bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcription Factor STE12α Has Distinct Roles in Morphogenesis, Virulence, and Ecological Fitness of the Primary Pathogenic YeastCryptococcus gattii
Authors: Ren Ping , Springer Deborah J. , Behr Melissa J. , Samsonoff William A. , Chaturvedi Sudha , Chaturvedi Vishnu 
Published: July 2006

ABSTRACTCryptococcus gattiiis a primary pathogenic yeast, increasingly important in public health, but factors responsible for its host predilection and geographical distribution remain largely unknown. We have characterizedC. gattii STE12α to probe its role in biology and pathogenesis because this transcription factor has been linked to virulence in many human and plant pathogenic fungi. A full-lengthSTE12α gene was cloned by colony hybridization and sequenced using primer walk and 3′ rapid amplification of cDNA ends strategies, and aste12αΔ gene knockout mutant was created byURA5insertion at the homologous site. A semiquantitative analysis revealed delayed and poor mating inste12αΔ mutant; this defect was not reversed by exogenous cyclic AMP.C. gattiiparent and mutant strains showed robust haploid fruiting. Among putative virulence factors tested, the laccase transcript and enzymatic activity were down regulated in theste12αΔ mutant, with diminished production of melanin. However, capsule, superoxide dismutase, phospholipase, and urease were unaffected. Similarly, Ste12 deficiency did not cause any auxotrophy, assimilation defects, or sensitivity to a large panel of chemicals and antifungals. Theste12αΔ mutant was markedly attenuated in virulence in both BALB/c and A/Jcr mice models of meningoencephalitis, and it also exhibited significant in vivo growth reduction and was highly susceptible to in vitro killing by human neutrophils (polymorphonuclear leukocytes). In tests designed to simulate theC. gattiinatural habitat, theste12αΔ mutant was poorly pigmented on wood agar prepared from two tree species and showed poor survival and multiplication in wood blocks. Thus,STE12α plays distinct roles inC. gattiimorphogenesis, virulence, and ecological fitness.
FsFKS1, the 1,3-β-Glucan Synthase from the Caspofungin-Resistant FungusFusarium solani
Authors: Ha Young-sil , Covert Sarah F. , Momany Michelle 
Published: July 2006

ABSTRACTThe cell wall, a mesh of carbohydrates and proteins, shapes and protects the fungal cell. The enzyme responsible for the synthesis of one of the main components of the fungal wall, 1,3-β-glucan synthase, is targeted by the antifungal caspofungin acetate (CFA). Clinical isolates ofCandida albicansandAspergillus fumigatusare much more sensitive to CFA than clinical isolates ofFusariumspecies. To better understand CFA resistance inFusariumspecies, we cloned and sequenced FsFKS1, which encodes theFusarium solanif. sp.pisiβ(1,3)-d-glucan synthase, used RNA interference to reduce its expression and complemented deletion of the essentialfksgene of the CFA-sensitive fungusA. fumigatuswith FsFKS1. Reduction of the FsFKS1message inF. solanif. sp.pisireduced spore viability and caused lysis of spores and hyphae, consistent with cell wall defects. Compensating for the loss ofA. fumigatus fks1with FsFKS1caused only a modest increase in the tolerance ofA. fumigatusfor CFA. Our results suggest that FsFKS1 is required for the proper construction ofF. solanicell walls and that the resistance ofF. solanito CFA is at best only partially due to resistance of the FsFKS1 enzyme to this antifungal agent.
Plasmodium falciparum
AMA1 Binds a Rhoptry Neck Protein Homologous to TgRON4, a Component of the Moving Junction in
Toxoplasma gondii
Authors: Alexander David L. , Arastu-Kapur Shirin , Dubremetz Jean-Francois , Boothroyd John C. 
Published: July 2006

ABSTRACT

Plasmodium falciparum
apical membrane antigen 1 (PfAMA1) coimmunoprecipitates with the
Plasmodium
homologue of TgRON4, a secreted rhoptry neck protein of
Toxoplasma gondii
that migrates at the moving junction in association with TgAMA1 during invasion. PfRON4 also originates in the rhoptry necks, suggesting that this unusual collaboration of micronemes and rhoptries is a conserved feature of
Apicomplexa
.
Gene Expression Induced by Copper Stress in the DiatomThalassiosira pseudonana
Authors: Davis Aubrey K. , Hildebrand Mark , Palenik Brian 
Published: July 2006

ABSTRACTUtilizing a PCR-based subtractive cDNA approach, we demonstrated that the marine diatomThalassiosira pseudonanaexhibits a rapid response at the gene level to elevated concentrations of copper and that this response attenuates over 24 h of continuous exposure. A total of 16 copper-induced genes were identified, 11 of which were completely novel; however, many of the predicted amino acid sequences had characteristics suggestive of roles in ameliorating copper toxicity. Most of the novel genes were not equivalently induced by H2O2- or Cd-induced stress, indicating specificity in response. Two genes that could be assigned functions based on homology were also induced under conditions of general cellular stress. Half of the identified genes were located within two inverted repeats in the genome, and novel genes in one inverted repeat had mRNA levels induced by ∼500- to 2,000-fold by exposure to copper for 1 h. Additionally, some of the inverted repeat genes demonstrated a dose-dependent response to Cu, but not Cd, and appear to belong to a multigene family. This multigene family may be the diatom functional homolog of metallothioneins.
cis
-Acting Site Controlling Bidirectional Transcription at the Growth-Differentiation Transition in
Dictyostelium discoideum
Authors: Hirose Shigenori , Payne Samuel H. , Loomis William F. 
Published: July 2006

ABSTRACT

A pair of adjacent genes,
impA
and
dia1
, are divergently transcribed but expressed at different stages in the life cycle of
Dictyostelium discoideum
. The intervening 654-bp region carries
cis
-acting regions that are essential for transcription in both directions as well as repression of
dia1
in growing cells. We have focused on a 112-bp region proximal to
dia1
that is essential for bidirectional transcription. Analyses of a set of internal deletions showed that the sequence between positions 80 and 97 (TTTGAATTTTTTGAATTT) is critical and that bases outside this region are dispensable. Site-directed mutations within this critical region confirmed the importance of this sequence for transcription both to the right and to the left. However, insertions of either 6 or 24 Ts into the run of 6 Ts separating the repeated GAA sequence had little effect on the functioning of the site in either direction, suggesting that factors recognize the half-sites TTGAATT separately. Inversion of the bases between positions 80 and 97 greatly reduced expression in both directions, indicating that orientation is critical for expression of both the nearby
impA
gene and the distal
dia1
gene, which is more than 500 bp away. Comparison of 38 mutant constructs with multiple random variations in the region indicated that transcription factors may bind to a range of related sequences and still retain function. All functional constructs directed transcription both leftward and rightward, while all nonfunctional constructs were impaired for transcription in both directions. It appears that the same transcription complex controls transcription of both
impA
and
dia1
.
A MADS Box Protein Interacts with a Mating-Type Protein and Is Required for Fruiting Body Development in the Homothallic Ascomycete
Sordaria macrospora
Authors: Nolting Nicole , Pöggeler Stefanie 
Published: July 2006

ABSTRACT

MADS box transcription factors control diverse developmental processes in plants, metazoans, and fungi. To analyze the involvement of MADS box proteins in fruiting body development of filamentous ascomycetes, we isolated the
mcm1
gene from the homothallic ascomycete
Sordaria macrospora
, which encodes a putative homologue of the
Saccharomyces cerevisiae
MADS box protein Mcm1p. Deletion of the
S. macrospora mcm1
gene resulted in reduced biomass, increased hyphal branching, and reduced hyphal compartment length during vegetative growth. Furthermore, the
S. macrospora Δmcm1
strain was unable to produce fruiting bodies or ascospores during sexual development. A yeast two-hybrid analysis in conjugation with in vitro analyses demonstrated that the
S. macrospora
MCM1 protein can interact with the putative transcription factor SMTA-1, encoded by the
S. macrospora
mating-type locus. These results suggest that the
S. macrospora
MCM1 protein is involved in the transcriptional regulation of mating-type-specific genes as well as in fruiting body development.
A Mitogen-Activated Protein Kinase Controls Differentiation of Bloodstream Forms of
Trypanosoma brucei
Authors: Domenicali Pfister Debora , Burkard Gabriela , Morand Sabine , Renggli Christina Kunz , Roditi Isabel , Vassella Erik 
Published: July 2006

ABSTRACT

African
trypanosomes undergo differentiation in order to adapt to the mammalian
host and the tsetse fly vector. To characterize the role of a
mitogen-activated protein (MAP) kinase homologue, TbMAPK5, in the
differentiation of
Trypanosoma brucei
, we constructed
a knockout in procyclic (insect) forms from a differentiation-competent
(pleomorphic) stock. Two independent knockout clones proliferated
normally in culture and were not essential for other life cycle stages
in the fly. They were also able to infect immunosuppressed mice, but
the peak parasitemia was 16-fold lower than that of the wild type.
Differentiation of the proliferating long slender to the
nonproliferating short stumpy bloodstream form is triggered by an
autocrine factor, stumpy induction factor (SIF). The knockout
differentiated prematurely in mice and in culture, suggestive of
increased sensitivity to SIF. In contrast, a null mutant of a cell line
refractory to SIF was able to proliferate normally. The differentiation
phenotype was partially rescued by complementation with wild-type
TbMAPK5 but exacerbated by introduction of a nonactivatable mutant
form. Our results indicate a regulatory function for TbMAPK5 in the
differentiation of bloodstream forms of
T. brucei
that might be exploitable as a target for chemotherapy against human
sleeping
sickness.
Changing Roles of Aurora-B Kinase in Two Life Cycle Stages of
Trypanosoma brucei
Authors: Li Ziyin , Wang C. C. 
Published: July 2006

ABSTRACT

Aurora-B kinase is a chromosomal passenger protein essential for chromosome segregation and cytokinesis. In the procyclic form of
Trypanosoma brucei
, depletion of an aurora-B kinase homologue TbAUK1 inhibited spindle formation, mitosis, cytokinesis, and organelle replication without altering cell morphology. In the present study, an RNA interference knockdown of TbAUK1 or overexpression of inactive mutant TbAUK1-K58R in the bloodstream form also resulted in defects in spindle formation, chromosome segregation, and cytokinesis but allowed multiple rounds of nuclear DNA synthesis, nucleolus multiplication, and continuous replication of kinetoplast, basal body, and flagellum. The typical trypanosome morphology was lost to an enlarged round shape filled with microtubules. It is thus apparent that there are distinctive mechanisms of action of TbAUK1 in regulating cell division between the two developmental stages of trypanosome. While it exerts a tight control on mitosis, organelle replication, and cytokinesis in the procyclic form, it regulates cytokinesis without rigid control over either nuclear DNA synthesis or organelle replication in the bloodstream form. The molecular basis underlining these discrepancies remains to be explored.
Celecoxib Treatment Alters the Gene Expression Profile of Normal Colonic Mucosa
Authors: Glebov Oleg K. , Rodriguez Luz M. , Lynch Patrick , Patterson Sherri , Lynch Henry , Nakahara Kenneth , Jenkins Jean , Cliatt Janet , Humbyrd Casey-Jo , DeNobile John , Soballe Peter , Gallinger Steven , Buchbinder Aby , Gordon Gary , Hawk Ernest , Kirsch Ilan R. 
Published: July 2006

Abstract
A clinical trial was recently conducted to evaluate the safety and efficacy of a selective inhibitor of cyclooxygenase-2 (celecoxib) in hereditary nonpolyposis colon cancer patients. In a randomized, placebo-controlled phase I/II multicenter trial, hereditary nonpolyposis colon cancer patients and gene carriers received either celecoxib at one of two doses or placebo. The goal was to evaluate the effects of these treatment arms on a number of endoscopic and tissue-based biomarker end points after 12 months of treatment. As part of this trial, we analyzed gene expression by cDNA array technology in normal descending (rectal) colonic mucosa of patients before and after treatment with celecoxib or placebo. We found that treatment of patients with celecoxib at recommended clinical doses (200 and 400 mg p.o. bid), in contrast to treatment with placebo, leads to changes in expression of &gt;1,400 genes in the healthy colon, although in general, the magnitude of changes is &lt;2-fold. Twenty-three of 25 pairs of colon biopsies taken before and after celecoxib treatment can be classified correctly by the pattern of gene expression in a leave-one-out cross-validation. Immune response, particularly T- and B-lymphocyte activation and early steps of inflammatory reaction, cell signaling and cell adhesion, response to stress, transforming growth factor-β signaling, and regulation of apoptosis, are the main biological processes targeted by celecoxib as shown by overrepresentation analysis of the distribution of celecoxib-affected genes across Gene Ontology categories. Analysis of possible cumulative effects of celecoxib-induced changes in gene expression indicates that in healthy colon, celecoxib may suppress the immune response and early steps of inflammation, inhibit formation of focal contacts, and stimulate transforming growth factor-β signaling. (Cancer Epidemiol Biomarkers Prev 2006;15(7):1382–91)
Mammographic Density Correlation with Gail Model Breast Cancer Risk Estimates and Component Risk Factors
Authors: Palomares Melanie R. , Machia Joelle R.B. , Lehman Constance D. , Daling Janet R. , McTiernan Anne 
Published: July 2006

AbstractBackground: The Gail model is a validated breast cancer risk assessment tool that is primarily based on nonmodifiable breast cancer risk factors. Conversely, mammographic breast density is strongly correlated with breast cancer risk and responds to risk-modifying interventions. The purpose of our study was to correlate mammographic density with breast cancer risk as calculated by the Gail model and to examine the relative association of each of the model covariates to mammographic density.Methods: The study included 99 participants of the National Surgical Breast and Bowel Project P-1 trial, ages 36 to 74 years, all of whom had a mammogram and Gail model risk estimates done upon trial entry. Baseline mammograms were retrieved and digitized, and mammographic density was assessed by both subjective and computer-assisted objective measures.Results: Mammographic density was 2-fold higher in women with a &gt;15% lifetime risk of breast cancer compared with those with &lt;15% risk, by all density assessment methods. This was equivalent to a 3% to 6% increase in density per 10% increase in risk. Gail model covariates that measured benign or premalignant breast tissue changes accounted for the majority (41%) of the relationship with increased mammographic density. Seven percent of density was not explained by risk factors included in the Gail model.Conclusions: The Gail model does not fully account for the association between breast density and calculated breast cancer risk. Because mammographic density is a modifiable marker, development of a breast cancer risk assessment tool that includes mammographic density could be beneficial for assessing individual risk. (Cancer Epidemiol Biomarkers Prev 2006;15(7):1324–30)
Comparative Analysis of 19 Genital Human Papillomavirus Types with Regard to p53 Degradation, Immortalization, Phylogeny, and Epidemiologic Risk Classification
Authors: Hiller Thomas , Poppelreuther Sven , Stubenrauch Frank , Iftner Thomas 
Published: July 2006

Abstract
We have analyzed E6 proteins of 19 papillomaviruses able to infect genital tissue with regard to their ability to degrade p53 and the thus far unknown immortalization potential of the genomes of human papillomaviruses (HPV) 53, 56, 58, 61, 66, and 82 in primary human keratinocytes. E6 proteins of HPV types 16, 18, 33, 35, 39, 45, 51, 52, 56, 58, and 66, defined as high-risk types, were able to induce p53 degradation in vitro, and HPV18-, HPV56-, and HPV58-immortalized keratinocytes revealed markedly reduced levels of p53. In contrast, the E6 proteins of HPV6 and 11 and HPV44, 54, and 61, regarded as possible carcinogenic or low-risk HPV types, respectively, did not degrade p53. Interestingly, the E6 proteins of HPV 53, 70, and 82 inconsistently risk classified in the literature were also found to induce p53 degradation. The genomes of HPV53 and 82 immortalized primary human keratinocytes that revealed almost absent nuclear levels of p53. These data suggest a strict correlation between the biological properties of certain HPV types with conserved nucleotide sequence (phylogeny), which is largely coherent with epidemiologic risk classification. HPV types 16, 18, 33, 35, 39, 45, 51, 52, 56, 58, and 66, generally accepted as high-risk types, behaved in our assays biologically different from HPV types 6, 11, 44, 54, and 61. In contrast, HPV70, regarded as low-risk type, and HPV53 or HPV82, with inconsistent described risk status, were indistinguishable with respect to p53 degradation and immortalization from prototype high-risk HPV types. This could imply that other important functional differences exist between phylogenetically highly related viruses displaying similar biological properties in tissue culture that may affect their carcinogenicity in vivo. (Cancer Epidemiol Biomarkers Prev 2006;15(7):1262–7)
Estimating Exposure to Polycyclic Aromatic Hydrocarbons: A Comparison of Survey, Biological Monitoring, and Geographic Information System–Based Methods
Authors: Gunier Robert B. , Reynolds Peggy , Hurley Susan E. , Yerabati Sauda , Hertz Andrew , Strickland Paul , Horn-Ross Pamela L. 
Published: July 2006

Abstract
Our objective was to compare polycyclic aromatic hydrocarbon (PAH) exposure estimates based on survey, biological monitoring, and geographic information system (GIS) methods. The 304 participants in this study supplied a urine sample and completed questionnaires about exposure to potential PAH sources. We assayed urine samples for 1-hydroxypyrene-O-glucuronide (1-OHPG), the major metabolite of pyrene, a common PAH. We used a GIS to estimate traffic exhaust exposure using vehicle count data at the residence and workplace. The five subjects who reported smoking during the 48-hour period had median 1-OHPG concentrations 10-fold that of nonsmokers (1.6 versus 0.16 pmol/mL; P = 0.01). Among nonsmokers, those who reported eating grilled, roasted, or broiled meat had significantly higher 1-OHPG concentrations than those who did not reported eating meat prepared by these methods (0.25 versus 0.06 pmol/mL; P = 0.02). Nonsmokers who reported traveling on roads for ≥3 hours during the 48-hour period also had significantly higher 1-OHPG levels than those who traveled &lt;3 hours (0.23 versus 0.11 pmol/mL; P = 0.03). 1-OHPG levels were also correlated with hours of secondhand smoke exposure among nonsmokers (P = 0.04). In this study, 1-OHPG urine concentrations were not associated with self-reported exposures to cooking smoke, wood burning, or traffic levels near the home or to traffic density or urban/rural status determined using a GIS. Self-reported indicators of residential proximity to high traffic volume were, however, associated with GIS traffic density measures. (Cancer Epidemiol Biomarkers Prev 2006;15(7):1376–81)
Folate Intake and Stomach Cancer Incidence in a Prospective Cohort of Swedish Women
Authors: Larsson Susanna C. , Giovannucci Edward , Wolk Alicja 
Published: July 2006

AbstractBackground: Experimental and epidemiologic evidence suggests that folate may play a role in the development of some cancers. Case-control studies and one prospective cohort study on folate intake in relation to stomach cancer risk have yielded inconsistent results.Methods: We prospectively investigated the relation between folate intake and the incidence of stomach cancer among 61,433 women in the Swedish Mammography Cohort. Participants completed a food frequency questionnaire at baseline (1987-1990) and again in 1997. During follow-up through December 2004, 156 incident stomach cancer cases were diagnosed. Cox proportional hazards models were used to calculate multivariate-adjusted hazard ratios.Results: There was no association between dietary folate intake (i.e., folate from food sources) and the risk of stomach cancer. The multivariate hazard ratio for the highest compared with the lowest category of updated average dietary folate intake was 1.04 (95% confidence interval, 0.61-1.86; Ptrend = 0.91). The relation between dietary folate intake and stomach cancer did not vary significantly by intake of alcohol, methionine, or caffeine.Conclusion: Results from this prospective study do not support an association between dietary folate intake and risk of stomach cancer. (Cancer Epidemiol Biomarkers Prev 2006;15(7):1409–12)
Motives of Belgian Adolescents for Using Sunscreen: The Role of Action Plans
Authors: de Vries Hein , Mesters Ilse , Riet Jonathan van't , Willems Karen , Reubsaet Astrid 
Published: July 2006

Abstract
The first objective of this study was to analyze the differences between adolescents who use sunscreen frequently and those who do not. The second objective was to explore the importance of specific action plans when planning sunscreen use. Data was gathered among 602 Belgian secondary school students. Frequent and infrequent users of sunscreen were compared on several determinants related with sunscreen use, and a regression analysis on sunscreen use was done. Frequent users of sunscreen measures had significantly higher scores on attitudes, social influence, self-efficacy, some awareness factors, intention, and action plans. The integrated model for exploring motivational and behavioral change (I-Change model) explained 57% of the total variance of using sunscreen every 2 hours. Frequent sunscreen use was most strongly predicted by action plans, followed by positive intentions to use sunscreen, wearing protective clothing, seeking shade, attitude toward sunscreen use, education, social influence, and exposure to the sun. Our results suggest that skin cancer prevention programs aimed at promoting sunscreen use need to emphasize the advantages of sunscreen to infrequent users and to increase feelings of self-efficacy. Moreover, support by friends and parents should be stimulated. Finally, developing specific action plans for the use of sunscreen should be promoted to more effectively translate general intentions into actual sunscreen use. (Cancer Epidemiol Biomarkers Prev 2006;15(7):1360–6)