bluuebunny/crossref_metadata_2025_split huggingface dataset:
Automatic extension of Gene Ontology with flexible identification of candidate terms
Authors: Lee Jin-Bok , Kim Jung-jae , Park Jong C. 
Published: January 2006

AbstractMotivation: Gene Ontology (GO) has been manually developed to provide a controlled vocabulary for gene product attributes. It continues to evolve with new concepts that are compiled mostly from existing concepts in a compositional way. If we consider the relatively slow growth rate of GO in the face of the fast accumulation of the biological data, it is much desirable to provide an automatic means for predicting new concepts from the existing ones.Results: We present a novel method that predicts more detailed concepts by utilizing syntactic relations among the existing concepts. We propose a validation measure for the automatically predicted concepts by matching the concepts to biomedical articles. We also suggest how to find a suitable direction for the extension of a constantly growing ontology such as GO.Availability: Contact: park@nlp.kaist.ac.krSupplementary information: Supplementary materials are available at Bioinformatics online.
Chloroplastic NAD(P)H Dehydrogenase in Tobacco Leaves Functions in Alleviation of Oxidative Damage Caused by Temperature Stress
Authors: Wang Peng , Duan Wei , Takabayashi Atsushi , Endo Tsuyoshi , Shikanai Toshiharu , Ye Ji-Yu , Mi Hualing 
Published: January 2006

Abstract
In this study, the function of the NAD(P)H dehydrogenase (NDH)-dependent pathway in suppressing the accumulation of reactive oxygen species in chloroplasts was investigated. Hydrogen peroxide accumulated in the leaves of tobacco (Nicotiana tabacum) defective in ndhC-ndhK-ndhJ (ΔndhCKJ) at 42°C and 4°C, and in that of wild-type leaves at 4°C. The maximum quantum efficiency of PSII decreased to a similar extent in both strains at 42°C, while it decreased more evidently in ΔndhCKJ at 4°C. The parameters linked to CO2 assimilation, such as the photochemical efficiency of PSII, the decrease of nonphotochemical quenching following the initial rise, and the photosynthetic O2 evolution, were inhibited more significantly in ΔndhCKJ than in wild type at 42°C and were seriously inhibited in both strains at 4°C. While cyclic electron flow around PSI mediated by NDH was remarkably enhanced at 42°C and suppressed at 4°C. The proton gradient across the thylakoid membranes and light-dependent ATP synthesis were higher in wild type than in ΔndhCKJ at either 25°C or 42°C, but were barely formed at 4°C. Based on these results, we suggest that cyclic photophosphorylation via the NDH pathway might play an important role in regulation of CO2 assimilation under heat-stressed condition but is less important under chilling-stressed condition, thus optimizing the photosynthetic electron transport and reducing the generation of reactive oxygen species.
The Arabidopsis Zinc Finger-Homeodomain Genes Encode Proteins with Unique Biochemical Properties That Are Coordinately Expressed during Floral Development
Authors: Tan Queenie K.-G. , Irish Vivian F. 
Published: January 2006

Abstract
Arabidopsis (Arabidopsis thaliana) contains approximately 100 homeobox genes, many of which have been shown to play critical roles in various developmental processes. Here we characterize the zinc finger-homeodomain (ZF-HD) subfamily of homeobox genes, consisting of 14 members in Arabidopsis. We demonstrate that the HDs of the ZF-HD proteins share some similarities with other known HDs in Arabidopsis, but they contain distinct features that cluster them as a unique class of plant HD-containing proteins. We have carried out mutational analyses to show that the noncanonical residues present in the HDs of this family of proteins are important for function. Yeast (Saccharomyces cerevisiae) two-hybrid matrix analyses of the ZF-HD proteins reveal that these proteins both homo- and heterodimerize, which may contribute to greater selectivity in DNA binding. These assays also show that most of these proteins do not contain an intrinsic activation domain, suggesting that interactions with other factors are required for transcriptional activation. We also show that the family members are all expressed predominantly or exclusively in floral tissue, indicating a likely regulatory role during floral development. Furthermore, we have identified loss-of-function mutations for six of these genes that individually show no obvious phenotype, supporting the idea that the encoded proteins have common roles in floral development. Based on these results, we propose the ZF-HD gene family encodes a group of transcriptional regulators with unique biochemical activities that play overlapping regulatory roles in Arabidopsis floral development.
Control of Floral Meristem Determinacy in Petunia by MADS-Box Transcription Factors
Authors: Ferrario Silvia , Shchennikova Anna V. , Franken John , Immink Richard G.H. , Angenent Gerco C. 
Published: January 2006

Abstract
The shoot apical meristem (SAM), a small group of undifferentiated dividing cells, is responsible for the continuous growth of plants. Several genes have been identified that control the development and maintenance of the SAM. Among these, WUSCHEL (WUS) from Arabidopsis (Arabidopsis thaliana) is thought to be required for maintenance of a stem cell pool in the SAM. The MADS-box gene AGAMOUS, in combination with an unknown factor, has been proposed as a possible negative regulator of WUS, leading to the termination of meristematic activity within the floral meristem. Transgenic petunia (Petunia hybrida) plants were produced in which the E-type and D-type MADS-box genes FLORAL BINDING PROTEIN2 (FBP2) and FBP11, respectively, are simultaneously overexpressed. These plants show an early arrest in development at the cotyledon stage. Molecular analysis of these transgenic plants revealed a possible combined action of FBP2 and FBP11 in repressing the petunia WUS homolog, TERMINATOR. Furthermore, the ectopic up-regulation of the C-type and D-type homeotic genes FBP6 and FBP7, respectively, suggests that they may also participate in a complex, which causes the determinacy in transgenic plants. These data support the model that a transcription factor complex consisting of C-, D-, and E-type MADS-box proteins controls the stem cell population in the floral meristem.
Extracellular ATP Induces the Accumulation of Superoxide via NADPH Oxidases in Arabidopsis
Authors: Song Charlotte J. , Steinebrunner Iris , Wang Xuanzhi , Stout Stephen C. , Roux Stanley J. 
Published: January 2006

AbstractExtracellular ATP can serve as a signaling agent in animal cells, and, as suggested by recent reports, may also do so in plant cells. In animal cells it induces the production of reactive oxygen species through the mediation of NADPH oxidase. Similarly, here we report that in leaves of Arabidopsis (Arabidopsis thaliana), applied ATP, but not AMP or phosphate, induces the accumulation of superoxide (O2 −) in a biphasic, dose-dependent manner, with a threshold at 500 nm ATP. This effect did not require ATP hydrolysis for it was mimicked by ATPγS. ATP also induced increased levels of Arabidopsis respiratory burst oxidase homolog D (AtrbohD) mRNA, but ATP-treated plants that had disrupted AtrbohD and AtrbohF genes did not accumulate O2 −, indicating that NADPH oxidases are responsible for the induced O2 − accumulation. Inhibitors of mammalian P2-type ATP receptors abolished ATP-induced O2 − production, suggesting that the ATP effects may be mediated through P2-like receptors in plants. Cytosolic Ca2+ and calmodulin are likely to help transduce the ATP responses, as they do in animal cells, because a Ca2+ channel blocker, a Ca2+ chelator, and calmodulin antagonist all reduced ATP-induced O2 − accumulation. Furthermore, ATP treatment enhanced the expression of genes that are induced by wounds and other stresses. The ATP measured at wound sites averaged 40 μ m, well above the level needed to induce O2 − accumulation and gene expression changes. Transgenic plants overexpressing an apyrase gene had reduced O2 − production in response to applied ATP and wounding. Together, these data suggest a possible role for extracellular ATP as a signal potentially in wound and stress responses.
Forward Genetic Analysis of the Circadian Clock Separates the Multiple Functions of ZEITLUPE
Authors: Kevei Éva , Gyula Péter , Hall Anthony , Kozma-Bognár László , Kim Woe-Yeon , Eriksson Maria E. , Tóth Réka , Hanano Shigeru , Fehér Balázs , Southern Megan M. , Bastow Ruth M. , Viczián András , Hibberd Victoria , Davis Seth J. , Somers David E. , Nagy Ferenc , Millar Andrew J. 
Published: January 2006

Abstract
The circadian system of Arabidopsis (Arabidopsis thaliana) includes feedback loops of gene regulation that generate 24-h oscillations. Components of these loops remain to be identified; none of the known components is completely understood, including ZEITLUPE (ZTL), a gene implicated in regulated protein degradation. ztl mutations affect both circadian and developmental responses to red light, possibly through ZTL interaction with PHYTOCHROME B (PHYB). We conducted a large-scale genetic screen that identified additional clock-affecting loci. Other mutants recovered include 11 new ztl alleles encompassing mutations in each of the ZTL protein domains. Each mutation lengthened the circadian period, even in dark-grown seedlings entrained to temperature cycles. A mutation of the LIGHT, OXYGEN, VOLTAGE (LOV)/Period-ARNT-Sim (PAS) domain was unique in retaining wild-type responses to red light both for the circadian period and for control of hypocotyl elongation. This uncoupling of ztl phenotypes indicates that interactions of ZTL protein with multiple factors must be disrupted to generate the full ztl mutant phenotype. Protein interaction assays showed that the ztl mutant phenotypes were not fully explained by impaired interactions with previously described partner proteins Arabidopsis S-phase kinase-related protein 1, TIMING OF CAB EXPRESSION 1, and PHYB. Interaction with PHYB was unaffected by mutation of any ZTL domain. Mutation of the kelch repeat domain affected protein binding at both the LOV/PAS and the F-box domains, indicating that interaction among ZTL domains leads to the strong phenotypes of kelch mutations. Forward genetics continues to provide insight regarding both known and newly discovered components of the circadian system, although current approaches have saturated mutations at some loci.
Identification and Characterization of the Arabidopsis Orthologs of Nuclear Transport Factor 2, the Nuclear Import Factor of Ran
Authors: Zhao Qiao , Leung Sara , Corbett Anita H. , Meier Iris 
Published: January 2006

Abstract
Ran is a multifunctional small GTPase that is involved in nucleocytoplasmic transport, mitotic spindle assembly, and nuclear envelope formation. Nuclear import of Ran relies on a small RanGDP-binding protein, Nuclear Transport Factor 2 (NTF2). Three proteins are expressed in Arabidopsis (Arabidopsis thaliana) that show significant sequence similarity to human and yeast (Saccharomyces cerevisiae) NTF2. Here, we demonstrate that two of them, AtNTF2a and AtNTF2b, can functionally replace the essential NTF2 gene in yeast. Consistent with this finding, both AtNTF2a and AtNTF2b interact with yeast and Arabidopsis Ran. The third NTF2-related protein, AtNTL, does not functionally replace NTF2 in yeast. Similar to yeast NTF2-green fluorescent protein (GFP), AtNTF2a-GFP and AtNTF2b-GFP accumulate at the nuclear rim. The AtNTF2a E38K and E91K mutants, which fail to bind Ran, are not functional in yeast, indicating conservation of the requirement for these key amino acids in plants and yeast. AtNTF2a overexpression, but not AtNTF2aE38K overexpression, blocks nuclear import of a plant transcription factor in Nicotiana benthamiana leaves, indicating that excess AtNTF2a disrupts nuclear import in a Ran-binding-dependent manner. On the basis of these results, we propose that AtNTF2a and AtNTF2b function in Ran import in Arabidopsis and that nuclear import of Ran is functionally conserved in plants.
Stimulation of CD8+T Cells following Diphtheria Toxin-Mediated Antigen Delivery into Dendritic Cells
Authors: Shaw Christine A. , Starnbach Michael N. 
Published: January 2006

ABSTRACTRecognition and clearance of many intracellular pathogens requires the activation and subsequent effector functions of CD8+T lymphocytes. To stimulate CD8+T cells by immunization, the target antigens must be delivered into the cytosol of host cells. There they can be processed into peptides and presented in the context of major histocompatibility complex class I molecules to antigen-specific CD8+T cells. One method of delivering antigens into the cytosol is to fuse them to modified bacterial toxins that are able to enter mammalian cells. The expression pattern of the toxin receptors in the host will determine the cell population that the toxin fusion protein targets and will thus restrict antigen-specific T-cell recognition to the same population. In this study we describe the development and characterization of a diphtheria toxin (DT)-based antigen delivery system. Using CD11c-DTR transgenic mice that express the DT receptor in dendritic cells (DC), this system allows for targeted delivery of CD8+T-cell antigen to DC. We show that antigen-specific CD8+T cells proliferate in CD11c-DTR mice following immunization with catalytically inactive DT-antigen fusion proteins. We also show that a toxin-based system that restricts antigen delivery to DC results in more robust antigen-specific CD8+T-cell proliferation than a toxin-based system that does not restrict delivery to a particular cell type. These results have implications for vaccine design, and they suggest that use of a toxin-based vector to target antigen to DC may be an effective way to induce a CD8+T-cell response.
Human Monoclonal Anti-Protective Antigen Antibody Completely Protects Rabbits and Is Synergistic with Ciprofloxacin in Protecting Mice and Guinea Pigs against Inhalation Anthrax
Authors: Peterson Johnny W. , Comer Jason E. , Noffsinger David M. , Wenglikowski Autumn , Walberg Kristin G. , Chatuev Bagram M. , Chopra Ashok K. , Stanberry Lawrence R. , Kang Angray S. , Scholz Wolfgang W. , Sircar Jagadish 
Published: January 2006

ABSTRACT

Prevention of inhalation anthrax requires early and extended antibiotic therapy, and therefore, alternative treatment strategies are needed. We investigated whether a human monoclonal antibody (AVP-21D9) to protective antigen (PA) would protect mice, guinea pigs, and rabbits against anthrax. Control animals challenged with
Bacillus anthracis
Ames spores by the intranasal route died within 3 to 7 days. AVP-21D9 alone provided minimal protection against anthrax in the murine model, but its efficacy was notably better in guinea pigs. When Swiss-Webster mice, challenged with five 50% lethal doses (LD
50
s) of anthrax spores, were given a single 16.7-mg/kg of body weight AVP-21D9 antibody dose combined with ciprofloxacin (30 mg/kg/day for 6 days) 24 h after challenge, 100% of the mice were protected for more than 30 days, while ciprofloxacin or AVP-21D9 alone showed minimal protection. Similarly, when AVP-21D9 antibody (10 to 50 mg/kg) was combined with a low, nonprotective dose of ciprofloxacin (3.7 mg/kg/day) and administered to guinea pigs for 6 days, synergistic protection against anthrax was observed. In contrast, a single dose of AVP-21D9 antibody (1, 5, 10, or 20 mg/kg) but not 0.2 mg/kg alone completely protected rabbits against challenge with 100 LD
50
s of
B. anthracis
Ames spores, and 100% of the rabbits survived rechallenge. Further, administration of AVP-21D9 (10 mg/kg) to rabbits at 0, 6, and 12 h after challenge with anthrax spores resulted in 100% survival; however, delay of antibody treatment by 24 and 48 h reduced survival to 80% and 60%, respectively. Serological analysis of sera from various surviving animals 30 days postprimary infection showed development of a species-specific PA enzyme-linked immunosorbent assay antibody titer that correlated with protection against reinfection. Taken together, the effectiveness of human anti-PA antibody alone or in combination with low ciprofloxacin levels may provide the basis for an improved strategy for prophylaxis or treatment following inhalation anthrax infection.
Identification of Proteins Secreted via
Vibrio parahaemolyticus
Type III Secretion System 1
Authors: Ono Takahiro , Park Kwon-Sam , Ueta Mayumi , Iida Tetsuya , Honda Takeshi 
Published: January 2006

ABSTRACT

Vibrio parahaemolyticus
, a gram-negative marine bacterium, is an important pathogen causing food-borne gastroenteritis or septicemia. Recent genome sequencing of the RIMD2210633 strain (a Kanagawa phenomenon-positive clinical isolate of serotype O3:K6) revealed that the strain has two sets of gene clusters that encode the type III secretion system (TTSS) apparatus. The first cluster, TTSS1, is located on the large chromosome, and the second, TTSS2, is on the small chromosome. Previously, we reported that TTSS1 is involved in the cytotoxicity of the RIMD2210633 strain against HeLa cells. Here, we analyzed proteins secreted via the TTSS apparatus encoded by TTSS1 by using two-dimensional gel electrophoresis and identified the proteins encoded by genes VP1680, VP1686, and VPA450. To investigate the roles of those secreted proteins, we constructed and analyzed a series of deletion mutants. Flow cytometry analysis using fluorescence-activated cell sorting with fluorescein isothiocyanate-labeled annexin V demonstrated that the TTSS1-dependent cell death was by apoptosis. The cytotoxicity to HeLa cells was related to one of the newly identified secreted proteins encoded by VP1680. Adenylate cyclase fusion protein studies proved that the newly identified secreted proteins were translocated into HeLa cells. Thus, these appear to be the TTSS effector proteins in
V. parahaemolyticus
.
TheBordetella bronchisepticaType III Secretion System Inhibits Gamma Interferon Production That Is Required for Efficient Antibody-Mediated Bacterial Clearance
Authors: Pilione Mylisa R. , Harvill Eric T. 
Published: January 2006

ABSTRACTSeveral species of pathogenic microorganisms have developed strategies to survive and persist in vital organs which are normally maintained as sterile by the generation of strong immune responses. Here, we report an immunomodulation involving theBordetella bronchisepticatype III secretion system (TTSS) which contributes to bacterial survival in the lower respiratory tract of the host. The prolonged persistence ofB. bronchisepticathat was observed in gamma interferon (IFN-γ)−/−mice indicates that the efficient clearance of bacteria from the lower respiratory tract requires not only B cells and antibodies but also IFN-γ production. Our data also suggest that interleukin-10 (IL-10)-producing splenocytes are generated early during infection and that IL-10 inhibits IFN-γ-producing cells and delays the clearance ofB. bronchisepticafrom the lungs. The TTSS ofB. bronchisepticainhibits the generation of IFN-γ-producing splenocytes and is required for long-term bacterial persistence in the lower respiratory tract in wild-type mice. This suggests that a mechanism involving the modulation of IFN-γ production by the TTSS facilitatesB. bronchisepticasurvival in the lower respiratory tract.
Role for Inducible Costimulator in Control ofSalmonella entericaSerovar Typhimurium Infection in Mice
Authors: Vidric Mariana , Bladt Anna Tafuri , Dianzani Umberto , Watts Tania H. 
Published: January 2006

ABSTRACTInducible costimulator (ICOS) is expressed on activated T cells and plays a key role in sustaining and enhancing the effector function of CD4 T cells. Given the function of this molecule in sustaining T-cell responses, we reasoned that ICOS might play an important role in a prolonged infection model, such asSalmonellainfection of mice. To test this hypothesis, wild-type (WT) and ICOS-deficient (ICOS−/−) mice were infected systemically with aSalmonella entericaserovar Typhimurium strain expressing the chicken ovalbumin gene (Salmonella-OVA). ICOS−/−mice exhibited greater splenomegaly than WT mice and showed delayed bacterial clearance. The acquired immune response in this model was slow to develop. Maximal T-cell responses toSalmonella-OVA were detected at 3 weeks postinfection in both WT and ICOS−/−mice. CD4 T-cell-dependent gamma interferon production and a class switch to immunoglobulin G2a were severely reduced in ICOS−/−mice. ICOS−/−mice also exhibited a substantial defect in antigen-specific CD8 T-cell responses. In vitro, the effect of anti-ICOS on CD8 T-cell division was greater when CD8 T cells rather than CD4 T cells expressed ICOS, suggesting that the in vivo effects of ICOS on CD8 T cells could be direct. Taken together, these studies show that ICOS plays a critical role in control ofSalmonellainfection in mice, with effects on antibody, Th1, and CD8 T-cell responses.
Construction and Phase I Clinical Evaluation of the Safety and Immunogenicity of a Candidate Enterotoxigenic
Escherichia coli
Vaccine Strain Expressing Colonization Factor Antigen CFA/I
Authors: Turner Arthur K. , Beavis Juliet C. , Stephens Jonathan C. , Greenwood Judith , Gewert Cornelia , Thomas Nicola , Deary Alison , Casula Gabriella , Daley Alexandra , Kelly Paul , Randall Roger , Darsley Michael J. 
Published: January 2006

ABSTRACT

Oral delivery of toxin-negative derivatives of enterotoxigenic
Escherichia coli
(ETEC) that express colonization factor antigens (CFA) with deletions of the
aroC
,
ompC
,
ompF
, and toxin genes may be an effective approach to vaccination against ETEC-associated diarrhea. We describe the creation and characterization of an attenuated CFA/I-expressing ETEC vaccine candidate, ACAM2010, from a virulent isolate in which the heat-stable enterotoxin (ST) and CFA/I genes were closely linked and on the same virulence plasmid as the enteroaggregative
E. coli
heat-stable toxin (EAST1) gene. A new suicide vector (pJCB12) was constructed and used to delete the ST and EAST1 genes and to introduce defined deletion mutations into the
aroC
,
ompC
, and
ompF
chromosomal genes. A phase I trial, consisting of an open-label dose escalation phase in 18 adult outpatient volunteers followed by a placebo-controlled double-blind phase in an additional 31 volunteers, was conducted. The vaccine was administered in two formulations, fresh culture and frozen suspension. These were both well tolerated, with no evidence of significant adverse events related to vaccination. Immunoglobulin A (IgA) and IgG antibody-secreting cells specific for CFA/I were assayed by ELISPOT. Positive responses (greater than twofold increase) were seen in 27 of 37 (73%) subjects who received the highest dose level of vaccine (nominally 5 × 10
9
CFU). Twenty-nine of these volunteers were secreting culturable vaccine organisms at day 3 following vaccination; five were still positive on day 7, with a single isolation on day 13. This live attenuated bacterial vaccine is safe and immunogenic in healthy adult volunteers.