bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors affecting production of inoculum of the blackleg fungus (Leptosphaeria maculans) in south-eastern Australia
Authors: Marcroft S. J. , Sprague S. J. , Pymer S. J. , Salisbury P. A. , Howlett B. J.
Published: November 2003

The production of windborne ascospore inoculum of the blackleg fungus (Leptosphaeria maculans) was determined during 2000 and 2001 in 3 environments (Birchip, low rainfall; Wonwondah, medium rainfall; Lake Bolac, high rainfall) in Victoria. The weight of canola stubble (kg/ha) remaining on the soil surface in paddocks was estimated 6, 18, 30 and 42 months after harvest of the original canola crop. In all 3 environments only small amounts of stubble were present 18 months after harvest. Eighty percent of the 6-month-old stubble comprised stems and branches, with the remaining 20% being root material, while 42-month-old stubble consisted only of root material. Paddocks subjected to raking and burning contained only half the weight of stubble compared with paddocks that were harrowed. Where canola was harvested in January, even when no management strategy was used, 80% of subsequent stubble was no longer on the soil surface by July of that year. Pseudothecia from 6-month-old stubble from the high rainfall environment discharged significantly more ascospores than stubble of the same age from the medium rainfall environment, which in turn discharged more than stubble from the low rainfall environment. In all environments, paddocks containing 6-month-old canola stubble discharged 30-fold as many ascospores per hectare as older stubble paddocks.
Murine cytomegalovirus paralyzes macrophages by blocking IFNγ-induced promoter assembly
Authors: Popkin Daniel L. , Watson Mark A. , Karaskov Elizabeth , Dunn Gavin P. , Bremner Rod , Virgin Herbert W.
Published: November 2003

Macrophages (Mϕ) are activated by IFNγ and are important cellular targets for infection by human and murine cytomegalovirus (MCMV), making it advantageous for CMVs to block IFNγ-induced Mϕ differentiation. We found that MCMV infection inhibited IFNγ regulation of many genes in Mϕ. MCMV infection blocked IFNγ responses at the level of transcription without blocking Janus kinase/signal transducer and activator of transcription pathway activation and targeted IFN response factor 1- and class II transactivator-dependent and independent promoters. MCMV did not alter basal transcription from IFNγ-responsive promoters and left the majority of cellular transcripts unchanged even after 48 h of infection. The effects of MCMV infection were specific to chromosomal rather than transiently transfected promoters. Characterization of the IFNγ-responsive chromosomal class II transactivator promoter revealed that MCMV infection blocked IFNγ-induced promoter assembly, allowing the virus to transcriptionally paralyze infected Mϕ responses while allowing basal transcription to proceed.
Adenosine gates synaptic plasticity at hippocampal mossy fiber synapses
Authors: Moore Kimberly A. , Nicoll Roger A. , Schmitz Dietmar
Published: November 2003

The release properties of synapses in the central nervous system vary greatly, not only across anatomically distinct types of synapses but also among the same class of synapse. This variation manifests itself in large part by differences in the probability of transmitter release, which affects such activity-dependent presynaptic forms of plasticity as paired-pulse facilitation and frequency facilitation. This heterogeneity in presynaptic function reflects differences in the intrinsic properties of the synaptic terminal and the activation of presynaptic neurotransmitter receptors. Here we show that the unique presynaptic properties of the hippocampal mossy fiber synapse are largely imparted onto the synapse by the continuous local action of extracellular adenosine at presynaptic A1 adenosine receptors, which maintains a low basal probability of transmitter release.
Chemical communication among bacteria
Authors: Taga Michiko E. , Bassler Bonnie L.
Published: November 2003

Cell–cell communication in bacteria is accomplished through the exchange of chemical signal molecules called autoinducers. This process, called quorum sensing, allows bacteria to monitor their environment for the presence of other bacteria and to respond to fluctuations in the number and/or species present by altering particular behaviors. Most quorum-sensing systems are species- or group-specific, which presumably prevents confusion in mixed-species environments. However, some quorum-sensing circuits control behaviors that involve interactions among bacterial species. These quorum-sensing circuits can involve both intra- and interspecies communication mechanisms. Finally, anti-quorumsensing strategies are present in both bacteria and eukaryotes, and these are apparently designed to combat bacteria that rely on cell–cell communication for the successful adaptation to particular niches.
Systemins: A functionally defined family of peptide signals that regulate defensive genes in Solanaceae species
Authors: Ryan Clarence A. , Pearce Gregory
Published: November 2003

Numerous plant species have been known for decades that respond to herbivore attacks by systemically synthesizing defensive chemicals to protect themselves from predators. The nature of systemic wound signals remained obscure until 1991, when an 18-aa peptide called systemin was isolated from tomato leaves and shown to be a primary signal for systemic defense. More recently, two new hydroxyproline-rich, glycosylated peptide defense signals have been isolated from tobacco leaves, and three from tomato leaves. Because of their origins in plants, small sizes, hydroxyproline contents (tomato systemin is proline-rich), and defense-signaling activities, the new peptides are included in a functionally defined family of signals collectively called systemins. Here, we review structural and biological properties of the systemin family, and discuss their possible roles in systemic wound signaling.
Differential hydrophobicity drives self-assembly in Huntington's disease
Authors: Burke Martin G. , Woscholski Rüdiger , Yaliraki S. N.
Published: November 2003

Identifying the driving forces and the mechanism of association of huntingtin-exon1, a close marker for the progress of Huntington's disease, is an important prerequisite to finding potential drug targets and, ultimately, a cure. We introduce here a modeling framework based on a key analogy of the physicochemical properties of the exon1 fragment to block copolymers. We use a systematic mesoscale methodology, based on dissipative particle dynamics, which is capable of overcoming kinetic barriers, thus capturing the dynamics of significantly larger systems over longer times than considered before. Our results reveal that the relative hydrophobicity of the poly(glutamine) block as compared with the rest of the (proline-based) exon1 fragment, ignored to date, constitutes a major factor in the initiation of the self-assembly process. We find that the assembly is governed by both the concentration of exon1 and the length of the poly(glutamine) stretch, with a low-length threshold for association, even at the lowest volume fractions we considered. Moreover, this self-association occurs irrespective of whether the glutamine stretch is in random-coil or hairpin configuration, leading to spherical or cylindrical assemblies, respectively. We discuss the implications of these results for reinterpretation of existing research within this context, including that the routes toward aggregation of exon1 may be distinct from those of the widely studied homopolymeric poly(glutamine) peptides.
Vaccinia virus encodes a previously uncharacterized mitochondrial-associated inhibitor of apoptosis
Authors: Wasilenko Shawn T. , Stewart Tara L. , Meyers Adrienne F. A. , Barry Michele
Published: November 2003

To circumvent apoptotic death, many viruses encode Bcl-2 homologous proteins that function at the mitochondria. Vaccinia virus, the prototypic member of the
Poxviridae
family, does not encode a Bcl-2 homolog but inhibits the mitochondrial arm of the apoptotic cascade by an unknown mechanism. We now report that F1L, a previously unidentified protein in vaccinia virus, is responsible for the inhibition of apoptosis. Cells infected with vaccinia virus are resistant to staurosporine-mediated cleavage of poly(ADP-ribose) polymerase, caspases 3 and 9, and release of cytochrome
c
. In contrast, a vaccinia virus deletion mutant, VV811, was unable to inhibit apoptosis; however, the antiapoptotic function was restored by expression of the F1L ORF, which is absent in VV811. Although F1L displays no homology to members of the Bcl-2 family, it localizes to the mitochondria through a C-terminal hydrophobic domain. We show that expression of F1L interferes with apoptosis by inhibiting the loss of the inner mitochondrial membrane potential and the release of cytochrome
c
.
A comprehensive analysis of 22q11 gene expression in the developing and adult brain
Authors: Maynard T. M. , Haskell G. T. , Peters A. Z. , Sikich L. , Lieberman J. A. , LaMantia A.-S.
Published: November 2003

Deletions at 22q11.2 are linked to DiGeorge or velocardiofacial syndrome (VCFS), whose hallmarks include heart, limb, and craniofacial anomalies, as well as learning disabilities and increased incidence of schizophrenia. To assess the potential contribution of 22q11 genes to cognitive and psychiatric phenotypes, we determined the CNS expression of 32 mouse orthologs of 22q11 genes, primarily in the 1.5-Mb minimal critical region consistently deleted in VCFS. None are uniquely expressed in the developing or adult mouse brain. Instead, 27 are localized in the embryonic forebrain as well as aortic arches, branchial arches, and limb buds. Each continues to be expressed at apparently constant levels in the fetal, postnatal, and adult brain, except forTbx1, ProDH2, andT10, which increase in adolescence and decline in maturity. At least six 22q11 proteins are seen primarily in subsets of neurons, including some in forebrain regions thought to be altered in schizophrenia. Thus, 22q11 deletion may disrupt expression of multiple genes during development and maturation of neurons and circuits compromised by cognitive and psychiatric disorders associated with VCFS.
Functional identification of distinct sets of antitumor activities mediated by the FKBP gene family
Authors: Fong Sylvia , Mounkes Leslie , Liu Yong , Maibaum Michael , Alonzo Eric , Desprez Pierre-Yves , Thor Ann D. , Kashani-Sabet Mohammed , Debs Robert J.
Published: November 2003

Assigning biologic function to the many sequenced but still uncharacterized genes remains the greatest obstacle confronting the human genome project. Differential gene expression profiling routinely detects uncharacterized genes aberrantly expressed in conditions such as cancer but cannot determine which genes are functionally involved in such complex phenotypes. Integrating gene expression profiling with specific modulation of gene expression in relevant disease models can identify complex biologic functions controlled by currently uncharacterized genes. Here, we used systemic gene transfer in tumor-bearing mice to identify novel antiinvasive and antimetastatic functions for Fkbp8, and subsequently for Fkbp1a. Fkbp8 is a previously uncharacterized member of the FK-506-binding protein (FKBP) gene family down-regulated in aggressive tumors. Antitumor effects produced by Fkbp1a gene expression are mediated by cellular pathways entirely distinct from those responsible for antitumor effects produced by Fkbp1a binding to its bacterially derived ligand, rapamycin. We then used gene expression profiling to identify syndecan 1 (Sdc1) and matrix metalloproteinase 9 (MMP9) as genes directly regulated by Fkbp1a and Fkbp8. FKBP gene expression coordinately induces the expression of the antiinvasive Sdc1 gene and suppresses the proinvasive MMP9 gene. Conversely, short interfering RNA-mediated suppression of Fkbp1a increases tumor cell invasion and MMP9 levels, while down-regulating Sdc1. Thus, syndecan 1 and MMP9 appear to mediate the antiinvasive and antimetastatic effects produced by FKBP gene expression. These studies show that uncharacterized genes differentially expressed in metastatic cancers can play important functional roles in the metastatic phenotype. Furthermore, identifying gene regulatory networks that function to control tumor progression may permit more accurate modeling of the complex molecular mechanisms of this disease.
Apoptosis induced by environmental stresses and amphotericin B inCandida albicans
Authors: Phillips Andrew J. , Sudbery Ian , Ramsdale Mark
Published: November 2003

New antifungal agents are urgently required to combat life-threatening infections caused by opportunistic fungal pathogens likeCandida albicans. The manipulation of endogenous fungal programmed cell death responses could provide a basis for future therapies. Here we assess the physiology of death inC. albicansin response to environmental stresses (acetic acid and hydrogen peroxide) and an antifungal agent (amphotericin B). Exposure ofC. albicansto 40-60 mM acetic acid, 5-10 mM hydrogen peroxide, or 4-8 μg·ml-1amphotericin B produced cellular changes reminiscent of mammalian apoptosis. Nonviable cells that excluded propidium iodide displayed the apoptotic marker phosphatidylserine (as shown by annexin-V-FITC labeling), were terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL)-positive (indicating nuclease-mediated double-strand DNA breakage), and produced reactive oxygen species. Ultrastructural changes in apoptotic cells included chromatin condensation and margination, separation of the nuclear envelope, and nuclear fragmentation.C. albicanscells treated at higher doses of these compounds showed cellular changes characteristic of necrosis. Necrotic cells displayed reduced TUNEL staining, a lack of surface phosphatidylserine, limited reactive oxygen species production, and an inability to exclude propidium iodide. Necrotic cells lacked defined nuclei and showed extensive intracellular vacuolization. Apoptosis inC. albicanswas associated with an accumulation of cells in the G2/M phase of the cell cycle, and under some apoptosis-inducing conditions, significant proportions of yeast cells switched to hyphal growth before dying. This is a demonstration of apoptosis in a medically important fungal pathogen.
Human targets of
Pseudomonas aeruginosa
pyocyanin
Authors: Ran Huimin , Hassett Daniel J. , Lau Gee W.
Published: November 2003

Pseudomonas aeruginosa
produces copious amounts of the redoxactive tricyclic compound pyocyanin that kills competing microbes and mammalian cells, especially during cystic fibrosis lung infection. Cross-phylum susceptibility to pyocyanin suggests the existence of evolutionarily conserved physiological targets. We screened a
Saccharomyces cerevisiae
deletion library to identify presumptive pyocyanin targets with the expectation that similar targets would be conserved in humans. Fifty
S. cerevisiae
targets were provisionally identified, of which 60% have orthologous human counterparts. These targets encompassed major cellular pathways involved in the cell cycle, electron transport and respiration, epidermal cell growth, protein sorting, vesicle transport, and the vacuolar ATPase. Using cultured human lung epithelial cells, we showed that pyocyanin-mediated reactive oxygen intermediates inactivate human vacuolar ATPase, supporting the validity of the yeast screen. We discuss how the inactivation of VATPase may negatively impact the lung function of cystic fibrosis patients.
In vivo
reduction of amyloid-β by a mutant copper transporter
Authors: Phinney Amie L. , Drisaldi Bettina , Schmidt Stephen D. , Lugowski Stan , Coronado Veronica , Liang Yan , Horne Patrick , Yang Jing , Sekoulidis Joannis , Coomaraswamy Janaky , Chishti M. Azhar , Cox Diane W. , Mathews Paul M. , Nixon Ralph A. , Carlson George A. , George-Hyslop Peter St , Westaway David
Published: November 2003

Cu ions have been suggested to enhance the assembly and pathogenic potential of the Alzheimer's disease amyloid-β (Aβ) peptide. To explore this relationship
in vivo
, toxic-milk (
tx
J
) mice with a mutant ATPase7b transporter favoring elevated Cu levels were analyzed in combination with the transgenic (Tg) CRND8 amyloid precursor protein mice exhibiting robust Aβ deposition. Unexpectedly, TgCRND8 mice homozygous for the recessive
tx
J
mutation examined at 6 months of age exhibited a reduced number of amyloid plaques and diminished plasma Aβ levels. In addition, homozygosity for
tx
J
increased survival of young TgCRND8 mice and lowered endogenous CNS Aβ at times before detectable increases in Cu in the CNS. These data suggest that the beneficial effect of the
tx
J
mutation on CNS Aβ burden may proceed by a previously undescribed mechanism, likely involving increased clearance of peripheral pools of Aβ peptide.
On the relation between fluctuation and response in biological systems
Authors: Sato Katsuhiko , Ito Yoichiro , Yomo Tetsuya , Kaneko Kunihiko
Published: November 2003

A general relationship between fluctuation and response in a biological system is presented. The fluctuation is given by the variance of some quantity, whereas the response is given as the average change of that quantity for a given parameter change. We propose a relationship where the two are proportional, in a similar way to the fluctuation–dissipation theorem in physics. By studying an evolution experiment where fluorescence of protein in bacteria increases, we confirm our relation by observing a positive correlation between the speed of fluorescence evolution and the phenotypic fluctuation of the fluorescence over clone bacteria. The generality of the relationship as well as its relevance to evolution is discussed.
Transcription-dependent degradation controls the stability of the SREBP family of transcription factors
Authors: Sundqvist Anders , Ericsson Johan
Published: November 2003

Cholesterol metabolism is tightly controlled by members of the sterol regulatory element-binding protein (SREBP) family of transcription factors. Here we demonstrate that the ubiquitination and degradation of SREBPs depend on their transcriptional activity. Mutations in the transactivation or DNA-binding domains of SREBPs inhibit their transcriptional activity and stabilize the proteins. The transcriptional activity and degradation of these mutants are restored when fused to heterologous transactivation or DNA-binding domains. When SREBP1a was fused to the DBD of Gal4, the ubiquitination and degradation of the fusion protein depended on coexpression of a promoter–reporter gene containing Gal4-binding sites. In addition, disruption of the interaction between WT SREBP and endogenous p300/CBP resulted in inhibition of SREBP-dependent transcription and stabilization of SREBP. Chemical inhibitors of transcription reduced the degradation of transcriptionally active SREBP1a, whereas they had no effect on the stability of transcriptionally inactive mutants, demonstrating that transcriptional activation plays an important role in the degradation of SREBPs. Thus, transcription-dependent degradation of SREBP constitutes a feedback mechanism to regulate the expression of genes involved in cholesterol metabolism and may represent a general mechanism to regulate the duration of transcriptional responses.
Folding a protein in a computer: An atomic description of the folding/unfolding of protein A
Authors: García Angel E. , Onuchic José N.
Published: November 2003

We study the folding mechanism of a three-helix bundle protein at atomic resolution, including effects of explicit water. Using replica exchange molecular dynamics we perform enough sampling over a wide range of temperatures to obtain the free energy, entropy, and enthalpy surfaces as a function of structural reaction coordinates. Simulations were started from different configurations covering the folded and unfolded states. Because many transitions between all minima at the free energy surface are observed, a quantitative determination of the free energy barriers and the ensemble of configurations associated with them is now possible. The kinetic bottlenecks for folding can be determined from the thermal ensembles of structures on the free energy barriers, provided the kinetically determined transition-state ensembles are similar to those determined from free energy barriers. A mechanism incorporating the interplay among backbone ordering, sidechain packing, and desolvation arises from these calculations. Large Φ values arise not only from native contacts, which mostly form at the transition state, but also from contacts already present in the unfolded state that are partially destroyed at the transition.
Atypical methylation of the interleukin-8 gene correlates strongly with the metastatic potential of breast carcinoma cells
Authors: De Larco Joseph E. , Wuertz Beverly R. K. , Yee Douglas , Rickert Brenda L. , Furcht Leo T.
Published: November 2003

Previously, we have shown that a strong correlation exists between the metastatic potential of breast carcinoma cell lines and their ectopic expression of IL-8. The undifferentiated, highly metastatic cell lines with high metastatic potential produce much more IL-8 than their differentiated lower metastatic counterparts. After eliminating the possibility that transcription factor activity was responsible for differences in IL-8 release, we examined the IL-8 gene for possible epigenetic modifications. Here, we report an aberrant methylation pattern that may be responsible for the differences in IL-8 release between the high and low metastatic cell lines. We determined that none of the deoxycytidylate-phosphate-deoxyguanylate (CpG) sites in the reported IL-8 promoter were methylated in either cell type. Much further upstream in the IL-8 gene, two CpG sites were identified that are differentially methylated. These two sites were fully methylated in the high metastatic cell lines, which produce large quantities of IL-8 and remain unmethylated in the low metastatic cell lines where the IL-8 gene is relatively silent. The DNA methylation results presented here differ from the common epigenetic paradigm in which methylation of promoter CpG islands silences gene expression, suggesting that there are additional epigenetic control mechanisms that as yet have not been fully appreciated or explored.
A pilot study of high-throughput, sequence-based mutational profiling of primary human acute myeloid leukemia cell genomes
Authors: Ley Timothy J. , Minx Patrick J. , Walter Matthew J. , Ries Rhonda E. , Sun Hui , McLellan Michael , DiPersio John F. , Link Daniel C. , Tomasson Michael H. , Graubert Timothy A. , McLeod Howard , Khoury Hanna , Watson Mark , Shannon William , Trinkaus Kathryn , Heath Sharon , Vardiman James W. , Caligiuri Michael A. , Bloomfield Clara D. , Milbrandt Jeffrey D. , Mardis Elaine R. , Wilson Richard K.
Published: November 2003

In this pilot study, we used primary human acute myeloid leukemia (AML) cell genomes as templates for exonic PCR amplification, followed by high-throughput resequencing, analyzing ≈7 million base pairs of DNA from 140 AML samples and 48 controls. We identified six previously described, and seven previously undescribed sequence changes that may be relevant for AML pathogenesis. Because the sequencing templates were generated from primary AML cells, the technique favors the detection of mutations from the most dominant clones within the tumor cell mixture. This strategy represents a viable approach for the detection of potentially relevant, nonrandom mutations in primary human cancer cell genomes.
Compensation by the muscle limits the metabolic consequences of lipodystrophy in PPARγ hypomorphic mice
Authors: Koutnikova Hana , Cock Terrie-Anne , Watanabe Mitsuhiro , Houten Sander M. , Champy Marie-France , Dierich Andrée , Auwerx Johan
Published: November 2003

Peroxisome proliferator-activated receptor γ (PPARγ) is a nuclear receptor, which controls adipocyte differentiation. We targeted with homologous recombination the PPARγ2-specific exon B, resulting in a white adipose tissue knockdown of PPARγ. Although homozygous (
PPAR
γ

hyp/hyp

) mice are born with similar weight as the WT mice, the
PPAR
γ

hyp/hyp

animals become growth retarded and develop severe lipodystrophy and hyperlipidemia. Almost half of these
PPAR
γ

hyp/hyp

mice die before adulthood, whereas the surviving
PPAR
γ

hyp/hyp

animals overcome the growth retardation, yet remain lipodystrophic. In contrast to most lipodystrophic models, the adult
PPAR
γ

hyp/hyp

mice only have mild glucose intolerance and do not have a fatty liver. These metabolic consequences of the lipodystrophy are relatively benign because of the induction of a compensatory gene expression program in the muscle that enables efficient oxidation of excess lipids. The
PPAR
γ

hyp/hyp

mice unequivocally demonstrate that PPARγ is the master regulator of adipogenesis
in vivo
and establish that lipid and glucose homeostasis can be relatively well maintained in the absence of white adipose tissue.
Replication protein A-mediated recruitment and activation of Rad17 complexes
Authors: Zou Lee , Liu Dou , Elledge Stephen J.
Published: November 2003

The human Rad17–Rfc2-5 and Rad9–Rad1–Hus1 complexes play crucial roles in the activation of the ATR-mediated DNA damage and DNA replication stress response pathways. In response to DNA damage, Rad9 is recruited to chromatin in a Rad17-dependent manner in human cells. However, the DNA structures recognized by the Rad17–Rfc2-5 complex during the damage response have not been defined. Here, we show that replication protein A (RPA) stimulates the binding of the Rad17–Rfc2-5 complex to single-stranded DNA (ssDNA), primed ssDNA, and a gapped DNA structure. Furthermore, RPA facilitates the recruitment of the Rad9–Rad1–Hus1 complex by the Rad17–Rfc2-5 complex to primed and gapped DNA structures
in vitro
. These findings suggest that RPA-coated ssDNA is an important part of the structures recognized by the Rad17–Rfc2-5 complex. Unlike replication factor C (RFC), which uses the 3′ primer/template junction to recruit proliferating cell nuclear antigen (PCNA), the Rad17–Rfc2-5 complex can use both the 5′ and the 3′ primer/template junctions to recruit the Rad9–Rad1–Hus1 complex, and it shows a preference for gapped DNA structures. These results explain how the Rad17–Rfc2-5 complex senses DNA damage and DNA replication stress to initiate checkpoint signaling.
Neuroactive steroids reduce neuronal excitability by selectively enhancing tonic inhibition mediated by δ subunit-containing GABA
A
receptors
Authors: Stell Brandon M. , Brickley Stephen G. , Tang C. Y. , Farrant Mark , Mody Istvan
Published: November 2003

Neuroactive steroids are potent modulators of γ-aminobutyric acid type A receptors (GABA
A
Rs), and their behavioral effects are generally viewed in terms of altered inhibitory synaptic transmission. Here we report that, at concentrations known to occur
in vivo
, neuroactive steroids specifically enhance a tonic inhibitory conductance in central neurons that is mediated by extrasynaptic δ subunit-containing GABA
A
Rs. The neurosteroid-induced augmentation of this tonic conductance decreases neuronal excitability. Fluctuations in the circulating concentrations of endogenous neuroactive steroids have been implicated in the genesis of premenstrual syndrome, postpartum depression, and other anxiety disorders. Recognition that δ subunit-containing GABA
A
Rs responsible for a tonic conductance are a preferential target for neuroactive steroids may lead to novel pharmacological approaches for the treatment of these common conditions.
Differential expression of iron-, carbon-, and oxygen-responsive mycobacterial genes in the lungs of chronically infected mice and tuberculosis patients
Authors: Timm Juliano , Post Frank A. , Bekker Linda-Gail , Walther Gabriele B. , Wainwright Helen C. , Manganelli Riccardo , Chan Wai-Tsing , Tsenova Liana , Gold Benjamin , Smith Issar , Kaplan Gilla , McKinney John D.
Published: November 2003

Pathogenetic processes that facilitate the entry, replication, and persistence ofMycobacterium tuberculosis(MTB) in the mammalian host likely include the regulated expression of specific sets of genes at different stages of infection. Identification of genes that are differentially expressedin vivowould provide insights into host-pathogen interactions in tuberculosis (TB); this approach might be particularly valuable for the study of human TB, where experimental opportunities are limited. In this study, the levels of selected MTB mRNAs were quantifiedin vitroin axenic culture,in vivoin the lungs of mice, and in lung specimens obtained from TB patients with active disease. We report the differential expression of MTB mRNAs associated with iron limitation, alternative carbon metabolism, and cellular hypoxia, conditions that are thought to exist within the granulomatous lesions of TB, in the lungs of wild-type C57BL/6 mice as compared with bacteria grownin vitro. Analysis of the same set of mRNAs in lung specimens obtained from TB patients revealed differences in MTB gene expression in humans as compared with mice.
Aphids do not avoid resistance in Australian lupin (Lupinus angustifolius, L. luteus) varieties
Authors: Edwards O.R. , Ridsdill-Smith T.J. , Berlandier F.A.
Published: November 2003

Laboratory bioassays and field trials were used to characterize resistance to three aphid species (Myzus persicae (Sulzer), Acyrthosiphon kondoi Shinji, Aphis craccivora (Koch) in two aphid-resistant varieties (Kalya, Tanjil) and one susceptible variety (Tallerack) of Lupinus angustifolius L., and in one resistant variety (Teo) and one susceptible variety (Wodjil) of L. luteus L. Host selection tests in the glasshouse showed that alates of all three species preferred L. luteus to L. angustifolius, but provided no evidence that alates selected susceptible varieties over resistant. These results were supported by a field trial, which showed no difference in the number of colonizing A. kondoi alates collected from the resistant and susceptible lines of each lupin species, but there were significantly more late-instar nymphs and apterous adults on the susceptible lines. In laboratory host suitability experiments, there was much greater suppression of aphid growth and survival on Teo than on Kalya and Tanjil. In field trials, the numbers of aphids were generally lower on resistant compared to susceptible lines of both lupin species with one notable exception: M. persicae numbers were not lower on the resistant variety Tanjil compared to the susceptible variety Tallerack (L. angustifolius). These results suggest that the resistance mechanisms in both lupin species do not affect the selection of hosts by colonizing aphids, but rather are affecting the growth, survival and possibly reproduction of aphids after settling.
Seed germination of ethylene perception mutants of tomato and Arabidopsis
Authors: Siriwitayawan Gunching , Geneve Robert L. , Bruce Downie A.
Published: November 2003

The involvement of ethylene in determining the time to radicle protrusion was investigated in ethylene-insensitive gain-of-function (GOF) receptor mutants in tomato and Arabidopsis, as well as in single and double loss-of-function (LOF) receptor mutants in Arabidopsis. Because ethylene evolution from seeds is coincident with radicle protrusion, and the ability to convert 1-aminocyclopropane-1-carboxylic acid (ACC) to ethylene is diagnostic for seed vigour, it was hypothesized that ethylene-insensitive mutants would require more time to complete germination compared to wild-type seeds. Mutant Never Ripe (Nr) tomato seeds from two genetic backgrounds refuted this hypothesis, while experiments with wild-type seeds, treated with the ethylene action inhibitors, 2,5-norbornadiene or silver thiosulphate, supported it. However, reciprocal crosses between wild-type and Nr demonstrated that ethylene insensitivity during seed development determined subsequent time to complete germination, rather than the ability of the embryo/endosperm to perceive ethylene in the mature seed during germination. Additionally, seed quality, determined by standard vigour tests, was reduced in Nr compared to wild-type seeds, establishing a disconnection between rapid completion of germination and seed vigour. In Arabidopsis, all ethylene-insensitive GOF, and five of six single LOF mutants, required more time to complete 50% radicle protrusion, while double LOF mutants required the same, or less, time to complete germination compared to wild-type seeds. These findings support a role for ethylene perception in determining the length of time Arabidopsis seeds remain in the lag phase prior to radicle protrusion.
Gentrification and the Middle-class Remaking of Inner London, 1961-2001
Authors: Hamnett Chris
Published: November 2003

This paper reviews the debates over the explanation of gentrification and argues that gentrification is best explained as the social and spatial manifestation of the transition from an industrial to a post-industrial economy based on financial, business and creative services, with associated changes in the nature and location of work, in the occupational class structure, earnings and incomes and the structure of the housing market. The paper sets out the links between these changes in the London context. It also examines the evidence for gentrification-induced displacement in London, arguing that it may be more appropriate to view the process partly as one of replacement.
Living in the Bubble: Gentrification and its 'Others' in North London
Authors: Butler Tim
Published: November 2003

The article examines aspects of middle-class life by a group of 75 gentrifiers in Islington in north London. The study demonstrates that in their day-to-day lives almost all the respondents lived quite apart from non-middle-class residents in Islington. This was demonstrated by their educational strategies which involved finding schooling for their children out of the borough in both the private and state sectors. Their children had almost no contact with children from other social backgrounds. It is suggested that, despite a strong rhetoric in favour of social integration, the current gentrifiers of Islington, unlike the pioneers of the 1960s and 1970s, are unwilling to invest social capital in the area and that their relationships are almost entirely with 'people like us'. It is suggested that this is likely to lead to an increasingly polarised social structure in which the middle classes and their children inhabit entirely separate social spaces from other, and more disadvantaged, groups. The long-term consequences of this are uncertain but are unlikely to lead to greater social cohesion.
Super-gentrification: The Case of Brooklyn Heights, New York City
Authors: Lees Loretta
Published: November 2003

This paper is an empirical examination of the process of 'super-gentrification' in the Brooklyn Heights neighbourhood of New York City. This intensified regentrification is happening in a few select areas of global cities like London and New York that have become the focus of intense investment and conspicuous consumption by a new generation of super-rich 'financifiers' fed by fortunes from the global finance and corporate service industries. This latest resurgence of gentrification can be distinguished from previous rounds of revitalisation and poses important questions about the historical continuity of current manifestations of gentrification with previous generations of neighbourhood change.
Family Gentrifiers: Challenging the City as a Place Simultaneously to Build a Career and to Raise Children
Authors: Karsten Lia
Published: November 2003

Suburbanisation by families with children can be considered as a dominant factor in determining the structure of a city's population. However, due to urban restructuring programmes, a modest counter process can be observed. Some families who could afford to buy a house in the suburbs decide instead to stay in the central areas of the city. In so doing, they form a relatively new category of gentrifiers: middle-class families with children. In this paper, they are identified as 'yupps': young urban professional parents. They combine the next step in their life cycle—having children—with continuing their career and their preference for an urban lifestyle. The Amsterdam study, reported here, gives some insight in the personal characteristics of yupps, their motivations to live centrally, their activity patterns and constraints. An analysis of their daily lives reveals the significance of the neighbourhood as a crucial factor in the daily integration of such contrasting demands as building a career, caring for children and keeping up with cultural pursuits and social contacts. It is further argued that—in a class-specific context-changing gender relations lie at the root of family gentrification, resulting in the construction of new male and female identities.
The influence of culture in emerging adulthood: Perspectives of Chinese college students
Authors: Nelson Larry J. , Badger Sarah , Wu Bo
Published: November 2003

Emerging adulthood refers to a time period (18–25 years of age) between adolescence and adulthood. Recent research suggests that it may be a cultural construction. More traditional, non-Western cultures may have a shortened period of emerging adulthood, or no emerging adulthood at all, because these cultures tend to place greater emphasis on practices that lead to an earlier transition to adulthood. The purpose of this study was to examine emerging adulthood in the Chinese culture, including (1) the types of criteria Chinese young people deem necessary for becoming an adult, (2) the types of behaviours Chinese emerging adults are engaging in, (3) identity-related issues, and (4) other aspects of Chinese culture that might suggest that emerging adulthood in China may be different than in the United States. Participants in this study were 207 students at Beijing Normal University located in Beijing, China. Results provided evidence to support the notion that emerging adulthood is affected by culture. Findings revealed that the majority of Chinese college students (1) feel they have reached adult status in their early twenties, (2) have culturally specific criteria for adult status, and (3) tend to engage in behaviours and have beliefs and values that appear to differ from emerging adults in Western cultures.
The Countryside in the City - Situating a Farmers' Market in Birmingham
Authors: Bentley Gillian , Hallsworth Alan G. , Bryan Anna
Published: November 2003

The City of Birmingham capitalized on the burgeoning trend in Farmer's Markets by establishing one in the city core. This paper first outlines the growth and origins of Farmer's Markets before offering empirical research on this particular market. The critical questions concern the advisability of putting such a market in a major city and issues surrounding the use made of the market by patrons. Stallholders and others are also interviewed to establish the balance of benefits and costs. The conclusions are that the effects have generally been positive and the initiative a worthwhile one.
Local Responses to Longterm Unemployment: Delivering Access to Employment in Edinburgh
Authors: Lindsay Colin , Sturgeon Garry
Published: November 2003

This paper examines locally developed policy responses to long-term unemployment in the city of Edinburgh: a labour market characterised by relatively lowunemployment and generally high levels of demand. Drawing upon in-depth interviews with 115 long-term unemployed people residing in the city, the paper first analyses the complex combination of barriers to work faced by members of this client group. Two recent labour market initiatives, developed by the local authority in partnership with other public and third sector agencies and (in one case) major employers, are then discussed. It is suggested that this locally focused, partnership-based approach may provide a useful model for local policy responses to long-term unemployment, particularly in buoyant labour markets.
‘Design-led’ Urban Regeneration: a Critical Perspective
Authors: Bell David , Jayne Mark
Published: November 2003

This paper develops a critical perspective on ‘design-led’ urban regeneration, which is a fuzzy term used to describe a diverse raft of economic development strategies. A definition of design is outlined and then utilised in an assessment of a number of local and regional design-led urban regeneration schemes. A more detailed critique of one such project, the North Staffordshire Design Initiative, is then undertaken. We argue that there is a lack of best practice models and empirical research to guide policy makers.
Rhetorical patterns in the Australian debate over war with Iraq
Authors: Dollery Brian , Crase Lin
Published: November 2003

Considerable public debate surrounded the Bush Administration's policy to invade Iraq if it did not dismantle its purported stockpile of 'Weapons of Mass Destruction' and the wisdom of Australian participation in such an attack. This paper invokes Albert Hirschman's well-known 'rhetoric of reaction' taxonomy to examine the patterns of persuasive discourse embodied in the Australian debate over the desirability of Australian involvement in a war with Iraq. We seek to establish whether the Hirschmanian typology does indeed adequately describe rhetorical patterns in the Australian debate and we attempt to identify shortcomings in the analytical system proposed by Hirschman.
MUC5AC mucin release from human airways in vitro: Effects of indomethacin and Bay X1005
Authors: Roger Patricia , Gascard Jean-Pierre , Bara Jacques , de Montpreville Vincent Thomas , Brink Charles
Published: November 2003

Background: Increased secretion of mucus is a hallmark of many respiratory diseases and contributes significantly to the airflow limitation experienced by many patients. While the current pharmacological approach to reducing mucus and sputum production in patients is limited, clinical studies have suggested that drugs which inhibit the cyclooxygenase and/or 5‐lipoxygenase enzymatic pathways may reduce secretory activity in patients with airway disease.

Aim: This study was performed to investigate the effects of indomethacin (cyclooxygenase inhibitor) and Bayx1005 (5‐lipoxygenase inhibitor) on MUC5AC release from human airways in vitro.

Methods: An immunoradiometric assay was used to determine the quantities of MUC5AC present in the biological fluids derived from human airways in vitro. The measurements were made with a mixture of eight monoclonal antibodies (MAbs; PM8) of which the 21 M1 MAb recognized a recombinant M1 mucin partially encoded by the MUC5AC gene.

Results: The quantities of MUC5AC detected in the biological fluids derived from human bronchial preparations were not modified after treatment with indomethacin (cyclooxygenase inhibitor) and/or an inhibitor of the 5‐lipoxygenase metabolic pathway (BAY x1005).

Conclusion: These results suggest that the cyclooxygenase and 5‐lipoxygenase metabolic pathways play little or no role in the release of MUC5AC from human airways.
Epithelium‐dependent effect of L‐glutamate on airways: involvement of prostaglandins
Authors: Hatziefthimiou Apostolia A. , Gourgoulianis Konstantinos I. , Molyvdas Paschalis-Adam
Published: November 2003

We investigated the effect of the excitatory amino acid (EAA) receptor agonists L‐glutamate, N‐methyl‐D‐aspartate (NMDA), (RS)‐a‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid (AMPA) and kainic acid on KCl‐induced contractions of rabbit tracheal smooth muscle, as well as the role of epithelium and endogenously produced nitric oxide and prostaglandins on these responses. L‐Glutamate decreased KCl‐induced contractions up to 30%. This effect was attenuated by epithelium removal, tetrodotoxin, methylene blue and indomethacin but not by NG‐nitro‐L‐arginine methyl ester. While NMDA, AMPA and kainic acid had no effect, the combination of NMDA + kainic acid decreased KCl‐induced contractions. These results suggest that, in rabbit trachea, L‐glutamate has, at least in part, an epithelium‐dependent effect mediated via prostaglandin formation and that the EAA receptors involved are nonclassical.
Biosynthesis and Control of Mosquito Gut Proteases
Authors: Borovsky Dov
Published: November 2003

Earlier investigations of the proteases that digest the blood meal in mosquitoes identified the midgut epithelial cells as the source of the main blood digesting protease, trypsin. Surgical manipulations and cytoimmunochemical studies indicated that trypsin in the mosquito is not stored in the epithelial cells as an inactive enzyme, but is synthesized, activated and released into the gut lumen after the blood meal. Using molecular biology techniques the major trypsin genes have been sequenced and some information on the transcription factors that regulate the induction of the genes have been reported. Although all the hormone(s) and the factors that are responsible for the induction of trypsin biosynthesis are not known, the termination of trypsin biosynthesis is controlled by a decapeptide hormone; trypsin modulating oostatic factor (TMOF) that is secreted by the mosquito ovary. Genetic engineering and expression of TMOF in bacteria, yeast and algae is emerging as a potential future larval control of mosquitoes in the field. IUBMB Life, 55: 435‐441, 2003
Lymphotoxin Is Required for Maintaining Physiological Levels of Serum IgE That Minimizes Th1-mediated Airway Inflammation
Authors: Kang Hyung-Sik , Blink Sarah E. , Chin Robert K. , Lee Youjin , Kim Oliver , Weinstock Joel , Waldschmidt Thomas , Conrad Daniel , Chen Bohao , Solway Julian , Sperling Anne I. , Fu Yang-Xin
Published: November 2003

Although elevated levels of IgE in asthmatic patients are strongly associated with lung infiltration by activated T helper (Th) 2 cells, the physiological role of immunoglobulin E (IgE) in the airway remains largely undefined. Lymphotoxin-deficient α (LTα−/−) mice exhibit increased airway inflammation, paradoxically accompanied by diminished levels of IgE and reduced airway hyperresponsiveness in response to both environmental and induced antigen challenge. The severe lung inflammation in LTα−/− mice is Th1 in nature and can be alleviated by IgE reconstitution. Conversely, depletion of IgE in wild-type mice recapitulates the lung pathologies of LTα−/− mice. Therefore, this work has revealed that lymphotoxin is essential for IgE production, and a physiological role of IgE in the airway may consist of maintaining the balance of Th1 and Th2 responses to prevent aberrant inflammation.
IL-4–Stat6 Signaling Induces Tristetraprolin Expression and Inhibits TNF-α Production in Mast Cells
Authors: Suzuki Kotaro , Nakajima Hiroshi , Ikeda Kei , Maezawa Yuko , Suto Akira , Takatori Hiroaki , Saito Yasushi , Iwamoto Itsuo
Published: November 2003

Increasing evidence has revealed that mast cell–derived tumor necrosis factor α (TNF-α) plays a critical role in a number of inflammatory responses by recruiting inflammatory leukocytes. In this paper, we investigated the regulatory role of interleukin 4 (IL-4) in TNF-α production in mast cells. IL-4 inhibited immunoglobulin E–induced TNF-α production and neutrophil recruitment in the peritoneal cavity in wild-type mice but not in signal transducers and activators of transcription 6 (Stat6)–deficient mice. IL-4 also inhibited TNF-α production in cultured mast cells by a Stat6-dependent mechanism. IL-4–Stat6 signaling induced TNF-α mRNA destabilization in an AU-rich element (ARE)–dependent manner, but did not affect TNF-α promoter activity. Furthermore, IL-4 induced the expression of tristetraprolin (TTP), an RNA-binding protein that promotes decay of ARE-containing mRNA, in mast cells by a Stat6-dependent mechanism, and the depletion of TTP expression by RNA interference prevented IL-4–induced down-regulation of TNF-α production in mast cells. These results suggest that IL-4–Stat6 signaling induces TTP expression and, thus, destabilizes TNF-α mRNA in an ARE-dependent manner.