Isofagomine increases lysosomal delivery of exogenous glucocerebrosidase

Intravenous enzyme replacement therapy (ERT) with purified glucocerebrosidase (GLA) leads to significant improvement of the clinical manifestations in patients with Type 1 Gaucher disease. However, the high doses required, slow response and inability to recover most of the infused enzyme in the target tissues may be attributed to losses occurring during transit en route to the lysosome. Preincubation of GLA with isofagomine (IFG), a slow-binding inhibitor, significantly increased stability of the enzyme to heat, neutral pH and denaturing agents in vitro. Preincubation of GLA with isofagomine prior to uptake by cultured cells results in increased intracellular enzyme activity accompanied by an increase in enzyme protein suggesting that reduced denaturation of GLA in the presence of isofagomine leads to a decrease in the degradation of the enzyme after internalization. Preincubation of GLA with slow-binding inhibitors before infusion may improve the effectiveness of ERT for Gaucher disease.     

Action spectra of phototactic responses of the flea beetle, Phyllotreta striolata

Abstract.  Adult flea beetles, Phyllotreta striolata , show a strong positive phototactic response. The action spectrum of phototaxis of dark-adapted beetles was measured with minimal required light intensity between the wavelength range of 300 nm and 600 nm. Male and female flea beetles showed identical phototacitc behaviours. The beetles were most sensitive to light with peak wavelengths between 350 nm and 430 nm in the morning. In the afternoon and evening, the sensitivity to wavelengths shorter than 430 nm decreased, but they remained most sensitive to 430 nm. These results suggest that changes in sensitivity of the photoreceptors or nervous integration influence the phototactic responses, and that the blue wavelengths are more attractive than others.     

Modulation of haloperidol induced electrophysiological alterations on cardiac action potential by various risk factors and gender difference

Haloperidol (HPL), well known antipsychotic drug can induce a marked QT prolongation and polymorphic arrhythmias. In this study we evaluated the influence of various induced risk factors such as electrolyte imbalance (hypokalemia and hypomagnesemia), gender difference, low pacing frequency, ischemia reperfusion insult on electrophysiological effect by haloperidol on electrically driven action potentials recorded from guinea pig papillary muscle. The doses of HPL ranging from 1 to 16 μM were used in this investigation. Action potentials (APs) were elicited electrically and recorded by classical microelectrode technique. HPL caused dose dependent prolongation of APD₉₀ the final stage of repolarization, increased triangulation, and led into dispersion of action potential, conduction delay and conduction block. Magnitude of the effect of haloperidol was amplified significantly by most of the risk factors. Among the various risk factors, electrolyte imbalance (hypokalemia, hypomagnesemia) caused more amplification of HPL effect. Most of the risk factors amplified prolongation of APD₉₀ by HPL. This effect is mainly due to the influence of these electrolytes and sex hormone on various ion channels involved in the repolarization phase of cardiac AP. This is the first report which provides an experimental evidence of amplification of electrophysiological effects of HPL in the presence of various risk factors.     

A novel insight into the cost–benefit model for the evolution of botanical carnivory

Background The cost–benefit model for the evolution of botanical carnivory provides a conceptual framework for interpreting a wide range of comparative and experimental studies on carnivorous plants. This model assumes that the modified leaves called traps represent a significant cost for the plant, and this cost is outweighed by the benefits from increased nutrient uptake from prey, in terms of enhancing the rate of photosynthesis per unit leaf mass or area (A_N) in the microsites inhabited by carnivorous plants.Scope This review summarizes results from the classical interpretation of the cost–benefit model for evolution of botanical carnivory and highlights the costs and benefits of active trapping mechanisms, including water pumping, electrical signalling and accumulation of jasmonates. Novel alternative sequestration strategies (utilization of leaf litter and faeces) in carnivorous plants are also discussed in the context of the cost–benefit model.Conclusions Traps of carnivorous plants have lower A_N than leaves, and the leaves have higher A_N after feeding. Prey digestion, water pumping and electrical signalling represent a significant carbon cost (as an increased rate of respiration, R_D) for carnivorous plants. On the other hand, jasmonate accumulation during the digestive period and reprogramming of gene expression from growth and photosynthesis to prey digestion optimizes enzyme production in comparison with constitutive secretion. This inducibility may have evolved as a cost-saving strategy beneficial for carnivorous plants. The similarities between plant defence mechanisms and botanical carnivory are highlighted.     

The use of digital video recorders in pollination biology

1. Digital video recording (DVR) devices, such as the GoPro Hero, have the potential to greatly benefit pollination ecology, but the advantages of digitally recording pollinator activity over direct human observation have not been formally assessed. 2. Two plant taxa, Lavandula angustifolia and Canna ‘sp.’, with differing floral morphology, were used to compare the value of DVR and direct observations in estimating honeybee (Apis mellifera) visitation, flower density and number of flowers visited per foraging bout. 3. The two methods yielded identical results when observing the structurally simple L. angustifolia at both high (10.54 ± 0.52 per plant) and low honeybee density (2.24 ± 0.20 per plant). However, DVR underestimated the number of flowers scored in the field of view (28.7 ± 1.8 direct vs. 22.7 ± 0.9 DVR), the number of honeybees observed (5.3 ± 0.8 direct vs. 3.7 ± 0.7 DVR) and the number of flowers visited during foraging bouts (8.3 ± 1.2 direct vs. 5.5 ± 1.0 DVR) on the more complex Canna ‘sp.’ 4. It is concluded that portable weatherproof DVR devices such as the GoPro Hero are valuable tools for pollination biologists, allowing a single researcher to make simultaneous observations of multiple plants in one or more sites, whilst also allowing the footage to be reviewed. However, DVR devices are limited by their depth and field of view when target plants are large or structurally complex.     

Cellulase Hydrolysis of Cotton Cellulose: The Effects of Mechanical Action,Enzyme Concentration and Dyed Substrates

Experiments with dyed and undyed cotton, using different cellulose concentration and with or with out mechanical action showed a high effect of those factors. The process with mechanical action have a higher weight-loss. Dyed cotton with vat and sulfur dyes have almost die same weight-loss than undyed cotton, but on reactive dyed cotton the cellulase hydrolysis is shorter. It was also verified a decrease of hydrolysis extent with an increase of the reactive dye concentration on the cotton substrate. Some synergism due to the enzyme concentration was apparently observed on the changes of the length of the leaving sugars.     

Antimicrobial evaluation and action mechanism of pyridinium-decorated 1,4-pentadien-3-one derivatives

A type of pyridinium-decorated 1,4-pentadien-3-one derivatives possessing flexible alkyls were designed and synthesized by integrating the key scaffolds of pyridinium cations and 1,4-pentadien-3-one skeleton in a single molecular architecture. Antimicrobial bioassays indicated that some of the target molecules exerted considerable bioactivities against six phytopathogenic strains, especially for Xanthomonas oryzae pv. oryzae, the minimal EC₅₀ value can reach to 0.504?µg/mL. A plausible action mechanism for this kind of compounds was proposed and confirmed by employing fluorescent spectroscopy, fluorescence microscopy, and scanning electron microscopy. We anticipated that this finding can promote high-efficient lead compounds discovery in the research of antimicrobial chemotherapy.     

Amlexanox provides a potential therapy for nonsense mutations in the lysosomal storage disorder Aspartylglucosaminuria

Aspartylglucosaminuria (AGU) is a lysosomal storage disorder caused by mutations in the gene for aspartylglucosaminidase (AGA). This enzyme participates in glycoprotein degradation in lysosomes. AGU results in progressive mental retardation, and no curative therapy is currently available. We have here characterized the consequences of AGA gene mutations in a compound heterozygous patient who exhibits a missense mutation producing a Ser72Pro substitution in one allele, and a nonsense mutation Trp168X in the other. Ser72 is not a catalytic residue, but is required for the stabilization of the active site conformation. Thus, Ser72Pro exchange impairs the autocatalytic activation of the AGA precursor, and results in a considerable reduction of the enzyme activity and in altered AGA precursor processing. Betaine, which can partially rescue the AGA activity in AGU patients carrying certain missense mutations, turned out to be ineffective in the case of Ser72Pro substitution. The Trp168X nonsense allele results in complete lack of AGA polypeptide due to nonsense-mediated decay (NMD) of the mRNA. Amlexanox, which inhibits NMD and causes a translational read-through, facilitated the synthesis of a full-length, functional AGA protein from the nonsense allele. This could be demonstrated as presence of the AGA polypeptide and increased enzyme activity upon Amlexanox treatment. Furthermore, in the Ser72Pro/Trp168X expressing cells, Amlexanox induced a synergistic increase in AGA activity and polypeptide processing due to enhanced processing of the Ser72Pro polypeptide. Our data show for the first time that Amlexanox might provide a valid therapy for AGU.