8 research outputs found
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Methods and compositions for modulation and inhibition of telomerase in vitro
It was found that normal human stem cells produce a regulated non-processive telomerase activity, while cancer cells produce a processive telomerase activity. Nucleotide analogs, such as 7-deaza-2'-deoxyquanosine-5'-triphosphate (7-deaza-dGTP) were found to be substrates for processive telomerase and incorporated into telomeric sequence. The incorporation of this nucleotide subsequently affected the processivity of telomerase, converting processive telomerase to non-processive telomerase. The incorporation of this nucleotide analogs was also found to inhibit formation of G-quartets by telomeric sequence. Other methods for converting cancer processive telomerase to the more benign non-processive telomerase include partially cleaving the telomerase RNA. The nucleoside analogs were found to be capable of a variety of activities including mediating allosteric-like inhibition of telomerase, premature termination and shortening of telomeric DNA, destabilization of telomeric structure and function and eventually cell death. Understanding the mechanisms of telomerase modulation by the 7-deaza-nucleotides has allowed the design of new telomerase inhibitors, modulators and agents for affecting telomere structure and function. These discoveries have application in the treatment of cancer.Board of Regents, University of Texas Syste
Recommended from our members
Methods for modulation and inhibition of telomerase
It was found that normal human stem cells produce a regulated non-processive telomerase activity, while cancer cells produce a processive telomerase activity. Nucleotide analogs, such as 7-deaza-2′-deoxyquanosine-5′-triphosphate (7-deaza-dGTP) were found to be substrates for processive telomerase and incorporated into telomeric sequence. The incorporation of this nucleotide subsequently affected the processivity of telomerase, converting processive telomerase to non-processive telomerase. The incorporation of this nucleotide analogs was also found to inhibit formation of G-quartets by telomeric sequence. Other methods for converting cancer processive telomerase to the more benign non-processive telomerase include partially cleaving the telomerase RNA. The nucleoside analogs were found to be capable of a variety of activities including mediating allosteric-like inhibition of telomerase, premature termination and shortening of telomeric DNA, destabilization of telomeric structure and function and eventually cell death. Understanding the mechanisms of telomerase modulation by the 7-deaza-nucleotides has allowed the design of new telomerase inhibitors, modulators and agents for affecting telomere structure and function. These discoveries have application in the treatment of cancer.Board of Regents, University of Texas Syste
Recommended from our members
Methods for modulation and inhibition of telomerase
It was found that normal human stem cells produce a regulated non-processive telomerase activity, while cancer cells produce a processive telomerase activity. Nucleotide analogs, such as 7-deaza-2'-deoxyquanosine-5'-triphosphate (7-deaza-dGTP) were found to be substrates for processive telomerase and incorporated into telomeric sequence. The incorporation of this nucleotide subsequently affected the processivity of telomerase, converting processive telomerase to non-processive telomerase. The incorporation of this nucleotide analogs was also found to inhibit formation of G-quartets by telomeric sequence. Other methods for converting cancer processive telomerase to the more benign non-processive telomerase include partially cleaving the telomerase RNA. The nucleoside analogs were found to be capable of a variety of activities including mediating allosteric-like inhibition of telomerase, premature termination and shortening of telomeric DNA, destabilization of telomeric structure and function and eventually cell death. Understanding the mechanisms of telomerase modulation by the 7-deazanucleotides has allowed the design of new telomerase inhibitors, modulators and agents for affecting telomere structure and function. These discoveries have application in the treatment of cancer.Board of Regents, University of Texas Syste
Importance of Academic Legacy on Student Success in First- and Second-Semester General Chemistry
This investigation sought to elucidate the influence of students' academic legacy on their prior knowledge and course outcomes providing crucial insights for educators who teach general chemistry. This six-semester analysis involved 6,914 students enrolled in classes across nine Texas universities. Explored were personal circumstances associated with students' successes and failures that influenced performance in on- and off-sequence, first- and second-semester general chemistry (Chem 1 and Chem 2). Students' academic legacy based on their categorization as first generation (neither grandparent nor parent/guardian with a 4-year bachelor's degree), second generation (at least one grandparent or parent/guardian with a bachelor's degree), or third generation (at least one grandparent and at least one parent/guardian hold a bachelor's degree) was investigated. Of the students in the dataset 33.8% (n = 2,340) self-identified as Hispanic. Results for Hispanic and non-Hispanic students indicated that first-generation students struggled more with Chem 1 and Chem 2 than students in the other two legacy groups. As students' academic legacy extended, they were more apt to succeed in general chemistry. Second- and third-generation students demonstrated stronger prior high-school chemistry backgrounds and were enrolled in more advanced mathematics courses. As expected, students with stronger academic backgrounds in chemistry and mathematics scored higher on the diagnostic MUST (Math-Up Skills Test), had greater self-efficacy relative to their preparation to succeed, and reported fewer paid work hours. First-generation students on the average entered with lower diagnostic MUST scores, felt less prepared to succeed, and disclosed a greater need to be employed
MUST-Know Pilot—Math Preparation Study from Texas
Since 2007, the reported SAT (reading + math) scores for the state of Texas have steadily fallen from a high of 999 to an all-time low of 944. Solving this problem requires a multifaceted approach. For our part as instructors of a known gateway course, general chemistry, we chose to focus on the most fundamental crosscutting topic in STEM: arithmetic. Hence, the MUST Know (Mathematics: Underlying Skills and Thinking) study was conceived and implemented. General chemistry is widely considered a gateway course because students\u27 success in general chemistry provides entry into several STEM and some non-STEM careers. Failure to succeed in general chemistry has been linked to students\u27 mathematics fluency that other researchers have attributed to poor algebra skills. However, is it possible that this relationship should really be attributed to students\u27 lack of must-know arithmetic skills? In Fall 2016-Spring 2017, a team of 11 chemical educators investigated the relationships between solving simple arithmetic problems and course grades for 2,127 students (60.3% female) enrolled in general chemistry I and II at six post-secondary institutions (3, large public research universities; 2 Hispanic Serving Institutions; and 1, 4-year private university) from varied geographic locations in the heart of the state of Texas overlaying 32,000 square miles. The arithmetic concepts evaluated for this study are introduced to most Texas students starting at the 4th-grade level. The selected concepts include multiplication, division, fractions, scientific notation, exponential notation, logarithms, square roots and balancing chemical equations. Results support that students, without the aid of a calculator, succeeded at the 40%-correct level (Chem I) and 60%-correct level (Chem II). Students\u27 algebra skills might be a better predictor of overall success, but the initiator of the problem we posit starts with lack of automaticity and fluency with basic arithmetic skills. Correlations between final course grades and mathematics fluency ranged from 0.2-0.5 with the Hispanic-serving classes being among the weakest correlations and the research universities exhibiting the strongest. Building a strong profile of a successful general chemistry student is beginning to form from this continuing investigation. Future plans include implementation of High-Impact Practices (HIPs) to increase numeracy followed by dissemination of outcomes and expansion of the study to include other needed success-producing skills like logical thinking, spatial ability, and quantitative reasoning ability
Is the STEM Gender Gap Closing?
The Networking for Science Advancement (NSA) team's institutions consist of nine universities located in one large southwestern US state. This study evaluated students enrolled from Spring 2017 to Fall 2019 in firstand second-semester general chemistry. Over 90% of the students (n = 6,694) have been exposed to a secondary school isomorphic curriculum. The population studied, Chem I (n = 4,619) and Chem II (n = 2,075), met entry-level criteria and are therefore expected to succeed (i.e., earn grades of A, B or C). This study's focus is to disaggregate data based on binary gender (M/F) in hopes of revealing patterns that might remain hidden when studying an undivided population. In Chem I, the female population was 59.6% and increased to 64.5% for Chem II. The 15- min., diagnostic Math-Up Skills Test’s (MUST) scores identified about half of all students who were unsuccessful (grades of D and F). Results from the study support that males enter Chem I and II with better automaticity skills (what can be done without using a calculator) than females. However, females outperformed males on course averages in Chem I but not Chem II. Our data provide supporting evidence that the gender gap may be closing