DNA helicases are a class of molecular motors that catalyze processive unwinding of double stranded DNA. In spite of much study, we know relatively little about the mechanisms by which these enzymes carry out the function for which they are named. Most current views are based on inferences from crystal structures. A prominent view is that the canonical ATPase motor exerts a force on the ssDNA resulting in “pulling” the duplex across a “pin” or “wedge” in the enzyme leading to (...) a mechanical separation of the two DNA strands. In such models, DNA base pair separation is tightly coupled to ssDNA translocation of the motors. However, recent studies of the Escherichia coli RecBCD helicase suggest an alternative model in which DNA base pair melting and ssDNA translocation occur separately. In this view, the enzyme‐DNA binding free energy is used to melt multiple DNA base pairs in an ATP‐independent manner, followed by ATP‐dependent translocation of the canonical motors along the newly formed ssDNA tracks. Repetition of these two steps results in processive DNA unwinding. We summarize recent evidence suggesting this mechanism for RecBCD helicase action. (shrink)

The mitochondrion is known as the “powerhouse” of eukaryotic cells since it is the main site of adenosine 5′‐triphosphate (ATP) production. Using a temperature‐sensitive fluorescent probe, it has recently been suggested that the stray free energy, not captured into ATP, is potentially sufficient to sustain mitochondrial temperatures higher than the cellular environment, possibly reaching up to 50 °C. By 50 °C, some DNA and mitochondrial proteins may reach their melting temperatures; how then do these biomolecules maintain their structure and (...) function? Further, the production of reactive oxygen species (ROS) accelerates with temperature, implying higher oxidative stresses in the mitochondrion than generally appreciated. Herein, it is proposed that mitochondrial heat shock proteins (particularly Hsp70), in addition to their roles in protein transport and folding, protect mitochondrial proteins and DNA from thermal and ROS damage. Other thermoprotectant mechanisms are also discussed. (shrink)

Natural selection of specific protobiomonomers during abiogenic development of the prototype genetic code is hindered by the diversity of structural, spatial, and rotational isomers that have identical elemental composition and molecular mass (M), but can vary significantly in their physicochemical characteristics, such as the melting temperature Tm, the Tm:M ratio, and the solubility in water, due to different positions of atoms in the molecule. These parameters differ between cis- and trans-isomers of dicarboxylic acids, spatial monosaccharide isomers, and structural isomers (...) of α-, β-, and γ-amino acids. The stable planar heterocyclic molecules of the major nucleobases comprise four (C, H, N, O) or three (C, H, N) elements and contain a single –C=C bond and two nitrogen atoms in each heterocycle involved in C–N and C=N bonds. They exist as isomeric resonance hybrids of single and double bonds and as a mixture of tautomer forms due to the presence of –C=O and/or –NH2 side groups. They are thermostable, insoluble in water, and exhibit solid-state stability, which is of central importance for DNA molecules as carriers of genetic information. In M–Tm diagrams, proteinogenic amino acids and the corresponding codons are distributed fairly regularly relative to the distinct clusters of purine and pyrimidine bases, reflecting the correspondence between codons and amino acids that was established in different periods of genetic code development. The body of data on the evolution of the genetic code system indicates that the elemental composition and molecular structure of protobiomonomers, and their M, Tm, photostability, and aqueous solubility determined their selection in the emergence of the standard genetic code. (shrink)

The ancient Greeks already used to give ethnic names to their different scales, and observations on differences in music of the various nations always raised the interest of musicians and philosophers. Yet, it was only in the late nineteenth century that “comparative musicology” became an institutional science. An important role in this process was played by Carl Stumpf, a former pupil of Brentano’s who pioneered these researches in Berlin. Stumpf founded the Phonogrammarchiv to collect recordings of folk and extra-European music (...) and a dedicated journal, the Sammelbände für vergleichende Musikwissenschaft. Gifted in the field of science no less than in that of musicology, Stumpf developed an empirically-oriented approach to phenomenology, deeply divergent from Husserl’s and highly influential over the Berlin school of Gestalt psychology. A self-declared “outsider” among armchair philosophers, Stumpf experimentally investigated the perception of sounds and the origins of musical consonance. Developing the physiological studies of Ernst Weber on the sense of touch, Stumpf discovered that two sensations of tone, given at the same time, tend to mix in a certain degree. Musical consonance – he claimed – lays in this level of “tonal fusion”, not in the allegedly “natural” series of the harmonic partials of a vibrating chord, as suggested by the naturalists of all times from Pythagoras to Stumpf’s great contemporary Hermann Helmholtz. Accordingly, no musical system can claim for preponderance over the others: Stumpf’s researches in comparative musicology served to corroborate his theses on “tonal fusion” and the psychological foundations of consonance. Although Stumpf later revised and finally abandoned this theory, its permanent value lays in its opposition to dominant naturalistic approaches. The commitment for comparative musicology at the Berlin School is then no concession to a positivistic fashion for exoticism. The fundamentally Eurocentric stance of naturalistic theories of music is also fiercely contrasted by Stumpf’s pupil Erich Hornbostel, who suggests that music ought to be considered as culture, rather than as nature, and focuses attention on the eventually melting human cultures. The Berlin school flourished until the Nazis forced most of its exponents to emigration and, for tragically obvious reasons, heavily discouraged researches on these topics. (shrink)

Methylation of DNA plays an important role in the control of gene expression in higher eukaryotes. This is largely achieved by the packaging of methylated DNA into chromatin structures that are inaccessible to transcription factors and other proteins. Methylation involves the addition of a methyl group to the 5‐position of the cytosine base in DNA, a reaction catalysed by a DNA (cytosine‐5) methyltransferase. This reaction occurs in nuclear replication foci where the chromatin structure is loosened for replication, thereby allowing access (...) to methyltransferases. Partly as a result of their recognising the presence of a methylcytosine on the parental strand following replication, these large enzymes are able to maintain the distribution of methyl groups along the DNA of somatic cells and, thereby, maintain tissue‐specific patterns of gene expression. (shrink)

Previous research with adults suggests that a catalog of minimally counterintuitive concepts, which underlies supernatural or religious concepts, may constitute a cognitive optimum and is therefore cognitively encoded and culturally transmitted more successfully than either entirely intuitive concepts or maximally counterintuitive concepts. This study examines whether children's concept recall similarly is sensitive to the degree of conceptual counterintuitiveness (operationalized as a concept's number of ontological domain violations) for items presented in the context of a fictional narrative. Seven- to nine-year-old children (...) who listened to a story including both intuitive and counterintuitive concepts recalled the counterintuitive concepts containing one (Experiment 1) or two (Experiment 2), but not three (Experiment 3), violations of intuitive ontological expectations significantly more and in greater detail than the intuitive concepts, both immediately after hearing the story and 1 week later. We conclude that one or two violations of expectation may be a cognitive optimum for children: They are more inferentially rich and therefore more memorable, whereas three or more violations diminish memorability for target concepts. These results suggest that the cognitive bias for minimally counterintuitive ideas is present and active early in human development, near the start of formal religious instruction. This finding supports a growing literature suggesting that diverse, early-emerging, evolved psychological biases predispose humans to hold and perform religious beliefs and practices whose primary form and content is not derived from arbitrary custom or the social environment alone. (shrink)

Mortal and immortal DNA : Craig Venter and the lure of "lamia" -- Homeopathy : Holmes, hogwarts, and the Prince of Wales -- Citizen Pinel and the madman at Bellevue -- The experimental pathology of stress : Hans Selye to Paris Hilton -- Gore's fever and Dante's Inferno : Chikungunya reaches Ravenna -- Giving things their proper names : Carl Linnaeus and W.H. Auden -- Spinal irritation and fibromyalgia : Lincoln's surgeon general and the three graces -- Tithonus and the (...) fruit fly : new science and old myths -- Swiftboating "America the beautiful" : Katharine Lee Bates and a Boston marriage -- Nothing makes sense in medicine except in the light of biology -- Apply directly to the forehead : Holmes, Zola, and Hennapecia -- Elizabeth Blackwell breaks the bonds -- Chronic lyme disease and medically unexplained syndromes -- Eugenics and the immigrant : Rosalyn Yalow and Rita Levi-Montalcini -- Science in the Middle East : Robert Koch and the cholera war -- How to win a Nobel prize : thinking inside and outside the box -- Homer Smith and the lungfish : the last gasp of intelligent design -- DDT is back : let us spray! -- Academic boycotts and the Royal Society -- Teach evolution, learn science : John William Draper and the "bone bill" -- Diderot and the yeti crab : the encyclopedias of life -- Dengue fever in Rio : Macumba versus Voltaire. (shrink)

DNA topoisomerases, capable of manipulating DNA topology, are ubiquitous and indispensable for cellular survival due to the numerous roles they play during DNA metabolism. As we review here, current structural approaches have revealed unprecedented insights into the complex DNA‐topoisomerase interaction and strand passage mechanism, helping to advance our understanding of their activities in vivo. This has been complemented by single‐molecule techniques, which have facilitated the detailed dissection of the various topoisomerase reactions. Recent work has also revealed the importance of topoisomerase (...) interactions with accessory proteins and other DNA‐associated proteins, supporting the idea that they often function as part of multi‐enzyme assemblies in vivo. In addition, novel topoisomerases have been identified and explored, such as topo VIII and Mini‐A. These new findings are advancing our understanding of DNA‐related processes and the vital functions topos fulfil, demonstrating their indispensability in virtually every aspect of DNA metabolism. (shrink)

The nuclear pore complex (NPC) is emerging as a center for recruitment of a class of “difficult to repair” lesions such as double‐strand breaks without a repair template and eroded telomeres in telomerase‐deficient cells. In addition to such pathological situations, a recent study by Su and colleagues shows that also physiological threats to genome integrity such as DNA secondary structure‐forming triplet repeat sequences relocalize to the NPC during DNA replication. Mutants that fail to reposition the triplet repeat locus to the (...) NPC cause repeat instability. Here, we review the types of DNA lesions that relocalize to the NPC, the putative mechanisms of relocalization, and the types of recombinational repair that are stimulated by the NPC, and present a model for NPC‐facilitated repair. (shrink)

Abstract6‐methyladenine (6mA) is fairly abundant in nuclear DNA of basal fungi, ciliates and green algae. In these organisms, 6mA is maintained near transcription start sites in ApT context by a parental‐strand instruction dependent maintenance methyltransferase and is positively associated with transcription. In animals and plants, 6mA levels are high only in organellar DNA. The 6mA levels in nuclear DNA are very low. They are attributable to nucleotide salvage and the activity of otherwise mitochondrial METTL4, and may be considered as a (...) price that cells pay for adenine methylation in RNA and/or organellar DNA. Cells minimize this price by sanitizing dNTP pools to limit 6mA incorporation, and by converting 6mA that has been incorporated into DNA back to adenine. Hence, 6mA in nuclear DNA should be described as an epigenetic mark only in basal fungi, ciliates and green algae, but not in animals and plants. (shrink)

The repair of chromosomal double‐strand breaks (DSBs) by homologous recombination is essential to maintain genome integrity. The key step in DSB repair is the RecA/Rad51‐mediated process to match sequences at the broken end to homologous donor sequences that can be used as a template to repair the lesion. Here, in reviewing research about DSB repair, I consider the many factors that appear to play important roles in the successful search for homology by several homologous recombination mechanisms.

Over 30 million people worldwide have taken a commercial at-home DNA test, because they were interested in their genetic ancestry, disease predisposition or inherited traits. Yet, these consumer DNA data are also increasingly used for a very different purpose: to identify suspects in criminal investigations. By matching a suspect’s DNA with DNA from a suspect’s distant relatives who have taken a commercial at-home DNA test, law enforcement can zero in on a perpetrator. Such forensic use of consumer DNA data has (...) been performed in over 200 criminal investigations. However, this practice of so-called investigative genetic genealogy raises ethical concerns. In this paper, we aim to broaden the bioethical analysis on IGG by showing the limitations of an individual-based model. We discuss two concerns central in the debate: privacy and informed consent. However, we argue that IGG raises pressing ethical concerns that extend beyond these individual-focused issues. The very nature of the genetic information entails that relatives may also be affected by the individual customer’s choices. In this respect, we explore to what extent the ethical approach in the biomedical genetic context on consent and consequences for relatives can be helpful for the debate on IGG. We argue that an individual-based model has significant limitations in an IGG context. The ethical debate is further complicated by the international, transgenerational and commercial nature of IGG. We conclude that IGG should not only be approached as an individual but also—and perhaps primarily—as a collective issue. There are no data in this work. (shrink)

This Christian sermon uses a DNA lab experience as a basis for theological reflection on ourselves and our offering. Who are we to God? What determines the self that we offer? Can the alphabet of DNA shed light for us on the Word of God in our lives? This first attempt to introduce the language and laboratory environment of genetic testing (represented by DNA fingerprinting) within a parish preaching context juxtaposes liturgical, scientific, and biblical language and settings for fresh insights.

Through analysis of film sequences focusing on DNA in two British Broadcasting Corporation nonfiction science television programs, Wonders of Life and Bang! Goes the Theory, first broadcast in 2013, contrasting “religious” and “secular” representations of science are identified. In the “religious” portrayal, immutable scientific knowledge is revealed to humanity by nature with minimal human intervention. Science provides a creation story, “explanatory omnicompetence,” and makes life existentially meaningful. In the “secular” portrayal, scientific knowledge is changeable; is produced through technical skill in (...) expert communities; and is ambiguous, potentially positive and negative for society. Television representations of science affect audience understandings, and this is particularly the case for nonfiction representations of science, as they are likely to be “taken more seriously” than fictional representations. The consequences of the “religious” representation of science are discussed, and it is argued that a widespread understanding of science as presented in the religious portrayal would negatively impact democracy. (shrink)

This book shows how the study of multi-hadron production phenomena in the years after the founding of CERN culminated in Hagedorn's pioneering idea of limiting temperature, leading on to the discovery of the quark-gluon plasma -- announced, in February 2000 at CERN. Following the foreword by Herwig Schopper -- the Director General (1981-1988) of CERN at the key historical juncture -- the first part is a tribute to Rolf Hagedorn (1919-2003) and includes contributions by contemporary friends and colleagues, and those (...) who were most touched by Hagedorn: Tamás Biró, Igor Dremin, Torleif Ericson, Marek Gaździcki, Mark Gorenstein, Hans Gutbrod, Maurice Jacob, István Montvay, Berndt Müller, Grazyna Odyniec, Emanuele Quercigh, Krzysztof Redlich, Helmut Satz, Luigi Sertorio, Ludwik Turko, and Gabriele Veneziano. The second and third parts retrace 20 years of developments that after discovery of the Hagedorn temperature in 1964 led to its recognition as the melting point of hadrons into boiling quarks, and to the rise of the experimental relativistic heavy ion collision program. These parts contain previously unpublished material authored by Hagedorn and Rafelski: conference retrospectives, research notes, workshop reports, in some instances abbreviated to avoid duplication of material, and rounded off with the editor's explanatory notes. About the editor: Johann Rafelski is a theoretical physicist working at The University of Arizona in Tucson, USA. Born in 1950 in Krakow, Poland, he received his Ph.D. with Walter Greiner in Frankfurt, Germany in 1973. Rafelski arrived at CERN in 1977, where in a joint effort with Hagedorn he contributed greatly to the establishment of the relativistic heavy ion collision, and quark-gluon plasma research fields. Moving on, with stops in Frankfurt and Cape Town, to Arizona, he invented and developed the strangeness quark flavor as the signature of quark-gluon plasma. (shrink)

Emerging evidence suggests that DNA topology plays an instructive role in cell fate control through regulation of gene expression. Transcription produces torsional stress, and the resultant supercoiling of the DNA molecule generates an array of secondary structures. In turn, local DNA architecture is harnessed by the cell, acting within sensory feedback mechanisms to mediate transcriptional output. MYC is a potent oncogene, which is upregulated in the majority of cancers; thus numerous studies have focused on detailed understanding of its regulation. Dissection (...) of regulatory regions within the MYC promoter provided the first hint that intimate feedback between DNA topology and associated DNA remodeling proteins is critical for moderating transcription. As evidence of such regulation is also found in the context of many other genes, here we expand on the prototypical example of the MYC promoter, and also explore DNA architecture in a genome-wide context as a global mechanism of transcriptional control. Torsional stress, and supercoiling generated by transcription, shape the topology of DNA. Furthermore, the resultant secondary DNA structures and their interacting partners provide feedback to regulate gene expression. Emerging evidence suggests these mechanisms, identified through analysis of the MYC promoter, are applicable genome-wide. (shrink)

With their intensive use of data to classify and price risk, insurers have often been confronted with data-related issues of fairness and discrimination. This paper provides a comparative review of discrimination issues raised by traditional statistics versus machine learning in the context of insurance. We first examine historical contestations of insurance classification, showing that it was organized along three types of bias: pure stereotypes, non-causal correlations, or causal effects that a society chooses to protect against, are thus the main sources (...) of dispute. The lens of this typology then allows us to look anew at the potential biases in insurance pricing implied by big data and machine learning, showing that despite utopic claims, social stereotypes continue to plague data, thus threaten to unconsciously reproduce these discriminations in insurance. To counter these effects, algorithmic fairness attempts to define mathematical indicators of non-bias. We argue that this may prove insufficient, since as it assumes the existence of specific protected groups, which could only be made visible through public debate and contestation. These are less likely if the right to explanation is realized through personalized algorithms, which could reinforce the individualized perception of the social that blocks rather than encourages collective mobilization. (shrink)

The aim of this paper is to explain the emergence and use of DNA fingerprinting technology in India, noting the specific concerns faced by the Indian Legal System related to the use of this novel forensic technology in the justice process. Furthermore, the proposed construction of a National DNA Data Bank is discussed taking into consideration the challenges faced by the government in legislating the DNA Bill into law. A critical analysis of the DNA Technology (Use and Application) Regulation Bill, (...) 2019 is provided to throw light upon many ethical, social, and legal issues that need to be addressed before the operationalization of the Bill to ensure that this technology is governed democratically to protect the civil liberties of citizens. (shrink)

Science; Ethics; Politics; Beyond recombinant dna.

Ribonucleotide reductase (RNR) catalyzes the rate limiting step in the production of deoxyribonucleotides needed for DNA synthesis. In addition to the well documented allosteric regulation, the synthesis of the enzyme is also tightly regulated at the level of transcription. mRNAs for both subunits are cell cycle regulated and inducible by DNA damage in all organisms examined, including E. coli, S. cerevisiae and H. sapiens. This DNA damage regulation is thought to provide a metabolic state that facilitates DNA replicational repair processes. (...) S. cerevisiae also encodes a second large subunit gene, RNR3, that is expressed only in the presence of DNA damage. Genetic analysis of the DNA damage response in S. cerevisiae has shown that RNR expression is under both positive and negative control. Among mutants constitutive for RNR expression are the general transcriptional repression genes, SSN6 and TUP1. Mutations in POL1 and POL3 also activate RNR expression, indicating that the DNA damage sensory network may respond directly to blocks in DNA synthesis. A protein kinase, Dun1, has been identified that controls inducibility of RNR1, RNR2 and RNR3 in response to DNA damage and replication blocks. This result suggests that the RNR genes in S. cerevisiae form a regulon that is coordinately regulated by protein phosphorylation in response to DNA damage. (shrink)

Recent studies based on next‐generation DNA sequencing have revealed that the female inactive X chromosome is replicated in a rapid, unorganized manner, and undergoes increased rates of mutation. These observations link the organization of DNA replication timing to gene regulation on one hand, and to the generation of mutations on the other hand. More generally, the exceptional biology of the inactive X chromosome highlights general principles of genome replication. Cells may control replication timing by a combination of intrinsic replication origin (...) properties, local chromatin states and global levels of replication factors, leading to a functional separation between the activity of genes and their mutation. (shrink)

Our potential for dissecting the complex processes involved in eukaryotic DNA replication has been dramatically increased with the recent development of cell‐free systems that recreate many of these processes in vitro. Initial results from these systems have drawn together work on the cell cycle, the enzymology of replication, and the structure of the nucleus.

Research has shown that minimally counterintuitive concepts are more memorable than concepts that are simply bizarre. However, this disparity may exist only in studies using cross-cultural samples. To test the impact of bizarreness on culturally homogeneous populations, we read a fictional narrative to 33 college-age students at a Midwestern university. This narrative featured 18 sets of target items – six which were intuitive, six which were counterintuitive, and six which were bizarre. After hearing the story, experimenters administered a written recall (...) task. As hypothesized, students did not differ in their recall of counterintuitive or bizarre target items. Therefore, we propose a minimally distinctive model of memorability, encompassing both counterintuitiveness and bizarreness. This model may help us better understand the memorability of expectation violations, especially those within religious stories. (shrink)

Here, the emerging data on DNA G‐quadruplexes (G4s) as epigenetic modulators are reviewed and integrated. This concept has appeared and evolved substantially in recent years. First, persistent G4s (e.g., those stabilized by exogenous ligands) were linked to the loss of the histone code. More recently, transient G4s (i.e., those formed upon replication or transcription and unfolded rapidly by helicases) were implicated in CpG island methylation maintenance and de novo CpG methylation control. The most recent data indicate that there are direct (...) interactions between G4s and chromatin remodeling factors. Finally, multiple findings support the indirect participation of G4s in chromatin reshaping via interactions with remodeling‐related transcription factors (TFs) or damage responders. Here, the links between the above processes are analyzed; also, how further elucidation of these processes may stimulate the progress of epigenetic therapy is discussed, and the remaining open questions are highlighted. (shrink)

This paper focuses on the question of whether DNA patents help or hinder scientific discovery and innovation. While DNA patents create a wide variety of possible benefits and harms for science and technology, the evidence we have at this point in time supports the conclusion that they will probably promote rather than hamper scientific discovery and innovation. However, since DNA patenting is a relatively recent phenomena and the biotechnology industry is in its infancy, we should continue to gather evidence about (...) the effects of DNA patenting on scientific innovation and discovery as well the economic, social, and legal conditions relating to intellectual property in biotechnology. We should give the free market, the courts, researchers, and patent offices a chance to settle issues related to innovation and discovery, before we seek legislative remedies, since new laws proposed at this point would lack adequate foresight and could do more harm than good. However, we should be open to new laws or regulations on DNA patents if they are required to in order to deal with some of the biases and limitations of the free market. (shrink)

Type II DNA topoisomerase activity is required to change DNA topology. It is important in the relaxation of DNA supercoils generated by cellular processes, such as transcription and replication, and it is essential for the condensation of chromosomes and their segregation during mitosis. In mammals this activity is derived from at least two isoforms, termed DNA topoisomerase IIα and β. The α isoform is involved in chromosome condensation and segregation, whereas the role of the β isoform is not yet clear. (...) DNA topoisomerase IIβ was first reported in 1987. Here we review the research on DNA topoisomerase IIβ over the last 10 years. BioEssays 20:215–226, 1998.© 1998 John Wiley & Sons, Inc. (shrink)

Type II DNA topoisomerase activity is required to change DNA topology. It is important in the relaxation of DNA supercoils generated by cellular processes, such as transcription and replication, and it is essential for the condensation of chromosomes and their segregation during mitosis. In mammals this activity is derived from at least two isoforms, termed DNA topoisomerase IIα and β. The α isoform is involved in chromosome condensation and segregation, whereas the role of the β isoform is not yet clear. (...) DNA topoisomerase IIβ was first reported in 1987. Here we review the research on DNA topoisomerase IIβ over the last 10 years. BioEssays 20:215–226, 1998.© 1998 John Wiley & Sons, Inc. (shrink)

As nation-states make greater efforts to regulate the flow of people on the move—refugees, economic migrants, and international travelers alike—advocates of DNA profiling technologies claim DNA testing provides a reliable and objective way of revealing a person’s true identity for immigration procedures. This article examines the use of DNA testing for family reunification in immigration cases in Finland, Germany, and the United States—the first transatlantic analysis of such cases—to explore the relationship between technology, the meaning of family, and immigration. Drawing (...) on our analyses of archival records, government documents, and interviews with immigration stakeholders, we argue that DNA testing is not conclusive about the meaning of family. While the technology may facilitate decision making for both would-be immigrants and state officials, our study shows hesitancy among the latter to let DNA testing make the final determination. We introduce the concept of social validity—whether the interpretation of test results matches social or political meanings in a given local context—in order to make sense of the complexities and challenges of DNA testing in practice. We show that DNA testing is not just a technology of belonging or a way to claim citizenship rights. It may also enable exclusion and denial of rights. (shrink)

Eukaryotic cells are able to mount several genetically complex cellular responses to DNA damage. The yeast Saccharomyces cerevisiae is a genetically well characterized organism that is also amenable to molecular and biochemical studies. Hence, this organism has provided a useful and informative model for dissecting the biochemistry and molecular biology of DNA repair in eukaryotes.

The catalyst for much of classical pragmatist political thought was the great waves of migration to the United States in the early 20th century. José-Antonio Orosco examines the work of several pragmatist social thinkers, including John Dewey, W. E. B. Du Bois, Josiah Royce, and Jane Addams, regarding the challenges large-scale immigration brings to American democracy. Orosco argues that the ideas of the classical pragmatists can help us understand the ways in which immigrants might strengthen the cultural foundations of the (...) United States in order to achieve a more deliberative and participatory democracy. Like earlier pragmatists, Orosco begins with a critique of the melting pot in favor of finding new ways to imagine the civic role of our immigrant population. He concludes that by applying the insights of American pragmatism, we can find guidance through controversial contemporary issues such as undocumented immigration, multicultural education, and racialized conceptions of citizenship. (shrink)

DNA methylation is a repressive epigenetic mark vital for normal development. Recent studies have uncovered an unexpected role for the DNA methylome in ensuring the correct targeting of the Polycomb repressive complexes throughout the genome. Here, we discuss the implications of these findings for cancer, where DNA methylation patterns are widely reprogrammed. We speculate that cancer‐associated reprogramming of the DNA methylome leads to an altered Polycomb binding landscape, influencing gene expression by multiple modes. As the Polycomb system is responsible for (...) the regulation of genes with key roles in cell fate decisions and cell cycle regulation, DNA methylation induced Polycomb mis‐targeting could directly drive carcinogenesis and disease progression.Editor's suggested further reading in BioEssays Unmasking risk loci: DNA methylation illuminates the biology of cancer predisposition Abstract. (shrink)

DNA methylation can be considered a component of epigenetic memory with a critical role during embryo development, and which undergoes dramatic reprogramming after fertilization. Though it has been a focus of research for many years, the reprogramming mechanism is still not fully understood. Recent results suggest that absence of maintenance at DNA replication is a major factor, and that there is an unexpected role for TET3-mediated oxidation of 5mC to 5hmC in guarding against de novo methylation. Base-resolution and genome-wide profiling (...) methods are enabling more comprehensive assessments of the extent to which ART might impair DNA methylation reprogramming, and which sequence elements are most vulnerable. Indeed, as we also review here, studies showing the effect of culture media, ovarian stimulation or embryo transfer on the methylation pattern of embryos emphasize the need to face ART-associated defects and search for strategies to mitigate adverse effects on the health of ART-derived children. DNA methylation, critical for embryo development, suffers significant changes after fertilization, including demethylation, remethylation and TET3-mediated oxidation of 5 mC to 5 hmC. In addition to infertility and environmental insults, ART could impact DNA methylation and ART related consequences in the offspring have been reported. (shrink)

DNA profiling is a well-established technology for use in the criminal justice system, both in courtrooms and elsewhere. The fact that DNA profiles are based on non-coding DNA and do not reveal details about the physical appearance of an individual has contributed to the acceptability of this type of evidence. Its success in criminal investigation, combined with major innovations in the field of genetics, have contributed to a change of role for this type of evidence. Nowadays DNA evidence is not (...) merely about identification, where trace evidence is compared to a sample taken from a suspect. An ever-growing role is anticipated for DNA profiling as an investigative tool, a technique aimed at generating a suspect where there is none. One of these applications is the inference of visible traits. As this article will show, racial classifications are at the heart of this application. The Netherlands and its legal regulation of 'externally visible traits' will serve as an example. It will be shown that, to make this technology work, a large number of actors has to be enrolled and their articulations invited. This indicates that instead of a 'silent witness', a DNA profile should rather be seen as an 'articulate collective'. Based on two cases, I argue that the normativity of visible traits is context-dependent. Taking into account the practices in which technology is put to use alerts us to novel ethical questions raised by their application. (shrink)

We are witnesses to a major reshaping of our world: the World and our lives as we used to know are ending and they are reshaping constantly and drastically under pressure. Everything we knew about this world, our old habits, values, human rights, ethical patterns et all. These days, since the pandemic outburst, I saw the perceptions we have/had on religious impositions and requirements changing for an unprecedented behavior and inconsiderably reshaping religious phenomenon could have ever think of. With the (...) title taken from the topic of this volume, Inspired by the conference titled, we have tried to envision the actual human environment through the ongoing pandemic that revolutions the entire human society in a way we had never considered as possible and so that we will not recognize in a year or so. Following the Philosophy of Dialectics and seeing a larger number of possibilities beyond those that were revealed to us in most obvious ways, we wonder thus, what makes us, in fact, do these changes – is the pandemic itself and its requirements or is it just US, humans, that were long longing for a change, a motif to do it all new again? It is though a human-divine desire to anew all from time to time and seek a reboot to all wrongness that grows in the world. (shrink)