Author Interviews, Genetic Research, Science / 04.05.2016
Why Has the DNA Code Been Frozen At 20 Amino Acids for 3 Billion Years?
MedicalResearch.com Interview with:
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Dr Lluís Ribas[/caption]
Lluís Ribas de Pouplana, Ph.D
IRB Barcelona
Barcelona 08028
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Ever since the discovery of the genetic code it became obvious that the system had not grown to its full theoretical potential of making proteins with 63 different amino acids.
Francis Crick called the code 'a frozen accident',
but it was unclear what had actually froze it.
In this article we offer an explanation to that, and we validate it experimentally.
What we find is that the central pieces of the genetic code, the transfer RNAs,
are unable to incorporate enough specific elements for the system to be able to
use 63 of them without confusion. Since you need a new tRNA for each new
amino acid, once the tRNA identification limit is reached you also reach the
maximum number of usable amino acids. This limit happened to be reached
at 20, and that's where it has stayed for 3 billion years.
Dr Lluís Ribas[/caption]
Lluís Ribas de Pouplana, Ph.D
IRB Barcelona
Barcelona 08028
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Ever since the discovery of the genetic code it became obvious that the system had not grown to its full theoretical potential of making proteins with 63 different amino acids.
Francis Crick called the code 'a frozen accident',
but it was unclear what had actually froze it.
In this article we offer an explanation to that, and we validate it experimentally.
What we find is that the central pieces of the genetic code, the transfer RNAs,
are unable to incorporate enough specific elements for the system to be able to
use 63 of them without confusion. Since you need a new tRNA for each new
amino acid, once the tRNA identification limit is reached you also reach the
maximum number of usable amino acids. This limit happened to be reached
at 20, and that's where it has stayed for 3 billion years.
Dr. Lihi Eder[/caption]
Lihi Eder, MD, PhD
Assistant Professor of Medicine
University of Toronto
Scientist, Women’s College Research Institute,Room 6326
Women’s College Hospital
Toronto, ON, Canada
MedicalResearch.com: What is the background for this study?
Dr. Eder: Psoriasis is a chronic immune-mediated skin disease affecting 2-3% of the general population. Psoriatic arthritis (PsA) affects 15-30% of patients with psoriasis. Until recently, only few studies assessed the risk of developing cardiovascular events in patients with PsA and while most studies found a higher cardiovascular risk in these patients, others reported cardiovascular rates that were similar to the general population.
Dr. Errol Singh[/caption]
Errol Singh, M.D.
Urologist and CEO of PercuVision
MedicalResearch.com: What is the background for this study?
Dr. Singh: We set out to better understand the American public’s fears around Foley catheters and hopefully bring attention to the fact that hospitalizations due to infections from urinary catheters are on the rise. Interestingly enough, 20 percent of hospital patients undergo a urinary catheterization, which is the second most common procedure following intravenous therapy. The procedure, however, often leads to complications including infections mostly caused by trauma.
MedicalResearch.com: What are the main findings?
Dr. Singh: The main findings of the 2016 Urinary Catheter Fear Survey revealed that three out of five men (58 percent) are fearful of urinary catheterizations, while one out of every four men is very fearful of the procedure. Younger men also seem to be more fearful than their older counterparts. More than two-thirds (68 percent) of men ages 18-34 surveyed are fearful of urinary catheterizations, compared to 43 percent of males 65 and over.
Clearly, females are less fearful, with 46 percent of women saying they are not fearful of urinary catheterizations, compared to 37 percent of men. It’s also important to note that half of all women surveyed say they fear the procedure, and 25 percent reporting they are very fearful. You can find more of the 2016 Urinary Catheter Fear Survey results on our website at
Dr. Orit Markowitz[/caption]
Orit Markowitz, MD, FAAD
Director of Pigmented Lesions and Skin Cancer
Assistant Professor of Dermatology
Mount Sinai Medical Center, NY, NY
Director of Pigmented lesions clinic
Brooklyn VA, Brooklyn, NY
Adjunct Professor, Dermatology
SUNY Downstate Medical Center, Brooklyn, NY
Chief of Dermatology
Queens General Hospital, Jamaica, NY
MedicalResearch.com: How common is skin cancer? Is the incidence rising in US adults? Who is most at risk?
Dr. Markowitz: The annual incidence of skin cancer is more than breast, colon, lung, and prostate cancer combined. Of the 7 most common skin cancers in the US melanoma is the only one whose incidence is increasing. The highest risk group for skin cancer are fair skin, adults with a history of sun exposure.
Dr. Jennifer Graves[/caption]
Jennifer Graves, MD, PhD, MAS
Adult and Pediatric Multiple Sclerosis Centers
UCSF
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Graves: Cessation of medications with effects on immune trafficking may be more likely to cause rebound inflammatory activity in autoimmune diseases such as multiple sclerosis. We observed 5 strikingly severe relapses consistent with rebound events following cessation of fingolimod treatment and identified several similar cases in the literature. At our center the rebound events occurred with an approximate 10% frequency.
MedicalResearch.com: What should clinicians and patients take away from your report?
Dr. Graves: Fingolimod cessation may be complicated by rebound phenomena in some patients, similar to what has been observed with natalizumab. Both of these medications have effects on immune cell trafficking, likely explaining the association with rebound events. Careful consideration must be taken in stopping these medications.
Dr. Saira Saeed Mirza[/caption]
Saira Saeed Mirza, MD, PhD
Department of Epidemiology
Erasmus MC, Rotterdam
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Mirza: Depressive symptoms appearing in late-life have been extensively studied for their relationship with dementia. They not only very frequently occur in demented patients, but also predict dementia. In this context, depressive symptoms have largely been assessed at a single time point only. However, depression is a disorder which remits and relapses, and symptoms do not remain same over the years. Given this pattern of disease progression, it is more important to study the course of depression over time in relation to long-term health outcomes such as dementia, rather than assessing it at a single time-point, which will neglect the course of depression. This is important as people follow different courses of depression, and different courses of depression might carry different risks of dementia.
When we studied the course of depressive symptoms over 11 years in community dwelling older adults in Rotterdam, and the subsequent risks of dementia, we observed that only those who had increasing or worsening depressive symptoms were at a higher risk of dementia. In this group of people, about one in five persons developed dementia. Interestingly, people suffering from high depressive symptoms at a single time point were not at a higher dementia risk than those without depressive symptoms.
Dr. Hope Weiler[/caption]
Hope Weiler, RD (CDO), PhD
Associate Professor
Canada Research Chair tier I, Nutrition and Health Across the Lifespan,
Director, Mary Emily Clinical Nutrition Research Unit
School of Dietetics and Human Nutrition
McGill University Macdonald Campus
Ste Anne de Bellevue, QC
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Weiler: Vitamin D is a fat soluble with important functions in growth during infancy and childhood, especially for the skeleton. It is for this reason that many policy recommendations for infants stipulate that newborn infants receive a supplemental form of vitamin D. In Canada, it is recommended by Health Canada (
Dr. Zachary Keff[/caption]
Zachary Y. Kerr, PhD, MPH
Sports Injury Epidemiologist
Director, NCAA Injury Surveillance Program
Datalys Center for Sports Injury Research and Prevention
Indianapolis, IN 46202
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Kerr: A 2013 Institutes of Medicine report called for more research on concussion in athletes aged 5-21 years. Although there is much research on the incidence of concussion across this age span, there is less related to outcomes such as symptoms and return to play time, let along comparisons by age.
In examining sport-related concussions that occurred in youth, high school, and college football, we found differences in the symptomatology and return to play time of concussed players. For example, the odds of return to play time being under 24 hours was higher in youth than in college. Also, over 40% of all concussions were returned to play in 2 weeks or more.
Dr. Corby Martin[/caption]
Dr. Corby K. Martin PhD
Department/Laboratory:
Ingestive Behavior Laboratory
Director for Behavioral Sciences and Epidemiology
Pennington Biomedical Research Lab
Baton Rouge, LA
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Martin: We know that calorie restriction extends the lifespan of many species and in humans calorie restriction or dieting might extend our healthspan, which is the length of time that we are free of disease. It is possible that more healthy weight or mildly overweight people might calorie restrict to improve their health, and one concern is the possible negative effects of calorie restriction on the quality of life of these individuals.
This study tested if 2 years of calorie restriction affected a number of quality of life measures compared to a group that did not calorie restrict and ate their usual diet and did not lose weight. People who enrolled in the study were normal weight to mildly overweight. The study found that calorie restriction improved mood, reduced tension and improved general health and sexual drive and relationship (a measure of sexual function) over two years. Further, the more weight that people lost, the greater their improvement in quality of life.
Dr. Asal Mohamadi Johnson[/caption]
Asal Mohamadi Johnson, PhD, MPH
Assistant Professor of Epidemiology, Integrative Health Science
Stetson University
DeLand, FL 32723
MedicalResearch.com: What is the background for this study?
Dr. Johnson: Public health research is primarily focused on neighborhood poverty and racial disparities by illustrating differences between white and black individuals or communities. For example, it has been established that African Americans have higher cancer mortality rates and are less likely to receive appropriate treatment that whites. What we wanted to know in this study was the impact of living in segregated areas apart from other area level characteristics such as poverty or education. Instead of solely looking at health disparities between whites and black patients, our study focused on differences in survival among black patients with early stage Non-Small Cell Lung Cancer (NSCLC) living in different levels of neighborhood segregation.
Dr. Heli Malm[/caption]
Heli Malm, MD, PhD
Specialist in Obstetrics and Gynecology
Teratology Information Service
Helsinki University and Helsinki University Hospital
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Malm: Animal studies have demonstrated that exposure to SSRIs during early brain development can result in depression-like behavior in adolescence. Today 6% of pregnant women in the US and 4% in Finland are on selective serotonin reuptake inhibitors (SSRIs) at some stage of pregnancy. SSRIs pass the placenta but no prior studies have followed children beyond childhood to monitor the development of depressive disorders, which typically emerge after puberty onset. Results on autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorders (ADHD) have been conflicting.
The study material is based on national register data from Finland. We investigated offspring psychiatric diagnoses, including depression, anxiety, ASD, and ADHD, of nearly 16,000 mothers who had used SSRIs during pregnancy between 1996 and 2010. Children in this cohort ranged in age from 0 to 15 years old. Because maternal psychiatric illness can affect offspring neurodevelopment in the absence of SSRIs, primary comparisons were made between offspring of the SSRI group and offspring of mothers with a psychiatric disorder diagnosis but no antidepressant use.
Children exposed to SSRIs during gestation were diagnosed with depression at an increasing rate after age 12, reaching a cumulative incidence of 8.2% by age 15, compared to 1.9% in the group of children exposed to maternal psychiatric illness but no antidepressants. Rates of anxiety, autism spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD) diagnoses did not differ significantly between the two groups.
Dr. Thijs Eijsvogels[/caption]
Thijs M.H. Eijsvogels, PhD
Department of Physiology
Radboud University Medical Center
Nijmegen, The Netherlands
MedicalResearch.com: What is the background for this study?
Dr. Eijsvogels: Regular exercise training is known to reduce the risk for future morbidity and mortality in the general and athletic population. For this purpose, national guidelines recommend to exercise 150 min/week at a moderate intensity or 75 min/week at a high intensity. Recent studies explored the dose-response relationship between weekly exercise volume and cardiovascular health and reported a potential U-shaped association, suggesting that high exercise volumes may attenuate the beneficial health effects.
The aim of the present study was to determine the relationship between lifelong exercise dose and the prevalence of cardiovascular morbidity in a physically active population. Therefore, we collected data in 21,266 participants of the Nijmegen Exercise Study.
Dr. Paul Nghiem[/caption]
Paul Nghiem, MD, PhD
Professor & Head, University of Washington Dermatology
George F. Odland Endowed Chair
Affiliate Investigator, Fred Hutchinson Cancer Research Center
Professor, Adjunct, of Pathology and Oral Health Sciences
Clinical Director, Skin Oncology, Seattle Cancer Care Alliance
UW Medical Center at Lake Union
Seattle WA 98109
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Nghiem: Merkel cell carcinoma (MCC) is about 30 times less common than malignant melanoma, but about 3 times more likely to kill a patient than a melanoma. There is no FDA-approved therapy for this cancer & chemotherapy typically only provides about 90 days prior to the cancer progressing. Because of the strong links between MCC and the immune system, including the fact that most MCCs are caused by a virus, there was interest in trying to use immune checkpoint therapy to treat advanced Merkel cell carcinoma. The response to immune stimulation with anti-PD1 therapy was about as frequent as to chemotherapy (56% of patients responded) but importantly, among the responders, 86% remained in ongoing responses at a median of 7.6 months. While still early, this appears to be strikingly more durable than responses to chemotherapy.
Dr. Stephen Freedland[/caption]
Stephen J. Freedland, MD
Associate Director, Faculty Development Samuel Oschin Comprehensive Cancer Institute
Co-Director, Cancer Genetics and Prevention Program
Director, Center for Integrated Research in Cancer and Lifestyle
Professor, Surgery
Warschaw Robertson Law Families Chair in Prostate Cancer
Cedars-Sinai, Los Angeles
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Freedland: PSA is a marker of prostate pathology. While often used to screen for prostate cancer, it is not prostate specific and can be elevated due to inflammation or enlarged prostate or other reasons. Whether it predicts the development of urinary symptoms is not clear. Among men with minimal to no urinary symptoms, we found that the higher the PSA, the greater the risk of future development of urinary symptoms.
MedicalResearch.com: What should clinicians and patients take away from your report?
Dr. Freedland: The readers should know that if a man has an elevated PSA and a negative prostate biopsy, the higher the PSA, the greater the risk of future urinary symptoms. These are men who may need closer follow-up.
Dr. Jacqueline French[/caption]
Jacqueline French, MD
Professor, Department of Neurology
Director Translational Research& Clinical Trials Epilepsy
NYU Langone Medical Center
MedicalResearch.com: What is the background for this study?
Dr. French: Tuberous sclerosis complex (TSC) is a disease associated with abnormal cell growth, caused by dysfunction of the TSC1 or TSC2 genes and dysruption of the MTOR pathway, which leads to cortical malformations, neuronal hyperexcitability, and seizures. Seizures in patients with TSC often start within the first year of life, and tend not to respond to traditional treatments. Everolimus is a marketed drug that has been used to treat other manifestations of TSC (including giant cell tumors of the brain, renal angiomyolipomas, and angiofibromas of the skin).
This study was a placebo-controlled add-on study of everolimus for the treatment of refractory seizures in children and adults with epilepsy.Following an 8-week baseline phase, patients aged 2-65 years (stratified by age) with TSC and refractory seizures on 1-3 antiepileptic drugs were randomized to EVE LT or HT Cmin target ranges or placebo, and treated in an 18 week Core Phase (6-wk titration + 12-wk maintenance). Primary endpoints were change from baseline in average weekly frequency of TSC-seizures (seizures not previously shown to be generalized in onset by EEG), expressed as response rate (≥50% reduction [RR]), and percentage reduction.
MedicalResearch.com: What are the main findings?
Dr. French: Overall, 366 patients were randomized to EVE LT (n=117), HT (n=130), or placebo (n=119). The median percentage reduction in TSC-seizures was significantly greater with EVE LT (29.3%, P=0.003) and HT (39.6%, P<0.001) vs placebo (14.9%). RR was also significantly greater with EVE LT (28.2%, P=0.008) and HT (40%, P<0.001) vs placebo (15.1%). The most frequent ≥10% all grade adverse events (AEs) reported with EVE LT/HT vs placebo included stomatitis (28.2%/30.8% vs 3.4%), diarrhea (17.1%/21.5% vs 5%), mouth ulceration (23.9%/21.5% vs 4.2%), nasopharyngitis (13.7%/16.2% vs 16%), upper respiratory tract infection (12.8%/15.4% vs 12.6%), aphthous ulcer (4.3%/14.6% vs 1.7%), and pyrexia (19.7%/13.8% vs 5%). Discontinuations due to AEs (5.1%/3.1% vs 1.7%) were low.
Dr. Alexander Egeberg[/caption]
Alexander Egeberg, MD PhD
National Allergy Research Centre, Departments of Dermato-Allergology and Cardiology
Herlev and Gentofte University Hospital
University of Copenhagen
Hellerup, Denmark
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Egeberg: Certain proteins and inflammatory processes have been found in increased levels in the skin of patients with rosacea, and these have also been linked to dementia, in particular Alzheimer's disease. While this may be one potential explanation, we cannot say for sure that this is the cause. Our team have recently shown a link between rosacea and other neurological diseases, and single-case reports have previously described a possible association between rosacea and Alzheimers disease.
However, this is the first comprehensive investigation of Alzheimer's disease in a large population of patients with rosacea. We found a slightly increased risk of dementia, in particular Alzheimer's disease in patients with rosacea.
Dr. Stephen Freedman[/caption]
Stephen B. Freedman MDCM, MSc,
Associate Professor
Department of Paediatrics, Sections of Emergency Medicine and Gastroenterology;
ACHRI Healthy Outcomes Theme Group Leader
Alberta Children’s Hospital, and Alberta Children’s Hospital Research Institute
University of Calgary,
Calgary, Canada
MedicalResearch.com: What is the background for this study?
Dr. Freedman: As a pediatric emergency medicine physician I continue to see large numbers of children who are brought for emergency care because of vomiting and diarrhea. In speaking with their caregivers it is clear that many of them try to administer electrolyte maintenance solutions at home but the children either refuse to drink them or they continue to vomit. As a researcher I have noticed that many children continue to receive intravenous rehydration despite not being significantly dehydrated and it appeared that this was often a physician’s response to a failed oral rehydration challenge in the emergency department, either due to refusal to consume the electrolyte maintenance solution supplied or because the children became more nauseous due to the poor palatability of the solution. It appeared that perhaps a less dogmatic approach aimed at providing fluids that children actually like, might overcome these problems leading to improved outcomes.
MedicalResearch.com: What are the main findings?
Dr. Freedman: Children with mild gastroenteritis and minimal dehydration experienced fewer treatment failures when offered dilute apple juice followed by their preferred fluid choice compared with those instructed to drink electrolyte maintenance solution to replace fluid losses. We found the benefit was greatest in those 24 to 60 months of age. The group provided and instructed to take their preferred fluids were administered intravenous rehydration less frequently.
Dr. Steven Hicks[/caption]
Steven Daniel Hicks, M.D., Ph.D.
Penn State Hershey Medical Group Hope Drive, Pediatrics
Hershey, PA 17033
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Hicks: This research was inspired by results of the CHARGE study (examining environmental influences on autism) which showed that specific pesticides (including pyrethroids) increased the risk of autism and developmental delay, particularly when mothers were exposed in the 3rdtrimester.
We recognized that the department of health sprayed pyrethroids from airplanes in a specific area near our regional medical center every summer to combat mosquito borne illnesses. We asked whether children from those areas had increased rates of autism and developmental delay. We found that they were about 25% more likely to be diagnosed with a developmental disorder at our medical center than children from control regions without aerial spraying of pyrethroids.
Dr. J. William Harbour[/caption]
Dr. Lisa Romero[/caption]
Lisa Romero DrPH, MPH
Division of Reproductive Health
National Center for Chronic Disease Prevention and Health Promotion
CDC
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Romero: Since 2006, teen birth rates have fallen almost half among Hispanic and black teens; dropping the national teen birth rate to an all-time low. While dramatic declines among Hispanic and black teens have helped reduce gaps, birth rates remain twice as high for these teens nationally compared to white teens, and more than three times as high in some states. Data also highlight the role socioeconomic conditions play, finding that higher unemployment and lower income and education are more common in communities with the highest teen birth rates, regardless of race.
Dr. Keir Menzies[/caption]
Keir Menzies PhD
Assistant Professor
University of Ottawa Brain and Mind Research Institute
University of Ottawa
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Menzies: Currently there is significant amount of research identifying the power of stem cells to regenerate damaged or aging tissue. Our research discovered that reduced stem cell health was linked to unusually low levels of a small molecule called NAD, one of the most important cellular molecules to maintain the performance of mitochondria, the engine of the cell. Then by boosting NAD levels, using a special form of vitamin B3 called nicotinamide riboside, stem cells could be rejuvenated during aging by improving mitochondrial function. We then go on to show that by improving stem cell function we could prolong the lifespan of mice, even when the treatment began at a relatively old age.
Dr. Jonathan Slaughter[/caption]
Jonathan Slaughter, MD, MPH
Assistant Professor of Pediatrics
Center for Perinatal Research
Nationwide Children's Hospital/The Ohio State University
Columbus, OH 43205
MedicalResearch.com: What is the background for this study?
Dr. Slaughter: Increasing data has emerged over the last decade showing potential harm following acid suppression use in newborns, older children, and adults. There are virtually no published data that show acid suppression via histamine-2-receptor antagonists (H2RAs) or proton-pump inhibitors (PPIs) is effective for gastroesophageal reflux disease (GERD) treatment or for other indications (stress ulcer prophylaxis, post-operative acid suppression) in healthy or sick newborns. Given the potentially limited effectiveness of these medications and increasing safety concerns following H2RA/PPI use in infants, we wanted to evaluate the frequency and duration of H2RA/PPI use among infants hospitalized within US children's hospital neonatal intensive care units (NICUs) to determine if these drugs appeared to be overused and if use appears to have changed over time. We also evaluated neonatal diagnoses associated with acid suppression to identify targets for future studies that may evaluate the usefulness of acid suppression in neonates following a given diagnosis.
Dr. Ashley Kranjac[/caption]
Ashley Wendell Kranjac, PhD
Department of Sociology and
Kinder Institute for Urban Research
Rice University
Houston, Texas and
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Dr. Robert Wagmiller[/caption]
Robert L. Wagmiller, Jr.
Associate Professor
Department of Sociology
Temple University
Philadelphia, PA 19122
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: The Center for Disease Control recently reported a decline in child obesity amongst 2-to5-year old children between 2003/4 and 2011/12 (see, Ogden et al. 2014). We aimed to identify the sources of this decline because this change occurred in a relatively short period of time. What we found is that the decline in obesity did not occur due to the things that you might expect like changes in physical activity or dietary practices (although there were some differences in these factors across years). But, rather, what we found is that because there were differences in obesity rates for the youngest and oldest children in this age range in 2003/4, but not in 2011/12, that the decline in obesity exists. In other words, because the oldest children in 2003/4 had significantly higher obesity rates than the youngest children in this time period, but this effect is not observable in 2011/12, we see a decline in obesity.