Activation of two types of brain glutamate dehydrogenase isoproteins by gabapentin

AbstractThe stimulatory effects of gabapentin on the activities of two types of glutamate dehydrogenase (GDH) isoproteins homogeneously purified from bovine brain have been studied at various conditions. When the effects of different gabapentin concentrations on GDH activities were studied in the direction of reductive amination of 2-oxoglutarate with NADPH as a coenzyme, a marked activation was observed for both isoproteins, whereas both isoproteins showed activation to a lesser extent with NADH as a coenzyme. Stimulatory effects of gabapentin on GDH activities in the direction of the oxidative deamination of glutamate were also observed, but to a much lesser extent than reductive amination. There were big differences between the two GDH isoproteins in their sensitivity to the action of gabapentin. The largest activation was observed with GDH II when NADPH was used as a coenzyme. Half-maximal stimulation was reached at around 1.5 mM. Gabapentin relieved the inhibition of GDH isoproteins by GTP and this resulted in an increase in the apparent activation by gabapentin in the presence of GTP. 2-Oxoglutarate was found to give rise to high substrate inhibition and gabapentin reduced the substrate inhibition in the presence of 0.2 mM NADH. Since there are neurodegenerative disorders in which GDH activity is decreased, the therapeutic modulation of the activity of this enzyme may be clinically useful

Point Mutation of Hoxd12 in Mice

Purpose: Genes of the HoxD cluster play a major role in vertebrate limb development, and changes that modify the Hoxd12 locus affect other genes also, suggesting that HoxD function is coordinated by a control mechanism involving multiple genes during limb morphogenesis. In this study, mutant phenotypes were produced by treatment of mice with chemical mutagen, N-ethyl-N-nitrosourea (ENU). We analyzed mutant mice exhibiting the specific microdactyly phenotype and examined the genes affected. Materials and Methods: We focused on phenotype characteristics including size, bone formation, and digit morphology of ENU-induced microdactyly mice. The expressions of several molecules were analyzed by genome-wide screening and quantitative real-time PCR to define the affected genes. Results: We report on limb phenotypes of an ENU-induced A-to-C mutation in the Hoxd12 gene, resulting in alanine-to-serine conversion. Microdactyly mice exhibited growth defects in the zeugopod and autopod, shortening of digits, a missing tip of digit I, limb growth affected, and dramatic increases in the expressions of Fgf4 and Lmx1b. However, the expression level of Shh was not changed Hoxd12 point mutated mice. Conclusion: These results suggest that point mutation rather than the entire deletion of Hoxd12, such as in knockout and transgenic mice, causes the abnormal limb phenotype in microdactyly mice. The precise nature of the spectrum of differences requires further investigation.link_to_subscribed_fulltex

Student Progression Through Developmental Sequences in Community Colleges

Developmental education is designed to provide students with weak academic skills the opportunity to strengthen those skills enough to prepare them for college-level coursework. The concept is simple enough—students who arrive unprepared for college are provided instruction to bring them up to an adequate level. But in practice, developmental education (or “remedial” education, we use these terms interchangeably) is complex and confusing. Experts do not agree on the meaning of being “college ready,” and policies governing assessment, placement, pedagogy, staffing, completion, and eligibility for enrollment in college-level, credit-bearing courses vary from state to state, college to college, and program to program. The developmental education process is confusing enough simply to describe, yet from the point of view of the student, especially one with very weak academic skills and little previous success in school, it may appear as a bewildering set of unanticipated obstacles involving several assessments, classes in more than one subject area, and sequences of courses requiring three or more semesters of study before the student (often a high school graduate) is judged prepared for college-level work

Lingerers in the Community College

Many community college students fail to graduate. Even among those students who enroll for a substantial period of time and who earn a significant number of college credits, many fail to complete an award. To improve completion rates in community colleges, administrators may want to focus attention on this group of students we call “lingerers.” Compared with other students, such as those who drop out early in their college careers, lingerers demonstrate persistence and a strong intention to complete a college program, yet they do not earn an award. This result is costly both for the students and the colleges they attend. In this analysis, we examine the following questions: What are the characteristics of lingerers in community college? How do their course-taking behaviors differ from those of students who complete an award? What prevents them from completing? Our analysis is based on extensive unit record data on cohorts of students at nine community colleges in three states. The data include information on student demographics, course enrollment and performance, credential completion, and transfer. We track students for up to five academic years. The data used in this analysis are from the 2005–06 first-time-in-college (FTIC) student cohort at these nine colleges. Credit students (i.e., those students who either placed into or enrolled in developmental education or those who either placed into or enrolled in college-level coursework) constituted 36 percent of the full FTIC sample. We limit our study to this subset of credit students in order to restrict our analysis to students who were mostly likely to earn an award or transfer to a four-year college. As a result, the full sample used in our analysis is 27,713 students. We define lingerers as students in the sample who completed 30 or more college-level semester credits and were still enrolled in the same community college in their fifth year but who had not yet earned a credential. About 9 percent of students in our sample were lingerers. We also make comparisons with “completers,” students who earned an associate degree at the community college within five years. About 6 percent of students in our sample were completers

New Evidence of Success for Community College Remedial English Students: Tracking the Outcomes of Students in the Accelerated Learning Program (ALP)

This paper presents the findings from a follow-up quantitative analysis of the Community College of Baltimore County’s Accelerated Learning Program (ALP). Our results suggest that among students who enroll in the highest level developmental writing course, participation in ALP is associated with substantially better outcomes in terms of English 101 completion and English 102 completion (college-level English courses), which corroborates the results of a similar analysis completed in 2010. These results were consistent, and in some cases, even stronger, when we used propensity score matching. Moreover, using a larger number of cohorts and tracking students over a longer period of time, we also found that ALP students were more likely to persist to the next year than non-ALP students. Specific subgroup analyses for earlier versus later cohorts, as well as for Black and low-income students, revealed relationships between ALP participation and student outcomes that were similar to those found in the larger sample, although ALP appeared to be more effective for White and high-income students on some outcomes. Finally, we compared college-ready students enrolled in ALP sections of English 101 with their counterparts in wholly college-ready sections, and found that those in ALP sections had equivalent performance within English 101 itself, but slightly lower subsequent college-level course enrollment and completion

Developmental Education in Community Colleges

Developmental students face tremendous barriers. Less than one quarter of community college students who enroll in developmental education complete a degree or certificate within eight years of enrollment. In comparison, almost 40 percent of community college students who do not enroll in any developmental education course complete college in the same time period. To meet the Obama administration's goal of increasing the number of community college graduates by 5 million by 2020, it is necessary to significantly improve outcomes for underprepared community college students. In this brief, the authors review evidence about the effectiveness of developmental education and provide information about the progression of students through developmental sequences. The authors then discuss problems associated with the assessments used to assign students to developmental courses, and briefly review costs. Finally, they describe three initiatives designed to improve the performance of remedial services

Get with the Program: Accelerating Community College Students' Entry into and Completion of Programs of Study

Most students who enter higher education through a community college fail to earn a postsecondary credential. One reason for this that has not received enough attention is that many students do not enter a college-level program of study. Many new students arrive at community colleges without clear goals for college and careers. Community colleges offer a wide array of programs but typically provide little guidance to help students choose and successfully enter a program of study. Community college departments often do not closely monitor the progress of students who do enter their programs to ensure that they complete. This paper, originally released in April 2011, presents a simple method that community colleges can use to measure rates of program entry and completion using data on students' actual course-taking behaviors rather than declared major or intent. This method is used to track the progress and outcomes of first-time college students over five years using data from an anonymous sample of community colleges. The analysis shows that it is essential for students to enter a program of study as soon as possible. Students who do not enter a program within a year of enrollment are far less likely to ever enter a program and therefore less likely to earn a credential. The paper offers suggestions for ways community colleges can rethink their practices at key stages of students' engagement to substantially increase rates of program entry and completion