Hebbian cell-assembly theory and attractor networks are good starting points for modeling cortical processing. Detailed cell models can be useful in understanding the dynamics of attractor networks. Cell assemblies are likely to be distributed, with the cortical column as the local processing unit. Synaptic memory may be dominant in all but the first couple of seconds.

Pulvermüller's work in extending Hebb's theory into the realm of language is exciting. However, we feel that what he characterizes as a single cell assembly is actually a set of cooperating cell assemblies that form parts of larger cognitive structures. These larger structures account more easily for a variety of phenomena, including the psycholinguistic.

Empirical evidence suggests that high frequency electrographic activity is involved in active representation of meaningful entities in the cortex. Theoretical work suggests that distributed cell assemblies also represent meaningful entities. However, we are still some way from understanding how these two are related. This commentary also makes suggestions for further investigation of the neural basis of language at the level of both words and sentence planning.

The cell assembly as a simple attractor cannot explain many cognitive phenomena. It must be a highly structured network that can sustain highly structured excitation patterns. Moreover, a cell assembly must be more widely distributed in space than on a square millimeter.

The cell assembly is an important concept for cognitive psychology. Cognitive processing will to a large extent depend on the relations that can exist between different assemblies. A potential relation between assemblies can already be seen in the occurrence of (classical) conditioning. However, the resulting associations between assemblies only produce behavioristic processing or so-called regular computation. Higher-level cognitive abilities most likely result from nonregular computation. I discuss the possibility of this form of computation in terms of (...) cell assemblies. (shrink)

The cell assembly model of language posits that words are laid down in the cortex by discrete sets of neurons distributed over specific parts of the brain. The strong internal links of these “word webs” may not only bind articulatory and acoustic knowledge of a lexical item, they may also link word and meaning; for example, by connecting neuron populations related to word forms to those of actions and perceptions to which the words refer. Therefore, the cortical activation elicited (...) by words should reflect aspects of word meaning, a postulate that has received strong support from recent work using neurophysiological and metabolic imaging. Segalowitz & Lane make the point that this neurobiological model can also be used to predict reaction times in behavioral experiments, using the behavioral distinction between content and function words as an example. We acclaim their view, but warn that response times might be related to different mechanisms at the neuronal level, including the cortical distribution and internal connectivity of cell assemblies along with their mutual connections in the grammatical (syntactic and semantic) network. (shrink)

Holistically ignited Hebbian models are fundamentally different from the serially organized connectionist implementations of language. This may be important for the recovery of language after injury, because connectionist models have provided useful insights into recovery of some cognitive functions. I ask whether cell assembly modelling can make an important contribution and whether the apparent incompatibility with successful connectionist modelling is a problem.

The premise of this paper is that an adequate model of consciousness will be able to account for the fundamental duality in experience typified by thought and feeling, objectivity and subjectivity, science and art, and that it will do so without any of these terms assimilating its counterpart. The paper argues that such an account is possible using existing models of the cell assembly, but only if consciousness is conceived in structural rather than information processing terms. To this end, (...) the paper contests the viability of information processing models that identify consciousness with a substrate-independent flow of information, and instead identifies consciousness with the physical structure of the cell assembly itself. This allows a fuller and more parsimonious account of consciousness than existing information processing models, as well as the integration of a range of key related matters from the fields of neuroanatomy, psychology, philosophy, and the physical sciences. (shrink)

The EEG and MEG studies cited in the target article found reduced gamma band power following pseudowords in comparison with words. Pulvermüller interprets this power difference in terms of reverberating lexical cell assemblies. An alternative interpretation in terms of latency jitter in the gamma band following pseudowords is proposed that does not appeal to lexical cell assemblies.

The idea of representing words with cell assemblies is very appealing. However, syntactic sequences need to be represented as well. This cannot be done by using the activity levels of assemblies. Instead, structural relations and operations between assemblies are needed to achieve serial order in syntactic word strings.

Pulvermüller restricts himself to an unnecessarily narrow range of evidence to support his claims. Evidence from neural modeling and behavioral experiments provides further support for an account of words encoded as transcortical cell assemblies. A cognitive neuroscience of language must include a range of methodologies (e.g., neural, computational, and behavioral) and will need to focus on the on-line processes of real-time language processing in more natural contexts.

Multiscale dynamics, linear approximations, global boundary conditions, experimental verification, and global influences on local cell assemblies are considered in the context of Wright & Liley's work. W&L provide a nice introduction to these issues and a reasonable simulation of intermediate scale dynamics, but the model does not adequately simulate combined local and global processes.

The thymus is a unique primary lymphoid organ that supports the production of self‐tolerant T‐cells essential for adaptive immunity. Intrathymic microenvironments are microanatomically compartmentalised, forming defined cortical, and medullary regions each differentially supporting critical aspects of thymus‐dependent T‐cell maturation. Importantly, the specific functional properties of thymic cortical and medullary compartments are defined by highly specialised thymic epithelial cells (TEC). For example, in the medulla heterogenous medullary TEC (mTEC) contribute to the enforcement of central tolerance by supporting deletion of autoreactive (...) T‐cell clones, thereby counterbalancing the potential for random T‐cell receptor generation to contribute to autoimmune disease. Recent advances have further shed light on the pathways and mechanisms that control heterogeneous mTEC development and how differential mTEC functionality contributes to control self‐tolerant T‐cell development. Here we discuss recent findings in relation to mTEC development and highlight examples of how mTEC diversity contribute to thymus medulla function. (shrink)

Terminally differentiating stratified squamous epithelial cells assemble a specialized protective barrier structure on their periphery termed the cornified cell envelope (CE). It is composed of numerous structural proteins that become cross‐linked by several transglutaminase enzymes into an insoluble macromolecular assembly. Several proteins are involved in the initial stages of CE assembly, but only certain proteins from a choice of more than 20 different proteins are used in the final stages of CE reinforcement, apparently to meet tissue‐specific requirements. In addition, (...) a variable selection of proteins may be upregulated in response to genetic defects of one of the CE proteins or tissue injury, in an effort to maintain an effective barrier. Additionally, in the epidermis and hair fiber cuticle, a layer of lipids is covalently attached to the proteins, which provides essential water barrier properties. Here we describe our current understanding of CE structure, a possible mechanism of its assembly, and various disorders that cause a defective barrier. BioEssays 24:789–800, 2002. Published 2002 Wiley Periodicals, Inc. (shrink)

Most lymphocytes of the T cell lineage develop along the CD4/CD8 pathway and express antigen receptors on their surfaces consisting of clonotypic αβ chains associated with invariant CD3‐γδε components and ζ chains, collectively referred to as the T cell antigen receptor complex (TCR). Expression of the TCR complex is dynamically regulated during T cell development, with immature CD4+CD8+ thymocytes expressing only 10% of the number of αβ TCR complexes on their surfaces expressed by mature CD4+ and CD8+ (...) T cells. Recent evidence demonstrates that low surface TCR density on CD4+CD8+ thymocytes results from the limited survival of a single TCR component within the ER, the TCRα chain, which has a half life of only 15 minutes in immature thymocytes, compared to >75 minutes in mature T cells. Instability of TCRα proteins in immature CD4+CD8+ thymocytes represents a novel mechanism by which expression of the multisubunit TCR complex is quantitatively regulated during T cell development. In the current review we discuss our recent findings concerning the assembly, intracellular transport, and expression of αβ TCR complexes in CD4+CD8+ thymocytes and comment on the functional significance of TCRα instability during T cell development. (shrink)

Understanding the mechanisms of early embryonic patterning and the timely allocation of specific cells to embryonic regions and fates as well as their development into tissues and organs, is a fundamental problem in Developmental Biology. The classical explanation for this process had been built around the notion of positional information. Accordingly the programmed appearance of sources of Morphogens at localized positions within a field of cells directs their differentiation. Recently, the development of organs and tissues from unpatterned and initially identical (...) stem cells (adult and embryonic) has challenged the need for positional information and even the integrity of the embryo, for pattern formation. Here we review the emerging area of organoid biology from the perspective of Developmental Biology. We argue that the events underlying the development of these systems are not purely linked to “self‐organization,” as often suggested, but rather to a process of genetically encoded self‐assembly where genetic programs encode and control the emergence of biological structures. (shrink)

Cell proliferation in response to growth factors is mediated by specific high affinity receptors. Ligand‐binding by receptors of the protein tyrosine kinase family results in the stimulation of several intracellular signal transduction pathways. Key signalling enzymes are recruited to the plasma membrane through the formation of stable complexes with activated receptors. These interactions are mediated by the conserved, non‐catalytic SH2 domains present in the signalling molecules, which bind with high affinity and specificity to tyrosine‐phosphorylated sequences on the receptors. The (...) assembly of enzyme complexes is emerging as a major mechanism of signal transduction and may regulate the pleiotropic effects of growth factors. (shrink)

Amit defines cell assemblies aslocal cortical neuron populationswith strong internal connections. However, Hebb himself proposed that cell assemblies are distributed over different cortical areas (nonlocal ortranscortical assemblies). We review evidence from cognitive neuroscience and neuropsychology supporting the assumption that cell assemblies are transcortical.

The endoplasmic reticulum (ER) uses various mechanisms to ensure that only properly folded proteins enter the secretory pathway. For proteins that oligomerize in the ER, the proper tertiary and quaternary structures must be achieved before their release. Although some proteins fold before oligomerization, others initiate oligomerization cotranslationally. Here, we discuss these different strategies and some of the unique problems they present for the ER quality control system. One mechanism used by the ER is thiol retention. Thiol retention operates by monitoring (...) the redox state of specific cysteine residue(s) and was discovered in studies on the assembly of IgM, a complex oligomeric glycoprotein. This system is also involved in retaining other unassembled proteins in the ER. Mutations that result in uneven numbers of cysteine residues can subject yet other proteins to thiol retention, altering their oligomerization status and function. The implications of these results on the effects of thiol retention on protein function and cell fate are discussed. BioEssays 20:546–554, 1998. © 1998 John Wiley & Sons Inc. (shrink)

Basement membranes are thin sheets of extracellular proteins situated in close contact with cells at various locations in the body. They have a great influence on tissue compartmentalization and cellular phenotypes from early embryonic development onwards. The major constituents of all basement membranes are collagen IV and laminin, which both exist as multiple isoforms and each form a huge irregular network by self assembly. These networks are connected by nidogen, which also binds to several other components (proteoglycans, fibulins). Basement membranes (...) are connected to cells by several receptors of the integrin family, which bind preferentially to laminins and collagen IV, and via some lectin‐type interactions. The formation of basement membranes requires cooperation between different cell types since nidogen, for example, is usually synthesized by cells other than those exposed to the basement membranes. Thus many molecular interactions, of variable affinities, determine the final shape of basement membranes and their preferred subanatomical localization. (shrink)

The developing vertebrate oocyte autonomously makes most of the components of the machinery for DNA and protein synthesis, as well as ‘maternal’ mRNAs, needed immediately after fertilization. However, specialized egg constituents such as yolk proteins, egg white, cholesterol, lipoproteins and egg coat substances, are formed in the liver, oviduct and perhaps in follicle cells. The assembly of the developing egg is therefore a fascinating example of division of labor among oocytes and extra‐oocyte tissues, the coordination of activities of the latter (...) being achieved by hormones. (shrink)

Despite its biological importance, the mechanism of formation of cutin, the polymeric matrix of plant cuticles, has not yet been fully clarified. Here, for the first time, we show the participation in the process of lipid vesicles formed by the self‐assembly of endogenous polyhydroxy fatty acids. The accumulation and fusion of these vesicles (cutinsomes) at the outer part of epidermal cell wall is proposed as the mechanism for early cuticle formation. BioEssays 30:273–277, 2008. © 2008 Wiley Periodicals, Inc.

Cell membranes are now emerging as finely tuned molecular systems, signifying that re‐evaluation of our understanding of their structure is essential. Although the idea that cell membrane lipid bilayers do little more than give shape and form to cells and limit diffusion between cells and their environment is totally passé, the structural, compositional, and functional complexity of lipid bilayers often catches cell and molecular biologists by surprise. Models of lipid bilayer structure have developed considerably since the heyday (...) of the fluid mosaic model, principally by the discovery of the restricted diffusion of membrane proteins and lipids within the plane of the bilayer. In reviewing this field, we now suggest that further refinement of current models is necessary and propose that describing lipid bilayers as “finely‐tuned molecular assemblies” best portrays their complexity and function. Also see the video abstract here: https://www.youtube.com/watch?v=ddkP-QRZTl8. (shrink)

Hydrogen fuel cells are likely to begin replacing conventional internal combustion engines as a power generation method for transportation applications in the near future. A life cycle analysis of a hydrogen fuel cell was performed to examine the major environmental impacts of such an engine in comparison with an internal combustion engine. To quantify the emissions, material consumption and energy consumption were identified by carrying out mass and energy balances, respectively. Wherever possible, a “well-to-wheel” approach was adopted to identify (...) all the processes involved. The size of the hydrogen fuel cell engine selected was 60 kW, which would power a small automobile weighing around 800 kg. This report briefly describes the materials and processes involved in assembling such an engine, with their respective environmental impacts. Different technologies to build a hydrogen economy also are discussed because hydrogen is an integral part of most fuel cell engines. The main conclusion is that if an environmentally sustainable system of hydrogen production is found, the use of hydrogen and, in turn, hydrogen fuel cell cars would be highly beneficial. Thus, the theoretical potential of fuel cells is great for environmental benefits, but practical applications might prove otherwise. (shrink)

Adult stem cell populations must coordinate their own maintenance with the generation of differentiated cell types to sustain organ physiology, in a spatially controlled manner and over long periods. Quantitative analyses of clonal dynamics have revealed that, in epithelia, homeostasis is achieved at the population rather than at the single stem cell level, suggesting that feedback mechanisms coordinate stem cell maintenance and progeny generation. In the central nervous system, however, little is known of the possible community (...) processes underlying neural stem cell maintenance. Recent work, in part based on intravital imaging made possible in the adult zebrafish, conclusively highlights that homeostasis in neural stem cell pools may rely on population asymmetry and long‐term spatiotemporal coordination of neural stem cell states and fates. These results suggest that neural stem cell assemblies in the vertebrate brain behave as self‐organized systems, such that the stem cells themselves generate their own intrinsic niche. (shrink)

The vertebrate immune system provides a remarkable showcase of the different ways the genome can be used to specify cellular identity and to mediate cellular function. It is arguably the leading mammalian system in which gene regulation programs that drive the acquisition of specific cell-type identities have been elucidated at the single cell level. More broadly for molecular genomics, the activation-induced gene expression pathways used in immune effector responses have provided textbook cases for fundamental elements of transcription factor (...) assembly at enhancers ; and immune system genes and gene clusters have provided key paradigms for the roles of long-range.. (shrink)

Targeted transitions in chromatin states at thousands of genes are essential drivers of eukaryotic development. Therefore, understanding the in vivo dynamics of epigenetic regulators is crucial for deciphering the mechanisms underpinning cell fate decisions. This review illustrates how, in addition to its cell memory function, the Polycomb group of transcriptional regulators orchestrates temporal, cell and tissue‐specific expression of master genes during development. These highly sophisticated developmental transitions are dependent on the context‐ and tissue‐specific assembly of the different (...) types of Polycomb Group (PcG) complexes, which regulates their targeting and/or activities on chromatin. Here, an overview is provided of how PcG complexes function at multiple scales to regulate transcription, local chromatin environment, and higher order structures that support normal differentiation and are perturbed in tumorigenesis. (shrink)

Chromosomes are not only carriers of the genetic material, but also actively regulate the assembly of complex intracellular architectures. During mitosis, chromosome‐induced microtubule polymerisation ensures spindle assembly in cells without centrosomes and plays a supportive role in centrosome‐containing cells. Chromosomal signals also mediate post‐mitotic nuclear envelope (NE) re‐formation. Recent studies using novel approaches to manipulate histones in oocytes, where functions can be analysed in the absence of transcription, have established that nucleosomes, but not DNA alone, mediate the chromosomal regulation of (...) spindle assembly and NE formation. Both processes require the generation of RanGTP by RCC1 recruited to nucleosomes but nucleosomes also acquire cell cycle stage specific regulators, Aurora B in mitosis and ELYS, the initiator of nuclear pore complex assembly, at mitotic exit. Here, we review the mechanisms by which nucleosomes control assembly and functions of the spindle and the NE, and discuss their implications for genome maintenance. (shrink)

The eyespot organelle of the green alga Chlamydomonas allows the cell to phototax toward (or away) from light to maximize the light intensity for photosynthesis and minimize photo‐damage. At cytokinesis, the eyespot is resorbed at the cleavage furrow and two new eyespots form in the daughter cells 180° from each other. The eyespots are positioned asymmetrically with respect to the microtubule cytoskeleton. Eyespots are assembled from all three chloroplast membranes and carotenoid‐filled granules, which form a sandwich structure overlaid by (...) the tightly apposed plasma membrane. This review describes (1) my interest in cellular asymmetry and organelle biology, (2) isolation of mutations that describe four genes governing eyespot placement and assembly, (3) the characterization of the EYE2 gene, which encodes a thioredoxin superfamily member, and (4) the characterization of the MIN1 gene, which is required for the layered organization of granules and membranes in the eyespot. BioEssays 25:410–416, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

Polarity is an inherent feature of almost all prokaryotic and eukaryotic cells. In most eukaryotic cells, growth polarity is due to the assembly of actin‐based growing domains at particular locations on the cell periphery. A contrasting scenario is that growth polarity results from the establishment of non‐growing domains, which are actively maintained at opposite end‐poles of the cell. This latter mode of growth is common in rod‐shaped bacteria and, surprisingly, also in the majority of plant cells, which elongate (...) along the apical–basal axes of plant organs. The available data indicate that the non‐growing end‐pole domains of plant cells are sites of intense endocytosis and recycling. These actin‐enriched end‐poles serve also as signaling platforms, allowing bidirectional exchange of diverse signals along the supracellular domains of longitudinal cell files. It is proposed that these actively remodeled end‐poles of elongating plant cells remotely resemble neuronal synapses. BioEssays 25:569–576, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

Microfluidic technology – the manipulation of fluids at micrometer scales – has revolutionized many areas of synthetic biology. The bottom‐up synthesis of “minimal” cell models has traditionally suffered from poor control of assembly conditions. Giant unilamellar vesicles (GUVs) are good models of living cells on account of their size and unilamellar membrane structure. In recent years, a number of microfluidic approaches for constructing GUVs has emerged. These provide control over traditionally elusive parameters of vesicular structure, such as size, lamellarity, (...) membrane composition, and internal contents. They also address sophisticated cellular functions such as division and protein synthesis. Microfluidic techniques for GUV synthesis can broadly be categorized as continuous‐flow based approaches and droplet‐based approaches. This review presents the state‐of‐the‐art of microfluidic technology, a robust platform for recapitulating complex cellular structure and function in synthetic models of biological cells. (shrink)

The hemidesmosome is a complex junction containing many proteins. The keratin cytoskeleton attaches to its cytoplasmic plaque, while its transmembrane elements interact with components of the extracellular matrix. Hemidesmosome assembly involves recruitment of α6β4 integrin heterodimers, as well as cytoskeletal elements and cytoskeleton-associated proteins to the cell surface. In our cell culture models, these phenomena appear to be triggered by laminin-5 in the extracellular matrix. Cell interaction with laminin-5 apparently induces both phosphorylation and dephosphorylation of subunits of (...) α6β4 integrin. There is emerging evidence that such events are necessary for subsequent cytoskeleton anchorage to the hemidesmosome cytoplasmic plaque. Once assembled, the hemidesmosome plays an essential role in maintaining firm epithelial adhesion to the basement membrane, with hemidesmosome disruption being a hallmark of certain devastating blistering diseases. However, the hemidesmosome is more than just a stable anchor, as it may also be the site of signal transduction, mediated by its α6β4 integrin component. This review discusses our current knowledge of the structure and assembly of the hemidesmosome. BioEssays 20:488–494, 1998. © 1998 John Wiley & Sons, Inc. (shrink)

Determination of cell fate in the developing eye of Drosophila depends on a precise sequence of cellular interactions which generate the stereotypic array of ommatidia. In the eye imaginal disc, an initially unpatterned epithelial sheath of cells, the first step in this process may be the specification of R8 photoreceptor cells at regular intervals. Genes such as Notch and scabrous, known to be involved in bristle development, alos participate in this process, suggesting that the specification of ommatidial founder cells (...) and the formation of sensory organs in the adult epidermis may involve a similar mechanism, that of lateral inhibition. The subsequent steps of ommatidial assembly, following R8 assignment, involve a different mechanism: Undetermined cells read their position based on the contacts they make with neighbors that have already begun to differentiate. The development of the R7 photoreceptor cell, one of the eight photoreceptor cells in the ommatidium, is best understood. An important role seems to be played by sevenless, a receptor tyrosine kinase on the surface of the R7 precursor. It transmits the positional information– most likely encoded by the boss protein on the neighboring R8 cell membrane – into the cell via its tyrosine kinase, which activates a signal transduction cascade. Constitutive activation of the sevenless kinase by overexpression of an N‐terminally truncated form results in the diversion of other ommatidial cells into the R7 pathway suggesting that activation of the sevenless signalling pathway is sufficient to specify R7 development. Genetic dissection of this pathway should therefore identify components of a signalling cascade activated by a tyrosine kinase. (shrink)

During early embryonic development in several metazoans, accurate DNA replication is ensured by high number of replication origins. This guarantees rapid genome duplication coordinated with fast cell divisions. In Xenopus laevis embryos this program switches to one with a lower number of origins at a developmental stage known as mid‐blastula transition (MBT) when cell cycle length increases and gene transcription starts. Consistent with this regulation, somatic nuclei replicate poorly when transferred to eggs, suggesting the existence of an epigenetic (...) memory suppressing replication assembly origins at all available sites. Recently, it was shown that histone H1 imposes a non‐permissive chromatin configuration preventing replication origin assembly on somatic nuclei. This somatic state can be erased by SSRP1, a subunit of the FACT complex. Here, we further develop the hypothesis that this novel form of epigenetic memory might impact on different areas of vertebrate biology going from nuclear reprogramming to cancer development. (shrink)

Recent developments in 3D cultures exploiting the self‐organization ability of pluripotent stem cells have enabled the generation of powerful in vitro systems termed brain organoids. These 3D tissues recapitulate many aspects of human brain development and disorders occurring in vivo. When combined with improved differentiation methods, these in vitro systems allow the generation of more complex “assembloids,” which are able to reveal cell diversities, microcircuits, and cell–cell interactions within their 3D organization. Here, the ways in which human (...) brain organoids have contributed to demystifying the complexities of brain development and modeling of developmental disorders is reviewed and discussed. Furthermore, challenging questions that are yet to be addressed by emerging brain organoid research are discussed. (shrink)

The fate of cells arrested in mitosis by antimitotic compounds is complex but is influenced by competition between pathways promoting cell death and pathways promoting mitotic exit. As components of both of these pathways are regulated by Cdc20‐dependent degradation, I hypothesize that variations in Cdc20 protein levels, rather than mutations in checkpoint genes, could affect cell fate during prolonged mitotic arrest. This hypothesis is supported by experiments where manipulation of Cdc20 levels affects the response to antimitotic compounds. The (...) observed differences in Cdc20 levels between cell lines likely reflects differences in the rate of synthesis or degradation of the protein; therefore, understanding these pathways at a molecular level could pave the way for modulating the activity of Cdc20, in turn presenting novel therapeutic possibilities. (shrink)

Assembly of minimal genomes revealed many genes encoding unknown functions. Three overlooked functional categories account for some of them. Cells are prone to make errors and age. As a first key function, discrimination between proper and changed entities is indispensable. Discrimination requires management of information, an authentic, yet abstract, cur- rency of reality. For example proteins age, sometimes very fast. The cell must identify, then get rid of old proteins without destroying young ones. Implementing discrimination in cells leads to (...) the second set of functions, usually ignored. Being abstract, information must nevertheless be embodied into material entities, with unavoidable idiosyncratic properties. This brings about novel unmet needs. Hence, the buildup of cells elicits specific but awkward material implementations, ‘kludges’ that become essential under particular settings, while difficult to identify. Finally, a third functional category char- acterizes the need for growth, with metabolic implementations allowing the cell to put together the growth of its cytoplasm, membranes, and genome, spanning different spatial dimensions. Solving this metabolic quandary, critical for engineering novel synthetic biology chassis, uncovered an unexpected role for CTP synthetase as the coordinator of nonhomothetic growth. Because a significant number of SynBio constructs aim at creating cell factories we expect that they will be attacked by viruses (it is not by chance that the function of the CRISPR system was identified in industrial settings). Substantiating the role of CTP, natural selection has dealt with this hurdle via synthesis of the antimetabolite 30-deoxy-30,40-didehydro- CTP, recruited for antiviral immunity in all domains of life. (shrink)

Red-2 is a computer program for red-cell antibody identification, a piece of "normal science". Abstracting from Red-2, a general problem solving mechanism is described that is especially suited for performing a form of abductive inference or best explanation finding. A problem solver embodying this mechanism synthesizes composite hypotheses by combining hypothesis parts. This is a common task of intelligence, and a component of scientific reasoning. The work addresses the question, 'How is science possible?' by showing how a simple but (...) powerful form of hypothesis synthesis is computationally feasible. (shrink)

Complexes of two or more proteins form many, if not most, of the intracellular “machines” that execute physical and chemical work, and transmit information. Complexes can form from stochastic post‐translational interactions of fully formed proteins, but recent attention has shifted to co‐translational interactions in which the most common mechanism involves binding of a mature constituent to an incomplete polypeptide emerging from a translating ribosome. Studies in yeast have revealed co‐translational interactions during formation of multiple major complexes, and together with recent (...) mammalian cell studies, suggest widespread utilization of the mechanism. These translation‐dependent interactions can involve a single or multiple mRNA templates, can be uni‐ or bi‐directional, and can use multi‐protein sub‐complexes as a binding component. Here, we discuss benefits of co‐translational complex assembly including accuracy and efficiency, overcoming hidden interfaces, localized and hierarchical assembly, and reduction of orphan protein degradation, toxicity, and dominant‐negative pathogenesis, all serving to improve cell fitness. (shrink)

The N‐terminal domain of histone H4 has been implicated in various nuclear functions, including gene silencing and activation and replication‐linked chromatin assembly. Many of these have been identified by using H4 mutants in the yeast S. cerevisiae. In a recent paper, Megee et al.(1) use this approach to show that mutants in which all four N‐terminal H4 lysines are substituted with glutamines accumulate increased levels of DNA damage. A single lysine, but not an arginine, anywhere in the N‐terminal domain suppresses (...) this phenotype. It is suggested that histone H4 plays a role in maintaining genome integrity through the cell cycle, possibly by a mechanism involving lysine acetylation. (shrink)

The assembly of a bipolar spindle is essential for the accurate segregation of replicated chromosomes during cell division. Do chromosomes rely solely on other cellular components to regulate the assembly of the bipolar spindle or are they masters of their own fate? In the Zhang and Nicklas(1) study reviewed here, micromanipulation techniques and video microscopy were used to demonstrate the different roles that chromosome arms, kinetochores and centrosomes play in bipolar spindle assembly.

Cell adhesion complexes are critical for the physical coordination of cell–cell interactions and the morphogenesis of tissues and organs. Many adhesion receptors are anchored to the plasma membrane by a glycosylphosphatidylinositol (GPI) moiety and are thereby partitioned into membrane rafts. In this review, we focus on reciprocal interactions between rafts and adhesion molecules, leading to receptor clustering and raft expansion and stability. A model for a three‐stage adhesion complex assembly process is also proposed. First, GPI‐anchored adhesion molecules (...) are recruited into rafts, which in turn promote receptor cis‐oligomerization and thereby produce precursory complexes primed for avid trans‐interactions. Second, trans‐interactions of the receptors cross‐link and stabilize large amalgams of rafts at sites of adhesion complex assembly. Finally, the enlarged and stabilized rafts acquire enhanced abilities to recruit the cytoskeleton and induce signaling. This process exemplifies how the domain structure of the plasma membrane can impact the function of its receptors. BioEssays 24:996–1003, 2002. © 2002 Wiley‐Periodicals, Inc. (shrink)

Early embryogenesis is marked by a frail Spindle Assembly Checkpoint (SAC). The time of SAC acquisition varies depending on the species, cell size or a yet to be uncovered developmental timer. This means that for a specific number of divisions, biorientation of sister chromatids occurs unsupervised. When error‐prone segregation is an issue, an aneuploidy‐selective apoptosis system can come into play to eliminate chromosomally unbalanced cells resulting in healthy newborns. However, aneuploidy content can be too great to overcome, endangering viability.SAC (...) generates a diffusible signal to lengthen time spent in mitosis if needed, ensuring correct chromosome segregation, a fundamental factor in the generation of euploid cells. Thus, it remains puzzling what benefit could come from delaying SAC acquisition till later in the development. In this review, we describe what is known on SAC acquisition in distinct species and highlight pending research as well as potential applications for such knowledge. (shrink)

Centriole duplication has been an area of interest since the late 1800s when Boveri suggested that these structures were central organizers for mitosis and cell division. Two groups1, 2 have delineated a linear pathway for centriole assembly. In C. elegans, Pelletier and coworkers1 have identified intermediates in the pathway using cryo‐electron tomography. Surprising, the first intermediate is a hollow tube of 60 nm that increases in diameter and then elongates before acquiring microtubules. Similar structures have not been observed to (...) date in other centrioles. BioEssays 29:630–634, 2007. © 2007 Wiley Periodicals, Inc. (shrink)