bluuebunny/crossref_metadata_2025 huggingface dataset:
Pools of selenium in some Indian soils at field capacity and submerged moisture regimes
Authors: Dhillon S. K. , Dhillon K. S.
Published: April 2004

Pools of soil selenium (Se) as influenced by moisture regimes were investigated in some normal and seleniferous (which produce vegetation containing >5 mg Se/kg—the maximum permissible level for animal consumption) soils of India. Soil samples were equilibrated with 75Se by subjecting to alternate wetting and drying cycles and incubated at field capacity and submerged moisture regimes. Each soil sample was subjected to either single extraction with 0.25 M KCl, 0.1 M KH2PO4, and 4 M HCl in a sequence or 7 extractions with KCl followed by 7 extractions with KH2PO4 and 2 with HCl. Amount of 75Se extracted from different soils incubated at field capacity through single extraction with 0.25 M KCl varied from 8.4 to 30.5% of applied 75Se for alkaline and 2.6 to 10.4% for acidic soils. Among alkaline soils, a greater amount of 75Se was extracted from highly calcareous non-seleniferous soils than seleniferous soils. The amount of selenium extracted through 7 sequential extractions with 0.25 M KCl was 1.5–7.0 times greater than that extracted through single extraction. A significant coefficient of correlation between 75Se extracted through repeated extractions with 0.25 M KCl and pH of the soils (r = 0.93, P�≤ 0.01) suggested greater availability of Se in alkaline than acidic soils. Specifically sorbed soil Se extracted with 0.1 M KH2PO4 through 7 sequential extractions ranged from 15.3 to 24.6% for alkaline and 24.4 to 40.1% for acidic soils. The amount of 75Se desorbed through multiple extractions with 4 M HCl was negatively correlated with pH (r�= –0.95, P ≤ 0.01) and electrical conductivity (r = –0.85, P ≤ 0.05) of the soils. After subjecting to single extraction, residual 75Se left in soils incubated at field capacity moisture varied from 11.7 to 59.7%. It was negatively correlated with pH (r = –0.85, P ≤ 0.05) and CaCO3 (r = –0.79, P ≤ 0.10) and positively correlated with ammonium oxalate extractable iron content (r = 0.76, P ≤ 0.10) of soils. Compared with the single extraction procedure, only a small amount (9–36%) of 75Se was left as residual 75Se after multiple extractions. Relatively less 75Se was released when the alkaline or acidic soils incubated under submergence were subjected to single or multiple extraction procedures. The multiple extraction procedure could better assess different soil Se pools than the single extraction procedure. At field capacity moisture, large amounts of Se occur in easily available forms. Under submerged conditions, substantial amounts of Se are maintained in the soil solution when Se is removed from the solution through plant uptake or leaching.
Quasi-equilibrium of organic carbon in shrink - swell soils of the subhumid tropics in India under forest, horticulture, and agricultural systems
Authors: Naitam R. , Bhattacharyya T.
Published: April 2004

Restoration of soil quality through soil organic carbon (SOC) management has been a major concern for tropical soils. SOC is sensitive to human activities such as deforestation, biomass burning, land-use changes, and environmental pollution. Our aim in this study was to elucidate the effect of land-use systems on quasi-equilibrium values (QEV) of SOC. To determine the QEV of SOC, 4 representative pedons from Nagpur district, Maharashtra, under horticulture (orange), agriculture (cotton, cotton + pigeonpea), and forest (teak) with the time of cultivation ranging from 20 years to centuries were selected. The study indicated that the QEV of SOC in the shrink–swell soils decreased when they were used for agricultural crop production. Since all these soils have similar substrate, the SOC equilibrium values obtained in soils of horticultural and forest ecosystems may also be attainable in the soils under agricultural system. In other words, addition of external sources of farmyard manure or other green manure may raise the QEV of SOC from 0.44–0.51% to 0.70–0.80% in soils of agricultural system.
Pseudomonas aeruginosaregulates flagellin expression as part of a global response to airway fluid from cystic fibrosis patients
Authors: Wolfgang Matthew C. , Jyot Jeevan , Goodman Andrew L. , Ramphal Reuben , Lory Stephen
Published: April 2004

Cystic fibrosis (CF) patients are highly susceptible to chronic lung infections by the environmental bacteriumPseudomonas aeruginosa. The overproduction and accumulation of dehydrated viscous respiratory mucus and excessive inflammation represents a defining feature of CF and constitutes the major environment encountered byP. aeruginosaduring chronic infections. We applied whole-genome microarray technology to investigate the ability ofP. aeruginosato respond to signals found in muco-purulent airway liquids collected from chronically infected CF patients. Particularly notable was the activation of the Rhl-dependent quorum-sensing (QS) network and repression offliC, which encodes flagellin. Activation of the Rhl branch of the QS network supports the observation that QS molecules are produced in the chronically infected CF lung. The shut-off of flagellin synthesis in response to CF airway liquids was rapid and independent of QS and the known regulatory networks controlling the hierarchical expression of flagellar genes. As flagellin is highly immunogenic and subject to detection by host pattern recognition receptors, its repression may represent an adaptive response that allowsP. aeruginosato avoid detection by host defense mechanisms and phagocytosis during the chronic phase of CF lung infections.
Direct regulation of CREB transcriptional activity by ATM in response to genotoxic stress
Authors: Shi Yuling , Venkataraman Sujatha L. , Dodson Gerald E. , Mabb Angela M. , LeBlanc Scott , Tibbetts Randal S.
Published: April 2004

Ataxia–telangiectasia (A–T) is a syndrome of cancer susceptibility, immune dysfunction, and neurodegeneration that is caused by mutations in the A–T-mutated (
ATM
) gene. ATM has been implicated as a critical regulator of cellular responses to DNA damage, including the activation of cell cycle checkpoints and induction of apoptosis. Although defective cell cycle-checkpoint regulation and associated genomic instability presumably contribute to cancer susceptibility in A–T, the mechanism of neurodegeneration in A–T is not well understood. In addition, although ATM is required for the induction of the p53 transcriptional program in response to DNA damage, the identities of the relevant transcription factors that mediate ATM-dependent changes in gene expression remain largely undetermined. In this article, we describe a signal transduction pathway linking ATM directly to the Ca
2+
/cAMP response element-binding protein, CREB, a transcription factor that regulates cell growth, homeostasis, and survival. ATM phosphorylated CREB
in vitro
and
in vivo
in response to ionizing radiation (IR) and H
2
O
2
on a stress-inducible domain. IR-induced phosphorylation of CREB correlated with a decrease in CREB transactivation potential and reduced interaction between CREB and its transcriptional coactivator, CREB-binding protein (CBP). A CREB mutant containing Ala substitutions at ATM phosphorylation sites displayed enhanced transactivation potential, resistance to inhibition by IR, and increased binding to CBP. We propose that ATM-mediated phosphorylation of CREB in response to DNA damage modulates CREB-dependent gene expression and that dysregulation of the ATM–CREB pathway may contribute to neurodegeneration in A–T.
New mechanistic studies on the proline-catalyzed aldol reaction
Authors: List Benjamin , Hoang Linh , Martin Harry J.
Published: April 2004

The mechanism of the proline-catalyzed aldol reaction has stimulated considerable debate, and despite limited experimental data, at least five different mechanisms have been proposed. Complementary to recent theoretical studies we have initiated an experimental program with the goal of clarifying some of the basic mechanistic questions concerning the proline-catalyzed aldol reaction. Here we summarize our discoveries in this area and provide further evidence for the involvement of enamine intermediates.
Evidence for the physiological role of a rhodanese-like protein for the biosynthesis of the molybdenum cofactor in humans
Authors: Matthies Andreas , Rajagopalan K. V. , Mendel Ralf R. , Leimkühler Silke
Published: April 2004

Recent studies have identified the human genes involved in the biosynthesis of the molybdenum cofactor. The human MOCS3 protein contains an N-terminal domain similar to the
Escherichia coli
MoeB protein and a C-terminal segment displaying similarities to the sulfurtransferase rhodanese. The MOCS3 protein is believed to catalyze both the adenylation and the subsequent generation of a thiocarboxylate group at the C terminus of the smaller subunit of molybdopterin (MPT) synthase. The MOCS3 rhodanese-like domain (MOCS3-RLD) was purified after heterologous expression in
E. coli
and was shown to catalyze the transfer of sulfur from thiosulfate to cyanide. In a defined
in vitro
system for the generation of MPT from precursor Z, the sulfurated form of MOCS3-RLD was able to provide the sulfur for the thiocarboxylation of MOCS2A, the small MPT synthase subunit in humans. Mutation of the putative persulfide-forming active-site cysteine residue C412 abolished the sulfurtransferase activity of MOCS3-RLD completely, showing the importance of this cysteine residue for catalysis. In contrast to other mammalian rhodaneses, which are mostly localized within mitochondria, MOCS3 in addition to the subunits of MPT synthase are localized in the cytosol.
Involvement of
S
-adenosylmethionine in G
1
cell-cycle regulation in
Saccharomyces cerevisiae
Authors: Mizunuma Masaki , Miyamura Kazunori , Hirata Dai , Yokoyama Hiroshi , Miyakawa Tokichi
Published: April 2004

S
-adenosyl-
l
-methionine (AdoMet) is a molecule central to general metabolism, serving as a principal methyl donor for methylation of various cellular constituents. The alteration in the availability of AdoMet has profound effect on cell growth. A mutant allele of
Saccharomyces cerevisiae
gene
SAH1
encoding
S
-adenosyl-
l
-homocysteine (AdoHcy) hydrolase, was isolated as a mutation that suppressed the Ca
2+
-sensitive phenotypes of the
zds1
Δ strain, such as the Ca
2+
-induced, Swe1p- and Cln2p-mediated G
2
cell-cycle arrest, and polarized bud growth. The mutation (
sah1
-
1
) led the cells to accumulate AdoMet besides AdoHcy, the substrate of Sah1p. The cells treated with exogenous AdoMet and AdoHcy had markedly decreased levels of
SWE1
and
CLN2
mRNA, providing the basis for the suppression of the Ca
2+
sensitivity by the
sah1
-
1
mutation. Exogenous AdoMet transiently led the cells to G
1
cell-cycle delay whereas AdoHcy caused growth inhibition irrelevant to the cell cycle. The effect of AdoMet in inducing the cell-cycle delay was exerted in a manner independent of Met4p, an overall transcriptional activator for MET genes. Our observation provides an insight into the role played by AdoMet in cell cycle regulation.
Human centromere repositioning “in progress”
Authors: Amor David J. , Bentley Karen , Ryan Jacinta , Perry Jo , Wong Lee , Slater Howard , Choo K. H. Andy
Published: April 2004

Centromere repositioning provides a potentially powerful evolutionary force for reproductive isolation and speciation, but the underlying mechanisms remain ill-defined. An attractive model is through the simultaneous inactivation of a normal centromere and the formation of a new centromere at a hitherto noncentromeric chromosomal location with minimal detrimental effect. We report a two-generation family in which the centromeric activity of one chromosome 4 has been relocated to a euchromatic site at 4q21.3 through the epigenetic formation of a neocentromere in otherwise cytogenetically normal and mitotically stable karyotypes. Strong epigenetic inactivation of the original centromere is suggested by retention of 1.3 megabases of centromeric α-satellite DNA, absence of detectable molecular alteration in chromosome 4-centromereproximal p- and q-arm sequences, and failure of the inactive centromere to be reactivated through extensive culturing or treatment with histone deacetylase inhibitor trichostatin A. The neocentromere binds functionally essential centromere proteins (CENP-A, CENP-C, CENP-E, CENP-I, BUB1, and HP1), although a moderate reduction in CENP-A binding and sister-chromatid cohesion compared with the typical centromeres suggests possible underlying structural/functional differences. The stable mitotic and meiotic transmissibility of this pseudodicentric-neocentric chromosome in healthy individuals and the ability of the neocentric activity to form in a euchromatic site in preference to a preexisting alphoid domain provide direct evidence for an inherent mechanism of human centromere repositioning and karyotype evolution “in progress.” We discuss the wider implication of such a mechanism for meiotic drive and the evolution of primate and other species.
Deformation mechanisms in free-standing nanoscale thin films: A quantitative
in situ
transmission electron microscope study
Authors: Haque M. A. , Saif M. T. A.
Published: April 2004

We have added force and displacement measurement capabilities in the transmission electron microscope (TEM) for
in situ
quantitative tensile experimentation on nanoscale specimens. Employing the technique, we measured the stress–strain response of several nanoscale free-standing aluminum and gold films subjected to several loading and unloading cycles. We observed low elastic modulus, nonlinear elasticity, lack of work hardening, and macroscopically brittle nature in these metals when their average grain size is 50 nm or less. Direct
in situ
TEM observation of the absence of dislocations in these films even at high stresses points to a grain-boundary-based mechanism as a dominant contributing factor in nanoscale metal deformation. When grain size is larger, the same metals regain their macroscopic behavior. Addition of quantitative capability makes the TEM a versatile tool for new fundamental investigations on materials and structures at the nanoscale.
Giant tortoises are not so slow: Rapid diversification and biogeographic consensus in the Galápagos
Authors: Beheregaray Luciano B. , Gibbs James P. , Havill Nathan , Fritts Thomas H. , Powell Jeffrey R. , Caccone Adalgisa
Published: April 2004

Isolated oceanic archipelagos have played a major role in the development of evolutionary theory by offering a unique setting for studying spatial and temporal patterns of biological diversification. However, the evolutionary events that cause associations between genetic variation and geography in archipelago radiations are largely unknown. This finding is especially true in the Galápagos Islands, where molecular studies have revealed conflicting biogeographic patterns. Here, we elucidate the history of diversification of giant Galápagos tortoises by using mtDNA sequences from 802 individuals representing all known extant populations. We test biogeographic predictions based on geological history and assess the roles of volcano emergence and island formation in driving evolutionary diversification. Patterns of colonization and lineage sorting appear highly consistent with the chronological formation of the archipelago. Populations from older islands are composed exclusively of endemic haplotypes that define divergent monophyletic clades. Younger populations, although currently differentiated, exhibit patterns of colonization, demographic variation and genetic interchange shaped by recent volcanism. Colonization probably occurs shortly after a volcano emerges through range expansion from older volcanoes. Volcanism can also create temporal shifts from historical to recurrent events, such as promoting gene flow by creating land bridges between isolated volcanoes. The association of spatial and temporal patterns of genetic variation with geophysical aspects of the environment can best be attributed to the limited dispersal and migration of tortoises following an oceanographic current. The endangered giant Galápagos tortoises represent a rapid allopatric radiation and further exemplify evolutionary processes in one of the world's greatest natural laboratories of evolution.
Irregular telomeres impair meiotic synapsis and recombination in mice
Authors: Liu Lin , Franco Sonia , Spyropoulos Barbara , Moens Peter B. , Blasco Maria A. , Keefe David L.
Published: April 2004

Telomere shortening can lead to chromosome instability, replicative senescence, and apoptosis in both somatic and male germ cells. To study roles for mammalian telomeres in homologous pairing and recombination, we characterized effects of telomere shortening on spermatogenesis and oogenesis in late-generation telomerase-deficient mice. We show that shortened telomeres of late-generation telomerase-deficient mice impair meiotic synapsis and decrease recombination, in particular, in females. In response to telomere shortening, male germ cells mostly undergo apoptosis, whereas female germ cells preferentially arrest in early meiosis, suggesting sexually dimorphic surveillance mechanisms for telomere dysfunction during meiosis in mice. Further, meiocytes of late-generation telomerase-deficient females with shortened telomeres, bred with early-generation males harboring relatively long telomeres, exhibit severely impaired chromosome pairing and synapsis and reduced meiotic recombination. These findings imply that functional telomeres are important in mammalian meiotic synapsis and recombination.
Transcriptional termination by RNA polymerase I requires the small subunit Rpa12p
Authors: Prescott Elizabeth M. , Osheim Yvonne N. , Jones Hannah S. , Alen Claudia M. , Roan Judith G. , Reeder Ronald H. , Beyer Ann L. , Proudfoot Nick J.
Published: April 2004

We identify Rpa12p of RNA polymerase I (Pol I) as a termination factor. Combined analyses using transcription run-on, electron microscopy-visualized chromatin spreading and RT-PCR have been applied to the rRNA-encoding genes of
Saccharomyces cerevisiae
. These confirm that Pol I termination occurs close to the Reb1p-dependent terminator in wild-type strains. However, deletion mutants for the 3′ end-processing enzyme Rnt1p or the Rpa12p subunit of Pol I both show Pol I transcription in the spacer. For Δ
rpa12
, these spacer polymerases are devoid of nascent transcripts, suggesting they are immediately degraded. The homology of Rpa12p to the small subunit Rpb9p of Pol II and Rpc11p of Pol III, both implicated in transcriptional termination, points to a common termination mechanism for all three classes of RNA polymerase.
Fas-disabling small exocyclic peptide mimetics limit apoptosis by an unexpected mechanism
Authors: Hasegawa Akihiro , Cheng Xin , Kajino Kiichi , Berezov Alan , Murata Kaoru , Nakayama Toshinori , Yagita Hideo , Murali Ramachandran , Greene Mark I.
Published: April 2004

Fas ligand- (FasL) mediated apoptosis is an important element of tissue-specific organ damage. We have developed biologically active small exocyclic peptide mimetics that disable apoptotic functions of Fas. The most effective mimetic binds to both its receptor and FasL with comparable affinity.In vitro, the most effective antagonist blocked FasL-induced cytotoxicity completely and specifically.In vivo, the antagonistic mimetic also prevented Concanavilin A (Con A) induced hepatitis, a CD4+T cell-mediated animal model of liver injury. Although current approaches prevent Fas receptor signaling by excluding FasL binding to Fas, the small molecule mimetics reported here disable Fas by promoting a defective Fas-FasL receptor complex. This event desensitizes FasL-mediated apoptosis by inhibiting extracellular signal regulated kinase activity and up-regulating NF-κB.
The immunomodulatory adapter proteins DAP12 and Fc receptor γ-chain (FcRγ) regulate development of functional osteoclasts through the Syk tyrosine kinase
Authors: Mócsai Attila , Humphrey Mary Beth , Van Ziffle Jessica A. G. , Hu Yongmei , Burghardt Andrew , Spusta Steven C. , Majumdar Sharmila , Lanier Lewis L. , Lowell Clifford A. , Nakamura Mary C.
Published: April 2004

Osteoclasts, the only bone-resorbing cells, are central to the pathogenesis of osteoporosis, yet their development and regulation are incompletely understood. Multiple receptors of the immune system use a common signaling paradigm whereby phosphorylated immunoreceptor tyrosine-based activation motifs (ITAMs) within receptor-associated adapter proteins recruit the Syk tyrosine kinase. Here we demonstrate that a similar mechanism is required for development of functional osteoclasts. Mice lacking two ITAM-bearing adapters, DAP12 and the Fc receptor γ-chain (FcRγ), are severely osteopetrotic.
DAP12
-/-
FcR
γ
-/-
bone marrow cells fail to differentiate into multinucleated osteoclasts or resorb bone
in vitro
and show impaired phosphorylation of the Syk tyrosine kinase.
syk
-/-
progenitors are similarly defective in osteoclast development and bone resorption. Intact SH2-domains of Syk, introduced by retroviral transduction, are required for functional reconstitution of
syk
-/-
osteoclasts, whereas intact ITAM-domains on DAP12 are required for reconstitution of
DAP12
-/-
FcR
γ
-/-
cells. These data indicate that recruitment of Syk to phosphorylated ITAMs is critical for osteoclastogenesis. Although DAP12 appears to be primarily responsible for osteoclast differentiation in cultures directly stimulated with macrophage-colony stimulating factor and receptor activator of NF-κB ligand cytokines, DAP12 and FcRγ have overlapping roles in supporting osteoclast development in osteoblast–osteoclast cocultures, which mirrors their overlapping functions
in vivo
. These results provide new insight into the biology of osteoclasts and suggest novel therapeutic targets in diseases of bony remodeling.
Proximity, Neighbourhood and the Efficacy of Exclusion
Authors: Lynch Allen K. , Rasmussen David W.
Published: April 2004

This paper uses data on over 2800 house sales in Jacksonville, Florida, to estimate the impact of neighbourhood characteristics on house prices. A GIS progamme is used to develop neighbourhood characteristics that are unique to each observation, thereby allowing the evaluation of the impact of neighbourhood attributes in proximity to the dwelling. Except for population density, the effects of neighbourhood characteristics on property values do not decay over a 3-4-mile distance from the dwelling and the results suggest that neighbourhood characteristics over a large geographical area may have a significant effect on property values. Because the study area is a single jurisdiction, the results suggest that the housing market may generate the Tiebout-like exclusion that is usually associated with fiscal fragmentation.
Neighbourhood Composition and Residential Land Prices: Does Exclusion Raise or Lower Values?
Authors: Cervero Robert , Duncan Michael
Published: April 2004

Hedonic price models are used to explore the degree to which land-use and racial composition, used as outcome proxies for local zoning practices, influence residential land values in Santa Clara County, California. Fiscal pressures have prompted many California communities to zone on the basis of tax-yield potential, especially in fast-growing settings like Santa Clara County. Controlling for variables related to job accessibility as well as proximity to regional transport infrastructure, the analysis shows that indicators of land-use diversity and jobs-housing balance generally correlate with high residential land prices. While the fiscal instincts of Californian municipalities is to shun housing in favour of commercial development and thus to create imbalanced land development patterns, this research suggests these fiscal advantages are partly offset by lower land values and thus lower property tax intake. Racial diversity, on the other hand, lowered residential property values, even when controlling for neighbourhood factors like average household income. This finding suggests that, to the degree that local zoning responds to land-market forces, exclusion in residential settings is more a product of racial than land-use composition. As long as land markets attach either values or disbenefits to land-use mix and racial diversity, market-sensitive zoning policies that reinforce these outcomes will be likely to prevail, particularly in buoyant real-estate markets like Santa Clara County.
An Economic History of Zoning and a Cure for its Exclusionary Effects
Authors: Fischel William A.
Published: April 2004

The paper outlines the 20th-century history of American zoning to explain how home-owners came to dominate its content and administration in most jurisdictions. Zoning's original purpose was to protect home-owners in residential areas from devaluation by industrial and apartment uses that had been made footloose by trucks and buses around 1910-20. Completion of the interstate highway system around 1970 made jobs and employees so mobile that suburbs adopted growth controls to stem the tide. If zoning is indeed a substitute for home-value insurance, it seems worthwhile to investigate the possibility of home-equity insurance to reduce the demand for exclusionary zoning.
Determinants of Suburban Development Controls: A Fischel Expedition
Authors: McDonald John F. , McMillen Daniel P.
Published: April 2004

In addition to land-use zoning, development controls in the suburban municipalities of metropolitan Chicago include architectural reviews, appearance regulations, historical preservation areas, enterprise zones, tax-increment financing districts, development impact fees and regulations pertaining to group homes, mobile homes, factory-assembled homes and adult uses. Results of a factor analysis imply that development control policies tend to cluster into quality development regulations, regulations aimed at lower-class development and growth controls. Subsequent econometric analysis suggests that larger suburbs make greater use of nearly all types of development control. Suburbs with new housing and high median household incomes tend to have complex single-family zoning provisions. Suburbs with lower incomes, larger minority populations and greater poverty rates are more likely to use Enterprise Zones and TIF districts, have more complex zoning for apartment buildings and tend not to have development impact fees.
Politics, Institutions and Local Land-use Regulation
Authors: Feiock Richard C.
Published: April 2004

This article investigates the factors that account for second-generation land-use restrictions that result from comprehensive planning processes. After a review of the evolution of growth management policy in the US variation among Florida counties in the adoption of development impact fees and regulatory complexity is examined. Political system institutions were found to be related to growth management policies as predicted by distributive theories of urban politics. In particular, elected mayor-commission government was linked to growth management. These results indicate that second-generation land-use regulation may be driven as much by the political incentives of local actors as the preferences of the median voter.
Heresthetics and Happenstance: Intentional and Unintentional Exclusionary Impacts of the Zoning Decision-making Process
Authors: Clingermayer James C.
Published: April 2004

This paper examines political and legal justifications for zoning and other land-use regulations that have exclusionary impacts. The paper argues that much exclusionary regulation is justified (and rationalised) by arguments that divert attention from the undesired incidence upon the poor and minorities by referring to other values (such as environmental protection, controlling urban sprawl, relieving traffic congestion, historical preservation and other 'good planning principles'). Sometimes this manipulation is deliberate and may be thought of as an example of the art of 'heresthetics'. At other times, this form of argument may be more coincidental (i.e. a 'happenstance'). Rationales for exclusionary zoning may be offered in good faith by policy-makers who are acting out of personal convictions or in response to the pressure from various political interests. Jurisdictions with homogeneous and small constituencies are conjectured to be more exclusionary in intent and will resort to heresthetics to justify zoning that redistributes wealth away from developers and low-income families and towards current property-owners. Jurisdictions with diverse and large populations are suggested to be less exclusionary in general, but may become more exclusionary and may resort to multiple, complicated rationales when their political environments are complex. Not only may the rationales become complex, but the decision-making process may become complicated as well, with multiple criteria under consideration at different levels of governmental organisation. This complexity may increase regulatory delay and offer greater numbers of opportunities for intervention by development opponents in administrative, legislative and judicial arenas. The likelihood of manipulation of any regulatory regime suggests that exclusion may never be achieved through a reform of zoning. Instead, more demand-oriented efforts to increase housing opportunities are recommended.
Local Land-use Controls and Demographic Outcomes in a Booming Economy
Authors: Quigley John M. , Raphael Steven , Rosenthal Larry A.
Published: April 2004

The article analyses the link between autarchic land-use policies adopted by local governments in California and the substantial redistribution of its population during the decade of the 1990s. Changes in population growth by racial and ethnic group in California cities are related to measures of the extent to which locally adopted policy favours expansion of the single-family housing stock. Controlling for the initial conditions of housing and labour markets by relying upon census measures for 1990, the paper accounts for the potential endogeneity of contemporaneous land-use policies by relying upon exogenous measures of the 'exclusivity' and 'pro-growth' propensities of the local public sector recorded by a state-wide survey in the early 1990s.
Urban Containment and Residential Segregation: A Preliminary Investigation
Authors: Nelson Arthur C. , Dawkins Casey J. , Sanchez Thomas W.
Published: April 2004

A fundamental purpose of traditional land-use controls is to exclude undesirable land uses from residential communities. However, such regulations have been shown to limit the ability of low-income households and people of colour to find suitable housing in decent neighbourhoods. Urban containment is an attempt to regulate land uses in ways that reduce if not eliminate social exclusion. This paper uses information from a nation-wide survey of metropolitan planning organisations to identify metropolitan areas with urban containment programmes in place. A theory is developed and a model is applied to 242 metropolitan statistical areas to test the hypothesis that areas with urban containment witnessed greater reductions in residential segregation than those without. Preliminary statistical investigations show this to be the case. Policy implications and an outline for further research are provided.
Moving Up by Moving Out? Planned Developments and Residential Segregation in California
Authors: Gordon Tracy M.
Published: April 2004

Individuals are increasingly opting to live in common interest developments (CIDs) such as condominiums, co-operatives and planned developments. Several commentators have linked this trend to increasing neighbourhood homogeneity and residential segregation. This paper investigates these claims for planned developments in California in 1990. Results indicate that planned developments are, on average, less diverse with respect to race but more diverse with respect to income due to greater representation among higher-income categories. The contribution of planned developments to overall metropolitan segregation, however, is minor. This finding is perhaps unsurprising in light of the relatively small proportion of the population living in planned developments as of 1990. As recent trends continue, it is conceivable that the effects of these communities on residential segregation will become more pronounced. Nevertheless, eliminating planned developments would not necessarily diminish segregation because these communities are but one mechanism for sorting behaviour.
Direct Democracy and Land Use Policy: Exchanging Public Goods for Development Rights
Authors: Gerber Elisabeth R. , Phillips Justin H.
Published: April 2004

To counter the power of pro-development interests, growth opponents in American communities have increasingly turned to the institutions of direct democracy. This study analyses the effects of one type of direct democracy-voter requirements for new development-on municipal growth. Analysing data from a sample of California communities, we consider the impact of voter requirements on the land use process and outcomes. We find that—in general-voter requirements fail to stop new development; property owners and developers can and do adapt to the constraints created by these direct democracy institutions. We also find, however, that voter requirements change the land use process in important ways. Specifically, they change the way developers interact with interest groups in the community and force developers to compensate current residents for enduring some of the negative aspects of growth.
Exclusionary Land-use Regulations within Suburban Communities: A Review of the Evidence and Policy Prescriptions
Authors: Ihlanfeldt Keith R.
Published: April 2004

This paper reviews the literature related to five questions that we would like to have answered about local land-use regulations that exclude lower-income households from suburban communities. Also reviewed are the policy options for dealing with this exclusion.
A Case Report of a Choroid Plexus Carcinoma Spontaneously Occurring in the Right Lateral Ventricle of a 14-Week-Old, Female Donryu Rat
Authors: Shimomoto Takasumi , Yoshida Midori , Takahashi Masakazu , Uematsu Fumiyuki , Maekawa Akihiko , Nakae Dai
Published: April 2004

We encountered a brain tumor arising in the right lateral ventricle of a 14-week-old, female Donryu rat and investigated its histological and immunohistochemical characteristics. Macroscopically, the tumor appeared as a grayish mass with a size of 10 mm in diameter, present in front of the right hemicerebrum and well circumscribed on the cut surface. Histological examination revealed the tumor to be a hypercellular mass occupying the front part of the right lateral ventricle and expanding into the area in front of the hemicerebrum, continuing to the ependymal area at its edge. The tumor was constituted by columnar- or pleomorphic-shaped, highly atypical cells of epithelial origin surrounding fibrovascular cores as single or multiple cell layers. Growth was papillary with high proliferating activity. Immunohistochemically, the tumor cells proved positive for cytokeratin but negative for vimentin, S100 protein or glial fibrillary acidic protein, a profile characteristic for the epithelial cells of the choroid plexus, whereas the ependymal cells were found to be positive for all 4 items. In conclusion, the present tumor was diagnosed as a rat choroid plexus carcinoma, only the third such case to be reported in the world literature, with particular features.
Antibodies that Label Paraffin-Embedded Mouse Tissues: A Collaborative Endeavor
Authors: Mikaelian Igor , Nanney Lillian B. , Parman Kelly S. , Kusewitt Donna F. , Ward Jerrold M. , Näf Dieter , Krupke Debra M. , Eppig Janan T. , Bult Carol J. , Seymour Rose , Ichiki Tsutomu , Sundberg John P.
Published: April 2004

Histology and immunohistochemistry are important tools in the study of human diseases and their respective animal models. The study of mouse models has been hampered by the absence of a large set of mouse-specific antibodies adapted to paraffin-embedded tissues. A total of 196 antibodies were tested on paraffin-embedded mouse tissues preserved in five different fixatives (Fekete's acid-alcohol-formalin, 10% neutral buffered formalin, 4% paraformaldehyde, IHC Zinc Fixative, and Bouin's fixative). The antibodies were targeted to proteins of the cytoplasm (n = 100), plasma membrane (n = 48), nucleus (n = 36), extracellular compartment (n = 5), cytoplasm/cell membrane (n = 4), and viral proteins (n = 3). A total of 83 antibodies provided an adequate signal to noise ratio. Of these, adequate labeling required heat-mediated epitope retrieval or enzymatic digestion for 32 and 8 antibodies, respectively. Epitope recognition was best for tissues fixed with Fekete's acid-alcohol-formalin. However, some proteins could be detected only in IHC Zinc Fixative, confirming that there is no single fixative suitable for the preservation of all epitopes. Four of 13 antibodies that failed to label their cellular targets on tissue sections successfully labeled whole-mount tissues, indicating that tissue processing plays an important role in epitope degradation. Regularly updated information on immunohistochemistry of normal and neoplastic mouse tissues is accessible online at ( http://tumor.informatics.jax.org ); links to antibody suppliers’ web sites are provided.
Evaluation of the Xpa-Deficient Transgenic Mouse Model for Short-Term Carcinogenicity Testing: 9-Month Studies with Haloperidol, Reserpine, Phenacetin, and D-Mannitol
Authors: Lina Ben A.R. , Woutersen Ruud A. , Bruijntjes Joost P. , Van Benthem Jan , Van Den Berg Jolanda A.H. , Monbaliu Johan , Thoolen Bob J.J.M. , Beems Rudolf B. , Van Kreijl Coen F.
Published: April 2004

As part of the international evaluation program coordinated by ILSI/HESI, the potential of DNA repair deficient Xpa- /- mice and the double knockout Xpa- /- .p53+ /- mice for short term carcinogenicity assays was evaluated. For comparison also wild-type C57BL/6 mice (WT) were included in these studies. Four test compounds were administered to groups of 15 male and 15 female Xpa- /- mice, Xpa- /- .p53+ /- mice and WT mice for 39 weeks. The model compounds investigated were haloperidol, reserpine (nongenotoxic rodent carcinogens, putative human noncarcinogens), phenacetin (genotoxic rodent carcinogen, suspected human carcinogen), and D-mannitol (noncarcinogen in rodents and humans). The test compounds were administered as admixture to rodent diet at levels up to 25 mg/kg diet for haloperidol, 7.5 mg/kg diet for reserpine, 0.75% for phenacetin, and 10% for D-mannitol. These levels included the maximum tolerable dose (MTD). Survival was not affected with any of the test compounds. Haloperidol, reserpine and D-mannitol were negative in the carcinogenicity assay with Xpa- /- and Xpa- /- .p53+ /- mice, showing low and comparable tumor incidences in controls and high-dose animals. The results obtained with phenacetin may be designated equivocal in Xpa- /- .p53+ /- mice, based on the occurrence of a single rare tumor in the target organ (kidney) accompanied by a low incidence of hyperplastic renal lesions and a high incidence of karyomegaly. These results are in agreement with the currently known carcinogenic potential of the 4 test compounds in humans.
Histopathological and Molecular Changes During Apoptosis Produced by 7H-Dibenzo[c,g]-Carbazole in Mouse Liver
Authors: Martín-Burriel Inmaculada , Roome Nigel O. , Dorchies Olivier , Prenez Annick
Published: April 2004

The topical administration of 7H-dibenzo[c,g]carbazole (7H-DBC) at very low but repeated doses causes genotoxic effects such as DNA adduct formation and produces hepatocellular apoptosis in mouse liver. The purpose of this work was to investigate the alterations in gene expression and protein levels of biomarkers associated with the p53 pathway in mouse liver after exposure to cumulative low doses of 7H-DBC by skin paint applications. The compound was administered topically at the dose of 13.35 μg per animal every 2 days to give either 6, 8, 10, or 12 applications. Animals were sacrificed 48 hours after the different treatments. The apoptotic index increased with the number of applications, with a major proportion of apoptotic cells in the periportal areas. A significant increase of Bax mRNA and protein expression was observed after the 8th application whereas the expression of mRNA levels of Fas and p53 did not show significant differences between treated and control animals. Nuclear staining of p53 was detected in hepatocyte nuclei showing the activation of this protein. Later in the apoptosis process we observed the up-regulation of TGF- β1 in parenchymal cells. In addition to the induction of the p53 apoptosis pathway in vivo by 7H-DBC, we have observed molecular changes related to cell proliferation such as the overexpression of the antiapoptotic gene Bcl-2.
Mucosal Toxicity Studies of a Gel Formulation of Native Pokeweed Antiviral Protein
Authors: D'Cruz Osmond J. , Waurzyniak Barbara , Uckun Fatih M.
Published: April 2004

Pokeweed antiviral protein (PAP), a 29-kDa plant-derived protein isolated from Phytolacca americana, is a promising nonspermicidal broad-spectrum antiviral microbicide. This study evaluated the mucosal toxicity potential of native PAP in the in vivo rabbit vaginal irritation model as well as the in vitro reconstituted human vaginal epithelial tissue model. Twenty-two New Zealand white rabbits in 4 subgroups were exposed intravaginally to a gel with and without 0.01, 0.1, or 1.0% native PAP for 10 consecutive days. The dose of PAP used represented nearly 200- to 20,000 times its in vitro anti-HIV IC50 value. Animals were euthanized on day 11 and vaginal tissues were evaluated for histologic and immunohistochemical evidence of mucosal toxicity, cellular inflammation, and hyperplasia. Blood was analyzed for changes in hematology and clinical chemistry profiles. Reconstituted human vaginal epithelial tissue grown on membrane filters was exposed to 0.1, 0.1, or 1.0% native PAP in medium or topically via a gel for 24 hours and tissue damage was evaluated by histological assessment. In the in vivo rabbit vaginal irritation model, half of all PAP-treated rabbits (8/16) exhibited an acceptable range of vaginal mucosal irritation (total score <8 out of a possible 16), whereas nearly a third of PAP-treated rabbits (5/16) developed moderate to marked vaginal mucosal irritation (total score >11). However, no treatment-related adverse effects were seen in hematological or clinical chemistry measurements. Furthermore, in vitro exposure of a 3-dimensional human vaginal tissue grown on polycarbonate membrane filters to identical concentrations of PAP either added to culture medium or applied topically via gel formulation did not result in direct toxicity as determined by histologic evaluation. These findings indicate careful monitoring of vaginal irritation will be required in the clinical development of PAP as a nonspermicidal microbicide.
Sequential Analysis of Development of Invasive Thyroid Follicular Cell Carcinomas in Inflamed Capsular Regions of Rats Treated with Sulfadimethoxine after N-bis(2-hydroxypropyl)nitrosamine-initiation
Authors: Imai Toshio , Onose Jun-Ichi , Hasumura Mai , Ueda Makoto , Takizawa Tamotsu , Hirose Masao
Published: April 2004

A 2-stage thyroid follicular carcinogenesis model in rats initiated with N-bis(2-hydroxypropyl)nitrosamine (DHPN) is widely used to detect modifying effects of chemicals on thyroid carcinogenesis. A number of goitrogens are known to strongly promote carcinogenesis, and the carcinomas often originate adjacent to the thyroid capsule and show invasive growth into the capsule or adjacent tissues. To clarify mechanisms of progression to invasive carcinomas, we sequentially evaluated histopathological and immunohistochemical characteristics of thyroids in male F344 rats treated with sulfadimethoxine (SDM, 0.1% in drinking water) for 0—10 weeks beginning 1 week after DHPN initiation (2800 mg/kg body weight, single s.c. injection). In DHPN-SDM-treated rats, multiple focal hyperplasias and adenomas developed in thyroid follicular parenchyma at weeks 4 to 6. Apart from the proliferative lesions, capsular thickening with inflammatory cell infiltration, mainly consisting of macrophages, and migration of follicular epithelium into the capsule were also observed. Focal hyperplasias/adenomas adjacent to the capsule progressively developed to invasive carcinomas at weeks 6 to 10. In thyroid parenchyma, malignant lesions were seldom observed. With SDM-treatment alone, although no neoplastic lesions were observed, capsular thickening with inflammation and epithelial migration resulted in intracapsular residual follicles. Intracapsular residual follicular cells as well as invasive and intrathyroidal carcinoma cells generally showed increased cell proliferative activity, coincidental with cytoplasmic/nuclear positivity for β-catenin. These results suggested that β -catenin activation related to capsular inflammation may play a role in development of invasive carcinomas but is insufficient for tumor formation by itself. Whether this is associated with mutations in the β-catenin gene remains to be clarified.
Image Compression in Morphometry Studies Requiring 21 CFR Part 11 Compliance: Procedure Is Key with TIFFs and Various JPEG Compression Strengths
Authors: Tengowski Mark W.
Published: April 2004

This study aims to compare the integrity and reproducibility of measurements created from uncompressed and compressed digital images in order to implement compliance with 21 CFR Part 11 for image analysis studies executed using 21 CFR Part 58 compliant capture systems. Images of a 400-mesh electron microscope grid and H&E stained rat liver tissue were captured on an upright microscope with digital camera using commercially available analysis software. Digital images were stored as either uncompressed TIFFs or in one of five different levels of JPEG compression. The grid images were analyzed with automatic detection of bright objects while the liver images were segmented using color cube-based morphometry techniques, respectively, using commercially-available image analysis software? When comparing the feature-extracted measurements from the TIFF uncompressed to the JPEG compressed images, the data suggest that JPEG compression does not alter the accuracy or reliability to reproduce individual data point measurements in all but the highest compression levels. There is, however, discordance if the initial measure was obtained with a TIFF format and subsequently saved as one of the JPEG levels, suggesting that the use of compression must precede feature extraction. It is a common practice in software packages to work with TIFF uncompressed images. However, this study suggests that the use of JPEG compression as part of the analysis work flow was an acceptable practice for these images and features. Investigators applying image file compression to other organ images will need to validate the utility of image compression in their work flow. A procedure to digitally acquire and JPEG compress images prior to image analysis has the potential to reduce file archiving demands without compromising reproducibility of data.