Countermanding in rats as a practical model for investigation of adaptive control of behaviour, lifespan changes in behavioural control and neurotransmitter function

The countermanding paradigm was designed to investigate the ability to cancel a prepotent response when a stop signal is presented and allows estimation of the stop signal response time (SSRT), an otherwise unobservable behaviour. Humans exhibit adaptive control of behaviour in the countermanding task, proactively lengthening response time (RT) in expectation of stopping and reactively lengthening RT following stop trials or errors. Human performance changes throughout the lifespan, with longer RT, SSRT and greater emphasis on post-error slowing reported for older compared to younger adults. Inhibition in the task has generally been improved by drugs that increase extracellular norepinephrine. The current thesis examined a novel choice response countermanding task in rats to explore whether rodent countermanding performance is a suitable model for the study of adaptive control of behaviour, lifespan changes in behavioural control and the role of neurotransmitters in these behaviours. Rats reactively adjusted RT in the countermanding task, shortening RT after consecutive correct go trials and lengthening RT following non-cancelled, but not cancelled stop trials, in sessions with a 10 s, but not a 1 s post-error timeout interval. Rats proactively lengthened RT in countermanding task sessions compared to go trial-only sessions. Together, these findings suggest that rats strategically lengthened RT in the countermanding task to improve accuracy and avoid longer, unrewarded timeout intervals. Next, rats exhibited longer RT and relatively conserved post-error slowing, but no significant change in SSRT when tested at 12, compared to 7 months of age, suggesting that rats exhibit changes in countermanding task performance with aging similar to those observed in humans. Finally, acute administration of yohimbine (1.25, 2.5 mg/kg) and d-amphetamine (0.25, 0.5 mg/kg), which putatively increase extracellular norepinephrine and dopamine respectively, resulted in RT shortening, baseline-dependent effects on SSRT, and attenuated adaptive RT adjustments in rats in the case of d-amphetamine. These findings suggest that dopamine and norepinephrine encouraged motivated, reward-seeking behaviour and supported inhibitory control in an inverted-U-like fashion. Taken together, these observations validate the rat countermanding task for further study of the neural correlates and neurotransmitters mediating adaptive control of behaviour and lifespan changes in behavioural control.

(Table 1) Age model of sediment core MD03-2705

A reconstruction of northwest African summer monsoon strength during the cold marine isotopic stage (MIS) 6 indicates a link to the seasonal migration of the Intertropical Convergence Zone (ITCZ). High-resolution studies of eolian dust supply and sea surface temperature recorded in marine core MD03-2705, on the Mauritanian margin, provide a better understanding about the penultimate glacial history of northwestern African aridity/humidity and upwelling coastal activity. Today, site MD03-2705 experiences increased upwelling and dust flux during the winter months, when the ITCZ is in a southerly position. Analyses of foraminifera isotopic composition suggest that during MIS 6.5 (180-168 ka) the average position of the ITCZ migrated north, marked by an increase in the strength of the summer monsoon, which decreased eolian dust transport and the coastal upwelling activity. The northward migration is in phase with a specific orbital combination of a low precessional index with a high obliquity signal. High-resolution analysis of stable isotopes (d18O and d13C) and microscale resolution geochemical (Ti/Al and quartz grain counts) determinations reveal that the transition between monsoonal humid (MIS 6.5) and dry (MIS 6.4) conditions has occurred in less than 1.3 ka. Such rapid changes suggest a nonlinear link between the African monsoonal rainfall system and environmental changes over the continent. This study provides new insights about the influence of vegetation and oceanic temperature feedbacks on the onset of African summer monsoon and demonstrates that, during the penultimate glacial period, changes in tropical dynamics had regional and global impacts.

Age model, radiocarbon dates and dinoflagellate cyst measurements from sediment core DA06-139G

A marine sediment core from Vaigat in Disko Bugt, West Greenland, has been analysed in terms of lithology, dinoflagellate cysts and foraminifera in order to evaluate the influence of oceanographic variability on West Greenland glacier stability. The data show that during the past 5200 years the Atlantic foraminiferal abundance in the subsurface waters of the West Greenland Current (WGC) episodically increased, indicating periods of increases in the inflow of subsurface warm Atlantic water at 2000 - 1500 cal. yr BP and 1300 cal. yr BP as well as periods of less pronounced increased bottom-water temperatures around 4700 - 4000 cal. yr BP, 3100 - 2800, 2600, 1000 - 800, 500 - 400, and at 200 cal. yr. The sedimentological and dinoflagellate cyst data indicate that these episodes with enhanced advection of Irminger Sea-derived waters are accompanied by increased iceberg rafting, which we link to increased iceberg calving in relation to destabilization of the Jakobshavn Isbrae. The long-term trend in the data documents the end of a late-Holocene Thermal Maximum between 5200 and 4300 cal. yr BP and a final onset of the Neoglaciation at 3500 cal. yr BP. Increased responses of the iceberg rafting after 3500 cal. yr BP, reflects a westward/seaward advance of the glacier margin in relation to onset of Neoglaciation and a development of the glacier into a floating tongue after 2000 cal. yr BP. A comparison of our record with a record from the eastern North Atlantic indicates that a NAO-like anomaly pattern between subsurface waters in West Greenland and atmospheric temperature in the Eastern North Atlantic may have been operating during most of the late Holocene. However, during the past 1000 years the NAO signal may have weakened as some other mode of climate variability overprints the anti-phase climate signal in this region.

Characterization of a complex chemosensory signal transduction system which controls twitching motility in Pseudomonas aeruginosa

Virulence of the opportunistic pathogen Pseudomonas aeruginosa involves the coordinate expression of a wide range of virulence factors including type IV pili which are required for colonization of host tissues and are associated with a form of surface translocation termed twitching motility. Twitching motility in P. aeruginosa is controlled by a complex signal transduction pathway which shares many modules in common with chemosensory systems controlling flagella rotation in bacteria and which is composed, in part, of the previously described proteins PilG, PilH, PilI, PilJ and PilK. Here we describe another three components of this pathway: ChpA, ChpB and ChpC, as well as two downstream genes, ChpD and ChpE, which may also be involved. The central component of the pathway, ChpA, possesses nine potential sites of phosphorylation: six histidine-containing phosphotransfer (HPt) domains, two novel serine- and threonine-containing phosphotransfer (SPt, TPt) domains and a CheY-like receiver domain at its C-terminus, and as such represents one of the most complex signalling proteins yet described in nature. We show that the Chp chemosensory system controls twitching motility and type IV pili biogenesis through control of pili assembly and/or retraction as well as expression of the pilin subunit gene pilA. The Chp system is also required for full virulence in a mouse model of acute pneumonia.

Model for growth hormone receptor activation based on subunit rotation within a receptor dimer

Growth hormone is believed to activate the growth hormone receptor (GHR) by dimerizing two identical receptor subunits, leading to activation of JAK2 kinase associated with the cytoplasmic domain. However, we have reported previously that dimerization alone is insufficient to activate full-length GHR. By comparing the crystal structure of the liganded and unliganded human GHR extracellular domain, we show here that there is no substantial change in its conformation on ligand binding. However, the receptor can be activated by rotation without ligand by inserting a defined number of alanine residues within the transmembrane domain. Fluorescence resonance energy transfer ( FRET), bioluminescence resonance energy transfer (BRET) and coimmunoprecipitation studies suggest that receptor subunits undergo specific transmembrane interactions independent of hormone binding. We propose an activation mechanism involving a relative rotation of subunits within a dimeric receptor as a result of asymmetric placement of the receptor-binding sites on the ligand.

Detecting finite bandwidth periodic signals in stationary noise using the signal coherence spectrum

All signals that appear to be periodic have some sort of variability from period to period regardless of how stable they appear to be in a data plot. A true sinusoidal time series is a deterministic function of time that never changes and thus has zero bandwidth around the sinusoid's frequency. A zero bandwidth is impossible in nature since all signals have some intrinsic variability over time. Deterministic sinusoids are used to model cycles as a mathematical convenience. Hinich [IEEE J. Oceanic Eng. 25 (2) (2000) 256-261] introduced a parametric statistical model, called the randomly modulated periodicity (RMP) that allows one to capture the intrinsic variability of a cycle. As with a deterministic periodic signal the RMP can have a number of harmonics. The likelihood ratio test for this model when the amplitudes and phases are known is given in [M.J. Hinich, Signal Processing 83 (2003) 1349-13521. A method for detecting a RMP whose amplitudes and phases are unknown random process plus a stationary noise process is addressed in this paper. The only assumption on the additive noise is that it has finite dependence and finite moments. Using simulations based on a simple RMP model we show a case where the new method can detect the signal when the signal is not detectable in a standard waterfall spectrograrn display. (c) 2005 Elsevier B.V. All rights reserved.

Divergent selection and the evolution of signal traits and mating preferences

Mating preferences are common in natural populations, and their divergence among populations is considered an important source of reproductive isolation during speciation. Although mechanisms for the divergence of mating preferences have received substantial theoretical treatment, complementary experimental tests are lacking. We conducted a laboratory evolution experiment, using the fruit fly Drosophila serrata, to explore the role of divergent selection between environments in the evolution of female mating preferences. Replicate populations of D. serrata were derived from a common ancestor and propagated in one of three resource environments: two novel environments and the ancestral laboratory environment. Adaptation to both novel environments involved changes in cuticular hydrocarbons, traits that predict mating success in these populations. Furthermore, female mating preferences for these cuticular hydrocarbons also diverged among populations. A component of this divergence occurred among treatment environments, accounting for at least 17.4% of the among- population divergence in linear mating preferences and 17.2% of the among-population divergence in nonlinear mating preferences. The divergence of mating preferences in correlation with environment is consistent with the classic by- product model of speciation in which premating isolation evolves as a side effect of divergent selection adapting populations to their different environments.

Biogenesis of caveolae: a structural model for caveolin-induced domain formation

Caveolae are striking morphological features of the plasma membrane of mammalian cells. Caveolins, the major proteins of caveolae, play a crucial role in the formation of these invaginations of the plasma membrane; however, the precise mechanisms involved are only just starting to be unravelled. Recent studies suggest that caveolae are stable structures first generated in the Golgi complex. Their formation and exit from the Golgi complex is associated with caveolin oligomerisation, acquisition of detergent insolubility, and association with cholesterol. Modelling of caveolin-membrane interactions together with in vitro studies of caveolin peptides are providing new insights into how caveolin-lipid interactions could generate the unique architecture of the caveolar domain.

Enhanced detection-guided NLMS estimation of sparse FIR-modeled signal channels

In various signal-channel-estimation problems, the channel being estimated may be well approximated by a discrete finite impulse response (FIR) model with sparsely separated active or nonzero taps. A common approach to estimating such channels involves a discrete normalized least-mean-square (NLMS) adaptive FIR filter, every tap of which is adapted at each sample interval. Such an approach suffers from slow convergence rates and poor tracking when the required FIR filter is "long." Recently, NLMS-based algorithms have been proposed that employ least-squares-based structural detection techniques to exploit possible sparse channel structure and subsequently provide improved estimation performance. However, these algorithms perform poorly when there is a large dynamic range amongst the active taps. In this paper, we propose two modifications to the previous algorithms, which essentially remove this limitation. The modifications also significantly improve the applicability of the detection technique to structurally time varying channels. Importantly, for sparse channels, the computational cost of the newly proposed detection-guided NLMS estimator is only marginally greater than that of the standard NLMS estimator. Simulations demonstrate the favourable performance of the newly proposed algorithm. © 2006 IEEE.

The roles of exercise-induced immune system disturbances in the pathology of heat stroke - The dual pathway model of heat stroke

Heat stroke is a life-threatening condition that can be fatal if not appropriately managed. Although heat stroke has been recognised as a medical condition for centuries, a universally accepted definition of heat stroke is lacking and the pathology of heat stroke is not fully understood. Information derived from autopsy reports and the clinical presentation of patients with heat stroke indicates that hyperthermia, septicaemia, central nervous system impairment and cardiovascular failure play important roles in the pathology of heat stroke. The current models of heat stroke advocate that heat stroke is triggered by hyperthermia but is driven by endotoxaemia. Endotoxaemia triggers the systemic inflammatory response, which can lead to systemic coagulation and haemorrhage, necrosis, cell death and multi-organ failure. However, the current heat stroke models cannot fully explain the discrepancies in high core temperature (Tc) as a trigger of heat stroke within and between individuals. Research on the concept of critical Tc: as a limitation to endurance exercise implies that a high Tc may function as a signal to trigger the protective mechanisms against heat stroke. Athletes undergoing a period of intense training are subjected to a variety of immune and gastrointestinal (GI) disturbances. The immune disturbances include the suppression of immune cells and their functions, suppression of cell-mediated immunity, translocation of lipopolysaccharide (LPS), suppression of anti-LPS antibodies, increased macrophage activity due to muscle tissue damage, and increased concentration of circulating inflammatory and pyrogenic cytokines. Common symptoms of exercise-induced GI disturbances include diarrhoea, vomiting, gastrointestinal bleeding, and cramps, which may increase gut-related LPS translocation. This article discusses the current evidence that supports the argument that these exercise-induced immune and GI disturbances may contribute to the development of endotoxaemia and heat stroke. When endotoxaemia can be tolerated or prevented, continuing exercise and heat exposure will elevate Tc to a higher level (> 42 degrees C), where heat stroke may occur through the direct thermal effects of heat on organ tissues and cells. We also discuss the evidence suggesting that heat stroke may occur through endotoxaemia (heat sepsis), the primary pathway of heat stroke, or hyperthermia, the secondary pathway of heat stroke. The existence of these two pathways of heat stroke and the contribution of exercise-induced immune and GI disturbances in the primary pathway of heat stroke are illustrated in the dual pathway model of heat stroke. This model of heat stroke suggests that prolonged intense exercise suppresses anti-LPS mechanisms, and promotes inflammatory and pyrogenic activities in the pathway of heat stroke.

Type III secretion contact-dependent model for the intracellular development of Chlamydia

The medically significant genus Chlamydia is a class of obligate intracellular bacterial pathogens that replicate within vacuoles in host eukaryotic cells termed inclusions. Chlamydia's developmental cycle involves two forms; an infectious extracellular form, known as an elementary body (EB), and a non-infectious form, known as the reticulate body (RB), that replicates inside the vacuoles of the host cells. The RB surface is covered in projections that are in intimate contact with the inclusion membrane. Late in the developmental cycle, these reticulate bodies differentiate into the elementary body form. In this paper, we present a hypothesis for the modulation of these developmental events involving the contact-dependent type III secretion (TTS) system. TTS surface projections mediate intimate contact between the RB and the inclusion membrane. Below a certain number of projections, detachment of the RB provides a signal for late differentiation of RB into EB. We use data and develop a mathematical model investigating this hypothesis. If the hypothesis proves to be accurate, then we have shown that increasing the number of inclusions per host cell will increase the number of infectious progeny EB until some optimal number of inclusions. For more inclusions than this optimum, the infectious yield is reduced because of spatial restrictions. We also predict that a reduction in the number of projections on the surface of the RB (and as early as possible during development) will significantly reduce the burst size of infectious EB particles. Many of the results predicted by the model can be tested experimentally and may lead to the identification of potential targets for drug design. © Society for Mathematical Biology 2006.

Branching genes are conserved across species. Genes controlling a novel signal in pea are coregulated by other long-distance signals

Physiological and genetic studies with the ramosus (rms) mutants in garden pea (Pisum sativum) and more axillary shoots (max) mutants in Arabidopsis (Arabidopsis thaliana) have shown that shoot branching is regulated by a network of long-distance signals. Orthologous genes RMS1 and MAX4 control the synthesis of a novel graft-transmissible branching signal that may be a carotenoid derivative and acts as a branching inhibitor. In this study, we demonstrate further conservation of the branching control system by showing that MAX2 and MAX3 are orthologous to RMS4 and RMS5, respectively. This is consistent with the longstanding hypothesis that branching in pea is regulated by a novel long-distance signal produced by RMS1 and RMS5 and that RMS4 is implicated in the response to this signal. We examine RMS5 expression and show that it is more highly expressed relative to RMS1, but under similar transcriptional regulation as RMS1. Further expression studies support the hypothesis that RMS4 functions in shoot and rootstock and participates in the feedback regulation of RMS1 and RMS5 expression. This feedback involves a second novel long-distance signal that is lacking in rms2 mutants. RMS1 and RMS5 are also independently regulated by indole-3-acetic acid. RMS1, rather than RMS5, appears to be a key regulator of the branching inhibitor. This study presents new interactions between RMS genes and provides further evidence toward the ongoing elucidation of a model of axillary bud outgrowth in pea.

Investigating the performance analysis of EASI algorithm and EKENS algorithm in nonlinear model

This paper investigates the performance of EASI algorithm and the proposed EKENS algorithm for linear and nonlinear mixtures. The proposed EKENS algorithm is based on the modified equivariant algorithm and kernel density estimation. Theory and characteristic of both the algorithms are discussed for blind source separation model. The separation structure of nonlinear mixtures is based on a nonlinear stage followed by a linear stage. Simulations with artificial and natural data demonstrate the feasibility and good performance of the proposed EKENS algorithm.

A simple electromagnetic model for understanding the operation of a MIMO system

Recent years have witnessed intense research in multiple input multiple output (MIMO) wireless communications systems, which use multiple element antennas (MEA) for signal transmission and reception. In this paper, we have described a novel electromagnetic model to investigate the effect of mutual coupling, inter-element spacing and array geometry on the capacity of MIMO systems. Simulation results have been presented illustrating the application of the proposed model. The presented model concept stems from a hollow waveguide analogue. Using this model other aspects such as richness of scattering environment (spacing and clustering), the effect of hard versus soft scatterers and pin hole effect can be investigated.

Investigations into the effect of LOS signal blocking on capacity of an indoor MIMO system

In indoor environments the properties of communication channel are affected by the presence of various objects which block the Line Of Sight signal propagation. For example, this occurs because of presence of movement of humans and furniture. In this paper, the effect of reflection and scattering due to the presence of such objects is studied with respect to the capacity of a multiple input multiple output (MIMO) wireless system. The carried out investigations are performed by applying a simple electromagnetic model, in which transmitting and receiving antennas of MIMO system, as well as signal blocking objects, are represented by wire dipoles. In order to provide a fair assessment, calculations of MIMO capacity are performed under both fixed transmitted power and fixed received power conditions.