Inhibiting the Actions of Essential Biomolecule Phosphopantetheine.

Phosphopantetheine is an essential biomolecule required for life. The enzyme phosphopantothenoylcysteine synthetase (PPCS) incorporates the reactive thiol moiety in the Coenzyme A (CoA) biosynthetic pathway. Two types of PPCS exist in bacteria: bifunctional fusion protein Type 1 and monofunctional Type 3. Previously developed cytidylate mimics were determined to have stronger binding affinity for Type 3 Streptococcus pneumoniae PPCS compared to Type 1. To explore the structure activity relationship of Type 3 PPCS, completely conserved residues of bacterial PPCS were probed via saturation mutagenesis in a developed knockout system. Mutagenesis revealed that conserved S. pneumoniae PPCS residues K123 and D93 were stringent, as only K123N/R/M and D93E/N were viable mutations. D93 was determined to be responsible for the association of divalent cations and CTP to the active site, as D93E and D93N exhibited a 1.5-2.7 fold (151-267 μM apparent Km) less affinity for CTP and D93N resulted in a 2-fold drop in MgCl2 affinity. K123 was identified as catalytically significant to the first half CTP utilizing reaction as the K123M and K123R mutations had 1.4-8.8 fold (142-872 μM apparent Km) loss in the binding affinity for CTP. Additionally, phosphopantetheine is the essential prosthetic group of acyl carrier protein (ACP), utilized by gram negative specific acyltransferases (LpxA and LpxD) to construct lipopolysaccharide (LPS). Peptide RJPXD33 (TNLYMLPKWDIP) was discovered to bind and inhibit both LpxA and LpxD (binding constants of 22 μM and 6.5 μM respectively), offering a probe for the development of a dual targeting small molecule inhibitor. The molecular binding mechanism by which RJPXD33 interacts with LpxD was elucidated via fluorescence polarization based binding assays of truncated and alanine-mutated peptide. RJPXD33 P7 was identified to be important to binding LpxD as mutation of the residue to alanine resulted in a binding constant >50 μM, while similar tests in LpxA had a limited effect on binding (9.4 ± 0.6 μM). Residue K8 appeared inconsequential, as mutation to alanine had little effect on binding to LpxA or LpxD (5.1 μM and 3.1 μM binding constants, respectively), but essential to inhibition. Photo-labile RJPXD33 probes were implemented for mapping LpxD-RJPXD33 protein-peptide interactions.PHDMedicinal ChemistryUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/111574/1/heslipky_1.pd

Teachers’ Perspectives on Instructional Teaching Practices

A problem exists with students’ reading achievement at an elementary school in the southcentral area of the United States. A high proportion of students had unsatisfactory scores on their reading achievement tests between 2016 and 2019. A possible contributing factor is that teachers have struggled to provide effective efforts, strategies, and interventions to improve the reading performance of the students over this span of time. The purpose of this basic qualitative exploratory study was to examine teachers’ perspectives on how instructional teaching practices were used to help students read at grade level at the elementary school under study. The conceptual framework for this study was Resnick’s self-perception theory. The research question for the study was used to determine how teachers’ perspectives on the instructional teaching practices were used to help students read at grade level at the elementary school under study. Data were collected from open-ended interviews with 8 teachers who had at least 3 years of experience working with students who did not read at grade level. Data were coded and analyzed from transcripts of the interviews. The key results, conclusions, and project of the final study were based on the following 6 emergent themes: (a) innovative instructional reading practices; (b) a general 9-week curriculum plan for teaching; (c) students who did not meet standards; (d) satisfactory instructional reading practices; (e) support from elementary school under study; and (f) quiet, motivating, and positive educational setting. This study might contribute to positive social change by benefiting students, teachers, administrators, parents, and community stakeholders by helping students read at grade level

Practices of Administrators and English as a Second Language Teachers for Third-Grade English Language Learners

AbstractThe problem under study was that administrators were challenged to support ELL teachers because current instructional strategies did not address the gap between the academic achievement of ELLs and non-ELLs. A basic qualitative design was used to investigate how administrators supported teachers’ implementation of instructional strategies for this population. The resulting project was a 1-week professional development instructional program for ELL administrators and teachers. Wright’s self-awareness theory was used as the conceptual framework approach to examine how administrators encouraged ELL teachers to attend and use professional development because current instructional strategies did not address the gap between the academic achievement of ELLs and non-ELLs. The research question addressed how administrators encouraged ELL teachers to attend and use professional development training. Data were gathered from the eight participants using eight semi-structured, open-ended interview questions. The resulting data were thematically analyzed and coded. The key results, the project, a program of professional development, and the conclusions of the final study were based on the following seven emerging themes: (a) monitoring the usage of strategies shared during professional development, (b) implementation of curricular sets comparable to their reading units, (c) encouraging ELL teachers to attend ELL training, (d) supporting strategies for ELLs, (e) comprehension discussions to determine ELLs’ needs, (f) time management of ELL administrators, and (g) districtwide modeling of ELL pedagogy. This project study might benefit ELL school districts by contributing to academic achievement, where positive social changes would transpire

Coding Reference: An Analytical Approach to Assessment

Poster presentation, ARL Assessment Conference 2012, Charlottesville, VAPurpose: The research consultation model at the Sheridan Libraries, Johns Hopkins University is a part of a two-tiered model that allows for sophisticated research transactions to be handled by librarians. This model is a core function of our university library system, and a function which we seek to improve. Design: Librarian consultations are documented within RefAnalytics, a tool that allows libraries to track reference transactions. Fields used in reporting include: question asked, answer given, patron type, contact type, resources used, and READ (Reference Effort Assessment Data) scale number assigned to the transaction. Methodology/Approach: In a collaboration between the Academic Liaison department and the User Experience Group, data from the past year of RefAnalytics transactions is coded through a carefully designed coding architecture. Using Nvivo, data is accessible through complex matrix queries which illuminate findings concerning user behavior and librarian reporting. Practical implications/Value: When analysis is complete, findings will inform more sophisticated understandings of services reporting and open avenues into ways in which we can innovate within the current service model. This analysis cycle is an important first step in beginning a rigorous assessment tradition within the Academic Liaison Department

Using the serious illness conversation guide to improve the quality of life of hematology-oncology patients: a pilot study

Introduction: Hematology-oncology patients are more likely to receive high intensity care (HIC), including ICU admission and active cancer treatment, than solid cancer patients near end of life (EOL). This prevents patients and their families from realistically planning for the future, and diminishes quality of life (QOL). We previously conducted a retrospective study to understand factors influencing HIC outcomes at EOL in hematology patients at McGill-affiliated hospitals. While non-curative goals, early level of intervention (LOI) discussions and palliative care (PC) involvement lowered the likelihood of HIC at EOL, the median time of LOI discussion and PC involvement to death was 22 and 9 days respectively. We hypothesize that a timely discussion aligning patient perspectives and goals with their treating team could improve QOL at EOL. Methods: We are conducting a pilot study looking at the impact of using the Serious Illness Conversation Guide (SICG), a validated conversation tool in the general oncology population, on the QOL of hematology patients. Participants are identified by their treating doctor or nurse practitioner to be at risk of dying in the next year. The primary aim is to decrease death in acute care. Secondary aims include reporting other HIC outcomes, time from LOI discussion and PC consult to death, and the short term benefit to QOL. In addition, qualitative analysis will explore participant perspectives on benefits of the SICG and areas to improve, and explore EOL QOL topics relevant to hematology patients. We have currently enrolled 2 patients. Interim analysis is projected for September 2023. &nbsp

Organogenesis and tumorigenesis: Insight from the JAK/STAT pathway in the Drosophila eye

The Janus kinase (JAK) signal transducer and activator of transcription (STAT) pathway is one of the main signaling pathways in eukaryotic cells. This pathway is used during diverse growth and developmental processes in multiple tissues to control cell proliferation, differentiation, survival, and apoptosis. In addition to its role during development, the JAK/STAT pathway has also been implicated in tumorigenesis. Drosophila melanogaster is a powerful genetic tool, and its eyes have been used extensively as a platform to study signaling pathways. Many reports have demonstrated that the JAK/STAT pathway plays pleiotropic roles in Drosophila eye development. Its functions and activation are decided by its interplay with other signal pathways and the epigenetic status. In this review, we focus on the functions and regulation of the JAK/STAT pathway during eye development and provide some insights into the study of this pathway in tumorigenesis. Developmental Dynamics 239:2522–2533, 2010. © 2010 Wiley-Liss, Inc

Centre internship / Stagiaire au CRDI

Critical appraisal of children's homes, schools and camps in Jamaica and Colombia. Activities, attitudes of personnel, programmes and recommendations for improvement are presented in the light of Canadian family welfare