Nucleic acid sequences that are rich in guanines can form G-quadruplex (G4) structures, which can impede DNA replication or repair. The FANCJ helicase plays a role in maintaining genomic stability by facilitating DNA replication through regions of DNA that form G4 structures. This activity has been associated with an AKKQ motif in FANCJ and it is thought that this motif retains the ability to also target 8-oxoguanine-modified G4 (8oxoG4) structures. We hypothesize that the molecular recognition of FANCJ AKKQ to 8oxoG4s is dependent upon the position of DNA damage, sequence composition, and substrate stability. We previously demonstrated that reducing the loop length between guanine tetrads increased the affinity of FANCJ AKKQ when 8-oxoguanines (8oxoGs) were located at the first and fifth positions of the G4 structure. In this work, we use fluorescence spectroscopy to measure the affinities of a FANCJ AKKQ peptide for G4s formed by (GGGT)4, (GGGTT)4, and (TTAGGG)4. G4 conformations and thermal stability were determined via circular dichroism spectroscopy. We substituted 8oxoGs at the first (8oxo1), third (8oxo3), and fifth (8oxo5) positions of each G4 sequence and found that the most destabilized structures were (GGGT)4 8oxo1, (GGGTT)4 8oxo1, and (TTAGGG)4 8oxo5 in KCl. The most destabilized structures in NaCl were (GGGT)4 8oxo1, (GGGTT)4 8oxo5, and (TTAGGG)4 8oxo5. The binding affinities of FANCJ AKKQ differed for the distinct damage positions for (GGGT)4 in KCl and for (TTAGGG)4 in NaCl. These findings suggest that FANCJ AKKQ targets G4s and 8oxoG4s in a manner dependent upon sequence composition and damage position. ### Competing Interest Statement The authors have declared no competing interest.
Breast Cancer Susceptibility Gene 1 ( BRCA1 ) plays a crucial role in the homologous recombination (HR) pathway to repair double-stranded breaks (DSBs) in human cells. Interactions between BRCA1 protein and DNA have been mapped to the central region, which could be further divided as two DNA binding domains (DBDs); however, the relative substrate preferences of the DBDs and their functional role in HR remain poorly understood. We hypothesize that the DBDs have distinct binding preferences for DNA repair intermediates, and we have measured the DNA binding affinities of DBD1 (amino acids (aa) 330-554), DBD2 (aa894-1057), and the BRCA1 C-terminal repeats (BRCT) for single-stranded (ssDNA), double-stranded (dsDNA), and G-quadruplex (G4) DNA using biolayer interferometry. Our results indicate that DBD1 has the highest affinity for dsDNA, while DBD2 and BRCT bound tightest to G4 and ssDNA. Based on these findings, we propose a model in which DBD1 targets BRCA1 to DSBs for the promotion of DNA end resection, whereas DBD2 and BRCT target BRCA1 to telomeres to function in chromatin remodeling and telomere regulation. ### Competing Interest Statement The authors have declared no competing interest.
Compassion Fatigue is a state that includes the symptoms of Post-Traumatic Stress Disorder. This text reviews events following the Hurricane Ivan and Katrina disasters and how Compassion Fatigue education helped to identify and ameliorate symptoms of the problem. I worked in a community center in the Pensacola area for one week following Ivan and in a shelter in my residential area of Houma, Louisiana for two months following Katrina. Examples of traumatic stories and coping with my own secondary stress are given. Implications include education regarding CF for all mental health professionals, especially during and following work in disasters or with populations of the traumatized.
I. ABSTRACT The content of this Eighth Grade interdisciplinary unit will dispel the stereotypical American images of China. Through reading The Good Earth, exploring China’s geography, and delving into China’s history, the student will understand China and its people from a new point of view. The strategies employed in the unit will address the needs of the general education and gifted populations as well as those students with various exceptionalities. Activities will range from experiential activities to keeping a diary.
Kinetics of the spontaneous decarboxylation of 6-nitrobenzisoxazole-3-carboxylic acid have been studied in the lyophases formed by anionic, cationic and nonionic surfactants: sodium dodecyl sulfate (SDS), myristyltrimethylammonium bromide (MTAB) and pentaethylene glycol mono-n-dodecylether (C12E5) respectively. This substrate was chosen for study because of the large amount of data available on its behavior in micellar solution. Without surfactants the reaction proceeds slowly in both acidic (pH 4.0) and alkaline (pH 9.0-11.0) water solutions, with the reaction rate similar to 0.7 x 10(-5) s(-1) (at 25 degrees C). Anionic SDS has no catalyzing effect on the reaction. Cationic MTAB significantly accelerates the reaction in all phases: isotropic, lamellar or cylindrical nematic. Nonionic C12E5 is the only surfactant which shows a catalyzing effect dependent on the type of the lyophase. The reaction goes similar to 1.5 times faster in the lamellar as compared to the isotropic phase.
The Human-Computer Interaction Lab worked with a team for the Library of Congress (LC) to develop and test interface designs for LC's National Digital Library Program. Three iterations are described and illustrate the progression of the project toward a compact design that minimizes scrolling and jumping and anchors users in a screen space that tightly couples search and results. Issues and resolutions are discussed for each iteration and reflect the challenges of incomplete metadata, data visualization, and the rapidly changing web environment.
米国議会図書館(LC)におけるディジタル・ライブラリーへの取り組みについてこれまでの成果や将来計画を述べた。1990年から94年に行われたアメリカン・メモリー試験プログラムにより開始されたディジタル・ライブラリーの新しい時代は,アメリカン・メモリーを基礎プログラムとして全米ディジタル・ライブラリー(NDL)プログラムへ引き継がれた。その試験プロジェクトの内容や評価に触れ,その後拡大され,現在LCのWWW上で公開されている内容を紹介した。将来展望として「壁のない」未来図書館と「壁のある」図書館が併存していくと強調した。
Findings are reported from a replicated evaluation of the psychometric properties of the Organizational Job Satisfaction Scale. Data lend strong support for the scale which assesses four dimensions of organizational job satisfaction. Principal component factor analysis of data from two independent samples of urban staff registered nurses (RNs) (n = 496; n = 532) confirmed four dimensions of pay, interaction, administration, and status. Cronbach's alpha for subscales ranged from .76 to .88. Pearson correlation coefficients for the interrelationships among subscales and an estimate of theta verified internal consistency. The Organizational Job Satisfaction Scale scores correlated significantly with a criterion measure of job enjoyment. Hypothesis testing of theoretically predictable relationships supported construct validity. Scores on the organizational job satisfaction subscales correlated significantly with automony, stress, and commitment. Item revisions and recommendations for future use of the instrument are discussed.
Music examinations frequently require students to harmonise chorale melodies ‘in the style of J. S. Bach’, but the manner in which the skill is taught generally emphasises the adding of chords below the melody note by note ‘arithmetically’, and may thus fail to develop inner hearing and a sense of overall harmonic direction. Using the system of ‘harmonic sketching’ which she developed originally as an approach to keyboard harmony and described in detail in her book Sketching at the Keyboard, Laura Campbell extended the technique to the harmonisation of chorale melodies, in the process comparing her students' choices of outline harmony with those employed by Bach in four settings of the same chorale. In this article she describes the experiment and comments upon its results, showing how the ‘sketching’ method, which reveals the fundamental ‘harmonic landscape’ of a melody, is an especially valuable tool in the acquisition of written harmony skills.
The Human-Computer Interaction Lab worked with a team for the Library of Congress (LC) to develop and test inter- face designs for LC's National Digital Library Program. Three iterations are described and illustrate the progres- sion of the project toward a compact design that minimizes scrolling and jumping and anchors users in a screen space that tightly couples search and results. Issues and resolu- tions are discussed for each iteration and reflect the chal- lenges of incomplete metadata, data visualization, and the rapidly changing web environment.
Gary Marchionini合作论文数School of Information and Library Science, University of North Carolina at Chapel Hill1