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

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

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

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