Epigenetics

"The expression “mental illness” arises historically in the course of conversations about our human relational living, in an attempt to visualize some regularities that occurred in it, thinking that if we could grasp them we would be able to solve some difficulties that we were encountering in our living together, thinking that we could do so through formalizing them with some adequate theory that we would invent. However, to do that, we have to abstract those regularities in our living together first; we must respect ourselves accepting that naming is not a trivial aspect of what we do in our living: names have arisen in our history of living together as operational elements of coordination of our doings, and reveal regularities in that living."

This paper addresses historical dimensions of epigenetic studies on human populations. We show that postgenomic research on health disparities in Latin America reintroduces old colonial views about the relations between race, environment, and social status. This especially refers to the idea – common in colonial humoralism and epigenetics – that different types of bodies are in balance and closely linked with particular local environments and lifestyles. These social differences become embodied as physiological and health differences. By comparing Spanish chronicles of the New World with recent epidemiological narratives on Mexican populations in social epigenetics (especially on obesity), we identify four characteristics that both share in distinguishing races, such as indigenous or mestizos from Spaniards or non-Mexicans: (i) Race is not intrinsic to bodies but emerges as a particular homeostatic body-environment relation; (ii) the stability of one's race is warranted through the stability of one's local environment and lifestyle, especially nutrition; (iii) every race faces specific life challenges in a local environment to maintain its health; and (iv) every race shows a unique social status that is closely linked to its biological status (e.g., disease susceptibility). Based on these similarities, we argue that currently in Latin America the field of epigenetics appears on the scene with a worrisome colonial shadow. It reintroduces long forgotten exclusionary and stereotypic perspectives on indigenous and mestizos, and biologizes as well as racializes social-cultural differences among human groups.

More than 7,000 rare diseases (RDs) exist worldwide, affecting approximately 350 million people, out of which only 5% have treatment. The development of novel genome sequencing techniques has accelerated the discovery and diagnosis in RDs. However, most patients remain undiagnosed. Epigenetics has emerged as a promise for diagnosis and therapies in common disorders (e.g., cancer) with several epimarkers and epidrugs already approved and used in clinical practice. Hence, it may also become an opportunity to uncover new disease mechanisms and therapeutic targets in RDs. In this “big data” age, the amount of information generated, collected, and managed in (bio)medicine is increasing, leading to the need for its rapid and efficient collection, analysis, and characterization. Artificial intelligence (AI), particularly deep learning, is already being successfully applied to analyze genomic information in basic research, diagnosis, and drug discovery and is gaining momentum in the epigene...

Renal cell carcinoma (RCC) is not a single disease, but comprises a group of tumors of renal epithelial origin, each with a different histology, displaying a different clinical course and caused by different genetic alterations. Since cure rates are inversely associated with stage and response to the available treatment regimes is limited to a subgroup of patients, diagnostic methods facilitating early detection and new therapeutic modalities are necessary. Increased knowledge of the underlying pathophysiology of RCC has resulted in the identification of genetic alterations involved in renal cell cancer carcinogenesis. Promising agents to target these pathways, especially the angiogenesis pathway, are being developed, some of which are already standard of care. In addition to genetics, knowledge on epigenetics in the process of renal tumorigenesis has been significantly increased in the last decades. Epigenetics will play an increasing role in the development of new therapeutic modalities and may deliver new prognostic and early diagnostic markers. In this review we discuss the background of RCC and the clinical applications of RCC genetics and epigenetics.

Approximately 3% of infants born have at least one serious congenital malformation. In the U.S., an average of 10 infants per thousand die before 1 y of life; about half of these deaths can be attributed to birth defects, low birth weight or prematurity. Although the causes of developmental abnormalities are clearly multifactorial in nature, we suggest that a common factor contributing to the occurrence of developmental abnormalities is suboptimal mineral nutrition during embryonic and fetal development. Using zinc and copper as examples, evidence is presented that nutritional deficiencies can rapidly affect the developing conceptus and result in gross structural abnormalities. Deficits of zinc or copper can result in rapid changes in cellular redox balance, tissue oxidative stress, inappropriate patterns of cell death, alterations in the migration of neural crest cells and changes in the expression of key patterning genes. In addition to well-recognized malformations, mineral deficiencies during perinatal development can result in behavioral, immunological and biochemical abnormalities that persist into adulthood. Although these persistent defects can in part be attributed to subtle morphological abnormalities, in other cases they may be secondary to epigenetic or developmental changes in DNA methylation patterns. Epigenetic defects combined with subtle morphological abnormalities can influence an individual's risk for certain chronic diseases and thus influence his or her risk for morbidity and mortality later in life.

Perfluorooctanoic acid (PFOA) is a widespread contaminant in
the environment, that is, implicated in several toxicities. The
intestinal wall is first surface of interaction with any toxicant
after exposure through the oral route. Previous studies have
demonstrated: increased intestinal bioaccumulation of
PFOA in different experimental animals, PFOA-induced
changes in DNA methylation of several tissues, and alterations
in expression of tight junction (TJ) genes due to epigenetics
changes. Nevertheless, evidence on the toxicity of
PFOA on intestinal epigenetics and TJ genes is limited.
Thus, the present work investigates PFOA-induced changes
in expression of epigenetic genes of the colon in relation to
TJ genes alterations. CD-1 mice were orally dosed with 4
different concentrations of PFOA (1, 5, 10, or 20 mg/kg/d)
for 10 consecutive days, and its bioaccumulation and
induced changes in the expression of TJ and epigenetic
genes in the colon were investigated. The PFOA was accumulated
in very high concentrations in the colon tissue and
decreased the expression levels of DNA methyltransferase
genes (Dnmt3a and DNMT3b). However, no significant
alterations were observed in expression levels of 10-11
translocation (TET1 and TET2) genes. We also found a
significant reduction in the mRNA expression of TJ
protein-1 (TJP1) at the highest concentration of PFOA.
Furthermore, the mRNA expression levels were significantly
increased for occludin (OCLN) and Claudins
(CLDN2, CLDN3, CLDN8) genes at higher concentrations.
Therefore, our study demonstrates that PFOA initiates
DNA methylation alterations and changes the expression
of genes necessary for preserving the integrity of the colon
barrier.

Białaczki należą do chorób rozrostowych układu krwionośnego. Współcześnie, zgodnie z klasyfikacją WHO z 2008 roku, wyróżnia się kilka typów białaczek różniących się pochodzeniem i przebiegiem [1]. Wiele z nich powiązanych zostało z określonymi zmianami genetycznymi. Przykładowo, przewlekła białaczka szpikowa (CML) wywoływana jest translokacją chromosomową t(9;22) (q34;q11), w wyniku której powstaje gen fuzyjny BCR-ABL kodujący onkogenną, konstytutywnie aktywną kinazę tyrozynową [2]. Choroba a c t a h a e m a t o l o g i c a p o l o n i c a 4 4 (2 0 1 3) 4 8-5 7 i n f o r m a c j e o a r t y k u l e Historia artykułu:

Today the hypothesis that experience might alter the cells and behavior of an individual’s children and grandchildren has become widely accepted. In animals, exposure to stress, cold, or high-fat diets has been shown to trigger metabolic changes in later generations. And small studies in humans exposed to traumatic conditions—among them the children of Holocaust survivors—suggest subtle biological and health changes in their children.
The implications are profound. If our experiences can have consequences that reverberate to our children or our children’s children, that’s a powerful argument against everything from smoking to immigration policies that split families.
But proving that emotional trauma, as distinct from physical stress, can be passed on to subsequent generations in people is a challenge.

The term “epigenetics” is critically analyzed basing on the differential concept of variability. A strict definition of epigenetic processes is proposed. The widely accepted tradition to oppose the words “genetic” and “epigenetic” is shown to be incorrect. An adequate antonym for the term “epigenetics” is proposed. Optimization of current genetic terminology due to epigenetics redefining is discussed.

FULL TEXT HERE: http://www.tandfonline.com/eprint/TisUSYK5gw3iQctC3e7w/full
Autism (AUT) is one of the most prevalent developmental disorders emerging during childhood, and can be amongst the most incapacitating mental disorders. Some individuals with AUT require a lifetime of supervised care. Autism Speaks reported estimated costs for 2012 at £34 billion in the UK; and $3.2 million-$126 billion in the US, Australia and Canada. Ethnicity and migration experiences appear to increase risks of AUT and relate to underlying biological risk factors. Sociobiological stress factors can affect the uterine environment, or relate to stress-induced epigenetic changes during pregnancy and delivery. Epigenetic risk factors associated with AUT also include poor pregnancy conditions, low birth weight, and congenital malformation. Recent studies report that children from migrant communities are at higher risk of AUT than children born to non-migrant mothers, with the exception of Hispanic children. This paper provides the first systematic review into prevalence and predictors of AUT with a particular focus on maternal migration stressors and epigenetic risk factors. AUT rates appear higher in certain migrant communities, potentially relating to epigenetic changes after stressful experiences. Although AUT remains a rare disorder, failures to recognize its public health urgency and local community needs continue to leave certain cultural groups at a disadvantage.

To address the challenge of identifying related members of a large family of genes, their variants and their patterns of expression, we have developed a novel technique known as targeted expressed gene display. Here, we demonstrate the general application of this technique by analyzing the SMAD genes and report that the loss of SMAD8 expression is associated with multiple types of cancers, including 31% of both breast and colon cancers. Epigenetic silencing of SMAD8 expression by DNA hypermethylation in cancers directly correlates with loss of SMAD8 expression. The SMAD8 alteration in a third of breast and colon cancers makes it a significant novel tumor marker as well as a potential therapeutic target. The utility of targeted expressed gene display for the analysis of highly homologous gene families as demonstrated by its application to the SMAD genes suggests that it is an efficient tool for the identification of novel members, simultaneous analysis of differential expression patterns, and initial discovery of alterations of expressed genes. MATERIALS AND METHODS Cell Culture, RNA Isolation, and cDNA Synthesis. Cancer cell lines were purchased from American Type Culture Collection or the Coriell Cell Repository and culture conditions were followed as suggested by the provider. Tumor samples, some of the cell lines, and their derivatives or nucleic acids isolated from the samples used in this study were obtained from Subra Kugathasan (

Novel phenotypes often arise in generations immediately following polyploidization. Previous studies have shown that separate lineages derived from a resynthesized Brassica napus allopolyploid rapidly evolved heritable differences in flowering time. These early-flowering and late-flowering polyploid lines were expected to be genetically identical because they were derived from a single, chromosome-doubled amphihaploid plant. In this study, we investigated the molecular genetic basis for these flowering time differences. We assessed the diploid B. rapa and B. oleracea parents and the early-and late-flowering B. napus lineages for changes in genome structure, and for changes in transcript levels of four sets of FLOWERING LOCUS C ( FLC ) genes. No such changes were observed for BnFLC1 , but we detected chromosomal rearrangements (e.g. de novo non-reciprocal transpositions) and changes in transcript level for BnFLC2 and BnFLC3 between the early-and late-flowering B. napus . A chromosomal rearrangement of a genomic segment containing BnFLC3 was responsible for 29% of the phenotypic variation among the B. napus lines. Expression of BnFLC5 was silenced in all polyploids, although no changes in genome structure were detected. An ongoing investigation of 50 identical B. napus allopolyploids may further reveal the dynamics of changes in phenotype, genome and transcriptome at the early stages in polyploid evolution.

In many eukaryotic organisms, gender is determined by a pair of heteromorphic sex chromosomes. Degeneration of the non-recombining Y chromosome is a general facet of sex chromosome evolution. Selective pressure to restore expression levels of X-linked genes relative to autosomes accompanies Y-chromosome degeneration, thus driving the evolution of dosage compensation mechanisms. This review focuses on evolutionary aspects of dosage compensation, in light of recent advances in comparative and functional genomics that have substantially increased our understanding of the molecular mechanisms of dosage compensation and how it evolved. We review processes involved in sex chromosome evolution, and discuss the dynamic interaction between Y degeneration and the acquisition of dosage compensation. We compare mechanisms of dosage compensation and the origin of dosage compensation genes between different taxa and comment on sex chromosomes that apparently lack compensation mechanisms. Finally, we discuss how dosage compensation systems can also influence the evolution of well-established sex chromosomes.

Explosions and molotov bomb throwing actions have prominent economic, psychological and social effects on the collective memory since they inflict nonrecoverable wounds. One of the prominent purposes of the crime scene investigation is to investigate the fingerprints in order to identify the identity of the offender. The purpose of this study is to determine the impact of heat on the quality of fingerprints on the findings obtained in crime scene and to create the standards to use as a routine investigation method in criminal laboratories of the law enforcers. Few studies have been published and little is known about this subject. The paper aims to discuss these issue. In this study, 720 fingerprint samples, which were created according to the conditions that would exist in the crime scenes after an explosion or handmade incendiary weapons incidents, had been 􀁈􀁛􀁄􀁐􀁌􀁑􀁈􀁇􀀑􀀃 􀂳􀀶􀁘􀁓􀁈􀁕􀀃􀀪􀁏􀁘􀁈􀂴􀀃􀁄􀁑􀁇􀀃 􀂳􀀶􀀳􀀵􀂴􀀃 􀁐􀁈􀁗􀁋􀁒􀁇􀁖􀀃 􀁚􀁈􀁕􀁈􀀃 􀁘􀁖􀁈􀁇􀀃 􀁒􀁑􀀃 􀁐􀁈􀁗􀁄􀁏􀀃 􀁄􀁑􀁇􀀃 􀁊􀁏􀁄􀁖􀁖􀀃 􀁖􀁄􀁐􀁓􀁏􀁈􀁖􀀃 􀁄􀁑􀁇􀀃 􀂳􀀱􀁌􀁑􀁋􀁜􀁇􀁕􀁌􀁑􀂴􀀃 method were used on paper samples in order to create fingerprints. All the samples were exposed to temperatures varying between 50oC-300oC. When different temperatures were taken into consideration, fingerprints suitable for comparison were obtained under all surface and environmental conditions up to 300oC. We are of the opinion that this study which is conducted for the first time in our country would significantly contribute to the identification of attackers and shed light on the incidents, especially in terrorist events.

There is now mounting evidence that heritable variation in ecologically relevant traits can be generated through a suite of epigenetic mechanisms, even in the absence of genetic
variation. Moreover, recent studies indicate that epigenetic variation in natural populations can be independent from genetic variation, and that in some cases environmentally induced epigenetic changes may be inherited by future generations. These novel findings are potentially highly relevant to ecologists because they could significantly improve our understanding of the mechanisms underlying natural phenotypic variation and the responses of organisms to environmental change. To understand the full significance of epigenetic processes, however, it is imperative to study them in an ecological context. Ecologists should therefore start using a combination of experimental approaches borrowed from ecological genetics, novel techniques to analyse and manipulate epigenetic variation, and genomic tools, to investigate the extent and structure of epigenetic variation within and among natural populations, as well as the interrelations between epigenetic variation, phenotypic variation and ecological interactions.

Проведен критический анализ традиционных представлений о мутациях. Показано, что понятие “мутация” используется в современной генетике неадекватно, охватывая слишком широкий спектр явлений. Предложена строгая трактовка данного понятия, позволяющая четко отграничивать мутации от всего разнообразия других проявлений изменчивости. Рассмотрены важнейшие принципы классификации мутаций. Уточнено значение понятия “комбинативная изменчивость”.

The Cancer Genome Atlas (TCGA) project has analyzed mRNA expression, miRNA expression, promoter methylation, and DNA copy number in 489 high-grade serous ovarian adenocarcinomas (HGS-OvCa) and the DNA sequences of exons from coding genes in 316 of these tumors. These results show that HGS-OvCa is characterized by TP53 mutations in almost all tumors (96%); low prevalence but statistically recurrent somatic mutations in 9 additional genes including NF1, BRCA1, BRCA2, RB1, and CDK12; 113 significant focal DNA copy number aberrations; and promoter methylation events involving 168 genes. Analyses delineated four ovarian cancer transcriptional subtypes, three miRNA subtypes, four promoter methylation subtypes, a transcriptional signature associated with survival duration and shed new light on the impact on survival of tumors with BRCA1/2 and CCNE1 aberrations. Pathway analyses suggested that homologous recombination is defective in about half of tumors, and that Notch and FOXM1 signaling are involved in serous ovarian cancer pathophysiology.

Background: Epigenetics is changing the widely accepted linear conception of genome function by explaining how environmental and psychological factors regulate the activity of our genome without involving changes in the DNA sequence. Research has identifi ed epigenetic mechanisms mediating between environmental and psychological factors that contribute to normal and abnormal behavioral development. Method: the emerging fi eld of epigenetics as related to psychology is reviewed. Results: the relationship between genes and behavior is reconsidered in terms of epigenetic mechanisms acting after birth and not only prenatally, as traditionally held. Behavioral epigenetics shows that our behavior could have long-term effects on the regulation of the genome function. In addition, epigenetic mechanisms would be related to psychopathology, as in the case of schizophrenia. In the latter case, it would be especially relevant to consider epigenetic factors such as life adversities (trauma, disorganized attachment, etc.) as related to its clinical manifestations, rather than genetic factors. Moreover, epigenetics implies overcoming classical dualist dichotomies such as nature-nurture, genotype-phenotype or pathogenesis-pathoplasty. Conclusions: In general, it can be stated that behavior and environment will fi nally take on a leading role in human development through epigenetic mechanisms.

В то время как геном идентичен во всех типах тканей и относительно стабилен в течение жизни, эпигеном многоклеточного организма постоянно изменяется во время развития и старения. Выраженное влияние возраста на одну из ключевых эпигенетических модификаций-уровень метилирования цитозина в ДНК-было продемонстрировано еще в 1960-х гг. Б. Ф. Ванюшиным и соавт. в НИИ ФХБ им. А. Н. Белозерского в МГУ. Это открытие по-служило толчком для многочисленных исследований метилирования ДНК, в результате которых стало возможным не только с невероятной точностью вычислять возраст организма, независимо от его физиологических показателей, но и выявлять в нем патологические изменения. Более того, в будущем эти открытия могут способствовать разработке нового направления-эпигенетической терапии.
Ключевые слова: старение, метилирование ДНК, эпигеном, эпигенетические часы, DNAm PhenoAge, биологический возраст, предиктор выживания,  RG108, dCas9, эпигенетическая терапия

EPIGENETICS OF AGING: A BREAKTHROUGH DIRECTION IN GERONTOLOGY?
D. E. Jagarovi
Whereas genome is identical in all types of tissue and relatively stable during the lifetime, the epigenome of the multicellular organism changes during development and aging. The strong effects of age
on one of the central epigenetic modifications — DNA cytosine methylation levels have been identified by Dr. B. F. Vanyushin et al., in the A. N. Belozersky Institute of Physico-Chemical Biology of MSU,
Moscow, Russia in the 1960s. This discovery served as an impetus to numerous studies of DNA methylation, as a result of which it became possible not only to calculate with an amazing accuracy the age of the
organism regardless of its physiological indices, but also to reveal pathological changes in it. Moreover, in the future, these discoveries can promote the development of a new direction of therapy — epigenetic therapy.
Key words: aging, DNA methylation, epigenome, epigenetic clock, DNAm PhenoAge, biological age,  RG108, dCas9, epigenetic therapy

γ-hydroxybutyric acid (GHB) causes retrograde amnesia in juveniles and young adults. Earlier, we have reported that in adolescent rat, GHB impairs the hidden platform task performance in the Morris water maze. In the present study, a classical fear conditioning paradigm was used to examine the effects of GHB on the acquisition of contextual conditioning, a hippocampus-dependent associative task, and cued tone conditioning, a hippocampus-independent task, in adolescent rats. Administration of GHB before the presentation of tone-shock pairings dose-dependently disrupted the acquisition of contextual conditioning with no effect on tone conditioning, when conditioned fear was measured 24 h later. Administering GHB prior to testing did not disrupt either contextual or tone conditioning. These results demonstrate that in the adolescent rat exposure to GHB preferentially disrupt hippocampal-dependent learning.

This paper suggests that in the search for particular practices that escape biological
determinism historians may be better off focusing on circulating men and cultural objects – on displaced figures – as they travel and adjust to new conditions. Strangers experience intense cognitive dissonance between the innate natural conditions of their upbringing and their cognitive values, and as such, these figures work out their mental capacities and exercise free-will more powerfully than well-embedded cultural figures. To adjust to new language and cultural practices, they wrestle with fixed habits. Natives, on the other end, experience estrangement when they encounter foreign cultural objects, reinterpret and place them in a fluid web of implied meanings. Both encounters generate sensations of estrangement, forcing humans to act beyond their inborn and habitual reactions. Therefore, in this current age of physical determinism, cultural networks and moving objects carry great potential in further developing cultural history and in re-stressing and maintaining culture as the expressive realm of the collective soul.

Background: Diseases are complex phenotypes often arising as an emergent property of a non-linear network of genetic and epigenetic interactions. To translate this resulting state into a causal relationship with a subset of regulatory features, many experiments deploy an array of laboratory assays from multiple modalities. Often, each of these resulting datasets is large, heterogeneous, and noisy. Thus, it is non-trivial to unify these complex datasets into an interpretable phenotype. Although recent methods address this problem with varying degrees of success, they are constrained by their scopes or limitations. Therefore, an important gap in the field is the lack of a universal data harmonizer with the capability to arbitrarily integrate multi-modal datasets. Results: In this review, we perform a critical analysis of methods with the explicit aim of harmonizing data, as opposed to case-specific integration. This revealed that matrix factorization, latent variable analysis, and deep learning are potent strategies. Finally, we describe the properties of an ideal universal data harmonization framework. Conclusions: A sufficiently advanced universal harmonizer has major medical implications, such as (i) identifying dysregulated biological pathways responsible for a disease is a powerful diagnostic tool; (2) investigating these pathways further allows the biological community to better understand a disease's mechanisms; and (3) precision medicine also benefits from developments in this area, particularly in the context of the growing field of selective epigenome editing, which can suppress or induce a desired phenotype.

This essay addresses a more global history of dioxin's drift via the herbicide 2,4,5-T, better known in Vietnam as the dioxin-tainted herbicide in Agent Orange, but also widely available as a commercial herbicide. Drawing on theories of metabolic flow that challenge Marxist and other notions of a social–nature divide, the essay uses 2,4,5-T and dioxin as a focus for writing a metabolic history to examine how the origins, delivery and fate of a herbicide can pass far beyond expected boundaries. It uses the concept of drift with respect to the herbicide and its contaminant to get at a core challenge facing writers in environmental history and the environmental humanities: how to describe environmental phenomena with multiple and often divergent cascades of causal effects in different social, economic and ecological settings. A focus on a toxic molecule's drift through multiple metabolic webs challenges readers to think beyond dominant moral frameworks and reorient themselves to a more dynamic, multi-threaded approach.

To explore the potential evolutionary relevance of heritable epigenetic variation, the National Evolutionary Synthesis Center recently hosted a catalysis meeting that brought together molecular epigeneticists, experimental evolutionary ecologists, and theoretical population and quantitative geneticists working across a wide variety of systems. The group discussed the methods available to investigate epigenetic variation and epigenetic inheritance, and how to evaluate their importance for phenotypic evolution. We found that understanding the relevance of epigenetic effects in phenotypic evolution will require clearly delineating epigenetics within existing terminology and expanding research efforts into ecologically relevant circumstances across model and nonmodel organisms. In addition, a critical component of understanding epigenetics will be the development of new and current statistical approaches and expansion of quantitative and population genetic theory. Although the importance of heritable epigenetic
effects on evolution is still under discussion, investigating them in the context of a multidisciplinary approach could transform the field.

The talk will open with a discussion of a set of poems from Lyn Hejinian's The Unfollowing, which puts a positive spin on the association of old age with childhood. a trope that is often deployed to infantilize and disenfranchize older people. By contrast, Hejinian uses it to highlight life's openness and contigency. Taking a cue from the poet, I will mobilize the notion of "the old child" to explore questions like: do we get less creative as we age? Are we born with certain talents and/or do we keep acquiring and developing them later in life? What obstacles get in the way of the expression of our multiple valences as we get older? We will survey the latest research on the epigenetic development of giftedness across the life span, dwell on the lives of exemplary polymaths and late bloomers and discuss how these matters relate to the topics of labor division, meritocracy and leisure.

The human B cell survival factor, B cell activation factor (BAFF), and its closely related homologue, a proliferation-inducing ligand (APRIL), modulate B cell functions by binding to three receptors, BAFFR, TACI and BCMA. APRIL binds more strongly to BCMA than to TACI while the opposite is true for BAFF.  In addition, BAFF, but not APRIL, binds to BAFF-R with high affinity.  Both BAFF and APRIL are known to form homotrimers and heterotrimers, which display different affinities for their cognate receptors.  To understand the structural basis underlying the different binding affinities, we solved the crystal structure of the APRIL-BAFF-BAFF heterotrimer, either alone or bound to TACI.  Analysis of these structures and comparative analysis of previously solved structures of BAFF and APRIL in complex with BAFFR, TACI or BCMA revealed that the charged residues of BAFF and APRIL are crucial determinants of receptor binding affinities, conferring homotrimers and heterotrimers with a variety of signaling strength to modulate responses of immune cells.

Social Legal Theory (SLT) has been heralded as the “third pillar” of jurisprudence, offering a social scientific alternative to the rational relativity of legal positivism and the moral determinism of natural law. Yet recently SLT’s most ardent champion, Professor Brian Tamanaha, appears to have broken ranks. Assuming a “holistic” perspective, Tamanaha now contends that law “emerges” from both social and naturalistic influences. This move not only undermines SLT, it seemingly transforms that view into the existing theory of jurisilience, which uses the holistic epistemology of consilience to provide a bio-socio-cultural account of law’s essence.

Despite outward appearances, however, these approaches are far from identical. Unlike the revamped version of SLT, which is ontologically constrained and conflicted, jurisilience explains law’s emergence through systems science and cutting-edge sociology. It shows that law is not a simple assemblage of social and/or natural forces. Instead, it is a complex information network of interdependent “jurisystems.” Grounded in our natural need for homeostasis, human legality originates in our genetic and neurobiological systems, scales up to our normative social systems, and becomes externalized as a supreme system of formal law. Once entrenched, law does not remain stagnant, but continuously coordinates human conflicts, relieves social stress, and reinforces social bonds. Over time, law’s dynamism changes social behavior and cultural memory, initiating a cycle of epigenetics and gene-culture coevolution that renews our biological disposition for legality. Given law’s systemic nature, any socio-centric jurisprudence now seems obsolete. The fact is, jurisilience and jurisystems do not just systematize SLT; they systematize SLT right out of existence.

“One of the most gifted science journalists of his generation, Carl Zimmer tells a gripping human story about heredity from misguided notions that have caused terrible harm to recent ongoing research that promises to unleash more powerful technologies than the world has ever known.  The breadth of his perspective is extraordinarily compelling, compassionate, and valuable.  Please read this book now.”
—Jennifer Doudna, UC Berkeley, coauthor of A Crack in Creation

Viele der jüngeren Generation befassen sich, vor allem in sozialen Netzwerken, mit der Erforschung Ihrer Vergangenheit. Es wird auch viel nach dem eigenen
Familiennamen gegoogelt. Das ist so beliebt, dass die Internet Adressen über Ahnenforschung im Internet auf Rang zwei kommen.
Die genealogische Datensammlung ist das Gerüst für das Verständnis der Kulturgeschichte. Dies gilt vor allem für das Land unserer böhmisch-mährischen-schlesischen Vorfahren im Kernland Europas, den Ländern der Böhmischen Krone.
Mein Anliegen ist, den jeweiligen Abschnitt der Familiengeschichte im betreffenden kulturhistorischen Rahmen darzustellen.
Im Rahmen meiner Beratungstätigkeit in der ČSSR, ČSFR und ČR seit 1990, meiner Forschungen und in vielen Gesprächen wurde deutlich, dass trotz ehemaliger
ideologiefixierter Geschichtsschreibung in der ehemaligen Tschechoslowakei, dem Deutschen Reich und der Bundesrepublik/DDR im Herzen Europas viele
kulturelle und familiäre Gemeinsamkeiten bestanden und bestehen.
Die Historiographie und Möglichkeiten der Forschung sind meiner Erfahrung nach in Österreich besonders wertvoll. Aber auch in der Tschechischen Republik hat
sich viel getan!
Auf die besondere Bedeutung von genetischen und epigenetischen Faktoren wird hingewiesen. Gerade die Epigenetik, die durch unterschiedlichste "Umweltfaktoren" intensiv beeinflusst wird, hat für die Entwicklung auch unserer Vorfahren eine zentrale Bedeutung, die erst seit einigen jahren in seiner Dimension zu erkennen begonnen wurde.

Growing evidence points to the role of epigenetic mechanisms, including DNA methylation, in substance use and addiction. We conducted a systematic review of 47 recent (2012-15) animal and human studies that investigate DNA methylation and substance use/exposure, spanning preconception to adulthood. The majority of extant studies (i) focused on exposure during adulthood, (ii) examined the effects of alcohol use, (iii) employed a candidate gene approach and (iv) were cross-sectional. While studies generally support an association between substance use/exposure and DNA methylation, and also suggest that developmental context and timing matter, dearth of longitudinal data and low comparability across studies currently limits the conclusions that can be drawn. Future challenges and directions for the field are discussed

Despite their unique histories, environments, and lifestyles, historically subjugated populations consistently show poorer health outcomes compared to the general population. The theory of historical trauma, which argues that a collective trauma experienced by one generation can negatively impact the wellbeing of future generations , is a potential framework to understand the adverse health outcomes seen among populations with histories of subjugation. However, the biological pathways through which historical trauma actually impacts health have been unclear. In this paper, we present a cumulative, two pathway model that describes how historical trauma can impact health in contemporary generations. The first pathway suggests that personal exposure to trauma or stressors, which are more common among populations that have experienced historical trauma, can induce epigenetic modifications that can contribute to the development of poor health. The second pathway posits that poor health can occur through intergenerational epigenetic modifications in response to parental and grand-parental trauma or stressor exposures. Taken together, these pathways can provide insight into the higher rates of adverse health outcomes among individuals from populations that have historically endured collective trauma. Importantly, the potential reversible nature of epigenetic modifications suggests that these trauma-induced epigenetic effects are not necessarily permanent and that improvements in environmental conditions could reduce the high prevalence of poor health among historically disadvantaged communities.

Human language appears to be unique among natural communication systems, and such uniqueness impinges on both nature and nurture. Human babies are endowed with cognitive abilities that predispose them to learn language, and this process cannot operate in an impoverished environment. To be effectively complete the acquisition of human language in human children requires highly socialised forms of learning, scaffolded over years of prolonged and intense caretaker-child interactions. How genes and environment operate in shaping language is unknown. These two components have traditionally been considered as independent, and often pitted against each other in terms of the nature versus nurture debate. This perspective article considers how innate abilities and experience might instead work together. In particular, it envisages potential scenarios for research, in which early caregiver verbal and non-verbal attachment practices may mediate or moderate the expression of human genetic systems for language.

Circadian rhythms refer to the endogenous rhythms that are generated to synchronize physiology and behavior with 24-h environmental cues. These rhythms are regulated by both external cues and molecular clock mechanisms in almost all cells. Disruption of circadian rhythms, which is called circadian disruption, affects many biological processes within the body and results in different long-term diseases, including cancer. Circadian regulatory pathways result in rhythmic epigenetic modifications and the formation of circadian epigenomes. Aberrant epigenetic modifications, such as hypermethylation, due to circadian disruption may be involved in the transformation of normal cells into cancer cells. Several studies have indicated an epigenetic basis for the carcinogenic effects of circadian disruption. In this review, I first discuss some of the circadian genes and regulatory proteins. Then, I summarize the current evidence related to the epigenetic modifications that result in circadian disruption. In addition, I explain the carcinogenic effects of circadian disruption and highlight its potential role in different human cancers using an epigenetic viewpoint. Finally, the importance of chronotherapy in cancer treatment is highlighted.

In two studies, this thesis depicts the relationship between minority group status in the United States, perceived discrimination, and coping with stress. Past literature on coping and its types – problem-focused versus emotion-focused – is inconsistent in terms of differences between minority status groups and majority groups. It remains unknown whether or why Black Americans and lesbian or gay Americans may demonstrate coping patterns that differ from White Americans and heterosexual Americans, respectively. What is altogether absent from the literature is the possible mediating factor of perceived discrimination experienced by these minority groups. That is, differences in internal, stable coping processes that manage stress may have been molded by one’s experience with discrimination. Study 1 examines the relationship between race (Black versus White) and coping, mediated by perceived discrimination. Study 2 examines the relationship between sexual orientation (lesbian or gay versus heterosexual) and coping, mediated by perceived discrimination. Both studies confirm the thesis that minority group members exhibit maladaptive, emotion-focused coping more than majority group
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members – but that this difference is explained by the minority group members’ perceived discrimination. Historical and political relevance, social implications, and possible limitations in design and interpretation are discussed.