Although random mutation is central to models of evolutionary change, a lack of clarity remains regarding the conceptual possibilities for thinking about the nature and role of mutation in evolution. We distinguish several claims at the intersection of mutation, evolution, and directionality and then characterize a previously unrecognized category: complex conditioned mutation. Empirical evidence in support of this category suggests that the historically famous fluctuation test should be revisited, and new experiments should be undertaken with emerging (...) experimental techniques to facilitate detecting mutation rates within specific loci at an ultra‐high, individual base pair resolution. (shrink)

Mutations in citizenship are crystallized in an ever-shifting landscape shaped by the flows of markets, technologies, and populations. We are moving beyond the citizenship-versus-statelessness model. First, the elements of citizenship are becoming disarticulated from each other, and becoming re-articulated with universalizing criteria of neoliberalism and human rights. Such ‘global assemblages’ define zones of political entitlements and claims. Second, the space of the ‘assemblage’, rather than the national terrain, becomes the site for political mobilizations by diverse groups in motion. Three contrasting (...) configurations are presented. In the EU zone, unregulated markets and migrant flows challenge liberal citizenship. In Asian zones, foreigners who display self-enterprising savoire faire gain rights and benefits of citizenship. In camps of the disenfranchised or displaced, sheer survival becomes the ground for political claims. Thus, particular constellations shape specific problems and resolutions to questions of contemporary living, further disarticulating and deterritorializing aspects of citizenship. (shrink)

Adaptive mutation is defined as a process that, during nonlethal selections, produces mutations that relieve the selective pressure whether or not other, nonselected mutations are also produced. Examples of adaptive mutation or related phenomena have been reported in bacteria and yeast but not yet outside of microorganisms. A decade of research on adaptive mutation has revealed mechanisms that may increase mutation rates under adverse conditions. This article focuses on mechanisms that produce adaptive mutations in one strain (...) of Escherichia coli, FC40. These mechanisms include recombination-induced DNA replication, the placement of genes on a conjugal plasmid, and a transient mutator state. The implications of these various phenomena for adaptive evolution in microorganisms are discussed. BioEssays 22:1067–1074, 2000. © 2000 John Wiley & Sons, Inc. (shrink)

Abstract‘Mutation frequency decline’ (MFD) was discovered about forty years ago, and described as the disappearance of a particular class of ultraviolet light‐induced mutations in Escherichia coli that occurred whenever protein synthesis was briefly inhibited immediately after irradiation. Later, MFD was interpreted as an excision repair anomaly uniquely affecting nonsense suppressor mutations induced in certain tRNA genes. Never fully understood, MFD has recently been linked to the newly discovered transcription‐coupled rapid repair of ultraviolet damage on the templat strand of active (...) genes. This article recalls the emergence and development of the MFD story, and offers a new way to explain it and its relation to strand‐specific excision repair. (shrink)

High‐throughput DNA analyses are increasingly being used to detect rare mutations in moderately sized genomes. These methods have yielded genome mutation rates that are markedly higher than those obtained using pre‐genomic strategies. Recent work in a variety of organisms has shown that mutation rate is strongly affected by sequence context and genome position. These observations suggest that high‐throughput DNA analyses will ultimately allow researchers to identify trans‐acting factors and cis sequences that underlie mutation rate variation. Such work (...) should provide insights on how mutation rate variability can impact genome organization and disease progression. (shrink)

A recent article by Galitski and Roth(1) characterizes adaptive reversion of chromosomal lac− mutations in Salmonella typhimurium LT2. Using a classical genetic approach they show that adaptive reversion, as characterized by the appearance of late revertant colonies, is an exception rather than a general phenomenon for reversion of nonsense, missense, frameshift and insertion mutations. For certain mutations, however, the number of late revertants exceeds the predicted number. These excess revertants suggest that adaptive mutability is applicable to chromosomal genes as well (...) as to genetic changes involving F plasmids and lysogenic phages. (shrink)

Adaptive mutation is defined as a process that, during nonlethal selections, produces mutations that relieve the selective pressure whether or not other, nonselected mutations are also produced. Examples of adaptive mutation or related phenomena have been reported in bacteria and yeast but not yet outside of microorganisms. A decade of research on adaptive mutation has revealed mechanisms that may increase mutation rates under adverse conditions. This article focuses on mechanisms that produce adaptive mutations in one strain (...) of Escherichia coli, FC40. These mechanisms include recombination-induced DNA replication, the placement of genes on a conjugal plasmid, and a transient mutator state. The implications of these various phenomena for adaptive evolution in microorganisms are discussed. BioEssays 22:1067–1074, 2000. © 2000 John Wiley & Sons, Inc. (shrink)

Un essai sur la portée épistémologique des instruments d'optique au XVIIe siècle, axé sur les travaux des Anglais, et notamment l'oeuvre de Robert Hooke, qui entre tous a su donner une consistance philosophique au modèle instrumental.

This article offers an explanation of perhaps Wittgenstein’s strangest and least intuitive thesis – the semantical mutation thesis – according to which one can never answer a mathematical conjecture because the new proof alters the very meanings of the terms involved in the original question. Instead of basing our justification on the distinction between mere calculation and proofs of isolated propositions, characteristic of Wittgenstein’s intermediary period, we generalize it to include conjectures involving effective procedures as well.

Here, we propose that the heterogeneity of mutational types in populations underpins alternative pathways of evolutionary adaptation. Point mutations, deletions, insertions, transpositions and duplications cause different biological effects and provide distinct adaptive possibilities. Experimental evidence for this notion comes from the mutational origins of adaptive radiations in large, clonal bacterial populations. Independent sympatric lineages with different phenotypes arise from distinct genetic events including gene duplication, different insertion sequence movements and several independent point mutations. The breadth of the mutational spectrum in (...) the ancestral population should be viewed as a form of bet‐hedging, reducing the risk of evolutionary dead ends and complementing the phenotypic and epigenetic heterogeneities that improve the survival capabilities of a population. Different mutational events arise from distinct cellular processes and are subject to separate environmental impacts, so the availability of any particular type of mutation may constrain or promote adaptive pathways in populations. (shrink)

En cette entame du troisième millénaire, la musique adresse une question aux autres arts comme aux sciences : comment ajuster les différentes écritures (musicale, mathématique, chorégraphique, biologique...) aux nouvelles matières sur lesquelles ces pensées embrayent? S'il est vrai que le système autonome d'écriture musicale (le solfège), inventé il y a près de 1 000 ans, s'avère désormais en partie inadapté aux nouveaux matériaux sonores qu'il s'agit de composer, la prolifération empirique des simples notations à laquelle on assiste aujourd'hui ne saurait (...) pourvoir aux mutations en jeu : en matière d'écriture musicale, il en va non de simples techniques neutres mais bien de logique musicale, donc de ce qu'un discours ou un développement veulent musicalement dire. S'il s'agit donc en cette affaire de penser les mutations en cours en matière de "logique musicale" et leurs exigences en matière de nouvelles "lettres/notes" musicales, qu'en est-il de soucis semblables dans les autres arts et dans les sciences? Qu'en est-il de mutations équivalentes dans les autres arts, singulièrement dans ceux qui entreprennent de se doter d'une écriture qui leur soit propre (la chorégraphie)? Qu'en est-il surtout dans les sciences, dans les mathématiques bien sûr mais aussi en logique comme dans les sciences ayant à nouer leurs propres lettres à l'impératif galiléen de s'écrire mathématiquement? Comment ce double dispositif (écriture mathématique importée/modes endogènes d'inscription) tend-il aujourd'hui à se nouer en physique, en chimie, en biologie, en informatique? Ce volume rassemble différentes contributions soutenues et discutées lors d'un colloque tenu à l'Ecole normale supérieure (Paris, Ulm) en octobre 2007. (shrink)

A cell contains many copies of mitochondrial DNA. The distribution of a mitochondrial gene mutation in a cell culture is governed by the way in which the mtDNA molecules of a cell are replicated and partitioned between the two daughter cells during mitosis. Assuming that this partition process is random, we describe the evolution of the mitochondrial genetic state of a cell culture. The mutated mtDNA is ultimately segregated and the rate of the trend to segregation is relatively slow. (...) It is nevertheless greatly accelerated if the model takes into account the spatial mtDNA partition by the mitochondrial compartments. (shrink)

Presenilin‐1 (PS1) is thought to regulate cell differentiation and survival by modulating the Notch signaling pathway. Mutations in PS1 have been shown to cause early‐onset inherited forms of Alzheimer's disease (AD) by a gain‐of‐function mechanism that alters proteolytic processing of the amyloid precursor protein (APP) resulting in increased production of neurotoxic forms of amyloid β‐peptide. The present article considers a second pathogenic mode of action of PS1 mutations, a defect in cellular calcium signaling characterized by overfilling of endoplasmic reticulum (ER) (...) calcium stores and altered capacitive calcium entry; this abnormality may impair synaptic plasticity and sensitize neurons to apoptosis and excitotoxicity. The calcium signaling defect has also been documented in lymphocytes, suggesting a contribution of immune dysfunction to the pathogenesis of AD. A better understanding of the calcium signaling defect resulting from PS1 mutations may lead to the development of novel preventative and therapeutic strategies for disorders of the nervous and immune systems. BioEssays 23:733–744, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

We address two points. First, one must explain how different, rare mutations ultimately lead to common psychopathological conditions. The developmental instability model offers one solution. Second, Keller & Miller perhaps miss the major processes other than variation fueled by rare deleterious mutations that account for interesting genetic variation in psychopathology, particularly when single alleles have non-negligible effects: Red Queen processes.

Clonal disease is often regarded as almost synonymous with cancer. However, it is becoming increasingly clear that our bodies harbor numerous mutant clones that are not tumors, and mostly give rise to no disease at all. Here we discuss three somatic mutations arising within the hematopoietic system: BCR‐ABL, characteristic of chronic myeloid leukemia; mutations of the PIG‐A gene, characteristic of paroxysmal nocturnal hemoglobinuria; the V617F mutation in the JAK2 gene, characteristic of myeloproliferative diseases. The population frequencies of these three (...) blood disorders fit well with a hierarchical model of hematopoiesis. The fate of any mutant clone will depend on the target cell and on the fitness advantage, if any, that the mutation confers on the cell. In general, we can expect that only a mutation in a hematopoietic stem cell will give long‐term disease; the same mutation taking place in a cell located more downstream may produce just a ripple in the hematopoietic ocean. (shrink)

A substantial portion of the human genome has been found to consist of simple sequence repeats, including microsatellites and minisatellites. Microsatellites, tandem repeats of 1–6 nucleotides, form the template for dynamic mutations, which involve heritable changes in the lengths of repeat sequences. In recent years, a large number of human disorders have been found to be caused by dynamic mutations, the most common of which are trinucleotide repeat expansion diseases. Dynamic mutations are common to numerous nervous system disorders, including Huntington's (...) disease, various spinocerebellar ataxias, fragile X syndrome, fragile X tremor/ataxia syndrome, Friedreich ataxia and other neurodegenerative disorders. The involvement of dynamic mutations in brain disorders will be reviewed, with a focus on the large group caused by CAG/glutamine repeat expansions. We will also outline a proposed role of tandem repeat polymorphisms (TRPs), with unique ‘digital’ genetic distributions, in modulating brain development and normal function, so as to generate additional mutational diversity upon which natural selection may act. BioEssays 29:525–535, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

Reproductive diseases are a long‐standing problem and have become more common in the world. Currently, 15% of the world's population suffers from infertility, and half of them are women. Maturation of oocytes, successful fertilization, and high‐quality embryos are prerequisites for pregnancy. With the development of assisted reproductive technology and advanced genetic assays, we have found that infertility in many young female patients is caused by mutations in various developmental regulators. These pathogenic factors may result in impediment of oocyte maturation, failure (...) of fertilization or early embryonic development arrest. In this review, we categorize these clinically‐identified, mutated genetic factors by their molecular characteristics: nuclear factors (PALT2, TRIP13, WEE2, TBPL2, REC114, MEI1 and CDC20), cytoplasmic factors (TLE6, PADI6, NLRP2/5, FBXO43, MOS and BTG4), a factor unique to primates (TUBB8), cell membrane factor (PANX1), and zona pellucida factors (ZP1‐3). We compared discrepancies observed in phenotypes between human and mouse models to provide clues for clinical diagnosis and treatment of related reproductive diseases. (shrink)

The following paper considers the immanent principles of digital media evolution. The features of the evolutional route of digital objects are conditioned by glitches, errors and bugs, which appear in media functioning, what in its turn gives birth to the new forms, structures and configurations of digital reality. The glitches are considered not only as a kind of digital mutations, but also as a sign of activity of media. Decisions elaborated from the programs’ failures enlarge the resolution capacity of new (...) technologies. The paper provides an analysis of certain errors and glitches, which engineers, programmers, game designers faced with during their work with digital environment. The theoretical framework includes Henri Bergson’s theory of creative evolution, Gram Harman’s object-oriented philosophy, media philosophical approach to the problem of the activity of object proposed by Valery Savchuk and the theory of self-organisation and autopoiesis of the social systems worked out by Niklas Luhmann. The analysis of digital objects activity demonstrates two levels of functioning. The first one, fictional level, reveals mainly (but not only) in the computer games and concerns the content of media, when we gain a habit to interact with digital objects/characters as if they are real. The second level, operational, realises in the digital environment in general and concerns the form of media. On this level, glitches and bugs have crucial meaning, because they might evoke the changes in the digital world organisation, starting from the local decisions for the certain program (e.g. the elaboration of the new ways in solving locomotional tasks in simulations, which might be later use in other projects) and ending with the replacement of practices and representations typical for the human of digital era. The paper shows that it is possible to talk about digital evolution not in terms of the history of technological inventions, but in terms of the changes in digital objects caused by the inner logic of media, independently from the human will and expectations. (shrink)

The fifth base in human DNA, 5‐methylcytosine, is inherently mutagenic. This has led to marked changes in the distribution of the CpG methyl acceptor site and an 80% depletion in its frequency of occurrence in vertebrate DNA. The coding regions of many genes contain CpGs which are methylated in sperm and serve as hot spots for mutation in human genetic diseases. Fully 30–40% of all human germline point mutations are thought to be methylation induced even though the CpG dinucleotide (...) is under‐represented and efficient cellular repair systems exist. Importantly, tumor suppressor genes such as p53 also contain methylated CpGs and these serve as hot spots for mutations in some, but not all, human cancers. Comparison of the spectrum of mutations present in this gene in different human cancers allows for predictions to be made on the molecular mechanisms of tumorigenesis. (shrink)

The Polycomb group of proteins (PcGs) are transcriptional repressor complexes that regulate important biological processes and play critical roles in cancer. Mutating or deleting EZH2 can have both oncogenic and tumor suppressive functions by increasing or decreasing H3K27me3. In contrast, mutations of SUZ12 and EED are reported to have tumor suppressive functions. EZH2 is overexpressed in many cancers, including prostate cancer, which can lead to silencing of tumor suppressors, genes regulating epithelial to mesenchymal transition (EMT), and interferon signaling. In some (...) cases, EZH2 overexpression also leads to its use of non‐histone substrates. Lastly, PRC2 associated factors can influence the progression of cancer through progressive mutations or by specific binding to certain target genes. Here, we discuss which mutations and deletions of the PRC2 complex have been detected in different cancers, with a specific focus on the overexpression of EZH2 in prostate cancer. (shrink)

Abstract: The optimum definition of the term "genocide" has been hotly contested almost since the term was coined. Definitional boundaries determine which acts are covered and excluded and thus to a great extent which cases will benefit from international attention, intervention, prosecution, and reparation. The extensive legal, political, and scholarly discussions prior to this article have typically (1) assumed "genocide" to be a fixed social object and attempted to define it as precisely as possible or (2) assumed the need for (...) a fixed convention and sought to stipulate the range of events that should be denoted by the term. Even if its meaning is a matter of convention, however, "genocide" is not a fixed object but varies by context and evolves in methods and forms over time. In fact, as relevant laws, legal interpretations, and political commitments develop, so do would-be perpetrators modify what genocide is in order to avoid political and legal consequences. This article advances an approach to a definition of "genocide" that allows even legal definitions to keep pace with this evolutionary process. (shrink)

A widely accepted tenet of evolutionary biology is that spontaneous mutations occur randomly with regard to their fitness effect. However, since the mutation rate varies along a genome and this variation can be subject to selection, organisms might evolve lower mutation rates at loci where mutations are most deleterious or increased rates where mutations are most needed. In fact, mechanisms of targeted hypermutation are known in organisms ranging from bacteria to humans. Here we review the main forces driving (...) the evolution of local mutation rates and identify the main limiting factors. Both targeted hyper‐ and hypomutation can evolve, although the former is restricted to loci under very frequent positive selection and the latter is severely limited by genetic drift. Nevertheless, we show how an association of repair with transcription or chromatin‐associated proteins could overcome the drift limit and lead to non‐random hypomutation along the genome in most organisms.Editor's suggested further reading in BioEssays Stress‐induced mutation via DNA breaks in Escherichia coli: A molecular mechanism with implications for evolution and medicine Abstract. (shrink)

This research note challenges the idea that Random Somatic Mutations are entirely random, highlighting their non-equiprobable nature and their influence on evolution, involution, or indeterminacy. It recalls the Neutrosophic Theory of Evolution, extending Darwin’s theory, and emphasizes the importance of distinguishing between different senses of ‘random mutation’ in evolutionary theory.

What is new about the present study is that the author approaches the religious metamorphosis from the perspective of the evolution of consciousness itself. The result of his exploration made the author realize that the development of European consciousness was not just an accidental historical process.

The human Y chromosome contains very low levels of nucleotide variation. It has been variously hypothesized that this invariance reflects historic reductions in the human male population, a very recent common ancestry, a slow rate of molecular evolution, an inability to evolve adaptively, or frequent selective sweeps acting on genes borne on the Y chromosome. We propose an alternative theory in which human Y chromosome evolution is driven by mutations in the maternally inherited mitochondrial genome, which impair male fertility and (...) ultimately lead to a reduction in the effective population size (Ne) and consequently the variability of the Y chromosome. BioEssays 24:275–279, 2002. © 2002 Wiley Periodicals, Inc.; DOI 10.1002/bies.10062. (shrink)

:Masculinity studies recognizes that masculinity is culturally variable, historically specific, multidimensional, and multiple. This mutability is reflected in concepts like hegemonic masculinity, hybrid masculinity, mosaic masculinities, personalized masculinities, sensual masculinity, and inclusive masculinity. Building on this idea of mutating masculinity, this paper addresses a theoretical problem acknowledged by many scholars: how to account for both the singular intimacy of lived experience and the commonality of shared social norms. In order to build a mutable model that encompasses both experience and norms (...) the paper borrows from Félix Guattari's technique of schizoanalytic cartography, which maps assemblages. This new approach to theorizing masculinity is illustrated by diagrams which map its institutional, discursive, cultural, existential, bodily, and biological aspects. (shrink)

Depuis une dizaine d'années, des centaines des millions d'internautes ont donné naissance à des édifices informationnels novateurs. Ces dispositifs dits Web 2.0 constituent de nouveaux modèles éditoriaux. Ces changements,qui s'inscrivent dans la continuité de l'histoire des techniques et des usages, accélèrent considérablement les processus historiques en cours. Par la métaphore des frontières, cet article analyse les profondes mutations intervenues dans le domaine des savoirs : question de l'accès, enjeux de la mémoire collective, transformation de la nature des savoirs.

In many species the mutation rate is higher in males than in females, a phenomenon denoted as male mutation bias. This is often observed in animals where males produce many more sperm than females produce eggs, and is thought to result from differences in the number of replication‐associated mutations accumulated in each sex. Thus, studies of male mutation bias have the capacity to reveal information about the replication‐dependent or replication‐independent nature of different mutations. The availability of whole (...) genome sequences for many species, as well as for multiple individuals within a species, has opened the door to studying factors, both sequence‐specific and those acting on the genome globally, that affect differences in mutation rates between males and females. Here, we assess the advantages that genomic sequences provide for studies of male mutation bias and general mutation mechanisms, discuss major challenges left unresolved, and speculate about the direction of future studies. (shrink)

Le changement institutionnel dans les pays post-soviétiques analysé à partir des politiques de la jeunesse en Estonie dans les années 1990-2013 montre la nécessité d’articuler les temporalités individuelles et institutionnelles pour pleinement comprendre l’évolution de ce secteur de l’action publique. Dans le cas de l’Estonie, en effet, la rupture institutionnelle ne s’est pas produite lors de l’effondrement de l’Union soviétique mais au moment du déménagement du ministère de l’Éducation hors de la capitale en 2001, en période de stabilité politique. La (...) PJ est alors considérée comme une politique trans-sectorielle, intégrée dans le processus de planification de l’État en fonction des objectifs de l’Union Européenne. L’État renforce simultanément son rôle stratégique de planification des politiques publiques. Au regard des temporalités individuelles, ce n’est pas la chute de l’URSS, mais le déménagement du ministère qui engendre une rupture dans les trajectoires des fonctionnaires d’État. Il s’accompagne de l’accès aux postes clé de jeunes agents socialisés aux politiques européennes. Le changement de la PJ en Estonie révèle que la socialisation politique des responsables de la politique publique est essentielle pour comprendre les comportements fortement hétérogènes des réformateurs des pays post-soviétiques. (shrink)

Academic misconduct is a problem of growing concern across the tertiary education sector. While plagiarism has been the most common form of academic misconduct, the advent of software programs to detect plagiarism has seen the problem of misconduct simply mutate. As universities attempt to function in an increasingly complex environment, the factors that contribute to academic misconduct are unlikely to be easily mitigated. A multiple case study approach examined how academic misconduct is perceived in universities in in Australia, New Zealand (...) and the United Kingdom via interviews with academics and administrators. The findings show that academic misconduct is a systemic problem that manifests in various ways and requires similarly diverse approaches to management. Greater consistency in policies and procedures, including a focus on preventative education for both staff and students, is key to managing the mutations of academic misconduct that continue to plague the higher education sector globally. (shrink)

Somatic mutations arising in human skin cancers are heterogeneously distributed across the genome, meaning that certain genomic regions (e.g., heterochromatin or transcription factor binding sites) have much higher mutation densities than others. Regional variations in mutation rates are typically not a consequence of selection, as the vast majority of somatic mutations in skin cancers are passenger mutations that do not promote cell growth or transformation. Instead, variations in DNA repair activity, due to chromatin organization and transcription factor binding, (...) have been proposed to be a primary driver of mutational heterogeneity in melanoma. However, as discussed in this review here, recent studies indicate that chromatin organization and transcription factor binding also significantly modulate the rate at which UV lesions form in DNA. The authors propose that local variations in lesion susceptibility may be an important driver of mutational hotspots in melanoma and other skin cancers, particularly at binding sites for ETS transcription factors. (shrink)

Information about the structure, function and regulation of the maize Suppressormutator (Spm) transposable element has emerged from the genetic and molecular characterization of both deletion mutations and an unconventional type of reversible genetic change (epimutation). The element is subject to an epigenetic mechanism that can either stably inactivate it or specify one of a variety of heritable programs of differential element expression in development. The essay explores the relationship between the Spm element's epigenetic developmental programming mechanism and the determinative events (...) central to plant development and differentiation. (shrink)

One central tenet of the Modern Evolutionary Synthesis , and the consensus view among biologists until now, is that all genetic mutations occur by “chance” or at “random” with respect to adaptation. However, the discovery of some molecular mechanisms enhancing mutation rate in response to environmental conditions has given rise to discussions among biologists, historians and philosophers of biology about the “chance” vs “directed” character of mutations . In fact, some argue that mutations due to a particular kind of (...) mutator mechanisms challenge the Modern Synthesis because they are produced when and where needed by the organisms concerned. This paper provides a defense of the Modern Synthesis’ consensus view about the chance nature of all genetic mutations by reacting to Jablonka and Lamb’s analysis of genetic mutations and the explicit Lamarckian flavor of their arguments. I argue that biologists can continue to talk about chance mutations according to what I call and define as the notion of “evolutionary chance,” which I claim is the Modern Synthesis’ consensus view and a reformulation of Darwin’s most influential idea of “chance” variation. Advances in molecular genetics are therefore significant but not revolutionary with respect to the Modern Synthesis’ paradigm. (shrink)

Recently, βIII spectrins have been recognized as ataxia disease genes, with the identification by Ikeda and co‐workers of pathogenic mutations in the SPTBN2 gene in three large (and mapped) SCA5 families of American and European origin.(1) With their discovery, the large “Lincoln” family has been traced back to the underlying genetic defect for the slowly progressive cerebellar ataxia. In addition, the involvement of this component of the cytoskeleton directs attention towards the possible role of organelle stability during neurodegeneration. The findings (...) suggest that the mechanical properties of neurons and their dynamics may be as important as altered Ca2+ homeostasis, transcriptional dysregulation, and impaired protein degradation in neurodegeneration conditions. BioEssays 28: 785–787, 2006. © 2006 Wiley Periodicals, Inc. (shrink)