HIV‐1 infects dendritic cells (DCs) without triggering an effective innate antiviral immune response. As a consequence, the induction of adaptive immune responses controlling virus spread is limited. In a recent issue of Immunity, Lahaye and colleagues show that intricate interactions of HIV capsid with the cellular cofactor cyclophilin A (CypA) control infection and innate immune activation in DCs. Manipulation of HIV‐1 capsid to increase its affinity for CypA results in reduced virus infectivity and facilitates access of the cytosolic DNA (...) sensor cGAS to reverse transcribed DNA. This in turn induces a strong host response. Here, we discuss these findings in the context of recent developments in innate immunity and consider the implications for disease control and vaccine design. (shrink)

Promyelocytic leukaemia nuclear bodies (PML NBs) are generally present in all mammalian cells, and their integrity correlates with normal differentiation of promyelocytes. Mice that lack PML NBs have impaired immune function, exhibit chromosome instability and are sensitive to carcinogens. Although their direct role in nuclear activity is unclear, PML NBs are implicated in the regulation of transcription, apoptosis, tumour suppression and the anti‐viral response. An emerging view is that they represent sites where multi‐subunit complexes form and where post‐translational modification of (...) regulatory factors, such as p53, occurs in response to cellular stress. Following DNA damage, several repair factors transit through PML NBs in a temporally regulated manner implicating these bodies in DNA repair. We propose that PML NBs are dynamic sensors of cellular stress, which rapidly disassemble following DNA damage into large supramolecular complexes, dispersing associated repair factors to sites of damage. The dramatically increased total surface area available would enhance interactions between PML‐associated factors regulating DNA repair and apoptosis. BioEssays 26:963–977, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

Timers and sensors are common devices that make our daily life safer, more convenient, and more efficient. In a cellular context, they arguably play an even more crucial role as they ensure the survival of cells in the presence of various extrinsic and intrinsic stresses. Biological timers and sensors generate distinct signaling profiles, enabling them to produce different types of cellular responses. Recent data suggest that they can work together to guarantee correct timing and responsiveness. By exploring examples of cellular (...) stress signaling from mitosis, DNA damage, and hypoxia, the authors discuss the common architecture of timer‐sensor integration, and how its added features contribute to the generation of desired signaling profiles when dealing with stresses of variable duration and strength. The authors propose timer‐sensor integration as a widespread mechanism with profound biological implications and therapeutic potential. -/- . (shrink)

Interferon stimulated gene 15 (ISG15) encodes a ubiquitin‐like protein that is highly induced upon activation of interferon signaling and cytoplasmic DNA sensing pathways. As part of the innate immune system ISG15 acts to inhibit viral replication and particle release via the covalent conjugation to both viral and host proteins. Unlike ubiquitin, unconjugated ISG15 also functions as an intracellular and extra‐cellular signaling molecule to modulate the immune response. Several recent studies have shown ISG15 to also function in a diverse array of (...) cellular processes and pathways outside of the innate immune response. This review explores the role of ISG15 in maintaining genome stability, particularly during DNA replication, and how this relates to cancer biology. It puts forth the hypothesis that ISG15, along with DNA sensors, function within a DNA replication fork surveillance pathway to help maintain genome stability. (shrink)

DNA replication stress threatens ordinary DNA synthesis. The evolutionarily conserved DNA replication stress response pathway involves sensor kinase Mec1/ATR, adaptor protein Mrc1/Claspin, and effector kinase Rad53/Chk1, which spurs a host of changes to stabilize replication forks and maintain genome integrity. DNA replication forks consist of largely distinct sets of proteins at leading and lagging strands that function autonomously in DNA synthesis in vitro. In this article, we discuss eSPAN and BrdU‐IP‐ssSeq, strand‐specific sequencing technologies that permit analysis of protein localization (...) and DNA synthesis at individual strands in budding yeast. Using these approaches, we show that under replication stress Rad53 stalls DNA synthesis on both leading and lagging strands. On lagging strands, it stimulates PCNA unloading, and on leading strands, it attenuates the replication function of Mrc1‐Tof1. We propose that in doing so, Rad53 couples leading and lagging strand DNA synthesis during replication stress, thereby preventing the emergence of harmful ssDNA. (shrink)

Ataxia‐telangiectasia (A‐T) is a pleiotropic recessive disorder characterized cerebellar ataxia, immunodeficiency, specific developmental defects, profound predisposition to cancer and acute radiosensitivity. Functional inactivation of single gene product, ATM, accounts for this compound phenotype. We suggest that ATM acts as a sensor of reactive oxygen species and/or oxidative damage cellular macromolecules, including DNA. In turn, ATM induces signalling through multiple pathways, thereby coordinating acute phase stress responses with cell cycle checkpoint control and repair of oxidative damage. Absence of ATM is (...) proposed to limit the repair of insidious oxidative damage that can occur under normal physiological conditions, ultimately leading to apoptosis of particularly sensitive cells, such as neurons and thymocytes. (shrink)

During the evolution of aerobic life, antioxidant defence systems developed that either directly prevent oxidative modifications of the cellular constituents or remove the modified components. An example of the latter is the proteasome, which removes cytosolic oxidised proteins. Recently, a novel mechanism of activation of the nuclear 20S proteasome was discovered: automodified poly‐(ADP‐ribose) polymerase‐1 (PARP‐1) activates the proteasome to facilitate selective degradation of oxidatively damaged histones. Since activation of the PARP‐1 itself is induced by DNA damage and is supposed (...) to play a role in DNA repair, these new results suggest a joint role of PARP‐1 in the removal of oxidised nucleoproteins and in DNA repair. We hypothesise that PARP‐1 could provide a co‐ordinative link between two nuclear antioxidant defence systems, whose concerted activation would produce a fast and efficient restoration of the native chromatin structure following oxidative stress. BioEssays 24:1060–1065, 2002. © 2002 Wiley‐Periodicals, Inc. (shrink)

Included in the acute response of lowlanders exposed to reduced oxygen availability is an elevated red blood cell count due to increased erythropoietin (Epo) synthesis. According to current thinking, hypoxia is “sensed” by hydroxylases that permit Hypoxia Inducible Factor 1α (HIF‐1α) to complex with HIF‐1β to form a transcriptional activator (HIF‐1) that drives expression of hypoxia‐sensitive genes (such as EPO) under hypoxic conditions. In altitude‐adapted Andean natives, the Epo hypoxic response may be blunted; however, our data indicate that the DNA (...) sequences of the genes encoding Epo (including the 3′ regulatory region) and HIF‐1α appear to be conserved. Hence, adaptive changes in the Andean hypoxic response are not a consequence of changes in the primary sequence of these proteins or of known transcriptional regulatory domains of EPO. These results suggest that the altered erthropoietic response in Andean natives reflects adaptations in hypoxia sensing, rather than hypoxia response, mechanisms. BioEssays 25:515–519, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

Poly(ADP‐ribosyl)ation is a post‐translational modification occurring in the nucleus. The most abundant and best‐characterized enzyme catalyzing this reaction, poly(ADP‐ribose) polymerase 1 (PARP1), participates in fundamental nuclear events. The enzyme functions as molecular “nick sensor”. It binds with high affinity to DNA single‐strand breaks resulting in the initiation of its catalytic activity. Activated PARP1 promotes base excision repair. In addition, PARP1 modifies several transcription factors and thereby precludes their binding to DNA. We propose that a major function of PARP1 includes (...) the silencing of transcription preventing expression of damaged genes. Concomitant stimulation of DNA repair suggests that PARP1 acts as a switch between transcription and DNA repair. Another PARP‐type enzyme, tankyrase, is involved in the regulation of telomere elongation. Tankyrase modifies a telomere‐associated protein and thereby prevents it masking telomeric repeats providing access of telomerase for telomere elongation. Therefore, poly(ADP‐ribosyl)ation reactions may act as molecular switches in DNA metabolism. BioEssays 23:543–548, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

The correct execution of the DNA replication process is crucially import for the maintenance of genome integrity of the cell. Several types of sources, both endogenous and exogenous, can give rise to DNA damage leading to the DNA replication fork arrest. The processes by which replication blockage is sensed by checkpoint sensors and how the pathway leading to resolution of stalled forks is activated are still not completely understood. However, recent emerging evidence suggests that one candidate for a sensor (...) of replication stress is ATR and that, together with a member of RecQ family helicases, Werner syndrome protein (WRN) and MRE11 complex, can collaborate to promote the restarting of DNA synthesis through the resolution of stalled replication forks. Here, we discuss how WRN, the MRE11 complex and the ATR kinase could work together in response to replication blockage to avoid DNA replication fork collapse and genome instability. BioEssays 26:306–313, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

The complexity of calcium profiles observed in plant cells has led to the realization that specific patterns of calcium propagation (now termed calcium signatures) encode specific information and relay it to downstream elements (effectors) for translation into corresponding cellular responses in higher plants. The concept of calcium signatures is now well established and the tight control of the temporal and spatial characteristics of cytosolic calcium alterations is considered to be responsible for the specificity of various cellular responses, in particular (...) to environment‐induced stresses. To date, three major classes of plant calcium sensors responsible for drought‐stress signal transduction during soil water deficit have been identified. Valuable pieces of the calcium signal‐specificity puzzle are being put together and are illustrated here for the calcium‐mediated signal‐transduction cascades that operate in the responses of higher plants to soil environmental deficits. BioEssays 30:634–641, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

The versatile clustered regularly interspaced short palindromic repeats (CRISPR)/Cas system has emerged as a promising technology for therapy and molecular diagnosis. It is especially suited for overcoming viral infections outbreaks, since their effective control relies on an efficient treatment, but also on a fast diagnosis to prevent disease dissemination. The CRISPR toolbox offers DNA‐ and RNA‐targeting nucleases that constitute dual weapons against viruses. They allow both the manipulation of viral and host genomes for therapeutic purposes and the detection of viral (...) nucleic acids in “Point of Care” sensor devices. Here, we thoroughly review recent advances in the use of the CRISPR/Cas system for the treatment and diagnosis of viral deleterious infections such as HIV or SARS‐CoV‐2, examining their strengths and limitations. We describe the main points to consider when designing CRISPR antiviral strategies and the scientific efforts to develop more sensitive CRISPR‐based viral detectors. Finally, we discuss future prospects to improve both applications. Also see the video abstract here: https://www.youtube.com/watch?v=C0z1dLpJWl4. (shrink)

The quantitative study of regulation of cell growth and proliferation began with the development of the technique for monolayer culture of vertebrate cells in the late 1960s. The basic parameters were defined in the early physiological studies, which continued through the next decade. These included specific and non-specific growth factors and the requirement for continuous exposure to such factors through most of the G1 period for progression to S. In the course of this work, the diversity of biochemical responses and (...) the critical role of increased protein synthesis and accumulation for the onset of DNA synthesis were elucidated. In particular, a central role of free cytosolic Mg2+ in direct regulation of protein synthesis and in ancillary processes as a response to membrane perturbation was established. Eventually, the physiological era was superseded by the molecular era beginning in the 1980s. This work focussed on specific receptors for growth factors that entrained a protein kinase cascade, which terminated in a higher frequency of initiation of protein synthesis. However, the molecular studies virtually ignored the key results of the physiological era. Recent studies of the penultimate molecular steps in the regulatory pathway of protein synthesis, however, have supported a model of growth regulation involving membrane perturbation and MgATP2− concentration, results that integrate the findings of the physiological and molecular eras. The resulting relatively simple “membrane, magnesium mitosis” (MMM) model of proliferation control can explain the seeming paradox of the variety of specific and non-specific growth-enhancing treatments that are mediated by the plasma membrane and which bring about a shared, complex but coordinated growth response that drives cell proliferation. BioEssays 27:311–320, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

Nuclear pore complexes mediate and control transport between the cytosol and the nucleus. They form a highly selective and, thus, tight nuclear barrier between these compartments. The nuclear barrier provides the cell with the opportunity to control access to its DNA, a defining feature of eukaryotes. The tightness of the nuclear barrier is therefore physiologically pivotal and any remarkable change in its structure and permeability can prove pathophysiological, e.g. as a result of viral attack. However, there is accumulating evidence that (...) nuclear barrier structure and permeability are highly responsive to hydrophobic cargos of crucial physiological and therapeutic relevance, glucocorticoids (steroid hormones). The present review highlights the glucocorticoid‐induced effects on the nuclear barrier structure and permeability concluding that they are physiologically essential to mediate glucocorticoid action. BioEssays 28: 935–942, 2006. © 2006 Wiley periodicals, Inc. (shrink)

The Mexico-U.S. border is a space considered `smart´ due to the amount of surveillance technology used for national security purposes. The technological ecology consists of integrated fixed towers, remote video surveillance systems, mobile video surveillance systems, Predator B surveillance drones, mobile X-ray units, automated license plate readers, cell phone tracking towers, implanted motion sensors, biometric data collection, and DNA sampling (Aizeki et al. Citation2021). Whilst these instruments are usually linked to irregular border crossers, transborder commuters, who physically cross the border (...) every day, also experience the same surveillance regime. This paper discusses the technological ‘self-defense’ protocol I developed in 2019 when conducting transborder research for my doctoral thesis, which required intense border crossings across Mexico and the U.S. During the ten months of fieldwork, U.S. CBP had the capacity to search my personal device and belongings without a warrant, raising ethical concerns about data protection. As a result, the protocol developed to protect data and participants considered the ‘smart’ border as part of the methods designed that included encrypting information. In hyper-surveilled spaces, data protection represents a challenge for border researchers and the people involved in such a project. (shrink)

How chromatin bridges are detected by the abscission checkpoint during mammalian cell division is unknown. Here, we discuss recent findings from our lab showing that the DNA topoisomerase IIα (Top2α) enzyme binds to catenated (“knotted”) DNA next to the midbody and forms abortive Top2‐DNA cleavage complexes (Top2ccs) on chromatin bridges. Top2ccs are then processed by the proteasome to promote localization of the DNA damage sensor protein Rad17 to Top2‐generated double‐strand DNA ends on DNA knots. In turn, Rad17 promotes local (...) recruitment of the MRN protein complex and downstream ATM‐Chk2‐INCENP signaling to delay abscission and prevent chromatin bridge breakage in cytokinesis. (shrink)

Based on earlier studies of J. C. R. Licklider, this article translocates the context of symbiosis between man and the machine into the built environment, and more specifically into contemporary methods for the design of domestic/residential spaces. According to this, a discussion is made concerning the implementation of media and sensor technologies within the architectural DNA that initiate the emergence of psychotropic spaces of Ballardian Architecture; structures that are capable of becoming extensions of the inhabitant’s mood, emotion and psyche. (...) Furthermore, this article presents Plinthos Pavilion, a collaborative artwork that confronts issues of transparency, ubiquity and invisibility; an example of synergy between the primary notions of architectural and media design, which blend with the use of electronic and digital technology, transforming a physical structure to an organism that breathes, reacts and communicates. (shrink)

The RNA editing enzyme ADAR1 seemingly has more functions besides RNA editing. Mouse models lacking ADAR1 and sensors of foreign RNA show that RNA editing by ADAR1 plays a crucial role in the innate immune response. Still, RNA editing alone cannot explain all observed phenotypes. Thus, additional roles for ADAR1 must exist. Binding of ADAR1 to RNA is independent of its RNA editing function. Thus, ADAR1 may compete with other RNA-binding proteins. A very recent manuscript elaborates on this and reports (...) competition of ADAR1 with STAUFEN1, thereby modulating RNA-degradation. ADAR1 is also known to recruit proteins such as DROSHA to nascent transcripts. Still, many open questions remain. For instance, the biological role of the Z-DNA binding domains in ADAR1 is not defined. Moreover, the impact of ADAR1 on the RNA-folding landscape is unclear. In sum, moonlighting functions of ADAR1 may be manifold and have a great impact on the transcriptome. Adenosine to inosine RNA editing by ADAR1 is mostly known for its role in the innate immune response to help discriminate self from non-self RNA. Here we discuss the other face of ADAR1 that impacts on cellular processes independent of its editing function. These include Staufen-mediated-decay, mRNA processing, or miRNA maturation. (shrink)

Proteins on the cell surface and secreted proteins are modified with sugar chains that generate and modulate biological complexity and diversity. Sugar chains not only contribute physically to the conformation and solubility of proteins, but also exert various functions via sugar-binding proteins that reside on the cell surface or in organelles of the secretory pathway. However, some glycosidases and lectins are found in the cytosol or nucleus. Recent studies of cytosolic sugar–related molecules have revealed that sugar chains on proteins (...) in the cytosol act as signals of adverse cellular conditions. In this review, we summarize recent reports that cytosolic sugar chains can trigger ubiquitination, followed by proteasomal and autophagic degradation to maintain cellular homeostasis. In addition, we discuss the functions of sugar-binding proteins revealed to date, along with possibilities not yet explored. The cytosolic N-glycans that normally reside on the cell surface or in organelles serves as a signal for the presence of unwanted proteins or organelles. Here, we review the monitoring system for cytosolic glycans including glycosidases and lectin in the cytosol. (shrink)

This editorial examines how sensing practices are transforming through proliferating sensor technologies and altered sensing relations. Rather than engage with sensing as a project of the human mind or body as usually delineated within sensory classifications, this overview of sensors and sensing practices documents how sensing entities are emerging that are composed of shifting ensembles of multiple humans and more-than-humans, environments and technologies, politics and practices. By decoupling sensing from its exclusive human orientation, the editorial and collection demonstrate how (...) reworked approaches to sensing make it possible to tune in to how involvement with environmental problems unfolds and endures. The collection asks how sensing practices might be crafted that attend to the distributed and accumulative inequalities of environmental problems and to speculate toward differential collectives for addressing environmental crisis and change. (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)

Some cognitive processes appear to have “phenomenal” properties that are directly revealed to the subject and not determined by physical properties. I suggest that the source of this appearance is the method by which our brain processes sensory information. The appearance is an illusion. Nonetheless, we are not mistaken when we judge that people sometimes fee lpain.

Computational intelligence techniques are being investigated as an extension of the traditional fault diagnosis methods. This article presents, for the first time, a scheme for fault detection and isolation via artificial neural networks and fuzzy logic. It deals with the sensor fault of a three-link selective compliance assembly robot arm robot. A second scheme is proposed for fault detection and accommodation via analytical redundancy, and it deals with the sensor fault of a three-link SCARA robot. These proposed FDI (...) approaches are implemented on Matlab/simulink software and tested under several types of faults. The results show the importance of this process. Then, the sensor faults are detected and isolated successfully. Also, the actuator faults are detected and a fault tolerance strategy is used for reconfigurable control using a sliding-mode observer. (shrink)

Sensor-based data are becoming increasingly widespread in social, behavioral and organizational sciences. Far from providing a neutral window on 'reality', sensor-based big-data are highly complex, constructed data sources. Nevertheless, a more systematic approach to the validation of sensors as a method of data collection is lacking, as their use and conceptualization have been spread out across different strands of social-, behavioral- and computer science literature. Further debunking the myth of raw data, the present article argues that, in order (...) to validate sensor-based data, researchers need to take into account the mutual interdependence between types of sensors available on the market, the conceptual (construct) choices made in the research process, and the contextual cues. Sensor-based data in research are usually combined with additional quantitative and qualitative data sources. However, the incompatibility between the highly granular nature of sensor data and the static, a-temporal character of traditional quantitative and qualitative data has not been sufficiently emphasized as a key limiting factor of sensor-based research. It is likely that the failure to consider the basic quality criteria of social science measurement indicators more explicitly may lead to the production of insignificant results, despite the availability of high volume and high-resolution data. The paper concludes with recommendations for designing and conducting mixed methods studies using sensors. (shrink)

A mass balance based model has been derived to represent the dynamical behavior of the ecosystem contained in an anaerobic digester. The model considers two bacterial populations: acidogenic and methanogenic bacteria. It forms the basis for the design of a software sensor considering both a model of the biological system and on-line gaseous measurements. The software sensor computes the concentration of inorganic carbon and volatile fatty acids (VFA) in the digester. Another software sensor is dedicated to the (...) estimation of the bacterial biomasses. The predictions of the software sensors for a real experiment are very close to the actual off-line measurements. The software sensors monitor the accumulation of VFA and thus very early detect a destabilization of the digester due to overloading. The presented methodology demonstrates the usefulness of advanced monitoring techniques for an improved understanding of the internal working of a biological system. (shrink)

Visions of an interconnected future are on the rise that foresee technologies moving toward ubiquitous "everywhere" computing and the rise of the "Internet of Things." This article examines emerging trends in informational connectivity that indicates shifts toward upcoming scenarios of re-imagined geographies and spatial landscapes that are sensored and networked. I examine how the relationships, processes, and flows between people, physical objects, and the environment will make implicit information explicit and engagement between the physical and the digital more commonplace. These (...) are the scenarios presented by emerging applications of location-specific, informationally augmented objects: a real-time sensored future. (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)

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)

A suite of technological advances based on nanotechnology has received substantial attention for its potential to affect privacy. Reports of the National Nanotechnology Initiative have recognized that the societal implications of nanotechnology will include better surveillance and information-gathering technologies. A variety of academic and popular publications have explained the potential effects of nanotechnology on privacy.The ways in which nanotechnology might affect privacy are varied. It may make current information technology better, make old information-gathering techniques more reliable, or expand information-gathering into (...) novel areas. My focus in this paper is on the privacy effects of one potential application of nanotechnology: sensors capable of detecting weapons agents or drugs—"nanosensors" or "sensors" for short. Nanotechnology may make possible small, accurate, and easy-to-use sensors to detect a variety of substances, including Chemical, Biological, Radiological, and Explosive agents , as well as drugs. Analyzing the potential effects on privacy of sensors can provide important insights into the nature and extent of privacy rights. (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)

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)

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)

DNA barcodes, like traditional sources of taxonomic information, are potentially powerful heuristics in the identification of described species but require mindful analytical interpretation. The role of DNA barcoding in generating hypotheses of new taxa in need of formal taxonomic treatment is discussed, and it is emphasized that the recursive process of character evaluation is both necessary and best served by understanding the empirical mechanics of the discovery process. These undertakings carry enormous ramifications not only for the translation of DNA sequence (...) data into taxonomic information but also for our comprehension of the magnitude of species diversity and its disappearance. This paper examines the potential strengths and pitfalls of integrating DNA sequence data, specifically in the form of DNA barcodes as they are currently generated and analyzed, with taxonomic practice. (shrink)

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)

The pedagogical function of science teaching may benefit from an analysis of the historical-epistemic dimension, without neglecting the socio-political context in which a given research was carried out. In the case of DNA structure, the background of its discovery is particularly complex. Starting from the analysis of some papers, the view on the circumstances that led to their drafting broadens. We try to answer the fundamental question for any educator: why teach all that? Ethics issues are related to the general (...) organisation of research, increasingly focused on speed and competition. Even teaching is affected by these dynamics, not only in higher education, but also at secondary level; students should be made aware of this trend. The history of science could therefore favour a more general awareness. _SUNTO_ La funzione pedagogica dell’insegnamento scientifico può trarre vantaggio da un’analisi della dimensione storico-epistemica, senza trascurare il contesto socio-politico nel quale una determinata ricerca è stata condotta. Nel caso della struttura del DNA, i retroscena della sua scoperta sono particolarmente complessi. Dopo l’analisi di alcuni articoli, si allarga gradualmente la vista sulle circostanze che hanno condotto alla loro stesura. Si cerca di rispondere a una domanda fondamentale per ogni educatore: perché insegnare tutto ciò? Le questioni etiche riguardano l’organizzazione generale della ricerca, sempre più tesa alla velocità e alla competizione. Persino l’insegnamento è influenzato da dinamiche simili, non solo in ambito accademico, ma anche a livello secondario; gli studenti dovrebbero essere a conoscenza di questa tendenza. La storia della scienza può dunque favorire una maggiore consapevolezza. (shrink)

At metaphase in mitotic cells, pulling forces at the kinetochore‐microtubule interface create tension by stretching the centromeric chromatin between oppositely oriented sister kinetochores. This tension is important for stabilizing the end‐on kinetochore microtubule attachment required for proper bi‐orientation of sister chromosomes as well as for satisfaction of the Spindle Assembly Checkpoint and entry into anaphase. How force is coupled by proteins to kinetochore microtubules and resisted by centromere stretch is becoming better understood as many of the proteins involved have been (...) identified. Recent application of genetically encoded fluorescent tension sensors within the mechanical linkage between the centromere and kinetochore microtubules are beginning to reveal – from live cell assays – protein specific contributions that are functionally important. (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)

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)

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.

The paper tries to show that an evolutionary perspective helps us to address what is called the adaptation problem, that is, the remarkable coherence, and seemingly successful design, existing between our cognitive tools and the phenomena of the material world. It argues that a fine-grained description of the structure and function of experimental techniques—as a special type amongst evolving scientific practices—is a condition for a better understanding and, ultimately, an explanation of how adaptation among the heterogeneous elements of experimental knowledge (...) is attained. Some apparently contradictory features of techniques, such as their high context-dependency and their capabilities to reproduce and diversify outside their original contexts, are addressed with the help of the concepts of technical variation and the historical entrenchment of phenomena in techniques. In order to do so, a case-study on the construction of satellite-DNA and the evolution of nucleic acid hybridization, a research project carried out by Roy J. Britten and his colleagues in the 1960s, is presented in detail. This case illustrates the close relationship existing between the evolution of techniques and the stabilization of phenomena in experimental biology. (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.

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)

Based on an ethnographic study in a Danish residential care center, this article shows how the interplay of a sensor-floor technology and currently influential values of person-centeredness, privacy, and security in care transforms care work and care interactions between residents and care workers. Based on an understanding of care as realized in a heterogeneous collective of human and nonhuman actors, this article illustrates how new modes of monitoring and interpreting residents’ care needs at a distance arise, and how a (...) new organization of work focusing on quick and responsive care is established. These new care practices lead to conflicts between the values of privacy and security, to ambivalent experiences among care workers of simultaneously increased security and insecurity in work, and, paradoxically, also often to a decentering rather than person-centering of care. Instead of accommodating simultaneous compliance to the values of privacy, security, and person-centeredness, the use of the sensor-floors makes the tensions between these values continuously and loudly present in daily care practices. (shrink)

Automatized scalable healthcare support solutions allow real-time 24/7 health monitoring of patients, prioritizing medical treatment according to health conditions, reducing medical appointments in clinics and hospitals, and enabling easy exchange of information among healthcare professionals. With recent health safety guidelines due to the COVID-19 pandemic, protecting the elderly has become imperative. However, state-of-the-art health wearable device platforms present limitations in hardware, parameter estimation algorithms, and software architecture. This paper proposes a complete framework for health systems composed of multi-sensor wearable (...) health devices, high-resolution parameter estimation, and real-time monitoring applications. The framework is appropriate for real-time monitoring of elderly patients' health without physical contact with healthcare professionals, maintaining safety standards. The hardware includes sensors for monitoring steps, pulse oximetry, heart rate, and temperature using low-power wireless communication. In terms of parameter estimation, the embedded circuit uses high-resolution signal processing algorithms that result in an improved measure of the HR. The proposed high-resolution signal processing-based approach outperforms state-of-the-art HR estimation measurements using the photoplethysmography sensor. (shrink)

DNA supercoiling is one of the mechanisms that can help unlinking of newly replicated DNA molecules. Although DNA topoisomerases, which catalyze the strand passing of DNA segments through one another, make the unlinking problem solvable in principle, it remains difficult to complete the process that enables the separation of the sister duplexes. A few different mechanisms were developed by nature to solve the problem. Some of the mechanisms are very intuitive while the others, like topology simplification by type II DNA (...) topoisomerases and DNA supercoiling, are not so evident. A computer simulation and analysis of linked sister plasmids formed inEscherichia colicells with suppressed topoisomerase IV suggests an insight into the latter mechanism. (shrink)

The prelims comprise: Introduction How it Works Sources of Error and Uncertainty DNA Typing Results as Legal Evidence The Legal Reception of DNA Typing DNA Typing and the Judicial Assessment of Scientific Evidence Social Impact: Criminal Investigation and Adjudication Conclusion Notes.

Analysis of the light‐induced changes of cytosolic Ca2+ ([Ca2+]i) in photoreceptor cells has been taken a step further with two recently published studies(1,2). In one, changes in [Ca2+]i were measured in single detached rod outer segments from Gecko in response to various light intensities. The advances of the other(2) are embodied in its employment of transgenic Drosophila, whose photoreceptors express a visual pigment that is insensitive to the wavelength of light used in the fluorescence imaging of [Ca2+]i. These studies (...) provide a better basis for understanding the regulation of Ca2+‐mediated events in photoreceptor cells. (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)

We describe a prototype ontology-driven information system (ODIS) that exploits what we call Portion of Reality (POR) representations. The system takes both sensor data and natural language text as inputs and composes on this basis logically structured POR assertions. The goal of our prototype is to represent both natural language and sensor data within a single framework that is able to support both axiomatic reasoning and computation. In addition, the framework should be capable of discovering and representing new (...) kinds of situations and thematic roles, (e.g., roles such as agent, patient and instrument), based on new compositions of existing representations. We applied our prototype in an intelligence analysis use case to test the hypothesis that a framework of this sort can produce usefully structured information from combined natural language and sensor data inputs. We further tested our hypothesis by adding an enhanced US Air Force ontology framework to our ODIS in order to (1) process a collection of sensor data, intel reports, and mission plans; (2) build composite POR representations from these data; and (3) machine analyze the fused results to infer mission threats. (shrink)