Evidence that GABA rho subunits contribute to functional ionotropic GABA receptors in mouse cerebellar Purkinje cells

Ionotropic gamma-amino butyric acid (GABA) receptors composed of heterogeneous molecular subunits are major mediators of inhibitory responses in the adult CNS. Here, we describe a novel ionotropic GABA receptor in mouse cerebellar Purkinje cells (PCs) using agents reported to have increased affinity for rho subunit-containing GABA(C) over other GABA receptors. Exogenous application of the GABA(C)-preferring agonist cis-4-aminocrotonic acid (CACA) evoked whole-cell currents in PCs, whilst equimolar concentrations of GABA evoked larger currents. CACA-evoked currents had a greater sensitivity to the selective GABA(C) antagonist (1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid (TPMPA) than GABA-evoked currents. Focal application of agonists produced a differential response profile; CACA-evoked currents displayed a much more pronounced attenuation with increasing distance from the PC soma, displayed a slower time-to-peak and exhibited less desensitization than GABA-evoked currents. However, CACA-evoked currents were also completely blocked by bicuculline, a selective agent for GABA(A) receptors. Thus, we describe a population of ionotropic GABA receptors with a mixed GABA(A)/GABA(C) pharmacology. TPMPA reduced inhibitory synaptic transmission at interneurone-Purkinje cell (IN-PC) synapses, causing clear reductions in miniature inhibitory postsynaptic current (mIPSC) amplitude and frequency. Combined application of NO-711 (a selective GABA transporter subtype 1 (GAT-1) antagonist) and SNAP-5114 (a GAT-(2)/3/4 antagonist) induced a tonic GABA conductance in PCs; however, TPMPA had no effect on this current. Immunohistochemical studies suggest that rho subunits are expressed predominantly in PC soma and proximal dendritic compartments with a lower level of expression in more distal dendrites; this selective immunoreactivity contrasted with a more uniform distribution of GABA(A) alpha 1 subunits in PCs. Finally, co-immunoprecipitation studies suggest that rho subunits can form complexes with GABA(A) receptor alpha 1 subunits in the cerebellar cortex. Overall, these data suggest that rho subunits contribute to functional ionotropic receptors that mediate a component of phasic inhibitory GABAergic transmission at IN-PC synapses in the cerebellum.

Classification of lactose and mandelic acid THz spectra using subspace and wavelet-packet algorithms

This work compares classification results of lactose, mandelic acid and dl-mandelic acid, obtained on the basis of their respective THz transients. The performance of three different pre-processing algorithms applied to the time-domain signatures obtained using a THz-transient spectrometer are contrasted by evaluating the classifier performance. A range of amplitudes of zero-mean white Gaussian noise are used to artificially degrade the signal-to-noise ratio of the time-domain signatures to generate the data sets that are presented to the classifier for both learning and validation purposes. This gradual degradation of interferograms by increasing the noise level is equivalent to performing measurements assuming a reduced integration time. Three signal processing algorithms were adopted for the evaluation of the complex insertion loss function of the samples under study; a) standard evaluation by ratioing the sample with the background spectra, b) a subspace identification algorithm and c) a novel wavelet-packet identification procedure. Within class and between class dispersion metrics are adopted for the three data sets. A discrimination metric evaluates how well the three classes can be distinguished within the frequency range 0. 1 - 1.0 THz using the above algorithms.

Learning and natal host influence host preference, handling time and sex allocation behaviour in a pupal parasitoid

The host choice and sex allocation decisions of a foraging female parasitoid will have an enormous influence on the life-history characteristics of her offspring. The pteromalid Pachycrepoideus vindemiae is a generalist idiobiont pupal parasitoid of many species of cyclorrhaphous Diptera. Wasps reared in Musca domestica were larger, had higher attack rates and greater male mating success than those reared in Drosophila melanogaster. In no-choice situations, naive female R vindemiae took significantly less time to accept hosts conspecific with their natal host. Parasitoids that emerged from M. domestica pupae spent similar amounts of time ovipositing in both D. melanogaster and M. domestica. Those parasitoids that had emerged from D. melanogaster spent significantly longer attacking M. domestica pupae. The host choice behaviour of female P. vindemiae was influenced by an interaction between natal host and experience. Female R vindemiae reared in M. domestica only showed a preference among hosts when allowed to gain experience attacking M. domestica, preferentially attacking that species. Similarly, female parasitoids reared on D. melanogaster only showed a preference among hosts when allowed to gain experience attacking D. melanogaster, again preferentially attacking that species. Wasp natal host also influenced sex allocation behaviour. While wasps from both hosts oviposited more females in the larger host, M. domestica, wasps that emerged from M. domestica had significantly more male-biased offspring sex ratios. These results indicate the importance of learning and natal host size in determining R vindemiae attack rates. mating success, host preference and sex allocation behaviour, all critical components of parasitoid fitness.

Phorbol ester, but not ischemic preconditioning, activates protein kinase D in the rat heart

The signal transduction pathways that mediate the cardioprotective effects of ischemic preconditioning remain unclear. Here we have determined the role of a novel kinase, protein kinase D (PKD), in mediating preconditioning in the rat heart. Isolated rat hearts (n=6/group) were subjected to either: (i) 36 min aerobic perfusion (control); (ii) 20 min aerobic perfusion plus 3 min no-flow ischemia, 3 min reperfusion, 5 min no-flow ischemia, 5 min reperfusion (ischemic preconditioning); (iii) 20 min aerobic perfusion plus 200 nmol/l phorbol 12-myristate 13-acetate (PMA) given as a substitute for ischemic preconditioning. The left ventricle then was excised, homogenized and PKD immunoprecipitated from the homogenate. Activity of the purified kinase was determined following bincubation with [γ32P]-ATP±syntide-2, a substrate for PKD. Significant PKD autophosphorylation and syntide-2 phosphorylation occurred in PMA-treated hearts, but not in control or preconditioned hearts. Additional studies confirmed that recovery of LVDP was greater and initiation of ischemic contracture and time-to-peak contracture were less, in ischemic preconditioned hearts compared with controls (P<0.05). Our results suggest that the early events that mediate ischemic preconditioning in the rat heart occur via a PKD-independent mechanism.

Entropy application to improve construction finance decisions

In financial decision-making processes, the adopted weights of the objective functions have significant impacts on the final decision outcome. However, conventional rating and weighting methods exhibit difficulty in deriving appropriate weights for complex decision-making problems with imprecise information. Entropy is a quantitative measure of uncertainty and has been useful in exploring weights of attributes in decision making. A fuzzy and entropy-based mathematical approach is employed to solve the weighting problem of the objective functions in an overall cash-flow model. The multiproject being undertaken by a medium-size construction firm in Hong Kong was used as a real case study to demonstrate the application of entropy. Its application in multiproject cash flow situations is demonstrated. The results indicate that the overall before-tax profit was HK$ 0.11 millions lower after the introduction of appropriate weights. In addition, the best time to invest in new projects arising from positive cash flow was identified to be two working months earlier than the nonweight system.

Lack of influence of test meal fatty acid composition on the contribution of intestinally-derived lipoproteins to postprandial lipaemia

The extent and duration of postprandial lipaemia have been linked to risk of CHD but the influence of dietary variables on, and the relative contributions of, exogenous (chylomicron) and endogenous (VLDL) triacylglycerols to the total lipaemic response have not been comprehensively evaluated. In the present study the triacylglycerol, apolipoprotein (apo) B-48 and retinyl ester (RE) responses to three test meals of varying monounsaturated (MUFA) and saturated fatty acid (SFA) content were measured in the triacylglycerol-rich lipoprotein (TRL) fraction of plasma (r ¼ 1·006 g/ml) for 9 h after meal consumption. Fifteen healthy normolipidaemic young men consumed, on separate occasions, three test meals which were identical apart from their MUFA and SFA contents. Expressed as a percentage of total energy the MUFA/SFA contents of the meals were: (1) 12 %/17 %; (2) 17 %/12% and (3) 24 %/5 %. The contribution of the intestinally-derived lipoproteins (chylomicrons) to the lipaemic response was investigated by determining the time to reach peak concentration and the total and incremental areas under the time response curves (AUC and incremental AUC) for RE, apoB-48 and triacylglycerol in the TRL fraction. No significant differences in these measurements were observed for the three meals. However, visual comparison of the postprandial responses to the three meals suggested that as meal MUFA content increased there was a tendency for the triacylglycerol, apoB-48 and RE responses to become biphasic as opposed to the typical monophasic response seen with the 12% MUFA/17% SFA meal. Comparison of the apoB-48 and RE responses for the three test meals confirmed other workers’ findings of delayed entry of RE relative to apoB-48 in TRL. The value of the two markers in investigating dietary fat absorption and metabolism is discussed.

Driving saccade to pursuit using image motion

Within the context of active vision, scant attention has been paid to the execution of motion saccades—rapid re-adjustments of the direction of gaze to attend to moving objects. In this paper we first develop a methodology for, and give real-time demonstrations of, the use of motion detection and segmentation processes to initiate capture saccades towards a moving object. The saccade is driven by both position and velocity of the moving target under the assumption of constant target velocity, using prediction to overcome the delay introduced by visual processing. We next demonstrate the use of a first order approximation to the segmented motion field to compute bounds on the time-to-contact in the presence of looming motion. If the bound falls below a safe limit, a panic saccade is fired, moving the camera away from the approaching object. We then describe the use of image motion to realize smooth pursuit, tracking using velocity information alone, where the camera is moved so as to null a single constant image motion fitted within a central image region. Finally, we glue together capture saccades with smooth pursuit, thus effecting changes in both what is being attended to and how it is being attended to. To couple the different visual activities of waiting, saccading, pursuing and panicking, we use a finite state machine which provides inherent robustness outside of visual processing and provides a means of making repeated exploration. We demonstrate in repeated trials that the transition from saccadic motion to tracking is more likely to succeed using position and velocity control, than when using position alone.

Liquidity in commercial property markets: deconstructing the transaction process

This paper draws from a wider research programme in the UK undertaken for the Investment Property Forum examining liquidity in commercial property. One aspect of liquidity is the process by which transactions occur including both how properties are selected for sale and the time taken to transact. The paper analyses data from three organisations; a property company, a major financial institution and an asset management company, formally a major public sector pension fund. The data covers three market states and includes sales completed in 1995, 2000 and 2002 in the UK. The research interviewed key individuals within the three organisations to identify any common patterns of activity within the sale process and also identified the timing of 187 actual transactions from inception of the sale to completion. The research developed a taxonomy of the transaction process. Interviews with vendors indicated that decisions to sell were a product of a combination of portfolio, specific property and market based issues. Properties were generally not kept in a “readiness for sale” state. The average time from first decision to sell the actual property to completion had a mean time of 298 days and a median of 190 days. It is concluded that this study may underestimate the true length of the time to transact for two reasons. Firstly, the pre-marketing period is rarely recorded in transaction files. Secondly, and more fundamentally, studies of sold properties may contain selection bias. The research indicated that vendors tended to sell properties which it was perceived could be sold at a ‘fair’ price in a reasonable period of time.

Investigating familiar interfaces to help older adults learn computer applications more easily

Many older adults wish to gain competence in using a computer, but many application interfaces are perceived as complex and difficult to use, deterring potential users from investing the time to learn them. Hence, this study looks at the potential of ‘familiar’ interface design which builds upon users’ knowledge of real world interactions, and applies existing skills to a new domain. Tools are provided in the form of familiar visual objects, and manipulated like real-world counterparts, rather than with buttons, icons and menus found in classic WIMP interfaces. This paper describes the formative evaluation of computer interactions that are based upon familiar real world tasks, which supports multitouch interaction, involves few buttons and icons, no menus, no right-clicks or double-clicks and no dialogs. Using an example of an email client to test the principles of using “familiarity”, the initial feedback was very encouraging, with 3 of the 4 participants being able to undertake some of the basic email tasks with no prior training and little or no help. The feedback has informed a number of refinements of the design principles, such as providing clearer affordance for visual objects. A full study is currently underway.

Development of a light scatter sensor technology for on-line monitoring of milk coagulation and whey separation

The objective of this study was to investigate a novel light backscatter sensor, with a large field of view relative to curd size, for continuous on-line monitoring of coagulation and syneresis to improve curd moisture content control. A three-level, central composite design was employed to study the effects of temperature, cutting time, and CaCl2 addition on cheese making parameters. The sensor signal was recorded and analyzed. The light backscatter ratio followed a sigmoid increase during coagulation and decreased asymptotically after gel cutting. Curd yield and curd moisture content were predicted from the time to the maximum slope of the first derivative of the light backscatter ratio during coagulation and the decrease in the sensor response during syneresis. Whey fat was affected by coagulation kinetics and cutting time, suggesting curd rheological properties at cutting are dominant factors determining fat losses. The proposed technology shows potential for on-line monitoring of coagulation and syneresis. 2007 Elsevier Ltd. All rights reserved..

Local gratings due to angular hole burning in a photorefractive polymer

We investigate the processes involved in writing real-time holographic gratings in a photorefractive polymer (PRP) that incorporates an azo-dye. In such systems there may be gratings due to mechanisms associated with trans–cis isomerization (angular hole burning (AHB) and/or angular redistribution), which appear in addition to those arising from the photorefractive (PR) effect. The work presented here helps to understand the interactions which may occur between these different gratings. The formation of local gratings due to mechanisms associated with photoisomerization is studied, in a new PRP based on the photoconductor poly(N-vinylcarbazole):2, 4, 7-trinitro-9-fluorenone, plasticized with N-ethylcarbazole. The polymer includes the azo-dye 4-nitro-4'-pentyloxy-azobenzene and we observe both PR and photoisomerization gratings. The gratings are shown to be both polarization-sensitive and reversible. The presence of the photoisomerization gratings (which diffract almost as strongly as the PR gratings) significantly affects the field-dependent diffractive behaviour of the composite. A measurement of the lifetime of the cis state is made (τcis = 38 s) using photoinduced dichroism. This is close to the decay time constant of the local gratings (τdecay = 42 s), and it is suggested that the local grating mechanism is AHB of the azo-dye. This is the first time (to the knowledge of the authors) that a local grating due to AHB has been demonstrated in a PRP.

Organic certification, export market access and the impacts of policy: Bayesian estimation of avocado smallholder “times-to-organic certification” in Michoacán Mexico

This study analyzes organic adoption decisions using a rich set of time-to-organic durations collected from avocado small-holders in Michoacán Mexico. We derive robust, intrasample predictions about the profiles of entry and exit within the conventional-versus-organic complex and we explore the sensitivity of these predictions to choice of functional form. The dynamic nature of the sample allows us to make retrospective predictions and we establish, precisely, the profile of organic entry had the respondents been availed optimal amounts of adoption-restraining resources. A fundamental problem in the dynamic adoption literature, hitherto unrecognized, is discussed and consequent extensions are suggested.

The role of phase separation and feed cycle length in leach beds coupled to methanogenic reactors for digestion of a solid substrate (Part 1): Optimisation of reactors’ performance

A two-phase system composed by a leach bed and a methanogenic reactor was modified for the first time to improve volumetric substrate degradation and methane yields from a complex substrate (maize; Zea mays). The system, which was operated for consecutive feed cycles of different durations for 120 days, was highly flexible and its performance improved by altering operational conditions. Daily substrate degradation was higher the shorter the feed cycle, reaching 8.5 g TSdestroyed d�1 (7-day feed cycle) but the overall substrate degradation was higher by up to 55% when longer feed cycles (14 and 28 days) were applied. The same occurred with volumetric methane yields, reaching 0.839 m3 (m3)�1 d�1. The system performed better than others on specific methane yields, reaching 0.434 m3 kg�1 TSadded, in the 14-day and 28-day systems. The UASB and AF designs performed similarly as second stage reactors on methane yields, SCOD and VFA removal efficiencies.

Multiple routes to mammalian diversity

The radiation of the mammals provides a 165-million-year test case for evolutionary theories of how species occupy and then fill ecological niches. It is widely assumed that species often diverge rapidly early in their evolution, and that this is followed by a longer, drawn-out period of slower evolutionary fine-tuning as natural selection fits organisms into an increasingly occupied niche space1,2. But recent studies have hinted that the process may not be so simple3–5. Here we apply statistical methods that automatically detect temporal shifts in the rate of evolution through time to a comprehensive mammalian phylogeny6 and data set7 of body sizes of 3,185 extant species. Unexpectedly, the majority of mammal species, including two of the most speciose orders (Rodentia and Chiroptera), have no history of substantial and sustained increases in the rates of evolution. Instead, a subset of the mammals has experienced an explosive increase (between 10- and 52-fold) in the rate of evolution along the single branch leading to the common ancestor of their monophyletic group (for example Chiroptera), followed by a quick return to lower or background levels. The remaining species are a taxonomically diverse assemblage showing a significant, sustained increase or decrease in their rates of evolution. These results necessarily decouple morphological diversification from speciation and suggest that the processes that give rise to the morphological diversity of a class of animals are far more free to vary than previously considered. Niches do not seem to fill up, and diversity seems to arise whenever, wherever and at whatever rate it is advantageous.

Identifying time lags in the restoration of grassland butterfly communities: a multi-site assessment

Although grasslands are crucial habitats for European butterflies, large-scale declines in quality and area have devastated many species. Grassland restoration can contribute to the recovery of butterfly populations, although there is a paucity of information on the long-term effects of management. Using eight UK data sets (9-21 years), we investigate changes in restoration success for (1) arable reversion sites, were grassland was established on bare ground using seed mixtures, and (2) grassland enhancement sites, where degraded grasslands are restored by scrub removal followed by the re-instigation of cutting/grazing. We also assessed the importance of individual butterfly traits and ecological characteristics in determining colonisation times. Consistent increases in restoration success over time were seen for arable reversion sites, with the most rapid rates of increase in restoration success seen over the first 10 years. For grasslands enhancement there were no consistent increases in restoration success over time. Butterfly colonisation times were fastest for species with widespread host plants or where host plants established well during restoration. Low mobility butterfly species took longer to colonise. We show that arable reversion is an effective tool for the management of butterfly communities. We suggest that as restoration takes time to achieve, its use as a mitigation tool against future environmental change (i.e. by decreasing isolation in fragmented landscapes) needs to take into account such time lags.