Bifurcation, Bursting, and Spike Frequency Adaptation

Many neural systems display adaptive properties that occur on timescales that are slower than the time scales associated withrepetitive firing of action potentials or bursting oscillations. Spike frequency adaptation is the name givento processes thatreduce the frequency of rhythmic tonic firing of action potentials,sometimes leading to the termination of spiking and the cell becomingquiescent. This article examines these processes mathematically,within the context of singularly perturbed dynamical systems.We place emphasis on the lengths of successive interspikeintervals during adaptation. Two different bifurcation mechanisms insingularly perturbed systems that correspond to the termination offiring are distinguished by the rate at which interspike intervalsslow near the termination of firing. We compare theoreticalpredictions to measurement of spike frequency adaptation in a modelof the LP cell of the lobster stomatogastric ganglion.     

The thrombomodulin-protein C system is essential for the maintenance of pregnancy

Disruption of the mouse gene encoding the blood coagulation inhibitor thrombomodulin (Thbd) leads to embryonic lethality caused by an unknown defect in the placenta. We show that the abortion of thrombomodulin-deficient embryos is caused by tissue factor-initiated activation of the blood coagulation cascade at the feto-maternal interface. Activated coagulation factors induce cell death and growth inhibition of placental trophoblast cells by two distinct mechanisms. The death of giant trophoblast cells is caused by conversion of the thrombin substrate fibrinogen to fibrin and subsequent formation of fibrin degradation products. In contrast, the growth arrest of trophoblast cells is not mediated by fibrin, but is a likely result of engagement of protease-activated receptors (PAR)-2 and PAR-4 by coagulation factors. These findings show a new function for the thrombomodulin-protein C system in controlling the growth and survival of trophoblast cells in the placenta. This function is essential for the maintenance of pregnancy.     

Branch growth of riparian cottonwoods: a hydrologically sensitive dendrochronological tool

 The conservation of riparian (river valley flood plain) forests relies on the provision of instream flows that are sufficient to sustain tree growth. In the present study, annual branch growth increments were investigated as an indicator of environmental favorability for riparian cottonwoods. Trees of three species, Populus angustifolia, P. balsamifera, and P. deltoides, and their natural interspecific hybrids, were studied at five sites along the Oldman and South Saskatchewan rivers in Alberta, Canada. Annual branch growth increments for the interval from 1983 to 1992 were positively correlated with stream flows (r ² = 0.79 at Lethbridge) and slightly negatively correlated with weather variables that contribute to water demand: evaporation, temperature, wind, and/or sunshine. The combination of January to May stream flow (water supply) and June evaporation (water demand) almost entirely accounted for the branch growth variation across years (r ² = 0.91 at Lethbridge). Tree ring increments were also investigated but were less closely correlated than branch increments across trees or with stream flow. Branch growth increments thus provide an accurate but short duration (1 or 2 decades) record of environmental favorability for growth. The close correlation between branch growth and stream flow indicates that water is the principal limitation to growth of these riparian cottonwoods and that these trees obtained their water from a source linked to the stream, the riparian water table. Analyses of branch increments should provide a management tool for (i) determining instream flow needs for riparian cottonwoods and (ii) analyzing impacts of stream flow alterations due to river damming or water diversion. Received: 8 May 1997 / Accepted: 23 September 1997     

Relationship between airway microvascular leakage, edema, and baseline airway functions

Matheson, Melissa, Ann-Christine Rynell, Melissa McClean,and Norbert Berend. Relationship between airway microvascular leakage, edema, and baseline airway functions. J. Appl. Physiol. 84(1): 77-81, 1998.This study wasdesigned to examine the relationship among microvascular leakage,edema, and baseline airway function. Microvascular leakage was inducedin the airways of anesthetized, tracheostomized New Zealand Whiterabbits (n = 22) by using nebulized N-formyl-methionyl-leucyl-phenylalanine(10 mg) and was measured in the trachea by using the Evans blue dyetechnique. Airway wall thickness was assessed morphometrically in theright main bronchus after Formalin fixation at a pressure of 25 cmH₂O. Areas calculated includedthe mucosal wall area, the adventitial wall area, the total wall area,and the percentage of total wall area consisting of blood vessels. Aneutrophil count was also performed by analyzing numbers of cells inboth the mucosal wall area and the adventitial wall area. Airwayfunction was assessed before and 30 min after challenge withN-formyl-methionyl-leucyl-phenylalanineby determining airway resistance, functional residual capacity,specific airway resistance, and flow-volume and pressure-volume curves(after paralysis of the animals with suxamethonium). The concentration of Evans blue dye in tracheal tissue ranged from 31.3 to 131.2 µg.There was a significant correlation between this concentration and boththe adventitial wall area (P < 0.01)and mucosal neutrophil numbers (P < 0.005). There was no correlation between Evans blue concentration andeither blood vessel area or changes in respiratory physiologyparameters before and after challenge. There was no significantdifference between any respiratory physiology measurements before andafter challenge. We conclude that an increase in microvascular leakagecorrelates with airway edema in the adventitia; however, these airwaychanges have no significant effect on airway elastic or resistiveproperties.

     

RNAi screen of Salmonella invasion shows role of COPI in membrane targeting of cholesterol and Cdc42

The pathogen Salmonella Typhimurium is a common cause of diarrhea and invades the gut tissue by injecting a cocktail of virulence factors into epithelial cells, triggering actin rearrangements, membrane ruffling and pathogen entry. One of these factors is SopE, a G‐nucleotide exchange factor for the host cellular Rho GTPases Rac1 and Cdc42. How SopE mediates cellular invasion is incompletely understood. Using genome‐scale RNAi screening we identified 72 known and novel host cell proteins affecting SopE‐mediated entry. Follow‐up assays assigned these ‘hits’ to particular steps of the invasion process; i.e., binding, effector injection, membrane ruffling, membrane closure and maturation of the Salmonella‐containing vacuole. Depletion of the COPI complex revealed a unique effect on virulence factor injection and membrane ruffling. Both effects are attributable to mislocalization of cholesterol, sphingolipids, Rac1 and Cdc42 away from the plasma membrane into a large intracellular compartment. Equivalent results were obtained with the vesicular stomatitis virus. Therefore, COPI‐facilitated maintenance of lipids may represent a novel, unifying mechanism essential for a wide range of pathogens, offering opportunities for designing new drugs.     

Visualization and 3D reconstruction of flame cells of Taenia solium (cestoda)

Background

Flame cells are the terminal cells of protonephridial systems, which are part of the excretory systems of invertebrates. Although the knowledge of their biological role is incomplete, there is a consensus that these cells perform excretion/secretion activities. It has been suggested that the flame cells participate in the maintenance of the osmotic environment that the cestodes require to live inside their hosts. In live Platyhelminthes, by light microscopy, the cells appear beating their flames rapidly and, at the ultrastructural, the cells have a large body enclosing a tuft of cilia. Few studies have been performed to define the localization of the cytoskeletal proteins of these cells, and it is unclear how these proteins are involved in cell function.

Methodology/Principal Findings

Parasites of two different developmental stages of T. solium were used: cysticerci recovered from naturally infected pigs and intestinal adults obtained from immunosuppressed and experimentally infected golden hamsters. Hamsters were fed viable cysticerci to recover adult parasites after one month of infection. In the present studies focusing on flame cells of cysticerci tissues was performed. Using several methods such as video, confocal and electron microscopy, in addition to computational analysis for reconstruction and modeling, we have provided a 3D visual rendition of the cytoskeletal architecture of Taenia solium flame cells.

Conclusions/Significance

We consider that visual representations of cells open a new way for understanding the role of these cells in the excretory systems of Platyhelminths. After reconstruction, the observation of high resolution 3D images allowed for virtual observation of the interior composition of cells. A combination of microscopic images, computational reconstructions and 3D modeling of cells appears to be useful for inferring the cellular dynamics of the flame cell cytoskeleton.     

Evolution and function of the mitotic checkpoint

The mitotic checkpoint evolved to prevent cell division when chromosomes have not established connections with the chromosome segregation machinery. Many of the fundamental molecular principles that underlie the checkpoint, its spatiotemporal activation, and its timely inactivation have been uncovered. Most of these are conserved in eukaryotes, but important differences between species exist. Here we review current concepts of mitotic checkpoint activation and silencing. Guided by studies in model organisms and our phylogenomics analysis of checkpoint constituents and their functional domains and motifs, we highlight ancient and taxa-specific aspects of the core checkpoint modules in the context of mitotic checkpoint function.     

Differentiating Psychopathy from General Antisociality Using the P3 as a Psychophysiological Correlate of Attentional Allocation

Recent studies have shown that while psychopathy and non-psychopathic antisociality overlap, they differ in the extent to which cognitive impairments are present. Specifically, psychopathy has been related to abnormal allocation of attention, a function that is traditionally believed to be indexed by event-related potentials (ERPs) of the P3-family. Previous research examining psychophysiological correlates of attention in psychopathic individuals has mainly focused on the parietally distributed P3b component to rare targets. In contrast, very little is known about the frontocentral P3a to infrequent novel events in psychopathy. Thus, findings on the P3 components in psychopathy are inconclusive, while results in non-psychopathic antisocial populations are clearer and point toward an inverse relationship between antisociality and P3 amplitudes. The present study adds to extant literature on the P3a and P3b in psychopathy by investigating component amplitudes in psychopathic offenders (N = 20), matched non-psychopathic offenders (N = 23) and healthy controls (N = 16). Also, it was assessed how well each offender group was able to differentially process rare novel and target events. The offender groups showed general amplitude reductions compared to healthy controls, but did not differ mutually on overall P3a/P3b amplitudes. However, the psychopathic group still exhibited normal neurophysiological differentiation when allocating attention to rare novel and target events, unlike the non-psychopathic sample. The results highlight differences between psychopathic and non-psychopathic offenders regarding the integrity of the neurocognitive processes driving attentional allocation, as well as the usefulness of alternative psychophysiological measures in differentiating psychopathy from general antisociality.