[The impact of today's environment on allergies: can we take action?] / Incidence de l'environnement actuel sur les allergies : peut-on agir ?

Allergic diseases have risen sharply in recent decades. After some epidemiological data, we take a look at the various hypotheses explaining this allergy "epidemic". Changes in our environment, such as pollution, are a source of climate change and an increase in allergic diseases through inflammation of epithelial barriers. Allergy prevention, a public health emergency, relies on environmental actions at both individual and collective levels.

[Multigenerational epigenetic inheritance in human: the past, present and perspectives]. / L'héritage épigénétique multigénérationnel chez l'Homme : le passé, le présent et les perspectives.

Nowadays, a growing body of evidence suggests that the developmental programs of each individual could be modified. The acquired new phenotypic changes could be persistent throughout the individual's life and even transmitted to the next generation. While the exact mechanism for that preservation is not well understood yet, there are many evidences showing that epigenetic alterations, which are robust and dynamic in response to the influence of the environmental factors, could be responsible for that inheritance. A growing number of external factors such as social stress, environmental pollution and climate changes make adaptation to these environmental changes rather challenging. According to the Developmental Origin of Human Disease theory, formulated by David Barker, environmental conditions experienced during the first phases of development can have long term effects on later phases of life. This phenomenon is linked to the biological plasticity of development, which allows reprogramming of physiological functions in response to different stimuli. Consequently, in utero exposure to environmental pollutants can increase predisposition to different pathologies that can occur both in early and later phases of life not only in the living generation but also in subsequent ones. Here, we have summarised some findings in human epigenetic research studies performed for the past few years which address the question whether transgenerational effects observed in model organisms could also occur in humans.

Title: L'héritage épigénétique multigénérationnel chez l'Homme : le passé, le présent et les perspectives. Abstract: De nos jours, de nombreuses études suggèrent que les programmes de développement de chaque individu seraient susceptibles d'être modifiés. Les changements phénotypiques acquis pourraient persister tout au long de la vie de l'individu et même être transmis à la génération suivante. Bien que le mécanisme exact de cette préservation ne soit pas encore bien compris, de nombreuses observations suggèrent que les altérations épigénétiques en réponse à l'influence des facteurs environnementaux seraient responsables de cette hérédité. Le nombre croissant de facteurs externes tels que le stress social, la pollution environnementale et les changements climatiques rend difficile l'adaptation à ce nouvel environnement. Selon la théorie de l'origine développementale des maladies humaines, formulée par David Barker, les conditions environnementales rencontrées au cours des premières phases du développement peuvent avoir des effets à long terme sur les phases ultérieures de la vie. Ce phénomène est lié à la plasticité biologique du développement, qui permet une reprogrammation des fonctions physiologiques en réponse à différents stimuli. L'exposition in utero à des polluants environnementaux accroîtrait la prédisposition à des pathologies survenant dans les phases précoces et tardives de la vie, non seulement pour les générations présentes mais aussi les suivantes. Nous avons résumé ici des résultats d'études épidémiologiques et épigénétiques menées ces dernières années sur des données humaines afin de savoir si les effets transgénérationnels observés dans des organismes modèles peuvent également exister chez l'homme.

[Epigenetics, principles and examples of applications]. / Épigénétique, principes et exemples d'applications.

Since the discovery of DNA as the support of genetic information, the challenge for generations of life scientists was to understand the mechanisms underlying the process that translate the sequence of a gene to a phenotype. In the 1950s, the concept of epigenetics was defined by the British biologist Conrad H. Waddington as the study of "epigenesis" that governs the biological processes involved in the development of any organism. The term epigenetics, now best defined as "above the DNA sequence" reflects the gene-environment interactions by which genes determine traits. Since, its first description, studies underlying the mechanisms involved in these processes has led to an increasing understanding of the regulation all genome transactions such as transcription, replication, repair and the biological pathways coordinated by these mechanisms. We will discuss here the main principles regulating epigenetic processes, their roles in physiology, their evolution over the life time and their implications in medicine.

[Epigenetics and myopia: Mechanisms and therapeutic targets]. / Épigénétique et myopie : mécanismes et perspectives thérapeutiques.

The development of myopia is influenced by multiple environmental and genetic factors. A third component, epigenetics, may shed light on some of the relationships between environmental and genetic factors. Epigenetics is defined as the study of modulations of gene activity that can be transmitted over cell divisions without involving mutation of the DNA sequence. Methylation is one of the main mechanisms by which gene expression is decreased. In the context of myopia, the study of epigenetic mechanisms also contributes to the understanding of the involvement of candidate genetic variants. The analysis of metabolic and signalling pathways associated with ocular development enables discussion of the biological significance associated with these candidate genes. A better understanding of epigenetic mechanisms would allow individual risk estimations for myopia and probably targeting of therapeutic interventions at a population level. Measuring the level of DNA methylation at candidate gene sites could be used to monitor the effectiveness of myopia prevention measures such as reducing near work and increasing outdoor activity. More specifically, one could consider activating the methylation of myopia promoter genes or, on the contrary, inhibiting the methylation of myopia repressor genes. Finally, the control of metabolic and signalling pathways could be considered by targeting, for example, the regulation of the G protein signalling pathway (RGS 2) with the expression of the adenosine A2a receptor (AdoRs).

Archetype and epigenetics - approximations: contributions of epigenetics to the clinical practice of analytical psychology.

In this paper we address the question of epigenetics by evidencing some mechanisms related to gene expression, which, we understand, can in a way be used as metaphors for movements occurring during the psychotherapeutic process. The possibility of a dialogue between epigenetics and analytical psychology begins with the hereditary and archetypal question and takes shape in the dimension of the analytical encounter. Through the Jungian attitude model, we propose a way of moving between the two sciences. This paper provides a brief review of the concept of archetype, covering recent publications. It then describes the main mechanisms of epigenetics and, finally, addresses the analytical process and presents the authors' proposal to consider the archetypal expression in the light of epigenetics.

Dans cet article nous étudions la question de l'épigénétique en montrant quelques mécanismes en lien avec l'expression d'un gène. Nous pensons que, d'une certaine manière, ces mécanismes peuvent être utilisés en tant que métaphores des mouvements qui se produisent durant le processus thérapeutique. La possibilité d'un dialogue entre l'épigénétique et la psychologie analytique commence par la question héréditaire et archétypale, et prend forme dans la dimension de la rencontre analytique. A travers le modèle de l'attitude Jungienne nous proposons une manière de circuler d'une science à l'autre. Cet article offre un bref examen du concept d'archétype, couvrant les publications récentes. Il décrit ensuite les mécanismes principaux de l'épigénétique et s'occupe finalement du processus analytique en présentant la proposition de l'auteur qui est de considérer l'expression archétypale à la lumière de l'épigénétique.

En este trabajo abordamos el tema de la epigenética al evidenciar algunos mecanismos relacionados con la expresión genética, la cual puede ser utilizada como metáforas para los movimientos que suceden durante el proceso terapéutico. La posibilidad de un diálogo entre epigenética y psicología analítica comienza con la pregunta sobre la herencia y el arquetipo y toma forma en la dimensión del encuentro analítico. A través del modelo de actitud analítica, proponemos una forma de movimiento entre dos ciencias. El presente trabajo ofrece una breve revisión del concepto de arquetipo, abarcando publicaciones recientes. Luego describe los mecanismos principales de la epigenética y finalmente, aborda el proceso analítico y presenta la propuesta de las autoras de considerar la expresión arquetípica a la luz de la epigenética.

Neste artigo, abordamos a questão da epigenética evidenciando alguns mecanismos relacionados à expressão gênica, que, entendemos, podem de certa forma ser usados como metáforas para movimentos que ocorrem durante o processo terapêutico. A possibilidade de um diálogo entre epigenética e psicologia analítica começa com a questão hereditária e arquetípica e toma forma na dimensão do encontro analítico. Através do modelo de atitude junguiana, propomos uma maneira de nos mover entre duas ciências. Este artigo fornece uma breve revisão do conceito de arquétipo, abrangendo publicações recentes. Em seguida, descreve os principais mecanismos da epigenética e, finalmente, aborda o processo analítico e apresenta a proposta do autor de considerar a expressão arquetípica à luz da epigenética.

Epigenetics and the return to the great mother archetype.

Epigenetics is the study of how signals from the environment can change gene expression through the creation of molecules and chemical bonds that can last a lifetime and, therefore, determine the phenotype (the characteristics of the individual resulting from the interaction of their genotype [genes] with their environment). Research in this field began at McGill University, Canada, where it was observed that rats' mothers who were more nurturing raised more resilient pups. Since then, many studies have been carried out with animals and humans, showing the link between epigenetic changes and the experience of the great mother archetype - with potential consequences for the emotional life of the individual and for society.

L'épigénétique est l'étude de comment les signaux provenant de l'environnement peuvent changer l'expression des gènes, par la création de molécules et de liens chimiques qui peuvent durer toute la vie et qui, de ce fait, déterminent le phénotype. La recherche dans ce domaine a commencé à l'université McGill au Canada: il y a été observé que les mères de rats plus maternelles élevaient des jeunes plus résilients. Depuis, de nombreuses études ont été menées avec des animaux et des humains, montrant le lien entre les changements épigénétiques et l'expérience de l'archétype de la grande mère, avec des conséquences potentielles pour la vie émotionnelle de l'individu et pour la société.

La epigenética es el estudio de cómo señales del medio ambiente pueden modificar la expresión genética, a través de la creación de moléculas y enlaces químicos que pueden durar toda la vida y, por lo tanto, determinar el fenotipo. Las investigaciones en este campo comenzaron en la Universidad McGill, en Canadá, donde fue observado que las madres de ratas que fueron más nutricias criaban crías más resilientes. Desde entonces, se han llevado a cabo muchos estudios con animales y humanos, mostrando el vínculo entre los cambios epigenéticos y la experiencia del arquetipo de la Gran Madre - con consecuencias potenciales para la vida emocional del individuo y de la sociedad.

A epigenética é o estudo de como o ambiente pode interferir na expressão gênica, através de moléculas e ligações químicas que podem durar por toda a vida e, portanto, determinar o fenótipo. Todas as pesquisas começaram na universidade McGill, onde observou-se que ratas mais cuidadosas, maior comportamento de limpar e lamber os filhotes, acabavam por desenvolver filhotes com mais resiliência. Desde então muitas pesquisas foram realizadas com animais e seres humanos evidenciando a ligação entre epigenética e a experiência dentro do arquétipo da grande mãe e suas potenciais consequências para com os aspectos emocionais do indivíduo e da sociedade.

43rd International Asilomar Chromatin, Chromosomes, and Epigenetics Conference.

The 43rd Asilomar Chromatin, Chromosomes, and Epigenetics Conference was held in an entirely online format from 9 to 11 December 2021. The conference enabled presenters at various career stages to share promising new findings, and presentations covered modern chromatin research across an array of model systems. Topics ranged from the fundamental principles of nuclear organization and transcription regulation to key mechanisms underlying human disease. The meeting featured five keynote speakers from diverse backgrounds and was organized by Juan Ausió, University of Victoria (British Columbia, Canada), James Davie, University of Manitoba (Manitoba, Canada), Philippe T. Georgel, Marshall University (West Virginia, USA), Michael Goldman, San Francisco State University (California, USA), LeAnn Howe, The University of British Columbia (British Columbia, Canada), Jennifer A. Mitchell, University of Toronto (Ontario, Canada), and Sally G. Pasion, San Francisco State University (California, USA).

Introgressed DNA within a Zea mays near-isogenic line displays lower levels of 24nt sRNA expression than the homologous region from the recurrent parent.

Near-isogenic lines (NILs) are classical genetic tools used to dissect the actions of an allele when placed in a uniform genetic background. Although the goal of NIL creation is to examine the effects of a single allele in isolation, DNA linked to the allele is invariably retained and can confound any allele-specific effects. In addition to genetic variation, highly polymorphic species such as Zea mays will contain introgressed polymorphisms encompassing transposable elements (TEs) and the cis-acting small RNA (sRNA) that represses them. Through transcriptomics, we described the differences in sRNA and TE transcriptional expression between a W22-derived introgression and its homologous B73 region. As anticipated, many differences in sRNA expression were observed. Unexpectedly, however, 24nt sRNA expression over the introgressed region was low overall compared to both the homologous B73 region and the rest of the genome. Across the introgression, low sRNA expression was accompanied by increased TE transcription. Possible explanations for the observed trends in sRNA and TE expression across the introgression region are discussed. These findings support the notion that any introgressed allele is in an epigenetic environment distinct from that found at the allele from the recurrent parent. Additionally, these results suggest that further study of sRNA expression levels during the introgression process is warranted.

Substitution of histone H3 arginine 72 to alanine leads to the deregulation of isoleucine biosynthesis in the budding yeast Saccharomyces cerevisiae.

Histone residues play an essential role in the regulation of various biological processes. In the present study, we utilized the H3/H4 histone mutant library to probe the functional aspects of histone residues in amino acid biosynthesis. We found that the histone residue H3R72 plays a crucial role in the regulation of isoleucine biosynthesis. Substitution of the arginine residue (H3R72) of histone H3 to alanine (H3R72A) renders yeast cells unable to grow in minimal medium. Histone mutant H3R72A requires external supplementation of either isoleucine, serine, or threonine for growth in minimal medium. We also observed that the H3R72 residue and leucine amino acid in synthetic complete medium might play a crucial role in determining the intake of isoleucine and threonine in yeast. Furthermore, gene deletion analysis of ILV1 and CHA1 in the H3R72A mutant confirmed that isoleucine is the sole requirement for growth in minimal medium. Altogether, we have identified that histone H3R72 residue may be crucial for yeast growth in minimal medium by regulating isoleucine biosynthesis through the Ilv1 enzyme in the budding yeast Saccharomyces cerevisiae.

Epigenetic mechanisms influencing COVID-19.

The COVID-19 pandemic is one of the most significant public health threats in recent history and has impacted the lives of almost everyone worldwide. Epigenetic mechanisms contribute to many aspects of the SARS-CoV-2 replication cycle, including expression levels of viral receptor ACE2, expression of cytokine genes as part of the host immune response, and the implication of various histone modifications in several aspects of COVID-19. SARS-CoV-2 proteins physically associate with many different host proteins over the course of infection, and notably there are several interactions between viral proteins and epigenetic enzymes such as HDACs and bromodomain-containing proteins as shown by correlation-based studies. The many contributions of epigenetic mechanisms to the viral life cycle and the host immune response to infection have resulted in epigenetic factors being identified as emerging biomarkers for COVID-19, and project epigenetic modifiers as promising therapeutic targets to combat COVID-19. This review article highlights the major epigenetic pathways at play during COVID-19 disease and discusses ongoing clinical trials that will hopefully contribute to slowing the spread of SARS-CoV-2.

Gut microbiome-mediated epigenetic regulation of brain disorder and application of machine learning for multi-omics data analysis.

The gut-brain axis (GBA) is a biochemical link that connects the central nervous system (CNS) and enteric nervous system (ENS). Clinical and experimental evidence suggests gut microbiota as a key regulator of the GBA. Microbes living in the gut not only interact locally with intestinal cells and the ENS but have also been found to modulate the CNS through neuroendocrine and metabolic pathways. Studies have also explored the involvement of gut microbiota dysbiosis in depression, anxiety, autism, stroke, and pathophysiology of other neurodegenerative diseases. Recent reports suggest that microbe-derived metabolites can influence host metabolism by acting as epigenetic regulators. Butyrate, an intestinal bacterial metabolite, is a known histone deacetylase inhibitor that has shown to improve learning and memory in animal models. Due to high disease variability amongst the population, a multi-omics approach that utilizes artificial intelligence and machine learning to analyze and integrate omics data is necessary to better understand the role of the GBA in pathogenesis of neurological disorders, to generate predictive models, and to develop precise and personalized therapeutics. This review examines our current understanding of epigenetic regulation of the GBA and proposes a framework to integrate multi-omics data for prediction, prevention, and development of precision health approaches to treat brain disorders.

Epigenetic regulation of ACE2, the receptor of the SARS-CoV-2 virus1.

The angiotensin-converting enzyme 2 (ACE2) is the receptor for the three coronaviruses HCoV-NL63, SARS-CoV, and SARS-CoV-2. ACE2 is involved in the regulation of the renin-angiotensin system and blood pressure. ACE2 is also involved in the regulation of several signaling pathways, including integrin signaling. ACE2 expression is regulated transcriptionally and post-transcriptionally. The expression of the gene is regulated by two promoters, with usage varying among tissues. ACE2 expression is greatest in the small intestine, kidney, and heart and detectable in a variety of tissues and cell types. Herein we review the chemical and mechanical signal transduction pathways regulating the expression of the ACE2 gene and the epigenetic/chromatin features of the expressed gene.

Hyperhomocysteinemia: an instigating factor for periodontal disease.

Hyperhomocysteinemia (HHcy) affects bone remodeling, since a destructive process in cortical alveolar bone has been linked to it; however, the mechanism remains at large. HHcy increases proinflammatory cytokines viz. TNF-α, IL-1b, IL-6, and IL-8 that leads to a cascade that negatively impacts methionine metabolism and homocysteine cycling. Further, chronic inflammation decreases vitamins B12, B6, and folic acid that are required for methionine homocysteine homeostasis. This study aims to investigate a HHcy mouse model (cystathionine ß-synthase deficient, CBS+/-) for studying the potential pathophysiological changes, if any, in the periodontium (gingiva, periodontal ligament, cement, and alveolar bone). We compared the periodontium side-by-side in the CBS+/- model with that of the wild-type (C57BL/6J) mice. Histology and histomorphometry of the mandibular bone along with gene expression analyses were carried out. Also, proangiogenic proteins and metalloproteinases were studied. To our knowledge, this research shows, for the first time, a direct connection between periodontal disease during CBS deficiency, thereby suggesting the existence of disease drivers during the hyperhomocysteinemic condition. Our findings offer opportunities to develop diagnostics/therapeutics for people who suffer from chronic metabolic disorders like HHcy.

The impact of sex and gender on heart-brain axis dysfunction: current concepts and novel perspectives.

The heart-brain axis (HBA) recapitulates all the circuits that regulate bidirectional flow of communication between heart and brain. Several mechanisms may underlie the interdependent relationship involving heterogeneous tissues at rest and during specific target organ injury such as myocardial infarction, heart failure, arrhythmia, stroke, mood disorders, or dementia. In-depth translational studies of the HBA dysfunction under single-organ injury should include both male and female animals to develop sex- and gender-oriented prevention, diagnosis, and treatment strategies. Indeed, sex and gender are determining factors as females and males exhibit significant differences in terms of susceptibility to risk factors, age of onset, severity of symptoms, and outcome. Despite most studies having focused on the male population, we have conducted a careful appraisal of the literature investigating HBA in females. In particular, we have (i) analyzed sex-related heart and brain illnesses, (ii) recapitulated the most significant studies simultaneously conducted on cardio- and cerebro-vascular systems in female populations, and (iii) hypothesized future perspectives for the development of a gender-based approach to HBA dysfunction. Although sex- and gender-oriented research is at its infancy, the impact of sex on HBA dysfunction is opening unexpected new avenues for managing the health of female subjects exposed to risk of lifestyle multi-organ disease.

The treatment of SARS-CoV2 with antivirals and mitigation of the cytokine storm syndrome: the role of gene expression.

In the absence of a vaccine, the treatment of SARS-CoV2 has focused on eliminating the virus with antivirals or mitigating the cytokine storm syndrome (CSS) that leads to the most common cause of death: respiratory failure. Herein we discuss the mechanisms of antiviral treatments for SARS-CoV2 and treatment strategies for the CSS. Antivirals that have shown in vitro activity against SARS-CoV2, or the closely related SARS-CoV1 and MERS-CoV, are compared on the enzymatic level and by potency in cells. For treatment of the CSS, we discuss medications that reduce the effects or expression of cytokines involved in the CSS with an emphasis on those that reduce IL-6 because of its central role in the development of the CSS. We show that some of the medications covered influence the activity or expression of enzymes involved in epigenetic processes and specifically those that add or remove modifications to histones or DNA. Where available, the latest clinical data showing the efficacy of the medications is presented. With respect to their mechanisms, we explain why some medications are successful, why others have failed, and why some untested medications may yet prove useful.

The chicken model organism for epigenomic research.

The chicken model organism has advanced the areas of developmental biology, virology, immunology, oncology, epigenetic regulation of gene expression, conservation biology, and genomics of domestication. Further, the chicken model organism has aided in our understanding of human disease. Through the recent advances in high-throughput sequencing and bioinformatic tools, researchers have successfully identified sequences in the chicken genome that have human orthologs, improving mammalian genome annotation. In this review, we highlight the importance of chicken as an animal model in basic and pre-clinical research. We will present the importance of chicken in poultry epigenetics and in genomic studies that trace back to their ancestor, the last link between human and chicken in the tree of life. There are still many genes of unknown function in the chicken genome yet to be characterized. By taking advantage of recent sequencing technologies, it is possible to gain further insight into the chicken epigenome.

[Developmental plasticity in plants: an interaction between hormones and epigenetics at the meristem level]. / La plasticité développementale chez les plantes : une interaction entre hormones et épigénétique dans les cellules souches méristématiques.

Plants are fixed organisms with continuous development throughout their life and great sensitivity to environmental variations. They react in this way by exhibiting large developmental phenotypic plasticity. This plasticity is partly controlled by (phyto)hormones, but recent studies also suggest the involvement of epigenetic mechanisms. It seems that these two factors may interact in a complex way and especially in the stem cells grouped together in meristems. The objective of this review is to present the current arguments about this interaction which would promote developmental plasticity. Three major points are thus addressed to justify this interaction between hormonal control and epigenetics (control at the chromatin level) for the developmental plasticity of plants: the arguments in favor of an effect of hormones on chromatin and vice versa, the arguments in favor of their roles on developmental plasticity and finally the arguments in favor of the central place of these interactions, the meristems. Various perspectives and applications are discussed.

TITLE: La plasticité développementale chez les plantes : une interaction entre hormones et épigénétique dans les cellules souches méristématiques. ABSTRACT: Les plantes sont des organismes fixés dont le développement est continu toute leur vie et qui ont une grande sensibilité aux variations environnementales. Elles réagissent ainsi en manifestant une importante plasticité phénotypique développementale. Cette plasticité est contrôlée pour partie par les (phyto)hormones mais des résultats récents suggèrent également l'implication des mécanismes épigénétiques. Ces deux facteurs interagiraient de manière complexe et notamment dans les cellules souches regroupées au niveau des méristèmes. L'objectif de cette revue est de présenter les arguments actuels concernant cette interaction qui favoriserait la plasticité développementale. Trois points majeurs sont ainsi abordés pour justifier cette interaction entre le contrôle hormonal et l'épigénétique (contrôle au niveau de la chromatine) pour la plasticité développementale des plantes : les arguments en faveur d'un effet des hormones sur la chromatine et vice-versa, les arguments en faveur de leurs rôles sur la plasticité développementale et enfin les arguments en faveur du lieu central de ces interactions, les méristèmes. Diverses perspectives et applications sont discutées.

Beyond the genome: challenges and potential for epigenetics-driven therapeutic approaches in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a devastating disease of the cardiopulmonary system caused by the narrowing of the pulmonary arteries, leading to increased vascular resistance and pressure. This leads to right ventricle remodeling, dysfunction, and eventually, death. While conventional therapies have largely focused on targeting vasodilation, other pathological features of PAH including aberrant inflammation, mitochondrial dynamics, cell proliferation, and migration have not been well explored. Thus, despite some recent improvements in PAH treatment, the life expectancy and quality of life for patients with PAH remains poor. Showing many similarities to cancers, PAH is characterized by increased pulmonary arterial smooth muscle cell proliferation, decreased apoptotic signaling pathways, and changes in metabolism. The recent successes of therapies targeting epigenetic modifiers for the treatment of cancer has prompted epigenetic research in PAH, revealing many new potential therapeutic targets. In this minireview we discuss the emergence of epigenetic dysregulation in PAH and highlight epigenetic-targeting compounds that may be effective for the treatment of PAH.

Starting strong: Dietary, behavioral, and environmental factors that promote "strength" from conception to age 2 years.

Beginning with conception and continuing through childhood and adolescence, the word "strength" connotes the totality of optimal early bone and tissue growth; neural wiring of the brain; and acquisition of fine motor, gross motor, language, and socioemotional skills. The robustness of each of these attributes depend on 3 critical epigenetic (external) factors: the quality of nutrition; positive adult nurturing; and experiences acquired within a stimulating, safe environment that affords free exploration. This review highlights the relationship between the epigenetic factors in the period of conception to age 2 years and a child's future health, cognitive capacity, and social aptitude, which collectively comprise their "strength". This paper was presented as part of the 2018 Strength Summit conference entitled, The Role of Strength in Optimal Health and Well-being. Novelty Strength in infants signifies the totality of optimal early growth and neural wiring of the brain. Strength at this life stage also includes the acquisition of motor, language, and socioemotional skills. Three epigenetic factors are critical during birth to 24 months: nutrition, nurturing, and free exploration.