Effects of Delta9-tetrahydrocannabivarin on [35S]GTPgammaS binding in mouse brain cerebellum and piriform cortex membranes

BACKGROUND AND PURPOSE: We have recently shown that the phytocannabinoid Delta9-tetrahydrocannabivarin (Delta9-THCV) and the CB1 receptor antagonist AM251 increase inhibitory neurotransmission in mouse cerebellum and also exhibit anticonvulsant activity in a rat piriform cortical (PC) model of epilepsy. Possible mechanisms underlying cannabinoid actions in the CNS include CB1 receptor antagonism (by displacing endocannabinergic tone) or inverse agonism at constitutively active CB1 receptors. Here, we investigate the mode of cannabinoid action in [35S]GTPgammaS binding assays. EXPERIMENTAL APPROACH: Effects of Delta9-THCV and AM251 were tested either alone or against WIN55,212-2-induced increases in [35S]GTPgammaS binding in mouse cerebellar and PC membranes. Effects on non-CB receptor expressing CHO-D2 cell membranes were also investigated. KEY RESULTS :Delta9-THCV and AM251 both acted as potent antagonists of WIN55,212-2-induced increases in [35S]GTPgammaS binding in cerebellar and PC membranes (Delta9-THCV: pA2=7.62 and 7.44 respectively; AM251: pA2=9.93 and 9.88 respectively). At micromolar concentrations, Delta9-THCV or AM251 alone caused significant decreases in [35S]GTPgammaS binding; Delta9-THCV caused larger decreases than AM251. When applied alone in CHO-D2 membranes, Delta9-THCV and AM251 also caused concentration-related decreases in G protein activity. CONCLUSIONS AND IMPLICATIONS: Delta9-THCV and AM251 act as CB1 receptors antagonists in the cerebellum and PC, with AM251 being more potent than Delta9-THCV in both brain regions. Individually, Delta9-THCV or AM251 exhibited similar potency at CB1 receptors in the cerebellum and the PC. At micromolar concentrations, Delta9-THCV and AM251 caused a non-CB receptor-mediated depression of basal [35S]GTPgammaS binding.

Beurling zeta functions, generalised primes, and fractal membranes

We study generalised prime systems P (1 < p(1) <= p(2) <= ..., with p(j) is an element of R tending to infinity) and the associated Beurling zeta function zeta p(s) = Pi(infinity)(j=1)(1 - p(j)(-s))(-1). Under appropriate assumptions, we establish various analytic properties of zeta p(s), including its analytic continuation, and we characterise the existence of a suitable generalised functional equation. In particular, we examine the relationship between a counterpart of the Prime Number Theorem (with error term) and the properties of the analytic continuation of zeta p(s). Further we study 'well-behaved' g-prime systems, namely, systems for which both the prime and integer counting function are asymptotically well-behaved. Finally, we show that there exists a natural correspondence between generalised prime systems and suitable orders on N-2. Some of the above results are relevant to the second author's theory of 'fractal membranes', whose spectral partition functions are given by Beurling-type zeta functions, as well as to joint work of that author and R. Nest on zeta functions attached to quasicrystals.

Chlorine tolerant, multilayer reverse-somosis membranes with high permeate flux and high salt rejection

A new class of high molecular weight polyethersulfone ionomers is described in which the ionic content can be varied, at will, over a very wide and fully-controllable range. A novel type of coating process enables these materials to be deposited from alcohol-type solvents as cohesive but very thin (50 – 250 nm) films on porous support-membranes, giving high-flux membranes (3.3 – 5.0 L m-2 h-1 bar-1) with very good, though not outstanding salt rejection (typically 92 - 96%). A secondary layer, of formaldehyde-cross-linked polyvinyl alcohol, can be deposited from aqueous solution on the surface of the ionomer membrane, and this layer increases salt rejection to greater than 99% without serious loss of water permeability. The final multi-layer membrane shows excellent chlorine tolerance in reverse-osmosis operation.

Pervaporation dehydration of isopropyl alcohol with NaY zeolite incorvorated hybrid membranes

With a solution technique, NaY zeolite incorporated, tetraethylorthosilicate-crosslinked poly(vinyl alcohol) membranes were prepared. The resulting membranes were tested for their ability to separate isopropyl alcohol/water mixtures by pervaporation in the temperature range of 30-50 degrees C. The effects of the zeolite content and feed composition on the pervaporation performance of the membranes were investigated. The experimental results demonstrated that both flux and selectivity increased simultaneously with increasing zeolite content in the membranes. This was explained on the basis of the enhancement of hydrophilicity, selective adsorption, and establishment of a molecular sieving action attributed to the creation of pores in the membrane matrix. The membrane containing 15 mass % zeolite exhibited the highest separation selectivity of 3991 with a flux of 5.39 X 10(-2) kg/m(2) h with 10 mass % water in the feed at 30 degrees C. The total flux and flux of water were close to each other for almost all the studied membranes, and this suggested that the membranes could be used effectively to break the azeotropic point of water/isopropyl alcohol mixtures to remove a small amount of water from isopropyl alcohol. From the temperature-dependent diffusion and permeation values, the Arrhenius activation parameters were estimated. The activation energy values obtained for water were significantly lower than those for isopropyl alcohol, and this suggested that the developed membranes had a higher separation efficiency for water/isopropyl alcohol systems. The activation energy values for total permeation and water permeation were found to be almost the same for all the membranes, and this signified that coupled transport was minimal because of the highly selective nature of the membranes. Positive heat of sorption values were observed in all the membranes, and this suggested that Henry's mode of sorption was predominant. (c) 2008 Wiley Periodicals, lnc.

Microblock ionomers: a new concept in high temperature, swelling-resistant membranes for PEM fuel cells

A novel series of polyaromatic ionomers with similar equivalent weights but very different sulphonic acid distributions along the ionomer backbone has been designed and prepared. By synthetically organising the sequence-distribution so that it consists of fully defined ionic segments (containing singlets, doublets or quadruplets of sulphonic acid groups) alternating strictly with equally well-defined nonionic spacer segments, a new class of polymers which may be described as microblock ionomers has been developed. These materials exhibit very different properties and morphologies from analogous randomly substituted systems. Progressively extending the nonionic spacer length in the repeat unit (maintaining a constant equivalent weight by increasing the degree of sulphonation. of the ionic segment) leads to an increasing degree of nanophase separation between hydrophilic and hydrophobic domains in these materials. Membranes cast from ionomers with the more highly phase-separated morphologies show significantly higher onset temperatures for uncontrolled swelling in water. This new type of ionomer design has enabled the fabrication of swelling-resistant hydrocarbon membranes, suitable for fuel cell operation, with very much higher ion exchange capacities (>2 meq g(-1)) than those previously reported in the literature. When tested in a fuel cell at high temperature (120 degrees C) and low relative humidity (35% RH), the best microblock membrane matched the performance of Nafion 112. Moreover, comparative low load cycle testing of membrane -electrode assemblies suggests that the durability of the new membranes under conditions of high temperature and low relative humidity is superior to that of conventional perfluorinated materials.

Ion-conducting polymers and membranes comprising them

An ion-conducting polymer wherein at least 80% of the repeat units comprise an ion-conducting region and a spacer region is disclosed. The ion-conducting region has an aromatic backbone of one or more aromatic groups, wherein at least one ion-conducting functional group is attached to each aromatic group. The spacer region has an aromatic backbone of at least four aromatic groups, wherein no ion-conducting functional groups are attached to the aromatic backbone. The polymer is suitable for use as a fuel cell membrane, and can be incorporated into membrane electrode assemblies.

Carbohydrate-based anti-adhesive inhibition of Vibrio cholerae toxin binding to GM1-OS immobilized into artificial planar lipid membranes

We have studied 'food grade' sialyloligosaccharides (SOS) as anti-adhesive drugs or receptor analogues, since the terminal sialic acid residue has already been shown to contribute significantly to the adhesion and pathogenesis of the Vibrio cholerae toxin (Ctx). GM1-oligosaccharide (GM1-OS) was immobilized into a supporting POPC lipid bilayer onto a surface plasmon resonance (SPR) chip, and the interaction between uninhibited Ctx and GM1-OS-POPC was measured. SOS inhibited 94.7% of the Ctx binding to GM1-OS-POPC at 10 mg/mL. The SOS EC50 value of 5.521 mg/mL is high compared with 0.2811 mu g/mL (182.5 pM or 1.825 x 10(-10) M) for GM1-OS. The commercially available sialyloligosaccharide (SOS) mixture Sunsial E (R) is impure, containing one monosialylated and two disialylated oligosaccharides in the ratio 9.6%. 6.5% and 17.5%, respectively, and 66.4% protein. However, these inexpensive food-grade molecules are derived from egg yolk and could be used to fortify conventional food additives, by way of emulsifiers, sweeteners and/or preservatives. The work further supports our hypothesis that SOS could be a promising natural anti-adhesive glycomimetic against Ctx and prevent subsequent onset of disease. (C) 2009 Elsevier Ltd. All rights reserved

Selective separation of the major whey proteins using ion exchange membranes

Synthetic microporous membranes with functional groups covalently attached were used to selectively separate beta-lactoglobulin, BSA, and alpha-lactalbumin from rennet whey. The selectivity and membrane performance of strong (quaternary ammonium) and weak (diethylamine) ion-exchange membranes were studied using breakthrough curves, measurement of binding capacity, and protein composition of the elution fraction to determine the binding behavior of each membrane. When the weak and strong anion exchange membranes were saturated with whey, they were both selective primarily for beta-lactoglobulin with less than 1% of the eluate consisting of alpha-lactalbumin or BSA. The binding capacity of a pure alpha-lactoglobulin solution was in excess of 1.5 mg/cm(2) of membrane. This binding capacity was reduced to approximately 1.2 mg/cm(2) when using a rennet whey solution (pH 6.4). This reduction in protein binding capacity can be explained by both the competitive effects of other whey proteins and the effect of ions present in whey. Using binary solution breakthrough curves and rennet whey breakthrough curves, it was shown that alpha-lactalbumin and BSA were displaced from the strong and weak anion exchange membranes by beta-lactoglobulin. Finally, the effect of ionic strength on the binding capacity of individual proteins for each membrane was determined by comparing model protein solutions in milk permeate (pH 6.4) and a 10 mM sodium phosphate buffer (pH 6.4). Binding capacities of beta-lactoglobulin, alpha-lactalbumin, and BSA in milk permeate were reduced by as much as 50%. This reduction in capacity coupled with the low binding capacity of current ion exchange membranes are 2 serious considerations for selectively separating complex and concentrated protein solutions.

Liposomes and skin: From drug delivery to model membranes

The early eighties saw the introduction of liposomes as skin drug delivery systems, initially promoted primarily for localised effects with minimal systemic delivery. Subsequently, a novel ultradeformable vesicular system (termed "Transfersomes" by the inventors) was reported for transdermal delivery with an efficiency similar to subcutaneous injection. Further research illustrated that the mechanisms of liposome action depended on the application regime and the vesicle composition and morphology. Ethical, health and supply problems with human skin have encouraged researchers to use skin models. 'IYaditional models involved polymer membranes and animal tissue, but whilst of value for release studies, such models are not always good mimics for the complex human skin barrier, particularly with respect to the stratum corneal intercellular lipid domains. These lipids have a multiply bilayered organization, a composition and organization somewhat similar to liposomes, Consequently researchers have used vesicles as skin model membranes. Early work first employed phospholipid liposomes and tested their interactions with skin penetration enhancers, typically using thermal analysis and spectroscopic analyses. Another approach probed how incorporation of compounds into liposomes led to the loss of entrapped markers, analogous to "fluidization" of stratum corneum lipids on treatment with a penetration enhancer. Subsequently scientists employed liposomes formulated with skin lipids in these types of studies. Following a brief description of the nature of the skin barrier to transdermal drug delivery and the use of liposomes in drug delivery through skin, this article critically reviews the relevance of using different types of vesicles as a model for human skin in permeation enhancement studies, concentrating primarily on liposomes after briefly surveying older models. The validity of different types of liposome is considered and traditional skin models are compared to vesicular model membranes for their precision and accuracy as skin membrane mimics. (c) 2008 Elsevier B.V. All rights reserved.

Biomimetic triblock copolymer membranes: from aqueous solutions to solid supports

In the present paper, we studied the preparation of biomimetic triblock copolymer (ABA) membranes in aqueous solution and their deposition into solid supports. The self-assembly structures of the ABA in aqueous solution was investigated by using optical microscopy, dynamic light scattering, electron microscopy (EM) and SAXS. Spherical and tubular polymersomes were found at the highest concentrations investigated. The mechanism of deposition on solid supports (mica and glass) was elucidated by using atomic force microscopy (AFM). The deposition results in the formation of a uniform defect-free membrane at suitable polymer concentrations.

Amphoteric nano-, micro-, and macrogels, membranes, and thin films

This review describes the state-of the-art of nano-, micro- and macrogels, membranes, micro- and nanocapsules, as well as multilayered thin films exhibiting amphoteric character. The synthetic strategies and physicochemical properties of amphoteric materials are outlined in light of the stimuli-responsive behavior and their potential application in nanotechnology, biotechnology and medicine.

Breathable roofing membranes and bats: interactions, outcomes and predictions

In order to achieve sustainability it is necessary to balance the interactions between the built and natural environment. Biodiversity plays an important part towards sustainability within the built environment, especially as the construction industry comes under increasing pressure to take ecological concerns into account. Bats constitute an important component of urban biodiversity and several species are now highly dependent on buildings, making them particularly vulnerable to anthropogenic and environmental changes. As many buildings suitable for use as bat roosts age, they often require re-roofing and traditional bituminous roofing felts are frequently being replaced with breathable roofing membranes (BRMs), which are designed to reduce condensation. Whilst the current position of bats is better in many respects than 30 years ago, new building regulations and modern materials, may substantially reduce the viability of existing roosts. At the same time building regulations require that materials be fit for purpose and with anecdotal evidence that both bats and BRMs may experience problems when the two interact, it is important to know what roost characteristics are essential for house dwelling bats and how these and BRMs may be affected. This paper reviews current literature and knowledge and considers the possible ways in which bats and BRMs may interact, how this could affect existing bat roosts within buildings and the implications for BRM service life predictions and warranties. It concludes that in order for the construction and conservation sectors to work together in solving this issue, a set of clear guidelines should be developed for use on a national level.

Double jeopardy: the potential for problems when bats interact with breathable roofing membranes in the United Kingdom

In order to reduce environmental impacts and achieve sustainability, it is important to balance the interactions between the built and natural environment. The construction industry is becoming more aware of ecological concerns and the importance that biodiversity and maintenance ecosystem services has for sustainability. Bats constitute an important component of urban biodiversity and several species in the UK are highly dependent on buildings, making them particularly vulnerable to anthropogenic and environmental changes. Many buildings suitable for use as bat roosts often require re-roofing as they age and traditional bituminous roofing felts are frequently being replaced with breathable roofing membranes (BRMs). In the UK new building regulations and modern materials may substantially reduce the viability of existing roosts, yet at thesame time building regulations require that materials be fit for purpose. Reports suggest that both bats and BRMs may experience problems when the two interact. Such information makes it important to understand how house dwelling bats and BRMs may be affected. This paper considers the possible ways in which bats and BRMs may interact, how this could affect existing bat roosts within buildings and the implications for BRM service life predictions and warranties. Keywords –Breathable Roofing Membranes, Bats in Buildings, Material Deterioration, Sustainability, Conservation, Biodiversit

Effect of "Pollutants" on the functionality of breathable roofing membranes in a bat roost

The performance of breathable roofing membranes (BRM’s) in buildings where bats roost have been investigated using experimental measurements and numerical simulations. Measurement techniques as outlined in BS EN ISO 12572 of membranes from manufacturers in its pure state and those that have been contaminated with bat urine, faeces and natural oils transmitted via fur because they were found in bat roost have been tested for their permeability functions. The findings from this shows that there are significant differences between the functionality of the pure samples compared to the contaminated samples, with an average of about 20-30% reduction in functionality. This paper integrates modelling techniques using a heat, air and mass software with a simulink interface on a Matlab platform to investigate the moisture transfer properties of the BRMs. The simulation results demonstrate high level of condensation formation when the BRM is contaminated as compared to when it is not.

The role of lipid composition on the interaction between a tryptophan-rich protein and model bacterial membranes

The interaction between tryptophan-rich puroindoline proteins and model bacterial membranes at the air-liquid interface has been investigated by FTIR spectroscopy, surface pressure measurements and Brewster angle microscopy. The role of different lipid constituents on the interactions between lipid membrane and protein was studied using wild type (Pin-b) and mutant (Trp44 to Arg44 mutant, Pin-bs) puroindoline proteins. The results show differences in the lipid selectivity of the two proteins in terms of preferential binding to specific lipid head groups in mixed lipid systems. Pin-b wild type was able to penetrate mixed layers of phosphatidylethanolamine (PE) and phosphatidylglycerol (PG) head groups more deeply compared to the mutant Pin-bs. Increasing saturation of the lipid tails increased penetration and adsorption of Pin-b wild type, but again the response of the mutant form differed. The results provide insight as to the role of membrane architecture, lipid composition and fluidity, on antimicrobial activity of proteins. Data show distinct differences in the lipid binding behavior of Pin-b as a result of a single residue mutation, highlighting the importance of hydrophobic and charged amino acids in antimicrobial protein and peptide activity.