bluuebunny/crossref_metadata_2025_split huggingface dataset:
The ExsY Protein Is Required for Complete Formation of the Exosporium of
Bacillus anthracis
Authors: Boydston Jeremy A. , Yue Ling , Kearney John F. , Turnbough Charles L. 
Published: October 2006

ABSTRACT

The outermost layer of the
Bacillus anthracis
spore is the exosporium, which is composed of a paracrystalline basal layer and an external hair-like nap. The filaments of the nap are formed by a collagen-like glycoprotein called BclA, while the basal layer contains several different proteins. One of the putative basal layer proteins is ExsY. In this study, we constructed a
ΔexsY
mutant of
B. anthracis
, which is devoid of ExsY, and examined the assembly of the exosporium on spores produced by this strain. Our results show that exosporium assembly on
ΔexsY
spores is aberrant, with assembly arrested after the formation of a cap-like fragment that covers one end of the forespore—always the end near the middle of the mother cell. The cap contains a normal hair-like nap but an irregular basal layer. The cap is retained on spores prepared on solid medium, even after spore purification, but it is lost from spores prepared in liquid medium. Microscopic inspection of
ΔexsY
spores prepared on solid medium revealed a fragile sac-like sublayer of the exosporium basal layer, to which caps were attached. Examination of purified
ΔexsY
spores devoid of exosporium showed that they lacked detectable levels of BclA and the basal layer proteins BxpB, BxpC, CotY, and inosine-uridine-preferring nucleoside hydrolase; however, these spores retained half the amount of alanine racemase presumed to be associated with the exosporium of wild-type spores. The
ΔexsY
mutation did not affect spore production and germination efficiencies or spore resistance but did influence the course of spore outgrowth.
Involvement of Nitric Oxide in Biofilm Dispersal of
Pseudomonas aeruginosa
Authors: Barraud Nicolas , Hassett Daniel J. , Hwang Sung-Hei , Rice Scott A. , Kjelleberg Staffan , Webb Jeremy S. 
Published: October 2006

ABSTRACT

Bacterial biofilms at times undergo regulated and coordinated dispersal events where sessile biofilm cells convert to free-swimming, planktonic bacteria. In the opportunistic pathogen
Pseudomonas aeruginosa
, we previously observed that dispersal occurs concurrently with three interrelated processes within mature biofilms: (i) production of oxidative or nitrosative stress-inducing molecules inside biofilm structures, (ii) bacteriophage induction, and (iii) cell lysis. Here we examine whether specific reactive oxygen or nitrogen intermediates play a role in cell dispersal from
P. aeruginosa
biofilms. We demonstrate the involvement of anaerobic respiration processes in
P. aeruginosa
biofilm dispersal and show that nitric oxide (NO), used widely as a signaling molecule in biological systems, causes dispersal of
P. aeruginosa
biofilm bacteria. Dispersal was induced with low, sublethal concentrations (25 to 500 nM) of the NO donor sodium nitroprusside (SNP). Moreover, a
P. aeruginosa
mutant lacking the only enzyme capable of generating metabolic NO through anaerobic respiration (nitrite reductase, Δ
nirS
) did not disperse, whereas a NO reductase mutant (Δ
norCB
) exhibited greatly enhanced dispersal. Strategies to induce biofilm dispersal are of interest due to their potential to prevent biofilms and biofilm-related infections. We observed that exposure to SNP (500 nM) greatly enhanced the efficacy of antimicrobial compounds (tobramycin, hydrogen peroxide, and sodium dodecyl sulfate) in the removal of established
P. aeruginosa
biofilms from a glass surface. Combined exposure to both NO and antimicrobial agents may therefore offer a novel strategy to control preestablished, persistent
P. aeruginosa
biofilms and biofilm-related infections.
Escherichia coli pfs
Transcription: Regulation and Proposed Roles in Autoinducer-2 Synthesis and Purine Excretion
Authors: Kim Youngbae , Lew Chih M. , Gralla Jay D. 
Published: October 2006

ABSTRACT

Pfs expression is required for several metabolic pathways and limits the production of autoinducer-2, a molecule proposed to play a central role in interspecies quorum sensing. The present study reveals physiological conditions and promoter DNA elements that regulate
Escherichia coli pfs
transcription. Pfs transcription is shown to rely on both sigma 70 and sigma 38 (
rpoS
), and the latter is subject to induction that increases
pfs
expression. Transcription is maximal as the cells approach stationary phase, and this level can be increased by salt stress through induction of sigma 38-dependent expression. The
pfs
promoter is shown to contain both positive and negative elements, which can be used by both forms of RNA polymerase. The negative element is contained within the overlapping
dgt
promoter, which is involved in purine metabolism. Consideration of the physiological roles of sigma 38 and
dgt
leads to a model for how autoinducer production is controlled under changing physiological conditions.
Loss of Caspase-8 Expression Does Not Correlate with MYCN Amplification, Aggressive Disease, or Prognosis in Neuroblastoma
Authors: Fulda Simone , Poremba Christopher , Berwanger Bernd , Häcker Sabine , Eilers Martin , Christiansen Holger , Hero Barbara , Debatin Klaus-Michael 
Published: October 2006

Abstract
Inactivation of caspase-8 because of aberrant gene methylation has been associated with amplification of the MYCN oncogene and aggressive disease in neuroblastoma, suggesting that caspase-8 may function as tumor suppressor. However, the prognostic effect of caspase-8 in neuroblastoma has remained obscure. Therefore, we investigated caspase-8 expression and its correlation with established prognostic markers and survival outcome in a large cohort of neuroblastoma patients. Here, we report that loss of caspase-8 protein expression occurs in the majority (75%) of neuroblastoma and is not restricted to advanced disease stages. Surprisingly, no correlation was observed between caspase-8 expression and MYCN amplification. Similarly, ectopic expression of MYCN or antisense-mediated down-regulation of MYCN had no effect on caspase-8 expression in neuroblastoma cell lines. In addition, caspase-8 expression did not correlate with other variables of high-risk disease (e.g., 1p36 aberrations, disease stage, age at diagnosis, or tumor histology). Most importantly, loss of caspase-8 protein had no effect on event-free or overall survival in the overall study population or in distinct subgroups of patients. By revealing no correlation between caspase-8 expression and MYCN amplification or other established variables of aggressive disease, our findings in a large cohort of neuroblastoma patients show that inactivation of caspase-8 is not a characteristic feature of aggressive neuroblastoma. Thus, our study provides novel insight into the biology of this tumor, which may have important clinical implications. (Cancer Res 2006; 66(20): 10016-23)
Induction of Senescence in Diterpene Ester–Treated Melanoma Cells via Protein Kinase C–Dependent Hyperactivation of the Mitogen-Activated Protein Kinase Pathway
Authors: Cozzi Sarah-Jane , Parsons Peter G. , Ogbourne Steven M. , Pedley Julie , Boyle Glen M. 
Published: October 2006

Abstract
The diterpene ester PEP005 is a novel anticancer agent that activates protein kinase C (PKC) and induces cell death in melanoma at high doses. We now describe the in vitro cytostatic effects of PEP005 and the diterpene ester phorbol 12-myristate 13-acetate, observed in 20% of human melanoma cell lines. Primary cultures of normal human neonatal fibroblasts were resistant to growth arrest, indicating a potential for tumor selectivity. Sensitive cell lines were induced to senesce and exhibited a G1 and G2-M arrest. There was sustained expression of p21WAF1/CIP1, irreversible dephosphorylation of the retinoblastoma protein, and transcriptional silencing of E2F-responsive genes in sensitive cell lines. Activation of mitogen-activated protein (MAP)/extracellular signal-regulated kinase (ERK) kinase (MEK) 1/2 by PKC was required for diterpene ester–induced senescence. Expression profiling revealed that the MAP kinase inhibitor HREV107 was expressed at a higher transcript level in resistant compared with sensitive cell lines. We propose that activation of PKC overstimulates the RAS/RAF/MEK/ERK pathway, resulting in molecular changes leading to the senescent phenotype. (Cancer Res 2006; 66(20): 10083-91)
Overexpression of Glycosylphosphatidylinositol (GPI) Transamidase Subunits Phosphatidylinositol Glycan Class T and/or GPI Anchor Attachment 1 Induces Tumorigenesis and Contributes to Invasion in Human Breast Cancer
Authors: Wu Guojun , Guo Zhongmin , Chatterjee Aditi , Huang Xin , Rubin Ethel , Wu Feng , Mambo Elizabeth , Chang Xiaofei , Osada Motonobu , Sook Kim Myoung , Moon Chulso , Califano Joseph A. , Ratovitski Edward A. , Gollin Susanne M. , Sukumar Saraswati , Sidransky David , Trink Barry 
Published: October 2006

Abstract
Based on the oncogenic role of phosphatidylinositol glycan (PIG) class U in human tumors, we explored the role of two additional subunits of the glycosylphosphatidylinositol (GPI) transamidase complex in human breast cancer. We found that PIG class T (PIG-T) and GPI anchor attachment 1 (GPAA1) were overexpressed in breast cancer cell lines and primary tumors. Forced expression of PIG-T and GPAA1 transformed NIH3T3 cells in vitro and increased tumorigenicity and invasion of these cells in vivo. Suppression of PIG-T expression in breast cancer cell lines led to inhibition of anchorage-independent growth. Moreover, we found that PIG-T and GPAA1 expression levels positively correlated with paxillin phosphorylation in invasive breast cancer cell lines. Furthermore, suppression of PIG-T and GPAA1 expression led to a decrease in paxillin phosphorylation with a concomitant decrease in invasion ability. These results suggest that the GPI transamidase complex is composed of a group of proto-oncogenes that individually or as a group contribute to breast cancer growth. This aberrant growth is mediated, at least partially, by phosphorylation of paxillin, contributing to invasion and progression of breast cancer. (Cancer Res 2006; 66(22): 9829-36) (Cancer Res 2006; 66(20): 9829-36)
Novel SN-38–Incorporating Polymeric Micelles, NK012, Eradicate Vascular Endothelial Growth Factor–Secreting Bulky Tumors
Authors: Koizumi Fumiaki , Kitagawa Masayuki , Negishi Takahito , Onda Takeshi , Matsumoto Shin-ichi , Hamaguchi Tetsuya , Matsumura Yasuhiro 
Published: October 2006

Abstract7-Ethyl-10-hydroxy-camptothecin (SN-38), a biological active metabolite of irinotecan hydrochloride (CPT-11), has potent antitumor activity but has not been used clinically because it is a water-insoluble drug. For delivery by i.v. injection, we have successfully developed NK012, a SN-38-releasing nanodevice. The purpose of this study is to investigate the pharmacologic character of NK012 as an anticancer agent, especially in a vascular endothelial growth factor (VEGF)–secreting tumor model. The particle size of NK012 was ∼20 nm with a narrow size distribution. NK012 exhibited a much higher cytotoxic effect against lung and colon cancer cell lines as compared with CPT-11. NK012 showed significantly potent antitumor activity against a human colorectal cancer HT-29 xenograft as compared with CPT-11. Enhanced and prolonged distribution of free SN-38 in the tumor was observed after the injection of NK012. NK012 also had significant antitumor activity against bulky SBC-3/Neo (1,533.1 ± 1,204.7 mm3) and SBC-3/VEGF tumors (1,620.7 ± 834.0 mm3) compared with CPT-11. Furthermore, NK012 eradicated bulky SBC-3/VEGF tumors in all mice but did not eradicate SBC-3/Neo tumors. In the drug distribution analysis, an increased accumulation of SN-38 in SBC-3/VEGF tumors was observed as compared with that in SBC-3/Neo tumors. NK012 markedly enhanced the antitumor activity of SN-38, especially in highly VEGF-secreting tumors, and could be a promising SN-38-based formulation. (Cancer Res 2006; 66(20): 10048-56)
Melatonin in Cancer Management: Progress and Promise
Authors: Jung Brittney , Ahmad Nihal 
Published: October 2006

Abstract
Physiologic and pharmacologic concentrations of the pineal hormone melatonin have shown chemopreventive, oncostatic, and tumor inhibitory effects in a variety of in vitro and in vivo experimental models of neoplasia. Multiple mechanisms have been suggested for the biological effects of melatonin. Not only does melatonin seem to control development alone but also has the potential to increase the efficacy and decrease the side effects of chemotherapy when used in adjuvant settings. This review critically evaluates progress in the ability of melatonin to prevent or reverse cancer development and progression. We also discuss future prospects of the possible development of melatonin as a chemopreventive agent. (Cancer Res 2006; 66(20): 9789-93)
Targeting Prostaglandin E EP Receptors to Inhibit Metastasis
Authors: Fulton Amy M. , Ma Xinrong , Kundu Namita 
Published: October 2006

Abstract
It is well established that high cyclooxygenase-2 (COX-2) expression contributes to the aggressive behavior of breast and other malignancies. Due to concerns regarding the safety of long-term use of COX-2 inhibitors as well as a desire to seek more effective alternatives to prevent and treat metastatic disease, we tested the hypothesis that inhibition of downstream signaling by the COX-2 product prostaglandin E2 (PGE2) would be as effective as inhibiting global prostaglandin synthesis. PGE2 acts through four G-protein–coupled receptors designated EP1-4. Here, we summarize data from many laboratories regarding the role of individual E-series of prostaglandin (EP) receptors on cancer behavior and we discuss our own recent findings that antagonists of the PGE receptor subtype 4, EP4, inhibit experimental metastasis in a murine model of hormone-resistant, metastatic breast cancer. These initial results indicate that selective targeting of individual EP receptors should be investigated as an approach to exploit the high COX-2 activity in many epithelial malignancies. (Cancer Res 2006; 66(20): 9794-7)
Role of the Mitogen-Activated Protein Kinase Signaling Pathway in the Regulation of Human Melanocytic Antigen Expression
Authors: Kono Michihiro , Dunn Ian S. , Durda Paul J. , Butera David , Rose Lenora B. , Haggerty Timothy J. , Benson Elizabeth M. , Kurnick James T. 
Published: October 2006

AbstractHeterogeneous expression of melanocytic antigens occurs frequently in melanomas and represents a potent barrier to immunotherapy. We previously showed that coordinated losses of several melanocytic antigens are generally attributable to down-regulation of antigen gene expression rather than irreversible mutation. Treatment of melanoma cells with mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinase (MEK) inhibitors blocks ERK activation and increases steady-state levels of mRNAs and corresponding protein expression for the melanocytic antigens Melan-A/MART-1, gp100, and tyrosinase. Although the degree of MEK inhibitor enhancement of antigen expression varied among different cell lines irrespective of their antigen expression status, all showed detectable responses. Notably, the antigen-enhancing effects of the MEK inhibitors could not be attributed to the master melanocytic regulator MITF-M. Because MAPK pathway activation via constitutively active mutant forms of BRAF is common in melanomas, correlation between BRAF function and antigen expression was investigated. No simple correlation of endogenous BRAF mutational status and antigen levels was observed, but transient overexpression of V600E BRAF increased ERK activation and reduced Melan-A/MART-1 levels in antigen-positive cell lines. These data indicate that whereas multiple factors may regulate antigen expression in melanomas, enhancement of MAPK signaling can act as a negative influence. Blocking such signaling with MEK inhibitors accordingly augments antigen levels, thereby enhancing Melan-A/MART-1–specific cytotoxic T-cell responses to antigen-negative cells following MEK inhibition treatment. Consequently, MAPK inhibition may assist targeting of melanomas for immunotherapy. (Mol Cancer Res 2006;4(10):779–92)
I. Analytic Third or Law? Reflection vs. Regulation in Psychotherapy Case Notes
Authors: Burman Erica 
Published: October 2006

Sally Swartz’s impassioned and poetic rendering of the possibilities of psychotherapy case-note writing as a forum in which to reflect and generate new interpretations on her therapeutic encounters inspired in me a sense of simultaneous exhilaration and envy. Her juxtaposition of Ogden’s (1994) notion of the ‘analytic third’ and other intersubjective psychoanalytic theorists (Stolorow and Atwood, 1992) alongside feminist, postcolonial and dialogical theorists, applying these to her work as a white African woman therapist with black and white clients (men and women), does indeed indicate something of the radical potential of such resources. The extracts from her therapy notes convey something of the struggle to find a way to forge communication across complex and interweaving power relationships that–in a therapy situation, as all others perhaps–are both structural and personal, and shift from moment to moment with particular effects and affects. As both (group) therapist and academic, I ache to see such work happen here in the postcolonial ‘centre’. For it speaks of real engagement and commitment to use therapy as an arena to explore the impacts and insults of racism, sexism and heterosexism in all their meticulous, gross and microscopic inscriptions on our bodies and minds. I know such work happens here (and I have tried to contribute to some of this–cf. Aitken and Burman, 1999; Gowrisunkur et al., 2002; Walker et al., 2002) – but it is becoming increasingly difficult to write and talk about. In the name of protecting the public and transparency, and in a climate where professions are both required to regulate their own practice and are increasingly subject to state scrutiny, psychotherapists in the UK are being recommended by their training organizations to keep as few notes as possible, and certainly not to own up to writing extensive notes. The legal ambiguities surrounding the notion
Assessing the validity of tuberculosis surveillance data in California
Authors: Sprinson Joan E , Lawton Elizabeth S , Porco Travis C , Flood Jennifer M , Westenhouse Janice L 
Published: October 2006

Abstract

Background
The Centers for Disease Control and Prevention (CDC) convened a workgroup to revise the tuberculosis (TB) case report in the United States of America (U.S.). The group proposed substantial revisions. Study objectives were to systematically assess the validity and completeness of reported TB case surveillance data in California and to inform TB case report revision process.

Methods
A sample of 594 cases was retrospectively selected from the cohort of all TB cases reported during 6/1/96-5/31/97 to the State TB Registry. Cases, stratified by treatment outcome, were randomly sampled within each outcome category. Data for 53 variables were abstracted from each case's public health medical record and compared to data recorded on the TB case report. Using the medical record as the "gold standard," estimates were developed for 1) concordance, sensitivity, and positive predictive value of reported data for categorical variables; 2) the absolute mean difference between the two information source for date variables; and 3) the completeness of data on the case report and in medical record.

Results
At least 90% of the values for 35 (79.5%) categorical variables submitted on the TB case report form were identical to values in the medical record. Concordance between data on the case report and medical record was lower for the remaining nine (20.5%) categorical variables: status of abnormal chest x-ray (46.8%); directly observed therapy (48.6%); smear result for tissue or body fluid other than sputum (49.2%); type(s) of tissue or body fluid for smears and cultures other than sputum (76.4% and 73.9% respectively); provider type (73.4%); occupation (84.4%); sputum culture conversion (85.4%); and sputum smear result (89.6%). Case report data were more complete than data in the medical record; 2.9% versus 9.8% of data were missing/unknown, respectively.

Conclusion
For most variables examined on the TB case report, data validity was excellent, indicating a robust surveillance system. However, lower data quality was noted for a small number of variables primarily impacting treatment adherence, including assessment and planning; advocacy; allocation and garnering of resources; and research. The study provides compelling evidence supporting the CDC workgroup's proposed revisions to the TB case report.
The effects of a controlled worksite environmental intervention on determinants of dietary behavior and self-reported fruit, vegetable and fat intake
Authors: Engbers Luuk H , van Poppel Mireille NM , Chin A Paw Marijke , van Mechelen Willem 
Published: October 2006

AbstractBackgroundEating patterns in Western industrialized countries are characterized by a high energy intake and an overconsumption of (saturated) fat, cholesterol, sugar and salt. Many chronic diseases are associated with unhealthy eating patterns. On the other hand, a healthy diet (low saturated fat intake and high fruit and vegetable intake) has been found important in the prevention of health problems, such as cancer and cardio-vascular disease (CVD). The worksite seems an ideal intervention setting to influence dietary behavior. The purpose of this study is to present the effects of a worksite environmental intervention on fruit, vegetable and fat intake and determinants of behavior.MethodsA controlled trial that included two different governmental companies (n = 515): one intervention and one control company. Outcome measurements (short-fat list and fruit and vegetable questionnaire) took place at baseline and 3 and 12 months after baseline. The relatively modest environmental intervention consisted of product information to facilitate healthier food choices (i.e., the caloric (kcal) value of foods in groups of products was translated into the number of minutes to perform a certain (occupational) activity to burn these calories).ResultsSignificant changes in psychosocial determinants of dietary behavior were found; subjects at the intervention worksite perceived more social support from their colleagues in eating less fat. But also counter intuitive effects were found: at 12 months the attitude and self-efficacy towards eating less fat became less positive in the intervention group. No effects were found on self-reported fat, fruit and vegetable intake.ConclusionThis environmental intervention was modestly effective in changing behavioral determinant towards eating less fat (social support, self-efficacy and attitude), but ineffective in positively changing actual fat, fruit and vegetable intake of office workers.