Although alterations in Ras signalling are found in about 30% of human cancers, the transforming activity of oncogenic Ras is not fully understood. In a recent paper, a putative Ras1 effector in S. pombe, named Scd1, was reported to localize to mitotic apindies. Scd1 physically associates with Moe1, a factor that may contribute to the inherent inatability of microtubules (MTs) and appears to be needed for proper apindle function. Altered MT dynamics within the spindle are likely to affect (...) class='Hi'>spindle assembly and chromosome capture, processes that need to be delicately controlled if cells are to guard against genome instability adn transformation. BloEssays 23: 307‐310,2001.©2001 John Willey & Sons, Inc. (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 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.

The mitotic spindle contains the machinery responsible for sister chromatid segregation. It is composed of a complex and dynamic array of microtubules, which are nucleated from the spindle poles. Studies of yeast spindle functions by molecular genetic analysis and by in vitro functional analysis have identified proteins that are mitosis‐specific and present at very low concentrations in the cell, and have revealed the molecular bases of several processes required for the formation and functioning of the mitotic (...) class='Hi'>spindle. Here I review the current knowledge of the processes that are common to most eukaryotes: microtubule nucleation at the spindle poles, bipolar spindle assembly, maintenance of the spindle structure, chromosome attachment to the spindle and chromosome separation on the spindle. (shrink)

The relationship between kinetochores and nuclear pore complexes (NPCs) is intimate but poorly understood. Several NPC components and associated proteins are relocated to mitotic kinetochores to assist in different activities that ensure faithful chromosome segregation. Such is the case of the Mad1‐c‐Mad2 complex, the catalytic core of the spindle assembly checkpoint (SAC), a surveillance pathway that delays anaphase until all kinetochores are attached to spindle microtubules. Mad1‐c‐Mad2 is recruited to discrete domains of unattached kinetochores from where it (...) promotes the rate‐limiting step in the assembly of anaphase‐inhibitory complexes. SAC proficiency further requires Mad1‐c‐Mad2 to be anchored at NPCs during interphase. However, the mechanistic relevance of this arrangement for SAC function remains ill‐defined. Recent studies uncover the molecular underpinnings that coordinate the release of Mad1‐c‐Mad2 from NPCs with its prompt recruitment to kinetochores. Here, current knowledge on Mad1‐c‐Mad2 function and spatiotemporal regulation is reviewed and the critical questions that remain unanswered are highlighted. (shrink)

In eukaryotic cells a specialized organelle called the microtubule organizing center (MTOC) is responsible for disposition of microtubules in a radial, polarized array in interphase cells and in the spindle in mitotic cells. Eukaryotic cells across different species, and different cell types within single species, have morphologically diverse MTOCs, but these share a common function of organizing microtubule arrays. MTOCs effect microtubule organization by initiating microtubule assembly and anchoring microtubules by their slowly growing minus ends, thus ensuring that (...) the rapidly growing plus ends extend distally in each microtubule array. The goal is to define molecular components of the MTOC responsible for regulating microtubule assembly. One approach to defining the molecules responsible for MTOC function is to look for molecules common to all MTOCs. A newly discovered centrosomal protein, γ‐tubulin, is found in MTOCs in cells from many different organisms, and has several properties which make it a candidate for both initiation of microtubule assembly and anchorage. The hypothesis that γ‐tubulin plays a role in MTOCs in microtubule initiation and anchorage is currently being tested by a variety of experimental approaches. (shrink)

Meiotic defects cause abnormal chromosome segregation leading to aneuploidy in mammalian oocytes. Chromosome segregation is particularly error‐prone in human oocytes, but the mechanisms behind such errors remain unclear. To explain the frequent chromosome segregation errors, recent investigations have identified multiple meiotic defects and explained how these defects occur in female meiosis. In particular, we review the causes of cohesin exhaustion, leaky spindle assembly checkpoint (SAC), inherently unstable meiotic spindle, fragmented kinetochores or centromeres, abnormal aurora kinases (AURK), and (...) clinical genetic variants in human oocytes. We mainly focus on meiotic defects in human oocytes, but also refer to the potential defects of female meiosis in mouse models. (shrink)

Adherens junctions play pivotal roles in cell and tissue organization and patterning by mediating cell adhesion and cell signaling. These junctions consist of large multiprotein complexes that join the actin cytoskeleton to the plasma membrane to form adhesive contacts between cells or between cells and extracellular matrix. The best-known adherens junction is the zonula adherens (ZA) that forms a belt surrounding the apical pole of epithelial cells. Recent studies in Drosophila have further illuminated the structure of adherens junctions. Scaffolding proteins (...) encoded by the stardust gene are novel components of the Crumbs complex, which plays a critical role in ZA assembly.1-3 The small GTPase Rap1 controls the symmetric re-assembly of the ZA after cell division.4 Finally, the asymmetric distribution of adherens junction material regulates spindle orientation during asymmetric cell division in the sensory organ lineage.5 BioEssays 24:690–695, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

Here we discuss a “chromosome separation checkpoint” that might regulate the anaphase‐telophase transition. The concept of cell cycle checkpoints was originally proposed to account for extrinsic control mechanisms that ensure the order of cell cycle events. Several checkpoints have been shown to regulate major cell cycle transitions, namely at G1‐S and G2‐M. At the onset of mitosis, the prophase‐prometaphase transition is controlled by several potential checkpoints, including the antephase checkpoint, while the spindle assembly checkpoint guards the metaphase‐anaphase transition. (...) Our hypothesis is based on the recently uncovered feedback control mechanism that delays chromosome decondensation and nuclear envelope reassembly until effective separation of sister chromatids during anaphase is achieved. A central player in this potential checkpoint is the establishment of a constitutive, midzone‐based Aurora B phosphorylation gradient that monitors the position of chromosomes along the spindle axis. We propose that this surveillance mechanism represents an additional step towards ensuring mitotic fidelity. (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)

Although the centrosome was first described over 100 years ago, we still know relatively little of the molecular mechanisms responsible for its functions. Recently, members of a novel family of centrosomal proteins have been identified in a wide variety of organisms. The transforming acidic coiled‐coil‐containing (TACC) proteins all appear to play important roles in cell division and cellular organisation in both embryonic and somatic systems. These closely related molecules have been implicated in microtubule stabilisation, acentrosomal spindle assembly, translational (...) regulation, haematopoietic development and cancer progression. In this review, I summarise what we already know of this protein family and will use the TACC proteins to illustrate the many facets that centrosomes have developed during the course of evolution. BioEssays 24:915–925, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

The chromosome passenger complex (CPC) localizes to chromosomes and microtubules, sometimes simultaneously. The CPC also has multiple domains for interacting with chromatin and microtubules. Interactions between the CPC and both the chromatin and microtubules is important for spindle assembly and error correction. Such dual chromatin‐microtubule interactions may increase the concentration of the CPC necessary for efficient kinase activity while also making it responsive to specific conditions or structures in the cell. CPC‐microtubule dependent functions are considered in the context (...) of the first meiotic division. Acentrosomal spindle assembly is a process that depends on transfer of the CPC from the chromosomes to the microtubules. Furthermore, transfer to the microtubules is not only to position the CPC for a later role in cytokinesis; metaphase I error correction and subsequent bi‐orientation of bivalents may depend on microtubule associated CPC interacting with the kinetochores. (shrink)

Zygote cytokinesis produces two symmetric blastomeres, which contain one copy of each parental genome. Contrary to this dogma, we recently discovered that mammalian zygotes can spontaneously segregate entire parental genomes into different blastomeres and coined this novel form of genome segregation heterogoneic division. The molecular mechanisms underlying the emergence of blastomeres with different parental genomes during the first mitotic cycle remain to be elucidated. Here, we speculate on which parental genome asymmetries could provide a mechanistic foundation for these remarkable zygote (...) divisions. In reviewing the field and considering our findings, we revisit the architecture of the first zygotic metaphase by invoking asymmetric interactions between the mitotic spindle and the parental kinetochores. We also speculate on how asynchronous parental cell cycles can be a source of heterogoneic zygote divisions through the formation of parental genome private spindles. (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)

The cellular processes of transport, division and, possibly, early development all involve microtubule‐based motors. Recent work shows that, unexpectedly, many of these cellular functions are carried out by different types of kinesin and kinesin‐related motor proteins. The kinesin proteins are a large and rapidly growing family of microtubule‐motor proteins that share a 340‐amino‐acid motor domain. Phylogenetic analysis of the conserved motor domains groups the kinesin proteins into a number of subfamilies, the members of which exhibit a common molecular organization and (...) related functions. The kinesin proteins that belong to different subfamilies differ in their rates and polarity of movement along microtubules, and probably in the particles/organelles that they transport. The kinesins arose early in eukaryotic evolution and gene duplication has allowed functional specialization to occur, resulting in a surprisingly large number of different classes of these proteins adapted for intracellular transport of vesicles and organelles, and for assembly and force generation in the meiotic and mitotic spindles. (shrink)

The nature of the forces that move chromosomes in mitosis is beginning to be revealed. The kinetochore, a specialized structure situated at the primary constriction of the chromosome, appears to translocate in both directions along the microtubules of the mitotic spindle. One or more members of the newly described families of microtubule motor molecules may power these movements. Microtubules of the mitotic spindle undergo rapid cycles of assembly and disassembly. These microtubule dynamics may contribute toward generating force (...) and regulating direction in chromosome movement. (shrink)

Stable maintenance of genetic information during meiosis and mitosis is dependent on accurate chromosome transmission. The centromere is a key component of the segregational machinery that couples chromosomes with the spindle apparatus. Most of what is known about the structure and function of the centromeres has been derived from studies on yeast cells. In Saccharomyces cerevisiae, the centromere DNA requirements for mitotic centromere function have been defined and some of the proteins required for an active complex have been identified. (...) Centromere DNA and the centromere proteins form a complex that has been studied extensively at the chromatin level. Finally, recent findings suggest that assembly and activation of the centromere are integrated in tethe cell cycle. (shrink)

A framework for understanding the complex movements of mitosis and meiosis has been provided by the recent discovery of microtubule motor proteins, required for the proper distribution of chromosomes or the structural integrity of the mitotic or meiotic spindle. Although overall features of mitosis and meiosis are often assumed to be similar in mechanism, it is now clear that they differ in several important aspects. These include spindle structure and assembly, and timing of chromosome segregation to opposite (...) poles. Here we review progress in the functional characterization of several newly identified microtubule motor proteins, emphasizing their possible roles in spindle structure and function. (shrink)

Recent evidence shows that dynamic instability is the dominant mechanism for the assembly of pure tubulin in vitro and for the great majority of microtubules in the mitotic spindle and the interphase cytoplasmic microtubule complex. The basic concepts of this model provide a framework for future characterization of the molecular basis of spatial and temporal regulation of microtubule dynamics in the cell and the function of microtubule dynamics in motile processes such as chromosome movement.

Molecular motor proteins, fueled by energy from ATP hydrolysis, move along actin filaments or microtubules, performing work in the cell. The kinesin microtubule motors transport vesicles or organelles, assemble bipolar spindles or depolymerize microtubules, functioning in basic cellular processes. The mechanism by which motor proteins convert energy from ATP hydrolysis into work is likely to differ in basic ways from man‐made machines. Several mechanical elements of the kinesin motors have now been tentatively identified, permitting researchers to begin to decipher the (...) mechanism of motor function. The force‐producing conformational changes of the motor and the means by which they are amplified are probably different for the plus‐ and minus‐end kinesin motors. BioEssays 25:1212–1219, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

The centromere is the region of the chromosome where the kinetochore forms. Kinetochores are the attachment sites for spindle microtubules that separate duplicated chromosomes in mitosis and meiosis. Kinetochore formation depends on a special chromatin structure containing the histone H3 variant CENP‐A. The epigenetic mechanisms that maintain CENP‐A chromatin throughout the cell cycle have been studied extensively but little is known about the mechanism that targets CENP‐A to naked centromeric DNA templates. In a recent report published in Science,1 such (...) de novo centromere assembly of CENP‐A is shown to be dependent on heterochromatin and the RNA interference pathway. BioEssays 30:526–529, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

In cells, microtubules (MTs) assemble from α/β‐tubulin subunits at nucleation sites containing the γ‐tubulin ring complex (γ‐TuRC). Within the γ‐TuRC, exposed γ‐tubulin molecules act as templates for MT assembly by interacting with α/β‐tubulin. The vertebrate γ‐TuRC is scaffolded by γ‐tubulin‐interacting proteins GCP2‐6 arranged in a specific order. Interestingly, the γ‐tubulin molecules in the γ‐TuRC deviate from the cylindrical geometry of MTs, raising the question of how the γ‐TuRC structure changes during MT nucleation. Recent studies on the structure of the (...) vertebrate γ‐TuRC attached to the end of MTs came to varying conclusions. In vitro assembly of MTs, facilitated by an α‐tubulin mutant, resulted in a closed, cylindrical γ‐TuRC showing canonical interactions between all γ‐tubulin molecules and α/β‐tubulin subunits. Conversely, native MTs formed in a frog extract were capped by a partially closed γ‐TuRC, with some γ‐tubulin molecules failing to align with α/β‐tubulin. This review discusses these outcomes, along with the broader implications. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:The Stumbling Block its IndexBrian Catling (bio)The Stumbling Block is a graphic font. This black plinth was once a brush or similar terminal that was the lips of an intense electrical arc. Industries proud and violent need spoke through it to turn the wheel or smelt and cast the constructed challenge. Now abandoned it finds benediction in seclusion. It has softened its mouth to hold water, so that small (...) animals and disjointed humans may drink or sign themselves in their passage. [End Page 218]The Stumbling Block has been used like an entrance step to sharpen knives on. Its fossil bristle of bright stone forcing the heavy blades down to a hiss along one edge. These are knives of gleaming hubris, long intentions honed for malice. They are magnetized and have been placed to construct a lectern. Each blade holding the next to form the platform. It may hold this index at its centre, hovering, placed outside in the aorta of streets. The removal of any of the blades from the assembled cluster will spill their fish bodies to the ground. The paper will drink any of the stains of their usage. [End Page 219]The Stumbling Block is an ark of extinction. A bouillon hive of the murdered past, frozen dry to a mass. Something has warmed its corner, the oxoed grit bleeds a vein of contagion, virulent in its passion to embrace and swim in human tides. [End Page 220]The Stumbling Block is unfound to the stained and unclear eye. But its nest, its negative hollow can be discovered in the mounds of waste and detritus that choke the streets. Its possible wedge, sphere or beam form is there; a vacant socket, easily trampled, destroyed or cleared away. It is watching. Its obstinate grace squinting across the demonstrations of power. It is the light in the eye of the needle grown solid with anger, a fat sugar that clogs the passage to any kind of paradise. [End Page 221]The Stumbling Block is a bell that sounds a deeper voice than the throats of men. Their image and cry shrinks the world.The communication of global gossip becomes a barbed wind of trivial penning; television enclosures of wired indifference, the reduction of memory removes the open field and causes blurred shivers to be understood as the same thing. The bell hums as acceleration eradicates silence, the foundation for stillness is removed. The speed of language clones its own restless manic hunger. The portable telephone, miniature televisions, satellites and their collection dishes are the cutlery for this gluttony.The inedible thinness they devour is obvious. To feed this addiction soapy fictions are boiled from the skin and bone of poverty. Tribes, villages, jungles and the very air itself can be wasted or burnt to secure a dry armpit in puppeted dramas of nightmare lives. Condensation is sweating inside the bell; a human modes sound that is unwelcome. It drips from the rim in whispers and pools beneath its limited protection. [End Page 222]The Stumbling Block is a shape shifter, a spirit bench that dwells in the cuffs of the expanding city. Over its warn layers of woven scars many forms have been stretched, clamped and tasted, licked and cut; reshaped. Anointed by abstraction, they are put back on the blinking streets, patted and set loose. In the deep pocketed burrows of the bench, termite-size clones dream white directions to colour the tiredness of their somnambulistic donors. [End Page 223]The Stumbling Block is a barrel organ dragged to the site of a crime. Its tin cup catching rain as it judders on the pounding box. The moon is caught between its throat and the water, and in the black gleam of its varnished vibration. It spills dance into the causeways, sucking revelers along the spindle of its cranked tune. They will spin and curl their lumpen massed centrifuge around the bellowing thing. The laughter is momentary but has soaked away the blood, only the scuffs of shoes and the scratched cobbles sing on. [End Page 224]The Stumbling Block is not a coffer, disguised by a wig of artifice. It cannot offer erudition or... (shrink)

Realism about mental disorders is a perennial area of dispute, but the controversy burns especially intensely for Attention Deficit Hyperactivity Disorder. In this dissertation, I clarify what is at issue in these debates, surveying how realists have typically argued for mental disorder realism: the definitional debate about health and illness. I argue that the realist need not be committed to the terms of the definitional debate and recommend that a better approach is to show that mental disorders are natural kinds. (...) While there are many accounts of kind-hood on offer, I adopt Richard Boyd’s homeostatic property cluster theory of kinds, which I interpret through the philosophy of neuroscience literature on mechanisms. In sum, I conclude that if ADHD is a natural kind – and thus real – then individuals diagnosed with the disorder should be sufficiently similar with respect to an underlying cognitive neurobiological mechanism. To determine whether ADHD individuals are similar in this way, I consider the question through Russell Barkley’s Executive Function Model of ADHD. Relying primarily on the cognitive neurobiological research, I argue that there is now reasonable evidence to conclude that the DSM classification of ADHD corresponds not to a single natural kind, but several. Thus, ADHD is thus real. (shrink)

This study surveyed investors to determine the extent to which they preferred ethical behavior to profits and their interest in having information about corporate ethical behavior reported in the corporate annual report. First, investors were asked to determine what penalties should be assessed against employees who engage in profitable, but unethical, behavior. Second, investors were asked about their interest in using the annual report to disclose the ethical performance of the corporation and company officials. Finally, investors were asked if they (...) felt that ethics reports should be audited.The survey results indicate that many shareholders (42%) do not expect a high level of ethical behavior from corporate employees or officers. There is a significant amount of interest in disclosure of ethical issues (72%) and unwillingness to trust management to provide unbiased reports of ethical behavior. If such reports are included with the financial statements, 32 percent of the investors surveyed would prefer to have them audited to provide independent verification. (shrink)

Recently, Quyn et al. demonstrated that cells within the stem cell zone of human and mouse intestinal crypts tend to align their mitotic spindles perpendicular to the basal membrane of the crypt. This is associated with asymmetric division, whereby particular proteins and individual chromatids are preferentially segregated to one daughter cell. In colonic mucosa containing a heterozygous adenomatous polyposis coli gene (APC) mutation the asymmetry is lost. Here, we discuss asymmetric stem cell division as an anti‐tumourigenic mechanism. We describe how (...) hierarchical tissue structures suppress somatic evolution, and discuss the relative merits of template strand retention to limit the accumulation of DNA replication errors. We suggest experiments to determine whether somatic mutations resulting in loss of spindle alignment confer an advantage within the stem cell niche. Finally, we discuss whether lack of spindle alignment constitutes an oncogenic event per se, with particular reference to studies in model organisms, and the timing of chromosomal instability in human cancers. (shrink)

We consider how an epistemic network might self-assemble from the ritualization of the individual decisions of simple heterogeneous agents. In such evolved social networks, inquirers may be significantly more successful than they could be investigating nature on their own. The evolved network may also dramatically lower the epistemic risk faced by even the most talented inquirers. We consider networks that self-assemble in the context of both perfect and imperfect communication and compare the behaviour of inquirers in each. This provides a (...) step in bringing together two new and developing research programs, the theory of self-assembling games and the theory of network epistemology. (shrink)

The assembly of nucleosomes and higher‐order chromatin structures has been extensively studied in vitro. Provided that non‐specific charge interactions are controlled, all the information for correct assembly is found to be inherent in the macromolecular components. Cellular extracts which can assemble chromatin in vitro with nucleosomes correctly spaced on the DNA have been studied in detail and also used to investigate the role of chromatin structure in transcription. However, the mechanisms of chromatin assembly in vivo are still (...) controversial. (shrink)

Sleep spindles are frequently studied for their relationship with state and trait cognitive variables, and they are thought to play an important role in sleep-related memory consolidation. Due to their frequent occurrence in NREM sleep, the detection of sleep spindles is only feasible using automatic algorithms, of which a large number is available. We compared subject averages of the spindle parameters computed by a fixed frequency (11-13 Hz for slow spindles, 13-15 Hz for fast spindles) automatic detection algorithm and (...) the individual adjustment method (IAM), which uses individual frequency bands for sleep spindle detection. Fast spindle duration and amplitude are strongly correlated in the two algorithms, but there is little overlap in fast spindle density and slow spindle parameters in general. The agreement between fixed and manually determined sleep spindle frequencies is limited, especially in case of slow spindles. This is the most likely reason for the poor agreement between the two detection methods in case of slow spindle parameters. Our results suggest that while various algorithms may reliably detect fast spindles, a more sophisticated algorithm primed to individual spindle frequencies is necessary for the detection of slow spindles as well as individual variations in the number of spindles in general. (shrink)

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.

This article considers how a generalized signalling game may self-assemble as the saliences of the agents evolve by reinforcement on those sources of information that in fact lead to successful action. On the present account, generalized signalling games self-assemble even as the agents co-evolve meaningful representations and successful dispositions for using those representations. We will see how reinforcement on successful information sources also provides a mechanism whereby simpler games might compose to form more complex games. Along the way, I consider (...) how an old game might be appropriated to a new context by reinforcement on successful associations between old and new saliences. (shrink)

The term ‘food security’ has been used in multiple ways and addresses not only issues around availability and accessibility of foods, but also, among others, the sustainability of livelihoods at the local community level—an issue often seen as a basis for the proliferation of local and alternative food networks. Accordingly, in this paper we attempt to develop a theoretical re-framing that is able to link food security with AFNs in arguing that the understanding of the two notions is dynamics and (...) contingent upon the elements that construct them. We use an assemblage approach to analyze a case of Dunedin, a small-size city in New Zealand, in which the community aims to achieve food security through a local food strategy. Through a series of interviews with a group of food activists and academics, public discussions, and two local food forums, we found that food security was understood and performed in its local context through assembling diverse actors and objectives within the AFN. In conclusion, we offer assemblage thinking as an analytical tool to understand how seemingly precarious local food relations are stabilized and assembled so as to open possibilities of achieving food security. (shrink)

Nurses working in outreach capacities frequently encounter disaffiliated or ‘hard to reach’ populations, such as those experiencing homelessness, those who use substances, and those with mental health concerns. Despite best efforts, nurses regularly fail to find meaningful engagement with these populations. Mobilizing the work of Deleuze and Guattari, this paper will critically examine conventional outreach nursing practices as rooted in the royal science of psychiatry, which many ‘survivors’ of psychiatric interventions reject. The field of Mad Studies offers an understanding of (...) patient resistance to outreach nursing interventions. Delueze and Guattari's concepts of packs and sorcerers provide a framework to envision alternative nursing practices as a form of resistance and creativity, where new alliances may be formed outside the coercive confines of traditional practices. In response to patient resistance, outreach nurses themselves must assemble packs and engage in acts of sorcery. (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 (...) class='Hi'>assembly of enzyme complexes is emerging as a major mechanism of signal transduction and may regulate the pleiotropic effects of growth factors. (shrink)

This paper offers a reconstruction of Xenocrates’ theory of indivisibles which would not commit him to the idea of ‘jerky motion’ criticized by Aristotle in Physica VI, yet would perfectly square with Plato’s Timaeus, the basis of Xenocrates’ canon. Relying on Alexander’s, Porphyry’s, and Themistius’s accounts of his theory, as well on a detailed analysis of De lineis insecabilibus, I suggest that Xenocrates’ minima, contrary to what Aristotle implies, are not to be understood as more or less stable particulars, like (...) tiny chunks of matter, moving about or leaping in physical space from point A to point B. Yet Xenocrates’ minima do remain ‘physical’ and ‘corporeal’ in a more Platonic sense of these words, not presupposing any kind of leaping, jumping, or jerking. This explains why Xenocrates associated the sensible realm with one of the three Fates, namely Clotho. (shrink)

Although Hurricane Katrina precipitated considerable reflection across various media, a practice crucial to our capacities to apprehend and interpret the disaster has not yet been analyzed as such. I call this practice generative assembly. I don’t mean the events of emergency and political gathering that took place in response to the massive storm and fatal, preventable levee failures—although I will propose connections between different forms of assembly. Instead I mean a kind of documentary practice. That practice, which can (...) be undertaken individually or in collaboration, and sometimes at anonymous remove, involves the work of assembling records and signifiers related to the disaster into particular kinds of media artifacts. Those artifacts— which take shape in formats as varied as comics, photobooks, paintings, films, exhibitions, and multithousand-item online archives—characteristically maintain the active appearance and interactive potential of selection and arrangement. In exhibiting such qualities, or so I will argue, these assembly-based artifacts support various articulable and often highly effective kinds of generativity. And thus, I will further suggest, these artifacts can constitute especially powerful means of intervening in prevailing conditions of representation and remembrance around events of environmental and social violence. Crucially, those material legacies of generative assembly can also fall short, fail, and deceive, and this is especially true of those assemblies that take digital forms. It is my contention, however, that we would be misguided if we thus entirely dismissed such assemblies or if we refused their potential for dissident reuse or generative reassembly. (shrink)

Asymmetric cell division generates cell diversity and contributes to cellular aging and rejuvenation. Here, we review the molecular mechanisms enabling budding yeast to recognize spindle pole bodies (SPB, centrosome equivalent) based on their age, and guide their non‐random mitotic segregation: SPB inheritance requires the distinction of old from new SPBs and is regulated by the SPB‐inheritance network (SPIN) and the mitotic exit network (MEN). The SPIN marks the pre‐existing SPB as old and the MEN recognizes these marks translating them (...) into spindle orientation. We next revisit other molecules and structures that partition depending on their age rather than their abundance at mitosis as, for example, DNA, centrosomes, mitochondria, and histones in yeast and other systems. The recurrence of this differential behavior suggests a functional significance for numerous cell types, which we then discuss. We conclude that non‐random segregation may facilitate asymmetric cell fate determination and thereby indirectly aging and rejuvenation. (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.

In this paper, I focus on a recent debate in extended cognition known as “cognitive assembly” and how cognitive assembly shares a certain kinship with the special composition question advanced in analytical metaphysics. Both the debate about cognitive assembly and the special composition question ask about the circumstances under which entities (broadly construed) compose or assemble another entity. The paper argues for two points. The first point is that insofar as the metaphysics of composition presupposes that composition (...) is a synchronic relation of dependence, then that presupposition is inconsistent with the temporal dynamics inherent in the process of cognitive assembly. The second point is that by developing a diachronic or temporally dynamic ontology for understanding the phenomenon of cognitive assembly, this lends support for a third wave of extended cognition. (shrink)

Newton Garver - Assembling Reminders: Studies in the Genesis of Wittgenstein's Concept of Philosophy - Journal of the History of Philosophy 45:4 Journal of the History of Philosophy 45.4 671-672 Muse Search Journals This Journal Contents Reviewed by Newton Garver University at Buffalo Alan Janik. Assembling Reminders: Studies in the Genesis of Wittgenstein's Concept of Philosophy. Stockholm: Santérus Academic Press, 2006. Pp. 246. Paper, $40.00. Janik's book is a wonderful achievement, filling an obvious and long-neglected gap in Wittgenstein scholarship. The (...) plan of the book is simple and straightforward. Citing the well-known passage in Culture and Value where Wittgenstein identifies ten persons from whom he has taken seminal ideas for his work of clarification, Janik clarifies how each contributed to the development of.. (shrink)

Localized mRNA translation is a biological process that allows mRNA to be translated on‐site, which is proposed to provide fine control in protein regulation, both spatially and temporally within a cell. We recently reported that Vasa, an RNA‐helicase, is a promising factor that appears to regulate this process on the spindle during the embryonic development of the sea urchin, yet the detailed roles and functional mechanisms of Vasa in this process are still largely unknown. In this review article, to (...) elucidate these remaining questions, we first summarize the prior knowledge and our recent findings in the area of Vasa research and further discuss how Vasa may function in localized mRNA translation, contributing to efficient protein regulation during rapid embryogenesis and cancer cell regulation. (shrink)