Langerhans cells (LCs), residing in the epidermis, are able to induce potent immunogenic responses and also to mediate immune tolerance. We propose that tolerogenic and immunogenic responses of LCs are directed by signaling from the epidermis and involve counter‐acting gene circuits that are coupled to a core maturation gene module. We base our analysis on recent genetic and genomic findings facilitating the understanding of the molecular mechanisms controlling these divergent immune functions. Comparing gene regulatory network (GRN) analyses of (...) various types of dendritic cells (DCs) including LCs we integrate signaling‐dependent (TGFβ, EpCAM, β‐Catenin) and transcription factor (IRF4, IRF1, NFκB) regulated gene circuits that appear to orchestrate the distinctive LC functional states. Our model proposes, that while epidermal signaling in the steady‐state promotes LC tolerogenic function, the disruption of cell‐cell contacts coupled with inflammatory signaling induces LC immunogenic programing. The conceptual framework emphasizes the sensing of discrete epidermal and inflammatory cues by resident LCs in dictating their genomic programing and cell state dynamics. (shrink)

Insulin is synthesized in pancreatic B‐cells of islets of Langerhans. Understanding the mechanisms of action of B‐cytotoxins on pancreatic islets seems to be important for elucidating not only the causes of diabetes mellitus but also its prevention.

Pancreatic β‐cells in the islet of Langerhans produce the hormone insulin, which maintains blood glucose homeostasis. Perturbations in β‐cell function may lead to impairment of insulin production and secretion and the onset of diabetes mellitus. Several essential β‐cell factors have been identified that are required for normal β‐cell function, including six genes that when mutated give rise to inherited forms of diabetes known as Maturity Onset Diabetes of the Young (MODY). However, the intracellular signaling pathways that control expression (...) of MODY and other factors continue to be revealed. Post‐transplant diabetes mellitus in patients taking the calcineurin inhibitors tacrolimus (FK506) or cyclosporin A indicates that calcineurin and its substrate the Nuclear Factor of Activated T‐cells (NFAT) may be required for β‐cell function. Here recent advances in our understanding of calcineurin and NFAT signaling in the β‐cell are reviewed. Novel therapeutic approaches for the treatment of diabetes are also discussed. BioEssays 29:1011–1021, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

The exact process that leads to the eruption of autoimmune reactions against β cells and the evolution of diabetes is not fully understood. Macrophages and T cells may launch an initial immune reaction against the pancreatic islets of Langerhans, provoking inflammation and destructive insulitis. The information on the molecular mechanisms of the emergence of β cell injury is controversial and points to possibly important roles for the perforin–granzyme, Fas–Fas-ligand (FasL) and tumor-necrosis-factor-mediated apoptotic pathways. FasL has several unique (...) features that make it a potentially ideal immunomodulatory tool. Most important, FasL is selectively toxic to cytotoxic T cells and less harmful to regulatory T cells. This review discusses the intrinsic sensitivity of β cells to FasL-mediated apoptosis, the conditions that underlie this β cell sensitivity, and the feasibility of using FasL to arrest autoimmunity and prevent islet allograft rejection. In both the autoimmune and transplant settings, it is imperative to progress from the administration of nonspecific immunosuppressive therapy to the concept of β-cell-specific immunomodulation. FasL evolves as a prime candidate for antigen-specific immunomodulation. BioEssays 28: 211–222, 2006. © 2006 Wiley periodicals, Inc. (shrink)

Among emotions, surprise has been extensively studied in psychology. In linguistics, surprise, like other emotions, has mainly been studied through the syntactic patterns involving surprise lexemes. However, little has been done so far to correlate the reaction of surprise investigated in psychological approaches and the effects of surprise on language. This cross-disciplinary volume aims to bridge the gap between emotion, cognition and language by bringing together nine contributions on surprise from different backgrounds - psychology, human-agent interaction, linguistics. Using different methods (...) at different levels of analysis, all contributors concur in defining surprise as a cognitive operation and as a component of emotion rather than as a pure emotion. Surprise results from expectations not being met and is therefore related to epistemicity. Linguistically, there does not exist an unequivocal marker of surprise. Surprise may be either described by surprise lexemes, which are often associated with figurative language, or it may be expressed by grammatical and syntactic constructions. Originally published as a special issue of Review of Cognitive Linguistics 13:2 (2015). (shrink)

Nous étudions dans cet article les différentes formes de prédication seconde détachée en position initiale dans un corpus comparable composé de textes d’économie en anglais et en français. Ce corpus a été annoté sous le logiciel Analec. L’enjeu est de montrer en quoi un même phénomène syntaxique est exploité, sur le plan discursif, de façon divergente dans chacune des deux langues. Une étude qualitative et quantitative des prédications secondes du corpus montre que la prédication seconde prend le plus souvent la (...) forme d’une participiale en –ing en anglais, où elle se spécialise dans un rôle méta-énonciatif de balise textuelle pour le lecteur, ce qui n’est pas le cas en français. (shrink)

This study presents a sociological profile of Peruvian female industrialists and some narratives of their struggle for personal independence and entrepreneurial success within the context of global restructuring and local deindustrialization. The study adopts the classical definition of woman's economic independence as a result of women's participation in the world of paid labor.

Surprise is treated as an affect in Aristotelian philosophy as well as in Cartesian philosophy. In experimental psychology, surprise is considered to be an emotion. In phenomenology, it is only addressed indirectly (Husserl, Heidegger, Levinas), with the important exception of Ricoeur and Maldiney; it is reduced to a break in cognition by cognitivists (Dennett). Only recently was it broached in linguistics, with a focus on lexico-syntactic categories. As for the expression of surprise, it has been studied in connection with evidentiality (...) in languages that encode surprise morphosyntactically. However, how surprise is encoded in languages that lack an evidential morphosyntactic system has been largely unexplored. This book provides new insights into the dynamics of surprise based on a heuristic hypothesis tested against the investigation of time, language and emotion. It is intended to arouse the interest of a multidisciplinary audience keen on crossing the disciplinary borders of phenomenology, cognitive sciences, and pragmatics. The theoretical approaches adopted in this collection of articles rely on experiments and corpus data. They advance knowledge by building on robust empirical results coming from psychology, microphenomenology, linguistics and physiology. (shrink)

While neuroscientists often characterize brain activity as representational, many philosophers have construed these accounts as just theorists’ glosses on the mechanism. Moreover, philosophical discussions commonly focus on finished accounts of explanation, not research in progress. I adopt a different perspective, considering how characterizations of neural activity as representational contributes to the development of mechanistic accounts, guiding the investigations neuroscientists pursue as they work from an initial proposal to a more detailed understanding of a mechanism. I develop one illustrative example involving (...) research on the information-processing mechanisms mammals employ in navigating their environments. This research was galvanized by the discovery in the 1970s of place cells in the hippocampus. This discovery prompted research in what the activity of these cells represents and how place representations figure in navigation. It also led to the discovery of a host of other types of neurons—grid cells, head-direction cells, boundary cells—that carry other types of spatial information and interact with place cells in the mechanism underlying spatial navigation. As I will try to make clear, the research is explicitly devoted to identifying representations and determining how they are constructed and used in an information processing mechanism. Construals of neural activity as representations are not mere glosses but are characterizations to which neuroscientists are committed in the development of their explanatory accounts. (shrink)

The two theories of pancreatic enzyme secretion, those of exocytosis and transmembrane flow, are described. Data thought to support the theory of transmembrane flow of single molecules from pancreatic acinar cells are first reviewed, and the conditions which could allow these data to be explained by the theory of exocytosis of enzyme quanta, i.e. secretory granules, are then discussed.The evidence suggesting short‐term modulation of the composition of pancreatic juice is also considered, and its possible explanations at the organ and (...) cellular level are discussed, in the light of suggested theories on enzyme secretion pathways. (shrink)

Telegraphy, the distant ancestor of Internet and GSM (Global System for Mobile Communications), was invented by Samuel Morse in 1838. One year later, William Grove invented the fuel cell. Although numerous highly successful innovations stemming from telegraphy may be observed, the development of fuel cells has been insignificant, slow, and erratic and has not yet resulted in notable positive socioeconomic effects. By comparing the modern development of fuel cells and hydrogen technology, that is, a potential radical innovation in (...) energy generation, with some aspects related to the evolution of two highly successful radical innovations, Internet and GSM, the author focuses on the role of innovation regimes and policy in a sectorial system of innovations perspective. In the slow pace in fuel cells and hydrogen technology development, two factors seem to interact negatively: weak and fragmented innovation regimes in the energy sector and the current hegemony of market-oriented R&D policies. (shrink)

Background With the huge number of patients who suffer from chronic and incurable diseases, medical scientists continue to search for new curative methods for patients in dire need of treatment. Interest in stem cells is growing, generating high expectations in terms of the possible benefits that could be derived from stem cell research and therapy. However, regardless of the hope of stem cells changing and improving lives, there are many ethical, religious, and political challenges and controversies that affect (...) the research, and mandated to establish ethical guidelines and regulations. In Saudi Arabia, key stakeholders play an active role in discussing the ethics of stem cell research and therapy. The focus of the study was to explore professionals’ perceptions related to the ethical challenges of using stem cells in research and treatment in Saudi Arabia. Results A qualitative research study was conducted to explore and describe the perceptions of 25 professionals employed at different tertiary hospitals in the various regions of Saudi. A thematic analysis was performed to search for and identify the most significant perceptions shared by the participants. Four themes were generated based on the ethical challenges of four areas related to stem cell use, including forbidden and permitted sources of stem cells, informed consent, beneficence, and ethical regulations and guidelines. Conclusion The study identified that there is a growing need to advance the knowledge, education, and awareness related to stem cell research and treatment in Saudi Arabia. (shrink)

An exciting development in the field of assisted reproductive technologies is In Vitro Gametogenesis (IVG) that enables production of functional gametes from stem cells in the laboratory. Currently, development of this technology is still at an early stage and has demonstrated to work only in rodents. Upon critically examining the ethical dimensions of various possible IVG applications in human fertility treatment from a Sunni Islamic perspective, together with benefit-harm (maslahah-mafsadah) assessment; it is concluded that utilization of IVG, once its (...) efficacy and safety are guaranteed, could be permissible by strictly adhering to Islamic ethical principles related to marriage, biological/genetic relatedness, sexual intercourse, and moral status of the embryo/fetus versus that of the gamete. As a result, IVG will be acceptable for treating primary infertility, age-related infertility, and preventing genetic diseases. However, it will be unacceptable for application in posthumous reproduction, donor gametes, genetic enhancement, and procreation in same-sex couples. (shrink)

A crescendo of panting to her stiff-lunged yearspressed in on her for three days and a bit before the succumbingno word could be wedged between gasps.A knife twist in her life’s two year tail two years’witness to others’ ministerings at her flesh-raw chestturned outward to the airenforced fluency in the language of lint.From nests of treason in her breastat night the insurgency pushed outinto the bloodlinesoutriders of a black hostthe dreadful propaganda of cellsbridgeheads locked down in bone and braina Reichstag (...) fire flowering in her backherstory crumblingmidnight dominoes along her spine.At the endat the panting postin the room curtained for deathher body spat and crackled with a foreign fevereven past the last breath and her eyes drying.In the bare room a malignant hum.When they came for her a thin smoke hung. (shrink)

: Experiments involving the transplantation of human stem cells and their derivatives into early fetal or embryonic nonhuman animals raise novel ethical issues due to their possible implications for enhancing the moral status of the chimeric individual. Although status-enhancing research is not necessarily objectionable from the perspective of the chimeric individual, there are grounds for objecting to it in the conditions in which it is likely to occur. Translating this ethical conclusion into a policy recommendation, however, is complicated by (...) the fact that substantial empirical and ethical uncertainties remain about which transplants, if any, would significantly enhance the chimeric individual's moral status. Considerations of moral status justify either an early-termination policy on chimeric embryos, or, in the absence of such a policy, restrictions on the introduction of pluripotent human stem cells into early-stage developing animals, pending the resolution of those uncertainties. (shrink)

In mice, dosage compensation of X‐linked gene expression is achieved through the inactivation of one of the two X‐chromosomes in XX female cells. The complex epigenetic process leading to X‐inactivation is largely controlled by Xist and Tsix, two non‐coding genes of opposing function. Xist RNA triggers X‐inactivation by coating the inactive X, while Tsix is critical for the designation of the active X‐chromosome through cis‐repression of Xist RNA accumulation. Recently, a plethora of trans‐acting factors and cis‐regulating elements have been (...) suggested to act as key regulators of either Xist, Tsix or both; these include ubiquitous factors such as Yy1 and Ctcf, developmental proteins such as Nanog, Oct4 and Sox2, and X‐linked regulators such as Rnf12. In this paper we summarise recent advances in our knowledge of the regulation of Xist and Tsix in embryonic stem (ES) and differentiating ES cells. (shrink)

The fate of root epidermal cells is controlled by a complex interplay of transcriptional regulators, generating a genetically determined, position‐biased arrangement of root hair cells. This pattern is altered during postembryonic development and in response to environmental signals to confer developmental plasticity that acclimates the plant to the prevailing conditions. Based on the hypothesis that events downstream of this initial mechanism can modulate the pattern installed during embryogenesis, we have developed a reaction diffusion model that reproduces the root (...) hair patterning previously observed experimentally. Under all growth conditions, an almost equal spacing between root hair forming cells was observed both in vitro and in silico, indicating that long‐range intercellular communication is crucial for the trichoblasts' decision to form a root hair. We assume that a hair growth promoter (HGP) is upregulated in root‐hair‐forming cells by a trichoblast‐specific component. Once established, HGP production is self‐enhancing. The autocatalytic regulation of HGP is antagonized by an HGP‐produced hair growth inhibitor (HGI). HGI is exported from trichoblasts and diffuses to neighboring cells, where it inhibits further HGP production and promotes the non‐hair cell fate. Under conditions of phosphate deficiency, we hypothesise that HGP production is increased and HGI diffusion rate is reduced, leading to a position‐independent formation of extra root hairs. BioEssays 30:75–81, 2008. © 2007 Wiley Periodicals, Inc. (shrink)

Electron microscopic examination of the non‐granulated cells of the adenohypophysis of several species has evidenced a unity of structure amongst vertebrates. Efforts to correlate structure and function have been made, but they have often been hampered by the scarcity or absence of direct experimental methods for the investigation of their function. Yet often the evidence in favor of a given role has been circumstantial, relying on coincidences between changes in the secretory activity of the gland and changes in the (...) ultrastructure of the non‐granulated cells or in colloid production. At the present time, the prevailing hypothesis is that, in addition to a possible role in mechanical support within the gland, the non‐granulated cells seem to be important with respect to the secretory process of the endocrine cells and/or to the metabolism of the adenohypophysis. (shrink)

Cellular reprogramming can manipulate the identity of cells to generate the desired cell types1– 3. The use of cell intrinsic components, including oocyte cytoplasm and transcription factors, can enforce somatic cell reprogramming to pluripotent stem cells4– 7. By contrast, chemical stimulation by exposure to small molecules offers an alternative approach that can manipulate cell fate in a simple and highly controllable manner8– 10. However, human somatic cells are refractory to chemical stimulation owing to their stable epigenome2,11,12 and reduced (...) plasticity13,14; it is therefore challenging to induce human pluripotent stem cells by chemical reprogramming. Here we demonstrate, by creating an intermediate plastic state, the chemical reprogramming of human somatic cells to human chemically induced pluripotent stem cells that exhibit key features of embryonic stem cells. The whole chemical reprogramming trajectory analysis delineated the induction of the intermediate plastic state at the early stage, during which chemical-induced dedifferentiation occurred, and this process was similar to the dedifferentiation process that occurs in axolotl limb regeneration. Moreover, we identified the JNK pathway as a major barrier to chemical reprogramming, the inhibition of which was indispensable for inducing cell plasticity and a regeneration-like program by suppressing pro-inflammatory pathways. Our chemical approach provides a platform for the generation and application of human pluripotent stem cells in biomedicine. This study lays foundations for developing regenerative therapeutic strategies that use well-defined chemicals to change cell fates in humans. (shrink)

Cancers often express hundreds of genes otherwise specific to germ cells, the germline/cancer (GC) genes. Here, we present and discuss the hypothesis that activation of a “germline program” promotes cancer cell malignancy. We do so by proposing four hallmark processes of the germline: meiosis, epigenetic plasticity, migration, and metabolic plasticity. Together, these hallmarks enable replicative immortality of germ cells as well as cancer cells. Especially meiotic genes are frequently expressed in cancer, implying that genes unique to meiosis (...) may play a role in oncogenesis. Because GC genes are not expressed in healthy somatic tissues, they form an appealing source of specific treatment targets with limited side effects besides infertility. Although it is still unclear why germ cell specific genes are so abundantly expressed in cancer, from our hypothesis it follows that the germline's reproductive program is intrinsic to cancer development. (shrink)

The prelims comprise: Why Embryonic Stem Cells? Stem Cells for Organ and Tissue Transplant Immortality A Guarded Welcome for Stem Cell Research The Precautionary Principle The Ethics of ES Cell Research Stem Cells from Early Embryos The Moral Status of the Embryo Lessons from Sexual Reproduction Establishing a Pregnancy by Sexual Reproduction The Incoherence of Current US Federal Law The Symbolic Value of Life ART and Spare Embryos Tissue from Fetuses Doing Something Good is Better than Doing (...) Nothing! Interim Conclusions Genetic Identity Moral Complicity Acknowledgments. (shrink)

Increasing interest has been paid to applications of fluorescence measurements to analyze physiological mechanisms in living cells. However, few studies have taken advantage of DNA quantification by fluorometry for dynamic assessment of chromatin organization as well as cell motion during the cell cycle. This approach involves both optimal conditions for DNA staining and cell tracking methods. In this context, this report describes a stoichiometric method for nuclear DNA specific staining, using the bisbenzimidazole dye Hoechst 33342 associated with verapamil, a (...) calcium membrane channel blocker. This method makes it possible to correlate variations of nuclear DNA content with cell motion in cells that are maintained alive. Motion measurement is the second goal of this paper and it explains the snake-spline method, and the associated cell following method. (shrink)

This article focuses on the legal and organisational regulation of human cells in the United Kingdom and France. French Bioethics Law regulates human cells for health according to European Union law where it is enforceable. But products unregulated by EU law and based on human cells are never considered as medicinal products, given the strict implementation of the principle of “nonpatrimonialité” of the human body and its elements. By comparison, in the UK such products can be qualified (...) as medicinal products. Moreover, the setting up of the UK stem cell bank gives rise to the development of policies which expand the stem cell as a legal object. The paper discusses how these societies’ ethical and legal commitments underlie organisational practices in order to analyse the relationship between the existence (or not) of a national stem cell bank and the broader regulation of human cells. (shrink)

Continuous culture techniques were developed in the early twentieth century to replace cumbersome studies of cell growth in batch cultures. In contrast to batch cultures, they constituted an open concept, as cells are forced to proliferate by adding new medium while cell suspension is constantly removed. During the 1940s and 1950s new devices have been designed—called “automatic syringe mechanism,” “turbidostat,” “chemostat,” “bactogen,” and “microbial auxanometer”—which allowed increasingly accurate quantitative measurements of bacterial growth. With these devices cell growth came under (...) the external control of the experimenters and thus accessible for developing a mathematical theory of growth kinetics—developed mainly by Jacques Monod, Aron Novick and Leo Szilard in the early 1950s and still in use today. The paper explores the development of continuous culture devices and claims that these devices are simulators for standard cells following specific requirements, in particular involving mathematical constraints in the design and setting of the devices as well as experiments. These requirements have led to contemporary designs of continuous culture techniques realizing a specific event-based flow algorithm able to simulate directed evolution and produce artificial cells and microorganisms. This current development is seen as an alternative approach to today’s synthetic biology. (shrink)

The emergence of individuality during the evolutionary transition from single cells to multicellularity poses a range of problems. A key issue is how variation in lower‐level individuals generates a corporate (collective) entity with Darwinian characteristics. Of central importance to this process is the evolution of a means of collective reproduction, however, the evolution of a means of collective reproduction is not a trivial issue, requiring careful consideration of mechanistic details. Calling upon observations from experiments, we draw attention to proto‐life (...) cycles that emerge via unconventional routes and that transition, in single steps, individuality to higher levels. One such life cycle arises from conflicts among levels of selection and invokes cheats as a primitive germ line: it lays the foundation for collective reproduction, the basis of a self‐policing system, the selective environment for the emergence of development, and hints at a plausible origin for a soma/germ line distinction. (shrink)

During somitogenesis an oscillatory mechanism termed the “segmentation” clock generates periodic waves of gene expression, which translate into the periodic spatial pattern manifest as somites. The dynamic expression of the clock genes shares the same periodicity as somitogenesis. Notch signaling is believed to play a role in the segmentation clock mechanism. The paper by Hirata et al.(1) identifies a biological clock in cultured cells that is dependent upon the Notch target gene Hes1, and which shows a periodicity similar to (...) that of the segmentation clock. This finding opens the possibility that the same oscillator mechanism might also operate in other tissues or cell types. BioEssays 25:200–203, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

New observations by Hatini et al.(1) on the ‘winged helix’ transcription factor BF‐2 will make us change our views about kiney development. This gene is only expressed in stromal cells associated with the kidney medulla and cortex, but the BF‐2 knockout has unexpected abnormalities. Although the stromal cells appear normal, the kidney is small, the ducts have limited branching and, instead of the many normal nephrogenic aggregates, there are relatively few large mesenchymal aggregates that fail to differentiate. The (...) stromal cells thus seem to produce factors regulating other aspects of kidney development, while the abnormalities highlight a series of unsolved problems in kidney morphogenesis. (shrink)

In 1956, I decided to apply my experience in microbial genetics to developing analogous systems for human cell lines, including the selection of mutants with either a loss or gain of a biochemical function. For instance, mutants resistant to azahypoxanthine showed a loss of the HPRT enzyme (hypoxanthine phosphoribosyl transferase), whereas gain of the same enzyme was accomplished by blocking de novo purine biosynthesis with aminopterin, while supplying hypoxanthine and thymine (HAT selection). Using HAT selection, we: (i) genetically transformed HPRT− (...) mutant cells to HPRT+ wild type by using DNA extracted from HPRT+ cells, and (ii) selected HPRT+ hybrid cells by fusing HPRT− D98/AH2 cells with skin cells. These approaches, which we dubbed in 1962 as a [first step toward gene therapy], contributed to the later development of (i) cell fusion techniques, (ii) the development of monoclonal antibodies, (iii) routine transformation of mammalian cells with cloned genes, and (iv) methods for creating transgenic organisms. (shrink)

Apoptosis is a physiological mechanism for the removal of unwanted or damaged cells. Apoptotic cells are rarely seen in living tissues, however, because of their rapid and efficient removal by phagocytosis. Phagocytotic cells such as macrophages or dendritic cells recognize apoptotic cells by specific changes of cell surface markers, which usually are not present on normal cells. One such event is the exposure of phosphatidylserine, which moves from the plasma membrane inner leaflet to the (...) outer leaflet in preapoptotic cells. An unresolved problem, however, was the nature of the phosphatidylserine receptor on the phagocytotic cells. In a recent issue of Nature, Fadok et al.(1) have reported the cloning of a phosphatidylserine receptor using an antibody raised against activated macrophages. Antibody treatment of these macrophages blocks this capacity to engulf. BioEssays 22:878–881, 2000. © 2000 John Wiley & Sons, Inc. (shrink)

Unlike eggs and diatoms, most single cells in nature do not have structured shells to provide extensive protection. It is a challenge to artificially confer shell structures on living cells to improve their inherent properties and functions. We discuss four different types of cellular shellizations: man‐made hydrogels, sol‐gels, polyelectrolytes, and mineral shells. We also explore potential applications, such as cell storage, protection, delivery, and therapy. We suggest that shellization could provide another means to regulate and functionalize cells. (...) Specifically, the integration of living cells and non‐living functional shells may be developed as a novel strategy to create “super” or intelligent cells. Unlike biological approaches, this material‐based bio‐interface regulation is inexpensive, effective, and convenient, opening up a novel avenue for cell‐based technologies and practices. (shrink)

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)

RNA processing in Escherichia coli and some of its phages is reviewed here, with primary emphasis on rRNA and tRNA processing. Three enzymes, RNase III, RNase E and RNase P are responsible for most of the primary endonucleolytic RNA processing events. The first two are proteins, while RNase P is a ribozyme. These three enzymes have unique functions and in their absence, the cleavage events they catalyze are not performed. On the other hand a relatively large number of exonucleases participate (...) in the trimming of the 3′ ends of tRNA precursor molecules and they can substitute for each other. Primary processing is the first event that happens to the nascent RNA molecule, while in secondary RNA processing, the substrate is a product of a primary processing event. Although most RNA processing occurs in RNP particles, it seems that only in secondary RNA processing is the RNP particle required for the reaction. Bacteria and especially bacteriophages contain self‐splicing introns which in cases were probably acquired from other species. (shrink)

Physiological concentrations of retinoic acid can induce acute alterations in the expression of the enzyme tissue transglutaminase in cultured macrophages. The induction of this enzyme offers a probe to study the mechanism of retinoid action in both normal and leukemic cells.