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CD8 T cells exist in a dynamic network whose repertoire remains static in the absence of infection but changes in the presence of foreign antigens. Individuals each have unique T-cell repertoires that continually evolve in the presence of antigen and of cross-reactive heterologous antigens, and homeostatic forces drive deletions in T-cell memory pools to accommodate the entry of new memory cells into a finite immune system.
We describe the capillary flow behavior of gels of beta-lactoglobulin (beta-lg) containing droplets of fibrils and the shear flow alignment of beta-lg fibers in dilute aqueous solutions. Polarized optical microscopy and laser scanning confocal microscopy are used to show that capillary shear flow does not affect the fibril droplet sizes in the beta-lg gels, the system behaving in this respect as a solution of compact colloidal particles under shear flow. Small-angle X-ray scattering (SAXS) on dilute aqueous solutions indicates that the fibers can be initially aligned under capillary shear, but this alignment is lost after 18 min of shear. Transmission electron microscopy experiments on the samples studied by SAXS suggest that the loss of orientation is due to a shear-induced breakup of the swollen fibril network. Dynamic and static light scattering on dilute beta-lg fibril aqueous solutions are used to show that before shear beta-lg fibrils behave as strongly interacting semiflexible polymers, while they behave as weakly interacting rods after 18 min of capillary shear.
Two highly dipolar merocyanine dyes were tethered by a rigid tris(n-dodecyloxy)xylylene unit that preorganizes the dyes for a supramolecular polymerization process through intermolecular aggregation of the dyes. UV/vis spectroscopy revealed a solvent dependent equilibrium between monomeric dyes and two different types of dye aggregates that are characterized by hypsochromically shifted D- and H-type absorption bands. Taking into account the ditopic nature of the supramolecular building blocks, the occurrence of the D-band indicates the formation of an oligomeric/polymeric supramolecular chain whereas the observation of the H-band suggests a higher order assembly. For the H-aggregated dyes, intrinsic viscosities exceed 0.65 L g(-1) in methylcyclohexane, values typically found for macromolecular solutions. At higher concentration, further association of these aggregates takes place by entanglement of the alkyl groups leading to a substantial increase in viscosity and gelation. Rheology studies show linear viscoelastic behavior which was attributed to the formation of an entangled dynamic network. AFM and cryo-TEM studies of the gel reveal long and stiff rod-type assemblies. X-ray diffraction studies for a solid film show columnar mesomorphism. Based on these results, a structural model is proposed in which six helically preorganized strands of the supramolecular polymer intertwine to form a rod with a diameter of about 5 nm. Within these rods all dyes are tightly aggregated in a tubular fashion giving rise to delocalized excitonic states, and the pi-conjugated tube is jacketed by the tridodecyloxy groups.
In plant cells, several cellular processes depend on rapid reorganization of a dynamic network of actin cytoskeletal elements in response to internal and environmental stimuli. Profilins, ubiqitous eukaryotic actin monomer-binding proteins with highly conserved three-dimensional structures, regulate the actin cytoskeleton and are considered to link the microfilament system with signal transduction pathways. Plant profilins have been grouped into two distinct classes, gametophytic (pollen-specific) and sporophytic. Here we report the isolation of a profilin gene that seems to be activated during tip growth of specialized cells of gametophytic as well as sporophytic origin. Identification of a genomic DNA clone containing a tobacco profilin gene, pronp1, and analysis of the pronp1 promoter-uidA fusion gene in transgenic Nicotiana tabacum plants revealed a prominent expression of pronp1 in mature pollen and elongating pollen tubes and significant activity in root hairs of developing seedlings. This expression pattern was distinct from that of any other profilin gene isolated so far. Pronp1 thus represents a unique profilin gene that is activated at the transcriptional level in two kinds of tip-growing cells, pollen tubes and root hairs, both of which require rapid organization of the actin cytoskeleton. The isolation of such a gene has fundamental importance for our understanding of modulation of the actin cytoskeleton at the molecular level.
Nuclear extracts (NE), capable of carrying out splicing of pre-mRNA, contain galectin-1 and galectin-3. NE depleted of galectins-1 and -3 concomitantly lose their splicing activity. The activity of the galectin-depleted extract can be reconstituted by the addition of either galectin-1 or galectin-3. These results suggest that galectins-1 and -3 serve as redundant splicing factors. Consistent with this notion, immunofluorescence staining showed that both galectins yielded a diffuse nucleoplasmic distribution, matching that of nascent transcripts and consistent with the hypothesis that bulk transcription and pre-mRNA processing occur throughout the nucleoplasm. Under some conditions, the galectins could be found in speckled structures and nuclear bodies but the prevailing thought is that these represent sites of storage and recycling rather than sites of action. Galectin-1 and galectin-3 bind directly to Gemin4, a component of the SMN core complex, which plays multiple roles in ribonucleoprotein assembly, including the biogenesis, delivery, and recycling of snRNPs to the spliceosome. Thus, galectin-1 and galectin-3 constitute a part of an interacting dynamic network of many factors involved in the splicing and transport of mRNA.
The actin cytoskeleton is a dynamic network that is composed of a variety of F-actin structures. To understand how these structures are produced, we tested the capacity of proteins to direct actin polymerization in a bead assay in vitro and in a mitochondrial-targeting assay in cells. We found that human zyxin and the related protein ActA of Listeria monocytogenes can generate new actin structures in a vasodilator-stimulated phosphoprotein-dependent (VASP) manner, but independently of the Arp2/3 complex. These results are consistent with the concept that there are multiple actin-polymerization machines in cells. With these simple tests it is possible to probe the specific function of proteins or identify novel molecules that act upon cellular actin polymerization.
We used neural ensemble recording to examine odor-evoked ensemble patterns in the moth antennal (olfactory) lobe. Different odors are thought to evoke unique spatiotemporal patterns of glomerular activity, but little is known about the population dynamics underlying formation of these patterns. Using a silicon multielectrode array, we observed dynamic network interactions within and between glomeruli. Whereas brief odor pulses repeatedly triggered activity in the same coding ensemble, the temporal pattern of synchronous activity superimposed on the ensemble was neither oscillatory nor odor specific. Rather, synchrony strongly depended on contextual variables such as odor intensity and intermittency. Also, because of emergent inhibitory circuit interactions, odor blends evoked temporal ensemble patterns that could not be predicted from the responses to the individual odorants. Thus even at this early stage of information processing, the timing of odor-evoked neural representations is modulated by key stimulus factors unrelated to the molecular identity of the odor.
Timing is crucial to many aspects of human performance. To better understand its neural underpinnings, we used event-related fMRI to examine the time course of activation associated with different components of a time perception task. We distinguished systems associated with encoding time intervals from those related to comparing intervals and implementing a response. Activation in the basal ganglia occurred early, and was uniquely associated with encoding time intervals, whereas cerebellar activation unfolded late, suggesting an involvement in processes other than explicit timing. Early cortical activation associated with encoding of time intervals was observed in the right inferior parietal cortex and bilateral premotor cortex, implicating these systems in attention and temporary maintenance of intervals. Late activation in the right dorsolateral prefrontal cortex emerged during comparison of time intervals. Our results illustrate a dynamic network of cortical-subcortical activation associated with different components of temporal information processing.
Plasticity in neural circuits can result from alterations in synaptic strength or connectivity, as well as from changes in the excitability of the neurons themselves. To better understand the role of plasticity in the brain, we need to establish how brain circuits work and the kinds of computations that different circuit structures achieve. By linking theoretical and experimental studies, we are beginning to reveal the consequences of plasticity mechanisms for network dynamics, in both simple invertebrate circuits and the complex circuits of mammalian cerebral cortex.
Mitochondria fuse and divide continuously within cells to form a dynamic network. One of the steps in apoptosis is the fragmentation of mitochondria, and recent evidence indicates that the mitochondrial fission machinery actively participates in the process of programmed cell death.
Mitochondria exist as dynamic networks that often change shape and subcellular distribution. The number and morphology of mitochondria within a cell are controlled by precisely regulated rates of organelle fusion and fission. Recent reports have described dramatic alterations in mitochondrial morphology during the early stages of apoptotic cell death, a fragmentation of the network and the remodeling of the cristae. Surprisingly, proteins discovered to control mitochondrial morphology appear to also participate in apoptosis and proteins associated with the regulation of apoptosis have been shown to affect mitochondrial ultrastructure. In this review the recent progress in understanding the mechanisms governing mitochondrial morphology and the latest advances connecting the regulation of mitochondrial morphology with programmed cell death are discussed.
PURPOSE: To examine the intralimbic localization and morphology of mesial temporal seizure onsets and to correlate the findings with patterns of initial seizure spread and the presence or absence of clinical manifestations. METHODS: Eighteen patients with temporal lobe epilepsy were investigated with intracranial depth electrodes implanted in the amygdala (AM), anterior hippocampus (HP), and parahippocampal gyrus (PH). Focal and regional ictal-onset morphologies were classified as rhythmic limbic spiking <2 Hz (RLS), spike-and-wave activity >2 Hz (S/W), rhythmic polyspike activity >13 Hz (RPS), and rhythmic sharp activity <13 Hz (RS). RESULTS: Onset morphologies in 389 total seizures (260 regional + 129 focal) were 50% RPS, 35% RS, 11% RLS, and 4% S/W. Focal AM or HP onsets (30% and 58% of focal onsets, respectively) were more likely to show RLS, whereas RPS was more common in regional onsets. Most patients showed two or more different morphologies and focal onsets at more than one ipsilateral limbic site. Seizure propagation and clinical manifestations were significantly more common with AM or PH onsets (both 67% clinical seizures): only 23% of focal HP onsets resulted in clinical seizures. CONCLUSIONS: (a) There is substantial inter- and intrapatient variability in the morphology and localization of mesial temporal seizure onsets, which suggests that the epileptogenic temporolimbic system may be conceptualized as a dynamic network containing a multiplicity of potential ictal generators; (b) Seizures beginning in the AM or PH are more likely to propagate and give rise to clinical manifestations than are focal-onset HP seizures, which suggests that inhibitory circuits within the HP may function to prevent seizure spread.
The success of a free microvascular tissue transfer is based on a sufficient microanastomosis which meets the following requirements: a pedicle placed without kinking or twisting, good drainage, a well-defined recipient vessel, integrity of the endothelium, and duration of ischemia. The extent of skin and muscle necrosis increases significantly with increases in ischemia time. Reperfusion of ischemic tissue results in local and systemic damage associated with the release of oxygen free radicals, polymorphonuclear leucocytes, and such endothelial hormones as endothelin-1, EDRF (endothelial-derived relaxing factor), thromboxane, complement, and cytokines. Ischemia-reperfusion disrupts the delicate balance that maintains homeostasis in the microcirculation. This review discusses the clinical and therapeutic aspects of such injury, concentrating on perioperative management in free flap transfer. It points out the possible influence of endothelin-1 on vasospasm at the site of anastomosis, and emphasizes the importance of the endothelium as a highly dynamic network. Finally, future diagnostic and therapeutical aspects are discussed.
The cellular cytoskeleton is a complex dynamical network that constantly remodels as cells divide and move. This reorganization process occurs not only at the cell membrane, but also in the cell interior (bulk). During locomotion, regulated actin assembly near the plasma membrane produces lamellipodia and filopodia. Therefore, most in vitro experiments explore phenomena taking place in the vicinity of a surface. To understand how the molecular machinery of a cell self-organizes in a more general way, we studied bulk polymerization of actin in the presence of actin-related protein 2/3 complex and a nucleation promoting factor as a model for actin assembly in the cell interior separate from membranes. Bulk polymerization of actin in the presence of the verprolin homology, cofilin homology, and acidic region, domain of Wiskott-Aldrich syndrome protein, and actin-related protein 2/3 complex results in spontaneous formation of diffuse aster-like structures. In the presence of fascin these asters transition into stars with bundles of actin filaments growing from the surface, similar to star-like structures recently observed in vivo. The transition from asters to stars depends on the ratio [fascin]/[G actin]. The polarity of the actin filaments during the transition is preserved, as in the transition from lamellipodia to filopodia. Capping protein inhibits star formation. Based on these experiments and kinetic Monte Carlo simulations, we propose a model for the spontaneous self-assembly of asters and their transition into stars. This mechanism may apply to the transition from lamellipodia to filopodia in vivo.
The computations involved in the processing of a visual scene invariably involve the interactions among neurons throughout all of visual cortex. One hypothesis is that the timing of neuronal activity, as well as the amplitude of activity, provides a means to encode features of objects. The experimental data from studies on cat [Gray, C. M., Konig, P., Engel, A. K. & Singer, W. (1989) Nature (London) 338, 334-337] support a view in which only synchronous (no phase lags) activity carries information about the visual scene. In contrast, theoretical studies suggest, on the one hand, the utility of multiple phases within a population of neurons as a means to encode independent visual features and, on the other hand, the likely existence of timing differences solely on the basis of network dynamics. Here we use widefield imaging in conjunction with voltage-sensitive dyes to record electrical activity from the virtually intact, unanesthetized turtle brain. Our data consist of single-trial measurements. We analyze our data in the frequency domain to isolate coherent events that lie in different frequency bands. Low frequency oscillations (<5 Hz) are seen in both ongoing activity and activity induced by visual stimuli. These oscillations propagate parallel to the afferent input. Higher frequency activity, with spectral peaks near 10 and 20 Hz, is seen solely in response to stimulation. This activity consists of plane waves and spiral-like waves, as well as more complex patterns. The plane waves have an average phase gradient of approximately pi/2 radians/mm and propagate orthogonally to the low frequency waves. Our results show that large-scale differences in neuronal timing are present and persistent during visual processing.
Mitochondria form a highly dynamic network that is shaped by continuous fission and fusion of these organelles. In the yeast Saccharomyces cerevisiae two machineries are involved in this process, one of which includes the mitochondrial fusion promoting GTPase Fzo1. Although a role for the F-box protein Mdm30 in regulating the stability of Fzo1 has been proposed, the molecular basis for the regulation of the fission to fusion ratio of mitochondria remains unknown. To discern the mechanism of the regulation of mitochondrial morphology, we arrested cells at different stages of the cell cycle and examined mitochondrial morphology as well as the stability of mitochondrial fission and fusion proteins. In response to a G1 arrest evoked by the mating pheromone alpha factor the mitochondrial network fragmented into small pieces, which was accompanied by dramatic down-regulation of Fzo1. Mating pheromone also triggered the degradation of Fzo1 produced under the control of a constitutive promoter, and Fzo1 was stabilized upon proteasome inhibition, indicating a role for the proteasome system in the degradation of Fzo1. However, deletion of MDM30 did not stabilize Fzo1 after mating pheromone treatment, showing a different mechanism from the previously reported process of steady state Fzo1 regulation. We show an example for a regulated change of the mitochondrial fission to fusion ratio during the life cycle of budding yeast. Proteasomal degradation of Fzo1 in response to the mating pheromone is proposed to mediate the remodeling of the mitochondrial network during the process of mating.
Decentralized command and control settings like those found in the military are rife with complexity and change. These settings typically involve dozens, if not hundreds to thousands, of heterogeneous players coordinating in a distributed fashion in a dynamically networked battlefield laden with sensor data, intelligence reports, communications, and plans emanating from many different perspectives. Consider the concept of team situation awareness in this setting. What does it mean for a team to be aware of a situation or, more importantly, of a critical change in a situation? Is it sufficient or necessary for all individuals on the team to be independently aware? Or is there some more holistic awareness that emerges as team members interact? We re-examine the concept of team situation awareness in decentralized systems beyond an individual-oriented knowledge-based construct by considering it as a team interaction-based phenomenon. A theoretical framework for a process-based measure called 'coordinated awareness of situations by teams' is outlined.
The extracellular matrix (ECM), the product of stromal cells, is now thought to make a dynamic network in tissues. Stromal cells can support other cells not only by direct contact but also via this ECM network. The regulated turnover and remodeling of ECM needs both ECM degrading enzymes named matrix metalloproteinases (MMPs) and their inhibitors called tissue inhibitors of metalloproteinases (TIMPs). Through an understanding of their molecular structure, the nature of the enzymic activity of MMPs and the inhibitory action of TIMPs against MMPs have been well elucidated. Considering their potent inhibitory action against MMPs, TIMPs are thought to play an important role in maintaining ECM. However, other unique functions of TIMPs have been reported, such as erythroid potentiating activity, cell growth-promoting activity, embryogenesis-stimulating activity, steroidogenesis-stimulating activity and so on. This review covers this new field, and discusses what role TIMPs can play in controlling life. In the second part, we briefly introduce our recent date on TIMPs and hematopoiesis. Because TIMPs have a dual function, i.e. a potent inhibitory action against MMPs and cell growth promoting action, TIMPs are good candidates for tissue fibrosis. Our recent measurements of TIMP-1 and TIMP-2 levels using serum and plasma from patients with platelet number disorders and cultured medium from various leukemia cell lines, shows that platelets are a rich source of TIMPs and that TIMP-1 is secreted in large amounts by megakaryoblastic- and erythro-leukemia cell lines. Proliferation of bone marrow fibroblasts can be stimulated by TIMP-1 and TIMP-2. Taken together, TIMPs might be one of the important factors for the process of myelofibrosis in some pathological conditions.