Receptor binding studies disclose a novel class of high-affinity inhibitors of the Escherichia coli FimH adhesin

Mannose-binding type 1 pili are important virulence factors for the establishment of Escherichia coli urinary tract infections (UTIs). These infections are initiated by adhesion of uropathogenic E. coli to uroplakin receptors in the uroepithelium via the FimH adhesin located at the tips of type 1 pili. Blocking of bacterial adhesion is able to prevent infection. Here, we provide for the first time binding data of the molecular events underlying type 1 fimbrial adherence, by crystallographic analyses of the FimH receptor binding domains from a uropathogenic and a K-12 strain, and affinity measurements with mannose, common mono- and disaccharides, and a series of alkyl and aryl mannosides. Our results illustrate that the lectin domain of the FimH adhesin is a stable and functional entity and that an exogenous butyl alpha- D-mannoside, bound in the crystal structures, exhibits a significantly better affinity for FimH (K-d = 0.15 muM) than mannose (K-d = 2.3 muM). Exploration of the binding affinities of alpha-D-mannosides with longer alkyl tails revealed affinities up to 5 nM. Aryl mannosides and fructose can also bind with high affinities to the FimH lectin domain, with a 100-fold improvement and 15-fold reduction in affinity, respectively, compared with mannose. Taken together, these relative FimH affinities correlate exceptionally well with the relative concentrations of the same glycans needed for the inhibition of adherence of type 1 piliated E. coli. We foresee that our findings will spark new ideas and initiatives for the development of UTI vaccines and anti-adhesive drugs to prevent anticipated and recurrent UTIs.

Mechanisms of acetohydroxyacid synthases

Acetohydroxyacid synthases are thiamin diphosphate- (ThDP-) dependent biosynthetic enzymes found in all autotrophic organisms. Over the past 4-5 years, their mechanisms have been clarified and illuminated by protein crystallography, engineered mutagenesis and detailed single-step kinetic analysis. Pairs of catalytic subunits form an intimate dimer containing two active sites, each of which lies across a dimer interface and involves both monomers. The ThDP adducts of pyruvate, acetaldehyde and the product acetohydroxyacids can be detected quantitatively after rapid quenching. Determination of the distribution of intermediates by NMR then makes it possible to calculate individual forward unimolecular rate constants. The enzyme is the target of several herbicides and structures of inhibitor-enzyme complexes explain the herbicide-enzyme interaction.

Acetohydroxyacid synthase and its role in the biosynthetic pathway for branched-chain amino acids

The branched-chain amino acids are synthesized by plants, fungi and microorganisms, but not by animals. Therefore, the enzymes of this pathway are potential target sites for the development of antifungal agents, antimicrobials and herbicides. Most research has focused upon the first enzyme in this biosynthetic pathway, acetohydroxyacid synthase (AHAS) largely because it is the target site for many commercial herbicides. In this review we provide a brief overview of the important properties of each enzyme within the pathway and a detailed summary of the most recent AHAS research, against the perspective of work that has been carried out over the past 50 years.

Active genetic elements present in the locus of enterocyte effacement in Escherichia coli O26 and their role in mobility

The locus of enterocyte effacement (LEE) is a large multigene chromosomal segment encoding gene products responsible for the generation of attaching and effacing lesions in many diarrheagenic Escherichia coli strains. A recently sequenced LEE harboring a pathogenicity island (PAI) from a Shiga toxin E. coli serotype 026 strain revealed a LEE PAI (designated LEE 026) almost identical to that obtained from a rabbit-specific enteropathogenic 015:H- strain. LEE 026 comprises 59,540 bp and is inserted at 94 min within the mature pheU tRNA locus. The LEE 026 PAI is flanked by two direct repeats of 137 and 136 bp (DR1 and DR2), as well as a gene encoding an integrase belonging to the P4 integrase family. We examined LEE 026 for horizontal gene transfer. By generating mini-LEE plasmids harboring only DR1 or DR2 with or without the integrase-like gene, we devised a simple assay to examine recombination processes between these sequences. Recombination was shown to be integrase dependent in a Delta recA E. coli K-12 strain background. Recombinant plasmids harboring a single direct repeat cloned either with or without the LEE 026 integrase gene were found to insert within the chromosomal pheU locus of E. coli K-12 strains with equal efficiency, suggesting that an endogenous P4-like integrase can substitute for this activity. An integrase with strong homology to the LEE 026 integrase was detected on the K-12 chromosome associated with the leuX tRNA locus at 97 min. Strains deleted for this integrase demonstrated a reduction in the insertion frequency of plasmids harboring only the DR into the pheU locus. These results provide strong evidence that LEE-harboring elements are indeed mobile and suggest that closely related integrases present on the chromosome of E. coli strains contribute to the dynamics of PAI mobility.

Defenses against oxidative stress in Neisseria gonorrhoeae: A system tailored for a challenging environment

Neisseria gonorrhoeae is a host-adapted pathogen that colonizes primarily the human genitourinary tract. This bacterium encounters reactive oxygen and reactive nitrogen species as a consequence of localized inflammatory responses in the urethra of males and endocervix of females and also of the activity of commensal lactobacilli in the vaginal flora. This review describes recent advances in the understanding of defense systems against oxidative stress in N. gonorrhoeae and shows that while some of its defenses have similarities to the paradigm established with Escherichia coli, there are also some key differences. These differences include the presence of a defense system against superoxide based on manganese ions and a glutathione-dependent system for defense against nitric oxide which is under the control of a novel MerR-like transcriptional regulator. An understanding of the defenses against oxidative stress in N. gonorrhoeae and their regulation may provide new insights into the ways in which this bacterium survives challenges from polymorphonuclear leukocytes and urogenital epithelial cells.

Проблеми в обучението на учителите по математика

Kiril Bankov What mathematics do teachers need to know to teach effectively? This question has been of great importance in the studies of mathematics teacher preparation for the last decade. Many theoretical papers have been published but there is not a common understanding yet. Large scale studies have also contributed to the issue. This paper presents some results of an international study in this area and discusses problems in preparation of mathematics teachers in Bulgaria.

Engagement experiences of Hispanic Generation 1.5 English language learners at a Massachusetts community college

Hispanic Generation 1.5 students are foreign-born, U.S. high school graduates who are socialized in the English dominant K-12 school system while still maintaining the native language and culture at home (Allison, 2006; Blumenthal, 2002; Harklau, Siegal, & Losey, 1999; Rumbault & Ima, 1988). When transitioning from high school to college, these students sometimes assess into ESL courses based on their English language abilities, and because of this ESL placement, Hispanic Generation 1.5 students might have different engagement experiences than their mainstream peers. Engagement is a critical factor in student success and long-term retention because students’ positive and negative engagement experiences affect their membership and sense of belonging at the institution. The purpose of this study was to describe the engagement and membership experiences of Hispanic Generation 1.5 students’ at a Massachusetts community college. This study employed naturalistic inquiry within an embedded descriptive case study design that included three units of analysis: the students’ engagement experiences in (a) ESL courses, (b) developmental courses, and (c) mainstream courses. The main source of data was in-depth interviews with Hispanic Generation 1.5 students at Commonwealth of Massachusetts Community College. Criterion sampling was used to select the interview participants, ensuring that all participants were native Spanish speakers and were taking or had taken at least one ESL course at the institution. The study findings show that these Hispanic Generation 1.5 students at the college did not perceive peer engagement as critical to academic success. Most times the participants avoided peer engagement outside of the classroom, especially with fellow Hispanic students, who they felt would deter them from their English language development and general academic work. Engagement with ESL faculty and ESL academic support staff played the most critical role in the participants’ sense of belonging and success, and students who were required to engage with faculty and academic support staff outside of the classroom were the most satisfied with their educational experiences. While the participants were all disappointed with some aspect of their ESL placement, they valued the ESL engagement experiences more than the engagement experiences while completing developmental and credit coursework.

Swimming against the tide: A study of a youth enrichment program seeking to empower inner-city Black youth

Serious inequities in our K-12 public education system, particularly in regard to the quality of education in predominately Black inner-city schools, are well-documented in the literature (Freeman, 1998; Ross, 1998). Moreover, there is general agreement that the most effective means of ameliorating that situation is through well-thought-out after-school programs and partnership initiatives (Beck, 1993; Gardner et al., 2001). ^ The purpose of this qualitative study was to examine the programmatic interventions of a youth enrichment program for inner-city Black youth currently in place at the Overtown Youth Center (OYC) in Miami, Florida, in order to: (a) discern those factors that support its claim that it is making a difference in students’ lives, (b) explore how any such factors are implemented, and (c) determine whether its interventions have served to equalize the playing field for these youth. ^ Two primary methods of data collection were used for this study. The first was participant observation conducted over the course of two years through a partnership initiative established and led by this author. The second was through in-depth interviews of the Center’s founder, staff, and students. Secondary methods used were the recording of informal conversations and the analysis of written documents. ^ Analysis of the data yielded four features of the Center that are indispensible to the students’ growth. The center provides the youth with (a) physical and psychological safety, (b) supportive relationships, (c) exposure to cultural and educational opportunities, and (d) assistance in building self-esteem. ^ The most significant finding of the study was that OYC has been successful at making a difference in students’ lives and at increasing their aspirations to attend college. By addressing the full spectrum of their needs, the Center has given them many of the necessary tools with which to compete and thereby helped equalize their opportunities to succeed in school and in life. ^ The study also noted a number of challenges for the Center to examine. The main issues that need to be addressed more seriously are staff turnover, staff indifference, nepotism, inconsistent student attendance, and insufficient focus on racial issues and African-American-centered education. Meeting those challenges would engender even greater positive outcomes.^

Using LatCrit, Autoethnography, and Counterstory to Teach About and Resist Latina/o Nihilism

Nihilism caused by inequalities and injustices hurts students of color. Educators can help these students with Critical Race theory and storytelling. Latina/o students also face nihilism but there is no clear solution. This study explores a way to use LatCrit in the K-12 classroom to fight for justice and equality.

The relationship of instructor technical literacy to the academic performance of students in career academies

Career Academy instructors' technical literacy is vital to the academic success of students. This nonexperimental ex post facto study examined the relationships between the level of technical literacy of instructors in career academies and student academic performance. It was also undertaken to explore the relationship between the pedagogical training of instructors and the academic performance of students. ^ Out of a heterogeneous population of 564 teachers in six targeted schools, 136 teachers (26.0 %) responded to an online survey. The survey was designed to gather demographic and teaching experience data. Each demographic item was linked by researchers to teachers' technology use in the classroom. Student achievement was measured by student learning gains as assessed by the reading section of the FCAT from the previous to the present school year. ^ Linear and hierarchical regressions were conducted to examine the research questions. To clarify the possibility of teacher gender and teacher race/ethnic group differences by research variable, a series of one-way ANOVAs were conducted. As revealed by the ANOVA results, there were not statistically significant group differences in any of the research variables by teacher gender or teacher race/ethnicity. Greater student learning gains were associated with greater teacher technical expertise integrating computers and technology into the classroom, even after controlling for teacher attitude towards computers. Neither teacher attitude toward technology integration nor years of experience in integrating computers into the curriculum significantly predicted student learning gains in the regression models. ^ Implications for HRD theory, research, and practice suggest that identifying teacher levels of technical literacy may help improve student academic performance by facilitating professional development strategies and new parameters for defining highly qualified instructors with 21st century skills. District professional development programs can benefit by increasing their offerings to include more computer and information communication technology courses. Teacher preparation programs can benefit by including technical literacy as part of their curriculum. State certification requirements could be expanded to include formal surveys to assess teacher use of technology.^

The Effect of Mobile Technology as an Active Student Response System on the Acquisition of U.S. History Content of Secondary Students with Specific Learning Disabilities

Students with specific learning disabilities (SLD) typically learn less history content than their peers without disabilities and show fewer learning gains. Even when they are provided with the same instructional strategies, many students with SLD struggle to grasp complex historical concepts and content area vocabulary. Many strategies involving technology have been used in the past to enhance learning for students with SLD in history classrooms. However, very few studies have explored the effectiveness of emerging mobile technology in K-12 history classrooms. This study investigated the effects of mobile devices (iPads) as an active student response (ASR) system on the acquisition of U.S. history content of middle school students with SLD. An alternating treatments single subject design was used to compare the effects of two interventions. There were two conditions and a series of pretest probesin this study. The conditions were: (a) direct instruction and studying from handwritten notes using the interactive notebook strategy and (b) direct instruction and studying using the Quizlet App on the iPad. There were three dependent variables in this study: (a) percent correct on tests, (b) rate of correct responses per minute, and (c) rate of errors per minute. A comparative analysis suggested that both interventions (studying from interactive notes and studying using Quizlet on the iPad) had varying degrees of effectiveness in increasing the learning gains of students with SLD. In most cases, both interventions were equally effective. During both interventions, all of the participants increased their percentage correct and increased their rate of correct responses. Most of the participants decreased their rate of errors. The results of this study suggest that teachers of students with SLD should consider a post lesson review in the form of mobile devices as an ASR system or studying from handwritten notes paired with existing evidence-based practices to facilitate students’ knowledge in U.S. history. Future research should focus on the use of other interactive applications on various mobile operating platforms, on other social studies subjects, and should explore various testing formats such as oral question-answer and multiple choice.

Formação docente para a inserção da história e filosofia da ciência no ensino: textos histórico-pedagógicos em discussão

The present dissertation focuses on specific problems in the educational context: challenges in the construction of historical narratives for pedagogical use as well as the difficult task of using them in the classroom. In this context, we seek to work in teacher training for insertion of History and Philosophy of Science (HPS) in classroom, and historical narratives become mediation elements to advance the dialogue with this specific audience. This initiative is in line with a recurring concern: one of the main challenges related to the didactic transposition of HFC would be the lack of teacher preparation. Historical contents and Nature of Science are still absent in classrooms. Insecurity and lack of knowledge by teachers are often mentioned as factors that contribute to this situation. It is important, therefore, that teachers (active and in training) take part in discussions concerning the inclusion of HPS in classroom. It is relevant that they know examples of historic-philosophical didactic proposals to address science and contents on science, develop skills to adapt them to their specific contexts and to develop their own proposals. It is believed that these issues are significant to undertake conscious initiatives to insert HPS in classrooms. It is considered that adapting educational proposals to particular educational contexts depends on understanding what these proposals indeed mean and how flexible they can be. In order to address these objectives, we elaborated an educational product, a didactic material focused on teacher training, which was used in an extension course at UFRN. The didactic material discusses the role of HPS in Education, Nature of Science and historiographical issues. It presents a series of dialogical activities on aspects of didactic transposition of HPS, especially those regarding historical narratives. A set of historicpedagogical texts on the History of Vacuum and Atmospheric Pressure is used as a mediation element in discussions. We address potential, possibilities and limitations historical narratives. To carry out the course, it was taken into account methodological concerns of so-called action research. There have been expected changes, modifications and effective actions in the own teacher training material in face of the experience of the researcher-lecturer in interactions with the participants of the course as well as in face of impressions reported by the participants. Developments in this direction have been incorporated into the teacher training material.

Student Independent Projects Environmental Studies 2011: Creating Federal Policies to Support Environmental Education in Canada.

Environmental Education is an essential component of childhood education and can play a vital role in the development of positive environmental attitudes, community involvement and environmental awareness. One of the main challenges faced by Canadian educators is the lack of support and funding to fully engage and participate in Environmental Education programs that are locally available. To better understand the viewpoint and challenges of educators and Environmental Education programs, this paper includes an interview series with three Environmental Education leaders, followed by a discussion section on significant commonalities. Through the research of peer-reviewed literature, federal documents, and environmental networks, this research paper aims to interpret the development and challenges of K-12 environmental education in North America as well as to review the established programs, networks, and resources availble to Canadian educators.

Oceans Deep: Lesson E (Plankton Police)

Teacher resources for Lesson E in the Discover Oceanography 'Scheme of Work' for use in schools.

Contexts That Inform Racial Awareness and Affect Teaching Practice: A Study of White Bilingual Teachers

Thesis (Ph.D.)--University of Washington, 2016-08