 300 amino acids long composed of a highly conserved catalytic domain found in a large protein family of epimerase/dehydratases. The recombinant epimerase has a predicted molecular mass of approximately 43 kD, although size-exclusion chromatography suggests that it may exist as a dimer (approximately 88 kD). AtUGlcAE1 forms UDP-GalA with an equilibrium constant value of approximately 1.9 and has an apparent Km value of 720 μm for UDP-GlcA. The enzyme has maximum activity at pH 7.5 and is active between 20°C and 55°C. Arabidopsis AtUGlcAE1 is not inhibited by UDP-Glc, UDP-Gal, or UMP. However, the enzyme is inhibited by UDP-Xyl and UDP-Ara, suggesting that these nucleotide sugars have a role in regulating the synthesis of pectin. The cloning of the AtUGlcAE1 gene will increase our ability to investigate the molecular factors that regulate pectin biosynthesis in plants. The availability of a functional recombinant UDP-GlcA 4-epimerase will be of considerable value for the facile generation of UDP-d-GalA in the amounts required for detailed studies of pectin biosynthesis.
Inactivation of the clpC1 Gene Encoding a Chloroplast Hsp100 Molecular Chaperone Causes Growth Retardation, Leaf Chlorosis, Lower Photosynthetic Activity, and a Specific Reduction in Photosystem Content
Authors: Sjögren Lars L.E. , MacDonald Tara M. , Sutinen Sirkka , Clarke Adrian K.
Published: December 2004

ClpC is a molecular chaperone of the Hsp100 family. In higher plants there are two chloroplast-localized paralogs (ClpC1 and ClpC2) that are approximately 93% similar in primary sequence. In this study, we have characterized two independent Arabidopsis (Arabidopsis thaliana) clpC1 T-DNA insertion mutants lacking on average 65% of total ClpC content. Both mutants display a retarded-growth phenotype, leaves with a homogenous chlorotic appearance throughout all developmental stages, and more perpendicular secondary influorescences. Photosynthetic performance was also impaired in both knockout lines, with relatively fewer photosystem I and photosystem II complexes, but no changes in ATPase and Rubisco content. However, despite the specific drop in photosystem I and photosystem II content, no changes in leaf cell anatomy or chloroplast ultrastructure were observed in the mutants compared to the wild type. Previously proposed functions for envelope-associated ClpC in chloroplast protein import and degradation of mistargeted precursors were examined and shown not to be significantly impaired in the clpC1 mutants. In the stroma, where the majority of ClpC protein is localized, marked increases of all ClpP paralogs were observed in the clpC1 mutants but less variation for the ClpR paralogs and a corresponding decrease in the other chloroplast-localized Hsp100 protein, ClpD. Increased amounts of other stromal molecular chaperones (Cpn60, Hsp70, and Hsp90) and several RNA-binding proteins were also observed. Our data suggest that overall ClpC as a stromal molecular chaperone plays a vital role in chloroplast function and leaf development and is likely involved in photosystem biogenesis.
Equilibrium time on the market (ETOM) for commercial real estate in the UK
Authors: Brown Gerald R. , Foo Sing Tien
Published: December 2004

Time on the market (TOM) has been widely tested in the US real estate literature using listing and selling data of houses captured in the multiple listing services (MLSs). Unfortunately in the UK there are no MLSs so it is not possible to undertake similar analyses. The approach adopted in this paper differs from traditional TOM analyses in that it focuses on the speed or time the market takes to correct for information differences between open market valuations and traded prices. In this context the paper introduces the concept of equilibrium time on the market (ETOM). The study therefore adopts a different approach to estimating TOM and in addition also examines the phenomenon within the UK commercial real estate sector. Based on a simple present value model, the time taken for the difference between an appraiser's estimate of open market value and known selling prices define our time on the market under equilibrium market conditions. Using the annualised UK Investment Property Databank all‐property total return index for a sample period of 17 years between 1983 and 1999, the average ETOM was estimated to be 8.4 months. This figure, however, varied and depended on market conditions.
How should unsmoothing affect pension plan asset allocation?
Authors: Booth Philip , Matysiak George
Published: December 2004

Examines the impact of using “unsmoothing” techniques on real estate data to take pension‐plan asset‐allocation decisions. It is generally believed that valuation‐based real estate indices give rise to returns figures which are “smoothed” versions of the underlying transaction prices. Unsmoothing techniques can be used to develop real estate return data series that are believed to be a more accurate representation of underlying transaction prices. If this is done, the resulting data reveal greater volatility of real estate returns. When such data are applied to portfolio selection models, they often reveal a reduced allocation to real estate in efficient portfolios. Looks at the impact of unsmoothing data when taking pension‐plan asset‐allocation decisions. Finds here that the unsmoothed data are more closely correlated with pension plan liabilities. As a result, efficient pension plan portfolios sometimes contain more real estate, rather than less. In general, there is little change in the efficient real estate allocation. These results are very important. They reveal that so‐called “valuation smoothing” may distort property investment decisions less than is commonly thought.
Addiction as a Computational Process Gone Awry
Authors: Redish A. David
Published: December 2004

Addictive drugs have been hypothesized to access the same neurophysiological mechanisms as natural learning systems. These natural learning systems can be modeled through temporal-difference reinforcement learning (TDRL), which requires a reward-error signal that has been hypothesized to be carried by dopamine. TDRL learns to predict reward by driving that reward-error signal to zero. By adding a noncompensable drug-induced dopamine increase to a TDRL model, a computational model of addiction is constructed that over-selects actions leading to drug receipt. The model provides an explanation for important aspects of the addiction literature and provides a theoretic view-point with which to address other aspects.
Targeting Malaria Virulence and Remodeling Proteins to the Host Erythrocyte
Authors: Marti Matthias , Good Robert T. , Rug Melanie , Knuepfer Ellen , Cowman Alan F.
Published: December 2004

To establish infection in the host, malaria parasites export remodeling and virulence proteins into the erythrocyte. These proteins can traverse a series of membranes, including the parasite membrane, the parasitophorous vacuole membrane, and the erythrocyte membrane. We show that a conserved pentameric sequence plays a central role in protein export into the host cell and predict the exported proteome in
Plasmodium falciparum
. We identified 400 putative erythrocyte-targeted proteins corresponding to ∼8% of all predicted genes, with 225 virulence proteins and a further 160 proteins likely to be involved in remodeling of the host erythrocyte. The conservation of this signal across
Plasmodium
species has implications for the development of new antimalarials.
Capuchin Stone Tool Use in Caatinga Dry Forest
Authors: de A. Moura A. C. , Lee P. C.
Published: December 2004

Wild capuchin monkeys inhabiting dry forest were found to customarily use tools as part of their extractive foraging techniques. Tools consisted of twigs and sticks, often modified, which were used to probe for insects and, most frequently, of stones of a variety of sizes and shapes used for cracking and digging. The use of tools for digging has been thought to be restricted to humans. These monkeys, living in a harsh dry habitat, survive food limitation and foraging time constraints through their extensive tool use.
A Host-Targeting Signal in Virulence Proteins Reveals a Secretome in Malarial Infection
Authors: Hiller N. Luisa , Bhattacharjee Souvik , van Ooij Christiaan , Liolios Konstantinos , Harrison Travis , Lopez-Estraño Carlos , Haldar Kasturi
Published: December 2004

Malaria parasites secrete proteins across the vacuolar membrane into the erythrocyte, inducing modifications linked to disease and parasite survival. We identified an 11–amino acid signal required for the secretion of proteins from the
Plasmodium falciparum
vacuole to the human erythrocyte. Bioinformatics predicted a secretome of >320 proteins and conservation of the signal across parasite species. Functional studies indicated the predictive value of the signal and its role in targeting virulence proteins to the erythrocyte and implicated its recognition by a receptor/transporter. Erythrocyte modification by the parasite may involve plasmodial heat shock proteins and be vastly more complex than hitherto realized.
Frequent Recombination in a Saltern Population of
Halorubrum
Authors: Papke R. Thane , Koenig Jeremy E. , Rodríguez-Valera Francísco , Doolittle W. Ford
Published: December 2004

Sex and recombination are driving forces in the evolution of eukaryotes. Homologous recombination is known to be the dominant process in the divergence of many bacterial species. For Archaea, the only direct evidence bearing on the importance or natural occurrence of homologous recombination is anecdotal reports of mosaicism from comparative genomic studies. Genetic studies, however, reveal that recombination may play a significant role in generating diversity among members of at least one archaeal group, the haloarchaea. We used multi-locus sequence typing to demonstrate that haloarchaea exchange genetic information promiscuously, exhibiting a degree of linkage equilibrium approaching that of a sexual population.
Defective Telomere Lagging Strand Synthesis in Cells Lacking WRN Helicase Activity
Authors: Crabbe Laure , Verdun Ramiro E. , Haggblom Candy I. , Karlseder Jan
Published: December 2004

Cells from Werner syndrome patients are characterized by slow growth rates, premature senescence, accelerated telomere shortening rates, and genome instability. The syndrome is caused by the loss of the RecQ helicase WRN, but the underlying molecular mechanism is unclear. Here we report that cells lacking WRN exhibit deletion of telomeres from single sister chromatids. Only telomeres replicated by lagging strand synthesis were affected, and prevention of loss of individual telomeres was dependent on the helicase activity of WRN. Telomere loss could be counteracted by telomerase activity. We propose that WRN is necessary for efficient replication of G-rich telomeric DNA, preventing telomere dysfunction and consequent genomic instability.
The G
s
-Linked Receptor GPR3 Maintains Meiotic Arrest in Mammalian Oocytes
Authors: Mehlmann Lisa M. , Saeki Yoshinaga , Tanaka Shigeru , Brennan Thomas J. , Evsikov Alexei V. , Pendola Frank L. , Knowles Barbara B. , Eppig John J. , Jaffe Laurinda A.
Published: December 2004

Mammalian oocytes are held in prophase arrest by an unknown signal from the surrounding somatic cells. Here we show that the orphan G
s
-linked receptor GPR3, which is localized in the oocyte, maintains this arrest. Oocytes from
Gpr3
knockout mice resume meiosis within antral follicles, independently of an increase in luteinizing hormone, and this phenotype can be reversed by injection of
Gpr3
RNA into the oocytes. Thus, the GPR3 receptor is a link in communication between the somatic cells and oocyte of the ovarian follicle and is crucial for the regulation of meiosis.
Host-Parasite Coevolutionary Conflict Between
Arabidopsis
and Downy Mildew
Authors: Allen Rebecca L. , Bittner-Eddy Peter D. , Grenville-Briggs Laura J. , Meitz Julia C. , Rehmany Anne P. , Rose Laura E. , Beynon Jim L.
Published: December 2004

Plants are constantly exposed to attack by an array of diverse pathogens but lack a somatically adaptive immune system. In spite of this, natural plant populations do not often suffer destructive disease epidemics. Elucidating how allelic diversity within plant genes that function to detect pathogens (resistance genes) counteracts changing structures of pathogen genes required for host invasion (pathogenicity effectors) is critical to our understanding of the dynamics of natural plant populations. The
RPP13
resistance gene is the most polymorphic gene analyzed to date in the model plant
Arabidopsis thaliana
. Here we report the cloning of the avirulence gene,
ATR13
, that triggers
RPP13
-mediated resistance, and we show that it too exhibits extreme levels of amino acid polymorphism. Evidence of diversifying selection visible in both components suggests that the host and pathogen may be locked in a coevolutionary conflict at these loci, where attempts to evade host resistance by the pathogen are matched by the development of new detection capabilities by the host.
Transient Interface Sharpening in Miscible Alloys
Authors: Erdélyi Zoltán , Sladecek Marcel , Stadler Lorenz-M. , Zizak Ivo , Langer Gábor A. , Kis-Varga Miklós , Beke Desző L. , Sepiol Bogdan
Published: December 2004

We observed that diffuse interfaces sharpen rather than broaden in completely miscible ideal binary systems. This is shown in situ during heat treatments at gradually increasing temperatures by scattering of synchrotron radiation in coherent Mo/V multilayers containing initially diffuse interfaces. This effect provides a useful tool for the improvement of interfaces and offers a way to fabricate better x-ray or neutron mirrors, microelectronic devices, or multilayers with giant magnetic resistance.
Parallel Worlds
Authors: Gouvêa Fernando Q.
Published: December 2004

János Bolyai, Non-Euclidean Geometry, and the Nature of Space
. by Jeremy J. Gray. MIT Press, Cambridge, MA, 2004. 224 pp. Paper, $20, £12.95. ISBN 0-262-57174-9. Burndy Library Publications.

The author describes the context and influence of Bolyai's 1832 paper, which opened the door to the field of non-Euclidean geometry; the book also contains a facsimile of the Latin original and G. B. Halsted's 1896 English translation.
Circumferential Curiosities
Authors: Maor Eli
Published: December 2004

π: A Biography of the World's Most Mysterious Number
. by Alfred S. Posamentier and Ingmar Lehmann. Prometheus, Amherst, NY, 2004. 324 pp. $26. ISBN 1-59102-200-2.

The authors sketch the history of π and present an engaging collection of curiosities about it.
UNDERSTANDING PRESENTATION OF VIRAL ANTIGENS TO CD8+T CELLS IN VIVO: The Key to Rational Vaccine Design
Authors: Yewdell Jonathan W. , Haeryfar S.M. Mansour
Published: December 2004

▪ Abstract  CD8+T cells play a critical role in antiviral immunity by exerting direct antiviral activity against infected cells. Because of their ability to recognize all types of viral proteins, they offer the promise of providing broad immunity to viruses that evade humoral immunity by varying their surface proteins. Consequently, there is considerable interest in developing vaccines that elicit effective antiviral TCD8+responses. Generating optimal vaccines ultimately requires rational design based on detailed knowledge of how TCD8+are activated in vivo under natural circumstances. Here we review recent progress obtained largely by in vivo studies in mice to understand the mechanistic basis for activation of naive TCD8+in virus infections. These studies point the way to detailed understanding and provide some key information for vaccine development, although much remains to be learned to enable truly rational vaccine design.
MOLECULAR GENETICS OF T CELL DEVELOPMENT
Authors: Rothenberg Ellen V. , Taghon Tom
Published: December 2004

▪ Abstract  T cell development is guided by a complex set of transcription factors that act recursively, in different combinations, at each of the developmental choice points from T-lineage specification to peripheral T cell specialization. This review describes the modes of action of the major T-lineage-defining transcription factors and the signal pathways that activate them during intrathymic differentiation from pluripotent precursors. Roles of Notch and its effector RBPSuh (CSL), GATA-3, E2A/HEB and Id proteins, c-Myb, TCF-1, and members of the Runx, Ets, and Ikaros families are critical. Less known transcription factors that are newly recognized as being required for T cell development at particular checkpoints are also described. The transcriptional regulation of T cell development is contrasted with that of B cell development, in terms of their different degrees of overlap with the stem-cell program and the different roles of key transcription factors in gene regulatory networks leading to lineage commitment.
Treatment of suckling rats with GLP-2 plus dexamethasone increases the ileal uptake of fatty acids in later life
Authors: Iordache Claudiu , Drozdowski Laurie , Clandinin M. Tom , Wild Gary , Todd Zoe , Thomson Alan B. R.
Published: December 2004

Glucocorticosteroids such as dexamethasone (Dex) increase sugar and lipid uptake in adult animals and accelerate the development of the immature intestine. The effect of Dex on the ontogeny of lipid absorption is unknown. In adult rats, glucagon-like peptide-2 (GLP-2) has a trophic effect on the intestine and enhances nutrient absorption. This study was undertaken to determine the effect of GLP-2 and Dex on the intestine uptake of lipids in suckling rats and to determine whether any such effect persists into the postweanling period. Sixty-four suckling rats were randomized into four groups. They were treated from days 11 to 21 with GLP-2 (0.1 μg·g−1·day−1sc), Dex (0.128 μg·g−1·day−1sc), GLP-2 plus Dex (GLP-2 0.1 μg·g−1·day−1sc + Dex 0.128 μg·g−1·day−1sc), or placebo. One-half the pups were killed at days 19–21 (“sucklings”), and one-half were killed 4 wk later (“weanlings”). The rate of intestinal uptake of six fatty acids (12:0, lauric; 16:0, palmitic; 18:0, stearic; 18:1, oleic; 18:2, linoleic; and 18:3, linolenic) and cholesterol was assessed using an in vitro ring technique. GLP-2 had no effect on lipid uptake. Dex increased the uptake of 18:3 in sucklings, and the ileal uptake of 18:0 was increased in weanlings. The combination of GLP-2 plus Dex had no effect in sucklings and increased the ileal uptake of 12:0, 18:0, 18:1, 18:2, and 18:3 in weanlings. The enhanced uptake of fatty acids with GLP-2 plus Dex was not explained by alterations in the animals' body or intestinal weights, intestinal morphology, or intestinal- or liver-fatty acid binding proteins. Unlike adults, GLP-2 does not enhance lipid uptake in sucklings. Dex has a modest enhancing effect on selected fatty acid uptake both in sucklings as well as weanlings. GLP-2 plus Dex has an enhancing effect on the ileal uptake of fatty acids in weanlings 4 wk after their previous injection with GLP-2 plus Dex. It remains to be established what is the nutritional importance of this late effect of prior exposure to Dex or GLP-2 plus Dex on the intestinal uptake of lipids.
Glucocorticoid responsiveness in developing human intestine: possible role in prevention of necrotizing enterocolitis
Authors: Nanthakumar N. Nanda , Young Cheryl , Ko Jae Sung , Meng Di , Chen Ji , Buie Timothy , Walker W. Allan
Published: December 2004

Necrotizing enterocolitis (NEC) is a major inflammatory disease of the premature human intestine that can be prevented by glucocorticoids if given prenatally before the 34th wk of gestation. This observation suggests that a finite period of steroid responsiveness exists as has been demonstrated in animal models. Human intestinal xenografts were used to determine whether a glucocorticoid responsive period exists in the developing human intestine. Developmental responsiveness was measured by lactase activity and inflammatory responsiveness by IL-8, IL-6, and monocyte chemotactic protein-1 (MCP-1) induction after an endogenous (IL-1β) or exogenous (LPS) proinflammatory stimulus, respectively. Functional development of ileal xenografts were monitored for 30 wk posttransplantation, and the lactase activity recapitulated that predicted by in utero development. Cortisone acetate accelerated the ontogeny of lactase at 20 wk (immature) but the effect was lost by 30 wk (mature) posttransplant. Concomitant with accelerated maturation, the IL-8 response to both IL-1β and LPS was significantly dampened (from 6- to 3-fold) by glucocorticoid pretreatment in the immature but not mature xenografts. The induction of IL-8 was reflected at the level of IL-8 mRNA, suggesting transcriptional regulation. The excessive activation of IL-8 in the immature gut was mediated by a prolonged activation of ERK and p38 kinases and nuclear translocation of NF-κB due to low levels of IκB. Steroid pretreatment in immature intestine dampens activation of all three signaling pathways in response to proinflammatory stimuli. Therefore, accelerating intestinal maturation by glucocorticoids within the responsive period by accelerating functional and inflammatory maturation may provide an effective preventive therapy for NEC.
p38 MAP kinase inhibitor reverses stress-induced cardiac myocyte dysfunction
Authors: Kan Hong , Birkle Dale , Jain Abnash C. , Failinger Conard , Xie Sherry , Finkel Mitchell S.
Published: December 2004

Stress is gaining increasing acceptance as an independent risk factor contributing to adverse cardiovascular outcomes. Potential mechanisms responsible for the deleterious effects of stress on the development and progression of cardiovascular disease remain to be elucidated. An established animal model of stress in humans is the prenatally stressed (PS) rat. We stressed rats in their third trimester of pregnancy by daily injections of saline and moving from cage to cage. Male offspring of these stressed dams (PS) and age-matched male control offspring (control) were further subjected to restraint stress (R) at 6 and 7 wk of age. Echocardiography revealed a significant decrease in fractional shortening in PS + R vs. controls + R (45.8 ± 3.9 vs. 61.9 ± 2.4%, PS + R vs. controls + R; P < 0.01; n = 12). Isolated adult rat ventricular myocytes from PS + R also revealed diminished fractional shortening (6.7 ± 0.8 vs. 12.7 ± 1.1%, PS + R vs. controls + R; P < 0.01; n = 24) and blunted inotropic responses to isoproterenol ( P < 0.01; n = 24) determined by automated border detection. The p38 mitogen-activated protein (MAP) kinase inhibitor SB-203580 blocked p38 MAP kinase phosphorylation, reversed the depression in fractional shortening, and partially ameliorated the blunted adrenergic signaling seen in adult rat ventricular myocytes from PS + R. Phosphorylation of p38 MAP kinase in cardiac myocytes by stress may be sufficient to lead to myocardial dysfunction in animal models and possibly humans.
Prediction of dilutional acidosis based on the revised classical dilution concept for bicarbonate
Authors: Lang Werner , Zander Rolf
Published: December 2004

Due to the controversy surrounding the term dilutional acidosis, the classical dilution concept for bicarbonate has been rigorously revised for the prediction of pH, actual bicarbonate concentration, and base excess. In the algorithms derived for buffer solutions, blood, and whole body (1-, 2-, and 3-fluid compartment), only bicarbonate is considered. On dilution at constant Pco2, the final concentration of bicarbonate is the sum in terms of pH, due to the following processes: dilution, formation from chemical reaction with the nonbicarbonate buffers phosphate, hemoglobin, and plasma proteins, and transfer from erythrocytes and interstitial fluid to plasma. At constant Pco2, the level of carbonic acid is held constant, whereas those of the buffer bases are reduced by dilution, resulting in acidosis. In mixed bicarbonate/phosphate buffer, the final concentration of HCO3− exceeds the diluted value due to additional buffering of H2CO3 by HPO42−. For whole blood in vitro, pH, and actual bicarbonate concentration are predicted from dilution with 0.9% saline from initial Hb (100%) to infinite dilution (pure saline). The acidosis from dilution of plasma bicarbonate is mitigated by contributions from plasma proteins (<1 mmol/l) and from the erythrocytes (∼5 mmol/l). Similarly, for whole body, the main contributions to combat primary dilutional acidosis in the range of hemodilution (relative Hb: 100–50%) are from the erythrocytes (1.2–2.2 mmol/l) and from the interstitial fluid (3.3–7.2 mmol/l). Perioperatively measured nonrespiratory acidosis is predictable if caused by hemodilution with fluids containing neither bicarbonate nor its precursors, irrespective of other electrolytes.
Insights by Peruvian scientists into the pathogenesis of human chronic hypoxic pulmonary hypertension
Authors: Reeves John T. , Grover Robert F.
Published: December 2004

Pulmonary hypertension had long been suspected in high-altitude natives of the Andes. However, it remained for a team of Peruvian scientists led by Dante Penaloza to provide not only the first clear evidence that humans living at high altitude did indeed have chronic, and occasionally severe, pulmonary hypertension, but more importantly, that this was a consequence of structural changes in the pulmonary vascular bed. Novel histological findings by one of the team, Javier Arias-Stella, indicated that hypoxia-induced thickening of the pulmonary arteriolar walls was the primary cause of the elevated pressure. Because the hypertension was not promptly reversed by vasodilators (oxygen inhalation or acetylcholine infusion), they found it differed from acute hypoxic pulmonary vasoconstriction. The team's other novel findings included a delay in the normal fall in pulmonary vascular resistance after birth and, in adults, a lack of vasodilation with muscular exercise. Furthermore, the altitude-related pulmonary hypertension resolved over time at sea level.
Hypoxic pulmonary vasoconstriction: redox events in oxygen sensing
Authors: Waypa Gregory B. , Schumacker Paul T.
Published: December 2004

Recently, the mitochondria have become the focus of attention as the site of O2sensing underlying hypoxic pulmonary vasoconstriction (HPV). However, two disparate models have emerged to explain how mitochondria react to a decrease in Po2. One model proposes that a drop in Po2decreases the rate of mitochondrial reactive oxygen species (ROS) generation, resulting in a decrease in oxidant stress and an accumulation of reducing equivalents. The resulting shift of the cytosol to a reduced state causes the inhibition of voltage-dependent potassium channels, membrane depolarization, and the influx of calcium through voltage-gated (L-type) calcium channels. A second and opposing model suggests that hypoxia triggers a paradoxical increase in a mitochondrial-induced ROS signal. The resulting shift of the cytosol to an oxidized state triggers the release of intracellular calcium stores, recruitment of calcium channels in the plasma membrane, and activation of contraction. This article summarizes the potential involvement of a mitochondria-induced ROS signal in these two very different models.
Automatic classification of activity and apneas using whole body plethysmography in newborn mice
Authors: Matrot B. , Durand E. , Dauger S. , Vardon G. , Gaultier C. , Gallego J.
Published: December 2004

An increasing number of studies in newborn mice are being performed to determine the mechanisms of sleep apnea, which is the hallmark of early breathing disorders. Whole body plethysmography is the method of choice, as it does not require immobilization, which affects behavioral states and breathing. However, activity inside the plethysmograph may disturb the respiratory signal. Visual classification of the respiratory signal into ventilatory activity, activity-related disturbances, or apneas is so time-consuming as to considerably hamper the phenotyping of large pup samples. We propose an automatic classification of activity based on respiratory disturbances and of apneas based on spectral analysis. This method was validated in newborn mice on the day of birth and on postnatal days 2, 5, and 10, under normoxic and hypoxic (5% O2) conditions. For both activity and apneas, visual and automatic scores showed high Pearson's correlation coefficients (0.92 and 0.98, respectively) and high intraclass correlation coefficients (0.96–0.99), supporting strong agreement between the two methods. The present results suggest that breathing disturbances may provide a valid indirect index of activity in freely moving newborn mice and that automatic apnea classification based on spectral analysis may be efficient in terms of precision and of time saved.
Effects of exercise and diet on chronic disease
Authors: Roberts Christian K. , Barnard R. James
Published: December 2004

Currently, modern chronic diseases, including cardiovascular diseases, Type 2 diabetes, metabolic syndrome, and cancer, are the leading killers in Westernized society and are increasing rampantly in developing nations. In fact, obesity, diabetes, and hypertension are now even commonplace in children. Clearly, however, there is a solution to this epidemic of metabolic disease that is inundating today’s societies worldwide: exercise and diet. Overwhelming evidence from a variety of sources, including epidemiological, prospective cohort, and intervention studies, links most chronic diseases seen in the world today to physical inactivity and inappropriate diet consumption. The purpose of this review is to 1) discuss the effects of exercise and diet in the prevention of chronic disease, 2) highlight the effects of lifestyle modification for both mitigating disease progression and reversing existing disease, and 3) suggest potential mechanisms for beneficial effects.
Aerobic power and insulin action improve in response to endurance exercise training in healthy 77–87 yr olds
Authors: Evans Ellen M. , Racette Susan B. , Peterson Linda R. , Villareal Dennis T. , Greiwe Jeffrey S. , Holloszy John O.
Published: December 2004

Previous studies have demonstrated that frail octogenarians have an attenuated capacity for cardiovascular adaptations to endurance exercise training. In the present study, we determined the magnitude of cardiovascular and metabolic adaptations to high-intensity endurance exercise training in healthy, nonfrail elderly subjects. Ten subjects [8 men, 2 women, 80.3 yr (SD2.5)] completed 10–12 mo (108 exercise sessions) of a supervised endurance exercise training program consisting of 2.5 sessions/wk (SD 0.2), 58 min/session (SD 6), at an intensity of 83% (SD 5) of peak heart rate. Primary outcomes were maximal attainable aerobic power [peak aerobic capacity (V̇o2peak)]; serum lipids, oral glucose tolerance, and insulin action during a hyperglycemic clamp; body composition by dual-energy X-ray absorptiometry, and energy expenditure using doubly labeled water and indirect calorimetry. The training program resulted in an increase in V̇o2peakof 15% (SD 7) [22.9 (SD 3.3) to 26.2 ml·kg−1·min−1(SD 4.0); P < 0.0001]. Favorable lipid changes included reductions in total cholesterol (−8%; P = 0.002) and LDL cholesterol (−10%; P = 0.003), with no significant change in HDL cholesterol or triglycerides. Insulin action improved, as evidenced by a 29% increase in glucose disposal rate relative to insulin concentration during the hyperglycemic clamp. Fat mass decreased by 1.8 kg (SD 1.4) ( P = 0.003); lean mass did not change. Total energy expenditure increased by 400 kcal/day because of an increase in physical activity. No change occurred in resting metabolism. In summary, healthy nonfrail octogenarians can adapt to high-intensity endurance exercise training with improvements in aerobic power, insulin action, and serum lipid and lipoprotein risk factors for coronary heart disease; however, the adaptations in aerobic power and insulin action are attenuated compared with middle-aged individuals.
Rat Phenome Project: The untapped potential of existing rat strains
Authors: Mashimo Tomoji , Voigt Birger , Kuramoto Takashi , Serikawa Tadao
Published: December 2004

The National Bio Resource Project for the Rat in Japan collects, preserves, and distributes rat strains. More than 250 inbred strains have been deposited thus far into the National Bio Resource Project for the Rat and are maintained as specific pathogen-free rats or cryopreserved embryos. We are now comprehensively characterizing deposited strains as part of the Rat Phenome Project to reevaluate their value as models of human diseases. Phenotypic data are being collected for 7 categories and 109 parameters: functional observational battery (neurobehavior), behavior studies, blood pressure, biochemical blood tests, hematology, urology, and anatomy. Furthermore, genotypes are being determined for 370 simple sequence-length polymorphism markers distributed through the whole rat genome. Here, we report these large-scale, high-throughput screening data that have already been collected for 54 rat strains. This comprehensive, original phenotypic data can be systematically viewed by “strain ranking” for each parameter. This allows investigators to explore the relationship between several rat strains, to identify new rat models, and to select the most suitable strains for specific experiments. The discovery of several potential models for human diseases, such as hypertension, hypotension, renal diseases, hyperlipemia, hematological disorders, and neurological disorders, illustrates the potential of many existing rat strains. All deposited strains and obtained data are freely available for any interested researcher worldwide at http://www.anim.med.kyoto-u.ac.jp/nbr .