Redox signaling between DNA repair proteins for efficient lesion detection
Published online before print August 31, 2009, doi: 10.1073/pnas.0908059106
PNAS September 8, 2009 vol. 106 no. 36
1. Amie K. Boala,
2. Joseph C. Genereuxa,
3. Pamela A. Sontza,
4. Jeffrey A. Gralnickb,
5. Dianne K. Newmanc,1 and
6. Jacqueline K. Bartona,1
+ Author Affiliations
1.
aDivision of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125;
2.
bDepartment of Microbiology, BioTechnology Institute, University of Minnesota, St. Paul, MN 55108; and
3.
cDepartments of Biology and Earth, Atomospheric and Planetary Science, and Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139
1.
Contributed by Jacqueline K. Barton, July 21, 2009 (received for review June 25, 2009)
Abstract
Base excision repair (BER) enzymes maintain the integrity of the genome, and in humans, BER mutations are associated with cancer. Given the remarkable sensitivity of DNA-mediated charge transport (CT) to mismatched and damaged base pairs, we have proposed that DNA repair glycosylases (EndoIII and MutY) containing a redox-active [4Fe4S] cluster could use DNA CT in signaling one another to search cooperatively for damage in the genome. Here, we examine this model, where we estimate that electron transfers over a few hundred base pairs are sufficient for rapid interrogation of the full genome. Using atomic force microscopy, we found a redistribution of repair proteins onto DNA strands containing a single base mismatch, consistent with our model for CT scanning. We also demonstrated in Escherichia coli a cooperativity between EndoIII and MutY that is predicted by the CT scanning model. This relationship does not require the enzymatic activity of the glycosylase. Y82A EndoIII, a mutation that renders the protein deficient in DNA-mediated CT, however, inhibits cooperativity between MutY and EndoIII. These results illustrate how repair proteins might efficiently locate DNA lesions and point to a biological role for DNA-mediated CT within the cell.
Thursday, September 10, 2009
Tuesday, September 8, 2009
sexual activity on cycle ergometer stress test parameters
Effect of sexual activity on cycle ergometer stress test parameters, on plasmatic testosterone levels and on concentration capacity - A study in high-level male athletes performed in the laboratory
Author(s): Sztajzel J, Periat M, Marti V, Krall P, Rutishauser W
Source: JOURNAL OF SPORTS MEDICINE AND PHYSICAL FITNESS
Volume: 40
Issue: 3
Pages: 233-239
Published: SEP 2000
Abstract: Background. The purpose of this study was to investigate the effect of sexual activity on cycle ergometer stress test parameters, on plasmatic testosterone levels and on concentration capacity in high-level mate athletes.
Methods. Experimental design. Analysis of two days of testing accomplished in a laboratory setting, comparing a day with to a day without sexual activity (control day). Participants. Fifteen high-level male athletes, consisting of 8 team players, 5 endurance athletes and 2 weight-lifters, participated in the study. Measures. Each subject completed the following on each test day: two maximal graded stress tests on a cycle ergometer and a one-hour exercise stress test coupled to an arithmetic mental concentration test. Blood samples of testosterone were obtained and cardiac activity of each athlete was monitored with a 24-hour ECG tape recording over the two test days.
Results, Significantly higher differences were achieved for posteffort heart rate (HR) values at 5 minutes (p<0.01) and at 10 minutes (p<0.01) during the recovery phase of the morning stress test 2 hours after sexual activity. These differences disappeared during the recovery phase of the afternoon stress test performed approximately 10 hours after sexual intercourse took place.
Conclusions, Our findings show that sexual activity had no detrimental influence on the maximal workload achieved and on the athletes' mental concentration. However, the higher posteffort HR values after the maximal stress test on the morning of sexual intercourse suggest that the recovery capacity of an athlete could be affected if he had sexual intercourse approximately 2 hours before a competition event.
Author(s): Sztajzel J, Periat M, Marti V, Krall P, Rutishauser W
Source: JOURNAL OF SPORTS MEDICINE AND PHYSICAL FITNESS
Volume: 40
Issue: 3
Pages: 233-239
Published: SEP 2000
Abstract: Background. The purpose of this study was to investigate the effect of sexual activity on cycle ergometer stress test parameters, on plasmatic testosterone levels and on concentration capacity in high-level mate athletes.
Methods. Experimental design. Analysis of two days of testing accomplished in a laboratory setting, comparing a day with to a day without sexual activity (control day). Participants. Fifteen high-level male athletes, consisting of 8 team players, 5 endurance athletes and 2 weight-lifters, participated in the study. Measures. Each subject completed the following on each test day: two maximal graded stress tests on a cycle ergometer and a one-hour exercise stress test coupled to an arithmetic mental concentration test. Blood samples of testosterone were obtained and cardiac activity of each athlete was monitored with a 24-hour ECG tape recording over the two test days.
Results, Significantly higher differences were achieved for posteffort heart rate (HR) values at 5 minutes (p<0.01) and at 10 minutes (p<0.01) during the recovery phase of the morning stress test 2 hours after sexual activity. These differences disappeared during the recovery phase of the afternoon stress test performed approximately 10 hours after sexual intercourse took place.
Conclusions, Our findings show that sexual activity had no detrimental influence on the maximal workload achieved and on the athletes' mental concentration. However, the higher posteffort HR values after the maximal stress test on the morning of sexual intercourse suggest that the recovery capacity of an athlete could be affected if he had sexual intercourse approximately 2 hours before a competition event.
Does Sex the Night Before Competition Decrease Performance?
Does Sex the Night Before Competition Decrease Performance?
McGlone, Samantha; Shrier, Ian MD, PhD*†
Author Information
*Department of Physiology, McGill University, and †Centre for Clinical Epidemiology and Community Studies, Montreal, Quebec, Canada
Received June 7, 1999; accepted August 9, 2000.
Address correspondence and reprint requests to Ian Shrier, MD, Centre for Clinical Epidemiology and Community Studies, 3755 Cote Sainte Catherine Road, Montreal, Quebec H3T 1E2, Canada.
For many years, football coaches, Olympic athletes, and even Muhammad Ali have advocated sexual abstinence the night before an athletic event. 1 Marty Liquori, one the world's number one-ranked 5,000-meter runner believes that “Sex makes you happy, and happy people don't run a 3:47 mile.”2 Marv Levy, head coach of the Buffalo Bills, insisted that the team be separated from their wives before their appearance in four Super Bowls; a policy that apparently was not successful (four losses out of four Super Bowls). On the other hand, there are also plenty of anecdotal stories of athletes who claim to have benefited from sex the night before an event. Both U.S. track star David Wottle and Canadian downhill skier Karin Lee Gardner attribute their Olympic gold medals in part to their “pre-race preparation.”2 As legendary New York Yankees manager Casey Stengel put it, “It's not the sex that wrecks these guys, it's staying up all night looking for it.” Considering the controversy surrounding the topic, the objective of this editorial is to summarize the literature on whether sex the night before competition affects performance, and to suggest possible future areas for research.
The long-standing myth that athletes should practice abstinence before important competitions may stem from the theory that sexual frustration leads to increased aggression, and that the act of ejaculation draws testosterone from the body. 1 In actual fact, sex could alter performance through either physiological or psychological factors. To answer this question, we searched SportDiscus (1975–1988/1989, key words: Coitus and Sexual Intercourse) and MEDLINE for relevant articles. Of the 31 articles we retrieved, only 3 were scientific studies (all physiological). All of these studies suggested that sex the night before competition does not alter physiological testing results. For instance, 14 married male former athletes were given a maximum-effort grip strength test the morning after coitus, and the same test following at least 6 days of abstinence. 3 The results suggested that strength and endurance of the palmar flexing muscles are not adversely affected by sex the previous night. An unpublished follow-up to this study was conducted by researchers at Colorado State University on 10 fit, married men, ages 18–45 years (cited in ref. 4). In their tests for grip strength, balance, lateral movement, reaction time, aerobic power (stair-climbing exercise), and VO2max (treadmill test), the results did not change with sexual activity. Finally, the results from a 1995 randomized cross-over study suggested that sexual intercourse 12 hours prior to the test had no significant effects on maximal aerobic power, oxygen pulse, or double product. 5
Based on the results of these studies, one might conclude that sexual activity the night before competition would not affect performance. However, each of the above-mentioned studies focused on the physiological effects of precompetition sex, which would only be expected to decrease performance if the activity led to exhaustion. Considering that normal sexual intercourse between married partners expends only 25–50 calories (the energy equivalent of walking up two flights of stairs), 6 it is doubtful that sex the previous night would affect laboratory physiological performance tests.
Remembering that the original hypothesis suggested that performance would only be affected through a change in aggression, researchers really should have measured variables that are affected by aggression (e.g., motivation, alertness, and attitude toward competition). According to the current “inverted U” sport psychology hypothesis, 4 there is an optimal level of alertness/anxiety before a competition, and a poor performance will result from either being too anxious or not alert enough. If athletes are too anxious and restless the night before an event, then sex may be a relaxing distraction. If they are already relaxed or, like some athletes, have little interest in sex the night before a big competition, then a good night's sleep is all they need. This theory predicts that the results will be dependent on individual preferences and routines. The night before an important race is not a good time for drastic changes in routine. Consistency is the key.
Clearly there is a need for more research on the topic of sexual activity and athletic performance. However, any research will have difficulty controlling factors related to such sexual behavior such as the time of day, frequency and duration of sexual activity, behavior of subjects between data collection, diet, fatigue, stress, and individual response to sexual activity. Anshel also poses a question worth considering: “How valid are test results when a natural activity such as coitus becomes a required act occurring within a specific time period?”7 In addition, results may be dependent on the sexual partner. For instance, heart rate and blood pressure responses are different if sex is with a spouse of 10 years, compared to a new partner or in strange surroundings. 8 Therefore, any future research will have to control for interindividual variation of the above-mentioned variables with a randomized design, or at least control for differences at the analysis stage.
Finally, the inverted U hypothesis for alertness/anxiety suggests that the performance of some people will improve with sex the night before competition (i.e., responders) and the performance of others will be hindered (i.e., nonresponders). If true, a randomized controlled trial may not be able to detect any differences. For instance, if the “truth” is that 50% of the population improves with sex the night before a competition and 50% is hindered by sex the night before competition, a randomized controlled trial will show that on average there is no effect. Therefore, the best way to test the hypothesis is with a repeated-measures, cross-over design in which the same athletes are tested several times following abstinence, and several times following sex the night before competition. This would allow one to determine not only if sex the night before competition affects performance in certain individuals, but also if there are indeed “responders” and “nonresponders.”
Back to Top
REFERENCES
1. Krieger L. Scoring before a big event. Winning 1997; 1:88–89. [Context Link]
2. Bloom M. The sex factor. Runner's World 1994; 11:71–74. [Context Link]
3. Johnson W. Muscular performance following coitus. J Sex Res 1968; 4:247–248. Library Holdings [Context Link]
4. Thornton J. Sexual activity and athletic performance: is there a relationship? Phys Sport Med 1990; 18:148–153. [Context Link]
5. Boone T, Gilmore S. Effects of sexual intercourse on maximal aerobic power, oxygen pulse, and double product in male sedentary subjects. J Sports Med Phys Fitness 1995; 35:214–217. Library Holdings [Context Link]
6. Mirkin G. Sex before competition. Report #6750. Mar. 10, 1996. http://drmirkin.com/archive/6750.html [Context Link]
7. Anshel M. Effects of sexual activity on athletic performance. Phys Sports Med 1981; 9:65–68. Library Holdings [Context Link]
8. Bohlen J, Held J, Sanderson M, et al. Heart rate, rate pressure point, and oxygen uptake during four sexual activities. Arch Intern Med 1984; 144:1745–1748. Bibliographic Links Library Holdings [Context Link]
McGlone, Samantha; Shrier, Ian MD, PhD*†
Author Information
*Department of Physiology, McGill University, and †Centre for Clinical Epidemiology and Community Studies, Montreal, Quebec, Canada
Received June 7, 1999; accepted August 9, 2000.
Address correspondence and reprint requests to Ian Shrier, MD, Centre for Clinical Epidemiology and Community Studies, 3755 Cote Sainte Catherine Road, Montreal, Quebec H3T 1E2, Canada.
For many years, football coaches, Olympic athletes, and even Muhammad Ali have advocated sexual abstinence the night before an athletic event. 1 Marty Liquori, one the world's number one-ranked 5,000-meter runner believes that “Sex makes you happy, and happy people don't run a 3:47 mile.”2 Marv Levy, head coach of the Buffalo Bills, insisted that the team be separated from their wives before their appearance in four Super Bowls; a policy that apparently was not successful (four losses out of four Super Bowls). On the other hand, there are also plenty of anecdotal stories of athletes who claim to have benefited from sex the night before an event. Both U.S. track star David Wottle and Canadian downhill skier Karin Lee Gardner attribute their Olympic gold medals in part to their “pre-race preparation.”2 As legendary New York Yankees manager Casey Stengel put it, “It's not the sex that wrecks these guys, it's staying up all night looking for it.” Considering the controversy surrounding the topic, the objective of this editorial is to summarize the literature on whether sex the night before competition affects performance, and to suggest possible future areas for research.
The long-standing myth that athletes should practice abstinence before important competitions may stem from the theory that sexual frustration leads to increased aggression, and that the act of ejaculation draws testosterone from the body. 1 In actual fact, sex could alter performance through either physiological or psychological factors. To answer this question, we searched SportDiscus (1975–1988/1989, key words: Coitus and Sexual Intercourse) and MEDLINE for relevant articles. Of the 31 articles we retrieved, only 3 were scientific studies (all physiological). All of these studies suggested that sex the night before competition does not alter physiological testing results. For instance, 14 married male former athletes were given a maximum-effort grip strength test the morning after coitus, and the same test following at least 6 days of abstinence. 3 The results suggested that strength and endurance of the palmar flexing muscles are not adversely affected by sex the previous night. An unpublished follow-up to this study was conducted by researchers at Colorado State University on 10 fit, married men, ages 18–45 years (cited in ref. 4). In their tests for grip strength, balance, lateral movement, reaction time, aerobic power (stair-climbing exercise), and VO2max (treadmill test), the results did not change with sexual activity. Finally, the results from a 1995 randomized cross-over study suggested that sexual intercourse 12 hours prior to the test had no significant effects on maximal aerobic power, oxygen pulse, or double product. 5
Based on the results of these studies, one might conclude that sexual activity the night before competition would not affect performance. However, each of the above-mentioned studies focused on the physiological effects of precompetition sex, which would only be expected to decrease performance if the activity led to exhaustion. Considering that normal sexual intercourse between married partners expends only 25–50 calories (the energy equivalent of walking up two flights of stairs), 6 it is doubtful that sex the previous night would affect laboratory physiological performance tests.
Remembering that the original hypothesis suggested that performance would only be affected through a change in aggression, researchers really should have measured variables that are affected by aggression (e.g., motivation, alertness, and attitude toward competition). According to the current “inverted U” sport psychology hypothesis, 4 there is an optimal level of alertness/anxiety before a competition, and a poor performance will result from either being too anxious or not alert enough. If athletes are too anxious and restless the night before an event, then sex may be a relaxing distraction. If they are already relaxed or, like some athletes, have little interest in sex the night before a big competition, then a good night's sleep is all they need. This theory predicts that the results will be dependent on individual preferences and routines. The night before an important race is not a good time for drastic changes in routine. Consistency is the key.
Clearly there is a need for more research on the topic of sexual activity and athletic performance. However, any research will have difficulty controlling factors related to such sexual behavior such as the time of day, frequency and duration of sexual activity, behavior of subjects between data collection, diet, fatigue, stress, and individual response to sexual activity. Anshel also poses a question worth considering: “How valid are test results when a natural activity such as coitus becomes a required act occurring within a specific time period?”7 In addition, results may be dependent on the sexual partner. For instance, heart rate and blood pressure responses are different if sex is with a spouse of 10 years, compared to a new partner or in strange surroundings. 8 Therefore, any future research will have to control for interindividual variation of the above-mentioned variables with a randomized design, or at least control for differences at the analysis stage.
Finally, the inverted U hypothesis for alertness/anxiety suggests that the performance of some people will improve with sex the night before competition (i.e., responders) and the performance of others will be hindered (i.e., nonresponders). If true, a randomized controlled trial may not be able to detect any differences. For instance, if the “truth” is that 50% of the population improves with sex the night before a competition and 50% is hindered by sex the night before competition, a randomized controlled trial will show that on average there is no effect. Therefore, the best way to test the hypothesis is with a repeated-measures, cross-over design in which the same athletes are tested several times following abstinence, and several times following sex the night before competition. This would allow one to determine not only if sex the night before competition affects performance in certain individuals, but also if there are indeed “responders” and “nonresponders.”
Back to Top
REFERENCES
1. Krieger L. Scoring before a big event. Winning 1997; 1:88–89. [Context Link]
2. Bloom M. The sex factor. Runner's World 1994; 11:71–74. [Context Link]
3. Johnson W. Muscular performance following coitus. J Sex Res 1968; 4:247–248. Library Holdings [Context Link]
4. Thornton J. Sexual activity and athletic performance: is there a relationship? Phys Sport Med 1990; 18:148–153. [Context Link]
5. Boone T, Gilmore S. Effects of sexual intercourse on maximal aerobic power, oxygen pulse, and double product in male sedentary subjects. J Sports Med Phys Fitness 1995; 35:214–217. Library Holdings [Context Link]
6. Mirkin G. Sex before competition. Report #6750. Mar. 10, 1996. http://drmirkin.com/archive/6750.html [Context Link]
7. Anshel M. Effects of sexual activity on athletic performance. Phys Sports Med 1981; 9:65–68. Library Holdings [Context Link]
8. Bohlen J, Held J, Sanderson M, et al. Heart rate, rate pressure point, and oxygen uptake during four sexual activities. Arch Intern Med 1984; 144:1745–1748. Bibliographic Links Library Holdings [Context Link]
The effect of losing virginity on academic performance
Reading, writing, and sex: The effect of losing virginity on academic performance
View full text from the publisher Blackwell Science
Author(s): Sabia JJ (Sabia, Joseph J.)
Source: ECONOMIC INQUIRY
Volume: 45
Issue: 4
Pages: 647-670
Published: OCT 2007
Abstract: Controlling for a wide set of individual- and family-level observables available in the National Longitudinal Study of Adolescent Health, ordinary least squares (OLS) estimates show that sexually active adolescents have grade point averages that are approximately 0.2 points lower than virgins. However, when information on the timing of intercourse decisions is exploited and individual fixed effects are included, the negative effect of sexual intercourse disappears for females, but persists for males. Taken together, the results of this study suggest that while there may be adverse academic spillovers from engaging in intercourse for some adolescents, previous studies' estimates are overstated due to unmeasured heterogeneity.
View full text from the publisher Blackwell Science
Author(s): Sabia JJ (Sabia, Joseph J.)
Source: ECONOMIC INQUIRY
Volume: 45
Issue: 4
Pages: 647-670
Published: OCT 2007
Abstract: Controlling for a wide set of individual- and family-level observables available in the National Longitudinal Study of Adolescent Health, ordinary least squares (OLS) estimates show that sexually active adolescents have grade point averages that are approximately 0.2 points lower than virgins. However, when information on the timing of intercourse decisions is exploited and individual fixed effects are included, the negative effect of sexual intercourse disappears for females, but persists for males. Taken together, the results of this study suggest that while there may be adverse academic spillovers from engaging in intercourse for some adolescents, previous studies' estimates are overstated due to unmeasured heterogeneity.
Wednesday, September 2, 2009
DNA methylation analysis by प्य्रोसेक़ुएन्किन्ग
Figure 1 - Enzymatic cascade of the pyrosequencing reaction in the example of a bisulfite-treated template sequence, including a CpG position that is methylated on approximately 50% of all molecules.
From the following article
DNA methylation analysis by pyrosequencing
Jörg Tost & Ivo G Gut
Nature Protocols 2, 2265 - 2275 (2007) Published online: 6 September 2007
doi:10.1038/nprot.2007.314
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