bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutations in HlyD, Part of the Type 1 Translocator for Hemolysin Secretion, Affect the Folding of the Secreted Toxin
Authors: Pimenta A. L. , Racher K. , Jamieson L. , Blight M. A. , Holland I. B. 
Published: October 2005

ABSTRACT

HlyD, a member of the membrane fusion protein family, is essential for the secretion of the RTX hemolytic toxin HlyA from
Escherichia coli
. Random point mutations affecting HlyA secretion were obtained, distributed in most periplasmic regions of the HlyD molecule. Analysis of the secretion phenotypes of different mutants allowed the identification of regions in HlyD involved in different steps of HlyA translocation. Four mutants, V349-I, T85-I, V334-I and L165-Q, were conditionally defective, a phenotype shown to be linked to the presence of inhibitory concentrations of Ca
2+
in extracellular medium. Hly mutant T85-I was defective at an early stage in secretion, while mutants V334-I and L165-Q appeared to accumulate HlyA in the cell envelope, indicating a block at an intermediate step. Mutants V349-I, V334-I, and L165-Q were only partially defective in secretion, allowing significant levels of HlyA to be transported, but in the case of V349-I and L165-Q the HlyA molecules secreted showed greatly reduced hemolytic activity. Hemolysin molecules secreted from V349-I and V334-I are defective in normal folding and can be reactivated in vitro to the same levels as HlyA secreted from the wild-type translocator. Both V349-I and V334-I mutations mapped to the C-terminal lipoyl repeat motif, involved in the switching from the helical hairpin to the extended form of HlyD during assembly of the functional transport channel. These results suggest that HlyD is an integral component of the transport pathway, whose integrity is essential for the final folding of secreted HlyA into its active form.
Metabolic and Evolutionary Relationships among
Pyrococcus
Species: Genetic Exchange within a Hydrothermal Vent Environment
Authors: Hamilton-Brehm Scott D. , Schut Gerrit J. , Adams Michael W. W. 
Published: October 2005

ABSTRACT

Pyrococcus furiosus
and
Pyrococcus woesei
grow optimally at temperatures near 100°C and were isolated from the same shallow marine volcanic vent system. Hybridization of genomic DNA from
P. woesei
to a DNA microarray containing all 2,065 open reading frames (ORFs) annotated in the
P. furiosus
genome, in combination with PCR analysis, indicated that homologs of 105 ORFs present in
P. furiosus
are absent from the uncharacterized genome of
P. woesei
. Pulsed-field electrophoresis indicated that the sizes of the two genomes are comparable, and the results were consistent with the hypothesis that
P. woesei
lacks the 105 ORFs found in
P. furiosus
. The missing ORFs are present in
P. furiosus
mainly in clusters. These clusters include one cluster (Mal I, PF1737 to PF1751) involved in maltose metabolism and another cluster (PF0691 to PF0695) whose products are thought to remove toxic reactive nitrogen species. Accordingly, it was found that
P. woesei
, in contrast to
P. furiosus
, is unable to utilize maltose as a carbon source for growth, and the growth of
P. woesei
on starch was inhibited by addition of a nitric oxide generator. In
P. furiosus
the ORF clusters not present in
P. woesei
are bracketed by or are in the vicinity of insertion sequences or long clusters of tandem repeats (LCTRs). While the role of LCTRs in lateral gene transfer is not known, the Mal I cluster in
P. furiosus
is a composite transposon that undergoes replicative transposition. The same locus in
P. woesei
lacks any evidence of insertion activity, indicating that
P. woesei
is a sister or even the parent of
P. furiosus. P. woesei
may have acquired by lateral gene transfer more than 100 ORFs from other organisms living in the same thermophilic environment to produce the type strain of
P. furiosus
.
QscR-Mediated Transcriptional Activation of Serine Cycle Genes in
Methylobacterium extorquens
AM1
Authors: Kalyuzhnaya Marina G. , Lidstrom Mary E. 
Published: October 2005

ABSTRACT

QscR, a LysR-type regulator, is the major regulator of assimilatory C
1
metabolism in
Methylobacterium extorquens
AM1. It has been shown to interact with the promoters of the two operons that encode the majority of the serine cycle enzymes (
sga-hpr-mtdA-fch
for the
qsc
1 operon and
mtkA-mtkB-ppc-mclA
for the
qsc
2 operon), as well as with the promoter of
glyA
and its own promoter. To obtain further insights into the mechanisms of this regulation, we mapped transcriptional start sites for the
qsc1
and
qsc2
operons and for
glyA
via primer extension analysis. We also identified the specific binding sites for QscR upstream of the
qsc1
and
qsc2
operons and
glyA
by DNase I footprinting. The QscR protected areas were located at nucleotides −216 to −165, nucleotides −59 to −26, and nucleotides −72 to −39 within the promoter-regulatory regions upstream of transcriptional starts of, respectively,
qsc1
,
qsc2
and
glyA
. To examine the nature of the metabolic signal that may influence QscR-mediated regulation of the serine cycle genes,
Pqsc1
::
xylE
translational fusions were constructed and expression of XylE monitored in the wild-type strain, as well as in knockout mutants defective in a variety of methylotrophy functions. The data from these experiments pointed toward formyl-H
4
F being a coinducer of QscR and possibly the major signal in the regulation of the serine cycle in
M. extorquens
AM1. The ability of formyl-H
4
F to enhance the binding of QscR to a specific region upstream of one of the serine cycle operons was demonstrated in gel retardation experiments.
Chlamydial GroEL Autoregulates Its Own Expression through Direct Interactions with the HrcA Repressor Protein
Authors: Wilson Adam C. , Wu Christine C. , Yates John R. , Tan Ming 
Published: October 2005

ABSTRACT

In the pathogenic bacterium
Chlamydia trachomatis
, a transcriptional repressor, HrcA, regulates the major heat shock operons,
dnaK
and
groE
. Cellular stress causes a transient increase in transcription of these heat shock operons through relief of HrcA-mediated repression, but the pathway leading to derepression is unclear. Elevated temperature alone is not sufficient, and it is hypothesized that additional chlamydial factors play a role. We used DNA affinity chromatography to purify proteins that interact with HrcA in vivo and identified a higher-order complex consisting of HrcA, GroEL, and GroES. This endogenous HrcA complex migrated differently than recombinant HrcA, but the complex could be disrupted, releasing native HrcA that resembled recombinant HrcA. In in vitro assays, GroEL increased the ability of HrcA to bind to the CIRCE operator and to repress transcription. Other chlamydial heat shock proteins, including the two additional GroEL paralogs present in all chlamydial species, did not modulate HrcA activity.
DIFFERENTIAL TOPOLOGY AND GEOMETRY OF SMOOTH EMBEDDED SURFACES: SELECTED TOPICS
Authors: CAZALS FRÉDÉRIC , POUGET MARC 
Published: October 2005

The understanding of surfaces embedded in E3 requires local and global concepts, which are respectively evocative of differential geometry and differential topology. While the local theory has been classical for decades, global objects such as the foliations defined by the lines of curvature, or the medial axis still pose challenging mathematical problems. This duality is also tangible from a practical perspective, since algorithms manipulating sampled smooth surfaces (meshes or point clouds) are more developed in the local than the global category. As a prerequisite for those interested in the development of algorithms for the manipulation of surfaces, we propose a concise overview of core concepts from differential topology applied to smooth embedded surfaces. We first recall the classification of umbilics, of curvature lines, and describe the corresponding stable foliations. Next, fundamentals of contact and singularity theory are recalled, together with the classification of points induced by the contact of the surface with a sphere. This classification is further used to define ridges and their properties, and to recall the stratification properties of the medial axis. Finally, properties of the medial axis are used to present sufficient conditions ensuring that two embedded surfaces are ambient isotopic. From a theoretical perspective, we expect this survey to ease the access to intricate notions scattered over several sources. From a practical standpoint, we hope it will be useful for those interested in certified approximations of smooth surfaces.
(DIS)BELIEF CHANGE AND ARGUED FEED-BACK DIALOG
Authors: PERRUSSEL LAURENT , THÉVENIN JEAN-MARC 
Published: October 2005

This paper focuses on the features of belief change in a multi-agent context where agents consider beliefs and disbeliefs. Disbeliefs represent explicit ignorance and are useful to prevent agents to entail conclusions due to their ignorance. Agents receive messages holding information from other agents and change their belief state accordingly. An agent may refuse to adopt incoming information if it prefers its own (dis)beliefs. For this, each agent maintains a preference relation over its own beliefs and disbeliefs in order to decide if it accepts or rejects incoming information whenever inconsistencies occur. This preference relation may be built by considering several criteria such as the reliability of the sender of statements or temporal aspects. This process leads to non-prioritized belief revision. In this context we first present the * and − operators which allow an agent to revise, respectively contract, its belief state in a non-prioritized way when it receives an incoming belief, respectively disbelief. We show that these operators behave properly. Based on this we then illustrate how the receiver and the sender may argue when the incoming (dis)belief is refused. We describe pieces of dialog where (i) the sender tries to convince the receiver by sending arguments in favor of the original (dis)belief and (ii) the receiver justifies its refusal by sending arguments against the original (dis)belief. We show that the notion of acceptability of these arguments can be represented in a simple way by using the non-prioritized change operators * and −. The advantage of argumentation dialogs is twofold. First whenever arguments are acceptable the sender or the receiver reconsider its belief state; the main result is an improvement of the reconsidered belief state. Second the sender may not be aware of some sets of rules which act as constraints to reach a specific conclusion and discover them through argumentation dialogs.
What Observation Scheme Should We Use for Profiling Floats to Achieve the Argo Goal for Salinity Measurement Accuracy? Suggestions from Software Calibration
Authors: Kobayashi Taiyo , Minato Shinya 
Published: October 2005

Abstract
To meet the Argo Project’s accuracy goal for salinity measurements (±0.01), several measurement schemes for profiling float observations were examined using the standard Argo software calibration for salinity. In this study, salinity calibration errors are evaluated in data series observed by employing several different measurement schemes. In the North Pacific the accuracy goal can be achieved by programming for constant measurements to a depth of 1500 db or more; however, measurements in the mixed water region require the adoption of a scheme that constantly measures salinity profiles to the marginal capability depth of floats (e.g., 2000 db), so that calibration errors can be minimized. In contrast, in the tropical regions of the Pacific and eastern Indian Ocean, 1000-db profiles provide salinity data of sufficient quality. When floats use a Park and Profile scheme, it is recommended that they be programmed to measure deeper profiles every observation cycle. Otherwise, it is impossible to detect and correct suspicious data, such as a salinity jump in which a salinity measurement suddenly differs from previous measurements by ±0.02–0.03 or more.
A Self-Contained Acoustic Scintillation Instrument for Path-Averaged Measurements of Flow and Turbulence with Application to Hydrothermal Vent and Bottom Boundary Layer Dynamics
Authors: Di Iorio D. , Lemon D. , Chave R. 
Published: October 2005

Abstract
A self-contained acoustical scintillation instrument is described that has been used to measure flow and turbulence characteristics in two diverse oceanographic settings. This instrument is a battery-operated and internally logging acoustic propagation system that is ideally suited to monitor long-term flow and small-scale effective refractive index fluctuations. When the temperature variability dominates the acoustic scattering, as is the case of a hydrothermal vent plume, then a measure of the vertical buoyancy-driven flow, together with the root-mean-square temperature fluctuations, can be obtained. Results for vent structure Hulk of the Main Endeavour vent field of the Juan de Fuca Ridge show that the long-term (71 days) temperature fluctuations, together with the vertical flow, can be used to estimate heat flux density. Measurements also show oscillations in the log-amplitude variance that result from plume advection by the ambient tidal currents and demonstrate the need for a long time series measurement. When the turbulent velocity dominates the acoustic scattering, as is the case in some energetic bottom boundary layer flows, then the turbulent kinetic energy dissipation rate is derived, assuming isotropic and homogeneous models. The methodology and results are summarized from an application to the Bosporus Canyon of the Black Sea, to monitor the flow and turbulence associated with Mediterranean seawater inflow.
Hematopoietic stem cell exhaustion impacted by p18INK4C and p21Cip1/Waf1 in opposite manners
Authors: Yu Hui , Yuan Youzhong , Shen Hongmei , Cheng Tao 
Published: October 2005

AbstractTransplantation-associated stress can compromise the hematopoietic potential of hematopoietic stem cells (HSCs). As a consequence, HSCs may undergo “exhaustion” in serial transplant recipients, for which the cellular and molecular bases are not well understood. Hematopoietic exhaustion appears to be accelerated in the absence of p21Cip1/Waf1 (p21), a cyclin-dependent kinase inhibitor (CKI) in irradiated hosts. Our recent study demonstrated that unlike loss of p21, deletion of p18INK4C (p18), a distinct CKI, results in improved long-term engraftment, largely because of increased self-renewing divisions of HSCs in vivo. We show here that HSCs deficient in p18 sustained their competitiveness to wild-type HSCs from unmanipulated young mice, and retained multilineage differentiation potential after multiple rounds of serial bone marrow transfer over a period of more than 3 years. Further, p18 absence significantly decelerated hematopoietic exhaustion caused by p21 deficiency. Such an effect was shown to occur at the stem cell level, likely by a counteracting mechanism against the cellular senescence outcome. Our current study provides new insights into the distinct impacts of these cell-cycle regulators on HSC exhaustion and possibly HSC aging as well under proliferative stress, thereby offering potential pharmacologic targets for sustaining the durability of stressed HSCs in transplantation or elderly patients.
A role for cofilin in the activation of store-operated calcium entry by de novo conformational coupling in human platelets
Authors: Redondo Pedro C. , Harper Matthew T. , Rosado Juan A. , Sage Stewart O. 
Published: October 2005

AbstractStore-operated Ca2+ entry (SOCE) is a major mechanism for Ca2+ influx in platelets and other cells. De novo conformational coupling between elements in the plasma membrane and Ca2+ stores, where the actin cytoskeleton plays an important regulatory role, has been proposed as the most likely mechanism to activate SOCE in platelets. Here we have examined for the first time changes in platelet F-actin levels on a subsecond time scale. Using stopped-flow fluorimetry and a quenched-flow approach, we provide evidence for the involvement of cofilin in actin filament reorganization and SOCE in platelets. Thrombin (0.1 U/mL) evoked an initial decrease in F-actin that commenced within 0.1 second and reached a minimum 0.9 second after stimulation, prior to the activation of SOCE. F-actin then increased, exceeding basal levels approximately 2.5 seconds after stimulation. Thrombin also induced cofilin dephosphorylation and activation, which paralleled the changes observed in F-actin, and rapid Btk activation. Inhibition of cofilin dephosphorylation by LFM-A13 resulted in the loss of net actin depolymerization and an increased delay in SOCE initiation. These results suggest that cofilin is important for the rapid actin remodeling necessary for the activation of SOCE in platelets through de novo conformational coupling.
EFA (9-β-D-erythrofuranosyladenine) is an effective salvage agent for methylthioadenosine phosphorylase-selective therapy of T-cell acute lymphoblastic leukemia with L-alanosine
Authors: Batova Ayse , Cottam Howard , Yu John , Diccianni Mitchell B. , Carrera Carlos J. , Yu Alice L. 
Published: October 2005

AbstractThe deficiency of methylthioadenosine phosphorylase (MTAP) in T-cell acute lymphoblastic leukemia (T-ALL) and other cancers, while constitutively expressed in normal cells, allows for selective therapy using L-alanosine, an inhibitor of de novo AMP synthesis. We demonstrate that MTAP- T-ALL cells obtained at relapse are as sensitive to L-alanosine toxicity as diagnosis samples. The therapeutic index of L-alanosine can be increased by the use of a MTAP substrate, which protects MTAP+ normal cells. Since MTAP substrates MTA and 5′deoxyadenosine are prone to toxicities associated with adenosine, we synthesized and evaluated a potentially nontoxic MTAP substrate, 9-β-D-erythrofuranosyladenine (EFA). The cytotoxicity of EFA to hematopoietic progenitors erythroid burst-forming units (BFU-Es) and granulocyte-macrophage colony-forming units (CFU-GMs) was at least 26- to 41-fold less than that of MTA. In addition, EFA selectively rescued MTAP+ MOLT-4 cells from L-alanosine toxicity at 25 μM with negligible toxicity even at 100 μM. As for MTA, significant, albeit incomplete, rescue was achieved at 12.5 μM, but higher concentrations were toxic. EFA at 20 μM or less rescued primary MTAP+ T-ALL cells and normal lymphocytes from L-alanosine toxicity. Collectively, these data indicate that EFA is an effective agent for salvaging MTAP+ cells from L-alanosine toxicity and is superior to MTA due to lower cytotoxicity.
Sub-chronic inhalation of high concentrations of manganese sulfate induces lower airway pathology in rhesus monkeys
Authors: Dorman David C , Struve Melanie F , Gross Elizabeth A , Wong Brian A , Howroyd Paul C 
Published: October 2005

AbstractBackgroundNeurotoxicity and pulmonary dysfunction are well-recognized problems associated with prolonged human exposure to high concentrations of airborne manganese. Surprisingly, histological characterization of pulmonary responses induced by manganese remains incomplete. The primary objective of this study was to characterize histologic changes in the monkey respiratory tract following manganese inhalation.MethodsSubchronic (6 hr/day, 5 days/week) inhalation exposure of young male rhesus monkeys to manganese sulfate was performed. One cohort of monkeys (n = 4–6 animals/exposure concentration) was exposed to air or manganese sulfate at 0.06, 0.3, or 1.5 mg Mn/m3for 65 exposure days. Another eight monkeys were exposed to manganese sulfate at 1.5 mg Mn/m3for 65 exposure days and held for 45 or 90 days before evaluation. A second cohort (n = 4 monkeys per time point) was exposed to manganese sulfate at 1.5 mg Mn/m3and evaluated after 15 or 33 exposure days. Evaluations included measurement of lung manganese concentrations and evaluation of respiratory histologic changes. Tissue manganese concentrations were compared for the exposure and control groups by tests for homogeneity of variance, analysis of variance, followed by Dunnett's multiple comparison. Histopathological findings were evaluated using a Pearson's Chi-Square test.ResultsAnimals exposed to manganese sulfate at ≥0.3 mg Mn/m3for 65 days had increased lung manganese concentrations. Exposure to manganese sulfate at 1.5 mg Mn/m3for ≥15 exposure days resulted in increased lung manganese concentrations, mild subacute bronchiolitis, alveolar duct inflammation, and proliferation of bronchus-associated lymphoid tissue. Bronchiolitis and alveolar duct inflammatory changes were absent 45 days post-exposure, suggesting that these lesions are reversible upon cessation of subchronic high-dose manganese exposure.ConclusionHigh-dose subchronic manganese sulfate inhalation is associated with increased lung manganese concentrations and small airway inflammatory changes in the absence of observable clinical signs. Subchronic exposure to manganese sulfate at exposure concentrations (≤0.3 mg Mn/m3) similar to the current 8-hr occupational threshold limit value established for inhaled manganese was not associated with pulmonary pathology.
Dynamic modeling of cis-regulatory circuits and gene expression prediction via cross-gene identification
Authors: Lin Li-Hsieh , Lee Hsiao-Ching , Li Wen-Hsiung , Chen Bor-Sen 
Published: October 2005

Abstract
Background
Gene expression programs depend on recognition of cis elements in promoter region of target genes by transcription factors (TFs), but how TFs regulate gene expression via recognition of cis elements is still not clear. To study this issue, we define the cis-regulatory circuit of a gene as a system that consists of its cis elements and the interactions among their recognizing TFs and develop a dynamic model to study the functional architecture and dynamics of the circuit. This is in contrast to traditional approaches where a cis-regulatory circuit is constructed by a mutagenesis or motif-deletion scheme. We estimate the regulatory functions of cis-regulatory circuits using microarray data.

Results
A novel cross-gene identification scheme is proposed to infer how multiple TFs coordinate to regulate gene transcription in the yeast cell cycle and to uncover hidden regulatory functions of a cis-regulatory circuit. Some advantages of this approach over most current methods are that it is based on data obtained from intact cis-regulatory circuits and that a dynamic model can quantitatively characterize the regulatory function of each TF and the interactions among the TFs. Our method may also be applicable to other genes if their expression profiles have been examined for a sufficiently long time.

Conclusion
In this study, we have developed a dynamic model to reconstruct cis-regulatory circuits and a cross-gene identification scheme to estimate the regulatory functions of the TFs that control the regulation of the genes under study. We have applied this method to cell cycle genes because the available expression profiles for these genes are long enough. Our method not only can quantify the regulatory strengths and synergy of the TFs but also can predict the expression profile of any gene having a subset of the cis elements studied.