1 1 52 ON DECEMBER 5, 2017, THE NATIONAL ACADEMIES OF SCIENCES, ENGINEERING, AND MEDICINE HOSTED A PUBLIC WORKSHOP TITLED NUTRIGENOMICS AND THE FUTURE OF NUTRITION IN WASHINGTON, DC, TO REVIEW CURRENT KNOWLEDGE IN THE FIELD OF NUTRIGENOMICS AS IT RELATES TO NUTRITION. WORKSHOP PARTICIPANTS EXPLORED THE INFLUENCE OF GENETIC AND EPIGENETIC EXPRESSION ON NUTRITIONAL STATUS AND THE POTENTIAL IMPACT OF PERSONALIZED NUTRITION ON HEALTH MAINTENANCE AND CHRONIC DISEASE PREVENTION. THIS PUBLICATION SUMMARIZES THE PRESENTATIONS AND DISCUSSIONS FROM THE WORKSHOP. 2018 2 4809 20 OBESITY PREVENTION. ONCE CONSIDERED A PROBLEM ONLY IN HIGH-INCOME COUNTRIES (HICS), OBESITY HAS BECOME A MAJOR CONTRIBUTOR TO THE GLOBAL DISEASE BURDEN (FINUCANE AND OTHERS 2011; MISRA AND KHURANA 2008). EXCESS ADIPOSITY, PARTICULARLY AROUND THE VISCERAL ABDOMINAL REGION, IS AN IMPORTANT RISK FACTOR FOR MORBIDITY AND MORTALITY FROM TYPE 2 DIABETES, CARDIOVASCULAR DISEASES, AND SOME CANCERS (DANAEI AND OTHERS 2009; WHITLOCK AND OTHERS 2009; WHO 2009). ALTHOUGH SOME STUDIES HAVE SUGGESTED LOWER MORTALITY AMONG OVERWEIGHT OR OBESE PERSONS THAN AMONG HEALTHY-WEIGHT PERSONS (CARNETHON AND OTHERS 2012), THIS OUTCOME HAS NOT BEEN OBSERVED IN STUDIES THAT PROPERLY ACCOUNT FOR THE CONFOUNDING EFFECTS OF SMOKING, PREEXISTING CHRONIC CONDITIONS, AND OTHER BIASES (GLOBAL BMI MORTALITY COLLABORATION 2016; TOBIAS, PAN, AND HU 2014). THE COSTS OF OBESITY AND COMORBID CONDITIONS ARE STAGGERING AS MEASURED BY BOTH HEALTH CARE EXPENDITURES AND QUALITY OF LIFE, UNDERSCORING THE IMPORTANCE OF IMPLEMENTING OBESITY PREVENTION STRATEGIES AND TREATMENT STRATEGIES ON A GLOBAL SCALE. THE CHANGES NEEDED TO REVERSE GLOBAL TRENDS IN OBESITY WILL LIKELY REQUIRE NUMEROUS INTERVENTIONS AND POLICY RECOMMENDATIONS THAT TARGET DIET, LIFESTYLE, ACCESS TO CARE, AND ENVIRONMENTAL RISK FACTORS. IN THIS CHAPTER, WE SUMMARIZE THE GLOBAL BURDEN OF OBESITY AND THE IMPACT OF A SPECTRUM OF OBESITY RISK FACTORS, RANGING FROM SOCIOPOLITICAL AND ECONOMIC FORCES THAT ARE LARGELY BEYOND AN INDIVIDUAL'S CONTROL TO MODIFIABLE LIFESTYLE FACTORS, AND DISCUSS GENETIC AND EPIGENETIC RISKS. WE ALSO REVIEW THE EFFECTIVENESS OF POPULATION-BASED INTERVENTIONS AND POLICIES FOR PREVENTING OBESITY, SOME INDIVIDUAL-LEVEL TREATMENT OPTIONS ACROSS VARIOUS PLATFORMS, AND THE COST-EFFECTIVENESS OF SELECT INTERVENTIONS. 2017 3 5000 16 PERINATAL PROGRAMMING PREVENTION MEASURES. OVER THE PAST 10 YEARS, THERE HAS BEEN OUTSTANDING SCIENTIFIC PROGRESS RELATED TO PERINATAL PROGRAMMING AND ITS EPIGENETIC EFFECTS IN HEALTH, AND WE CAN ANTICIPATE THIS TREND WILL CONTINUE IN THE NEAR FUTURE. WE NEED TO MAKE USE AND APPLY THESE ACHIEVEMENTS TO HUMAN NEURODEVELOPMENT VIA PREVENTION INTERVENTIONS. BASED ON THE CONCEPT OF THE INTERACTION BETWEEN GENOME AND AMBIOME, THIS CHAPTER PROPOSES LOW-COST EASY-IMPLEMENTATION PREVENTIVE STRATEGIES FOR MATERNAL AND INFANT HEALTH INSTITUTIONS.BREASTFEEDING AND HUMAN MILK ADMINISTRATION ARE THE FIRST PREVENTIVE MEASURES, AS HAS BEEN REVIEWED IN THE POLICY STATEMENT OF THE AMERICAN ACADEMY OF PEDIATRICS. ANOTHER STRATEGY IS THE SAFE AND FAMILY-CENTERED MATERNITY HOSPITALS INITIATIVE THAT PROMOTES AND EMPOWERS THE INCLUSION OF THE FAMILIES AND THE RESPECT FOR THEIR RIGHTS, ESPECIALLY DURING PREGNANCY AND BIRTH. (THIS CHANGE OF PARADIGM WAS APPROVED AND IS RECOMMENDED BY BOTH UNITED NATIONS CHILDREN'S FUND, UNICEF, AND PAN AMERICAN HEALTH ORGANIZATION, PAHO.) THEN, THERE IS ALSO AN IMPORTANT EMPHASIS GIVEN TO THE SACRED HOUR-WHICH HIGHLIGHTS THE IMPACT OF BONDING, ATTACHMENT, AND BREASTFEEDING DURING THE FIRST HOUR OF LIFE-THE PAIN PREVENTION AND TREATMENT IN NEWBORNS, THE CONTROL OF THE "NEW MORBIDITY" REPRESENTED BY LATE PRETERM INFANTS, AND FINALLY, THE IMPORTANCE OF AVOIDING INTRAUTERINE AND EXTRAUTERINE GROWTH RESTRICTION. (HOWEVER, THERE ARE NOT YET CLEAR RECOMMENDATIONS ABOUT NUTRITIONAL INTERVENTIONS IN ORDER TO DIMINISH THE POTENTIAL METABOLIC SYNDROME CONSEQUENCE IN THE ADULT.). 2015 4 28 18 A BIOMIMETIC NATURAL SCIENCES APPROACH TO UNDERSTANDING THE MECHANISMS OF AGEING IN BURDEN OF LIFESTYLE DISEASES. THE WORLDWIDE LANDSCAPE OF AN AGEING POPULATION AND AGE-RELATED DISEASE BRINGS WITH IT HUGE SOCIO-ECONOMIC AND PUBLIC HEALTHCARE CONCERNS ACROSS NATIONS. CORRESPONDINGLY, MONUMENTAL HUMAN AND FINANCIAL RESOURCES HAVE BEEN INVESTED IN BIOMEDICAL RESEARCH, WITH A MISSION TO DECODE THE MECHANISMS OF AGEING AND HOW THESE CONTRIBUTE TO AGE-RELATED DISEASE. MULTIPLE HALLMARKS OF AGEING HAVE BEEN IDENTIFIED THAT ARE COMMON ACROSS TAXA, HIGHLIGHTING THEIR FUNDAMENTAL IMPORTANCE. THESE INCLUDE DYSREGULATED MITOCHONDRIAL METABOLISM AND TELOMERES BIOLOGY, EPIGENETIC MODIFICATIONS, CELL-MATRIX INTERACTIONS, PROTEOSTASIS, DYSREGULATED NUTRIENT SENSING, STEM CELL EXHAUSTION, INFLAMMAGEING AND IMMUNO-SENESCENCE. WHILE OUR UNDERSTANDING OF THE MOLECULAR BASIS OF AGEING IS IMPROVING, IT REMAINS A COMPLEX AND MULTIFACTORIAL PROCESS THAT REMAINS TO BE FULLY UNDERSTOOD. A KEY ASPECT OF THE SHORTFALL IN OUR UNDERSTANDING OF THE AGEING PROCESS LIES IN TRANSLATING DATA FROM STANDARD ANIMAL MODELS TO HUMANS. CONSEQUENTLY, WE SUGGEST THAT A 'BIOMIMETIC' AND COMPARATIVE APPROACH, INTEGRATING KNOWLEDGE FROM SPECIES IN THE WILD, AS OPPOSED TO INBRED GENETICALLY HOMOGENOUS LABORATORY ANIMALS, CAN PROVIDE POWERFUL INSIGHTS INTO HUMAN AGEING PROCESSES. HERE WE DISCUSS SOME PARTICULARITIES AND COMPARATIVE PATTERNS AMONG SEVERAL SPECIES FROM THE ANIMAL KINGDOM, ENDOWED WITH LONGEVITY OR SHORT LIFESPANS AND UNIQUE METABOLIC PROFILES THAT COULD BE POTENTIALLY EXPLOITED TO THE UNDERSTANDING OF AGEING AND AGE-RELATED DISEASES. BASED UPON LESSONS FROM NATURE, WE ALSO HIGHLIGHT SEVERAL AVENUES FOR RENEWED FOCUS IN THE PATHOPHYSIOLOGY OF AGEING AND AGE-RELATED DISEASE (I.E. DIET-MICROBIOME-HEALTH AXIS, OXIDATIVE PROTEIN DAMAGE, ADAPTIVE HOMOEOSTASIS AND PLANETARY HEALTH). WE PROPOSE THAT A BIOMIMETIC ALLIANCE WITH COLLABORATIVE RESEARCH FROM DIFFERENT DISCIPLINES CAN IMPROVE OUR UNDERSTANDING OF AGEING AND AGE-RELATED DISEASES WITH LONG-TERM SUSTAINABLE UTILITY. 2021 5 1927 16 ENVIRONMENTAL EPIGENOMICS AND DISEASE SUSCEPTIBILITY. KEYSTONE SYMPOSIA ON MOLECULAR AND CELLULAR BIOLOGY. THE GROVE PARK HOTEL & SPA, ASHVILLE, NC, USA, 27 MARCH-1 APRIL 2011. THE MAIN OBJECTIVE OF THIS CONFERENCE WAS TO PROVIDE SOLID EVIDENCE THAT ENVIRONMENTAL EXPOSURES DURING EARLY DEVELOPMENT CAN AFFECT FAITHFUL REPRODUCTION OF INDIVIDUAL PARENTAL EPIGENOMES WITHOUT CHANGING DNA SEQUENCE IN THE OFFSPRING. NO DOUBT, THIS IMPORTANT GOAL HAS BEEN SUCCESSFULLY ACHIEVED OWING TO THE HIGH QUALITY OF PRESENTED EPIDEMIOLOGICAL AND EXPERIMENTAL STUDIES AND ENGAGING DISCUSSIONS OF MANY YET TO BE PUBLISHED RESULTS. COMPELLING DATA SUGGESTED A STRONG CAUSAL LINK BETWEEN PRENATAL VULNERABILITY OF FUTURE PARENTAL EPIGENOMES TO DAMAGING ENVIRONMENTAL FACTORS AGGRAVATED BY ABNORMAL SOCIO-CULTURAL CONDITIONS (INCLUDING, FOR INSTANCE, MALNUTRITION AND CHRONIC STRESS) AND THE ALARMING RISK OF DEVELOPING HERITABLE COMPLEX MEDICAL CONDITIONS LATER IN LIFE, SUCH AS ASTHMA, AUTISM, CANCER, CARDIOVASCULAR DISEASE, DIABETES, OBESITY, SCHIZOPHRENIA AND A WHOLE RANGE OF RARE NEUROMUSCULAR PATHOLOGIES. IT WAS CONCLUDED THAT MODERN EPIGENETIC RESEARCH PROMISES TO MARKEDLY IMPROVE OUR ABILITY TO DIAGNOSE, PREVENT AND TREAT THESE AND OTHER PATHOLOGICAL CONDITIONS OF HUMANS. HOWEVER, THE COMPLEX HERITABILITY PATTERN OF 'EPIGENETIC SYNDROMES' ALSO INTRODUCES UNIQUE LEGAL AND ETHICAL ISSUES THAT WERE DISCUSSED AT THE END OF THIS OUTSTANDING MEETING. 2011 6 6784 17 [CHRONIC STRESS AND EPIGENETICS. RELATION BETWEEN ACADEMIC SCIENCES AND THEOLOGY]. THE AUTHOR GIVES A SHORT ACCOUNT ON THE PRINCIPLES OF SELYE'S STRESS THEORY, AND DISCUSSES SIMILARITIES AND DISSIMILARITIES OF ACUTE AND CHRONIC STRESS. BOTH THE EXTERNAL, AND THE INTERNAL ENVIRONMENT, AS WELL AS THE PSYCHO-MENTAL STATUS ARE INVOLVED IN THE NOTION OF THE ENVIRONMENT. BASIC PRINCIPLES OF EPIGENETICS ARE REVIEWED: INTERACTION BETWEEN ENVIRONMENT AND GENES, NEUROENDOCRINE AND ENZYMATIC MECHANISMS INVOLVED IN SILENCING AND ACTIVATION OF GENES, NOTIONS OF PHENOTYPIC PLASTICITY, AND EPIGENETIC REPROGRAMMING ARE DISCUSSED. EPIGENETIC MECHANISMS OF INTERRELATION BETWEEN PATHOLOGICAL CLINICAL STATES (DISEASES) AND THE CHARACTERISTIC PHENOTYPES, CAUSATIVE ROLE OF PSYCHO-MENTAL STATUS IN EVOKING PATHOLOGICAL SOMATIC ALTERATIONS, AND THE POTENTIAL THERAPEUTIC CONSEQUENCES ARE BRIEFLY DISCUSSED. THE ETIOLOGICAL ROLE OF CHRONIC, CIVILIZATION STRESS IN PRODUCING THE WORLDWIDE INCREMENT OF CARDIOVASCULAR MORBIDITY IS CITED, ARGUMENTATION AND CRITICISM OF THE CURRENT THERAPEUTICAL PRACTICE IS DISCUSSED. THE AUTHOR CONCLUDES THAT RECENT ADVANCES IN EPIGENETIC KNOWLEDGE SEEM TO SOLVE THE CONTROVERSY BETWEEN THE ACADEMIC AND THEOLOGICAL SCIENCES. 2012 7 1377 20 DEVELOPMENTAL PROGRAMMING: STATE-OF-THE-SCIENCE AND FUTURE DIRECTIONS-SUMMARY FROM A PENNINGTON BIOMEDICAL SYMPOSIUM. OBJECTIVE: ON DECEMBER 8-9, 2014, THE PENNINGTON BIOMEDICAL RESEARCH CENTER CONVENED A SCIENTIFIC SYMPOSIUM TO REVIEW THE STATE-OF-THE-SCIENCE AND FUTURE DIRECTIONS FOR THE STUDY OF DEVELOPMENTAL PROGRAMMING OF OBESITY AND CHRONIC DISEASE. THE OBJECTIVES OF THE SYMPOSIUM WERE TO DISCUSS: (I) PAST AND CURRENT SCIENTIFIC ADVANCES IN ANIMAL MODELS, POPULATION-BASED COHORT STUDIES, AND HUMAN CLINICAL TRIALS, (II) THE STATE-OF-THE-SCIENCE OF EPIGENETIC-BASED RESEARCH, AND (III) CONSIDERATIONS FOR FUTURE STUDIES. RESULTS: THIS SYMPOSIUM PROVIDED A COMPREHENSIVE ASSESSMENT OF THE STATE OF THE SCIENTIFIC FIELD AND IDENTIFIED RESEARCH GAPS AND OPPORTUNITIES FOR FUTURE RESEARCH IN ORDER TO UNDERSTAND THE MECHANISMS CONTRIBUTING TO THE DEVELOPMENTAL PROGRAMMING OF HEALTH AND DISEASE. CONCLUSIONS: IDENTIFYING THE MECHANISMS WHICH CAUSE OR CONTRIBUTE TO DEVELOPMENTAL PROGRAMMING OF FUTURE GENERATIONS WILL BE INVALUABLE TO THE SCIENTIFIC AND MEDICAL COMMUNITY. THE ABILITY TO INTERVENE DURING CRITICAL PERIODS OF PRENATAL AND EARLY POSTNATAL LIFE TO PROMOTE LIFELONG HEALTH IS THE ULTIMATE GOAL. CONSIDERATIONS FOR FUTURE RESEARCH INCLUDING THE USE OF ANIMAL MODELS, THE STUDY DESIGN IN HUMAN COHORTS WITH CONSIDERATIONS ABOUT THE TIMING OF THE INTRAUTERINE EXPOSURE, AND THE RESULTING TISSUE-SPECIFIC EPIGENETIC SIGNATURE WERE EXTENSIVELY DISCUSSED AND ARE PRESENTED IN THIS MEETING SUMMARY. 2016 8 4808 16 OBESITY MANAGEMENT: AT THE FOREFRONT AGAINST DISEASE STIGMA AND THERAPEUTIC INERTIA. OBESITY IS A COMPLEX CHRONIC RELAPSING DISEASE, RESULTING FROM THE INTERACTION BETWEEN MULTIPLE ENVIRONMENTAL, GENETIC AND EPIGENETIC CAUSES, AND SUPPORTED BY CHANGES IN THE NEUROENDOCRINE MECHANISMS REGULATING ENERGY BALANCE AND BODY WEIGHT. ADIPOSE TISSUE DYSFUNCTION CONTRIBUTES TO OBESITY-RELATED COMPLICATIONS. HOWEVER, THE PREVALENT NARRATIVE ABOUT THE CAUSES AND MECHANISMS OF OBESITY REMAINS A MUCH MORE SIMPLISTIC ONE, BASED ON THE FALSE ASSUMPTION THAT INDIVIDUALS CAN FULLY CONTROL THEIR BODY WEIGHT THROUGH APPROPRIATE BEHAVIOURAL CHOICES. ACCORDING TO THIS NARRATIVE, OBESITY IS SIMPLY REVERSIBLE "PERSUADING" THE PATIENT TO FOLLOW HEALTHIER AND MORE VIRTUOUS INDIVIDUAL BEHAVIOURS (MORAL JUDGEMENT). THIS PERSISTENT NARRATIVE FORMS THE DEEP ROOT OF THE STIGMATISATION OF PEOPLE WITH OBESITY AT THE INDIVIDUAL LEVEL AND CREATES A CLEAR DISCREPANCY ON HOW OBESITY PREVENTION AND CURE ARE DESIGNED IN COMPARISON WITH THE CASE OF OTHER NON-COMMUNICABLE CHRONIC DISEASES (CLINICAL STIGMA). THE PROMOTION OF SYSTEMIC PREVENTIVE MEASURES AGAINST OBESITY IS NOT SUPPORTED AT A POLITICAL AND SOCIAL LEVEL BY THE PERSISTENCE OF A NARRATIVE OF OBESITY AS THE SIMPLE CONSEQUENCE OF INDIVIDUAL FAILURES AND LACK OF WILLPOWER. THE SIMPLISTIC NARRATIVE OF OBESITY AS A SELF-IMPOSED CONDITION WITH AN EASY WAY-OUT ("EAT LESS AND MOVE MORE") CREATES A CLEAR DISCREPANCY ON HOW OBESITY IS MANAGED BY HEALTH CARE SYSTEMS IN COMPARISON WITH OTHER NCDS. THE OVER-ESTIMATION OF THE EFFICACY OF THERAPEUTIC INTERVENTION SOLELY BASED ON PATIENTS EDUCATION AND LIFESTYLE MODIFICATION IS RESPONSIBLE OF THERAPEUTIC INERTIA IN HEALTH CARE PROFESSIONALS AND IN CLINICAL GUIDELINES, LIMITING OR DELAYING THE ADOPTION OF MORE EFFECTIVE THERAPEUTIC STRATEGIES, LIKE ANTI-OBESITY MEDICATIONS AND BARIATRIC SURGERY. IN CONCLUSION, THE PERSISTENCE OF A NARRATIVE DESCRIBING OBESITY AS A SELF-INDUCED EASILY REVERSIBLE CONDITION HAS PROFOUND CONSEQUENCES ON HOW OBESITY PREVENTION AND MANAGEMENT ARE BUILD, INCLUDING THE DESIGN AND IMPLEMENTATION OF OBESITY MANAGEMENT GUIDELINES AND A TENDENCY TO THERAPEUTIC INERTIA.LEVEL OF EVIDENCE: NO LEVEL OF EVIDENCE. 2022 9 650 14 BISPHENOL A AND HUMAN CHRONIC DISEASES: CURRENT EVIDENCES, POSSIBLE MECHANISMS, AND FUTURE PERSPECTIVES. BISPHENOL-A (BPA) IS ONE OF THE HIGHEST VOLUME CHEMICALS PRODUCED WORLDWIDE, WITH OVER 6BILLION POUNDS PRODUCED AND OVER 100T RELEASED INTO THE ATMOSPHERE EACH YEAR. RECENT EXTENSIVE LITERATURE HAS RAISED CONCERNS ABOUT ITS POSSIBLE IMPLICATION IN THE ETIOLOGY OF SOME HUMAN CHRONIC DISEASES SUCH AS DIABETES, OBESITY, REPRODUCTIVE DISORDERS, CARDIOVASCULAR DISEASES, BIRTH DEFECTS, CHRONIC RESPIRATORY AND KIDNEY DISEASES AND BREAST CANCER. IN THIS REVIEW, WE PRESENT THE HIGHLIGHTED EVIDENCES ON THE RELATIONSHIP BETWEEN BPA EXPOSURE AND HUMAN CHRONIC DISEASES AND WE DISCUSS ITS EVENTUAL MECHANISMS OF ACTION, ESPECIALLY GENETIC, EPIGENETIC AND ENDOCRINE DISRUPTION MECHANISMS WITH THE POSSIBLE INVOLVEMENT OF OXIDATIVE STRESS, MITOCHONDRIAL DYSFUNCTION AND CELL SIGNALING. 2014 10 6454 25 THIRD JESUS CULEBRAS LECTURE - MOLECULAR BIOLOGY AND CLINICAL NUTRITION; WHERE DO WE STAND AND WHERE DO WE GO? NUTRITION PLAYS A FUNDAMENTAL ROLE IN THE MAINTENANCE OF HEALTH AND THE TREATMENT OF DISEASE, AND SERVES AS THE CROSSROADS FOR MANY DISCIPLINES. BIOCHEMISTRY AND MOLECULAR BIOLOGY REPRESENTS A KEY BRAND OF SCIENCE TO ASCERTAIN THE MECHANISM OF ACTION OF NUTRIENTS AND OTHER FOOD BIOACTIVE COMPOUNDS IN HEALTH AND DISEASE. THE AIM OF THE PRESENT JESUS M. CULEBRAS LECTURE IS TO CONSIDER THE FUTURE OF THE RELATIONSHIPS BETWEEN MOLECULAR BIOLOGY AND CLINICAL NUTRITION AND TO DISCUSS THE USE OF MOLECULAR AND GENETIC TOOLS TO STUDY MOLECULAR RESPONSES TO DIETARY FACTORS AND THE METABOLIC CONSEQUENCES OF FOOD AND TO CONSIDER MAJOR CHALLENGES ON HUMAN NUTRITION SCIENCES IN THE 21(ST) CENTURY. PARTICULAR EMPHASIS IS GIVEN TO THE IDENTIFICATION AND USE OF NOVEL BIOMARKERS IN INFLAMMATORY DISEASES. LIKEWISE, THE IMPORTANCE OF THE HUMAN MICROBIOME AND HOW MICROORGANISMS CAN BE SAFELY UTILIZED IN THE PREVENTION AND MANAGEMENT OF INFECTIOUS AND CHRONIC DISEASES ARE DISCUSSED. MOREOVER, THE KEY ROLE OF NUTRIGENETICS, NUTRIGENOMICS AND EPIGENETICS IN THE NEW ERA OF NUTRITION IS CONSIDERED. NUTRIGENETICS REFERS TO THE ROLE OF DNA SEQUENCE VARIATION IN THE RESPONSES TO NUTRIENTS, WHEREAS NUTRIGENOMICS IS THE STUDY OF THE ROLE OF NUTRIENTS IN GENE EXPRESSION. EPIGENETICS IS THE STUDY OF MITOTICALLY HERITABLE ALTERATIONS IN GENE EXPRESSION POTENTIAL THAT ARE NOT CAUSED BY DNA SEQUENCE ALTERATIONS. IN THE PAST DECADE, IT HAS INCREASINGLY BEEN RECOGNIZED THAT DYSREGULATION OF EPIGENETIC MECHANISMS MAY PLAY AN IMPORTANT ROLE IN HUMAN DISEASE. INDEED, THERE IS INCREASING INTEREST IN EPIGENETIC MECHANISMS UNDERLYING PHENOTYPE MODIFICATION MODULATED BY NUTRIENTS. FURTHER RESEARCH IN THOSE AREAS SHOULD CONTRIBUTE TO EVALUATE FUNCTIONALITY OF SPECIFIC NUTRIENTS AND BIOACTIVE COMPOUNDS IN CLINICAL NUTRITION AND ALLOW PERSONALIZED NUTRITIONAL ADVICE. 2013 11 4399 13 MODULATION OF GENOMIC AND POSTGENOMIC ALTERATIONS IN NONCANCER DISEASES AND CRITICAL PERIODS OF LIFE. GENOMIC AND POSTGENOMIC CHANGES ARE EXTENSIVELY INVESTIGATED IN CANCER RESEARCH. SIMILAR ALTERATIONS, AFFECTING GENOME, TRANSCRIPTOME, MIRNOME AND/OR PROTEOME END-POINTS, HAVE BEEN DETECTED IN A VARIETY OF OTHER CHRONIC DEGENERATIVE DISEASES, SUCH AS ATHEROSCLEROSIS, DEGENERATIVE HEART DISEASES, CHRONIC OBSTRUCTIVE PULMONARY DISEASES, NEUROLOGICAL DISORDERS, EYE DISEASES, DIABETES, METABOLIC SYNDROME, SKIN AGEING AND ALOPECIA. NO GENERALIZATION CAN BE MADE DUE TO THE MYRIAD OF DIVERSE CLINICAL ENTITIES CLASSIFIED AS CHRONIC DEGENERATIVE DISEASES. MOREOVER, THE DETECTION OF MOLECULAR CHANGES DOES NOT AUTOMATICALLY IMPLY THEIR CAUSAL ROLE. NEVERTHELESS, COMMON MECHANISMS, SUCH AS DNA DAMAGE, EPIGENETIC ALTERATIONS, OXIDATIVE STRESS, AND CHRONIC INFLAMMATION, IN ADDITION TO GENETIC PREDISPOSITION, ARE OFTEN INVOLVED IN NONCANCER DISEASES. WE DEBATE HERE IN MORE DETAIL THE SUBJECTS OF CARDIOVASCULAR DISEASES AND OF SKIN DISEASES. MOREOVER, WE DISCUSS OUR EXPERIMENTAL STUDIES SUGGESTING THAT GENOMIC AND POSTGENOMIC CHANGES DO ALSO OCCUR DURING CRITICAL PERIODS OF LIFE, INCLUDING THE PRENATAL LIFE, THE PERINATAL PERIOD, AND AGEING. IN ADDITION, WE COMMENT ON THE FINDING THAT STEM-DERIVED CELLS ARE MORE SUSCEPTIBLE TO MOLECULAR DAMAGE THAN MORE DIFFERENTIATED CELLS. ALL THESE DATA ARE VIEWED IN THE PERSPECTIVE OF PREVENTIVE MEDICINE. IN FACT, THERE IS EVIDENCE THAT THE GENOMIC AND POSTGENOMIC ALTERATIONS OCCURRING NOT ONLY IN SEVERAL PATHOLOGICAL CONDITIONS BUT ALSO IN PARAPHYSIOLOGICAL SITUATIONS THAT AFFECT CRITICAL PERIODS OF LIFE CAN BE MODULATED BY MEANS OF DIETARY AND PHARMACOLOGICAL AGENTS. THE DISCOVERY THAT CHEMOPREVENTIVE AGENTS ARE ALSO ABLE TO ATTENUATE NUCLEOTIDE DAMAGE IN STEM-DERIVED CELLS WARRANTS FURTHER STUDIES IN VIEW OF POSSIBLE CLINICAL APPLICATIONS. 2009 12 705 14 BUILDING RISK-ON-A-CHIP MODELS TO IMPROVE BREAST CANCER RISK ASSESSMENT AND PREVENTION. PREVENTIVE ACTIONS FOR CHRONIC DISEASES HOLD THE PROMISE OF IMPROVING LIVES AND REDUCING HEALTHCARE COSTS. FOR SEVERAL DISEASES, INCLUDING BREAST CANCER, MULTIPLE RISK AND PROTECTIVE FACTORS HAVE BEEN IDENTIFIED BY EPIDEMIOLOGISTS. THE IMPACT OF MOST OF THESE FACTORS HAS YET TO BE FULLY UNDERSTOOD AT THE ORGANISM, TISSUE, CELLULAR AND MOLECULAR LEVELS. IMPORTANTLY, COMBINATIONS OF EXTERNAL AND INTERNAL RISK AND PROTECTIVE FACTORS INVOLVE COOPERATIVITY THUS, SYNERGIZING OR ANTAGONIZING DISEASE ONSET. MODELS ARE NEEDED TO MECHANISTICALLY DECIPHER CANCER RISKS UNDER DEFINED CELLULAR AND MICROENVIRONMENTAL CONDITIONS. HERE, WE BRIEFLY REVIEW BREAST CANCER RISK MODELS BASED ON 3D CELL CULTURE AND PROPOSE TO IMPROVE RISK MODELING WITH LAB-ON-A-CHIP APPROACHES. WE SUGGEST EPITHELIAL TISSUE POLARITY, DNA REPAIR AND EPIGENETIC PROFILES AS ENDPOINTS IN RISK ASSESSMENT MODELS AND DISCUSS THE DEVELOPMENT OF 'RISKS-ON-CHIPS' INTEGRATING BIOSENSORS OF THESE ENDPOINTS AND OF GENERAL TISSUE HOMEOSTASIS. RISKS-ON-CHIPS WILL HELP IDENTIFY BIOMARKERS OF RISK, SERVE AS SCREENING PLATFORMS FOR CANCER PREVENTIVE AGENTS, AND PROVIDE A BETTER UNDERSTANDING OF RISK MECHANISMS, HENCE RESULTING IN NOVEL DEVELOPMENTS IN DISEASE PREVENTION. 2013 13 6350 18 THE ROLE OF EPIGENOMICS IN AQUATIC TOXICOLOGY. OVER THE PAST DECADE, THE FIELD OF MOLECULAR BIOLOGY HAS RAPIDLY INCORPORATED EPIGENETIC STUDIES TO EVALUATE ORGANISM-ENVIRONMENT INTERACTIONS THAT CAN RESULT IN CHRONIC EFFECTS. SUCH RESPONSES ARISE FROM EARLY LIFE STAGE STRESS, THE UTILIZATION OF GENETIC INFORMATION OVER AN INDIVIDUAL'S LIFE TIME, AND TRANSGENERATIONAL INHERITANCE. KNOWLEDGE OF EPIGENETIC MECHANISMS PROVIDES THE POTENTIAL FOR A COMPREHENSIVE EVALUATION OF MULTIGENERATIONAL AND HERITABLE EFFECTS FROM ENVIRONMENTAL STRESSORS, SUCH AS CONTAMINANTS. FOCUSED STUDIES HAVE PROVIDED A GREATER UNDERSTANDING OF HOW MANY RESPONSES TO ENVIRONMENTAL STRESSORS ARE DRIVEN BY EPIGENETIC MODIFIERS. WE DISCUSS THE PROMISE OF EPIGENETICS AND SUGGEST FUTURE RESEARCH DIRECTIONS WITHIN THE FIELD OF AQUATIC TOXICOLOGY, WITH A PARTICULAR FOCUS ON THE POTENTIAL FOR IDENTIFYING KEY HERITABLE MARKS WITH CONSEQUENTIAL IMPACTS AT THE ORGANISM AND POPULATION LEVELS. ENVIRON TOXICOL CHEM 2017;36:2565-2573. (C) 2017 SETAC. 2017 14 2690 20 EVOLUTION OF DOHAD: THE IMPACT OF ENVIRONMENTAL HEALTH SCIENCES. ENVIRONMENTAL EXPOSURES HAVE A SIGNIFICANT INFLUENCE ON THE CHRONIC HEALTH CONDITIONS PLAGUING CHILDREN AND ADULTS. ALTHOUGH THE DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE (DOHAD) PARADIGM HISTORICALLY HAS FOCUSED ON NUTRITION, AN EXPANDING BODY OF RESEARCH SPECIFICALLY COMMUNICATES THE EFFECTS OF CHEMICAL EXPOSURES ON EARLY-LIFE DEVELOPMENT AND THE PROPAGATION OF NON-COMMUNICABLE DISEASE ACROSS THE LIFESPAN. THIS PAPER PROVIDES AN OVERVIEW OF 20 YEARS OF RESEARCH EFFORTS AIMED AT IDENTIFYING CRITICAL WINDOWS OF SUSCEPTIBILITY TO ENVIRONMENTAL EXPOSURES AND THE SIGNALING CHANGES AND EPIGENETIC INFLUENCES ASSOCIATED WITH DISEASE PROGRESSION. DOHAD GRANTS FUNDED BY THE NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES (NIEHS) IN 1991, 2001 AND 2011 ARE IDENTIFIED BY GRANT-ANALYSIS SOFTWARE, AND EACH PORTFOLIO IS ANALYZED FOR EXPOSURES, DISEASE ENDPOINTS, WINDOWS OF EXPOSURE, STUDY DESIGN AND IMPACT ON THE FIELD BASED ON PUBLICATION DATA. RESULTS SHOW THAT THE 1991 AND 2001 PORTFOLIOS COMPRISED METALS, PCBS AND AIR POLLUTANTS; HOWEVER, BY 2011, THE PORTFOLIO HAS EVOLVED TO INCLUDE OR EXPAND THE VARIETY OF ENDOCRINE DISRUPTORS, PESTICIDES/PERSISTENT ORGANIC POLLUTANTS AND METALS. AN ASSORTMENT OF BRAIN-HEALTH ENDPOINTS IS MOST TARGETED ACROSS THE PORTFOLIOS, WHEREAS REPRODUCTION AND CANCER INCREASE STEADILY OVER THE SAME TIME PERIOD, AND NEW ENDPOINTS LIKE OBESITY ARE INTRODUCED BY 2011. WITH MOUNTING EVIDENCE CONNECTING EARLY-LIFE EXPOSURES TO LATER-LIFE DISEASE, WE CONCLUDE THAT IT IS CRITICAL TO EXPAND THE ORIGINAL DOHAD CONCEPT TO INCLUDE ENVIRONMENTAL CHEMICAL EXPOSURES, AND TO CONTINUE A RESEARCH AGENDA THAT EMPHASIZES DEFINING SENSITIVE WINDOWS OF EXPOSURE AND THE MECHANISMS THAT CAUSE DISEASE. 2015 15 1865 22 EMERGING CONCEPTS ON THE ROLE OF EPIGENETICS IN THE RELATIONSHIPS BETWEEN NUTRITION AND HEALTH. UNDERSTANDING THE PHYSIOLOGICAL AND METABOLIC UNDERPINNINGS THAT CONFER INDIVIDUAL DIFFERENCES IN RESPONSES TO DIET AND DIET-RELATED CHRONIC DISEASE IS ESSENTIAL TO ADVANCE THE FIELD OF NUTRITION. THIS INCLUDES ELUCIDATING THE DIFFERENCES IN GENE EXPRESSION THAT ARE MEDIATED THROUGH PROGRAMMING OF THE GENOME THROUGH EPIGENETIC CHROMATIN MODIFICATIONS. EPIGENETIC LANDSCAPES ARE INFLUENCED BY AGE, GENETICS, TOXINS AND OTHER ENVIRONMENTAL FACTORS, INCLUDING DIETARY EXPOSURES AND NUTRITIONAL STATUS. EPIGENETIC MODIFICATIONS INFLUENCE TRANSCRIPTION AND GENOME STABILITY ARE ESTABLISHED DURING DEVELOPMENT WITH LIFE-LONG CONSEQUENCES. THEY CAN BE INHERITED FROM ONE GENERATION TO THE NEXT. THE COVALENT MODIFICATIONS OF CHROMATIN, WHICH INCLUDE METHYLATION AND ACETYLATION, ON DNA NUCLEOTIDE BASES, HISTONE PROTEINS AND RNA ARE DERIVED FROM INTERMEDIATES OF ONE-CARBON METABOLISM AND CENTRAL METABOLISM. THEY INFLUENCE KEY PHYSIOLOGICAL PROCESSES THROUGHOUT LIFE, AND TOGETHER WITH INHERITED DNA PRIMARY SEQUENCE, CONTRIBUTE TO RESPONSIVENESS TO ENVIRONMENTAL STRESSES, DIET AND RISK FOR AGE-RELATED CHRONIC DISEASE. REVEALING DIET-EPIGENETIC RELATIONSHIPS HAS THE POTENTIAL TO TRANSFORM NUTRITION SCIENCE BY INCREASING OUR FUNDAMENTAL UNDERSTANDING OF: (I) THE ROLE OF NUTRIENTS IN BIOLOGICAL SYSTEMS, (II) THE RESILIENCE OF LIVING ORGANISMS IN RESPONDING TO ENVIRONMENTAL PERTURBATIONS, AND (III) THE DEVELOPMENT OF DIETARY PATTERNS THAT PROGRAMME PHYSIOLOGY FOR LIFE-LONG HEALTH. EPIGENETICS MAY ALSO ENABLE THE CLASSIFICATION OF INDIVIDUALS WITH CHRONIC DISEASE FOR SPECIFIC DIETARY MANAGEMENT AND/OR FOR EFFICACIOUS DIET-PHARMACEUTICAL COMBINATION THERAPIES. THESE NEW EMERGING CONCEPTS AT THE INTERFACE OF NUTRITION AND EPIGENETICS WERE DISCUSSED, AND FUTURE RESEARCH NEEDS IDENTIFIED BY LEADING EXPERTS AT THE 26TH MARABOU SYMPOSIUM ENTITLED 'NUTRITION, EPIGENETICS, GENETICS: IMPACT ON HEALTH AND DISEASE'. FOR A COMPILATION OF THE GENERAL DISCUSSION AT THE MARABOU SYMPOSIUM, CLICK HERE HTTP://WWW.MARABOUSYMPOSIUM.ORG/. 2018 16 6730 14 WALK MORE, EAT LESS, DON'T STRESS. UNHEALTHY DIET, OBESITY, LACK OF PHYSICAL ACTIVITY, AND PSYCHOLOGIC STRESS ARE ASSOCIATED WITH INCREASED INFLAMMATION, OXIDATIVE STRESS, INSULIN RESISTANCE, AND DNA METHYLATION, WHICH ARE THE MAIN MECHANISMS OF CHRONIC DISEASES SUCH AS CANCER, HYPERTENSION, DIABETES, CARDIOVASCULAR DISEASE, AND ALZHEIMER'S DISEASE. IT HAS RECENTLY BEEN FOUND THAT HEALTHY DIET AND PHYSICAL ACTIVITY CAN REDUCE INFLAMMATORY MARKERS AND IMPROVE INSULIN SENSITIVITY RESULTING IN BETTER SURVIVORSHIP OUTCOMES IN PATIENTS WITH PROSTATE CANCER. AN "ANTI-INFLAMMATORY" LIFESTYLE, INCLUDING PHYSICAL ACTIVITY, HEALTHY BODY WEIGHT, HEALTHY DIET, AND STRESS REDUCTION, HAS BEEN ASSOCIATED WITH DECREASED CANCER RISK AND PROGRESSION. EPIGENETIC CHANGES DUE TO DNA METHYLATION AND ALTERED GENE EXPRESSION ASSOCIATED WITH UNHEALTHY LIFESTYLE CAN BE MODULATED BY HEALTHY BEHAVIORS. NATIONAL CENTER FOR COMPLEMENTARY AND INTEGRATIVE HEALTH (NCCIH) FOCUSES ON HEALTHY LIFESTYLE, AND IT SUPPORTS RESEARCH ON PSYCHOLOGIC AND PHYSICAL APPROACHES INCLUDING DIETARY SUPPLEMENTS AND PLANT-BASED PRODUCTS, AS WELL AS MIND AND BODY APPROACHES, SUCH AS YOGA, MASSAGE, MEDITATION, MINDFULNESS-BASED STRESS REDUCTION, AND ACUPUNCTURE. SEE RELATED ARTICLE BY LANGLAIS ET AL., P. 1760. 2022 17 2616 13 EPIGENOME MODULATION INDUCED BY KETOGENIC DIETS. KETOGENIC DIETS (KD) ARE DIETARY STRATEGIES LOW IN CARBOHYDRATES, NORMAL IN PROTEIN, AND HIGH, NORMAL, OR REDUCED IN FAT WITH OR WITHOUT (VERY LOW-CALORIES KETOGENIC DIET, VLCKD) A REDUCED CALORIC INTAKE. KDS HAVE BEEN SHOWN TO BE USEFUL IN THE TREATMENT OF OBESITY, METABOLIC DISEASES AND RELATED DISORDERS, NEUROLOGICAL DISEASES, AND VARIOUS PATHOLOGICAL CONDITIONS SUCH AS CANCER, NONALCOHOLIC LIVER DISEASE, AND CHRONIC PAIN. SEVERAL STUDIES HAVE INVESTIGATED THE INTRACELLULAR METABOLIC PATHWAYS THAT CONTRIBUTE TO THE BENEFICIAL EFFECTS OF THESE DIETS. ALTHOUGH EPIGENETIC CHANGES ARE AMONG THE MOST IMPORTANT DETERMINANTS OF AN ORGANISM'S ABILITY TO ADAPT TO ENVIRONMENTAL CHANGES, DATA ON THE EPIGENETIC CHANGES ASSOCIATED WITH THESE DIETARY PATHWAYS ARE STILL LIMITED. THIS REVIEW PROVIDES AN OVERVIEW OF THE MAJOR EPIGENETIC CHANGES ASSOCIATED WITH KDS. 2022 18 4871 19 OUR GENES ARE NOT OUR DESTINY: INCORPORATING MOLECULAR MEDICINE INTO CLINICAL PRACTICE. IN MANY DEVELOPED NATIONS, THE STATE OF PUBLICLY ADMINISTERED HEALTH CARE IS INCREASINGLY PRECARIOUS AS A RESULT OF ESCALATING NUMBERS OF CHRONICALLY ILL PATIENTS, INADEQUATE MEDICAL PERSONNEL AND HOSPITAL FACILITIES, AS WELL AS SPARSE FUNDING FOR ONGOING UPGRADES TO STATE-OF-THE-ART DIAGNOSTIC AND THERAPEUTIC TECHNOLOGY - AN INCREASED EMPHASIS ON AETIOLOGY-CENTRED MEDICINE SHOULD BE CONSIDERED IN ORDER TO ACHIEVE IMPROVED HEALTH FOR PATIENTS AND POPULATIONS. MEDICAL PRACTICE PATTERNS WHICH ARE DESIGNED TO PROVIDE QUICK AND EFFECTIVE AMELIORATION OF SIGNS AND SYMPTOMS ARE FREQUENTLY NOT AN ENDURING SOLUTION TO MANY HEALTH AFFLICTIONS AND CHRONIC DISEASE STATES. RECENT SCIENTIFIC DISCOVERY HAS RENDERED THE DRUG-ORIENTED ALGORITHMIC PARADIGM COMMONLY FOUND IN CONTEMPORARY EVIDENCE-BASED MEDICINE TO BE A REDUCTIONIST APPROACH TO CLINICAL PRACTICE. UNFOLDING EVIDENCE APPEARS TO SUPPORT A GENETIC PREDISPOSITION MODEL OF HEALTH AND ILLNESS RATHER THAN A FATALISTIC PREDESTINATION CONSTRUCT - MODIFIABLE EPIGENETIC AND ENVIRONMENTAL FACTORS HAVE ENORMOUS POTENTIAL TO INFLUENCE CLINICAL OUTCOMES. BY UNDERSTANDING AND APPLYING FUNDAMENTAL CLINICAL PRINCIPLES RELATING TO THE EMERGING FIELDS OF MOLECULAR MEDICINE, NUTRIGENOMICS AND HUMAN EXPOSURE ASSESSMENT, DOCTORS WILL BE EMPOWERED TO ADDRESS CAUSALITY OF AFFLICTION WHEN POSSIBLE AND ACHIEVE SUSTAINED REPRIEVE FOR MANY SUFFERING PATIENTS. 2008 19 4592 15 NATURAL ENVIRONMENTS, NATURE RELATEDNESS AND THE ECOLOGICAL THEATER: CONNECTING SATELLITES AND SEQUENCING TO SHINRIN-YOKU. RECENT ADVANCES IN RESEARCH CONCERNING THE PUBLIC HEALTH VALUE OF NATURAL ENVIRONMENTS HAVE BEEN REMARKABLE. THE GROWING INTEREST IN THIS TOPIC (OFTEN HOUSED UNDER TERMS SUCH AS GREEN AND/OR BLUE SPACE) HAS BEEN OCCURRING IN PARALLEL WITH THE MICROBIOME REVOLUTION AND AN INCREASED USE OF REMOTE SENSING TECHNOLOGY IN PUBLIC HEALTH. IN THE CONTEXT OF BIODIVERSITY LOSS, RAPID URBANIZATION, AND ALARMING RATES OF GLOBAL NON-COMMUNICABLE DISEASES (MANY ASSOCIATED WITH CHRONIC, LOW-GRADE INFLAMMATION), DISCUSSIONS OF NATURAL VIS-A-VIS BUILT ENVIRONMENTS ARE NOT MERELY FODDER FOR INTELLECTUAL CURIOSITY. HERE, WE ARGUE FOR INCREASED INTERDISCIPLINARY COLLABORATION WITH THE AIM OF BETTER UNDERSTANDING THE MECHANISMS-INCLUDING AEROBIOLOGICAL AND EPIGENETIC-THAT MIGHT HELP EXPLAIN SOME OF THE NOTED POSITIVE HEALTH OUTCOMES. IT IS OUR CONTENTION THAT SOME OF THESE MECHANISMS ARE RELATED TO ECODIVERSITY (I.E., THE SUM OF BIODIVERSITY AND GEODIVERSITY, INCLUDING BIOTIC AND ABIOTIC CONSTITUENTS). WE ALSO ENCOURAGE RESEARCHERS TO MORE CLOSELY EXAMINE INDIVIDUAL NATURE RELATEDNESS AND HOW IT MIGHT INFLUENCE MANY OUTCOMES THAT ARE AT THE INTERFACE OF LIFESTYLE HABITS AND CONTACT WITH ECODIVERSITY. 2016 20 49 16 A CURRENT GENETIC AND EPIGENETIC VIEW ON HUMAN AGING MECHANISMS. THE PROCESS OF AGING IS ONE OF THE MOST COMPLEX AND INTRIGUING BIOLOGICAL PHENOMENONS. AGING IS A GENETICALLY REGULATED PROCESS IN WHICH THE ORGANISM'S MAXIMUM LIFESPAN POTENTIAL IS PRE-DETERMINED, WHILE THE RATE OF AGING IS INFLUENCED BY ENVIRONMENTAL FACTORS AND LIFESTYLE. CONSIDERING THE COMPLEXITY OF MECHANISMS INVOLVED IN THE REGULATION OF AGING PROCESS, UP TO THIS DATE THERE ISN'T A MAJOR, UNIFYING THEORY WHICH COULD EXPLAIN THEM. AS GENETIC/EPIGENETIC AND ENVIRONMENTAL FACTORS BOTH INEVITABLY INFLUENCE THE AGING PROCESS, HERE WE PRESENT A REVIEW ON THE GENETIC AND EPIGENETIC REGULATION OF THE MOST IMPORTANT MOLECULAR AND CELLULAR MECHANISMS INVOLVED IN THE PROCESS OF AGING. BASED ON THE STUDIES ON OXIDATIVE STRESS, METABOLISM, GENOME STABILITY, EPIGENETIC MODIFICATIONS AND CELLULAR SENESCENCE IN ANIMAL MODELS AND HUMANS, WE GIVE AN OVERVIEW OF KEY GENETIC AND MOLECULAR PATHWAYS RELATED TO AGING. AS MOST OF GENETIC MANIPULATIONS WHICH INFLUENCE THE AGING PROCESS ALSO AFFECT REPRODUCTION, WE DISCUSS AGING IN HUMANS AS A POST-REPRODUCTIVE GENETICALLY DETERMINED PROCESS. AFTER THE AGE OF REPRODUCTIVE SUCCESS, AGING CONTINOUSLY PROGRESSES WHICH CLINICALLY COINCIDES WITH THE ONSET OF MOST CHRONIC DISEASES, CANCERS AND DEMENTIONS. AS EVOLUTION SHAPES THE GENOMES FOR REPRODUCTIVE SUCCESS AND NOT FOR POST-REPRODUCTIVE SURVIVAL, AGING COULD BE DEFINED AS A PROTECTIVE MECHANISM WHICH ENSURES THE PRESERVATION AND PROGRESS OF SPECIES THROUGH THE MODIFICATION, TRASMISSION AND IMPROVEMENT OF GENETIC MATERIAL. 2009