bluuebunny/crossref_metadata_2025_split huggingface dataset:
Three novel mutations in KIF21A highlight the importance of the third coiled-coil stalk domain in the etiology of CFEOM1
Authors: Chan Wai-Man , Andrews Caroline , Dragan Laryssa , Fredrick Douglas , Armstrong Linlea , Lyons Christopher , Geraghty Michael T , Hunter David G , Yazdani Ahmad , Traboulsi Elias I , Pott Jan WR , Gutowski Nicholas J , Ellard Sian , Young Elizabeth , Hanisch Frank , Koc Feray , Schnall Bruce , Engle Elizabeth C 
Published: May 2007

Abstract

Background
Congenital fibrosis of the extraocular muscles types 1 and 3 (CFEOM1/CFEOM3) are autosomal dominant strabismus disorders that appear to result from maldevelopment of ocular nuclei and nerves. We previously reported that most individuals with CFEOM1 and rare individuals with CFEOM3 harbor heterozygous mutations in KIF21A. KIF21A encodes a kinesin motor involved in anterograde axonal transport, and the familial and de novo mutations reported to date predictably alter one of only a few KIF21A amino acids – three within the third coiled-coil region of the stalk and one in the distal motor domain, suggesting they result in altered KIF21A function. To further define the spectrum of KIF21A mutations in CFEOM we have now identified all CFEOM probands newly enrolled in our study and determined if they harbor mutations in KIF21A.

Results
Sixteen CFEOM1 and 29 CFEOM3 probands were studied. Three previously unreported de novo KIF21A mutations were identified in three CFEOM1 probands, all located in the same coiled-coil region of the stalk that contains all but one of the previously reported mutations. Eight additional CFEOM1 probands harbored three of the mutations previously reported in KIF21A; seven had one of the two most common mutations, while one harbored the mutation in the distal motor domain. No mutation was detected in 5 CFEOM1 or any CFEOM3 probands.

Conclusion
Analysis of sixteen CFEOM1 probands revealed three novel KIF21A mutations and confirmed three reported mutations, bringing the total number of reported KIF21A mutations in CFEOM1 to 11 mutations among 70 mutation positive probands. All three new mutations alter amino acids in heptad repeats within the third coiled-coil region of the KIF21A stalk, further highlighting the importance of alterations in this domain in the etiology of CFEOM1.
Indole is an inter-species biofilm signal mediated by SdiA
Authors: Lee Jintae , Jayaraman Arul , Wood Thomas K 
Published: May 2007

Abstract

Background
As a stationary phase signal, indole is secreted in large quantities into rich medium by Escherichia coli and has been shown to control several genes (e.g., astD, tnaB, gabT), multi-drug exporters, and the pathogenicity island of E. coli; however, its impact on biofilm formation has not been well-studied.

Results
Through a series of global transcriptome analyses, confocal microscopy, isogenic mutants, and dual-species biofilms, we show here that indole is a non-toxic signal that controls E. coli biofilms by repressing motility, inducing the sensor of the quorum sensing signal autoinducer-1 (SdiA), and influencing acid resistance (e.g., hdeABD, gadABCEX). Isogenic mutants showed these associated proteins are directly related to biofilm formation (e.g., the sdiA mutation increased biofilm formation 50-fold), and SdiA-mediated transcription was shown to be influenced by indole. The reduction in motility due to indole addition results in the biofilm architecture changing from scattered towers to flat colonies. Additionally, there are 12-fold more E. coli cells in dual-species biofilms grown in the presence of Pseudomonas cells engineered to express toluene o- monooxygenase (TOM, which converts indole to an insoluble indigoid) than in biofilms with pseudomonads that do not express TOM due to a 22-fold reduction in extracellular indole. Also, indole stimulates biofilm formation in pseudomonads. Further evidence that the indole effects are mediated by SdiA and homoserine lactone quorum sensing is that the addition of N-butyryl-, N-hexanoyl-, and N-octanoyl-L-homoserine lactones repress E. coli biofilm formation in the wild-type strain but not with the sdiA mutant.

Conclusion
Indole is an interspecies signal that decreases E. coli biofilms through SdiA and increases those of pseudomonads. Indole may be manipulated to control biofilm formation by oxygenases of bacteria that do not synthesize it in a dual-species biofilm. Furthermore, E. coli changes its biofilm in response to signals it cannot synthesize (homoserine lactones), and pseudomonads respond to signals they do not synthesize (indole).
Characterizing structural features of cuticle-degrading proteases from fungi by molecular modeling
Authors: Liu Shu-Qun , Meng Zhao-Hui , Yang Jin-Kui , Fu Yun-Xin , Zhang Ke-Qin 
Published: May 2007

Abstract

Background
Serine proteases secreted by nematode and insect pathogenic fungi are bio-control agents which have commercial potential for developing into effective bio-pesticides. A thorough understanding of the structural and functional features of these proteases would significantly assist with targeting the design of efficient bio-control agents.

Results
Structural models of serine proteases PR1 from entomophagous fungus, Ver112 and VCP1 from nematophagous fungi, have been modeled using the homology modeling technique based on the crystal coordinate of the proteinase K. In combination with multiple sequence alignment, these models suggest one similar calcium-binding site and two common disulfide bridges in the three cuticle-degrading enzymes. In addition, the predicted models of the three cuticle-degrading enzymes present an essentially identical backbone topology and similar geometric properties with the exception of a limited number of sites exhibiting relatively large local conformational differences only in some surface loops and the N-, C termini. However, they differ from each other in the electrostatic surface potential, in hydrophobicity and size of the S4 substrate-binding pocket, and in the number and distribution of hydrogen bonds and salt bridges within regions that are part of or in close proximity to the S2-loop.

Conclusion
These differences likely lead to variations in substrate specificity and catalytic efficiency among the three enzymes. Amino acid polymorphisms in cuticle-degrading enzymes were discussed with respect to functional effects and host preference. It is hoped that these structural models would provide a further basis for exploitation of these serine proteases from pathogenic fungi as effective bio-control agents.
Rivoflavin may interfere with on-line monitoring of secreted green fluorescence protein fusion proteins in Pichia pastoris
Authors: Surribas Anna , Resina David , Ferrer Pau , Valero Francisco 
Published: May 2007

Abstract

Background
Together with the development of optical sensors, fluorometry is becoming an increasingly attractive tool for the monitoring of cultivation processes. In this context, the green fluorescence protein (GFP) has been proposed as a molecular reporter when fused to target proteins to study their subcellular localization or secretion behaviour. The present work evaluates the use of the GFP fusion partner for monitoring extracellular production of a Rhizopus oryzae lipase (ROL) in Pichia pastoris by means of 2D-fluorimetric techniques

Results
In this study, the GFP-ROL fusion protein was successfully produced as a secreted fusion form in P. pastoris batch cultivations. Furthermore, both the fusion enzyme and the fluorescent protein (GFP S65T mutant) retained their biological activity. However, when multiwavelength spectrofluorometry was used for extracellular fusion protein monitoring, riboflavin appeared as a major interfering component with GFP signal. Only when riboflavin was removed by ultrafiltration from cultivation supernatants, GFP fluorescence signal linearly correlated to lipase activity

Conclusion

P. pastoris appears to secrete/excrete significant amounts of riboflavin to the culture medium. When attempting to monitor extracellular protein production in P. pastoris using GFP fusions combined with multiwavelength spectrofluorimetric techniques, riboflavin may interfere with GFP fluorescence signal, thus limiting the application of some GFP variants for on-line extracellular recombinant protein quantification and monitoring purposes.
Receptor for advanced glycation end products (RAGE) in a dash to the rescue: inflammatory signals gone awry in the primal response to stress
Authors: Herold Kevan , Moser Bernhard , Chen Yali , Zeng Shan , Yan Shi Fang , Ramasamy Ravichandran , Emond Jean , Clynes Raphael , Schmidt Ann Marie 
Published: May 2007

AbstractThe multiligand receptor for advanced glycation end products (RAGE) of the Ig superfamily transduces the biological impact of discrete families of ligands, including advanced glycation end products, certain members of the S100/calgranulin family, high mobility group box-1, Mac-1 (αMβ2, CD11b/CD18), and amyloid-β peptide and β-sheet fibrils. Although structurally dissimilar, at least at the monomeric level, recent evidence suggests that oligomeric forms of these RAGE ligands may be especially apt to activate the receptor and up-regulate a program of inflammatory and tissue injury-provoking genes. The challenge in probing the biology of RAGE and its impact in acute responses to stress and the potential development of chronic disease is to draw the line between mechanisms that evoke repair versus those that sustain inflammation and tissue damage. In this review, we suggest the concept that the ligands of RAGE comprise a primal program in the acute response to stress. When up-regulated in environments laden with oxidative stress, inflammation, innate aging, or high glucose, as examples, the function of these ligand families may be transformed from ones linked to rapid repair to those that drive chronic disease. Identification of the threshold beyond which ligands of RAGE mediate repair versus injury is a central component in delineating optimal strategies to target RAGE in the clinic.
Provider Counseling About Health Behaviors Among Cancer Survivors in the United States
Authors: Sabatino Susan A. , Coates Ralph J. , Uhler Robert J. , Pollack Lori A. , Alley Linda G. , Zauderer Laura J. 
Published: May 2007

Purpose To examine provider discussion or counseling of US cancer survivors about diet, exercise, and tobacco use. Methods We used 2000 National Health Interview Survey data to examine whether US cancer survivors reported that, within 1 year, a provider (1) discussed diet, (2) recommended they begin or continue exercise, or (3) asked about smoking. We included survivors more than 1 year beyond diagnosis (n = 1,600) and adults without cancer (AWCs; n = 24,636) who saw/talked to a provider within 1 year. We used generalized linear contrasts in bivariable analyses and logistic regression to calculate predicted marginals adjusted for age, sex, comorbidity, usual source of care, and number of provider visits in the prior year. Results Few survivors reported discussions or recommendations for all three health behaviors (10% of survivors v 9% of AWCs; P = .57). Although report was more likely than among AWCs, few survivors reported diet discussions (30% of survivors v 23% of AWCs; P < .0001) or exercise recommendations (26% of survivors v 23% of AWCs; P < .005), and a minority were asked about smoking (42% of survivors v 41% of AWCs; P = .41). After adjustment, survivors were less likely to report exercise recommendations than were AWCs (22% v 24%, respectively; P = .02). Colorectal cancer survivors were less likely than were AWCs of similar age range to report exercise recommendations (16% v 27%, respectively; P < .003) or smoking discussions (31% v 41%, respectively; P < .05). Cervical cancer survivors were more likely than AWCs of similar age range to discuss smoking (58% v 43%, respectively; P < .001). Conclusion Findings from this nationally representative sample suggest that many providers may miss opportunities to counsel survivors about healthy behaviors, perhaps particularly colorectal cancer survivors.
Screening for a BRCA2 Rearrangement in High-Risk Breast/Ovarian Cancer Families: Evidence for a Founder Effect and Analysis of the Associated Phenotypes
Authors: Machado Patrícia M. , Brandão Rita D. , Cavaco Branca M. , Eugénio Joana , Bento Sandra , Nave Mónica , Rodrigues Paula , Fernandes Aires , Vaz Fátima 
Published: May 2007

Purpose BRCA2 rearrangements are rare genetic events. A large BRCA2 genomic insertion was recurrently observed in our participants, and we sought to characterize it at the molecular and phenotypic level. Patients and Methods We studied 210 high-risk breast/ovarian cancer families. Fifty-three probands were fully screened for BRCA1/2 mutations, and three of 53 had a large insertion in exon 3 of BRCA2. This finding was analyzed by polymerase chain reaction (PCR), reverse transcriptase PCR (RT-PCR), and sequencing. An additional 157 consecutive families were screened for this mutation by a three-step PCR method. Phenotype and haplotype analysis was also performed. Results Sixteen BRCA mutations were observed in 19 of 53 patients (36% detection rate). A recurrent Alu motif insertion in position c.156_157 was observed after sequencing of an abnormal fragment obtained after the amplification of BRCA2 exon 3. RT-PCR revealed exon 3 skipping. Screening of this rearrangement identified 14 additional families (out of 157). In total, 17 (8%) of 210 high-risk families ascertained in our clinic were positive for this mutation. Segregation of a common haplotype (from D13S260 to D13S1695) confirmed a common origin, estimated to have occurred 2,400 to 2,600 years ago. The following four cancer phenotypes were observed in the 17 positive families: female breast (n = 9), male breast (n = 4), breast/ovarian (n = 2), and heterogeneous (n = 2). Male breast cancer was more frequently observed in c.156_157insAlu–positive families compared with negative families (23% v 12%, respectively), and 33% of all male breast cancer families with an identified BRCA mutation were c.156_157insAlu positive. Conclusion c.156_157insAlu is a founder mutation of Portuguese origin and is the most frequent BRCA2 rearrangement described to date.
Impact of a Peer-Delivered Telephone Intervention for Women Experiencing a Breast Cancer Recurrence
Authors: Gotay Carolyn Cook , Moinpour Carol M. , Unger Joseph M. , Jiang Caroline S. , Coleman Dorothy , Martino Silvana , Parker Beverly J. , Bearden James D. , Dakhil Shaker , Gross Howard M. , Lippman Scott , Albain Kathy S. 
Published: May 2007

Purpose A first breast cancer recurrence creates considerable distress, yet few psychosocial interventions directed at this population have been reported. The Southwest Oncology Group conducted a phase III randomized trial to evaluate the effectiveness of a brief telephone intervention. Patients and Methods Three hundred five women experiencing a first recurrence of breast cancer were randomly assigned to standard care or intervention. The intervention consisted of four to eight telephone calls delivered over a 1-month period. The calls were conducted by trained peer counselors at a breast cancer advocacy organization, the Y-ME National Breast Cancer Organization, and followed a standard curriculum. Psychosocial distress (Cancer Rehabilitation Evaluation System–Short Form [CARES-SF]) and depressive symptoms (Center for Epidemiologic Studies Depression Scale [CES-D]) outcomes were assessed at baseline and 3 and 6 months. The 3-month assessment was the primary end point and is the focus of this article. Results Analysis revealed no differences in distress or depressive symptoms at 3 months between the intervention and control groups; at 3 months, 70% of control patients and 66% of intervention patients reported psychosocial distress, and 40% of control patients and 47% of intervention patients exhibited depressive symptoms. Conclusion Telephone peer counseling did not lead to better psychosocial outcomes. The persistent distress in these women supports the urgent need for the development and testing of more intensive or different supportive interventions for this group of patients.
Multiple Drug Resistance in Osteogenic Sarcoma: INT0133 From the Children's Oncology Group
Authors: Schwartz Cindy L. , Gorlick Richard , Teot Lisa , Krailo Mark , Chen Zhengjia , Goorin Allen , Grier Holcombe E. , Bernstein Mark L. , Meyers Paul 
Published: May 2007

Purpose Multiple drug resistance due to P-glycoprotein (P-gp) expression has been reported to be a cause of disease recurrence in osteosarcoma. Tumor specimens derived from children and young adults with osteosarcoma enrolled onto a national Intergroup trial (INT0133) were analyzed prospectively to determine the role of multiple drug resistance in osteosarcoma. Patients and Methods From October 15, 1992, to November 25, 1997, 685 patients with localized, high-grade osteosarcoma were enrolled onto INT0133. Paraffin-embedded diagnostic tumor specimens were assayed for P-gp using monoclonal antibodies C-494 (139 patients) and JSB-1 (133 patients). Percent necrosis at the time of definitive surgery (NEC), event-free survival (EFS), and overall survival (OS) were evaluated as outcome measures for patients with P-gp–positive disease and were compared with patients with P-gp–negative disease. Results P-gp expression in the biopsy specimen did not significantly increase the risk for adverse outcomes as measured by EFS, OS, or NEC. EFS for those patients with C-494–positive tumors was 59% at 4 years versus 61% at 4 years for patients with C-494–negative tumors (P = .79), or 58% at 4 years versus 61% at 4 years for patients with JSB-1–positive versus JSB-1–negative tumors (P = .65). OS for patients with C-494–positive tumors was 82% at 4 years versus 82% at 4 years for patients with C-494–negative tumors (P = .61). Conclusion Prospective analysis of the role of multiple drug resistance in localized osteosarcoma did not find that immunohistochemical analysis of P-gp expression predicted outcome for patients treated on INT0133.
Phase III Study of Oral Compared With Intravenous Topotecan As Second-Line Therapy in Small-Cell Lung Cancer
Authors: Eckardt John R. , von Pawel Joachim , Pujol Jean-Louis , Papai Zsolt , Quoix Elisabeth , Ardizzoni Andrea , Poulin Ruth , Preston Alaknanda J. , Dane Graham , Ross Graham 
Published: May 2007

Purpose Single-agent intravenous (IV) topotecan is an effective treatment for small-cell lung cancer (SCLC) after failure of first-line chemotherapy. This open-label, randomized, phase III study compared oral and IV topotecan in patients with SCLC sensitive to initial chemotherapy. Patients and Methods Patients with limited- or extensive-disease SCLC, documented complete or partial response to first-line therapy, Eastern Cooperative Oncology Group performance status ≤ 2, and measurable recurrent disease (WHO criteria) with a treatment-free interval of ≥ 90 days were assigned to treatment with either oral topotecan 2.3 mg/m2/d on days 1 through 5 or IV topotecan 1.5 mg/m2/d on days 1 through 5 every 21 days. Primary end point was response rate as confirmed by an external reviewer blinded to treatment. Results A total of 309 patients were randomly assigned. In intent-to-treat analysis, response rates were 18.3% with oral topotecan (n = 153) and 21.9% with IV topotecan (n = 151), with a difference (oral –IV) of −3.6% (95% CI, −12.6% to 5.5%). Median survival time was 33.0 weeks for oral and 35.0 weeks for IV topotecan; 1- and 2-year survival rates were 32.6% and 12.4% for oral topotecan, respectively, and 29.2% and 7.1% for IV topotecan, respectively. Third-line chemotherapy was similar for both groups (33% for oral; 35% for IV). Incidence of grade 4 toxicity in patients who received oral and IV topotecan was as follows: neutropenia in 47% and 64%, thrombocytopenia in 29% and 18%, grade 3 or 4 anemia in 23% and 31%, and sepsis in 3% and 3%, respectively. The most frequent nonhematologic adverse events (all grades) included nausea (43% oral; 42% IV), alopecia (26% oral; 30% IV), fatigue (31% oral; 36% IV), and diarrhea (36% oral; 20% IV). Conclusion Oral topotecan demonstrates activity and tolerability similar to IV topotecan in chemotherapy-sensitive SCLC patients and offers patients a convenient alternative to IV therapy.
Predicting the Outcome of Salvage Radiation Therapy for Recurrent Prostate Cancer After Radical Prostatectomy
Authors: Stephenson Andrew J. , Scardino Peter T. , Kattan Michael W. , Pisansky Thomas M. , Slawin Kevin M. , Klein Eric A. , Anscher Mitchell S. , Michalski Jeff M. , Sandler Howard M. , Lin Daniel W. , Forman Jeffrey D. , Zelefsky Michael J. , Kestin Larry L. , Roehrborn Claus G. , Catton Charles N. , DeWeese Theodore L. , Liauw Stanley L. , Valicenti Richard K. , Kuban Deborah A. , Pollack Alan 
Published: May 2007

Purpose An increasing serum prostate-specific antigen (PSA) level is the initial sign of recurrent prostate cancer among patients treated with radical prostatectomy. Salvage radiation therapy (SRT) may eradicate locally recurrent cancer, but studies to distinguish local from systemic recurrence lack adequate sensitivity and specificity. We developed a nomogram to predict the probability of cancer control at 6 years after SRT for PSA-defined recurrence. Patients and Methods Using multivariable Cox regression analysis, we constructed a model to predict the probability of disease progression after SRT in a multi-institutional cohort of 1,540 patients. Results The 6-year progression-free probability was 32% (95% CI, 28% to 35%) overall. Forty-eight percent (95% CI, 40% to 56%) of patients treated with SRT alone at PSA levels of 0.50 ng/mL or lower were disease free at 6 years, including 41% (95% CI, 31% to 51%) who also had a PSA doubling time of 10 months or less or poorly differentiated (Gleason grade 8 to 10) cancer. Significant variables in the model were PSA level before SRT (P < .001), prostatectomy Gleason grade (P < .001), PSA doubling time (P < .001), surgical margins (P < .001), androgen-deprivation therapy before or during SRT (P < .001), and lymph node metastasis (P = .019). The resultant nomogram was internally validated and had a concordance index of 0.69. Conclusion Nearly half of patients with recurrent prostate cancer after radical prostatectomy have a long-term PSA response to SRT when treatment is administered at the earliest sign of recurrence. The nomogram we developed predicts the outcome of SRT and should prove valuable for medical decision making for patients with a rising PSA level.