How cell polarity is established and maintained is an important question in diverse biological contexts. Molecular mechanisms used to localize polarity proteins to distinct domains are likely context‐dependent and provide a feedback loop in order to maintain polarity. One such mechanism is the localized translation of mRNAs encoding polarity proteins, which will be the focus of this review and may play a more important role in the establishment and maintenance of polarity than is currently known. Localized translation of mRNAs encoding (...) polarity proteins can be used to establish polarity in response to an external signal, and to maintain polarity by local production of polarity determinants. The importance of this mechanism is illustrated by recent findings, including orb2‐dependent localized translation of aPKC mRNA at the apical end of elongating spermatid tails in the Drosophila testis, and the apical localization of stardust A mRNA in Drosophila follicle and embryonic epithelia. (shrink)

Recent studies have shown that some maternal mRNAs are localized in specific cytoplasmic regions of eggs and embryos and are rearranged in concert with the cytoplasmic movements that fix the embryonic axes. The localization and ooplasmic segregation of mRNA molecules may be mediated by their association with specific egg cytoskeletal domains.

In the mammalian central nervous system (CNS), each neuron receives signals from other neurons through numerous synapses located on its cell body and dendrites. Molecules involved in the postsynaptic signaling pathways need to be targeted to the appropriate subcellular domains at the right time during both synaptogenesis and the maintenance of synaptic functions. The presence of messenger RNAs (mRNAs) in dendrites offers a mechanism for synthesizing the appropriate molecules at the right place in response to local extracellular stimuli. Several dendritic (...) mRNAs have been identified, and the mechanisms controlling their localization are beginning to be understood. In many cell types, controls on mRNA stability play an important role in the regulation of gene expression, but it is unclear to what extent this type of control operates in dendrites. The regulation of protein synthesis and the control of mRNA stability in dendrites could have important implications for neuronal function. BioEssays 20:70–78, 1998. © 1998 John Wiley & Sons, Inc. (shrink)

In the mammalian central nervous system (CNS), each neuron receives signals from other neurons through numerous synapses located on its cell body and dendrites. Molecules involved in the postsynaptic signaling pathways need to be targeted to the appropriate subcellular domains at the right time during both synaptogenesis and the maintenance of synaptic functions. The presence of messenger RNAs (mRNAs) in dendrites offers a mechanism for synthesizing the appropriate molecules at the right place in response to local extracellular stimuli. Several dendritic (...) mRNAs have been identified, and the mechanisms controlling their localization are beginning to be understood. In many cell types, controls on mRNA stability play an important role in the regulation of gene expression, but it is unclear to what extent this type of control operates in dendrites. The regulation of protein synthesis and the control of mRNA stability in dendrites could have important implications for neuronal function. BioEssays 20:70–78, 1998. © 1998 John Wiley & Sons, Inc. (shrink)

hiCLIP (RNA hybrid and individual‐nucleotide resolution ultraviolet cross‐linking and immunoprecipitation), is a novel technique developed by Sugimoto et al. (2015). Here, the use of different adaptors permits a controlled ligation of the two strands of a RNA duplex allowing the identification of each arm in the duplex upon sequencing. The authors chose a notoriously difficult to study double‐stranded RNA‐binding protein (dsRBP) termed Staufen1, a mammalian homolog of Drosophila Staufen involved in mRNA localization and translational control. Using hiCLIP, they (...) discovered a dominance of intramolecular RNA duplexes compared to the total RNA duplexes identified. Importantly, the authors discovered two different types of intramolecular duplexes in the cell: highly translated mRNAs with long‐range duplexes in their 3′‐UTRs and poorly translated mRNAs with duplexes in their coding region. In conclusion, the authors establish hiCLIP as an important novel technique for the identification of RNA secondary structures that serve as in vivo binding sites for dsRBPs. (shrink)

The multistep pathway of eukaryotic gene expression involves a series of highly regulated events in the nucleus and cytoplasm. In the nucleus, genes are transcribed into pre‐messenger RNAs which undergo a series of nuclear processing steps. Mature mRNAs are then transported to the cytoplasm, where they are translated into protein and degraded at a rate dictated by transcript‐ and cell‐type‐specific cues. Until recently, these individual nuclear and cytoplasmic events were thought to be primarily regulated by different RNA‐ and DNA‐binding proteins (...) that are localized either only in the nucleus or only the cytoplasm. Here, we describe multifunctional proteins that control both nuclear and cytoplasmic steps of gene expression. One such class of multifunctional proteins (e.g., Bicoid and Y‐box proteins) regulates both transcription and translation whereas another class (e.g., Sex‐lethal) regulates both nuclear RNA processing and translation. Other events controlled by multifunctional proteins include assembly of spliceosome components, spliceosome recycling, RNA editing, cytoplasmic mRNA localization, and cytoplasmic RNA stability. The existence of multifunctional proteins may explain the paradoxical involvement of the nucleus in an RNA surveillance pathway (nonsense‐mediated decay) that detects cytoplasmic signals (premature termination codons). We speculate that shuttling multifunctional proteins serve to efficiently link RNA metabolism in the cytoplasmic and nuclear compartments. BioEssays 23:775–787, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

In a recent issue of Nature Communications Ukleja and co‐workers reported a cryo‐EM 3D reconstruction of the Ccr4‐Not complex from Schizosaccharomyces pombe with an immunolocalization of the different subunits. The newly gained architectural knowledge provides cues to apprehend the functional diversity of this major eukaryotic regulator. Indeed, in the cytoplasm alone, Ccr4‐Not regulates translational repression, decapping and deadenylation, and the Not module additionally plays a positive role in translation. The spatial distribution of the subunits within the structure is compatible with (...) a model proposing that the Ccr4‐Not complex interacts with the 5′ and 3′ ends of target mRNAs, allowing different functional modules of the complex to act at different stages of the translation process, possibly within a circular constellation of the mRNA. This work opens new avenues, and reveals important gaps in our understanding regarding structure and mode of function of the Ccr4‐Not complex that need to be addressed in the future. (shrink)

Regulation of the subcellular localization of certain proteins is a mechanism for the regulation of their biological activities. FGF‐2 can be produced as distinct isoforms by alternative initiation of translation on a single mRNA and the isoforms are differently sorted in cells. High molecular weight FGF‐2 isoforms are not secreted from the cell, but are transported to the nucleus where they regulate cell growth or behavior in an intracrine fashion. 18 kDa FGF‐2 can be secreted to the extracellular (...) medium where it acts as a conventional growth factor by binding to and activation of cell‐surface receptors. Furthermore, following receptor‐mediated endocytosis, the exogenous FGF‐2 can be transported to the nuclei of target cells, and this is of importance for the transmittance of a mitogenic signal. The growth factor is able to interact with several intracellular proteins. Here, the mode of action and biological role of intracellular FGF‐2 are discussed. BioEssays 28: 504–514, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

Regulation of the subcellular localization of certain proteins is a mechanism for the regulation of their biological activities. FGF‐2 can be produced as distinct isoforms by alternative initiation of translation on a single mRNA and the isoforms are differently sorted in cells. High molecular weight FGF‐2 isoforms are not secreted from the cell, but are transported to the nucleus where they regulate cell growth or behavior in an intracrine fashion. 18 kDa FGF‐2 can be secreted to the extracellular (...) medium where it acts as a conventional growth factor by binding to and activation of cell‐surface receptors. Furthermore, following receptor‐mediated endocytosis, the exogenous FGF‐2 can be transported to the nuclei of target cells, and this is of importance for the transmittance of a mitogenic signal. The growth factor is able to interact with several intracellular proteins. Here, the mode of action and biological role of intracellular FGF‐2 are discussed. BioEssays 28: 504–514, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

Asymmetric RNA localization is required for many developmental processes in a wide range of organisms. For example, wingless and pair‐rule transcripts are localized to the apical membrane of polarized cells. It has been unclear, however, if this localization is important for biological activity and, in addition, how the transcripts are transported. Two recent studies(1,2) have identified cis‐elements and trans‐acting factors that are required for the asymmetric localization of mRNAs. Correct localization is shown to be required for (...) biological activity, and a mechanism of RNA transport involving the microtubule motor dynein has been revealed. BioEssays 23:869–872, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

Central to the differentiation and patterning of the Drosophila oocyte is the asymmetric intracellular localization of numerous mRNA and protein molecules involved in developmental signalling. Recent advances have identified some of the molecules mediating oocyte differentiation, specification of the anterior pole of the embryo, and determination of the embryonic germ line. This work is considered in the context of the classical model of the germ plasm as a cytoplasmic determinant for germ cell formation.

Post‐transcriptional regulation faces a distinctive challenge in gametes. Transcription is limited when the germ cells enter the division phase due to condensed chromatin, while gene expression during gamete maturation, fertilization, and early cleavage depends on existing mRNA post‐transcriptional coordination. The dynamics of the 3ʹ‐poly(A) tail play crucial roles in defining mRNA fate. The 3ʹ‐poly(A) tail is covered with poly(A)‐binding proteins (PABPs) that help to mediate mRNA metabolism and recent work has shed light on the number and function (...) of germ cell‐specific expressed PABPs. There are two structurally different PABP groups distinguished by their cytoplasmic and nuclear localization. Both lack catalytic activity but are coupled with various roles through their interaction with multifunctional partners during mRNA metabolism. Here, we present a synopsis of PABP function during gametogenesis and early embryogenesis and describe both conventional and current models of the functions and regulation of PABPs, with an emphasis on the physiological significance of how germ cell‐specific PABPs potentially affect human fertility. (shrink)

An analysis of two heuristic strategies for the development of mechanistic models, illustrated with historical examples from the life sciences. In Discovering Complexity, William Bechtel and Robert Richardson examine two heuristics that guided the development of mechanistic models in the life sciences: decomposition and localization. Drawing on historical cases from disciplines including cell biology, cognitive neuroscience, and genetics, they identify a number of "choice points" that life scientists confront in developing mechanistic explanations and show how different choices result in (...) divergent explanatory models. Describing decomposition as the attempt to differentiate functional and structural components of a system and localization as the assignment of responsibility for specific functions to specific structures, Bechtel and Richardson examine the usefulness of these heuristics as well as their fallibility—the sometimes false assumption underlying them that nature is significantly decomposable and hierarchically organized. When Discovering Complexity was originally published in 1993, few philosophers of science perceived the centrality of seeking mechanisms to explain phenomena in biology, relying instead on the model of nomological explanation advanced by the logical positivists (a model Bechtel and Richardson found to be utterly inapplicable to the examples from the life sciences in their study). Since then, mechanism and mechanistic explanation have become widely discussed. In a substantive new introduction to this MIT Press edition of their book, Bechtel and Richardson examine both philosophical and scientific developments in research on mechanistic models since 1993. (shrink)

Nuclear pre‐mRNAs must be precisely processed to give rise to mature cytoplasmic mRNAs. This maturation process, known as splicing, involves excision of intron sequences and ligation of the exon sequences. One of the major problems in understanding this process is how splice sites, the sequences which form the boundaries between introns and exons, can be accurately selected. A number of studies have defined conserved sequences within introns which were later shown to interact with small nuclear ribonucleoproteins (snRNPs). However, due to (...) the simplicity of these conserved sequences it has become clear that other elements must be involved and a number of studies have indicated the importance of secondary structures within pre‐mRNAs. Using various examples, we shall show that such structures can help to specify splice sites by modifying physical distances within introns or by being involved in the definition of exons and, lastly, that they can be part of the regulation of alternative splicing. (shrink)

This paper describes one style of functional analysis commonly used in the neurosciences called task-bound functional analysis. The concept of function invoked by this style of analysis is distinctive in virtue of the dependence relations it bears to transient environmental properties. It is argued that task-bound functional analysis cannot explain the presence of structural properties in nervous systems. An alternative concept of neural function is introduced that draws on the theoretical neuroscience literature, and an argument is given to show that (...) this alternative concept of may help to overcome the explanatory limitations of task-bound functional analysis. (shrink)

Spontaneous localization theories are a class of quantum theories which solve the so-called measurement problem by non-linearly and stochastically modifying the Schrödinger dynamics. In this paper I briefly explain where these theories are coming from, what their driving ideas and main features are, and how they were historically developed. Also, I discuss their empirical and ontological adequacy, as well as their relativistic extensions and their experimental confirmation.

Spontaneous localization theory is a quantum theory proposed by GianCarlo Ghirardi, together with Alberto Rimini and Tullio Weber in 1986. However, soon it became clear to Ghirardi that his work was more than just one theory: he actually developed a framework, a family of theories in which the wavefunction jumps, but where the ontology of the theory is underdetermined. After acknowledging that the wavefunction did not provide a satisfactory ontology, he assumed that matter was described by a continuous matter (...) density field in three-dimensional space, whose evolution is governed by a stochastic wavefunction evolution. Alternatively, Bell assumed that the wavefunction would govern a spatiotemporal event ontology, dubbed ‘flashes.’ However, not much work has been done with the perhaps most obvious possibility, namely that physical objects are made of particles. This paper has two aims. First to explain the reason why people require spontaneous localization theory to be more than just a theory about the wavefunction. This is done by showing how the problem everyone in the foundation of quantum mechanics take to be the fundamental problem of quantum mechanics, namely the measurement problem, is a red herring. Then, the paper explores the possibility of spontaneous localization theories of particles. I argue that this discussion is not a mere exercise, as spontaneous localization theories of particles may be amenable to a relativistic extension which does not require a foliation, and because in general the peculiar type of indeterminism of spontaneous localization theories may help shedding new light on the nature of the tension between quantum theory and relativity. (shrink)

Neuronal signalling involves multiple neuropeptides that are diverse in structure and function. Complex patterns of tissue‐specific expression arise from alternate RNA splicing of neuropeptide‐encoding gene transcripts. The pattern of expression and its role in cell signalling is diffecult to study at the level of single neurons in the complex vertebrate brain. However, in the model molluscan system, Lymnaea, it is possible to show that alternate mRNA expression of the FMRFamide gene is specific to single identified neurons. Two different transcripts (...) are expressed in a mutually exclusive manner in different neurons. Post‐translational processing of the two precursor proteins leads to completely distinct sets of neuropeptide transmitters. The function of these transmitter cocktails, resulting from alternate mRNA splicing, was studied physiologically in identified neurons forming part of a behaviourally important network regulating heartbeat. (shrink)

Alzheimer's disease is characterized by amyloid-beta peptide -loaded plaques in the brain. Abeta is a cleavage fragment of amyloid-beta protein precursor and over production of APP may lead to amyloidogenesis. The regulatory region of the APP gene contains consensus sites recognized by the transcription factor, specificity protein 1 , which has been shown to be required for the regulation of APP and Abeta. To understand the role of SP1 in APP biogenesis, herein we have characterized the relative distribution and (...) class='Hi'>localization of SP1, APP, and Abeta in various brain regions of rodent and primate models using immunohistochemistry. We observed that overall distribution and cellular localization of SP1, APP, and Abeta are similar and neuronal in origin. Their distribution is abundant in various layers of neocortex, but restricted to the Purkinje cell layer of the cerebellum, and the pyramidal cell layer of hippocampus. These findings suggest that overproduction of Abeta in vivo may be associated with transcriptional pathways involving SP1 and the APP gene. (shrink)

Case studies in the psychophysics, modeling and localization of human vision are presented as an example of.

Starting from the phase space representation of quantum mechanics we provide an Euclidean system of covariance for the photon. In particular, we consider systems with the Poincaré group as the symmetry group and use a standard procedure in order to build a phase space and a localization observable on the phase space. Then we focus on the massless representations of the Poincaré group that we use to build a space localization observable for the photon.

Six years ago, the Singer lab published a landmark paper which described how individual mRNA particles cross the nuclear pore complex in mammalian tissue culture cells. This involved the simultaneous imaging of mRNAs, each labeled by a large number of tethered fluorescent proteins and fluorescently tagged nuclear pore components. Now two groups have applied this technique to the budding yeast Saccharomyces cerevisiae. Their results indicate that in the course of nuclear export, mRNAs likely engage complexes that are present on (...) either side of the pore and that these interactions are modulated by proteins present in the messenger ribonucleoprotein (mRNP) complex. These findings lend support to the notion that just before and/or after the completion of nuclear export, mRNPs undergo one or more maturation steps that prepare the packaged mRNAs for translation. These results represent new and exciting insights into the mechanism of mRNA nuclear export. (shrink)

The main topics of this second part of a two-part essay are some consequences of the phenomenon of vacuum polarization as the most important physical manifestation of modular localization. Besides philosophically unexpected consequences, it has led to a new constructive “outside-inwards approach” in which the pointlike fields and the compactly localized operator algebras which they generate only appear from intersecting much simpler algebras localized in noncompact wedge regions whose generators have extremely mild almost free field behavior. -/- Another consequence (...) of vacuum polarization presented in this essay is the localization entropy near a causal horizon which follows a logarithmically modified area law in which a dimensionless area (the area divided by the square of dR where dR is the thickness of a light-sheet) appears. There are arguments that this logarithmically modified area law corresponds to the volume law of the standard heat bath thermal behavior. We also explain the symmetry enhancing effect of holographic projections onto the causal horizon of a region and show that the resulting infinite dimensional symmetry groups contain the Bondi–Metzner–Sachs group. This essay is the second part of a partitioned longer paper. (shrink)

Messenger RNA is a flexible tool box that plays a key role in the dynamic regulation of gene expression. RNA modifications variegate the message conveyed by the mRNA. Similar to DNA and histone modifications, mRNA modifications are reversible and play a key role in the regulation of molecular events. Our understanding about the landscape of RNA modifications is still rudimentary in contrast to DNA and histone modifications. The major obstacle has been the lack of sensitive detection methods since (...) they are non-editing events. However, with the advent of next-generation sequencing techniques, RNA modifications are being identified precisely at single nucleotide resolution. In recent years, methylation at the N6 position of adenine has gained the attention of RNA biologists. The m6A modification has a set of writers, erasers, and readers. Here, we provide a summary of interesting facts, conflicting findings, and recent advances in the technical and functional aspects of the m6A epitranscriptome. The recent outburst of studies has brought the key role of mRNA N6-methyladenosine modification in post-transcriptional processing steps into the limelight. This review summarizes the current progress and the future prospective of m6A methylome. We addressed the debatable function of m6A modification and related modifiers in tumorigenesis and tumor progression. (shrink)

The main aim of this work is to relate integrability in QFT with a complete particle interpretation directly to the principle of causal localization, circumventing the standard method of finding sufficiently many conservation laws. Its precise conceptual-mathematical formulation as “modular localization” within the setting of local operator algebras also suggests novel ways of looking at general (non-integrable) QFTs which are not based on quantizing classical field theories.Conformal QFT, which is known to admit no particle interpretation, suggest the presence (...) of a “partial” integrability, referred to as “conformal integrability”. This manifests itself in a “braid-permutation” group structure which contains in particular informations about the anomalous dimensional spectrum. For chiral conformal models this reduces to the braid group as it is represented in Hecke- or Birman-Wenzl-algebras associated to chiral models.Another application of modular localization mentioned in this work is an alternative to the BRST formulation of gauge theories in terms of stringlike vectorpotentials within a Hilbert space setting. (shrink)

This paper is concerned with n-localization property introduced by Newelski and Rosłanowski in [10] and getting it for CS iterations of forcing notions.

Nuclear proteins are synthesized in the cytoplasm and must subsequently enter the nucleus. Recent experiments indicate some similarities and some differences between protein localization to the nucleus and localization to other organelles.

The progression of theories suggested for our world, from ego- to geo- to helio-centric models to universe and multiverse theories and beyond, shows one tendency: The size of the described worlds increases, with humans being expelled from their center to ever more remote and random locations. If pushed too far, a potential theory of everything (TOE) is actually more a theories of nothing (TON). Indeed such theories have already been developed. I show that including observer localization into such theories (...) is necessary and sufficient to avoid this problem. I develop a quantitative recipe to identify TOEs and distinguish them from TONs and theories in-between. This precisely shows what the problem is with some recently suggested universal TOEs. (shrink)

Objective: Atypical patterns of language lateralization due to early reorganizational processes constitute a challenge in the pre-surgical evaluation of patients with pharmaco-resistant epilepsy. There is no consensus on an optimal analysis method used for the identification of language dominance in MEG. This study examines the concordance between MEG source localization of beta power desynchronization and fMRI with regard to lateralization and localization of expressive and receptive language areas using a visual verb generation task.Methods: Twenty-five patients with pharmaco-resistant epilepsy, (...) including six patients with atypical language lateralization, and ten right-handed controls obtained MEG and fMRI language assessment. Fourteen patients additionally underwent the Wada test. We analyzed MEG beta power desynchronization in sensor (controls) and source space (patients and controls). Beta power decrease between 13 and 35 Hz was localized applying Dynamic Imaging of Coherent Sources Beamformer technique. Statistical inferences were grounded on cluster-based permutation testing for single subjects.Results: Event-related desynchronization of beta power in MEG was seen within the language-dominant frontal and temporal lobe and within the premotor cortex. Our analysis pipeline consistently yielded left language dominance with high laterality indices in controls. Language lateralization in MEG and Wada test agreed in all 14 patients for inferior frontal, temporal and pari... (shrink)

Eukaryotic gene expression is extensively controlled at the level of mRNA stability and the mechanisms underlying this regulation are markedly different from their archaeal and bacterial counterparts. We propose that two such mechanisms, nonsense‐mediated decay (NMD) and motif‐specific transcript destabilization by CCCH‐type zinc finger RNA‐binding proteins, originated as a part of cellular defense against RNA pathogens. These branches of the mRNA turnover pathway might have been used by primeval eukaryotes alongside RNA interference to distinguish their own messages from (...) those of RNA viruses and retrotransposable elements. We further hypothesize that the subsequent advent of “professional” innate and adaptive immunity systems allowed NMD and the motif‐triggered mechanisms to be efficiently repurposed for regulation of endogenous cellular transcripts. This scenario explains the rapid emergence of archetypical mRNA destabilization pathways in eukaryotes and argues that other aspects of post‐transcriptional gene regulation in this lineage might have been derived through a similar exaptation route. -/- . (shrink)

ABSTRACT This article elaborates a concept of localization through interpreting key arguments in Colombian philosopher Santiago Castro-Gómez’s early works grouped by the author under the name “genealogies of coloniality.” Following the role localization in his genealogies of coloniality reveals what Castro-Gómez calls “heterarchic articulations.” Heterarchic articulations delineate an analytic model of power that traces how multiple technologies and formations of power operating at different levels, from colonial geopolitics to individual “corpopolitics” of desire, converge and configure radically localized processes (...) of subjectivation. Localization understood in these terms, the author argues, allows Castro-Gómez to radicalize, transform, and combine Foucault’s genealogical approach and decolonial theory. The article concludes by showing that, besides radicalizing and combining genealogy and decoloniality, the localization at work in Castro-Gómez’s genealogies of coloniality serves to interpret theorizations and phenomena of contemporary violence by turning to Mexican transfeminist philosopher Sayak Valencia’s analysis of “gore capitalism.”. (shrink)

Despite a library full of literature on miRNA biology, core issues relating to miRNA target detection, biological effect, and mode of action remain controversial. This essay proposes that the predominant mechanism of direct miRNA action is translational inhibition, whereas the bulk of miRNA effects are mRNA based. It explores several issues confounding miRNA target detection, and discusses their impact on the dominance of “miRNA seed” dogma and the exploration of non‐canonical binding sites. Finally, it makes comparisons between miRNA target (...) prediction and transcription factor binding prediction, and questions the value of characterizing miRNA binding sites based on which miRNA nucleotides are paired with an mRNA. (shrink)

This study aims to assess the localization of Schema.org for manuscript description in the Iranian-Islamic information context using documentary and qualitative content analysis. The schema.org introduces schemas for different Web content objects so as to generate structured data. Given that the structure of Schema.org is ontological, the inheritance of the manuscript types from the properties of their parent types, as well as the localization and description of the specific properties of the manuscripts in the Iranian-Islamic information context were (...) investigated in order to improve their indexability and semantic visibility in the Web search engines. The proposed properties specific to the manuscript type and the six proposed properties to be added to the “CreativeWork” type are found to be consistent with other schema properties. In turn, these properties lead to the localization of the existing schema for the manuscript type compatibility with the Iranian-Islamic information context. This schema is also applicable to centers with published records on the Web, and if markup with these properties, their indexability and semantic visibility in Web search engines increases accordingly. The generation of structured data in the Web environment through this schema is deemed to promote the concept of the Semantic Web, and make data and knowledge retrieval easier. (shrink)

In the general relativity theory gravitational energy-momentum density is usually described by a pseudo-tensor with strange transformation properties so that one does not have localization of gravitational energy. It is proposed to set up a gravitational energy-momentum density tensor having a unique form in a given coordinate system by making use of a bimetric formalism. Two versions are considered: (1) a bimetric theory with a flat-space background metric which retains the physics of the general relativity theory and (2) one (...) with a background corresponding to a space of constant curvature which introduces modifications into general relativity under certain conditions. The gravitational energy density in the case of the Schwarzschild solution is obtained. (shrink)

The neuromuscular junction has been used for several decades as an excellent model system to examine the cellular and molecular events involved in the formation and maintenance of a differentiated chemical synapse. In this context, several laboratories have focused their efforts over the last 15 years on the important contribution of transcriptional mechanisms to the regulation of the development and plasticity of the postsynaptic apparatus in muscle fibers. Converging lines of evidence now indicate that post‐transcriptional events, operating at the level (...) of mRNA stability and targeting, are likely to also play key roles at the neuromuscular junction. Here, we present the recent findings highlighting the role of these additional molecular events and extend our review to include data showing that post‐transcriptional events are also important in the control of the expression of genes encoding synaptic proteins in muscle cells placed under different conditions. Finally, we discuss the possibility that mis‐regulation of post‐transcriptional events can occur in certain neuromuscular diseases and cause abnormalities of the neuromuscular junction. BioEssays 25:25–31, 2003. © 2002 Wiley Periodicals, Inc. (shrink)

The expression of certain eukaryotic genes is – at least in part – controlled at the level of mRNA translation. The step of translational initiation represents the primary target for regulation. The regulation of the intracellular iron storage protein ferritin in response to iron levels provides a good example of translational control by a reversible RNA/protein interaction in the 5' untranslated region of an mRNA. We consider mechanisms by which mRNA/protein interactions may impede translation initiation and discuss (...) recent data suggesting that the ferritin example may represent the ‘tip of the iceberg’ of a more general theme for translational control. (shrink)

We show how trajectories can be reintroduced in quantum mechanics provided that its spatial continuum is modelled by a variable real number (qr-number) continuum. Such a continuum can be constructed using only standard Hilbert space entities. In this approach, the geometry of atoms and subatomic objects differs from that of classical objects. The systems that are non-local when measured in the classical space-time continuum may be localized in the quantum continuum. We compare trajectories in this new description of space-time with (...) the corresponding Bohmian picture. (shrink)