bluuebunny/crossref_metadata_2025 huggingface dataset:
Proteolytic activation of PKN by caspase-3 or related protease during apoptosis
Authors: Takahashi Mikiko , Mukai Hideyuki , Toshimori Masanao , Miyamoto Masaaki , Ono Yoshitaka
Published: July 2002

PKN, a fatty acid- and Rho-activated serine/threonine kinase having a catalytic domain highly homologous to protein kinase C (PKC), was cleaved at specific sites in apoptotic Jurkat and U937 cells on Fas ligation and treatment with staurosporin or etoposide, respectively. The cleavage of PKN occurred with a time course similar to that of PKCδ, a known caspase substrate. This proteolysis was inhibited by a caspase inhibitor, acetyl-Asp-Glu-Val-Asp-aldehyde. The cleavage fragments were generatedin vitrofrom PKN by treatment with recombinant caspase-3. Site-directed mutagenesis of specific aspartate residues prevented the appearance of these fragments. These results indicate that PKN is cleaved by caspase-3 or related protease during apoptosis. The major proteolysis took place between the amino-terminal regulatory domain and the carboxyl-terminal catalytic domain, and it generated a constitutively active kinase fragment. The cleavage of PKN may contribute to signal transduction, eventually leading to apoptosis.
The helical domain of intestinal fatty acid binding protein is critical for collisional transfer of fatty acids to phospholipid membranes
Authors: Corsico Betina , Cistola David P. , Frieden Carl , Storch Judith
Published: July 2002

Fatty acid binding proteins (FABPs) exhibit a β-barrel topology, comprising 10 antiparallel β-sheets capped by two short α-helical segments. Previous studies suggested that fatty acid transfer from several FABPs occurs during interaction between the protein and the acceptor membrane, and that the helical domain of the FABPs plays an important role in this process. In this study, we employed a helix-less variant of intestinal FABP (IFABP-HL) and examined the rate and mechanism of transfer of fluorescent anthroyloxy fatty acids (AOFA) from this protein to model membranes in comparison to the wild type (wIFABP). In marked contrast to wIFABP, IFABP-HL does not show significant modification of the AOFA transfer rate as a function of either the concentration or the composition of the acceptor membranes. These results suggest that the transfer of fatty acids from IFABP-HL occurs by an aqueous diffusion-mediated process, i.e., in the absence of the helical domain, effective collisional transfer of fatty acids to membranes does not occur. Binding of wIFABP and IFABP-HL to membranes was directly analyzed by using a cytochrome
c
competition assay, and it was shown that IFABP-HL was 80% less efficient in preventing cytochrome
c
from binding to membranes than the native IFABP. Collectively, these results indicate that the α-helical region of IFABP is involved in membrane interactions and thus plays a critical role in the collisional mechanism of fatty acid transfer from IFABP to phospholipid membranes.
Doxycycline control of prion protein transgene expression modulates prion disease in mice
Authors: Tremblay Patrick , Meiner Zeev , Galou Maria , Heinrich Cornelia , Petromilli Chris , Lisse Thomas , Cayetano Juliana , Torchia Marilyn , Mobley William , Bujard Hermann , DeArmond Stephen J. , Prusiner Stanley B.
Published: July 2002

Conversion of the cellular prion protein (PrP
C
) into the pathogenic isoform (PrP
Sc
) is the fundamental event underlying transmission and pathogenesis of prion diseases. To control the expression of PrP
C
in transgenic (Tg) mice, we used a tetracycline controlled transactivator (tTA) driven by the PrP gene control elements and a tTA-responsive promoter linked to a PrP gene [Gossen, M. and Bujard, H. (1992)
Proc. Natl. Acad. Sci. USA
89, 5547–5551]. Adult Tg mice showed no deleterious effects upon repression of PrP
C
expression (>90%) by oral doxycycline, but the mice developed progressive ataxia at ≈50 days after inoculation with prions unless maintained on doxycycline. Although Tg mice on doxycycline accumulated low levels of PrP
Sc
, they showed no neurologic dysfunction, indicating that low levels of PrP
Sc
can be tolerated. Use of the tTA system to control PrP expression allowed production of Tg mice with high levels of PrP that otherwise cause many embryonic and neonatal deaths. Measurement of PrP
Sc
clearance in Tg mice should be possible, facilitating the development of pharmacotherapeutics.
Light-induced exposure of the cytoplasmic end of transmembrane helix seven in rhodopsin
Authors: Abdulaev Najmoutin G. , Ridge Kevin D.
Published: July 2002

A key step in signal transduction in the visual cell is the light-induced conformational change of rhodopsin that triggers the binding and activation of the guanine nucleotide-binding protein. Site-directed mAbs against bovine rhodopsin were produced and used to detect and characterize these conformational changes upon light activation. Among several antibodies that bound exclusively to the light-activated state, an antibody (IgG subclass) with the highest affinity (
K
a
≈ 6 × 10
−9
M) was further purified and characterized. The epitope of this antibody was mapped to the amino acid sequence 304–311. This epitope extends from the central region to the cytoplasmic end of the seventh transmembrane helix and incorporates a part of a highly conserved NPXXY motif, a critical region for signaling and agonist-induced internalization of several biogenic amine and peptide receptors. In the dark state, no binding of the antibody to rhodopsin was detected. Accessibility of the epitope to the antibody correlated with formation of the metarhodopsin II photointermediate and was reduced significantly at the metarhodopsin III intermediate. Further, incubation of the antigen–antibody complex with 11-
cis
-retinal failed to regenerate the native rhodopsin chromophore. These results suggest significant and reversible conformational changes in close proximity to the cytoplasmic end of the seventh transmembrane helix of rhodopsin that might be important for folding and signaling.
The
Arabidopsis
CHL1 protein plays a major role in high-affinity nitrate uptake
Authors: Wang Rongchen , Liu Dong , Crawford Nigel M.
Published: July 2002

The
CHL1
(
NRT1
) gene of
Arabidopsis
encodes a nitrate-inducible nitrate transporter that is thought to be a component of the low-affinity (mechanism II) nitrate-uptake system in plants. A search was performed to find high-affinity (mechanism I) uptake mutants by using chlorate selections on plants containing
Tag1
transposable elements. Chlorate-resistant mutants defective in high-affinity nitrate uptake were identified, and one had a
Tag1
insertion in
chl1
, which was responsible for the phenotype. Further analysis showed that
chl1
mutants have reduced high-affinity uptake in induced plants and are missing a saturable component of the constitutive, high-affinity uptake system in addition to reduced low-affinity uptake. The contribution of CHL1 to constitutive high-affinity uptake is higher when plants are grown at more acidic pH, conditions that increase the level of
CHL1
mRNA.
chl1
mutants show reduced membrane depolarization in root epidermal cells in response to low (250 μM) and high (10 mM) concentrations of nitrate. Low levels of nitrate (100 μM) induce a rapid increase in
CHL1
mRNA. These results show that CHL1 is an important component of both the high-affinity and the low-affinity nitrate-uptake systems and indicate that CHL1 may be a dual-affinity nitrate transporter.
Induction of monocyte chemoattractant protein-1 in HIV-1 Tat-stimulated astrocytes and elevation in AIDS dementia
Authors: Conant Katherine , Garzino-Demo Alfredo , Nath Avindra , McArthur Justin C. , Halliday William , Power Christopher , Gallo Robert C. , Major Eugene O.
Published: July 2002

Activated monocytes release a number of substances, including inflammatory cytokines and eicosanoids, that are highly toxic to cells of the central nervous system. Because monocytic infiltration of the central nervous system closely correlates with HIV-1-associated dementia, it has been suggested that monocyte-derived toxins mediate nervous system damage. In the present study, we show that the HIV-1 transactivator protein Tat significantly increases astrocytic expression and release of monocyte chemoattractant protein-1 (MCP-1). Astrocytic release of β-chemokines, which are relatively less selective for monocytes, including RANTES, macrophage inflammatory protein-1α, and macrophage inflammatory protein-1β, was not observed. We also show that MCP-1 is expressed in the brains of patients with HIV-1-associated dementia and that, of the β-chemokines tested, only MCP-1 could be detected in the cerebrospinal fluid of patients with this condition. Together, these data provide a potential link between the presence of HIV-1 in the brain and the monocytic infiltration that may substantially contribute to dementia.
Loss of bombesin-induced feeding suppression in gastrin-releasing peptide receptor-deficient mice
Authors: Hampton Lori L. , Ladenheim Ellen E. , Akeson Mark , Way James M. , Weber H. Christian , Sutliff Vince E. , Jensen Robert T. , Wine Lara J. , Arnheiter Heinz , Battey James F.
Published: July 2002

The gastrin-releasing peptide receptor (GRP-R) is one of three members of the mammalian bombesin subfamily of seven-transmembrane G protein-coupled receptors that mediate diverse biological responses including secretion, neuromodulation, chemotaxis, and growth. The X chromosome-linked GRP-R gene is expressed widely during embryonic development and predominantly in gastrointestinal, neuronal, and neuroendocrine systems in the adult. Surprisingly, gene-targeted mice lacking a functional GRP-R gene develop and reproduce normally and show no gross phenotypic abnormalities. However, peripheral administration of bombesin at dosages up to 32 nmol/kg to such mice had no effect on the suppression of glucose intake, whereas normal mice showed a dose-dependent suppression of glucose intake. These data suggest that selective agonists for the GRP-R may be useful in inducing satiety.
Control of zinc transfer between thionein, metallothionein, and zinc proteins
Authors: Jacob Claus , Maret Wolfgang , Vallee Bert L.
Published: July 2002

Metallothionein (MT), despite its high metal binding
constant (
K
Zn
= 3.2 × 10
13
M
−1
at pH 7.4), can transfer zinc to the apoforms of zinc
enzymes that have inherently lower stability constants. To gain insight
into this paradox, we have studied zinc transfer between zinc enzymes
and MT. Zinc can be transferred in both directions—i.e., from the
enzymes to thionein (the apoform of MT) and from MT to the apoenzymes.
Agents that mediate or enhance zinc transfer have been identified that
provide kinetic pathways in either direction. MT does not transfer all
of its seven zinc atoms to an apoenzyme, but apparently contains at
least one that is more prone to transfer than the others. Modification
of thiol ligands in MT zinc clusters increases the total number of zinc
ions released and, hence, the extent of transfer. Aside from disulfide
reagents, we show that selenium compounds are potential cellular
enhancers of zinc transfer from MT to apoenzymes. Zinc transfer from
zinc enzymes to thionein, on the other hand, is mediated by
zinc-chelating agents such as Tris buffer, citrate, or glutathione.
Redox agents are asymmetrically involved in both directions of zinc
transfer. For example, reduced glutathione mediates zinc transfer from
enzymes to thionein, whereas glutathione disulfide oxidizes MT with
enhanced release of zinc and transfer of zinc to apoenzymes. Therefore,
the cellular redox state as well as the concentration of other
biological chelating agents might well determine the direction of zinc
transfer and ultimately affect zinc distribution.
Aging accentuates and bone marrow transplantation ameliorates metabolic defects in Fabry disease mice
Authors: Ohshima Toshio , Schiffmann Raphael , Murray Gary J. , Kopp Jeffrey , Quirk Jane M. , Stahl Stefanie , Chan Chi-Chao , Zerfas Patricia , Tao-Cheng Jung-Hwa , Ward J. M. , Brady Roscoe O. , Kulkarni Ashok B.
Published: July 2002

Fabry disease is an X-linked metabolic disorder caused by a deficiency of α-galactosidase A (α-Gal A). The enzyme defect leads to the systemic accumulation of glycosphingolipids with α-galactosyl moieties consisting predominantly of globotriaosylceramide (Gb3). In patients with this disorder, glycolipid deposition in endothelial cells leads to renal failure and cardiac and cerebrovascular disease. Recently, we generated α-Gal A gene knockout mouse lines and described the phenotype of 10-week-old mice. In the present study, we characterize the progression of the disease with aging and explore the effects of bone marrow transplantation (BMT) on the phenotype. Histopathological analysis of α-
Gal A −/0
mice revealed subclinical lesions in the Kupffer cells in the liver and macrophages in the skin with no gross lesions in the endothelial cells. Gb3 accumulation and pathological lesions in the affected organs increased with age. Treatment with BMT from the wild-type mice resulted in the clearance of accumulated Gb3 in the liver, spleen, and heart with concomitant elevation of α-Gal A activity. These findings suggest that BMT may have a potential role in the management of patients with Fabry disease.
Biodiversity assessment at multiple scales: Linking remotely sensed data with field information
Authors: Nagendra Harini , Gadgil Madhav
Published: July 2002

We examine the efficacy of a scheme of multiscale assessment of biodiversity linking remote sensing on larger spatial scales with localized field sampling. A classification of ecological entities from biosphere to individual organisms in the form of a nested hierarchy is employed, such that entities at any level are differentiated in terms of their composition/configuration involving entities at the next lower level. We employ the following hierarchy: biosphere (10
14
m
2
), ecoregions (10
11
–10
12
m
2
), ecomosaics (10
8
–10
10
m
2
), ecotopes (10
3
–10
6
m
2
), and individual organisms (10
−4
–10
2
m
2
). Focusing on a case study of West Coast–Western Ghats ecoregion (1.7 × 10
11
m
2
) from India, we demonstrate that remotely sensed data permit discrimination of 205 patches of 11 types of sufficiently distinctive ecomosaics (10
8
–10
10
m
2
) through unsupervised classification by using distribution parameters of the Normalized Difference Vegetation Index, with a pixel size of 3.24 × 10
6
m
2
. At the ecomosaic scale, Indian Remote Sensing LISS-2 satellite data with a pixel size of 10
3
m
2
permit discrimination of ≈30 types of sufficiently distinctive ecotopes on the basis of supervised classification. Field investigations of angiosperm species distributions based on quadrats of 1–10
2
m
2
in one particular landscape of 27.5 × 10
6
m
2
show that the seven ecotope types distinguished in that locality are significantly different from each other in terms of plant species composition. This suggests that we can effectively link localized field investigations of biodiversity with remotely sensed information to permit extrapolations at progressively higher scales.
Folding of a large ribozyme during transcription and the effect of the elongation factor NusA
Authors: Pan Tao , Artsimovitch Irina , Fang Xing-wang , Landick Robert , Sosnick Tobin R.
Published: July 2002

We compared
in vitro
transcription-initiated folding of the ribozyme from
Bacillus subtilis
RNase P to refolding from the full-length, denatured state by monitoring the appearance of its catalytic activity. At 37°C, Mg
2+
-initiated refolding of the wild type and a circularly permutate ribozyme takes minutes and is limited by a kinetic trap. Transcription by T7 RNA polymerase alters the folding pathway of both RNAs and introduces new kinetic traps. Transcription by the core
Escherichia coli
RNA polymerase yields the same result, in spite of its 4-fold-slower elongation rate. However, the presence of its elongation factor NusA accelerates more than 10-fold the transcription-initiated folding of the circularly, permutated ribozyme by
E. coli
RNA polymerase. The effect of NusA likely is caused by its enhancement of transcriptional pausing because NusA did not accelerate transcription-initiated folding using a mutant RNA polymerase that failed to pause or respond to NusA during ribozyme synthesis. We conclude that both transcription and specific pausing therein can alter RNA-folding pathways.
Myeloid DAP12-associating lectin (MDL)-1 is a cell surface receptor involved in the activation of myeloid cells
Authors: Bakker Alexander B. H. , Baker Elizabeth , Sutherland Grant R. , Phillips Joseph H. , Lanier Lewis L.
Published: July 2002

Crosslinking of immunoreceptor tyrosine-based activation motif (ITAM)-containing receptor complexes on a variety of cells leads to their activation through the sequential triggering of protein tyrosine kinases. Recently, DAP12 has been identified as an ITAM-bearing signaling molecule that is noncovalently associated with activating isoforms of MHC class I receptors on natural killer cells. In addition to natural killer cells, DAP12 is expressed in peripheral blood monocytes, macrophages, and dendritic cells, suggesting association with other receptors present in these cell types. In the present study, we report the molecular cloning of the myeloid DAP12-associating lectin-1 (MDL-1), a DAP12-associating membrane receptor expressed exclusively in monocytes and macrophages. MDL-1 is a type II transmembrane protein belonging to the C type lectin superfamily and contains a charged residue in the transmembrane region that enables it to pair with DAP12. Crosslinking of MDL-1/DAP12 complexes in J774 mouse macrophage cells resulted in calcium mobilization. These findings suggest that signaling via MDL-1/DAP12 complexes may constitute a significant activation pathway in myeloid cells.
Role of the Hrp type III protein secretion system in growth of
Pseudomonas syringae
pv.
syringae
B728a on host plants in the field
Authors: Hirano Susan S. , Charkowski Amy O. , Collmer Alan , Willis David K. , Upper Christen D.
Published: July 2002

hrp
genes are reportedly required for pathogenicity in
Pseudomonas syringae
pv.
syringae
(Pss) and other phytopathogenic bacterial species. A subset of these genes encodes a type III secretion system through which virulence factors are thought to be delivered to plant cells. In this study, we sought to better understand the role that
hrp
genes play in interactions of Pss with its host as they occur naturally under field conditions. Population sizes of
hrp
mutants with defects in genes that encode components of the Hrp secretion system (Δ
hrcC∷npt
II and
hrpJ∷
ΩSpc) and a protein secreted via the system (Δ
hrpZ∷npt
II) were similar to B728a on germinating seeds. However, phyllosphere (i.e., leaf) population sizes of the
hrcC
and
hrpJ
secretion mutants, but not the
hrpZ
mutant, were significantly reduced relative to B728a. Thus, the Hrp type III secretion system, but not HrpZ, plays an important role in enabling Pss to flourish in the phyllosphere, but not the spermosphere. The
hrcC
and
hrpJ
mutants caused brown spot lesions on primary leaves at a low frequency when they were inoculated onto seeds at the time of planting. Pathogenic reactions also were found when the
hrp
secretion mutants were co-infiltrated into bean leaves with a non-lesion-forming
gacS
mutant of B728a. In both cases, the occurrence of disease was associated with elevated population sizes of the
hrp
secretion mutants. The role of the Hrp type III secretion system in pathogenicity appears to be largely mediated by its requirement for growth of Pss in the phyllosphere. Without growth, disease does not occur.
Altered anxiety and weight gain in corticotropin-releasing hormone-binding protein-deficient mice
Authors: Karolyi I. Jill , Burrows Heather L. , Ramesh Tennore M. , Nakajima Masaharu , Lesh J. Shonee , Seong Eunju , Camper Sally A. , Seasholtz Audrey F.
Published: July 2002

Corticotropin-releasing hormone (CRH) is widely recognized as the primary mediator of the neuroendocrine and behavioral responses to stress, including stress-induced anxiety. The biological activity of CRH and other mammalian CRH-like peptides, such as urocortin, may be modulated by CRH-binding protein (CRH-BP). To assess directly the CRH-BP function, we created a mouse model of CRH-BP deficiency by gene targeting. Basal adrenocorticotropic hormone and corticosterone levels are unchanged in the CRH-BP-deficient mice, and the animals demonstrate a normal increase in adrenocorticotropic hormone and corticosterone after restraint stress. In contrast, adult male CRH-BP-deficient mice show significantly reduced body weight when compared with wild-type controls. CRH-BP-deficient mice also exhibit a significant increase in anxiogenic-like behavior as assessed by the elevated plus maze and defensive withdrawal tests. The increased anorectic and anxiogenic-like behavior most likely is caused by increased “free” CRH and/or urocortin levels in the brain of CRH-BP-deficient animals, suggesting an important role for CRH-BP in maintaining appropriate levels of these peptides in the central nervous system.
Horizontal cells reveal cone type-specific adaptation in primate retina
Authors: Lee Barry B. , Dacey Dennis M. , Smith Vivianne C. , Pokorny Joel
Published: July 2002

The human cone visual system maintains contrast sensitivity over a wide range of ambient illumination, a property known as light adaptation. The first stage in light adaptation is believed to take place at the first neural step in vision, within the long, middle, and short wavelength sensitive cone photoreceptors. To determine the properties of adaptation in primate outer retina, we measured cone signals in second-order interneurons, the horizontal cells, of the macaque monkey. Horizontal cells provide a unique site for studying early adaptational mechanisms; they are but one synapse away from the photoreceptors, and each horizontal cell receives excitatory inputs from many cones. Light adaptation occurred over the entire range of light levels evaluated, a luminance range of 15–1,850 trolands. Adaptation was demonstrated to be independent in each cone type and to be spatially restricted. Thus, in primates, a major source of sensitivity regulation occurs before summation of cone signals in the horizontal cell.
Functional MRI reveals spatially specific attentional modulation in human primary visual cortex
Authors: Somers David C. , Dale Anders M. , Seiffert Adriane E. , Tootell Roger B. H.
Published: July 2002

Selective visual attention can strongly influence perceptual
processing, even for apparently low-level visual stimuli. Although it
is largely accepted that attention modulates neural activity in
extrastriate visual cortex, the extent to which attention operates in
the first cortical stage, striate visual cortex (area V1), remains
controversial. Here, functional MRI was used at high field strength (3
T) to study humans during attentionally demanding visual
discriminations. Similar, robust attentional modulations were observed
in both striate and extrastriate cortical areas. Functional mapping of
cortical retinotopy demonstrates that attentional modulations were
spatially specific, enhancing responses to attended stimuli and
suppressing responses when attention was directed elsewhere. The
spatial pattern of modulation reveals a complex attentional window that
is consistent with object-based attention but is inconsistent with a
simple attentional spotlight. These data suggest that neural processing
in V1 is not governed simply by sensory stimulation, but, like
extrastriate regions, V1 can be strongly and specifically influenced by
attention.
Epithelial sodium channel regulated by aldosterone-induced protein sgk
Authors: Chen Sei-yu , Bhargava Aditi , Mastroberardino Luca , Meijer Onno C. , Wang Jian , Buse Patricia , Firestone Gary L. , Verrey Francois , Pearce David
Published: July 2002

Sodium homeostasis in terrestrial and freshwater vertebrates is controlled by the corticosteroid hormones, principally aldosterone, which stimulate electrogenic Na
+
absorption in tight epithelia. Although aldosterone is known to increase apical membrane Na
+
permeability in target cells through changes in gene transcription, the mechanistic basis of this effect remains poorly understood. The predominant early effect of aldosterone is to increase the activity of the epithelial sodium channel (ENaC), although ENaC mRNA and protein levels do not change initially. Rather, the open probability and/or number of channels in the apical membrane are greatly increased by unknown modulators. To identify hormone-stimulated gene products that modulate ENaC activity, a subtracted cDNA library was generated from A6 cells, a stable cell line of renal distal nephron origin, and the effect of candidates on ENaC activity was tested in a coexpression assay. We report here the identification of sgk (serum and glucocorticoid-regulated kinase), a member of the serine–threonine kinase family, as an aldosterone-induced regulator of ENaC activity. sgk mRNA and protein were strongly and rapidly hormone stimulated both in A6 cells and in rat kidney. Furthermore, sgk stimulated ENaC activity approximately 7-fold when they were coexpressed in
Xenopus laevis
oocytes. These data suggest that sgk plays a central role in aldosterone regulation of Na
+
absorption and thus in the control of extracellular fluid volume, blood pressure, and sodium homeostasis.
The role of threonine 37 in flavin reactivity of the old yellow enzyme
Authors: Xu Dong , Kohli Rahul M. , Massey Vincent
Published: July 2002

Threonine 37 is conserved among all the members of the old yellow enzyme (OYE) family. The hydroxyl group of this residue forms a hydrogen bond with the C-4 oxygen atom of the FMN reaction center of the enzyme [Fox, K. M. & Karplus, P. A. (1994)
Structure
2, 1089–1105]. The position of Thr-37 and its interaction with flavin allow for speculations about its role in enzyme activity. This residue was mutated to alanine and the mutant enzyme was studied and compared with the wild-type OYE1 to evaluate its mechanistic function. The mutation has different effects on the two separate half-reactions of the enzyme. The mutant enzyme has enhanced activity in the oxidative half-reaction but the reductive half-reaction is slowed down by more than one order of magnitude. The peaks of the absorption spectra for enzyme bound with phenolic compounds are shifted toward shorter wavelengths than those of wild-type OYE1, consistent with its lower redox potential. It is suggested that Thr-37 in the wild-type OYE1 increases the redox potential of the enzyme by stabilizing the negative charge of the reduced flavin through hydrogen bonding with it.
Pulling a single chromatin fiber reveals the forces that maintain its higher-order structure
Authors: Cui Yujia , Bustamante Carlos
Published: July 2002

Single chicken erythrocyte chromatin fibers were stretched and released at room temperature with force-measuring laser tweezers. In low ionic strength, the stretch-release curves reveal a process of continuous deformation with little or no internucleosomal attraction. A persistence length of 30 nm and a stretch modulus of ≈5 pN is determined for the fibers. At forces of 20 pN and higher, the fibers are modified irreversibly, probably through the mechanical removal of the histone cores from native chromatin. In 40–150 mM NaCl, a distinctive condensation-decondensation transition appears between 5 and 6 pN, corresponding to an internucleosomal attraction energy of ≈2.0 kcal/mol per nucleosome. Thus, in physiological ionic strength the fibers possess a dynamic structure in which the fiber locally interconverting between “open” and “closed” states because of thermal fluctuations.
Olenid trilobites: The oldest known chemoautotrophic symbionts?
Authors: Fortey Richard
Published: July 2002

Late Cambrian to early Ordovician trilobites, the family Olenidae, were tolerant of oxygen-poor, sulfur-rich sea floor conditions, and a case is made that they were chemoautotrophic symbionts. Olenids were uniquely adapted to this habitat in the Lower Paleozoic, which was widespread in the Late Cambrian over Scandinavia. This life habit explains distinctive aspects of olenid morphology: wide thoraces and large numbers of thoracic segments, thin cuticle and, in some species, degenerate hypostome, and the occasional development of brood pouches. Geochemical and field evidence is consistent with this interpretation. Olenids occupied their specialized habitat for 60 million years until their extinction at the end of the Ordovician.
Plants and animals share functionally common bacterial virulence factors
Authors: Rahme Laurence G. , Ausubel Frederick M. , Cao Hui , Drenkard Eliana , Goumnerov Boyan C. , Lau Gee W. , Mahajan-Miklos Shalina , Plotnikova Julia , Tan Man-Wah , Tsongalis John , Walendziewicz Cynthia L. , Tompkins Ronald G.
Published: July 2002

By exploiting the ability of
Pseudomonas aeruginosa
to infect a variety of vertebrate and nonvertebrate hosts, we have
developed model systems that use plants and nematodes as adjuncts to
mammalian models to help elucidate the molecular basis of
P.
aeruginosa
pathogenesis. Our studies reveal a remarkable degree
of conservation in the virulence mechanisms used by
P.
aeruginosa
to infect hosts of divergent evolutionary origins.
Pathogen-specific loss of host resistance in mice lacking the IFN-γ-inducible gene IGTP
Authors: Taylor Gregory A. , Collazo Carmen M. , Yap George S. , Nguyen Khuong , Gregorio Theresa A. , Taylor Lynn S. , Eagleson Bryn , Secrest Lisa , Southon Eileen A. , Reid Susan W. , Tessarollo Lino , Bray Mike , McVicar Dan W. , Komschlies Kristin L. , Young Howard A. , Biron Christine A. , Sher Alan , Vande Woude George F.
Published: July 2002

Interferon-γ (IFN-γ) is critical for defense against pathogens, but the molecules that mediate its antimicrobial responses are largely unknown. IGTP is the prototype for a family of IFN-γ-regulated genes that encode 48-kDa GTP-binding proteins that localize to the endoplasmic reticulum. We have generated IGTP-deficient mice and found that, despite normal immune cell development and normal clearance ofListeria monocytogenesand cytomegalovirus infections, the mice displayed a profound loss of host resistance to acute infections of the protozoan parasiteToxoplasma gondii. By contrast, IFN-γ receptor-deficient mice have increased susceptibility to all three pathogens. Thus, IGTP defines an IFN-γ-regulated pathway with a specialized role in antimicrobial resistance.
A cross-link breaker has sustained effects on arterial and ventricular properties in older rhesus monkeys
Authors: Vaitkevicius Peter V. , Lane Mark , Spurgeon Harold , Ingram Donald K. , Roth George S. , Egan John J. , Vasan Sara , Wagle Dilip R. , Ulrich Peter , Brines Michael , Wuerth Jean Paul , Cerami Anthony , Lakatta Edward G.
Published: July 2002

Nonenzymatic glycosylation and cross-linking of proteins by glucose
contributes to an age-associated increase in vascular and myocardial
stiffness. Some recently sythesized thiazolium compounds selectively
break these protein cross-links, reducing collagen stiffness. We
investigated the effects of 3-phenacyl-4,5-dimethylthiazolium
chloride (ALT-711) on arterial and left ventricular (LV) properties and
their coupling in old, healthy, nondiabetic
Macaca
mulatta
primates (age 21 ± 3.6 years). Serial
measurements of arterial stiffness indices [i.e., aortic pulse wave
velocity (PWV) and augmentation (AGI) of carotid arterial pressure
waveform] as well as echocardiographic determinations of LV structure
and function were made before and for 39 weeks after 11 intramuscular
injections of ALT-711 at 1.0 mg/kg body weight every other day. Heart
rate, brachial blood pressure, and body weight were unchanged by the
drug. PWV and AGI decreased to a nadir at 6 weeks [PWV to 74.2 ±
4.4% of baseline (B),
P
= 0.007; AGI to 41 ±
7.3% of B,
P
= 0.046], and thereafter gradually
returned to baseline. Concomitant increases in LV end diastolic
diameter to 116.7 ± 2.7% of B,
P
= 0.02;
stroke volume index (SV
index
) to 173.1 ± 40.1%
of B,
P
= 0.01; and systolic fractional shortening
to 180 ± 29.7% of B,
P
= 0.01 occurred after
drug treatment. The LV end systolic pressure/SV
index
, an
estimate of total LV vascular load, decreased to 60 ± 12.1% of B
(
P
= 0.02). The LV end systolic
diameter/SV
index
, an estimate of arterio-ventricular
coupling, was improved (decreased to 54.3 ± 11% of B,
P
< 0.002). Thus, in healthy older primates
without diabetes, ALT-711 improved both arterial and ventricular
function and optimized ventriculo-vascular coupling. This previously
unidentified cross-link breaker may be an effective pharmacological
therapy to improve impaired cardiovascular function that occurs in the
context of heart failure associated with aging, diabetes, or
hypertension, conditions in which arterial and ventricular stiffness
are increased.
Cultural Differences in the Relation between Self‐discrepancy and Life Satisfaction
Authors: Radhakrishnan Phanikiran , Chan Darius K.‐S.
Published: July 2002

Cultural differences in the relation between self‐discrepancy and subjective well‐being were examined. Participants from India (N = 54) and the United States (N = 55) listed 10 goals they set for themselves and their parents set for them. They rated the importance of own and parental goals from their own and their parents' perspective. They also completed measures of collectivism and well‐being. Americans, who were less collectivistic than Indians, rated their own goals to be more important than their parents' goals for them, whereas Indians regarded their own and their parents' goals as equally important. Americans' well‐being was predicted by discrepancies between own and parental ratings on personal goals. However, discrepancies between own and parental ratings on parental goals were predictive of Indians' well‐being. Theoretical implications of these findings are discussed.
Front Rentiers to Rantiers: 'Active Entrepreneurs', 'Structural Speculators' and the Politics of Marketing the City
Authors: Ward Kevin G.
Published: July 2002

This paper explores the formation and practices of Marketing Manchester in the context of the rise of the partnership model of urban management and the apparent emergence of what some have referred to as growth coalitions. The combination of the growth in local unelected agencies and a shift in the national urban policy paradigm has demanded from cities a particular set of political responses and economic strategies. This paper uses Manchester to explore the transformation in the `business' of regeneration and seeks to tease out some of its theoretical implications. Drawing on a study of the city's political and economic elite, it is argued that the formation of Marketing Manchester and the disputes over its attempt to 'brand' Manchester feed into wider debates on the governance of cities, the politics around partnership formation and efforts to market cities.
Begging, Rough Sleeping and Social Exclusion: Implications for Social Policy
Authors: Kennedy Catherine , Fitzpatrick Suzanne
Published: July 2002

Begging has become highly visible in the urban centres of Britain in recent years, yet the experiences and motivations of people involved in this activity have remained underresearched. This paper explores the implications for social policy arising from a detailed study of begging in Glasgow and Edinburgh. It reassesses the common understanding of begging as a 'homelessness issue' and demonstrates that, while rough sleeping was almost invariably implicated in people's routes into begging in these cities, securing accommodation was far from a guaranteed 'route out'. It emphasises the need for holistic services and effective policy co-ordination in responding to the wide-ranging social exclusion of people who beg. It also explores the importance, and difficulties, of securing their active involvement in policy and service development.
Civic Culture, Community and Citizen Participation in Contrasting Neighbourhoods
Authors: Docherty Iain , Goodlad Robina , Paddison Ronan
Published: July 2002

This paper uses survey and qualitative evidence from four neighbourhoods in two cities to explore the hypothesis that citizen participation in urban governance is fostered by political structures and public policy as well as by a civic culture supportive of citizen involvement. The analysis shows that although the prospects for citizen participation are likely to be least propitious in poor neighbourhoods demonstrating lower educational attainment levels, for example, such factors may be mitigated by political mobilisation and the approaches to urban governance, including citizen participation, adopted by local institutions. Citizen participation may be fostered as much by the creation of opportunity structures that build confidence in the efficacy of participation as by the intrinsic levels of civic culture. The key policy lesson is that the effort devoted to creating greater institutional thickness and participatory structures is not wasted.
Tacit Knowledge, Innovation and Economic Geography
Authors: Howells Jeremy R. L.
Published: July 2002

The aim of this paper is to outline the importance of tacit knowledge in the innovation process and to highlight the way that geographical location not only influences the relationship between knowledge and innovative activity, but also affects the way that such interaction influences the geography of innovation and economic activity. After a discussion about the nature of knowledge, the paper explores the relationship that exists between knowledge and geography. The paper then reviews, using as an analytical lens, the growing body of literature on knowledge spillovers which affirm the importance of geography. However, the discussion then seeks to outline some crucial gaps that remain in our conceptualisation of the knowledge spillover and transfer process. The paper then highlights the neglected role of knowledge demand and consumption in a spatial context, before concluding with a review of areas for future research.
China's Urban Housing Reform: Price-Rent Ratio and Market Equilibrium
Authors: Chen Aimin
Published: July 2002

China's urban housing marketisation hinges on a sensible ratio of housing price to rent. This research derives a rational level for such a ratio and examines its distortions under the Chinese system. It shows that the prevailing housing price to rent ratios are significantly higher than the rational level for both subsidised and free-market housing. Unique Chinese housing market equilibria are analysed and policy recommendations on commercialising Chinese urban housing are suggested.
A Two-stage Housing Choice Forecasting Model
Authors: Tu Yong , Goldfinch Judy
Published: July 2002

A new housing choice forecasting model is developed here to answer a practical question: how to forecast housing demand at a disaggregate level. Being different from the previous housing choice models, this model is derived from housing sub-market structure based on a random utility approach. Housing choice is thought to be a joint choice of all the components associated with a dwelling, These components create a huge bundle of dwelling alternatives resulting in an empirical calculation problem. To avoid this problem, the model developed in this paper separates the joint choice behaviour into two stages: the choices of the key dwelling components which construct the housing sub-markets and the choices of the non-key dwelling components which distinguish individual dwellings in each housing sub-market. Some policy simulations are presented based on this model.
Identifying Households which Need Housing Assistance
Authors: Thalmann Philippe
Published: July 2002

This paper proposes a method for identifying housing affordability problems. The housing market being imperfect, high rent-to-income ratios might be the result not only of a taste for spacious housing but also of rent premia. Conversely, some households currently in advantageous housing may face difficulty when they move. A better indicator of affordability compares income to the average rent the market charges for housing deemed appropriate for a household, and a second indicator compares current housing consumption with appropriate consumption. We find that more than two households out of three that have high rent burdens could afford appropriate housing. Almost one household in two that cannot afford appropriate housing manages to keep its rent burden low. This paper makes a point for co-ordinating tenant-based assistance with other instruments of housing aid.
Urban Regeneration and Transport Investment: A Case Study of Sheffield 1992-96
Authors: Lawless Paul , Gore Tony
Published: July 2002

There has been little work exploring the impact of transport investment on economic regeneration at the urban scale. This lack of attention is in part related to theoretical inadequacies and methodological difficulties, not least the separating out and attribution of effects. Such issues were addressed by a major empirical study conducted in Sheffield during the early 1990s. This paper outlines the research methods adopted, which involved breaking down impacts into five thematic areas (image; property; land use; business location and operations; and labour market), and exploring the different mechanisms whereby effects might have become apparent in each. The findings from each of the themes are briefly summarised, the overall conclusion being that, in current circumstances, the impact of transport investment on regeneration is not particularly strong. In a broader policy context, however, the study also pointed to the improbability of securing regeneration benefits from transport infrastructure, given the lack of co-ordination and integration between the two policy areas, and the increasingly fragmented nature of urban governance in general.
Trends in adolescent research for the new millennium
Authors: Galambos Nancy L. , Leadbeater Bonnie J.
Published: July 2002

This article highlights several promising trends in research on adolescence and discusses the likely future course of several recent developments in adolescent research. Current trends include a focus on the transition to young adulthood, the increasing examination of the context and co-occurrence of adolescent problems, and emphasis on the resilience of adolescents in high-risk circumstances. There is a strong need for more research on the cognitive and neurocognitive gains and changes of adolescence and on positive psychosocial behaviours and outcomes for youth. We are just beginning to understand within-group differences in adolescent development, including the life experiences of minority youth, adolescents with disabilities, and homosexual adolescents. The impact of social context and social change on adolescents is also receiving more attention. Methodological approaches likely to be seen more in the future include the use of pattern-centred analyses to complement traditional variable-centred approaches and a greater appreciation for qualitative data analysis as a route to gaining insights into adolescent development. Finally, university-community partnerships are promoted as a way to solve the problems of youth and improve the probability of their healthy futures.
Acceptance and Leadership--Hegemonies of E-Commerce Policy Perspectives
Authors: Corbitt Brian J. , Thanasankit Theerasak
Published: July 2002

This paper presents an analysis of the e-Commerce policies developed and implemented in the USA, Canada, Australia, Victoria, Finland, Norway, the UK, Ireland, the EU (by the OECD), Singapore, Japan, Malaysia, Thailand and Hong Kong (Special Administrative Region). The paper shows that e-Commerce policy adopted is generally trying to achieve two fundamental aims: 1. to minimize regulatory environments for e-Commerce; and 2. to ease logistical problems in doing e-Commerce - i.e. in paying electronically, in delivery of goods and in customs, tariffs and duties. These strategies are designed to create an environment where e-Commerce is adopted by business and government in these countries to achieve 'best practice', to become 'modern', to gain 'efficiencies', because 'it is the way to go', because 'we must have it, because everybody has it', and because they 'perceive the benefits of it'. In essence it is being used to gain hegemony in the economic competitiveness of the geopolitical environment created by the Internet. This paper argues that differentiating types of policy is related to ideology and hegemony in the various countries.
Classical Economic Man: was he Interested in Keeping Up with the Joneses?
Authors: Kern William S.
Published: July 2002

One of the significant contributions of the The Wealth of Nations was to bring to the consciousness of economists the centrality of the pursuit of self-interest in economic affairs. Following the publication of the The Wealth of Nations, economists increasingly assumed that the pursuit of self-interest was the prime psychological drive of mankind. As economics developed, modifications of the self-interest postulate occurred. Economists began to formally model the pursuit of self-interest and a specific form of the pursuit of self-interest ultimately came to dominate economists' thinking. Specifically, economists have taken a methodologically individualistic approach to this question. With rare exception, economists presume that the individual pursues self-interest more or less in “isolation.” As Frank Knight pointed out, the purely rational action of the economic man requires the complete absence of personal relations, in effect requiring persons to treat each other as vending machines (Knight 1960, p. 73). Robinson Crusoe alone on his island is thus the epitome of the economic man assumed by neoclassical economic theory.
Mutagenicity, developmental toxicity and carcinogenicity of cannabis
Authors: MARSELOS MARIOS , KARAMANAKOS PETROS
Published: July 2002

Data on the mutagenicity, developmental toxicity and carcinogenicity of cannabis are reviewed in this article. The available evidence on the possible mutagenic effects of cannabinoids is still inconclusive. There is no consensus on the induction of point mutations, while some experimental results suggest that cannabinoids may cause chromosomal damage. Concerning the developmental effects of cannabis, an increased embryolethality and somatic growth retardation have been observed in animals, as well as changes in motor behaviour, after perinatal exposure to cannabinoids. An elevated risk for infertility has been suggested for women smoking marijuana. On the other hand, intrauterine exposure to cannabinoids may be followed by changes of behaviour later in childhood. Finally, the experimental work concerning the possible carcinogenic action of cannabinoids has shown that cannabis acts as a tumour promotor in animals. Epidemiological studies have incriminated cannabis smoking for the development of head and neck carcinomas and for carcinomas of the respiratory tract in humans, but several confounding factors have rendered this evidence inconclusive. At least part of the great popularity of cannabis smoking is due to the widespread belief that it is harmless. However, the studies presented in this review show that, despite their low acute toxicity profile, cannabinoids represent several risks in terms of chronic toxicity.