bluuebunny/crossref_metadata_2025 huggingface dataset:
Polyploid formation created unique avenues for response to selection in
Gossypium
(cotton)
Authors: Jiang Chun-xiao , Wright Robert J. , El-Zik Kamal M. , Paterson Andrew H.
Published: July 2002

A detailed restriction fragment length polymorphism map was used to determine the chromosomal locations and subgenomic distributions of quantitative trait loci (QTLs) segregating in a cross between cultivars of allotetraploid (AADD)
Gossypium hirsutum
(“Upland” cotton) and
Gossypium barbadense
(“Sea Island,” “Pima,” or “Egyptian” cotton) that differ markedly in the quality and quantity of seed epidermal fibers. Most QTLs influencing fiber quality and yield are located on the “D” subgenome, derived from an ancestor that does not produce spinnable fibers. D subgenome QTLs may partly account for the fact that domestication and breeding of tetraploid cottons has resulted in fiber yield and quality levels superior to those achieved by parallel improvement of “A” genome diploid cottons. The merger of two genomes with different evolutionary histories in a common nucleus appears to offer unique avenues for phenotypic response to selection. This may partly compensate for reduction in quantitative variation associated with polyploid formation and be one basis for the prominence of polyploids among extant angiosperms. These findings impel molecular dissection of the roles of divergent subgenomes in quantitative inheritance in many other polyploids and further exploration of both “synthetic” polyploids and exotic diploid genotypes for agriculturally useful variation.
Systemic biosynthesis of prostacyclin by cyclooxygenase (COX)-2: The human pharmacology of a selective inhibitor of COX-2
Authors: McAdam B. F. , Catella-Lawson F. , Mardini I. A. , Kapoor S. , Lawson J. A. , FitzGerald G. A.
Published: July 2002

Prostaglandins (PG) are synthesized by two isoforms of the enzyme PG G/H synthase [cyclooxygenase (COX)]. To examine selectivity of tolerated doses of an inhibitor of the inducible COX-2 in humans, we examined the effects of celecoxib on indices of COX-1-dependent platelet thromboxane (Tx) A
2
and on systemic biosynthesis of prostacyclin
in vivo
. Volunteers received doses of 100, 400, or 800 mg of celecoxib or 800 mg of a nonselective inhibitor, ibuprofen. Ibuprofen, but not celecoxib, significantly inhibited TxA
2
-dependent aggregation, induced
ex vivo
by arachidonic acid (83 ± 11% vs. 11.9 ± 2.2%;
P
< 0.005) and by collagen. Neither agent altered aggregation induced by thromboxane mimetic, U46619. Ibuprofen reduced serum TxB
2
(−95 ± 2% vs. −6.9 ± 4.2%;
P
< 0.001) and urinary excretion of the major Tx metabolite, 11-dehydro TxB
2
(−70 ± 9.9% vs. −20.3 ± 5.3%;
P
< 0.05) when compared with placebo. Despite a failure to suppress TxA
2
-dependant platelet aggregation, celecoxib had a modest but significant inhibitory effect on serum TxB
2
4 hr after dosing. By contrast, both ibuprofen and celecoxib suppressed a biochemical index of COX-2 activity (endotoxin induced PGE
2
in whole blood
ex vivo
) to a comparable degree (−93.3 ± 2% vs. −83 ± 6.1%). There was no significant difference between the doses of celecoxib on COX-2 inhibition. Celecoxib and ibuprofen suppressed urinary excretion of the prostacyclin metabolite 2,3 dinor 6-keto PGF
1α
. These data suggest that (
i
) platelet COX-1-dependent aggregation is not inhibited by up to 800 mg of celecoxib; (
ii
) comparable COX-2 inhibition is attained by celecoxib (100–800 mg) and ibuprofen (800 mg) after acute dosing; and (
iii
) COX-2 is a major source of systemic prostacyclin biosynthesis in healthy humans.
Suppression of angiogenesis and tumor growth by the inhibitor K1–5 generated by plasmin-mediated proteolysis
Authors: Cao Renhai , Wu Hua-Lin , Veitonmäki Niina , Linden Philip , Farnebo Jacob , Shi Guey-Yueh , Cao Yihai
Published: July 2002

Proteolytic enzymes are involved in generation of a number of endogenous angiogenesis inhibitors. Previously, we reported that angiostatin, a potent angiogenesis inhibitor, is a proteolytic fragment containing the first four kringle modules of plasminogen. In this report, we demonstrate that urokinase-activated plasmin can process plasminogen to release an angiogenesis inhibitor, K1–5 (protease-activated kringles 1–5). K1–5 inhibits endothelial-cell proliferation with a half-maximal concentration of approximately 50 pM. This inhibitory effect is endothelial-cell-specific and appears to be at least approximately 50-fold greater than that of angiostatin. A synergistic efficacy of endothelial inhibition was observed when angiostatin and kringle 5 (K5) were coincubated with capillary endothelial cells. The synergistic effect is comparable to that produced by K1–5 alone. Systemic treatment of mice with K1–5 at a low dose significantly blocked the fibroblast growth factor-induced corneal neovascularization, whereas angiostatin had no effect at the same dose. K1–5 also suppressed angiogenesis in chicken embryos. Systemic administration of K1–5 at a low dose at which angiostatin was ineffective significantly suppressed the growth of a murine T241 fibrosarcoma in mice. The antitumor effect correlates with the reduced neovascularization. These findings suggest that the plasmin-mediated proteolysis may be involved in the negative switch of angiogenesis.
Requirement for membrane lymphotoxin in natural killer cell development
Authors: Iizuka Koho , Chaplin David D. , Wang Yang , Wu Qiang , Pegg Lyle E. , Yokoyama Wayne M. , Fu Yang-Xin
Published: July 2002

Development of natural killer (NK) cells is thought to depend on interactions between NK progenitors and the bone marrow (BM) microenvironment; however, little is known about the molecular signals involved. Here we show that lymphotoxin (LT) provides an important signal for the development of both NK cells and NK/T cells. LTα
−/−
mice show marked reduction in splenic and BM NK and NK/T cell numbers and dramatically impaired NK and NK/T cell function. Mice deficient in either tumor necrosis factor receptor (TNFR)-I or TNFR-II have normal numbers of NK and NK/T cells, implying that neither of the TNFRs nor soluble LTα
3
is required for development of these cell types. Reciprocal BM transfers between LTα
−/−
and wild-type mice suggest that close interactions between membrane LT-expressing NK cell precursors and LT-responsive radioresistant stromal cells are necessary for NK cell development. When LT-deficient BM cells are incubated with IL-15, NK cells are formed. In addition, LT-deficient BM cells produce IL-15 after activation. Thus, membrane LT appears to deliver a signal for NK cell development that is either independent of IL-15 or upstream in the IL-15 pathway. These results reveal a novel function for membrane LT in NK and NK/T cell development. They also support a cellular and molecular mechanism by which NK cell precursors themselves deliver essential signals, through the membrane ligand, that induce the microenvironment to promote further NK cell and NK/T cell development.
Somatotopy of the lateral line projection in larval zebrafish
Authors: Alexandre Daniel , Ghysen Alain
Published: July 2002

We examined the topography of the lateral line primary projection in zebrafish larvae by double labeling. The projections of two identified neuromasts of the posterior lateral line are seen as two separate sets of fibers that show reproducible spatial relationships: the projection of the anterior neuromast is always ventrolateral to that of a more posteriorly located neuromast. The same rule applies to the projection of anterior lateral line neuromasts. The position of the neuromasts along the antero posterior axis of the fish therefore is represented in the central projection of the sensory neurons. This somatotopy is similar to, and may be at the origin of, the tonotopic projection of the cochlear hair cells in mammals.
Prevalent CD8+T cell response against one peptide/MHC complex in autoimmune diabetes
Authors: Anderson Brad , Park Bjung-Ju , Verdaguer Joan , Amrani Abdelaziz , Santamaria Pere
Published: July 2002

Spontaneous autoimmune diabetes in nonobese diabetic (NOD) mice is the result of a CD4+and CD8+T cell-dependent autoimmune process directed against the pancreatic beta cells. CD8+T cells play a critical role in the initiation and progression of diabetes, but the specificity and diversity of their antigenic repertoire remain unknown. Here, we define the structure of a peptide mimotope that elicits the proliferation, cytokine secretion, differentiation, and cytotoxicity of a diabetogenic H-2Kd-restricted CD8+T cell specificity (NY8.3) that uses a T cell receptor α (TCRα) rearrangement frequently expressed by CD8+T cells propagated from the earliest insulitic lesions of NOD mice (Vα17-Jα42 elements, often joined by the N-region sequence M-R-D/E). Stimulation of splenic CD8+T cells from single-chain 8.3-TCRβ-transgenic NOD mice with this mimotope leads to preferential expansion of T cells bearing an endogenously derived TCRα chain identical to the one used by their islet-associated CD8+T cells, which is also identical to the 8.3-TCRα sequence. Cytotoxicity assays using islet-derived CD8+T cell clones from nontransgenic NOD mice as effectors and peptide-pulsed H-2Kd-transfected RMA-S cells as targets indicate that nearly half of the CD8+T cells recruited to islets in NOD mice specifically recognize the same peptide/H-2Kdcomplex. This work demonstrates that beta cell-reactive CD8+T cells mount a prevalent response against a single peptide/MHC complex and provides one peptide ligand for CD8+T cells in autoimmune diabetes.
Evidence relating human verbal memory to hippocampal
N
-methyl-
d-
aspartate receptors
Authors: Grunwald Thomas , Beck Heinz , Lehnertz Klaus , Blümcke Ingmar , Pezer Nico , Kurthen Martin , Fernández Guillen , Van Roost Dirk , Heinze Hans J. , Kutas Marta , Elger Christian E.
Published: July 2002

Studies in rodents and nonhuman primates have linked the activity of
N
-methyl-
d
-aspartate (NMDA) receptors within the hippocampus to animals’ performance on memory-related tasks. However, whether these receptors are similarly essential for human memory is still an open question. Here we present evidence suggesting that hippocampal NMDA receptors, most likely within the CA1 region, do participate in human verbal memory processes. Words elicit a negative event-related potential (ERP) peaking around 400 ms within the anterior mesial temporal lobe (AMTL-N400). Ketamine, an NMDA-receptor antagonist, reduces the amplitude of the AMTL-N400 (in contrast to other hippocampal potentials) on initial presentation, eliminates the typical AMTL-N400 amplitude reduction with repetition, and leads to significant memory impairment. Of the various hippocampal subfields, only the density of CA1 neurons correlates with the word-related ERPs that are reduced by ketamine. Altogether, our behavioral, anatomical, and electrophysiological results indicate that hippocampal NMDA receptors are involved in
human
memory.
Induction of Purkinje fiber differentiation by coronary arterialization
Authors: Hyer Jeanette , Johansen Mikkel , Prasad Aparna , Wessels Andy , Kirby Margaret L. , Gourdie Robert G. , Mikawa Takashi
Published: July 2002

A synchronized heart beat is controlled by pacemaking impulses conducted through Purkinje fibers. In chicks, these impulse-conducting cells are recruited during embryogenesis from myocytes in direct association with developing coronary arteries. In culture, the vascular cytokine endothelin converts embryonic myocytes to Purkinje cells, implying that selection of conduction phenotype may be mediated by an instructive cue from arteries. To investigate this hypothesis, coronary arterial development in the chicken embryo was either inhibited by neural crest ablation or activated by ectopic expression of fibroblast growth factor (FGF). Ablation of cardiac neural crest resulted in ≈70% reductions (
P
< 0.01) in the density of intramural coronary arteries and associated Purkinje fibers. Activation of coronary arterial branching was induced by retrovirus-mediated overexpression of FGF. At sites of FGF-induced hypervascularization, ectopic Purkinje fibers differentiated adjacent to newly induced coronary arteries. Our data indicate the necessity and sufficiency of developing arterial bed for converting a juxtaposed myocyte into a Purkinje fiber cell and provide evidence for an inductive function for arteriogenesis in heart development distinct from its role in establishing coronary blood circulation.
Differences in frontal cortical activation by a working memory task after substitution of risperidone for typical antipsychotic drugs in patients with schizophrenia
Authors: Honey Garry D. , Bullmore Edward T. , Soni William , Varatheesan Malini , Williams Steve C. R. , Sharma Tonmoy
Published: July 2002

Antipsychotic drug treatment of schizophrenia may be complicated by side effects of widespread dopaminergic antagonism, including exacerbation of negative and cognitive symptoms due to frontal cortical hypodopaminergia. Atypical antipsychotics have been shown to enhance frontal dopaminergic activity in animal models. We predicted that substitution of risperidone for typical antipsychotic drugs in the treatment of schizophrenia would be associated with enhanced functional activation of frontal cortex. We measured cerebral blood oxygenation changes during periodic performance of a verbal working memory task, using functional MRI, on two occasions (baseline and 6 weeks later) in two cohorts of schizophrenic patients. One cohort (
n
= 10) was treated with typical antipsychotic drugs throughout the study. Risperidone was substituted for typical antipsychotics after baseline assessment in the second cohort (
n
= 10). A matched group of healthy volunteers (
n
= 10) was also studied on a single occasion. A network comprising bilateral dorsolateral prefrontal and lateral premotor cortex, the supplementary motor area, and posterior parietal cortex was activated by working memory task performance in both the patients and comparison subjects. A two-way analysis of covariance was used to estimate the effect of substituting risperidone for typical antipsychotics on power of functional response in the patient group. Substitution of risperidone increased functional activation in right prefrontal cortex, supplementary motor area, and posterior parietal cortex at both voxel and regional levels of analysis. This study provides direct evidence for significantly enhanced frontal function in schizophrenic patients after substitution of risperidone for typical antipsychotic drugs, and it indicates the potential value of functional MRI as a tool for longitudinal assessment of psychopharmacological effects on cerebral physiology.
Emergence of a highly pathogenic simian/human immunodeficiency virus in a rhesus macaque treated with anti-CD8 mAb during a primary infection with a nonpathogenic virus
Authors: Igarashi Tatsuhiko , Endo Yasuyuki , Englund George , Sadjadpour Reza , Matano Tetsuro , Buckler Charles , Buckler-White Alicia , Plishka Ron , Theodore Ted , Shibata Riri , Martin Malcolm
Published: July 2002

Although simian/human immunodeficiency virus (SHIV) strain DH12 replicates to high titers and causes immunodeficiency in pig-tailed macaques, virus loads measured in SHIV
DH12
-infected rhesus monkeys are consistently 100-fold lower and none of 22 inoculated animals have developed disease. We previously reported that the administration of anti-human CD8 mAb to rhesus macaques at the time of primary SHIV
DH12
infection resulted in marked elevations of virus loads. One of the treated animals experienced rapid and profound depletions of circulating CD4
+
T lymphocytes. Although the CD4
+
T cell number partially recovered, this monkey subsequently suffered significant weight loss and was euthanized. A tissue culture virus stock derived from this animal, designated SHIV
DH12R
, induced marked and rapid CD4
+
cell loss after i.v. inoculation of rhesus monkeys. Retrospective analyses of clinical specimens, collected during the emergence of SHIV
DH12R
indicated: (
i
) the input cloned SHIV remained the predominant virus during the first 5–7 months of infection; (
ii
) variants bearing only a few of the SHIV
DH12R
consensus changes first appeared 7 months after the administration of anti-CD8 mAb; (
iii
) high titers of neutralizing antibody directed against the input SHIV were detected by week 10 and persisted throughout the infection; and (
iv
) no neutralizing antibody against SHIV
DH12R
ever developed.
The heme-copper oxidases of
Thermus thermophilus
catalyze the reduction of nitric oxide: Evolutionary implications
Authors: Giuffrè Alessandro , Stubauer Gottfried , Sarti Paolo , Brunori Maurizio , Zumft Walter G. , Buse Gerhard , Soulimane Tewfik
Published: July 2002

We show that the heme-copper terminal oxidases of
Thermus thermophilus
(called
ba
3
and
caa
3
) are able to catalyze the reduction of nitric oxide (NO) to nitrous oxide (N
2
O) under reducing anaerobic conditions. The rate of NO consumption and N
2
O production were found to be linearly dependent on enzyme concentration, and activity was abolished by enzyme denaturation. Thus, contrary to the eukaryotic enzyme, both
T. thermophilus
oxidases display a NO reductase activity (3.0 ± 0.7 mol NO/mol
ba
3
× min and 32 ± 8 mol NO/mol
caa
3
× min at [NO] ≈ 50 μM and 20°C) that, though considerably lower than that of bona fide NO reductases (300–4,500 mol NO/mol enzyme × min), is definitely significant. We also show that for
ba
3
oxidase, NO reduction is associated to oxidation of cytochrome
b
at a rate compatible with turnover, suggesting a mechanism consistent with the stoichiometry of the overall reaction. We propose that the NO reductase activity of
T. thermophilus
oxidases may depend on a peculiar Cu
B
+
coordination, which may be revealed by the forthcoming three-dimensional structure. These findings support the hypothesis of a common phylogeny of aerobic respiration and bacterial denitrification, which was proposed on the basis of structural similarities between the
Pseudomonas stutzeri
NO reductase and the
cbb
3
terminal oxidases. Our findings represent functional evidence in support of this hypothesis.
Nuclear localization of the C1 factor (host cell factor) in sensory neurons correlates with reactivation of herpes simplex virus from latency
Authors: Kristie Thomas M. , Vogel Jodi L. , Sears Amy E.
Published: July 2002

After a primary infection, herpes simplex virus is maintained in a
latent state in neurons of sensory ganglia until complex stimuli
reactivate viral lytic replication. Although the mechanisms governing
reactivation from the latent state remain unknown, the regulated
expression of the viral immediate early genes represents a critical
point in this process. These genes are controlled by transcription
enhancer complexes whose assembly requires and is coordinated by the
cellular C1 factor (host cell factor). In contrast to other tissues,
the C1 factor is not detected in the nuclei of sensory neurons.
Experimental conditions that induce the reactivation of herpes simplex
virus in mouse model systems result in rapid nuclear localization of
the protein, indicating that the C1 factor is sequestered in these
cells until reactivation signals induce a redistribution of the
protein. The regulated localization suggests that C1 is a critical
switch determinant of the viral lytic–latent cycle.
Interactions between human cyclin T, Tat, and the transactivation response element (TAR) are disrupted by a cysteine to tyrosine substitution found in mouse cyclin T
Authors: Fujinaga Koh , Taube Ran , Wimmer Jörg , Cujec Thomas P. , Peterlin B. Matija
Published: July 2002

The transcriptional transactivator Tat from HIV binds to the
transactivation response element (TAR) RNA to increase rates of
elongation of viral transcription. Human cyclin T supports these
interactions between Tat and TAR. In this study, we report the sequence
of mouse cyclin T and identify the residues from positions 1 to 281 in
human cyclin T that bind to Tat and TAR. Mouse cyclin T binds to Tat
weakly and is unable to facilitate interactions between Tat and TAR.
Reciprocal exchanges of the cysteine and tyrosine at position 261 in
human and mouse cyclin T proteins also render human cyclin T inactive
and mouse cyclin T active. These findings reveal the molecular basis
for the restriction of Tat transactivation in rodent cells.
Effects of changes in membrane sodium flux on virulence gene expression in
Vibrio cholerae
Authors: Häse Claudia C. , Mekalanos John J.
Published: July 2002

The expression of several virulence factors of
Vibrio cholerae
is coordinately regulated by the ToxT molecule and the membrane proteins TcpP/H and ToxR/S, which are required for
toxT
transcription. To identify proteins that negatively affect
toxT
transcription, we screened transposon mutants of
V. cholerae
carrying a chromosomally integrated
toxT
∷
lacZ
reporter construct for darker blue colonies on media containing 5-bromo-4-chlor-3-indolyl β-
d
galactoside (X-gal). Two mutants had transposon insertions in a region homologous to the
nqr
gene cluster of
Vibrio alginolyticus
, encoding a sodium-translocating NADH–ubiquinone oxidoreductase (NQR). In
V. alginolyticus
, NQR is a respiration-linked Na
+
extrusion pump generating a sodium motive force that can be used for solute import, ATP synthesis, and flagella rotation. Inhibition of NQR enzyme function in
V. cholerae
by the specific inhibitor 2-
n
-heptyl-4-hydroxyquinoline
N-
oxide (HQNO) resulted in elevated
toxT
∷
lacZ
activity. Increased
toxT
∷
lacZ
expression in an
nqr
mutant strain compared with the parental strain was observed when the TcpP/H molecules alone were strongly expressed, suggesting that the negative effect of the NQR complex on
toxT
transcription is mediated through TcpP/H. However, the ability of the TcpP/H proteins to activate the
toxT
∷
lacZ
reporter construct was greatly diminished in the presence of high NaCl concentrations in the growth medium. The flagellar motor of
V. cholerae
appears to be driven by a sodium motive force, and modulation of flagella rotation by inhibitory drugs, high media viscosity, or specific mutations resulted in increases of
toxT
∷
lacZ
expression. Thus, the regulation of the main virulence factors of
V. cholerae
appears to be modulated by endogenous and exogenous sodium levels in a complex way.
Genetic basis in plants for interactions with disease-suppressive bacteria
Authors: Smith Kevin P. , Handelsman Jo , Goodman Robert M.
Published: July 2002

Plant health depends, in part, on associations with disease-suppressive microflora, but little is known about the role of plant genes in establishing such associations. Identifying such genes will contribute to understanding the basis for plant health in natural communities and to new strategies to reduce dependence on pesticides in agriculture. To assess the role of the plant host in disease suppression, we used a genetic mapping population of tomato to evaluate the efficacy of the biocontrol agent
Bacillus cereus
against the seed pathogen
Pythium torulosum
. We detected significant phenotypic variation among recombinant inbred lines that comprise the mapping population for resistance to
P. torulosum
, disease suppression by
B. cereus
, and growth of
B. cereus
on the seed. Genetic analysis revealed that three quantitative trait loci (QTL) associated with disease suppression by
B. cereus
explained 38% of the phenotypic variation among the recombinant inbred lines. In two cases, QTL for disease suppression by
B. cereus
map to the same locations as QTL for other traits, suggesting that the host effect on biocontrol is mediated by different mechanisms. The discovery of a genetic basis in the host for interactions with a biocontrol agent suggests new opportunities to exploit natural genetic variation in host species to enhance our understanding of beneficial plant—microbe interactions and develop ecologically sound strategies for disease control in agriculture.
Bifurcation of the mitotic checkpoint pathway in budding yeast
Authors: Li Rong
Published: July 2002

The coordination of mitotic events is ensured through the spindle assembly checkpoint.
BFA1
is required for this checkpoint in budding yeast because its disruption abolishes the mitotic arrest when spindle assembly is inhibited. Analysis of the genetic interaction of
BFA1
with known mitotic checkpoint genes suggest that Bfa1 functions in the same pathway with Bub2 but not with Mad1 or Mad2. Both Bfa1 and Bub2 localize to spindle poles, and overexpression of Bfa1 arrests the cell cycle in anaphase. These findings suggest a bifurcation of the spindle assembly checkpoint: whereas one branch of the pathway, consisting of Mad1–3, Bub1 and 3, and Mps1, may prevent premature disjunction of sister chromosomes, the other, consisting of Bfa1 and Bub2, may function at spindle poles to prevent cytokinesis before the completion of chromosome segregation.
Disruption of gene
mg218
of
Mycoplasma genitalium
through homologous recombination leads to an adherence-deficient phenotype
Authors: Dhandayuthapani S. , Rasmussen W. G. , Baseman J. B.
Published: July 2002

Although the complete genome of
Mycoplasma genitalium
has been sequenced, the functional identification of various genes, including those involved in virulence, has not been accomplished. Further compounding these difficulties has been the failure to develop genetic tools in mycoplasmas that permit the assessment of gene and operon function and regulation. To determine whether homologous recombination could be developed as a tool to analyze the function of genes in
M. genitalium
, a plasmid that replicates in
Escherichia coli
but not in
M. genitalium
was constructed to disrupt the cytadherence-related gene
mg218
of
M. genitalium
. The electroporation of this disruption plasmid into wild-type hemadsorption-positive (HA
+
)
M. genitalium
cells permitted the isolation of HA
−
(strain JB1) and partial HA
+
(strains JB2 and JB20) transformants. Analysis of the transformants by Southern hybridization indicated that homologous recombination occurred at the
mg218
locus by single-crossover events in JB1 and JB2 and by a double-crossover event in JB20. While integration of the disruption construct abolished the expression MG218 in JB1, strains JB2 and JB20 exhibited a truncated MG218 protein (160 kDa), possibly because of in-frame fusion of the disrupted
mg218
gene with sequences downstream of the gentamycin-resistance gene present in the disruption construct. Strain JB1, which lacked MG218, displayed a post-translational defect, being unable to maintain the structural integrity of the major adhesin P140 and its operon-related protein P110, in contrast to JB2 and JB20. It appears that MG218 influences the stability of other cytadherence-related proteins
in vivo
. Thus, targeted gene disruption through homologous recombination will be a powerful and promising tool for investigating the biology and pathogenesis of
M. genitalium
.
A unique virus complex causes
Ageratum
yellow vein disease
Authors: Saunders Keith , Bedford Ian D. , Briddon Rob W. , Markham Peter G. , Wong Sek Man , Stanley John
Published: July 2002

Ageratum conyzoides
L., a weed species widely distributed throughout southeast Asia, frequently exhibits striking yellow vein symptoms associated with infection by
Ageratum
yellow vein virus (AYVV), a member of the
Geminiviridae
(genus
Begomovirus
). Most begomoviruses have bipartite genomes (DNAs A and B), but only a DNA A has been identified for AYVV. We demonstrate that yellow vein disease of
A. conyzoides
results from co-infection by AYVV DNA A (2,741 nt) and a circular DNA that is approximately half its size (1,347 nt) that we designate DNA β. Apart from the sequence TAATATTAC, common to all geminiviruses and containing the initiation site of rolling circle replication, DNA β shows negligible sequence homology either to AYVV DNA A or to DNA B associated with bipartite begomoviruses. DNA β depends on DNA A for replication and is encapsidated by DNA A-encoded coat protein and so has characteristics of a DNA satellite. However, systemic infection of
A. conyzoides
by DNA A alone is sporadic and asymptomatic, and DNA A accumulation is reduced to 5% or less of its accumulation in the presence of DNA β. Therefore, DNA A and DNA β together form a previously unrecognized disease-inducing complex. Our data also demonstrate that the nanovirus-like DNA 1 component associated with infected
A. conyzoides
plays no essential role in the disease and represents a satellite-like DNA. Furthermore, the satellite DNA previously found associated with tomato leaf curl virus is probably a defective DNA β homologue.
Molecular and cell biology aspects of plague
Authors: Cornelis Guy R.
Published: July 2002

A 70-kb virulence plasmid (sometimes called pYV) enablesYersiniaspp. to survive and multiply in the lymphoid tissues of their host. It encodes the Yop virulon, a system consisting of secreted proteins called Yops and their dedicated type III secretion apparatus called Ysc. The Ysc apparatus forms a channel composed of 29 proteins. Of these, 10 have counterparts in almost every type III system. Secretion of some Yops requires the assistance, in the bacterial cytosol, of small individual chaperones called the Syc proteins. These chaperones act as bodyguards or secretion pilots for their partner Yop. Yop proteins fall into two categories. Some are intracellular effectors, whereas the others are “translocators” needed to deliver the effectors across the eukaryotic plasma membrane, into eukaryotic cells. The translocators (YopB, YopD, LcrV) form a pore of 16–23 Å in the eukaryotic cell plasma membrane. The effector Yops are YopE, YopH, YpkA/YopO, YopP/YopJ, YopM, and YopT. YopH is a powerful phosphotyrosine phosphatase playing an antiphagocytic role by dephosphorylating several focal adhesion proteins. YopE and YopT contribute to antiphagocytic effects by inactivating GTPases controlling cytoskeleton dynamics. YopP/YopJ plays an anti-inflammatory role by preventing the activation of the transcription factor NF-κB. It also induces rapid apoptosis of macrophages. Less is known about the role of the phosphoserine kinase YopO/YpkA and YopM.
Unusual1H NMR chemical shifts support (His) Cɛ1—H⋅⋅⋅O⩵C H-bond: Proposal for reaction-driven ring flip mechanism in serine protease catalysis
Authors: Ash Elissa L. , Sudmeier James L. , Day Regina M. , Vincent Matthew , Torchilin Ekaterina V. , Haddad Kristin Coffman , Bradshaw Elizabeth M. , Sanford David G. , Bachovchin William W.
Published: July 2002

13C-selective NMR, combined with inhibitor perturbation experiments, shows that the Cɛ1—H proton of the catalytic histidine in resting α-lytic protease and subtilisin BPN′ resonates, when protonated, at 9.22 ppm and 9.18 ppm, respectively, which is outside the normal range for such protons and ≈0.6 to 0.8 ppm further downfield than previously reported. They also show that the previous α-lytic protease assignments [Markley, J. L., Neves, D. E., Westler, W. M., Ibanez, I. B., Porubcan, M. A. & Baillargeon, M. W. (1980)Front. Protein Chem.10, 31–61] were to signals from inactive or denatured protein. Simulations of linewidth vs. pH demonstrate that the true signal is more difficult to detect than corresponding signals from inactive derivatives, owing to higher imidazole pKavalues and larger chemical shift differences between protonated and neutral forms. A compilation and analysis of available NMR data indicates that the true Cɛ1—H signals from other serine proteases are similarly displaced downfield, with past assignments to more upfield signals probably in error. The downfield displacement of these proton resonances is shown to be consistent with an H-bond involving the histidine Cɛ1—H as donor, confirming the original hypothesis of Derewendaet al.[Derewenda, Z. S., Derewenda, U. & Kobos, P. M. (1994)J. Mol. Biol.241, 83–93], which was based on an analysis of literature x-ray crystal structures of serine hydrolases. The invariability of this H-bond among enzymes containing Asp-His-Ser triads indicates functional importance. Here, we propose that it enables a reaction-driven imidazole ring flip mechanism, overcoming a major dilemma inherent in all previous mechanisms, namely how these enzymes catalyze both the formation and productive breakdown of tetrahedral intermediates.
RNA folding energy landscapes
Authors: Chen Shi-Jie , Dill Ken A.
Published: July 2002

Using a statistical mechanical treatment, we study RNA folding energy landscapes. We first validate the theory by showing that, for the RNA molecules we tested having only secondary structures, this treatment (
i
) predicts about the same native structures as the Zuker method, and (
ii
) qualitatively predicts the melting curve peaks and shoulders seen in experiments. We then predict thermodynamic folding intermediates. For one hairpin sequence, unfolding is a simple unzipping process. But for another sequence, unfolding is more complex. It involves multiple stable intermediates and a rezipping into a completely non-native conformation before unfolding. The principle that emerges, for which there is growing experimental support, is that although protein folding tends to involve highly cooperative two-state thermodynamic transitions, without detectable intermediates, the folding of RNA secondary structures may involve rugged landscapes, often with more complex intermediate states.
Plant organ size control:
AINTEGUMENTA
regulates growth and cell numbers during organogenesis
Authors: Mizukami Yukiko , Fischer Robert L.
Published: July 2002

The control of cell proliferation during organogenesis plays an important role in initiation, growth, and acquisition of the intrinsic size of organs in higher plants. To understand the developmental mechanism that controls intrinsic organ size by regulating the number and extent of cell division during organogenesis, we examined the function of the
Arabidopsis
regulatory gene
AINTEGUMENATA
(
ANT
). Previous observations revealed that
ANT
regulates cell division in integuments during ovule development and is necessary for floral organ growth. Here we show that ANT controls plant organ cell number and organ size throughout shoot development. Loss of
ANT
function reduces the size of all lateral shoot organs by decreasing cell number. Conversely, gain of
ANT
function, via ectopic expression of a
35S
::
ANT
transgene, enlarges embryonic and all shoot organs without altering superficial morphology by increasing cell number in both
Arabidopsis
and tobacco plants. This hyperplasia results from an extended period of cell proliferation and organ growth. Furthermore, cells ectopically expressing
ANT
in fully differentiated organs exhibit neoplastic activity by producing calli and adventitious roots and shoots. Based on these results, we propose that
ANT
regulates cell proliferation and organ growth by maintaining the meristematic competence of cells during organogenesis.
Unusual DNA structure of the diabetes susceptibility locus
IDDM2
and its effect on transcription by the insulin promoter factor Pur-1/MAZ
Authors: Lew Amy , Rutter William J. , Kennedy Giulia C.
Published: July 2002

One of the loci responsible for genetic susceptibility to
insulin-dependent diabetes mellitus (IDDM) is the insulin-linked
polymorphic region (ILPR, also known as
IDDM2
). This
polymorphic G-rich minisatellite, located in the promoter region of the
human insulin gene, comprises a variable number of tandemly repeating
sequences related to ACAGGGGTGTGGGG. An interesting characteristic of
the ILPR is its ability to form unusual DNA structures
in
vitro
, presumably through formation of G-quartets. This ability
to form G-quartets raises the intriguing possibility that
transcriptional activity of the insulin gene may in fact be influenced
by the quaternary DNA topology of the ILPR. We now show that single
nucleotide differences in the ILPR known to affect insulin
transcription are correlated with ability to form unusual DNA
structures. Through the design and testing of two high transcriptional
activity ILPR repeats, we demonstrate that both inter- and
intramolecular G-quartet formation in the ILPR can influence
transcriptional activity of the human insulin gene, and thus, may
contribute to that portion of diabetes susceptibility attributed to the
IDDM2
locus.
Decreasing variability in the development of graphic production
Authors: Braswell Gregory S. , Rosengren Karl K.
Published: July 2002

Several recent theories of development have begun to recognise the importance of variability in mechanisms of change. The present study’s aim was to map variability in the drawing process. We examined changes in cognitive and biomechanical factors that influence drawing behaviour by investigating how simple shapes and complex pictures are drawn. In order to assess changes in variability with age across individuals, children (4- to 7-year-olds) and adults copied a series of geometric shapes and more complex images. In order to assess changes in variability with age within individuals, participants also made repeated copies of simple shapes and characters. Overall, both types of variability decreased with age. It is suggested that increasing biomechanical efficiency and enculturated drawing conventions contribute to these decreases.
Contexts as Moderators of Observed Interactions: A study of Costa Rican Mothers and Infants from Differing Socioeconomic Backgrounds
Authors: Leyendecker Birgit , Lamb Michael E. , Schölmerich Axel , Fricke Delia Miranda
Published: July 2002

Twenty first-born infants from low SES families and 20 first-born infants from middle SES families in Costa Rica were observed for 12 hours when they were 14 weeks old. The goals of this study were to: (1) study the impact of length of observation and context on our measures of interactional engagement; and (2) compare the interactional experiences of the infants in the two groups in various functional (e.g. feeding, object play) and social (e.g. with mother, with mother and others) contexts. Attuned and disharmonious interactions, as well as the frequency of positive affect, soothing, and vocalisation, varied considerably across the functional contexts. In addition, disharmonious interactions increased and interactional engagement decreased when mothers and infants were joined by others. Highly unstable measures of individual differences were obtained when observations were limited to 45-minute blocks, but stability increased considerably as the duration of the observations expanded. The groups did not differ with respect to amounts of time spent in various functional and social contexts, in attuned or disharmonious states, or in high levels of interactional engagement. Within some of the functional contexts, however, significant group differences in levels of attuned interactions, infant vocalisation, and maternal response vocalisation were found. Overall, functional and social contexts clearly moderated interactional experiences. SES effects on verbal and other interactional measures were limited to some contexts and may thus represent the infants’ overall experiences quite poorly. Consequently, comparisons based on a single context may be inadequate for studies of subjects from differing socioeconomic backgrounds.
Relationships between Traumatic Events, Children’s Gender, and Political Activity, and Perceptions of Parenting Styles
Authors: Punamäki Raija-Leena , Qouta Samir , El Sarraj Eyad
Published: July 2002

The associations between traumatic events, children’s gender and political activity, and parenting styles were examined among 108 Palestinians of 11-12 years of age. The results showed that the more the children were exposed to traumatic events, the more they perceived both their parents as strictly disciplining, rejecting, and hostile, and their mothers as more negatively evaluating. The boys perceived both their parents as treating them more negatively than the girls did. Affectionate parenting, such as intimacy and love, for its part, was not associated with traumatic events, and did not vary according to the child’s gender or political activity. The gender of the child affected the association between traumatic events, political activity, and perceived parenting. Traumatic events increased perceived parental rejection and hostility only among the boys, and perceived strict disciplining only among the girls. Although politically active children perceived both of their parents as more negative in general, in the families exposed to a high level of traumatic events, passive boys perceived their fathers as more rejecting and hostile than active boys did. It is suggested that mothers and fathers rear girls restrictively and with greater attention, and boys with rejection, when the family faces traumatic events. In exposed families, fathers also tend to discourage boys’ political passivity and apparently encourage activity.
Nominations, Ratings, and the Dimensions of Sociometric Status
Authors: Maassen Gerard H. , van der Linden Jos L. , Akkermans Wies
Published: July 2002

In 1944, U. Bronfenbrenner remarked on the need for a two-dimensional model of sociometric status. The low value of the correlation between the variables liking and disliking-assumed basic dimensions of sociometric status-is often cited as evidence for the correctness of Bronfenbrenner’ssuggestion. Sociometric status is derived from a coalescence of judgements at the individual level. In this article we argue that score attribution at this level (where one group member assesses another) is one-dimensional along the liking-disliking continuum. Two-dimensionality of sociometric status arises at the group level. However, we also show that at this level liking and disliking are not two distinct dimensions, but the poles of just one, the other being visibility (or impact).

If the one-dimensional model of liking score attribution on the individual level is accepted, the obvious thing to do is to instruct respondents accordingly. Rating scales are suitable for this. The rating-scale methods we suggested in previous publications (e.g. Maassen, Akkermans, & van der Linden, 1996) are in keeping with this argument. Moreover, these methods may be recommended for their reliability, validity and for the variety of research designs to which they can be applied.
A Comparison of the Adjustment of Adolescent and Young Adult Inter-country Adoptees and their Siblings
Authors: Westhues Anne , Cohen Joyce S.
Published: July 2002

Results of studies to determine how well children, who have been adopted internationally, have adjusted are inconclusive. Little is known about the adjustment of adolescents (12-17 years of age) in relation to young adults (18-25 years of age). This study compares the adjustment by age and by gender for 86 adolescent inter-country adoptees with that of 33 of their adolescent siblings raised in the same family. Also examined is the adjustment of 49 young adult adoptees (18-25 years of age) in comparison with 65 of their young adult siblings.
cAMP analogues downregulate the expression of granulocyte macrophage colony‐stimulating factor (GM‐CSF) in human bone marrow stromal cells in vitro
Authors: Bug G. , Aman J. , Huber C. , Peschel C. , Derigs H. G.
Published: July 2002

The stimulation of granulocyte macrophage‐colony stimulating factor (GM‐CSF) by interleukin‐1 (IL‐1) has been shown to be counteracted in different mesenchymal cell systems by cyclic adenosine monophosphate (cAMP) agonists. The aim of this study was the evaluation of different cAMP agonists on GM‐CSF expression in human bone marrow stromal cells. Incubation of secondary haematopoietic progenitor cell deprived human stromal cell cultures with IL‐1 or TNF‐ α induced GM‐CSF protein expression in culture supernatants and GM‐CSFmRNA in adherent stromal cells. The coincubation with 8‐bromo‐cAMP (8BrcAMP), a water soluble cAMP analogue, inhibited this GM‐CSF stimulation at the protein and the m RNA level. This effect was dose dependent with a maximal inhibition of about 65% occurring at a 8BrcAMP concentration of 0.75 mM. In addition to 8BrcAMP, other cAMP agonists such as dibutyryl‐cAMP, forskolin, pertussis toxin, or prostaglandin E2 (PGE2) had the same inhibitory effect on GM‐CSF stimulation by IL‐1. Coincubation with the cyclooxygenase inhibitor indomethacin had no significant influence on GM‐CSF expression in stromal cells. Our results provide evidence that the previously described inhibitory effect of cAMP agonist PGE2 on haematopoietic progenitor cells in vivo is, at least in part, mediated by modulating the expression of GMCSF in bone marrow stromal cells.
Constitutive expression of E‐and P‐selectin cognate ligands in human endothelial cells
Authors: Palma C. , Bellarosa D. , Nardelli F. , Mannori G. , Manzini S.
Published: July 2002

On human endothelial cells from umbilical cord (HUVEC) are present, in addition to E‐and P‐selectins, their cognate ligands. Differently from selectins, the ligand expression is constitutive and not modulated by interleukin‐1β . Such ligands appear to be different from the ones present in promyelocytic cells in order to promote cell adhesion to immobilized selectins. The expression of selectin‐ligands on HUVEC cells suggest that selectins can participate in endothelial signalling besides their role as adhesion molecules for circulating blood cells. However, despite their role in chemotaxis, selectins do not contribute to HUVEC tube formation in Matrigel.
The Emperor's Clothes
Authors: Davis John B.
Published: July 2002

David Colander argued to this Society two years ago that the term “neoclassical economics” ought to be declared dead (Colander 2000). I concur with him on the verdict, but do so for different reasons. Colander's argument was that neoclassicism possessed six primary attributes, and much of mainstream economics cannot be characterized in these terms. My argument is simpler. It is that neoclassical economics was primarily a theory of the human individual in economic life (albeit a flawed one), but contemporary mainstream economics does not possess a theory of the human individual. This conclusion may not surprise those who have reflected on the rise of formalism in economics in the postwar period. But for two reasons I think it important to emphasize the disappearance of a theory of the individual from economics. First, because neoclassicism implemented and defended for nearly a century one particular philosophical conception of the individual central to western thought since the Enlightenment, the abandonment of this commitment by mainstream economics is an important part of our understanding of its evolution and its relation to social thinking generally. Second, the demise of the individual in mainstream economics is also significant because, having abandoned the individual, mainstream economics is no longer capable of offering a defense of the individual in contemporary society. Indeed its project, I will suggest, is in important respects anti-individualist. It may be naïve on my part to think contemporary society still engaged in a defense of the individual. Nonetheless, I hold that thinking about the individual remains fundamental to how many people think about the social world, and that consequently mainstream economics' abandonment of the individual may render it historically irrelevant, perhaps contributing to its fragmentation and dissolution as an identifiable approach in economics. Thus the important conclusion to draw may not be Colander's: that we have seen the death of neoclassical economics. It may be that at issue today is the death of mainstream economics.
Cognitive Impairment in Individuals Currently Using Methamphetamine
Authors: Simon Sara L. , Domier Catherine , Carnell Jennifer , Brethen Paul , Rawson Richard , Ling Walter
Published: July 2002

Although there are increasing reports of methamphetamine use, studies examining the cognitive consequences of methamphetamine have not been performed on a population currently using the drug. To characterize this population, 65 people currently using MA regularly and 65 non‐users were given a battery of cognitive tests. The battery included recall, recognition, Digit Symbol, Trail Making A & B, Stroop, Wisconsin Card Sort, backward digit span, and the FAS test of verbal fluency. The methamphetamine users were significantly more impaired on recall tasks, digit symbol, Stroop color words, and Trail Making B, but scores fell within the normal ranges on the other measures.