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This article seeks to address what the work of Catherine Malabou can offer to the thinking and understanding of history. Characterizing Malabou's intellectual project as a meditation on the relation between history and possible knowledge, it situates the philosopher's work in the tradition of historical epistemology. It will be argued that, in its engagement with philosophical and (neuro)biological theories of plasticity and epigenesis, the historical constitution of Malabou's philosophical system problematizes the practical and ontological difficulty behind any commitment to a historically bounded knowledge of what here will be called, following Heidegger and Foucault, 'pure finitude'. The article concludes by suggesting that, if placed alongside the work of intellectual historian Quentin Skinner, Malabou's historical epistemology makes a decisive and useful contribution to contemporary debates regarding historical method by underscoring the (neuro)biological rooting of persistent epistemic gaps between historical understanding and experience. [ABSTRACT FROM AUTHOR]

Considering the recent epigenetic studies on the transgenerational transmission of trauma, this article aims to 1) explore its ethical implications for the concept and nature of moral damage, and 2) offer normative suggestions on collective responsibilities both synchronic and diachronic. To do so, I first address recent epigenetic studies' showing the crystallization of emotional information through generations, and second, defend that a unified approach to the concept of ghost damage may be useful to categorize this phenomenon, facilitate future research on this type of moral damage, and recognize its importance in the identification of hermeneutical injustice. Finally, I suggest that granting a right to transgenerational information may help avoid the perpetuation of inherited damage that jeopardize mental and physical health in the offspring. [ABSTRACT FROM AUTHOR]

Defining mechanisms of cardiomyocyte proliferation should guide the understanding of endogenous cardiac regeneration and could lead to novel treatments for diseases such as myocardial infarction. In the neonatal heart, energy metabolic reprogramming (phenotypic alteration of glucose, fatty acid, and amino acid metabolism) parallels cell cycle arrest of cardiomyocytes. The metabolic reprogramming occurring shortly after birth is associated with alterations in blood oxygen levels, metabolic substrate availability, hemodynamic stress, and hormone release. In the adult heart, myocardial infarction causes metabolic reprogramming but these changes cannot stimulate sufficient cardiomyocyte proliferation to replace those lost by the ischemic injury. Some putative pro-proliferative interventions can induce the metabolic reprogramming. Recent data show that altering the metabolic enzymes PKM2 [pyruvate kinase 2], LDHA [lactate dehydrogenase A], PDK4 [pyruvate dehydrogenase kinase 4], SDH [succinate dehydrogenase], CPT1b [carnitine palmitoyl transferase 1b], or HMGCS2 [3-hydroxy-3-methylglutaryl-CoA synthase 2] is sufficient to partially reverse metabolic reprogramming and promotes adult cardiomyocyte proliferation. How metabolic reprogramming regulates cardiomyocyte proliferation is not clearly defined. The possible mechanisms involve biosynthetic pathways from the glycolysis shunts and the epigenetic regulation induced by metabolic intermediates. Metabolic manipulation could represent a new approach to stimulate cardiac regeneration; however, the efficacy of these manipulations requires optimization, and novel molecular targets need to be defined. In this review, we summarize the features, triggers, and molecular regulatory networks responsible for metabolic reprogramming and discuss the current understanding of metabolic reprogramming as a critical determinant of cardiomyocyte proliferation. [ABSTRACT FROM AUTHOR]

Zing-Yang Kuo (1898–1970), hailed as China's behaviorist psychologist, earned "Out-Watsons Mr. Watson" in the international anti-instinct movement. His contributions to the field on behavioral neuroembryology (1929–1939) are often overlooked in comparison to his achievements in psychology. We retrieved the titles of all of Kuo's publications from 1929 to 1939 and examined those related to his research on the origins and development of embryonic behavioral ontogeny and the neural basis of embryonic behavior. Remarkably, Kuo concurrently focused on embryos during the same period as North American neuroembryologists. He maintained an independent stance in the debate over the sequence of behavioral ontogeny, represented by the embryonic neuroscientists Coghill and Windle, and critically pointed out limitations in research on both sides of the debate. Drawing from his experiments with chicken embryos, Kuo proposed the theory of behavioral epigenesis, which attempted to end the nature–nurture dichotomy and promote the transformation of the research path of behavioral embryology from elementary physiological anatomy toward a deep "comprehensive science." Kuo's achievements directly laid the foundation for the interdisciplinary field of developmental psychobiology, constructing a new conceptual framework for the systematic analysis of behavioral development and promoting the establishment and development of a new approach to epiphenotype epigenetics. [ABSTRACT FROM AUTHOR]

The idea that birds are maniraptoran theropod dinosaurs is now considered an evolutionary consensus. An "open" (i.e., completely or substantially perforate) acetabulum is considered an important synapomorphy verifying the bird–dinosaur nexus. Here, I present anatomical evidence from the acetabulum and its important appurtenances, the supracetabular crest and the antitrochanter, that hip anatomy differs substantially between dinosaurs and birds. Given the thin bone of the acetabular walls and the varied tissue, both hard and soft, in the acetabular region and especially the lower part of the basin, it is apparent that many avian skeletons exhibit some anatomical loss of soft tissue and thin bone, some perhaps related to changes in gait, but also in part related to the dramatic trend in bone reduction associated with flight, especially in more advanced crown taxa. Many basal birds and early diverging neornithines tend to have a nearly closed or partially closed acetabula, thus rendering the current terms "open" or "closed" acetabula inaccurate; they should be modified or replaced. Given new evidence presented here, the relationship of "dinosaurs" and birds must be re-evaluated. [ABSTRACT FROM AUTHOR]

Bleomycin (BL) is a widely used anticancer drug that can cause pulmonary fibrosis due to increased fibroblast proliferation and increased secretion of extracellular matrix. RASSF1A is a tumor suppressor gene that is down-regulated by DNA methylation during fibrosis. Disulfiram (DSF), a noncytosine DNA methyltransferase inhibitor, can revert epigenetic biomarkers and re-express silenced genes. We investigated anti-inflammatory and anti-fibrotic effects of DSF on regulation of epigenetic molecules and histopathology in a rat model of BL induced pulmonary fibrosis. We used six groups of rats: sesame oil (SO) control (Co) group, BL group, BL + SO group and three BL + DSF groups administered 1 mg/kg DSF (BL + DSF), 10 mg/kg DSF (BL + DSF10) or 100 mg/kg DSF (BL + DSF100), respectively. BL was administered intratracheally to induce pulmonary fibrosis. DSF and SO were injected intraperitoneally (i.p.) 2 days before BL administration; these injections were continued for 3 weeks. At the end of the study, lung tissues were removed for molecular and histopathologic studies. Administration of 10 or 100 mg/kg DSF after BL induced pulmonary inflammation and fibrosis, and up-regulated RASSF1A and down-regulated TNF-α and IL-1 β compared to the BL and BL + SO groups. A RASSF1A unmethylated band was observed using the methylation-specific PCR technique in rats that had been administered 10 and 100 mg/kg DSF, which indicated partial DNA demethylation. Histopathologic evaluation revealed that fibrosis and all inflammatory scores were decreased significantly in the BL + DSF10 and BL + DSF100 groups compared to the BL group. Our findings indicate that DSF modified DNA methylation by up-regulating RASSF1A, which reduced inflammation and fibrosis in BL induced pulmonary inflammation and fibrosis. [ABSTRACT FROM AUTHOR]

The article presents the results of studies of postsedimentary processes in Silurian carbonate rocks of the central part of the Chernyshev Ridge. A complex combination of secondary transformations in carbonate reservoir is shown. The sedimentary sequences show manifestations of regional and superimposed lithogenesis. In addition to stagewise catagenetic changes, the sediments were also subjected to regressive infiltration catagenesis (epigenesis), which was accompanied by leaching and dolomitization of limestone. All this significantly affected the filtration–capacitive properties. The obtained data can contribute to the identification of new objects for exploration drilling and optimization of exploration works in complex regions. [ABSTRACT FROM AUTHOR]

The identity of germ cells, the progenitors of life, is thought to be acquired by two modes; either by maternal signals (preformed) or induced de novo from pluripotent cells (epigenesis) in the developing embryos. However, paternal roles seem enshrouded or completely overlooked in this fundamental biological process. Hence, we investigated the presence of germplasm transcripts in the sperm of Gambusia holbrooki , a live-bearing fish, demonstrating their presence and suggesting paternal contributions. Interestingly, not all germplasm markers were present (nanos1 and tdrd6) in the sperm, but some were conspicuous (dazl , dnd-α , piwi II , and vasa), indicating that the latter is required for establishing germ cell identity in the progeny, with a possible parent-specific role. Furthermore, there were also spatial differences in the distribution of these determinants, suggesting additional roles in sperm physiology and/or fertility. Our results support the hypothesis that dads also play a vital role in establishing the germ cell identity, especially in G. holbrooki , which shares elements of both preformation and induction modes of germline determination. This, coupled with its life history traits, makes G. holbrooki an excellent system for dissecting evolutionary relationships between the two germline determination modes, their underpinning mechanisms and ultimately the perpetuity of life. [Display omitted] • First study to show evidence for paternal determinants of germ cell specification. • Spatial pattern of the determinants implies roles beyond germ cell specification. • Validates retention of both modes of germplasm specification in this species. • The study collectively highlights utility of G. holbrooki as a developmental model. [ABSTRACT FROM AUTHOR]

New insights in epigenetics have declared depression a genetic malady. For psychiatric disorders, the evaluation of the epigenetic basis influenced by environmental insults showed a deeper understanding of complex multifactorial psychiatric disorders like Major depressive disorder (MDD). The WHO 2008 report has ranked MDD globally as the third leading cause of burden of diseases and predicted it to be the number one by 2030. Eight hallmarks of insults that lead to MDD are contaminated air, soil, food/water, ecological stressors, chemicals in households, occupational hazards, and food or diet linked to the absence of essential nutrients. Epigenetics, according to the National Human Genome Research Institute, refers to changes in gene function causing their activation or deactivation without any alteration in DNA sequence. Epigenetics include histone modifications, DNA methylations, miRNAs and lncRNAs. Hypermethylation of the serotonin transporter gene has been consistently found in loci encoding Brain-derived neurotrophic factors (BDNF) and SLC6A4. During pregnancy, fetal epigenetic reprogramming may occur due to maternal stress and nutritional restriction. Increased cortisol or malnutrition in mothers, down-regulate the cortisol enzyme, decreasing its expression in the fetal cortex, making these children four times more at risk of stress later in life. Histone modifications, including methylation and acetylation at the lysine moiety during posttranslational modifications, affect neurons in the CNS significantly, leading to the pathophysiology of MDD. Dysregulation of miRNAs and lncRNAs cause negative neural plasticity, stress responses, neurotrophic factors expression, neuroinflammation, neurotransmission, the hypothalamic-pituitary-adrenal axis (HPA axis), neurogenesis and gliogenesis and neural stem cell maintenance. Among epigenetic multifactorial disorders, psychiatric ailments have received more prominence in etiology than other diseases. [ABSTRACT FROM AUTHOR]

Background: Preterm infants are uniquely vulnerable to early toxic stress exposure while in the neonatal intensive care unit (NICU) and also being at risk for suboptimal neurodevelopmental outcomes. However, the complex biological mechanisms responsible for variations in preterm infants' neurodevelopmental outcomes because of early toxic stress exposure in the NICU remain unknown. Innovative preterm behavioral epigenetics research offers a possible mechanism and describes how early toxic stress exposure may lead to epigenetic alterations, potentially affecting short- and long-term outcomes. Objective: The aim of this study was to review the relationships between early toxic stress exposures in the NICU and epigenetic alterations in preterm infants. The measurement of early toxic stress exposure in the NICU and effect of epigenetic alterations on neurodevelopmental outcomes in preterm infants were also examined. Methods: We conducted a scoping review of the literature published between January 2011 and December 2021 using databases PubMed, CINAHL, Cochrance Library, PsycINFO, and Web of Science. Primary data-based research that examined epigenetics, stress, and preterm infants or NICU were included. Results: A total of 13 articles from nine studies were included. DNA methylations of six specific genes were studied in relation to early toxic stress exposure in the NICU: SLC6A4, SLC6A3, OPRMI, NR3C1, HSD11B2 , and PLAGL1. These genes are responsible for regulating serotonin, dopamine, and cortisol. Poorer neurodevelopmental outcomes were associated with alterations in DNA methylation of SLC6A4, NR3C1 , and HSD11B2. Measurements of early toxic stress exposure in the NICU were inconsistent among the studies. Discussion: Epigenetic alterations secondary to early toxic stress exposures in the NICU may be associated with future neurodevelopmental outcomes in preterm infants. Common data elements of toxic stress exposure in preterm infants are needed. Identification of the epigenome and mechanisms by which early toxic stress exposure leads to epigenetic alterations in this vulnerable population will provide evidence to design and test individualized intervention. [ABSTRACT FROM AUTHOR]

Parasitism of mice by Toxoplasma gondii reduces the host's aversion to cat odours, likely increasing predation and transmission of the parasite to its definitive host. This behavioural change suggests a parasitic manipulation where host behaviour becomes an extended phenotype of the parasite.Independently, epigenetic changes within an organism are now known to create behavioural change.The results described here provide an experimental connection between these disparate strands of extended phenotypes and the role of epigenetics in behavioural diversity.Using mice captured on Kangaroo Island in Australia, we demonstrate that Toxoplasma gondii infection leads to specific DNA hypomethylation events in the host brain.Previous laboratory studies have shown that these epigenetic changes underlie the central processing of cat odours. We posit that the concept of extended phenotype can be expanded to extended epiphenotype, thus linking parasite genes to host behaviour through epigenesis. This phenomenon has broad implications for inter‐species relationships. Read the free Plain Language Summary for this article on the Journal blog. [ABSTRACT FROM AUTHOR]

This article describes and analyzes various aspects related to the neurobiology of disorganized attachment (DA), which is associated with personality, eating, affective, dissociative, and addictive disorders. We included primary studies in humans, published in PubMed from 2000 to 2022. Eight genetic and one epigenetic study were considered. Three molecular studies describe possible roles of oxytocin and cortisol, seven neurophysiological studies investigated functional correlates, and five morphological studies describe anatomical changes. Findings in candidate genes involved in dopaminergic, serotonergic, and oxytonergic systems have not been able to be replicated in large-scale human studies. Alterations in the functioning of cortisol and oxytocin are preliminary. Neurophysiological studies show changes in subcortical structures (mainly in the hippocampus) and occipital, temporal, parietal, and insular cortices. Since there is a lack of robust evidence on the neurobiology of DA in humans, the possible inferences of these studies are preliminary, which restricts their translation to clinical parameters. [ABSTRACT FROM AUTHOR]

Context • Mainstream explicative paradigms on biological evolution are currently open to discussion. > Problem • As Maturana and I have previously argued, an organism-centered view of biological evolution needs to be developed. > Method • I reassess the main biological phenomena from a systemic-dynamic perspective. > Results • Behavior, and not genetics, is the main factor driving the course of structural changes of organisms, in both ontogeny and phylogeny. > Implications • The conceptual view developed in this article should lead to a critical appraisal of the fundaments of current mainstream thinking on biological evolution. > Constructivist content • The concept of natural drift explicated in this article draws on Maturana's view on systems dynamics, historical processes, biological autonomy, recursivity, and subject-dependent reality. [ABSTRACT FROM AUTHOR]

Paleo-karst controls reservoirs in the fourth member of the Sinian Dengying formation in the Sichuan Basin. It is crucial to characterize the paleo-karst zone architecture to understand better the distribution of reservoirs controlled by the multi-stage ancient water tables. We divide vertical paleo-karst zones using cores and formation micro-scanner images based on the groundwater movement and development of pores and fractures. Then we analyze positions and variations of paleo-karst water tables according to the characteristics of different paleo-karst zones. Besides, we illustrate the distribution of underflow subzones and the development of reservoirs in each subzone. This paper reveals the relationship between paleo-karst landform relative elevation, paleo-karst zone thickness and reservoir thickness. Thus, we build the paleo-karst evolutionary pattern in the study area. Research suggests that vadose, underflow, and slow flow zones develop in the intended interval. We identify four underflow subzones in response to four paleo-karst water tables. Compared with the vadose zone, the underflow zone is thicker and holds more reservoirs, mainly distributed in the upper part of the single underflow subzone. Higher paleo-karst landform can possess a thicker vadose zone and thinner underflow zone. Besides, an excellent positive linear correlation exists between reservoir thickness and paleo-karst zone thickness. The thickness of the subzone constrains the development of reservoirs in it. The second and third underflow subzones are the most favorable intervals, owning more reservoirs. [ABSTRACT FROM AUTHOR]

Medically assisted reproduction, now considered a routine, successful treatment for infertility worldwide, has produced at least 8 million live births. However, a growing body of evidence is pointing toward an increased incidence of epigenetic/imprinting disorders in the offspring, raising concern that the techniques involved may have an impact on crucial stages of early embryo and fetal development highly vulnerable to epigenetic influence. In this paper, the key role of methylation processes in epigenesis, namely the essential biochemical/metabolic pathways involving folates and one-carbon cycles necessary for correct DNA/histone methylation, is discussed. Furthermore, potential contributors to epigenetics dysregulation during the three phases of assisted reproduction: preparation for and controlled ovarian hyperstimulation (COH); methylation processes during the preimplantation embryo culture stages; the effects of unmetabolized folic acid (UMFA) during embryogenesis on imprinting methyl "tags", are described. Advances in technology have opened a window into developmental processes that were previously inaccessible to research: it is now clear that ART procedures have the potential to influence DNA methylation in embryonic and fetal life, with an impact on health and disease risk in future generations. Critical re-evaluation of protocols and procedures is now an urgent priority, with a focus on interventions targeted toward improving ART procedures, with special attention to in vitro culture protocols and the effects of excessive folic acid intake. [ABSTRACT FROM AUTHOR]

Compelling evidence has demonstrated that tumor bulk comprises distinctive subset of cells generally referred as cancer stem cells (CSCs) that have been proposed as a strong sustainer and promoter of tumorigenesis and therapeutic resistance. These distinguished properties of CSCs have raised interest in understanding the molecular mechanisms that govern the maintenance of these cells. Numerous experimental and epidemiological studies have demonstrated that exposure to environmental toxins such as the polycyclic aromatic hydrocarbons (PAHs) is strongly involved in cancer initiation and progression. The PAH-induced carcinogenesis is shown to be mediated through the activation of a cytosolic receptor, aryl hydrocarbon receptor (AhR)/Cytochrome P4501A pathway, suggesting a possible direct link between AhR and CSCs. Several recent studies have investigated the role of AhR in CSCs self-renewal and maintenance, however the molecular mechanisms and particularly the epigenetic regulations of CSCs by the AhR/CYP1A pathway have not been reviewed before. In this review, we first summarize the crosstalk between AhR and cancer genetics, with a particular emphasis on the mechanisms relevant to CSCs such as Wnt/β-catenin, Notch, NF-κB, and PTEN-PI3K/Akt signaling pathways. The second part of this review discusses the recent advances and studies highlighting the epigenetic mechanisms mediated by the AhR/CYP1A pathway that control CSC gene expression, self-renewal, and chemoresistance in various human cancers. Furthermore, the review also sheds light on the importance of targeting the epigenetic pathways as a novel therapeutic approach against CSCs. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this paper is to describe some aspects of the intra-cellular mechanism of action of neuroleptics, drugs widely used in psychiatry in treatment of psychotic and affective disorders. The ability of neuroleptics to influence and modify the metabolic, energetic and structural processes of neurons, as well as their apoptosis, probably influence their therapeutic potential. The direct and indirect mechanisms of antipsychotics are discussed on the basis of epigenetic, intra-cellular and post-transcription processes. Views: Antipsychotic drugs facilitate chromatin remodeling, decreasing or increasing histone acetylation, and affect DNA methylation differently. Antipsychotics modulate the intracellular signaling cascades like the cyclic adenosine monophosphate (cAMP), AKT/glycogen synthase kinase-3 (GSK-3) pathway and mitogen-activated protein kinase (MAPK) in a variety of ways that contribute to their different clinical and side-effect profiles. Among the cellular processes involved in the activity of antipsychotics are energy and metabolism, protein synthesis and processing, cytoskeleton functions like microtubule dynamics, dendritic branching, and spine dynamics, as well as cell adhesion and synaptic activity. Finally, antipsychotics have the ability to modulate the expression of a large number of miRNAs, which is related to oxidative stress and metabolism. Conclusions: Despite the efficacy of antipsychotics in treating schizophrenia and bipolar disorders over the last several decades, their molecular mechanisms of action turn out to be very complex and have not yet been fully elucidated. Recent thinking about a more personalized and endophenotype-specific diagnosing and treatment requires a more advanced genomic and proteomic approach and seems to be the next step in the treatment of mental disorders. [ABSTRACT FROM AUTHOR]

Recent advances in neurobiology, paleontology, and paleogenetics allow us to associate changes in brain size and organization with threemain "moments" of increased behavioral complexity and, more speculatively, language development. First, Australopiths display a significant increase in brain size relative to the great apes and an incipient extension of postnatal brain development. However, their cortical organization remains essentially similar to that of apes. Second, over the last 2 My, with two notable exceptions, brain size increases dramatically, partly in relation to changes in body size. Differential enlargements and reorganizations of cortical areas lay the foundation for the "language-ready" brain and cumulative culture of later Homo species. Third, in Homo sapiens, brain size remains fairly stable over the last 300,000 years but an important cerebral reorganization takes place. It affects the frontal and temporal lobes, the parietal areas and the cerebellum and resulted in a more globular shape of the brain. These changes are associated, among others, with an increased development of long-distance--horizontal--connections. A few regulatory genetic events took place in the course of this hominization process with, in particular, enhanced neuronal proliferation and global brain connectivity. [ABSTRACT FROM AUTHOR]

Background: The pathogenic missense variant p.G125R in TBX5 (T-box transcription factor 5) causes Holt-Oram syndrome (also known as hand-heart syndrome) and early onset of atrial fibrillation. Revealing how an altered key developmental transcription factor modulates cardiac physiology in vivo will provide unique insights into the mechanisms underlying atrial fibrillation in these patients.Methods: We analyzed ECGs of an extended family pedigree of Holt-Oram syndrome patients. Next, we introduced the TBX5-p.G125R variant in the mouse genome (Tbx5G125R) and performed electrophysiologic analyses (ECG, optical mapping, patch clamp, intracellular calcium measurements), transcriptomics (single-nuclei and tissue RNA sequencing), and epigenetic profiling (assay for transposase-accessible chromatin using sequencing, H3K27ac [histone H3 lysine 27 acetylation] CUT&RUN [cleavage under targets and release under nuclease sequencing]).Results: We discovered high incidence of atrial extra systoles and atrioventricular conduction disturbances in Holt-Oram syndrome patients. Tbx5G125R/+ mice were morphologically unaffected and displayed variable RR intervals, atrial extra systoles, and susceptibility to atrial fibrillation, reminiscent of TBX5-p.G125R patients. Atrial conduction velocity was not affected but systolic and diastolic intracellular calcium concentrations were decreased and action potentials were prolonged in isolated cardiomyocytes of Tbx5G125R/+ mice compared with controls. Transcriptional profiling of atria revealed the most profound transcriptional changes in cardiomyocytes versus other cell types, and identified over a thousand coding and noncoding transcripts that were differentially expressed. Epigenetic profiling uncovered thousands of TBX5-p.G125R-sensitive, putative regulatory elements (including enhancers) that gained accessibility in atrial cardiomyocytes. The majority of sites with increased accessibility were occupied by Tbx5. The small group of sites with reduced accessibility was enriched for DNA-binding motifs of members of the SP (specificity protein) and KLF (Krüppel-like factor) families of transcription factors. These data show that Tbx5-p.G125R induces changes in regulatory element activity, alters transcriptional regulation, and changes cardiomyocyte behavior, possibly caused by altered DNA binding and cooperativity properties.Conclusions: Our data reveal that a disease-causing missense variant in TBX5 induces profound changes in the atrial transcriptional regulatory network and epigenetic state in vivo, leading to arrhythmia reminiscent of those seen in human TBX5-p.G125R variant carriers. [ABSTRACT FROM AUTHOR]

A critical step in animal development is the specification of primordial germ cells (PGCs), the precursors of the germline. Two seemingly mutually exclusive mechanisms are implemented across the animal kingdom: epigenesis and preformation. In epigenesis, PGC specification is non-autonomous and depends on extrinsic signaling pathways. The BMP pathway provides the key PGC specification signals in mammals. Preformation is autonomous and mediated by determinants localized within PGCs. In Drosophila, a classic example of preformation, constituents of the germ plasm localized at the embryonic posterior are thought to be both necessary and sufficient for proper determination of PGCs. Contrary to this longstanding model, here we show that these localized determinants are insufficient by themselves to direct PGC specification in blastoderm stage embryos. Instead, we find that the BMP signaling pathway is required at multiple steps during the specification process and functions in conjunction with components of the germ plasm to orchestrate PGC fate. Author summary: Proper specification of primordial germ cells (PGCs) is crucial as PGCs serve as the precursors of germline stem cells. To specify PGC fate, invertebrates rely upon cell autonomous preformation involving maternally deposited germ plasm. In Drosophila melanogaster, to insulate newly formed PGCs from the adverse effects of the cell-cell signaling pathways, germ plasm determinants silence transcription and attenuate the cell cycle. However, our data on the BMP signaling pathway challenge this long-held view of PGC specification and suggest that appropriate specification of embryonic PGCs is sensitive to the BMP ligand, decapentaplegic (dpp), and its cognate receptor, thickveins. We find that PGCs are not only capable of responding to BMP signals from the soma, but also that these signals impact the proper determination of the germ cells. Based on these unanticipated similarities between mammals and flies, we propose a model integrating contribution of both the cell-autonomous (preformation) and non-autonomous (epigenesis) pathways during PGC determination. Consistent with the model, we have observed dominant genetic interactions between, oskar, the maternal determinant of PGC fate, and the BMP pathway ligand dpp. [ABSTRACT FROM AUTHOR]

The mechanism and action concerning epigenetic modifications, especially that of histone modifications, are not fully understood. However, it is clear that histone modifications play an essential role in several biological processes that are involved in cell proliferation and differentiation. In this article, we focused on how histone acetylation may result in differentiation into mesenchymal stem cells as well as histone acetylation function. Moreover, histone acetylation followed by the action of histone deacetylase inhibitors, which can result in the differentiation of stem cells into other types of cells such as adipocytes, chondrocytes, osteocytes, neurons, and other lineages, were also reviewed. [ABSTRACT FROM AUTHOR]

Common variable immunodeficiency (CVID) is the most prevalent form of symptomatic primary humoral immunodeficiencies characterized by failure in the final differentiation of B lymphocytes. The majority of CVID cases have no identified genetic defect, and epigenetic alteration could be involved in the pathogenesis of CVID. Hence, we aimed to evaluate the expression of hsa-miR-125b-5p -and, B lymphocyte-induced maturation protein-1(BLIMP-1) and interferon regulatory protein-4 (IRF-4) in a group of CVID patients with no definitive genetic diagnosis in comparison with healthy individuals. Ten CVID patients (all known genes excluded) and 10 age and sex-matched healthy controls participated in the study. B lymphocytes were isolated and expression of miR-125b-5p, IRF4, and BLIMP1 were evaluated by real-time polymerase chain reaction (RT-PCR). Moreover, B cell subsets were analyzed by flow cytometry. The results showed that the relative expression of miR-125b-5p in CVID patients was increased while it was decreased for the BLIMP1 and IRF4 transcription factors compared with the healthy controls. Although a reduction was observed in switched and non-switched memory B cells among all high-miR patients, these subsets were decreased in patients with normal miR expression (71.0% and 85.0%, respectively). Our results suggest that overexpression of miR-125b-5p affects the terminal differentiation of B cells in a selected group of CVID patients by downregulating the BLIMP-1 gene and more intensively for the IRF-4 gene expressions. [ABSTRACT FROM AUTHOR]

Sex differences in the rates of affective disorders have been recognized for decades. Studies of physiologic sex-related differences in animals and humans, however, have generally yielded little in terms of explaining these differences. Furthermore, the significance of these findings is difficult to interpret given the dynamic, integrative, and highly context-dependent nature of human physiology. In this article, we provide an overview of the current literature on sex differences as they relate to mood disorders, organizing existing findings into five levels at which sex differences conceivably influence physiology relevant to affective states. These levels include the following: brain structure, network connectivity, signal transduction, transcription/translation, and epigenesis. We then evaluate the importance and limitations of this body of work, as well as offer perspectives on the future of research into sex differences. In creating this overview, we attempt to bring perspective to a body of research that is complex, poorly synthesized, and far from complete, as well as provide a theoretical framework for thinking about the role that sex differences ultimately play in affective regulation. Despite the overall gaps regarding both the underlying pathogenesis of affective illness and the role of sex-related factors in the development of affective disorders, it is evident that sex should be considered as an important contributor to alterations in neural function giving rise to susceptibility to and expression of depression. [ABSTRACT FROM AUTHOR]

In this article, I first problematize the concept of rationality as educational ideal through the use of feminist philosophy. I then offer an alternative concept of rationality as educational ideal based on my reading of Catherine Malabou's work on plasticity, epigenesis, and rationality. In a last part, I explore the ontological and normative dimensions of this new concept of rationality through Maurice Merleau-Ponty's concept of "hyper-dialectics." [ABSTRACT FROM AUTHOR]

This paper takes an organicist perspective of W. Harvey's conception of epigenesis in his work Exercitationes de generatione animalium (1651). In line with this reading, I provide a critical assessment of the different interpretations (mechanistic or vitalist) of Harvey's idea of epigenesis. The English physician develops his conception of embryogenesis as a process that cannot be understood from the categories of human art, as is apparent in his criticisms towards his teacher, Fabricius. Nor is it accurate to say that his position is animistic. An immersion in this last question will show us his organic conception of the soul, as an extension of the Aristotelian-Galenic tradition. [ABSTRACT FROM AUTHOR]

Background: Epigenetic mechanisms are critical in the pathogenesis of pulmonary arterial hypertension (PAH). Previous studies have suggested that hypermethylation of the BMPR2 (bone morphogenetic protein receptor type 2) promoter is associated with BMPR2 downregulation and progression of PAH. Here, we investigated for the first time the role of SIN3a (switch-independent 3a), a transcriptional regulator, in the epigenetic mechanisms underlying hypermethylation of BMPR2 in the pathogenesis of PAH.Methods: We used lung samples from PAH patients and non-PAH controls, preclinical mouse and rat PAH models, and human pulmonary arterial smooth muscle cells. Expression of SIN3a was modulated using a lentiviral vector or a siRNA in vitro and a specific adeno-associated virus serotype 1 or a lentivirus encoding for human SIN3a in vivo.Results: SIN3a is a known transcriptional regulator; however, its role in cardiovascular diseases, especially PAH, is unknown. It is interesting that we detected a dysregulation of SIN3 expression in patients and in rodent models, which is strongly associated with decreased BMPR2 expression. SIN3a is known to regulate epigenetic changes. Therefore, we tested its role in the regulation of BMPR2 and found that BMPR2 is regulated by SIN3a. It is interesting that SIN3a overexpression inhibited human pulmonary arterial smooth muscle cells proliferation and upregulated BMPR2 expression by preventing the methylation of the BMPR2 promoter region. RNA-sequencing analysis suggested that SIN3a downregulated the expression of DNA and histone methyltransferases such as DNMT1 (DNA methyltransferase 1) and EZH2 (enhancer of zeste 2 polycomb repressive complex 2) while promoting the expression of the DNA demethylase TET1 (ten-eleven translocation methylcytosine dioxygenase 1). Mechanistically, SIN3a promoted BMPR2 expression by decreasing CTCF (CCCTC-binding factor) binding to the BMPR2 promoter. Last, we identified intratracheal delivery of adeno-associated virus serotype human SIN3a to be a beneficial therapeutic approach in PAH by attenuating pulmonary vascular and right ventricle remodeling, decreasing right ventricle systolic pressure and mean pulmonary arterial pressure, and restoring BMPR2 expression in rodent models of PAH.Conclusions: All together, our study unveiled the protective and beneficial role of SIN3a in pulmonary hypertension. We also identified a novel and distinct molecular mechanism by which SIN3a regulates BMPR2 in human pulmonary arterial smooth muscle cells. Our study also identified lung-targeted SIN3a gene therapy using adeno-associated virus serotype 1 as a new promising therapeutic strategy for treating patients with PAH. [ABSTRACT FROM AUTHOR]

Epigenetics is defined as changes in gene function that do not change the DNA sequence, but result in changes in the functions and regulation mechanisms of DNA, proteins and RNAs. Studies conducted in the field of epigenetics with the developing technology in recent years have enabled us to discover its important effects on humans and to understand its relationship with diseases. Many diseases occur as a result of excessive increase / suppression of the expression of genes by error or irregularity in the regulation of epigenetic mechanisms. The epigenetic mechanism that has been studied a lot and the most known epigenetic mechanism is DNA and RNA methylation. In addition to methylations, molecular-level research on DNA and RNA demethylation processes has gained great importance in understanding and evaluating epigenetic disease mechanisms. [ABSTRACT FROM AUTHOR]

A comparative analysis of the composition and structure of the surface facies of carbonatite weathering crusts (profiles) in the Chuktukon (Russia) and Seis Lagos (Brazil) deposits and ultra-rich rare metal ores in the Tomtor deposit (Russia) is presented. It is shown that the main geochemical trends in the formation of the Tomtor-type ultra-rich rare metal ores and the surface facies of weathering profiles are opposite. The obtained results do not confirm the genetic link between the unique Tomtor ores and the surface facies of the crust of carbonatites, but serve as evidence of their later formation due to the reductive epigenesis of carbonatite weathering products under the influence of solutions draining the overlying coaliferous rocks. Wide distribution of the phenomena of colloidal liquid layering into manganese and ferruginous fractions was established for the first time in surface facies of the weathering crust of carbonatites, and active lateral colloidal migration of Ti from the host rocks was revealed. [ABSTRACT FROM AUTHOR]

Development has intrigued humanity since ancient times. Today, the main paradigm in developmental biology and evolutionary developmental biology (evo-devo) is the genetic program, in which development is explained by the interplay and interaction of genes, that is, by the action of gene regulatory networks (GRNs). However, it is not even clear that a GRN, no matter how complex, can be translated into a form. Therefore, the fundamental enigma of development still remains: how is a complex organism formed from a single cell? This question unfolded the historical drama and the dialectical tension between preformation and epigenesis. In order to shed light on these issues, I studied the development of crabs (infraorder Brachyura), as representative of the subphylum Crustacea, using network theory. The external morphology of the different phases of brachyuran metamorphosis were modeled as networks and their main characteristics analyzed. As one could expect, the parameters usually regarded as indicative of network complexity, such as modularity and hierarchy, increased during development. However, when more sophisticated complexity measures were tested, it was evidenced that whereas a group of complexity measures increased during development, another group decreased. This led to consider that two kinds of complexities were being measured. I called them intensive and extensive complexity. In view of these results, I propose that crab development involves a passage from an intensive to an extensive complexity. In other words, crab development can be interpreted as a process of unfolding of an intensive, preexistent complexity. [ABSTRACT FROM AUTHOR]

Introduction: Current medications used for acute lymphoblastic leukemia (ALL) such as mercaptopurine target molecular factors involved in its onset and progression including DNA methyltransferases (DNMTs) because these enzymes are implicated in methylation and therefore expression of genes which are related to cell proliferation. This study evaluated the effect of mercaptopurine on the DNMT3A gene expression. Materials and Methods: The study was an analytical study of before and after type, performed on 8 children with B-cell ALL referred to children’s medical center of Tehran enrolled by convenience sampling. Their blood samples were taken in pre-treatment phase as well as 2 months after treatment with mercaptopurine. Ten healthy children referred to Yazd central medical laboratory were also sampled. RNA was extracted from the blood samples, and DNMT3Agene expression was measured by reverse transcriptase polymerase chain reaction (RT-PCR). Results: DNMT3A gene expression in patients with B-cell ALL who received mercaptopurine was significantly higher compared with pre-treatment time (P<0.05).Conclusion: Increased expression of this regulatory gene occurred due to drug mercaptopurine. So, the mechanism of action of this drug may be through epigenetic processes due to higher methylation of DNA in leukemic cells. [ABSTRACT FROM AUTHOR]

Background: One of the acute hematologic malignancies is acute promyelocytic leukemia (APL) that resulted in translocation of chromosomes 15 and 17, t (15; 17), and cessation in the maturation of myeloid cell line, and ultimate aggregation of neoplastic promyelocytes. Regarding that appetence of using herbal and marine medicine studies is increasing, and on the other hand, the features of Cassiopea andromeda Venom remained unclear; this study was conducted to determine its effects on NB4 cells as a model for APL. Materials and Methods: In this experimental study, the cells were treated with C. andromeda Venom concentrations at different periods and times. Growth inhibition and toxic effects of C. andromeda Venom were evaluated through methyl thiazole tetrazolium salt reduction (MTT test). The flow cytometry analysis was carried out using 7AAD and Annexin V stains for evaluating this venom's effect on apoptotic pathways. Besides, Real-Time polymerase chain reaction was performed to evaluate the relative gene expression. Results: C. andromeda Venom inhibited the growth of NB4 cells as correlated with concentration and time. Cell growth was inhibited by 49.1%, after 24 hours of treating NB4 cells with 1000µg/mL C. andromeda Venom. This venom increased the apoptotic process, which was then verified by 7AAD/AnnexinV staining. The fold change of p15INK4b, p21 WAF1/CIP1, P53, DNMT1, and Bcl-2 genes in the NB4 cell line were 144, 2.78, 1.75, 15.24, and 0.33, respectively, which meant that the expression level of p15INK4b, p21 WAF1/CIP1, P53, and DNMT1 were increased by 14400%, 278%, 175%, and 1524%, respectively and the expression of Bcl-2 was decreased by 67%. Conclusion: Considering the inhibitory property of C. andromeda Venom, the authors recommended it as a part of combinational medication for treating APL in animal trials and for other leukemias' in vitro studies. [ABSTRACT FROM AUTHOR]

Noncoding RNAs are proclaimed to be expressed in various cancer types and one such type is found to be pancreatic ductal adenocarcinoma (PDAC). The long noncoding RNAs (LncRNAs) affect the migration, invasion, and growth of tumor cells by playing important roles in the process of epigenesis, post-transcription, and transcriptional regulation along with the maintenance of apoptosis and cell cycle. It is quite subtle whether the alterations in lncRNAs would impact PDAC progression and development. This review throws a spotlight on the lncRNAs associated with tumor functions: MALAT-1, HOTAIR, HOXA13, H19, LINC01559, LINC00460, SNHG14, SNHG16, DLX6-AS1, MSC-AS1, ABHD11-AS1, DUXAP8, DANCR, XIST, DLEU2, etc. are upregulated lncRNAs whereas GAS5, HMlincRNA717, MIAT, LINC01111, lncRNA KCNK15-AS1, etc. are downregulated lncRNAs inhibiting the invasion and progression of PDAC. These data provided helps in the assessment of lncRNAs in the development, metastasis, and occurrence of PDAC and also play a vital role in the evolution of biomarkers and therapeutic agents for the treatment of PDAC. [ABSTRACT FROM AUTHOR]

In 1835, the meaning of the cleavage furrows in the division of frog eggs was the cause of a heated argument between the Italian naturalist Mauro Rusconi and Karl Ernst von Baer. These furrows were first described by Prévost and Dumas (Ann Sci Nat 2:100–121, 129–149, 1824b) who did not realize they cut the egg into separate masses. Rusconi (Développement de la grenouille comune depuis le moment de sa naissance jusque a son état parfait, Giusti, Milano, 1826) hypothesized a connection between the furrows and a peculiar crystallization of the content of the egg which eventually produced elementary molecules as the building blocks of the embryo. von Baer (Arch Anat Phys Wiss Med 6:481–509, 1834) was the first to establish a link between the furrows and an active process of dichotomous division he considered to be the basis for all further development and differentiation. The present paper analyses the theoretical reasons behind these divergent interpretations and focuses attention on their implications for the development of the cell theory and the conceptions of life. Prévost, Dumas and Rusconi interpreted cleavage and the whole embryonic development in the light of eighteenth-century scientific theories and the French materialism of the early nineteenth century, which explained life in terms of ordered molecular movement. Starting from other premises partly rooted in German philosophy von Baer (1834) gave a totally different picture which anticipated the cell theory and modern embryology. [ABSTRACT FROM AUTHOR]

Considerable progress has been made in elucidating the relationships between early life psychobiological and environmental risk factors and the development of tobacco addiction. However, a comprehensive understanding of the heterogeneity in tobacco addiction phenotypes requires integrating research findings. The probabilistic epigenesis meta-theory offers a valuable framework for this integration, considering systemic, multilevel, developmental, and evolutionary perspectives. In this paper, we critically review relevant research on early developmental risks associated with tobacco addiction and highlight the integrative heuristic value of the probabilistic epigenesis framework for this research. For this, we propose a four-level systems approach as an initial step towards integration, analyzing complex interactions among different levels of influence. Additionally, we explore a coaction approach to examine key interactions between early risk factors. Moreover, we introduce developmental pathways to understand interindividual differences in tobacco addiction risk during development. This integrative approach holds promise for advancing our understanding of tobacco addiction etiology and informing potentially effective intervention strategies. • Considerable progress in early risk factors for tobacco abuse requires integration. • The probabilistic epigenesis meta-theory is valuable for this integration. • A critical and integrative review informed by this theory is performed. • The proposed integrative advances could enhance tobacco abuse etiology understanding. [ABSTRACT FROM AUTHOR]

"On Epigenesis" consists of a series of interrelated short articles examining the philosophical concept of epigenesis, with a particular focus on Catherine Malabou's development of it in contemporary thought. Alexander Miller introduces the topic of epigenesis and considers its significance as a new paradigm. He also presents the reader with an overview of Malabou's work on the topic: Drawing from recent advances in the life sciences as well as the Western philosophical tradition, he claims, Malabou has proposed "an epigenetic paradigm for rationality" for the 21st century. Catherine Malabou explains that when, in 2001, the scientific journal Nature published virtually the entire sequence of three billion bases that make up the human genome, people were surprised: Only five percent of the sequence turned out to actually be genes. Assembled in bunches and clusters, they are separated by vast expanses of so-called gene deserts made up of DNA characterized as "junk" or "repetitive," which is to say, non-coding. The sequencing of the genome did not offer the revelations that people had expected, marking the end of the "everything is genetic" creed and announcing the rise of the "epigenetic paradigm." The present article analyzes the implications of this new paradigm in biology, philosophy, and hermeneutics. Emily Apter situates Catherine Malabou's theory of epigenesis within a broader disciplinary context of Continental philosophy, the cognitive turn, and what a brain does or "is" as an object of aesthetic representation. Peter Szendy argues that even if they are not the central focus of her philosophical work, media and medial metaphors play a key role in Catherine Malabou's understanding of epigenetics. Indeed, her views on the epigenetic paradigm shift could lead to a rethinking of mediality. A medium, according to such an epigenetic approach, would be neither simply a storage space nor a carrier: It would be what happens along with the events (whether they involve works or data) that it hosts or transports. Emanuela Bianchi asks whether the epigenesis of "pure reason" can in any sense be "pure," since epigenesis necessarily involves empirical processes. Foregrounding the topological involvement of the developing organism in its environment in both biological and psychoanalytic registers, she suggests a way forward can be found in thinking of the genesis of reason as both empirical and rational. Alexander R. Galloway traces an etymological path from "epigenetic" back to the Greek verb "gignomai," meaning "to be born" or "to become." But what is becoming? And why is becoming better than (mere) being? One answer is that becoming helps one to escape the confines of identity and rote determination. But what happens when the epigenetic paradigm becomes dominant, when contingency, evolution, and becoming prevail over essence, stasis, and determinism? [ABSTRACT FROM AUTHOR]

Changes in microRNA (miRNA) levels are present in numerous diseases. Although these changes are particularly noted in male infertility, little is known about the effects of increased miR-16-1 in sperm from infertile men. In this study, we assessed the effects of increased mir-16-1 expression on the developmental process, epigenetic changes, and target gene expressions. IVF embryos, 6 h after insemination, were divided into three groups: control, control negative (CN), and miR-16-1 harboring plasmid microinjection. The developmental rates of these embryos were recorded after 24, 48, 72, and 96 h of culture. The levels of histone H3 lysine 4 tri-methylation (H3K4me3) and histone H3 lysine 27 tri-methylation (H3K27me3) were assessed in the 2-cell and blastocyst stages by immunofluorescence staining. Expression profiles of the miR16-1, Bax, Bcl-2, Suz12, and Kmt2a genes were measured by quantitative real-time polymerase chain reaction (qRT-PCR). There was a significant decrease from the 8-cell stage to the blastocyst stage of embryo development in the miR-16-1 harboring plasmid microinjection group. We observed substantial reductions in the amounts of H3K4me3 and H3K27me3 in the 2-cell and the blastocyst stages in the miR-16-1 harboring plasmid microinjection group (P ≤ 0.05). The miR-16-1 level in the miRNA group was higher than the control group in the 2-cell and the blastocyst stages. There was a significant increase (P ≤ 0.05) in Bax and decreases in Bcl2, Suz12, and Kmt2a following the injection of the miR-16-1 harboring plasmid. These results suggest that a change in miR-16-1 expression can significantly affect embryo development, epigenetic changes, and target gene expressions. [ABSTRACT FROM AUTHOR]

This article aims to analyze the dialogue held between Kant and both Plato and Aristotle in his Reflexionen and Vorlesungsnachschriften. This dialogue will be examined from the positions which ascribe Plato and Aristotle the main sources of, respectively, innatism and sensualism. Although he refuses the dogmatic exclusivity of one and the other theories of representation, Kant still admits a form of innatism. Furthermore, he opts by epigenesis, an embryological theory whose bases had been cast by Aristotle. This course will allow us to underscore Kant's debt regarding certain crystallized versions of Plato's and Aristotle's philosophies, such as, for instance, Hissmann's published critique, recommended by Kant himself, of Dutens' work: Recherches sur l'origine des découvertes attribuées aux modernes. [ABSTRACT FROM AUTHOR]

Direct reprogramming, also known as a trans-differentiation, is a technique to allow mature cells to be converted into other types of cells without inducing a pluripotent stage. It has been suggested as a major strategy to acquire the desired type of cells in cell-based therapies to repair damaged tissues. Studies related to switching the fate of cells through epigenetic modification have been progressing and they can bypass safety issues raised by the virus-based transfection methods. In this study, a protocol was established to directly convert fully differentiated fibroblasts into diverse mesenchymal-lineage cells, such as osteoblasts, adipocytes, chondrocytes, and ectodermal cells, including neurons, by means of DNA demethylation, immediately followed by culturing in various differentiating media. First, 24 h exposure of 5-azacytidine (5-aza-CN), a well-characterized DNA methyl transferase inhibitor, to NIH-3T3 murine fibroblast cells induced the expression of stem-cell markers, that is, increasing cell plasticity. Next, 5-aza-CN treated fibroblasts were cultured in osteogenic, adipogenic, chondrogenic, and neurogenic media with or without bone morphogenetic protein 2 for a designated period. Differentiation of each desired type of cell was verified by quantitative reverse transcriptase-polymerase chain reaction/western blot assays for appropriate marker expression and by various staining methods, such as alkaline phosphatase/alizarin red S/oil red O/alcian blue. These proposed procedures allowed easier acquisition of the desired cells without any transgenic modification, using direct reprogramming technology, and thus may help make it more available in the clinical fields of regenerative medicine. [ABSTRACT FROM AUTHOR]

Systemic sclerosis (SSc) is a chronic progressive autoimmune disease characterized by immune inflammation, vasculopathy, and fibrosis. There are still numerous uncertainties in the understanding of disease initiation and progression. Pulmonary involvement in SSc, and particularly pulmonary fibrosis, is critical for all organ systems affections in this disease. This review is aimed to describe and analyze new findings in the pathophysiology of SSc-associated pulmonary involvement and to explore perspective diagnostic and therapeutic strategies. A myriad of cellular interactions is explored in the dynamics of progressive interstitial lung disease (ILD) and pulmonary hypertension (PH) in SSc. The role of exosomes, microvesicles, and apoptotic bodies is examined and the impact of micro and long non-coding RNAs, DNA methylation, and histone modification in SSc is discussed. [ABSTRACT FROM AUTHOR]

Embryonic development, which inspired the first theories of biological form, was eventually excluded from the conceptual framework of the Modern Synthesis as irrelevant. A major question during the last decades has centred on understanding whether new advances in developmental biology are compatible with the standard view or whether they compel a new theory. Here, I argue that the answer to this question depends on which concept of morphogenesis is held. Morphogenesis can be conceived as (1) a chemically driven or (2) a mechanically driven process. According to the first option, genetic regulatory networks drive morphogenesis. According to the second, morphogenesis results from an invariant tendency of embryonic tissues to restore changes in mechanical stress. While chemically driven morphogenesis allows an extension of the standard view, mechanically driven morphogenesis would deeply transform it. Which of these hypotheses has wider explanatory power is unknown. At present, the problem of biological form remains unsolved. [ABSTRACT FROM AUTHOR]

It is a commonplace that evolution proceeds by selection of the fittest with elimination of organisms less well adapted to the environment. Along with this, the appearance of novel form arises from preliminary stages in growth, not as additions to the endpoints of prior specialization. The mechanisms of evolutionary change, from earlier form-building layers and specification by elimination, have been described in morphogenesis as prolongation of pre-terminal stages in development and winnowing of redundancy to achieve specificity. In earlier writings, these trends in evolutionary and developmental growth were the basis of an account of the nature of the symptom (error) with focal brain lesion. This paper extends the argument from pathology to subjective experience, namely that patterns in evolutionary and fetal growth that are carried over into adult cognition can explain the emergence of intrapersonal phenomena in human mind conceived as a kind of organism, with activity in the mental (mind/brain) state interpreted as a dynamic process of growth. [ABSTRACT FROM AUTHOR]

This article will attempt to elucidate Kant's expression 'epigenesis of pure reason' in relation to the order of the transcendental foundation of constitution of objectivity, as presented in the Critique of Pure Reason. By using the passage entitled 'Refutation of idealism', the fundamental relationship existing between time and space will be examined, and the thesis according to which space has logically and intuitively priority over time will be defended. Along with this, the article proposes an interpretation of the Schematism and Analogies of Experience, which is able to give an account of a spatialization of time in Kant's thought. [ABSTRACT FROM AUTHOR]

Background: Decitabine (5-aza-2'-deoxycytidine, DAC) is a deoxycytidine analog currently used as an effective drug against myelodysplastic syndromes and acute myeloid leukemia. Although various studies have pointed out the epigenetic effects of this drug, its epigenetic mechanisms in different leukemic cell lines are not specified. In this lab trial study, possible epigenetic effects of decitabine on leukemia cell lines Hl-60 (acute promyelocytic leukemia) and Nalm-6 (acute pre-B cell lymphoblastic leukemia) vs. normal peripheral blood mononuclear cells (PBMCs) are compared. Materias and Methods: At the logarithmic phase of growth, the cultured cells Hl-60 and Nalm-6 obtained from Tehran Pasteur Institute, Iran, were treated for 24 hr with 1 µM of decitabine, a dose selected from literature and the MTT viability assay. Normal PBMCs were obtained from a pool of 3 healthy adult volunteer males, and cultured simultaneously in the same manner. The gene expressions of epigenetic enzymes DNA methyltransferases (DNMTs) were assessed with the real-time PCR technique before and after treatment. The GAPDH gene expression served as the calibrator, while normal PBMCs were used for comparison. Results: The expressions of DNMT1 and DNMT3B in lymphoblasts were significantly (p=0.0017 and p=0.0489, respectively) decreased after treatment with decitabine, while the expression of DNMT3A was significantly (p=0.0022) increased. In leukemic promyelocytes the expressions of DNMT1 and DNMT3B in lymphoblasts were significantly (p=0.0222 and p=0.0452, respectively) decreased after treatment with decitabine, while the expression of DNMT3A was significantly (p=0.0013) increased. Conclusion: One of the mechanisms by decitabine to inhibit the proliferation of both myeloid and lymphoid acute leukemia cells maybe by altering the gene expression of DNMTs. [ABSTRACT FROM AUTHOR]

Objectives: Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of apparently mature B-type lymphocytes in the lymphohematopoietic organs. Methylation in promoters of tumor suppressor genes is one of the mechanisms that causes blood malignancy. In this study, we evaluated the promoter DNA methylation status of miR-129-2 tumor suppressor gene and its association with clinical and laboratory parameters of patients with CLL. Methods: We studied the promoter DNA methylation frequency of the miR-129-2 gene in 50 patients with CLL and 50 healthy controls using methylation-specific polymerase chain reaction methods. Statistical analysis was performed using SPSS-18 software, and a p-value < 0.050 was considered statistically significant. Results: The frequency ofpromoter DNA methylation ofthe miR-129-2 gene was significantly higher in the CLL group compared with control group (38.0% vs. 0.0%, p < 0.001; χ² = 23.457). The promoter DNA methylation frequency of miR-129-2 gene was not significantly different between the two sexes (p = 0.236). A significant but weak correlation was seen between the methylated state of the miR-129-2 gene and organomegaly (p = 0.019, r = 0.330) as well as hemoglobin levels (p = 0.020, r = -0.233). However, binary logistic regression analysis indicated organomegaly as the only clinical biomarker with a statistically significant association with the hypermethylated miR-129-2 gene state (p = 0.046). Conclusions: The high frequency of promoter DNA methylation of the miR-129-2 gene in the CLL group compared to the control group, as well as its significant association with organomegaly, suggests the importance of this epigenetic biomarker in the pathogenesis and prognosis of CLL disease. [ABSTRACT FROM AUTHOR]

The article reflects the study results of oil and gas bearing rocks of the North-Taz Basin. The interconnection of oil seismology and hydrothermal processes is pointed by the example of local and integral seismic effects. We determined that the fluidization processes are associated with the activation of abdominal faults and are secondary to the previously formed classical zones of epigenesis. Based on paragenetic mineral associations and epigenetic changes in the rocks of the study area, new types of hydrothermal-metasomatic formations are identified - mudstones and fluidisites. The lithogeochemical anomalies of potassium, phosphorus, iron, fluorine, and arsenic confirm the presence of vertical migration and are linked to the morphological features of the reflecting horizons of the study area. The results of determining the petrochemical modules for the Turonian-Maastrian reserves confirm that the lithogeochemical anomalies of the selected group of elements are associated with the Late Cretaceous stage of activation of deep-seated processes. According to the results of X-ray diffraction analysis, three main complexes of clay minerals of the sedimentary section were identified: montmorillonite-kaolinite, hydromicaceous-chlorite, hydromicaceous-chlorite-zeolite. It was established that the presence of montmorillonite is a distinctive feature of these reserves and its presence leads both to high reliability of tires and to a significant deterioration in the reservoir properties of sand varieties. Zeolites are defined as indicators of diagenetic transformation of rocks. For micaceous mineral, the most common polytypic varieties were identified, characterizing the presence of a hydrothermal process. According to electron microscopic studies of the composition of the rocks, their pore space, and the analysis of the geological characteristics of the study area, six types of integral fluidization zones and three local levels were established. The mineral composition of the fluidization zones was characterized as a result of hydrothermal-metasomatic transformations of the corresponding rock complexes. Assumptions are made about the forms of bodies of hydrothermally transformed rocks, defined in the field of seismic waves, as the results of the development of fluid zones of a certain mineral type and similar to primary halos of ore reserves. The characteristics of the zones of colmatation of two types are given that affect the flow rate of wells and form a new type of metasomatic traps for oil and gas reserves. [ABSTRACT FROM AUTHOR]

Aristotle made important contributions to the study of developmental biology, including the complete metamorphosis of insects. One concept in particular, that of the perfect or complete state, underlies Aristotle's ideas about metamorphosis, the necessity of fertilization for embryonic development, and whether morphogenesis involves an autonomous process of self-assembly. Importantly, the philosopher erroneously views metamorphosis as a necessary developmental response to lack of previous fertilization of the female parent, a view that is intimately connected with his readiness to accept the idea of the spontaneous generation of life. Aristotle's work underpins that of the major seventeenth century students of metamorphosis, Harvey, Redi, Malpighi and Swammerdam, all of whom make frequent reference to Aristotle in their writings. Although both Aristotle and Harvey are often credited with inspiring the later prolonged debate between proponents of epigenesis and preformation, neither actually held firm views on the subject. Aristotle's idea of the perfect stage also underlies his proposal that the eggs of holometabolous insects hatch 'before their time', an idea that is the direct precursor of the much later proposals by Lubbock and Berlese that the larval stages of holometabolous insects are due to the 'premature hatching' from the egg of an imperfect embryonic stage. This article is part of the theme issue 'The evolution of complete metamorphosis'. [ABSTRACT FROM AUTHOR]

The potential for an intervention by epigenetics into cultural theory and literary analysis has been a topic of recent inquiry from several directions. However, these approaches sometimes too easily align epigenetics with the Lamarckian 'inheritance of acquired characteristics', which presumes the direct influence of environment on the existence of particular traits across generations. This emphasis on environment in turn looks back to eighteenth- and nineteenth-century racial science that attributed degrees of civilisation or savagery to the combined influence of heredity and climate. By instead tracing epigenetics in the older concept of 'epigenesis' from Romantic biology, we can identify the interpretive role of the organism itself in the expression of inherited traits and in the mediation of environmental stimuli. An epigenetic reading of Jane Eyre identifies how Brontë uses the creative agency of the developing body to challenge the 'genetic' and environmental coordinates of racial anthropology. In so doing, she links imperial violence to domestic tyranny and protests against the injustice of both. [ABSTRACT FROM AUTHOR]

Ovarian structure and functions are important for female fertility. The development and maturation of reproduction, and maintains of ovarian function and fertility, are mainly regulated by the hypothalamic -pituitary -ovarian (HPO) axis and the local factors of ovary, such as transforming growth factor-P (TGF-P)，epidermal growth factor (EGF) and insulin-like growth factor (IGF). It was reported that the adverse maternal environment during pregnancy (such as prenatal xenobiotics exposure, maternal nutrition disorder and disease, etc.) was associated with the reproductive development in offspring, which would lead to diminished ovarian reserve such as premature ovarian failure (POF) in some adult offspring. The mechanism of fetal-derived POF is related to the theory of "intrauterine programming", including they abnormalities of neuroendocrine programming and epigenetic modification. In this review, we discussed the intrauterine programming mechanism of fetal-derived POF, and the potential markers of early warning, prevention and treatment of this disease. [ABSTRACT FROM AUTHOR]

This paper takes an organicist perspective of Jan Swammerdam's conception of metamorphis which allows us to identify a continuity betweem W. Harvey's epigenetism and G.W. Leibniz' preformationism -- two historically opposed perspectives. In line with this reading, I provide a critical assessment of the different preformationist interpretations of Swammerdam. The thesis that I defend in this paper is that the idea of preformation does not imply so much a theory about the origin of the embryo but a model of ontogenetic development that cannot be catalogued as mechanistic or as vitalist. [ABSTRACT FROM AUTHOR]

Summary: Plant growth is largely post‐embryonic and depends on meristems that are active throughout the lifespan of an individual. Developmental patterns rely on the coordinated spatio‐temporal expression of different genes, and the activity of transcription factors is particularly important during most morphogenetic processes. MADS‐box genes constitute a transcription factor family in eukaryotes. In Arabidopsis, their proteins participate in all major aspects of shoot development, but their role in root development is still not well characterized. In this review we synthetize current knowledge pertaining to the function of MADS‐box genes highly expressed in roots: XAL1,XAL2,ANR1 and AGL21, as well as available data for other MADS‐box genes expressed in this organ. The role of Trithorax group and Polycomb group complexes on MADS‐box genes' epigenetic regulation is also discussed. We argue that understanding the role of MADS‐box genes in root development of species with contrasting architectures is still a challenge. Finally, we propose that MADS‐box genes are key components of the gene regulatory networks that underlie various gene expression patterns, each one associated with the distinct developmental fates observed in the root. In the case of XAL1 and XAL2, their role within these networks could be mediated by regulatory feedbacks with auxin. [ABSTRACT FROM AUTHOR]