All posts by Laura Damiano

Rotating night shift work is linked to several diseases

Cancer, Health, , , , , , , , , , ,
"MoonClouds" by Smatprt - Own work. Licensed under CC BY-SA 3.0 via Wikimedia Commons - http://commons.wikimedia.org/wiki/File:MoonClouds.JPG#mediaviewer/File:MoonClouds.JPG
“MoonClouds” by Smatprt – Own work. Licensed under CC BY-SA 3.0 via Wikimedia Commons – http://commons.wikimedia.org/wiki/File:MoonClouds.JPG#mediaviewer/File:MoonClouds.JPG

Doing activities and working during the night affects the circadian system, causing sleeping disorders thus severely affecting health.

A large prospective study has been published this month on the American Journal of Preventive Medicine using data from the Nurses’ Health Study (NHS), linking night shift rotation, cardiovascular diseases (CVDs), and some types of cancer mortality1. The NHS was established in 1976 enrolling more than 100,000 nurses aged 30–55 years. Women with previous CVD or cancer or nurses who did not provide information about their shift were excluded from the study; therefore only the information on 74,862 nurses was used during 22 years of follow-up.

The nurses were classified in four groups according to the years of rotating night shift work: never, 1–5, 6–14, and >15 years. Working rotating night shifts for more than five years significantly correlated with all-cause, CVD, in particular ischemic heart disease, and some type of cancer mortality. Lung cancer was the most significantly correlated cause of cancer mortality, followed by colorectal and breast cancers, but overall cancer mortality was not significantly increased in nurses who worked rotating night shift for more than five years. Also lifestyle factors—such as physical activity, dietary habits, and smoking—body mass index, diabetes, cholesterol were considered, but no significant correlations were identified. Women working rotating night shifts tended to be older, be more physically active, drink less alcohol, eat less cereal, and were more likely to have diabetes, hypertension, and hypercholesterolemia than women without night shift work.

Undoubtedly working rotating night shifts disrupts circadian rhythms, causing not only sleeping pattern disorders, but also affecting health. Many studies have correlated night work and exposure to light during nighttime with cardiovascular diseases and cancer, thus the WHO classified night work as a probable carcinogen in 19972,3,4. The molecular mechanism underlying this correlation is not fully known. Circadian rhythms are controlled by melatonin, the hormone produced during nighttime by the pineal gland in the brain. Any disturbance in sleeping pattern, or exposure to light during night affects melatonin production and the pathways controlled by this hormone. Melatonin has been involved in several processes (metabolism, immune response, reproduction, etc.); therefore it is not surprising that this hormone can affect several diseases.

Although in this study only nurses were considered and no other professions, this is the largest prospective cohort available worldwide with a high proportion of women working rotating night shift and with a very long follow-up period, thus making it a reliable collection of data without confounding occupation-related diseases.

Moral of the story: Don’t work during the night!

 

1Total and Cause-Specific Mortality of U.S. Nurses Working Rotating Night Shifts. Gu F, Han J, Laden F, Pan A, Caporaso NE, Stampfer MJ, Kawachi I, Rexrode KM, Willett WC, Hankinson SE, Speizer FE, Schernhammer ES. Am J Prev Med. 2015 Jan 6. pii: S0749-3797(14)00623-0. doi: 10.1016/j.amepre.2014.10.018

2Melatonin, sleep disturbance and cancer risk. Blask DE.Sleep Med Rev. 2009 Aug;13(4):257-64. doi: 10.1016/j.smrv.2008.07.007. Epub 2008 Dec 17. Review.

3Rotating night shifts and risk of breast cancer in women participating in the nurses’ health study.Schernhammer ES, Laden F, Speizer FE, Willett WC, Hunter DJ, Kawachi I, Colditz GA.J Natl Cancer Inst. 2001 Oct 17;93(20):1563-8.

4Carcinogenicity of shift-work, painting, and fire-fighting. Straif K, Baan R, Grosse Y, Secretan B, El Ghissassi F, Bouvard V, Altieri A, Benbrahim-Tallaa L, Cogliano V. Lancet Oncol. 2007 Dec;8(12):1065-6.

See also http://damianodemaria.scienceblog.com/80/light-exposure-at-night-induces-resistance-to-therapy-in-breast-cancer/

Keep an eye on retractions

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http://commons.wikimedia.org/wiki/Eye#mediaviewer/File:Eagle(owl)-eye_-_modified.JPG

A blog, named Retraction Watch (retractionwatch.com), has been created in 2010 to collect retractions of scientific papers. The blog is produced by Ivan Oransky—now vice president and global editorial director of MedPage Today, vice president of the Association of Health Care Journalists, and a journalist teacher—and Adam Marcus—managing editor of Gastroenterology & Endoscopy News and Anesthesiology News. They created the blog for a couple of reasons that you can read on their first post (http://retractionwatch.com/2010/08/03/why-write-a-blog-about-retractions/). The one that attracted my attention is the intention to publicize retractions because they are not well publicized. This was true when the blog was started, but the trend is changing, maybe slowly. You may find here and there articles on scientists’ misconduct, but it is true that it is not easy to find all retractions listed in one place. The blog is not only a list of retractions, but a description of each case, sometimes also citing people’s comments. My post doesn’t want to advertise Retraction Watch, but I was impressed from the number of posts they have every month—a couple every day. If you want to have a comprehensive and updated view of the retraction landscape, this is the website to visit. You may find interesting posts.

When I started writing this blog, my intention was to report highlights on the most recent scientific findings in biomedical research. Now I am here writing my third post on reporting bad science. Unfortunately, these days science is not only about innovation and research advance. In each number of each journal there is at least a retraction or an article discussing retractions or reproducibility of the results. Instead of reporting science, we write on how science is performed and how it should be performed. We should instead use the pages of a journal or of a website to report innovation.

I hope that the future will be more about highlighting good scientific results than publicizing bad science.

Happy Holidays!

 

 

Rescuing Science

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http://commons.wikimedia.org/wiki/Category:Scientists#mediaviewer/File:Scientist.svg
http://commons.wikimedia.org/wiki/Category:Scientists#mediaviewer/File:Scientist.svg

Last week, the same editorial was published on the two top scientific journals, Nature and Science1,2, describing the intent of the scientific community to address reproducibility and transparency of scientific results.

Last June, a group of editors of scientific journals, members of funding agencies, and scientific leaders have met to discuss guidelines and principles for future publication policy to guarantee reliable scientific methods. The meeting resulted in the publication of a list of guidelines that the journal should follow to report preclinical studies (http://www.nih.gov/about/reporting-preclinical-research.htm). According to the guidelines, the journals should carefully check accuracy of statistical analysis use a checklist to assure a complete report of the methodology (standards, replicates, statistics, sample size, blinding, inclusion and exclusion criteria); the journal should encourage sharing datasets and software in public domains, be responsible of refutations, and guarantee the accurate description of all sources as well as check for image manipulation.

Sometimes it is difficult to incorporate all the information on the methodology in a paper, especially because of the word count limit. To guarantee a careful and accurate description of all the methodologies, some journal should revise the word count limit that induces the author to cut or to move a huge part of the methods section to the supplementary section. To encourage accuracy, some journals are already requesting a minimum word count for the methods section. To assure a good quality of the research published on both high and low impact journals, the new guidelines should be followed by all the journals and not only by a set of top scientific journals, otherwise affecting the whole research reliability.

These guidelines should not only be adopted by the journals but also by all researchers. Honestly, I thought that the principles outlined in the guidelines—statistics, blindness, sample size, etc.—were obvious steps when outlining an experiment. Obviously, they are not, since the scientific community had to meet and had to delineate them in an official document. The increasing number of retractions—the last most clamorous case of the Obokata’s papers published on Nature and then retracted previously this year—highlights the necessity to draft such a guide. To avoid future problems on science reliability, a training should be provided not only to the new generation of scientists but also to the old generation, who is mostly responsible of the recent scientific scandals. Unfortunately, scientists are not the only responsible for what is happening in science: everyone in the scientific community is guilty from the journals to the funding agencies.

I am still shocked that the people in the scientific community had to meet and draft these guidelines. Now it is time to slow down and to promote transparency and reliability instead than sensationalism.

1Journals unite for reproducibility. Nature. 2014 Nov 6;515(7525):7. doi: 10.1038/515007a.

 2 Journals unite for reproducibility. McNutt M. Science. 2014 Nov 7;346(6210):679.

Smoking affects fertility

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http://commons.wikimedia.org/wiki/Cigarette#mediaviewer/File:Papierosa_1_ubt_0069.jpeg
http://commons.wikimedia.org/wiki/Cigarette#mediaviewer/File:Papierosa_1_ubt_0069.jpeg

A recent study shows that smoking during pregnancy and breastfeeding may impair sons’ fertility.

We all know that smoking affects our health causing primary respiratory and cardiovascular problems. In pregnant women cigarette smoke can affect not only mom’s health but also child’s health, causing premature birth, growth retardation, miscarriages, reduced birth weight, and sudden infant death syndrome 1,2,3,4.

The team led by Professor Mc Laughlin at the University of Newcastle (New South Wales, Australia) published a study in Human Reproduction on the effect of maternal smoking using a mouse model 5. They exposed 27 female animals to cigarette smoking before, during, and after pregnancy and analyzed the the pups and the adult male mice. Smoking affected the viability of germ cells, the diameter of seminiferous tubules, and the morphology of neonatal testes in the pups. In the adult mice, germ cells showed DNA damage and Sertoli cell (cells that promote sperm cell development) showed aberrant function; these phenomena were accompanied by alteration in the expression of genes involved in several pathways, including spermatogenesis, oxidative stress, and Sertoli cell function. Furthermore mice from “smoking” mothers had fewer sperm with affected motility and fertilization ability (binding to the zona pellucida of the egg). This work is a comprehensive demonstration in a mouse model that maternal cigarette smoke compromises the fertility of the male offspring. Previous studies suggested the same effects but they were not conclusive.

When a woman gets pregnant, she receives many warnings on what she may or may not do. Some of these warnings are based off common sense, previous observational and epidemiological  studies or surveys, and the woman doesn’t really get an explanation of the precise consequences of her acts if she doesn’t follow the instructions—this is not always the case—but all she gets is a warning. In contrast, the consequences of cigarette smoke are known and are not short-term (miscarriage, reduced birth weight, etc.) but long-term consequences. The study described above is an accurate demonstration This study should really be a deterrent for pregnant women who are still smoking, that are around 13–20% in the United States(the reports are controversial) and 4–20% in Europe (depending on the country) 6. Further studies in the future may highlight other long-term damages and may focus on the damages of not only maternal smoke but also secondhand smoke.

 

1Perinatal complications associated with maternal tobacco use.Andres RL, Day MC. Semin Neonatol. 2000 Aug;5(3):231-41. Review.

2Revisiting the effect of maternal smoking during pregnancy on offspring birthweight: a quasi-experimental sibling analysis in Sweden. Juárez SP, Merlo J. PLoS One. 2013 Apr 17;8(4):e61734.

3Environmental tobacco smoke and risk of spontaneous abortion. George L, Granath F, Johansson AL, Annerén G, Cnattingius S. Epidemiology. 2006 Sep;17(5):500-5.

4Prenatal smoking among adolescents and risk of fetal demise before and during labor.Aliyu MH, Salihu HM, Alio AP, Wilson RE, Chakrabarty S, Clayton HB.J Pediatr Adolesc Gynecol. 2010 Jun;23(3):129-35Epidemiology. 2006 Sep;17(5):500-5.

5Damaging legacy: maternal cigarette smoking has long-term consequences for male offspring fertility.Sobinoff AP, Sutherland JM, Beckett EL, Stanger SJ, Johnson R, Jarnicki AG, McCluskey A, John JC, Hansbro PM, McLaughlin EA.Hum Reprod. 2014 Sep 30. pii: deu235.

6Characteristics of women who continue smoking during pregnancy: a cross-sectional study of pregnant women and new mothers in 15 European countries.Smedberg J, Lupattelli A, Mårdby AC, Nordeng H.BMC Pregnancy Childbirth 2014 Jun 25;14:213.

The increase in bilateral mastectomy for treating breast cancer might not be justified

Cancer, Uncategorized, , , , , , , , , , , , , , ,
September 2014
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Bilateral mastectomy has become a common procedure to treat and to prevent breast cancer. The rate of bilateral mastectomy is increasing in the United States, in the United Kingdom, and also in Singapore among women with high grade and high risk of breast cancer1–3.

An observational study published this month on The Journal of American Medical Association4 compared the use and the mortality rate of bilateral mastectomy, unilateral mastectomy, and breast conserving surgery in 189,734 women diagnosed with stage 0–III breast cancer in California between 1998 and 2011. The team from the Cancer Prevention Institute of California and Stanford University found that bilateral mastectomy had an annual increase of 14.3% (from 2.0 % in 1998 to 12.3% in 2011), and it was more common among younger, white non-Hispanic women, with bigger and  higher grade tumors, higher education, and a private insurance. On the other hand, unilateral mastectomy was more diffuse in women older than 64 years, of Asian, Hispanic, and American Indian ethnicity, with large tumor size, high grade, and no private insurance. Compared with bilateral mastectomy, unilateral mastectomy was associated with 30% increased all-cause mortality; instead, there was no difference in mortality rate between bilateral mastectomy and breast-conserving surgery. Comparing all three procedures in early stage breast cancer patients, there was no benefit on survival associated with bilateral mastectomy over breast-conserving surgery; higher mortality was only associated with unilateral mastectomy.

This is the first study presenting a comparison among the three procedures. Other studies were published in the past comparing only two procedures at a time, but never all three together. The authors of this study state that maybe the use of bilateral mastectomy could be reduced, because there are no elements to support its benefits over other, less invasive treatments, such as breast-conserving surgery. This study was performed to identify whether the rise in bilateral mastectomies could be somehow justified, or whether the procedure could be substituted with a less expensive one. Bilateral mastectomy is an expensive procedure, and in a private healthcare system clinicians need to present supportive data to justify the selection of a procedure over another one.

If there are not enough data supporting this rise, the increase might have been caused by excessive precaution or fear. Whether it was fear or something else, patients have the right to know the real risks and benefits of each treatment based on actual data, because they are going to make the last decision, not the clinicians or the health policy makers.

 

  1. Trends in the use of bilateral mastectomy in England from 2002 to 2011: retrospective analysis of hospital episode statistics. Neuburger J, Macneill F, Jeevan R, van der Meulen JH, Cromwell DA. BMJ Open. 2013 Aug 1;3(8). pii: e003179. doi: 10.1136/bmjopen-2013-003179.
  2. Contralateral prophylactic mastectomy in an Asian population: a single institution review. Sim Y, Tan VK, Ho GH, Wong CY, Madhukumar P, Tan BK, Yong WS, Ng YY, Ong KW. Breast. 2014 Feb;23(1):56-62. doi: 10.1016/j.breast.2013.10.008. Epub 2013 Nov 23.
  3. Contralateral prophylactic mastectomy in women with breast cancer: trends, predictors, and areas for future research. Tracy MS, Rosenberg SM, Dominici L, Partridge AH. Breast Cancer Res Treat. 2013 Aug;140(3):447-52. doi: 10.1007/s10549-013-2643-6. Epub 2013 Jul 28. Review.
  4. Use of and mortality after bilateral mastectomy compared with other surgical treatments for breast cancer in California, 1998-2011. Kurian AW, Lichtensztajn DY, Keegan TH, Nelson DO, Clarke CA, SL. JAMA. 2014 Sep 3, 312(9):902-14. doi: 10.1001/jama.2014.10707.

Light exposure at night induces resistance to therapy in breast cancer

Cancer, Uncategorized, , , , , , , , , , ,

The disruption of melatonin production during the night through light exposure reduces tumor latency and drives resistance to tamoxifen in a model of estrogen receptor positive alpha (ERa+) breast cancer.

http://commons.wikimedia.org/wiki/File:Luz_en_Movimiento.jpg
http://commons.wikimedia.org/wiki/File:Luz_en_Movimiento.jpg

Melatonin is an hormone mainly produced by the pineal gland in the brain and primarily regulates sleeping habits. Its production is light sensitive; therefore, it is produced only in complete darkness, and sleeping in synthetic lights can interfere with its production. Melatonin has also been involved in the regulation of reproduction, timing of ovulation, aging, immune function, and cancer1. In 2001 a study linked night shift rotation with a moderate increase in breast cancer risk2. Studies have shown that melatonin antagonizes the metabolism of linoleic acid, the most prevalent polyunsaturated fatty acid present in the Western diet that upregulates the expression of genes controlling ER expression, cell cycle, and growth.

A group led by Dr. Steven Hill at the Tulane University (Louisiana)3 investigated how disruption of melatonin production influences not only growth but also response to tamoxifen of ERa+ tumors implanted into rats (xenograft). They did two sets of experiments. In the first set they compared animals kept under normal conditions with animals kept under dim light exposure at night (dLEN); in the second set, they compared dLEN mice with dLEN mice supplemented with nighttime melatonin. They found that tumors implanted in the dLEN rats had a shorter latency and a 2.6-fold increase in the growth rate compared with the controls. These tumors were also totally resistant to tamoxifen, whereas the control animals responded to the therapy. The dLED tumors showed high levels of proliferative markers, increased metabolism, and low apoptosis. Strikingly, when the nighttime melatonin was supplemented in the dLEN mice, tumor growth latency was reduced and resistance to tamoxifen was reestablished, with reduction of metabolism, proliferation markers, and increase in apoptosis.

Many studies have shown that melatonin can affect tumor growth in different cancer models, but this is the first study involving melatonin in resistance to therapy. The resistance to tamoxifen is a big problem in the treatment of ER+ breast cancer; about 30% of patients show resistance, and the causes are not totally understood. Strikingly, this research indicates that melatonin disruption affects resistance to therapy, through a molecular mechanism that may involve ER phosphorylation. Several lifestyle habits can influence cancer risk, cancer development, and resistance to therapy—e.g. diet, smoking, exercise. In addition, this report indicates that even sleeping in the darkness might be more beneficial against cancer.

Sleep in the dark!

1Melatonin, sleep disturbance and cancer risk. Blask DE.Sleep Med Rev. 2009 Aug;13(4):257-64. doi: 10.1016/j.smrv.2008.07.007. Epub 2008 Dec 17. Review.

2Rotating night shifts and risk of breast cancer in women participating in the nurses’ health study.Schernhammer ES, Laden F, Speizer FE, Willett WC, Hunter DJ, Kawachi I, Colditz GA.J Natl Cancer Inst. 2001 Oct 17;93(20):1563-8.

3Circadian and melatonin disruption by exposure to light at night drives intrinsic resistance to tamoxifen therapy in breast cancer. Dauchy RT, Xiang S, Mao L, Brimer S, Wren MA, Yuan L, Anbalagan M, Hauch A, Frasch T, Rowan BG, Blask DE, Hill SM. Cancer Res. 2014 Aug 1;74(15):4099-110. doi: 10.1158/0008-5472.CAN-13-3156.

Smoking Increases the Risk of Estrogen Receptor Positive Breast Cancer

Cancer, , , , , , , , , , , , ,

A study from the Fred Hutchinson Cancer Center shows that smoking among young women may increase the risk of developing estrogen receptor (ER)-positive breast cancer, but not triple negative breast cancer (TNBC).

The group led by Dr. Christopher Li conducted a population-based study among women from 22 to 44 years old diagnosed with breast cancer between January 2004 and June 2010 in the July 2014. The patients were 938 women in the control group, 778 in the ER-positive group, and 182 in the TNBC group. The researchers interviewed the patients and obtained detailed information about different aspects of their lifestyle—reproductive history, demographics, physical activity, alcohol drinking, medical history—and smoking habits—regency, number of cigarettes smoked per day, ages when smoked. The patients were divided in never smokers and ever smokers (current or former). The ever-smoker group was further categorized based on the number of pack of cigarettes smoked per year.

Smokers had increased risk of developing breast cancer overall (30%), without any significative change when the total number of years of smoking or the age women first started were considered. Although the small number of TNBC cases, the risk was associated with ER-positive breast cancer and not with TNBC. However, among current smokers, women who had been smoking for more than fifteen years had 50% increased risk of developing ER-positive breast cancer compared with women who had been smoking for fewer years. Of note is that, in women who had not been smoking for more than ten years the risk of developing ER-positive breast cancer decreased dramatically.

Various studies have correlated smoking to the risk of breast cancer, but this is one of the few studies linking smoking to ER-positive breast cancers in premenopausal women. Metabolites of tobacco, found in the breast fluid and breast tissue of current smokers, have been shown to have an estrogenic effect in in vitro studies, thus explaining the increased risk of ER-positive breast cancer in young women found in this research.

Smoking has several adverse effects and has been associated to different cancers. This is not only a study that supports previous reports linking smoking to breast cancer, but this study links smoking to a specific subtype of breast cancer (ER-positive) in young women.

 

Masaaki Kawai, Kathleen E. Malone, Mei-Tzu C. Tang, Christopher I. Li. Height, body mass index (BMI), BMI change, and the risk of estrogen receptor-positive, HER2-positive, and triple-negative breast cancer among women ages 20 to 44 years. Cancer, 2014

Resveratrol: just a fair-weather friend?

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JUne 2014Since its first mention in a Japansee article in 19391, over the years many beneficial effects have been attributed to the natural compound, resveratrol—anticancer, anti-inflammatory, anti-aging—which is even used in skincare cosmetic. Although a large number of studies suggest its health benefits, recently some reports have been questioning these potentials.

Resveratrol is a natural phenol and antioxidant compound found in various colored vegetables and fruit, especially in the skin of red grape. Its name comes probably from the combination if the term resorcinol (chemical compund) and Veratrum (the plant where resveratrol was first isolated). It is thought to influence inflammation, aging, neuronal degeneration, and metabolism through the serine deacetylase, sirtuin-1 (SIRT-1), the cAMP pathway, or AMP-activated protein kinase2. However the exact mechanism of action is not known. A new role for resveratrol as a partial agonist of the estrogen receptor alpha (ERalpha) has been recently described3. According to this study, resveratrol binds to the ERalpha that is recruited to the interleukin-6 (IL-6) promoter and alters the binding of coregulators, such as SIRT-1, and the activity of transcriptional activators, leading to reduced inflammation. Resveratrol was identified in a previous screening for ERalpha agonists that inhibit IL-6 transciption4; thus resveratrol may have a selective role on the ERalpha pathway, inhibiting inflammation without promoting cell proliferation.

The amount of resveratrol found in foods varies greatly. It is mainly found in the skin of red grapes, red wine, peanuts, berries, and in lower amount in cocoa powder and dark chocolate5. However, the amount of resveratrol in foods is thought to be not enough to justify and mediate its effects. To understand whether resveratrol levels present in the diet can influence inflammation, cancer, cardiovascular disease, and mortality in humans, a prospective cohort study has been conducted in the Chianti region in Italy (InCHIANTI—“Aging in the Chianti Region”), in a population-based sample of 783 community-dwelling men and women 65 years or older who consume a diet rich in resveratrol6. The group of researchers, who have been studying aging in this population for fifteen years, measured the concentration of resveratrol metabolites present in the urine and found that it was not associated with inflammatory markers, cardiovascular disease, or cancer. This study shows that the amount of resveratrol present in the diet is not responsible for beneficial health effects. It is possible that the health benefits that come from the diet consumed in that region are not due to resveratrol, but to other substances present in the food. On the other hand resveratrol is rapidly metabolized in sulfate and glucuronide conjugates and it has long been believed that this could limit its bioavailability. However, a study from the University of Leicester shows that resveratrol is not rendered ineffective after it is metabolized by the body: it can be generated by resveratrol sulfate and be even more effective than the un-metabolized compound7.

Supplements that contain high quantity of resveratrol are available in the market. However, people should be careful with them, because we still don’t know the repercussions of high amount of resveratrol on human health. A very recent study published on the June issue of The FASEB Journal shows that the use of resveratrol during pregnancy can have beneficial effects on the blood flow in the placenta and on the liver function (decreased placental inflammation and liver triglyceride deposition), but can increase fetal pancreatic mass and exocrine proliferation, leading to unknown consequences on the development of the fetus8.

To date, there are not definitive studies on the benefits of resveratrol. The literature is full of controversial or incomplete reports. Therefore, be careful in listening to advertisements that sell resveratrol as a health serum.

1Takaoka M, Resveratrol, a new phenolic compound, from Veratrum grandiflorum. M Takaoka, Journal of the Chemical Society of Japan, 193 (2012):1090-1100.

2Tennen RI, Michishita-Kioi E, Chua KF. “Finding a target for resveratrol”. Cell 2012,148 (3): 387–9.

3Nwachukwu J,Srinivasan S, Bruno NE, Parent AA, Hughes TS, Pollock JA, Gjyshi O, Cavett V, Nowak J, Garcia-Ordonez RD, Houtman R, Griffin PR, Kojetin DJ, Katzenellenbogen JA, Conkright MD, Nettles KW. Resveratrol modulates the inflammatory response via an estrogen receptor-signal integration network. eLife, (2014).

4Srinivasan S., Nwachukwu J.C., Parent AA, Cavett V, Nowak J, Hughes TS, Kojetin DJ, Katzenellenbogen JA, and Nettles KW. Ligand-binding dynamics rewire cellular signaling via estrogen receptor-alpha. Nat Chem Biol (2013) 9, 326-332.

5Hurst WJ, Glinski JA, Miller KB, Apgar J, Davey MH, Stuart DA. “Survey of the trans-resveratrol and trans-piceid content of cocoa-containing and chocolate products”. Journal of Agricultural and Food Chemistry (2008) 56 (18): 8374–8.

6Semba RD, Luigi Ferrucci L, Bartali B, Urpí-Sarda M, Zamora-Ros R, Sun K, Cherubini A, Bandinelli S, Andres-Lacueva C. Resveratrol Levels and All-Cause Mortality in Older Community-Dwelling Adults. JAMA Internal Medicine, (2014) May 12.

7Patel KR, Andreadi C, Britton RG, Horner-Glister E, Karmokar A, Sale S, Brown VA, Brenner DE, Singh R, Steward WP, Gescher AJ and Brown K. Sulfate Metabolites Provide an Intracellular Pool for Resveratrol Generation and Induce Autophagy with Senescence. Science Translational Medicine, (2013) Oct 2;5(205).

8Roberts VHJ, Pound LD, Thorn SR, Gillingham MB, Thornburg KL, Friedman JE, Frias AE, and Grove KL. Beneficial and cautionary outcomes of resveratrol supplementation in pregnant nonhuman primates. FASEB J. (2014) June 28:2466-2477.

Fruit and vegetable consumption: a longer life

Nutrition, , , , , , , , ,

We all know that fruit and vegetables are healthy, but did you know that eating vegetables is more effective than eating fruit in reducing mortality?

May 2014A recent study published on Journal of Epidemiology & Community Health1 reports the association of fruit and vegetable consumption with all-cause, cancer, and cardiovascular mortality in 65,226 English people included in the Health Survey for England from 2001 to 2013. Oyebode et al. found that people who consumed more vegetable and fruit were generally older, non-smokers, women, educated, and physically more active than the rest of the population. Fruit and vegetable consumption was inversely correlated with all-cause, cancer, and cardiovascular disease (CVD) mortality, with a threshold of seven or more portions a day for all-cause and CVD mortality, five and less for cancer, and seven or more for CVD. When vegetable and fruit consumption were considered separately, vegetable were more beneficial than fruit on cancer and CVD survival. Specifically, fresh vegetables, salad, fresh fruit, and dried fruit were inversely correlated with mortality; instead canned/ frozen fruit consumption was directly correlated with increased mortality. This could be because some fresh vegetables and all fresh fruit are consumed raw, preserving all their nutrition facts; instead, canned fruit have a high content of sugar that can cause health problems if consumed in excess. As the authors discuss, usually frozen fruit is considered to be equivalent to raw fruit; therefore, the ambiguity of this study might be due to the way the survey was conducted with questions that didn’t distinguish between canned and frozen fruit.

”In 1990, the WHO issued recommendations for a minimum daily intake of 400 g of fruit and vegetables, based on evidence that higher levels were protective against [. . .] CVD and some cancers,”1 leading to various campaigns in Europe, the United States, and Australia for inducing people to consume more vegetables and fruits, not based on any valuable evidence. The present study provides this evidence. Although the study might be missing some information because of the self-report survey, this is the first analysis correlating fruit and vegetable consumption with mortality on a nationwide population.

This report shows that eating seven or more portions of vegetables a day decreases mortality. Unfortunately, vegetables and fruit are more expensive than the majority of unhealthy chips, sauces, or cookies that are sold on the aisles of the grocery stores, leading to a less consumption of vegetable and fruit in low-income houses2. Nutritional campaigns might not be effective in promoting a healthier diet, if the prices of healthy food remain high.

A more incisive policy should be carried out: it should be based on price cut and not only limited to surveys and statistics.

1. Oyebode O., Gordon-Dseagu V., Walker A., Mindell, JS. Fruit and vegetable consumption and all-cause, cancer and CVD mortality: analysis of Health Survey for England data. J Epidemiol Community Health, 31 March 2014

2. Thompson J. ‘Diet and healthy eating’. Chapter 5 In: Craig R, Shelton N, eds. Health Survey for England 2007. Knowledge, attitudes and behaviours. London: NHS Information Centre, 2008;107–48

 

 

New information on mammalian expression patterns

Biology, , , , , , , , , , , , , ,

April 2014An extended atlas of transcription initiation sites (TSSs) has been described by the functional annotation of the mammalian genome 5 (FANTOM5) consortium in a recent  article on Nature1. It is a comprehensive overview of expression profiles in mice and humans complementing and extending the information already present in other datasets, such as ENCODE2.

The large international FANTOM consortium led by RIKEN PMI has performed cap analysis of gene expression (CAGE)3 —a technique that sequences the 5’ of the RNA messenger —on a large cohort of mouse and human samples: 573 human primary cells, 128 mouse primary cells, 250 cancer cells lines, 152 human post-mortem tissues, and 271 mouse tissue samples.  They found more than three million peaks in humans and more than two million in mice, including sequences in internal exons. To reduce the background, they applied tag evidence threshold. The TSSs found were confirmed to belong to known promoters, based on known sequence analyses— expressed sequence tags, histone H3 lysine 4 trimethylation marks and DNase hypersensitive sites. The peaks were classified as non-ubiquitous/cell-type specific (cell-adhesion and signal transduction), ubiquitous-uniform/housekeeping (ribonucleoprotein complex and RNA processing), and ubiquitous non-uniform (cell cycle genes). Most of the peaks belong to cell-type specific genes, highlighting the abundance of tissue specific gene regulation; also, the housekeeping genes are the most conserved between human and mouse, confirming the importance of their function. Although some level of conservation, only 43% of human TSSs could be aligned to the mouse genome and only 39% of mouse TSSs could be aligned to the human genome, thus indicating a remodeling of transcription initiation during evolution.

This is research offers more than a collection of information. For instance, it also analyzed TSSs in cancer cells opposed to primary cells, finding that transcription factors are more expressed in the transformed than in the primary cells, because of chromosomal rearrangements and mutations; this highlights an underestimated problem of using cancer cells for transcription studies.

The FANTOM5 atlas provides an extensive  collection and material on TSSs, which is available online (http://fantom.gsc.riken.jp/5) together with specialized tools (ZENBU3 or SSTAR)3 to analyze the data and integrate the information from the ENCODE and the FANTOM consortium datasets, thus allowing scientists to have the access to a  huge amount of information on mammalian gene regulation.

 

1FANTOM Consortium and the RIKEN PMI and CLST (DGT). (2014) A promoter-level mammalian expression atlas.Nature 507(7493):462-70. doi: 10.1038/nature13182.

2ENCODE Project Consortium, Birney E, Stamatoyannopoulos JA, Dutta A, Guigó R, Gingeras TR, Margulies EH, Weng Z, Snyder M, Dermitzakis ET, et al. (2007).“Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project”. Nature 447 (7146): 799–816. .doi:10.1038/nature05874

3 Shiraki T, Kondo S, Katayama S, Waki K, Kasukawa T, Kawaji H, Kodzius R, Watahiki A, Nakamura M, Arakawa T, Fukuda S, Sasaki D, Podhajska A, Harbers M, Kawai J, Carninci P, Hayashizaki Y. (2003) Cap analysis gene expression for high-throughput analysis of transcriptional starting point and identification of promoter usage”. Proc Natl Acad Sci U S A. 100 (26): 15776–81.. doi:10.1073/pnas.2136655100.

4Jessica Severin, Marina Lizio, Jayson Harshbarger, Hideya Kawaji, Carsten O Daub, Yoshihide Hayashizaki, the FANTOM consortium, Nicolas Bertin, and Alistair RR Forrest. (2014) “Interactive visualization and analysis of large-scale NGS data-sets using ZENBU”. Nature Biotechnology,