Molecule Modeling of Human Pentameric alpha(7) Neuronal Nicotinic Acetylcholine Receptor and Its Interaction with its Agonist and Competitive Antagonist

The nicotinic Acetylcholine Receptor (nAChR) is the major class of neurotransmitter receptors that is involved in many neurodegenerative conditions such as schizophrenia, Alzheimer's and Parkinson's diseases. The N-terminal region or Ligand Binding Domain (LBD) of nAChR is located at pre- and post-synaptic nervous system, which mediates synaptic transmission. nAChR acts as the drug target for agonist and competitive antagonist molecules that modulate signal transmission at the nerve terminals. Based on Acetylcholine Binding Protein (AChBP) from Lymnea stagnalis as the structural template, the homology modeling approach was carried out to build three dimensional model of the N-terminal region of human alpha(7)nAChR. This theoretical model is an assembly of five alpha(7) subunits with 5 fold axis symmetry, constituting a channel, with the binding picket present at the interface region of the subunits. alpha-netlrotoxin is a potent nAChR competitive antagonist that readily blocks the channel resulting in paralysis. The molecular interaction of alpha-Bungarotoxin, a long chain alpha-neurotoxin from (Bungarus multicinctus) and human alpha(7)nAChR seas studied. Agonists such as acetylcholine, nicotine, which are used in it diverse array of biological activities, such as enhancements of cognitive performances, were also docked with the theoretical model of human alpha(7)nAChR. These docked complexes were analyzed further for identifying the crucial residues involved i interaction. These results provide the details of interaction of agonists and competitive antagonists with three dimensional model of the N-terminal region of human alpha(7)nAChR and thereby point to the design of novel lead compounds.

Data definition and manipulation languages for a CAD database

In this paper the main features of ARDBID (A Relational Database for Interactive Design) have been described. An overview of the organization of the database has been presented and a detailed description of the data definition and manipulation languages has been given. These have been implemented on a DEC 1090 system.

Dietary composition manipulation to enhance the performance of juvenile barramundi (Lates calcarifer Bloch) reared in cool water

Barramundi Lates calcarifer reared in cool water (20-22 degrees C) grow slowly and feed is used poorly compared with fish in warm water (28-32 degrees C). Two comparative slaughter growth assays were carried out with juvenile barramundi to see if increasing the digestible energy (DE) and/or the n-3 highly unsaturated fatty acid (n-3 HUFA) content of the feed would improve growth of fish raised in cool water. Increasing the DE content of the feed from 15 to 17 or 19 MJ kg(-1) while maintaining a constant protein to energy ratio in Experiment 1 brought about significant improvements in feed conversion ratio (FCR) (from 2.01 to 1.19) and daily growth coefficient (DGC; from 0.69 to 1.08%/day) for fish at 20 degrees C. For fish at 29 degrees C, improvements, while significant, were of a lesser magnitude: from 1.32 to 0.97 for FCR and from 3.24 to 3.65%/day for DGC. Increasing the absolute amount of dietary n-3 HUFA, expressed as the sum of eicosapentaenoic and docosahexaenoic fatty acids, from 0.5% to 2.0% in Experiment 2 improved DGC linearly and FCR curvilinearly for fish at 29 degrees C whereas at 20 degrees C, DGC was not affected while FCR improved slightly (from 1.83 to 1.68). Feed conversion ratio was optimized with a dietary n-3 HUFA of about 1.5%. Providing barramundi with a feed that is high in DE (viz 19 MJ kg(-1)) and a digestible protein to DE ratio of 22.5 g MJ(-1) is a practical strategy for improving the productivity of barramundi cultured in cool water whereas increasing dietary n-3 HUFA conferred very little additional benefit.

Improving crustacean aquaculture production efficiencies through androgenic gland manipulation

The investigation of androgenic gland manipulations a mean for creating an all female P monodon populations.

Intraguild relationships between sympatric predators exposed to lethal control: predator manipulation experiments

INTRODUCTION:Terrestrial top-predators are expected to regulate and stabilise food webs through their consumptive and non-consumptive effects on sympatric mesopredators and prey. The lethal control of top-predators has therefore been predicted to inhibit top-predator function, generate the release of mesopredators and indirectly harm native fauna through trophic cascade effects. Understanding the outcomes of lethal control on interactions within terrestrial predator guilds is important for zoologists, conservation biologists and wildlife managers. However, few studies have the capacity to test these predictions experimentally, and no such studies have previously been conducted on the eclectic suite of native and exotic, mammalian and reptilian taxa we simultaneously assess. We conducted a series of landscape-scale, multi-year, manipulative experiments at nine sites spanning five ecosystem types across the Australian continental rangelands to investigate the responses of mesopredators (red foxes, feral cats and goannas) to contemporary poison-baiting programs intended to control top-predators (dingoes) for livestock protection.RESULT:Short-term behavioural releases of mesopredators were not apparent, and in almost all cases, the three mesopredators we assessed were in similar or greater abundance in unbaited areas relative to baited areas, with mesopredator abundance trends typically either uncorrelated or positively correlated with top-predator abundance trends over time. The exotic mammals and native reptile we assessed responded similarly (poorly) to top-predator population manipulation. This is because poison baits were taken by multiple target and non-target predators and top-predator populations quickly recovered to pre-control levels, thus reducing the overall impact of baiting on top-predators and averting a trophic cascade.CONCLUSIONS:These results are in accord with other predator manipulation experiments conducted worldwide, and suggest that Australian populations of native prey fauna at lower trophic levels are unlikely to be negatively affected by contemporary dingo control practices through the release of mesopredators. We conclude that contemporary lethal control practices used on some top-predator populations do not produce the conditions required to generate positive responses from mesopredators. Functional relationships between sympatric terrestrial predators may not be altered by exposure to spatially and temporally sporadic application of non-selective lethal control.

Fuel manipulation with herbicide treatments to reduce fire hazard in young pine (Pinus elliottii × P. caribaea) plantations in south-east Queensland, Australia

Wildfire represents a major risk to pine plantations. This risk is particularly great for young plantations (generally less than 10 m in height) where prescribed fire cannot be used to manipulate fuel biomass, and where flammable grasses are abundant in the understorey. We report results from a replicated field experiment designed to determine the effects of two rates of glyphosate (450 g L–1) application, two extents of application (inter-row only and inter-row and row) with applications being applied once or twice, on understorey fine fuel biomass, fuel structure and composition in south-east Queensland, Australia. Two herbicide applications (~9 months apart) were more effective than a once-off treatment for reducing standing biomass, grass continuity, grass height, percentage grass dry weight and the density of shrubs. In addition, the 6-L ha–1 rate of application was more effective than the 3-L ha–1 rate of application in periodically reducing grass continuity and shrub density in the inter-rows and in reducing standing biomass in the tree rows, and application in the inter-rows and rows significantly reduced shrub density relative to the inter-row-only application. Herbicide treatment in the inter-rows and rows is likely to be useful for managing fuels before prescribed fire in young pine plantations because such treatment minimised tree scorch height during prescribed burns. Further, herbicide treatments had no adverse effects on plantation trees, and in some cases tree growth was enhanced by treatments. However, the effectiveness of herbicide treatments in reducing the risk of tree damage or mortality under wildfire conditions remains untested.

Sympatric prey responses to lethal top-predator control: predator manipulation experiments

Introduction Many prey species around the world are suffering declines due to a variety of interacting causes such as land use change, climate change, invasive species and novel disease. Recent studies on the ecological roles of top-predators have suggested that lethal top-predator control by humans (typically undertaken to protect livestock or managed game from predation) is an indirect additional cause of prey declines through trophic cascade effects. Such studies have prompted calls to prohibit lethal top-predator control with the expectation that doing so will result in widespread benefits for biodiversity at all trophic levels. However, applied experiments investigating in situ responses of prey populations to contemporary top-predator management practices are few and none have previously been conducted on the eclectic suite of native and exotic mammalian, reptilian, avian and amphibian predator and prey taxa we simultaneously assess. We conducted a series of landscape-scale, multi-year, manipulative experiments at nine sites spanning five ecosystem types across the Australian continental rangelands to investigate the responses of sympatric prey populations to contemporary poison-baiting programs intended to control top-predators (dingoes) for livestock protection. Results Prey populations were almost always in similar or greater abundances in baited areas. Short-term prey responses to baiting were seldom apparent. Longer-term prey population trends fluctuated independently of baiting for every prey species at all sites, and divergence or convergence of prey population trends occurred rarely. Top-predator population trends fluctuated independently of baiting in all cases, and never did diverge or converge. Mesopredator population trends likewise fluctuated independently of baiting in almost all cases, but did diverge or converge in a few instances. Conclusions These results demonstrate that Australian populations of prey fauna at lower trophic levels are typically unaffected by top-predator control because top-predator populations are not substantially affected by contemporary control practices, thus averting a trophic cascade. We conclude that alteration of current top-predator management practices is probably unnecessary for enhancing fauna recovery in the Australian rangelands. More generally, our results suggest that theoretical and observational studies advancing the idea that lethal control of top-predators induces trophic cascades may not be as universal as previously supposed.

Sterochemical studies on cyclic peptides-VIII. Conformational analysis of hydrogen bonded cyclohexaglycyl molecule with a centre of inversion symmetry

A study on the conformational aspects of cyclo-hexaglycyl having inversion symmetry has been made. The cyclic backbone has been assumed to have two internal 4→1 types of NH... O hydrogen bonds. This molecule has been found to take up two types of conformations designated asA* andB* having nearly the same energy values. The theoretical conformations have been compared with the conformations of cyclohexaglycyl hemihydrate observed in the crystal structure. Two molecules with an approximate inversion symmetry are close to the conformation of the typeB* and two other molecules with exact inversino symmetry correspond nearly to the typesB* andA*. comparison with the theoretically possible conformations of cyclohexaglycyl molecule with 2-fold symmetry has been made. The preference of inversion symmetry and preferred ranges ofψ for glycyl molecules is discussed.

Evaluation of methods and applications for behavioural profiling of transgenic mice

During the last 10-15 years interest in mouse behavioural analysis has evolved considerably. The driving force is development in molecular biological techniques that allow manipulation of the mouse genome by changing the expression of genes. Therefore, with some limitations it is possible to study how genes participate in regulation of physiological functions and to create models explaining genetic contribution to various pathological conditions. The first aim of our study was to establish a framework for behavioural phenotyping of genetically modified mice. We established comprehensive battery of tests for the initial screening of mutant mice. These included tests for exploratory and locomotor activity, emotional behaviour, sensory functions, and cognitive performance. Our interest was in the behavioural patterns of common background strains used for genetic manipulations in mice. Additionally we studied the behavioural effect of sex differences, test history, and individual housing. Our findings highlight the importance of careful consideration of genetic background for analysis of mutant mice. It was evident that some backgrounds may mask or modify the behavioural phenotype of mutants and thereby lead to false positive or negative findings. Moreover, there is no universal strain that is equally suitable for all tests, and using different backgrounds allows one to address possible phenotype modifying factors. We discovered that previous experience affected performance in several tasks. The most sensitive traits were the exploratory and emotional behaviour, as well as motor and nociceptive functions. Therefore, it may be essential to repeat some of the tests in naïve animals for assuring the phenotype. Social isolation for a long time period had strong effects on exploratory behaviour, but also on learning and memory. All experiments revealed significant interactions between strain and environmental factors (test history or housing condition) indicating genotype-dependent effects of environmental manipulations. Several mutant line analyses utilize this information. For example, we studied mice overexpressing as well as those lacking extracellular matrix protein heparin-binding growth-associated molecule (HB-GAM), and mice lacking N-syndecan (a receptor for HB-GAM). All mutant mice appeared to be fertile and healthy, without any apparent neurological or sensory defects. The lack of HB-GAM and N-syndecan, however, significantly reduced the learning capacity of the mice. On the other hand, overexpression of HB-GAM resulted in facilitated learning. Moreover, HB-GAM knockout mice displayed higher anxiety-like behaviour, whereas anxiety was reduced in HB-GAM overexpressing mice. Changes in hippocampal plasticity accompanied the behavioural phenotypes. We conclude that HB-GAM and N-syndecan are involved in the modulation of synaptic plasticity in hippocampus and play a role in regulation of anxiety- and learning-related behaviour.

Development of a robust framework for an outdoor mobile manipulation UAV

There is a growing interest to autonomously collect or manipulate objects in remote or unknown environments, such as mountains, gullies, bush-land, or rough terrain. There are several limitations of conventional methods using manned or remotely controlled aircraft. The capability of small Unmanned Aerial Vehicles (UAV) used in parallel with robotic manipulators could overcome some of these limitations. By enabling the autonomous exploration of both naturally hazardous environments, or areas which are biologically, chemically, or radioactively contaminated, it is possible to collect samples and data from such environments without directly exposing personnel to such risks. This paper covers the design, integration, and initial testing of a framework for outdoor mobile manipulation UAV. The framework is designed to allow further integration and testing of complex control theories, with the capability to operate outdoors in unknown environments. The results obtained act as a reference for the effectiveness of the integrated sensors and low-level control methods used for the preliminary testing, as well as identifying the key technologies needed for the development of an outdoor capable system.

Heparin-binding growth-associated molecule (HB-GAM) in activity-dependent neuronal plasticity in hippocampus

Cell adhesion and extracellular matrix (ECM) molecules play a significant role in neuronal plasticity both during development and in the adult. Plastic changes in which ECM components are implicated may underlie important nervous system functions, such as memory formation and learning. Heparin-binding growthassociated molecule (HB-GAM, also known as pleiotrophin), is an ECM protein involved in neurite outgrowth, axonal guidance and synaptogenesis during perinatal period. In the adult brain HB-GAM expression is restricted to the regions which display pronounced synaptic plasticity (e.g., hippocampal CA3-CA1 areas, cerebral cortex laminae II-IV, olfactory bulb). Expression of HB-GAM is regulated in an activity-dependent manner and is also induced in response to neuronal injury. In this work mutant mice were used to study the in vivo function of HB-GAM and its receptor syndecan-3 in hippocampal synaptic plasticity and in hippocampus-dependent behavioral tasks. Phenotypic analysis of HBGAM null mutants and mice overexpressing HB-GAM revealed that opposite genetic manipulations result in reverse changes in synaptic plasticity as well as behavior in the mutants. Electrophysiological recordings showed that mice lacking HB-GAM have an increased level of long-term potentiation (LTP) in the area CA1 of hippocampus and impaired spatial learning, whereas animals with enhanced level of HB-GAM expression have attenuated LTP, but outperformed their wild-type controls in spatial learning. It was also found that GABA(A) receptor-mediated synaptic transmission is altered in the transgenic mice overexpressing HB-GAM. The results suggest that these animals have accentuated hippocampal GABAergic inhibition, which may contribute to the altered glutamatergic synaptic plasticity. Structural studies of HB-GAM demonstrated that this protein belongs to the thrombospondin type I repeat (TSR) superfamily and contains two β-sheet domains connected by a flexible linker. It was found that didomain structure is necessary for biological activity of HB-GAM and electrophysiological phenotype displayed by the HB-GAM mutants. The individual domains displayed weaker binding to heparan sulfate and failed to promote neurite outgrowth as well as affect hippocampal LTP. Effects of HB-GAM on hippocampal synaptic plasticity are believed to be mediated by one of its (co-)receptor molecules, namely syndecan-3. In support of that, HB-GAM did not attenuate LTP in mice deficient in syndecan-3 as it did in wild-type controls. In addition, syndecan-3 knockout mice displayed electrophysiological and behavioral phenotype similar to that of HB-GAM knockouts (i.e. enhanced LTP and impaired learning in Morris water-maze). Thus HB-GAM and syndecan-3 are important modulators of synaptic plasticity in hippocampus and play a role in regulation of learning-related behavior.