bluuebunny/crossref_metadata_2025 huggingface dataset:
Oxidized, deaminated cytosines are a source of C → T transitions
in vivo
Authors: Kreutzer Deborah A. , Essigmann John M.
Published: July 2002

The most common base substitution arising from oxidative damage of DNA is a GC → AT transition. In an effort to determine the oxidized lesion(s) that gives rise to this mutation, the mutagenicity of three oxidized cytosines, 5-hydroxycytosine, 5-hydroxyuracil, and uracil glycol, were investigated in
Escherichia coli
. An M13 viral genome was constructed to contain a single oxidized cytosine at a specific site. Replication
in vivo
of the single-stranded genomes yielded mutation frequencies of 0.05%, 83%, and 80% for 5-hydroxycytosine, 5-hydroxyuracil, and uracil glycol, respectively. The predominant mutation observed was C → T. A model for C → T oxidative mutagenesis is suggested in which initial cytosine oxidation is followed by deamination to a poorly repaired uracil derivative that is strongly miscoding during replication.
The role of enzyme distortion in the single displacement mechanism of family 19 chitinases
Authors: Brameld Ken A. , Goddard William A.
Published: July 2002

By using molecular dynamics simulations, we have examined the binding of a hexaNAG substrate and two potential hydrolysis intermediates (an oxazoline ion and an oxocarbenium ion) to a family 19 barley chitinase. We find the hexaNAG substrate binds with all sugars in a chair conformation, unlike the family 18 chitinase which causes substrate distortion. Glu 67 is in a position to protonate the anomeric oxygen linking sugar residues D and E whereas Asn 199 serves to hydrogen bond with the C2′
N
-acetyl group of sugar D, thus preventing the formation of an oxazoline ion intermediate. In addition, Glu 89 is part of a flexible loop region allowing a conformational change to occur within the active site to bring the oxocarbenium ion intermediate and Glu 89 closer by 4–5 Å. A hydrolysis product with inversion of the anomeric configuration occurs because of nucleophilic attack by a water molecule that is coordinated by Glu 89 and Ser 120. Issues important for the design of inhibitors specific to family 19 chitinases over family 18 chitinases also are discussed.
Targeted mutation reveals a central role for SR-BI in hepatic selective uptake of high density lipoprotein cholesterol
Authors: Varban Mariet Lee , Rinninger Franz , Wang Nan , Fairchild-Huntress Victoria , Dunmore Judy H. , Fang Qing , Gosselin Michael L. , Dixon Kristen L. , Deeds James D. , Acton Susan L. , Tall Alan R. , Huszar Dennis
Published: July 2002

Scavenger receptor BI (SR-BI) is a cell surface receptor that binds high density lipoproteins (HDL) and mediates selective uptake of HDL cholesteryl esters (CE) in transfected cells. To address the physiological role of SR-BI in HDL cholesterol homeostasis, mice were generated bearing an SR-BI promoter mutation that resulted in decreased expression of the receptor in homozygous mutant (designated SR-BI att) mice. Hepatic expression of the receptor was reduced by 53% with a corresponding increase in total plasma cholesterol levels of 50–70% in SR-BI att mice, attributable almost exclusively to elevated plasma HDL. In addition to increased HDL-CE, HDL phospholipids and apo A-1 levels were elevated, and there was an increase in HDL particle size in mutant mice. Metabolic studies using HDL bearing nondegradable radiolabels in both the protein and lipid components demonstrated that reducing hepatic SR-BI expression by half was associated with a decrease of 47% in selective uptake of CE by the liver, and a corresponding reduction of 53% in selective removal of HDL-CE from plasma. Taken together, these findings strongly support a pivotal role for hepatic SR-BI expression in regulating plasma HDL levels and indicate that SR-BI is the major molecule mediating selective CE uptake by the liver. The inverse correlation between plasma HDL levels and atherosclerosis further suggests that SR-BI may influence the development of coronary artery disease.
Expression of human estrogen receptor-α and -β, progesterone receptor, and androgen receptor mRNA in normal and malignant ovarian epithelial cells
Authors: Lau Kin-Mang , Mok Samuel C. , Ho Shuk-Mei
Published: July 2002

Our understanding of the roles played by sex hormones in ovarian carcinogenesis has been limited by a lack of data concerning the mode of sex hormone action in human ovarian surface epithelial (HOSE) cells, the tissue of origin of >90% of ovarian cancers. We have compared the relative abundance of estrogen receptor (ER)α, ERβ, progesterone receptor (PR), and androgen receptor (AR) mRNA in four primary cultures of HOSE cells obtained from postmenopausal women to those found in late serous adenocarcinoma primary cell cultures and established ovarian cancer cell lines. We observed coexpression of ERα and ERβ mRNA along with AR and PR transcripts in normal HOSE cells and disruption of ERα mRNA expression as well as dramatic down-regulation of PR and AR transcript expression in most ovarian cancer cells. In contrast, levels of ERβ mRNA were unaffected by the malignant state. Additionally, a novel mutation involving a 32-bp deletion in exon 1 of ERα transcripts was detected in the SKOV3 cell line. This mutation would explain why SKOV3 was reported to be ER-positive but estrogen-insensitive. Taken together, these findings suggest that estrogens, signaling via either or both ER subtypes, may play an indispensable role in regulating normal HOSE cell functions. Therefore, loss of ERα, PR, and AR mRNA expression in HOSE cells may be responsible for neoplastic transformation in this cell type. In contrast, the roles played by ERβ in normal and malignant HOSE cells remain elusive. Finally, the coexistence of mutated ERα mRNA and normal ERβ transcripts in SKOV3 argues in favor of a dependency of ERβ action on functional ERαs.
Four intracellular genomes direct weevil biology: Nuclear, mitochondrial, principal endosymbiont, andWolbachia
Authors: Heddi Abdelaziz , Grenier Anne-Marie , Khatchadourian Chaqué , Charles Hubert , Nardon Paul
Published: July 2002

Cell physiology in the weevilSitophilus oryzaeis coordinated by three integrated genomes: nuclear, mitochondrial, and the “S. oryzaeprincipal endosymbiont” (SOPE). SOPE, a cytoplasmic bacterium (2 × 103bacteria per specialized bacteriocyte cell and 3 × 106bacteria per weevil) that belongs to the proteobacteria γ3-subgroup, is present in all weevils studied. We discovered a fourth prokaryotic genome in somatic and germ tissues of 57% of weevil strains of three species,S. oryzae, Sitophilus zeamais,andSitophilus granarius,distributed worldwide. We assigned this Gram-negative prokaryote to theWolbachiagroup (α-proteobacteria), on the basis of 16S rDNA sequence and fluorescencein situDNA–RNA hybridization (FISH). Both bacteria, SOPE andWolbachia, were selectively eliminated by combined heat and antibiotic treatments. Study of bacteria involvement in this insect’s genetics and physiology revealed that SOPE, which induces the specific differentiation of the bacteriocytes, increases mitochondrial oxidative phosphorylation through the supply of pantothenic acid and riboflavin. Elimination of this γ3-proteobacterium impairs many physiological traits. By contrast, neither the presence nor the absence ofWolbachiasignificantly affects the weevil’s physiology.Wolbachia, disseminated throughout the body cells, is in particularly high density in the germ cells, where it causes nucleocytoplasmic incompatibility. The coexistence of two distinct types of intracellular proteobacteria at different levels of symbiont integration in insects illustrates the genetic complexity of animal tissue. Furthermore, evolutionary timing can be inferred: first nucleocytoplasm, then mitochondria, then SOPE, and finallyWolbachia. Symbiogenesis, the genetic integration of long-term associated members of different species, in the weevil appears to be a mechanism of speciation (withWolbachia) and provides a means for animals to acquire new genes that permit better adaptation to the environment (with SOPE).
Wiskott-Aldrich syndrome protein regulates podosomes in primary human macrophages
Authors: Linder Stefan , Nelson David , Weiss Michael , Aepfelbacher Martin
Published: July 2002

Wiskott-Aldrich syndrome protein (WASp) is a hematopoietic-specific, multidomain protein whose mutation is responsible for the immunodeficiency disorder Wiskott-Aldrich syndrome. WASp contains a binding motif for the Rho GTPase CDC42Hs as well as verprolin/cofilin-like actin-regulatory domains, but no specific actin structure regulated by CDC42Hs-WASp has been identified. We found that WASp colocalizes with CDC42Hs and actin in the core of podosomes, a highly dynamic adhesion structure of human blood-derived macrophages. Microinjection of constitutively active V12CDC42Hs or a constitutively active WASp fragment consisting of the verprolin/cofilin-like domains led to the disassemly of podosomes. Conversely, macrophages from patients expressing truncated forms of WASp completely lacked podosomes. These findings indicate that WASp controls podosome assembly and, in cooperation with CDC42Hs, podosome disassembly in primary human macrophages.
Active hair-bundle movements can amplify a hair cell’s response to oscillatory mechanical stimuli
Authors: Martin Pascal , Hudspeth A. J.
Published: July 2002

To enhance their mechanical sensitivity and frequency selectivity, hair cells amplify the mechanical stimuli to which they respond. Although cell-body contractions of outer hair cells are thought to mediate the active process in the mammalian cochlea, vertebrates without outer hair cells display highly sensitive, sharply tuned hearing and spontaneous otoacoustic emissions. In these animals the amplifier must reside elsewhere. We report physiological evidence that amplification can stem from active movement of the hair bundle, the hair cell’s mechanosensitive organelle. We performed experiments on hair cells from the sacculus of the bullfrog. Using a two-compartment recording chamber that permits exposure of the hair cell’s apical and basolateral surfaces to different solutions, we examined active hair-bundle motion in circumstances similar to those
in vivo
. When the apical surface was bathed in artificial endolymph, many hair bundles exhibited spontaneous oscillations of amplitudes as great as 50 nm and frequencies in the range 5 to 40 Hz. We stimulated hair bundles with a flexible glass probe and recorded their mechanical responses with a photometric system. When the stimulus frequency lay within a band enclosing a hair cell’s frequency of spontaneous oscillation, mechanical stimuli as small as ±5 nm entrained the hair-bundle oscillations. For small stimuli, the bundle movement was larger than the stimulus. Because the energy dissipated by viscous drag exceeded the work provided by the stimulus probe, the hair bundles powered their motion and therefore amplified it.
Global response of
Saccharomyces cerevisiae
to an alkylating agent
Authors: Jelinsky Scott A. , Samson Leona D.
Published: July 2002

DNA chip technology enables simultaneous examination of how
≈6,200
Saccharomyces cerevisiae
gene transcript
levels, representing the entire genome, respond to environmental
change. By using chips bearing oligonucleotide arrays, we show that,
after exposure to the alkylating agent methyl methanesulfonate, ≈325
gene transcript levels are increased and ≈76 are decreased. Of the 21
genes that already were known to be induced by a DNA-damaging agent, 18
can be scored as inducible in this data set, and surprisingly, most of
the newly identified inducible genes are induced even more strongly
than these 18. We examined 42 responsive and 8 nonresponsive ORFs by
conventional Northern blotting, and 48 of these 50 ORFs responded as
they did by DNA chip analysis, with magnitudes displaying a correlation
coefficient of 0.79. Responsive genes fall into several expected and
many unexpected categories. Evidence for the induction of a program to
eliminate and replace alkylated proteins is presented.
Cytochrome P450 CYP1B1 determines susceptibility to 7,12-dimethylbenz[
a
]anthracene-induced lymphomas
Authors: Buters Jeroen T. M. , Sakai Shuichi , Richter Thomas , Pineau Thierry , Alexander David L. , Savas Uzen , Doehmer Johannes , Ward Jerrold M. , Jefcoate Colin R. , Gonzalez Frank J.
Published: July 2002

CYP1B1-null mice, created by targeted gene disruption in embryonic stem cells, were born at the expected frequency from heterozygous matings with no observable phenotype, thus establishing that CYP1B1 is not required for mouse development. CYP1B1 was not detectable in cultured embryonic fibroblast (EF) or in different tissues, such as lung, of the CYP1B1-null mouse treated with the aryl hydrocarbon receptor agonist 2,3,7,8-tetrachlorodibenzo-
p
-dioxin whereas the equivalent wild-type EF cells express basal and substantial inducible CYP1B1 and lung expresses inducible CYP1B1. CYP1A1 is induced to far higher levels than CYP1B1 in liver, kidney, and lung in wild-type mice and is induced to a similar extent in CYP1B1-null mice. 7,12-dimethylbenz[
a
]anthracene (DMBA) was toxic in wild-type EFs that express CYP1B1 but not CYP1A1. These cells effectively metabolized DMBA, consistent with CYP1B1 involvement in producing the procarcinogenic 3,4-dihydrodiol as a major metabolite, whereas CYP1B1-null EF showed no significant metabolism and were resistant to DMBA-mediated toxicity. When wild-type mice were administered high levels of DMBA intragastrically, 70% developed highly malignant lymphomas whereas only 7.5% of CYP1B1-null mice had lymphomas. Skin hyperplasia and tumors were also more frequent in wild-type mice. These results establish that CYP1B1, located exclusively at extrahepatic sites, mediates the carcinogenicity of DMBA. Surprisingly, CYP1A1, which has a high rate of DMBA metabolism
in vitro
, is not sufficient for this carcinogenesis, which demonstrates the importance of extrahepatic P450s in determining susceptibility to chemical carcinogens and validates the search for associations between P450 expression and cancer risk in humans.
Conformational changes in tertiary structure near the ligand binding site of an integrin I domain
Authors: Oxvig Claus , Lu Chafen , Springer Timothy A.
Published: July 2002

For efficient ligand binding, integrins must be activated. Specifically, a conformational change has been proposed in a ligand binding domain present within some integrins, the inserted (I) domain [Lee, J., Bankston, L., Arnaout, M. & Liddington, R. C. (1995)Structure (London)3, 1333–1340]. This proposal remains controversial, however, despite extensive crystal structure studies on the I domain [Lee, J., Bankston, L., Arnaout, M. & Liddington, R. C. (1995)Structure (London)3, 1333–1340; Liddington, R. & Bankston, L. (1998)Structure (London)6, 937–938; Qu, A. & Leahy, D. J. (1996)Structure (London)4, 931–942; and Baldwin, E. T., Sarver, R. W., Bryant, G. L., Jr., Curry, K. A., Fairbanks, M. B., Finzel, B. C., Garlick, R. L., Heinrikson, R. L., Horton, N. C. & Kelly, L. L. (1998)Structure (London)6, 923–935]. By defining the residues present in the epitope of a mAb against the human Mac-1 integrin (αMβ2, CD11b/CD18) that binds only the active receptor, we provide biochemical evidence that the I domain itself undergoes a conformational change with activation. This mAb, CBRM1/5, binds the I domain very close to the ligand binding site in a region that is widely exposed regardless of activation as judged by reactivity with other antibodies. The conformation of the epitope differs in two crystal forms of the I domain, previously suggested to represent active and inactive receptor. Our data suggests that conformational differences in the I domain are physiologically relevant and not merely a consequence of different crystal lattice interactions. We also demonstrate that the transition between the two conformational states depends on species-specific residues at the bottom of the I domain, which are proposed to be in an interface with another integrin domain, and that this transition correlates with functional activity.
Potential effects of gas hydrate on human welfare
Authors: Kvenvolden Keith A.
Published: July 2002

For almost 30 years. serious interest has been directed toward natural gas hydrate, a crystalline solid composed of water and methane, as a potential (i) energy resource, (ii) factor in global climate change, and (iii) submarine geohazard. Although each of these issues can affect human welfare, only (iii) is considered to be of immediate importance. Assessments of gas hydrate as an energy resource have often been overly optimistic, based in part on its very high methane content and on its worldwide occurrence in continental margins. Although these attributes are attractive, geologic settings, reservoir properties, and phase-equilibria considerations diminish the energy resource potential of natural gas hydrate. The possible role of gas hydrate in global climate change has been often overstated. Although methane is a “greenhouse” gas in the atmosphere, much methane from dissociated gas hydrate may never reach the atmosphere, but rather may be converted to carbon dioxide and sequestered by the hydrosphere/biosphere before reaching the atmosphere. Thus, methane from gas hydrate may have little opportunity to affect global climate change. However, submarine geohazards (such as sediment instabilities and slope failures on local and regional scales, leading to debris flows, slumps, slides, and possible tsunamis) caused by gas-hydrate dissociation are of immediate and increasing importance as humankind moves to exploit seabed resources in ever-deepening waters of coastal oceans. The vulnerability of gas hydrate to temperature and sea level changes enhances the instability of deep-water oceanic sediments, and thus human activities and installations in this setting can be affected.
Health impacts of domestic coal use in China
Authors: Finkelman Robert B. , Belkin Harvey E. , Zheng Baoshan
Published: July 2002

Domestic coal combustion has had profound adverse effects on the
health of millions of people worldwide. In China alone several hundred
million people commonly burn raw coal in unvented stoves that permeate
their homes with high levels of toxic metals and organic compounds. At
least 3,000 people in Guizhou Province in southwest China are suffering
from severe arsenic poisoning. The primary source of the arsenic
appears to be consumption of chili peppers dried over fires fueled with
high-arsenic coal. Coal samples in the region were found to contain up
to 35,000 ppm arsenic. Chili peppers dried over high-arsenic coal fires
adsorb 500 ppm arsenic on average. More than 10 million people in
Guizhou Province and surrounding areas suffer from dental and skeletal
fluorosis. The excess fluorine is caused by eating corn dried over
burning briquettes made from high-fluorine coals and high-fluorine clay
binders. Polycyclic aromatic hydrocarbons formed during coal combustion
are believed to cause or contribute to the high incidence of esophageal
and lung cancers in parts of China. Domestic coal combustion also has
caused selenium poisoning and possibly mercury poisoning. Better
knowledge of coal quality parameters may help to reduce some of these
health problems. For example, information on concentrations and
distributions of potentially toxic elements in coal may help delineate
areas of a coal deposit to be avoided. Information on the modes of
occurrence of these elements and the textural relations of the minerals
and macerals in coal may help predict the behavior of the potentially
toxic components during coal combustion.
Rapid pole-to-pole oscillation of a protein required for directing division to the middle of
Escherichia coli
Authors: Raskin David M. , de Boer Piet A. J.
Published: July 2002

Accurate placement of the division septum at the midpoint of
Escherichia coli
cells requires the combined action of a general division inhibitor (MinC), a site-specific suppressor of division inhibition (MinE), and an ATPase (MinD) that is required for proper functioning of both MinC and MinE. We previously showed that a functional MinE-Gfp fusion accumulates in a ring structure at/near the middle of cells. Here we show that functional Gfp-MinD accumulates alternately in either one of the cell halves in what appears to be a rapidly oscillating membrane association-dissociation cycle imposed by MinE. The results indicate that MinD represents a novel type of dynamic cellular element in bacteria, with multiple roles in directing the division apparatus to the middle of the cell.
BRCA1 interacts with components of the histone deacetylase complex
Authors: Yarden Ronit I. , Brody Lawrence C.
Published: July 2002

Germ-line mutations in the
BRCA1
tumor-suppressor gene are associated with an increased susceptibility to breast and ovarian cancer. BRCA1 contains a carboxyl-terminal domain (BRCT) that is shared with several other proteins involved in maintaining genome integrity. In an effort to understand the function of BRCA1, we sought to isolate proteins that interact with the BRCT domain. Purified BRCT polypeptide was used as a probe to screen a human placenta cDNA expression library by Far Western analysis. Here we report that BRCA1 interacts
in vivo
and
in vitro
with the Rb-binding proteins, RbAp46 and RbAp48, as well as with Rb. Moreover, the BRCT domain associates with the histone deacetylases HDAC1 and HDAC2. These results demonstrate that BRCA1 interacts with components of the histone deacetylase complex, and therefore may explain the involvement of BRCA1 in multiple processes such as transcription, DNA repair, and recombination.
Estrogen receptors α and β in the rodent mammary gland
Authors: Saji Shigehira , Jensen Elwood V. , Nilsson Stefan , Rylander Tove , Warner Margaret , Gustafsson Jan-Åke
Published: July 2002

An obligatory role for estrogen in growth, development, and functions of the mammary gland is well established, but the roles of the two estrogen receptors remain unclear. With the use of specific antibodies, it was found that both estrogen receptors, ERα and ERβ, are expressed in the rat mammary gland but the presence and cellular distribution of the two receptors are distinct. In prepubertal rats, ERα was detected in 40% of the epithelial cell nuclei. This decreased to 30% at puberty and continued to decrease throughout pregnancy to a low of 5% at day 14. During lactation there was a large induction of ERα with up to 70% of the nuclei positive at day 21. Approximately 60–70% of epithelial cells expressed ERβ at all stages of breast development. Cells coexpressing ERα and ERβ were rare during pregnancy, a proliferative phase, but they represented up to 60% of the epithelial cells during lactation, a postproliferative phase. Western blot analysis and sucrose gradient centrifugation confirmed this pattern of expression. During pregnancy, the proliferating cell nuclear antigen was not expressed in ERα-positive cells but was observed in 3–7% of ERβ-containing cells. Because more than 90% of ERβ-bearing cells do not proliferate, and 55–70% of the dividing cells have neither ERα nor ERβ, it is clear that the presence of these receptors in epithelial cells is not a prerequisite for estrogen-mediated proliferation.
Repression of human papillomavirus oncogenes in HeLa cervical carcinoma cells causes the orderly reactivation of dormant tumor suppressor pathways
Authors: Goodwin Edward C. , DiMaio Daniel
Published: July 2002

Most cervical carcinomas express high-risk human papillomaviruses
(HPVs) E6 and E7 proteins, which neutralize cellular tumor suppressor
function. To determine the consequences of removing the E6 and E7
proteins from cervical cancer cells, we infected HeLa cells, a cervical
carcinoma cell line that contains HPV18 DNA, with a recombinant virus
that expresses the bovine papillomavirus E2 protein. Expression of the
E2 protein resulted in rapid repression of HPV E6 and E7 expression,
followed ≈12 h later by profound inhibition of cellular DNA
synthesis. Shortly after E6/E7 repression, there was dramatic
posttranscriptional induction of p53. Two p53-responsive genes, mdm2
and p21, were induced with slightly slower kinetics than p53 and
appeared to be functional, as assessed by inhibition of
cyclin-dependent kinase activity and p53 destabilization. There was
also dramatic posttranscriptional induction of p105
Rb
and
p107 after E6/E7 repression, followed shortly thereafter by induction
of p130. By 24 h after infection, only hypophosphorylated
p105
Rb
was detectable and transcription of several
Rb/E2F-regulated genes was dramatically repressed. Constitutive
expression of the HPV16 E6/E7 genes alleviated E2-induced growth
inhibition and impaired activation of the Rb pathway and repression of
E2F-responsive genes. This dynamic response strongly suggests that the
p53 and Rb tumor suppressor pathways are intact in HeLa cells and that
repression of HPV E6 and E7 mobilizes these pathways in an orderly
fashion to deliver growth inhibitory signals to the cells. Strikingly,
the major alterations in the cell cycle machinery underlying cervical
carcinogenesis can be reversed by repression of the
endogenous HPV oncogenes.
Single-target molecule detection with nonbleaching multicolor optical immunolabels
Authors: Schultz Sheldon , Smith David R. , Mock Jack J. , Schultz David A.
Published: July 2002

We introduce and demonstrate the use of colloidal silver plasmon-resonant particles (PRPs) as optical reporters in typical biological assays. PRPs are ultrabright, nanosized optical scatterers, which scatter light elastically and can be prepared with a scattering peak at any color in the visible spectrum. PRPs are readily observed individually with a microscope configured for dark-field microscopy, with white-light illumination of typical power. Here we illustrate the use of PRPs, surface coated with standard ligands, as target-specific labels in an
in situ
hybridization and an immunocytology assay. We propose that PRPs can replace or complement established labels, such as those based on radioactivity, fluorescence, chemiluminescence, or enzymatic/colorimetric detection that are used routinely in biochemistry, cell biology, and medical diagnostic applications. Moreover, because PRP labels are nonbleaching and bright enough to be rapidly identified and counted, an ultrasensitive assay format based on single-target molecule detection is now practical. We also present the results of a model sandwich immunoassay for goat anti-biotin antibody, in which the number of PRP labels counted in an image constitutes the measured signal.
Two terrestrial records of rapid climatic change during the glacial–Holocene transition (14,000– 9,000 calendar years B.P.) from Europe
Authors: Birks Hilary H. , Ammann Brigitta
Published: July 2002

Two independent multidisciplinary studies of climatic change during the glacial–Holocene transition (
ca.
14,000–9,000 calendar yr B.P.) from Norway and Switzerland have assessed organism responses to the rapid climatic changes and made quantitative temperature reconstructions with modern calibration data sets (transfer functions). Chronology at Kråkenes, western Norway, was derived from calibration of a high-resolution series of
14
C dates. Chronologies at Gerzensee and Leysin, Switzerland, were derived by comparison of δ
18
O in lake carbonates with the δ
18
O record from the Greenland Ice Core Project. Both studies demonstrate the sensitivity of terrestrial and aquatic organisms to rapid temperature changes and their value for quantitative reconstruction of the magnitudes and rates of the climatic changes. The rates in these two terrestrial records are comparable to those in Greenland ice cores, but the actual temperatures inferred apply to the terrestrial environments of the two regions.
Constitutive activation of Stat3 signaling abrogates apoptosis in squamous cell carcinogenesisin vivo
Authors: Grandis Jennifer Rubin , Drenning Stephanie D. , Zeng Qing , Watkins Simon C. , Melhem Mona F. , Endo Sohei , Johnson Daniel E. , Huang Leaf , He Yukai , Kim Jae D.
Published: July 2002

Field cancerization predisposes the upper aerodigestive tract mucosa to the formation of multiple primary tumors, when exposed to environmental carcinogens. Up-regulation of epidermal growth factor receptor occurs early in squamous cell carcinogenesis and is critical for the loss of growth control in a variety of human cancers, including head and neck squamous cell carcinomas. In these tumor cells in culture, epidermal growth factor receptor stimulation initiates signaling via persistent activation of selective STAT proteins. To determine the timing of Stat3 activation in head and neck carcinogenesis, we studied the expression and constitutive activation of Stat3 in tumors and normal mucosa from patients with head and neck cancer compared with mucosa from controls without cancer. Stat3 was up-regulated and constitutively activated in both primary human head and neck tumors as well as in normal mucosa from these cancer patients compared with control normal mucosa from patients without cancer.In vivoliposome-mediated gene therapy with a Stat3 antisense plasmid efficiently inhibited Stat3 activation, increased tumor cell apoptosis, and decreased Bcl-xLexpression in a head and neck xenograft model. These findings provide evidence that constitutively activated Stat3 is an early event in head and neck carcinogenesis that contributes to the loss of growth control by an anti-apoptotic mechanism.
Antigenic and genetic heterogeneity of
Borrelia burgdorferi
populations transmitted by ticks
Authors: Ohnishi Jun , Piesman Joseph , de Silva Aravinda M.
Published: July 2002

The genome of
Borrelia burgdorferi
encodes a large
number of lipoproteins, many of which are expressed only at certain
stages of the spirochete's life cycle. In the current study we
describe the
B. burgdorferi
population structure with
respect to the production of two lipoproteins [outer surface protein A
(OspA) and outer surface protein C (OspC)] during transmission from
the tick vector to the mammalian host. Before the blood meal, the
bacteria in the tick were a homogeneous population that mainly produced
OspA only. During the blood meal, the population became more
heterogeneous; many bacteria produced both OspA and OspC, whereas
others produced only a single Osp and a few produced neither Osp. From
the heterogeneous spirochetal population in the gut, a subset depleted
of OspA entered the salivary glands and stably infected the host at
time points >53 hr into the blood meal. We also examined genetic
heterogeneity at the
B. burgdorferi vlsE
locus before
and during the blood meal. In unfed ticks, the
vlsE
locus was stable and one predominant and two minor alleles were
detected. During the blood meal, multiple
vlsE
alleles
were observed in the tick. Tick feeding may increase recombination at
the
vlsE
locus or selectively amplify rare
vlsE
alleles present in unfed ticks. On the basis of our
data we propose a model, which is different from the established model
for
B. burgdorferi
transmission. Implicit in our model
is the concept that tick transmission converts a homogeneous spirochete
population into a heterogeneous population that is poised to infect the
mammalian host.
A 1.2-Å snapshot of the final step of bacterial cell wall biosynthesis
Authors: Lee Wenlin , McDonough Michael A. , Kotra Lakshmi P. , Li Zhi-Hong , Silvaggi Nicholas R. , Takeda Yoshifumi , Kelly Judith A. , Mobashery Shahriar
Published: July 2002

The cell wall imparts structural strength and shape to bacteria. It
is made up of polymeric glycan chains with peptide branches that are
cross-linked to form the cell wall. The cross-linking reaction,
catalyzed by transpeptidases, is the last step in cell wall
biosynthesis. These enzymes are members of the family of
penicillin-binding proteins, the targets of β-lactam antibiotics. We
report herein the structure of a penicillin-binding protein complexed
with a cephalosporin designed to probe the mechanism of the
cross-linking reaction catalyzed by transpeptidases. The 1.2-Å
resolution x-ray structure of this cephalosporin bound to the active
site of the bifunctional serine type
d
-alanyl-
d
-alanine
carboxypeptidase/transpeptidase (EC
3.4.16.4
) from
Streptomyces sp.
strain R61 reveals how the two peptide
strands from the polymeric substrates are sequestered in the active
site of a transpeptidase. The structure of this complex provides a
snapshot of the enzyme and the bound cell wall components poised for
the final and critical cross-linking step of cell wall biosynthesis.
Arabidopsis genomes uncoupled 5
(
GUN5
) mutant reveals the involvement of Mg-chelatase H subunit in plastid-to-nucleus signal transduction
Authors: Mochizuki Nobuyoshi , Brusslan Judy A. , Larkin Robert , Nagatani Akira , Chory Joanne
Published: July 2002

A plastid-derived signal plays an important role in the coordinated
expression of both nuclear- and chloroplast-localized genes that encode
photosynthesis-related proteins.
Arabidopsis GUN
(
g
enomes
un
coupled) loci have been
identified as components of plastid-to-nucleus signal transduction.
Unlike wild-type plants,
gun
mutants have nuclear
Lhcb1
expression in the absence of chloroplast
development. We observed a synergistic phenotype in some
gun
double-mutant combinations, suggesting there are at
least two independent pathways in plastid-to-nucleus signal
transduction. There is a reduction of chlorophyll accumulation in
gun4
and
gun5
mutant plants, and a
gun4gun5
double mutant shows an albino phenotype. We
cloned the
GUN5
gene, which encodes the ChlH subunit of
Mg-chelatase. We also show that
gun2
and
gun3
are alleles of the known photomorphogenic mutants,
hy1
and
hy2
, which are required for
phytochromobilin synthesis from heme. These findings suggest that
certain perturbations of the tetrapyrrole biosynthetic pathway generate
a signal from chloroplasts that causes transcriptional repression of
nuclear genes encoding plastid-localized proteins. The comparison of
mutant phenotypes of
gun5
and another Mg-chelatase
subunit (ChlI) mutant suggests a specific function for ChlH protein in
the plastid-signaling pathway.
The material and the symbolic in theorizing social stratification: issues of gender, ethnicity and class
Authors: Anthias Floya
Published: July 2002

Within most approaches to stratification gender and ethnicity are seen to pertain primarily to the symbolic or cultural realms, whilst class is regarded as pertaining to material inequality. This constructs gender and ethnic positioning as entailing honour, deference, worth, value and differential treatment (sometimes expressed through the notion of ‘status’), but the social relations around these are themselves not seen as constitutive of social stratification. In this paper I will rethink social stratification away from the polarity between the material and the symbolic, and argue that material inequality, as a set of outcomes relating to life conditions, life chances and solidary processes, is informed by claims and struggles over resources of different types, undertaken in terms of gender, ethnicity/race and class. This formulation allows us to include these categorial formations, alongside class, as important elements of social stratification i.e. as determining the allocation of socially valued resources and social places/locations.
‘Sites’ of resistance: alternative websites and state‐society relations 1
Authors: Ho K. C. , Baber Zaheer , Khondker Habibul
Published: July 2002

Much attention has been focused on Singapore's attempt to use information technology to build a knowledge‐based economy. This paper examines the implications of the unintended consequences of the Internet in the restructuring of state and society relations in Singapore.

We use the data on Singapore‐based and Singapore‐related websites to show (a) the diversity of positions expressed by civil society organizations, fringe groups and even mainstream segments of society; (b) the negotiation process between the state and civil society over various rights and how developments in cyber‐space have implications for ‘reality’; (c) how censorship and content regulation itself is a more complex multi‐dimensional process such that while local politics is regulated, the multi‐ethnic character of the resident population has led to greater religious tolerance such that religious groups banned in some countries have found a safe haven in Singapore and have used the city‐state as a strategic Internet node.
Tightness‐Looseness Revisited: Some Preliminary Analyses in Japan and the United States
Authors: Chan Darius K.‐S. , Gelfand Michele J. , Triandis Harry C. , Tzeng Oliver
Published: July 2002

The construct of tightness‐looseness is considered to be important in differentiating cultures (Pelto, 1968; Triandis, 1977, 1989). The objective of the present paper is to advance understanding of this construct. Specifically, we present a conceptual framework for the construct and formulate some general research hypotheses derived from our conceptualization. In addition, we examine one of our general hypotheses that cultures differing in the tight‐loose dimension will differ in the way language is used. Using a data set from Osgood, May, and Miron (1975), we compared the Japanese and the US samples of this study and found evidence supporting the hypothesis that Japan is a tighter culture, as compared to the USA. In addition to studying the construct of individualism‐collectivism, we suggest that tightness‐looseness is an important cultural dimension that can explain and predict cultural differences in many kinds of social behaviour.
Coase, Spatial Pricing and Self -organising Cities
Authors: Webster Chris , Wu Fulong
Published: July 2002

Modern computational techniques offer new horizons for urban economics in the form of agent-based simulation frameworks. This paper reports on a cellular automata (CA) simulation in which urban land transforms on the basis of locally optimal bargaining between developers and local communities (local governments). Because CA is an explicitly spatial modelling methodology, the space-time-specific paths to global equilibrium can be observed. Because it is an atomistic methodology (cells represent decision units), it is suitable for articulating microeconomic theories of urban processes including planning. We present a space-time-specific simulation of cities evolving under two alternative planning regimes. In one, the community has property rights and uses planning conditions, planning gain, impact fees and so on to ensure that each development occurs at a socially optimal density. This is a theoretically simplified rendition of the British development control system-simplified in the sense of acting from a position of perfect knowledge and having a single objective of optimising locational externalities. In the other simulation, developers have the right to develop but the community is allowed to make (rather than receive) compensatory payments in order to achieve socially optimal land-use patterns and densities. Decision-making in both systems is local and socially efficient. However, case-by-case ad hoc development control with compensatory exactions has the effect of steering development to the least-polluting locations. Although socially optimal densities can occur under alternative control regimes (as the second simulation demonstrates), the stylised British development control process acts like a decentralised locational pricing system and, by definition, yields a superior land-use pattern than any other style of planning system. At one level, our model articulates the Coasian invariance theorem-the same partial equilibrium outcome can be achieved whichever way the property rights (over land development) fall. At another level, the results demonstrate that in a spatial resource allocation problem such as land-use planning, global equilibrium is not independent of property rights. The total social product in the urban land economy is greater when the community holds rights over development.
Theorising Urban Playscapes: Producing, Regulating and Consuming Youthful Nightlife City Spaces
Authors: Chatterton Paul , Hollands Robert
Published: July 2002

This article develops a theoretical understanding of the relationship between young people and city space. More specifically, our focus concerns what we have termed 'urban playscapes'—young people's activities in bars, pubs, night-clubs and music venues within the night-time entertainment economy. The paper theoretically and empirically explores three interrelated aspects of these playscapes: production and the increasing role of a small number of large-scale corporate leisure and entertainment operators providing sanitised, 'branded' experiences ; regulation in which the development of urban playscapes can be understood through a night-time entertainment regime based around a modified relationship between state, developers and consumers, including enhanced forms of surveillance and control; and consumption which is characterised by segmentation and differentiation and based around more 'exclusive' and 'up-market' identities. We argue that these three aspects combine to create a dominant mode of 'mainstream' urban nightlife, with 'alternative' and 'residual' nightlife increasingly under threat or squeezed out. In conclusion, we discuss some of the interrelationships between production, regulation and consumption and suggest a number of potential future scenarios for nightlife development.
Governing the Spaces of Difference: Regulation and Globalisation in London
Authors: Goodwin Mark
Published: July 2002

This paper sets out a research agenda for using regulation theory to analyse local governance in the global city. It initially considers results from the 1991 census to explore social inequalities in London, and investigates how these differ from inequalities in other British metropolitan areas. The paper then looks at the changing nature of local governance in London, examining the notion of post-Fordist local governance as well as the idea of local governance in a post-Fordist society. Finally, the paper examines the ways in which the recent emergence of London as a global city articulates with the changing structures of governance. Whilst on the surface there appears to be a good fit between the restructuring of local governance and the globalisation of London's key economic sectors, the paper argues that there are both empirical and theoretical grounds for rejecting the claim that we are moving towards a new mode of regulation in the global city.
Urban Marginality in the Coming Millennium
Authors: Wacquant Loïc
Published: July 2002

This paper sketches a characterisation of the regime of urban marginality that has emerged in advanced societies since the close of the Fordist era, highlighting four logics that combine to produce it: a macrosocietal drift towards inequality, the mutation of wage labour (entailing both deproletarianisation and casualisation), the retrenchment of welfare states, and the spatial concentration and stigmatisation of poverty. The rise of this new marginality does not signal a transatlantic convergence on the American pattern: European neighbourhoods of relegation are deeply penetrated by the state and ethnoracial tensions in them are fuelled, not by the growing gap between immigrants and natives, but by their increasing propinquity in social and physical space. To cope with emergent forms of urban marginality, societies face a three-pronged alternative: they can patch up existing programmes of the welfare state, criminalise poverty via the punitive containment of the poor, or institute new social rights that sever subsistence from performance in the labour market.
The Past, Present and Future of School Improvement: Towards the Third Age
Authors: Hopkins David , Reynolds David
Published: July 2002

Abstract The article outlines the three phases that school improvement has been through since the mid‐1980s, paying particular attention to the characteristics of the recent ‘third age’ improvement paradigm. It is argued that these new models of improvement stand a chance of overcoming the difficulties that past improvement has had in affecting outcomes, and a number of areas of potential development for the paradigm are outlined for it to fulfil its promise, particularly in the areas of context specificity, focusing on learning in classrooms and concentrating on understanding ‘the capacity for improvement’. The contributions of ‘Third Age’ school improvement to resolving a number of conundrums that have affected the field are also explored.
‘Square‐girls', Femininity and the Negotiation of Academic Success in the Primary School
Authors: Renold Emma
Published: July 2002

Abstract Recent achievement debates in both the media and academic press have focused predominately on the apparent underachievement of boys. The relative ‘high achievement’ of girls has often been perceived as unproblematic and thus neglected, or achieved at the expense of boys. This article redresses the balance by redirecting the research focus to the processes and experiences of girls' academic achievements, particularly the intersection of and relationship between academic success and the construction of femininity. Drawing on data from an ethnographic study of two primary schools, the article traces the stories of four girls who were subordinately positioned as ‘square’ for their rejection of dominant modes of femininity and visible status as high academic achievers. Their experiences illuminate a broader debate on the fear and negativity associated with academic success and the contradiction of being ‘clever’ with being ‘feminine’.
Change and constancy in developmental contexts
Authors: Shanahan Michael J. , Sulloway Frank J. , Hofer Scott M.
Published: July 2002

As the 21st century begins, social forces are creating substantial diversity in developmental settings through the child’s early life course. Aconsiderable proportion of youth will experience disruptions in family structure, fluctuations in levels of economic resources, and residential moves that may involve changes in peer groups and schools. This paper reviews a set of conceptual distinctions that are well suited to the study of the dynamic properties of context. The paper also underscores the importance of integrating the life course with behavioural genetics to determine more accurately the joint contributions of environments like the family and genotypes to development. Because both person and context exhibit change and stability through time, an understanding of these complex interactions will require generative collaborations among developmentalists from diverse disciplinary backgrounds.
Authoritative and Authoritarian Parenting Practices and Social and School Performance in Chinese Children
Authors: Chen Xinyin , Dong Qi , Zhou Hong
Published: July 2002

The purpose of the study was to examine the relations between authoritative and authoritarian parenting styles and social and school adjustment in Chinese children. A sample of second grade children, aged eight years, and their parents in Beijing, People’s Republic of China, participated in this study. The children were group administered a peer assessment measure of social behaviour and a sociometric nomination measure. Teachers completed a rating scale on school-related social competence and problems for each child. Data concerning child-rearing practices were obtained from parents. In addition, information on children’s academic and social competence was obtained from school records. It was found that authoritarian parenting was associated positively with aggression and negatively with peer acceptance, sociability-competence, distinguished studentship and school academic achievement. In contrast, parental authoritative style was associated positively with indices of social and school adjustment and negatively with adjustment problems. The results indicated that, inconsistent with the argument in the literature (e.g. Steinberg, Dornbusch, & Brown, 1992), authoritative and authoritarian parenting practices were relevant to social and academic performance in Chinese children.