Bicyclic nucleoside inhibitors of Varicella-Zoster virus: the effect of branching in the p-alkylphenyl side chain

Further to the discovery of bicyclic furanopyrimidine nucleoside analogues (BCNAs) as potent anti-VZV agents, a branched series of this family of compounds was synthesised. The aim was to study the impact of the geometry and steric hindrance in the side chain as well as lipophilic role of this moiety on biological activity. The results showed a detrimental effect of branching on antiviral activity, with a different magnitude depending on the position of branching in the side chain. This study again showed the importance of this moiety for biological activity, as well as the limited efficacy of the ClogP value as a tool for predicting the potency of BCNAs, while suggesting an alternative rationale behind the design of future series.     

Dynamic Service Discovery for Mobile Computing: Intelligent Agents Meet Jini in the Aether

The emergence of ad-hoc pervasive connectivity for devices based on Bluetooth-like systems provides a new way to create applications for mobile systems. We seek to realize ubiquitous computing systems based on the cooperation of autonomous, dynamic and adaptive components (hardware as well as software) which are located in vicinity of one another. In this paper we present this vision. We also describe a prototype system we have developed that implements parts of this vision – in particular a system that combines agent oriented and service oriented approaches and provides dynamic service discovery. We point out why existing systems such as Jini are not suited for this task, and how our system improves on them.     

Climate Change,Vector-borne Disease and Interdisciplinary Research: Social Science Perspectives on an Environment and Health Controversy

Over the last two decades, the science of climate change’s theoretical impacts on vector-borne disease has generated controversy related to its methodological validity and relevance to disease control policy. Critical social science analysis, drawing on science and technology studies and the sociology of social movements, demonstrates consistency between this controversy and the theory that climate change is serving as a collective action frame for some health researchers. Within this frame, vector-borne disease data are interpreted as a symptom of climate change, with the need for further interdisiplinary research put forth as the logical and necessary next step. Reaction to this tendency on the part of a handful of vector-borne disease specialists exhibits characteristics of academic boundary work aimed at preserving the integrity of existing disciplinary boundaries. Possible reasons for this conflict include the leadership role for health professionals and disciplines in the envisioned interdiscipline, and disagreements over the appropriate scale of interventions to control vector-borne diseases. Analysis of the competing frames in this controversy also allows identification of excluded voices and themes, such as international political economic explanations for the health problems in question. A logical conclusion of this analysis, therefore, is the need for critical reflection on environment and health research and policy to achieve integration with considerations of global health equity.     

棘腹蛙生物学特性及资源保护研究进展

棘腹蛙(Quasipaaboulengeri)是无尾目(Anura)叉舌蛙科(Dicroglossidae)棘胸蛙属的两栖动物。因其以农业和森林害虫为食且对生存环境要求高的特点,故有保护和监测环境的生态功能。但由于生态环境恶化和过度捕捉等原因,造成野生棘腹蛙数量急剧下降,被《中国脊椎动物红色名录》列为易危种。本文从棘腹蛙的习性、生存环境特征、系统进化、人工养殖和资源保护等方面进行了综述,为进一步研究棘腹蛙提供基础资料和理论依据。     

Luxury uptake of phosphorus by microalgae in waste stabilisation ponds: current understanding and future direction

There is a need to improve phosphorus removal for the tens of thousands of small communities around the world that currently rely on waste stabilisation ponds for their wastewater treatment. We now know that microalgae in pond systems are capable of accumulating phosphorus within their cells as polyphosphate in a process known as luxury uptake, but this knowledge has not yet been applied to engineer a new process to improve phosphorus removal. This paper summarises the current understanding of this mechanism, discusses the key factors influencing polyphosphate accumulation and provides future direction for research in this field. There have only been a limited number of studies that have focussed on luxury uptake of polyphosphate by microalgae in high phosphorus concentration environments such as those found in waste stabilisation pond systems. However, from this review it has been shown that the environmental factors which influence polyphosphate storage are the phosphate concentration, light intensity and temperature. Currently we are limited to a black box understanding of the bulk population and as a result future research needs to focus on a systematic evaluation of different microalgal genera under a wide range of environmental, biological and process variables in order to reveal the conditions needed to reliably trigger this phenomenon. This will then provide the basis for developing a new algal biotechnology optimised for luxury uptake of polyphosphate. While there are still several key questions that need to be answered there is potential for this to lead to a process which could be as significant to pond systems as the development of enhanced biological phosphorus removal was for the activated sludge process.     

Progress and prospects in the use of peroxidase to study cell development

The need for peroxidase purification is stressed as a requirement for comparative studies on isoenzyme structure as well as for detailed investigations on biosynthesis. A single cationic protein possessing the major peroxidase activity was isolated from the medium in which peanut cells had grown. The antibodies raised against this pure protein were employed as a probe to study the site of synthesis of peroxidase in the cell as well as the proportion of total synthesized protein which was peroxidase. Structural studies on the purified isoenzymes suggest the presence of three gene loci for peroxidase in cultured peanut cells. The results are discussed together with potential assays for induction of this enzyme and the relationship to cell development.     

Obtaining high sequence coverage in matrix-assisted laser desorption time-of-flight mass spectrometry for studies of protein modification: analysis of human serum albumin as a model

Several approaches were explored for obtaining high sequence coverage in protein modification studies performed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Human serum albumin (HSA, 66.5kDa) was used as a model protein for this work. Experimental factors considered in this study included the type of matrix used for MALDI-TOF MS, the protein digestion method, and the use of fractionation for peptide digests prior to MALDI-TOF MS analysis. A mixture of alpha-cyano-4-hydroxycinnamic acid and 2,5-dihydroxybenzoic acid was employed as the final matrix for HSA. When used with a tryptic digest, this gave unique information on only half of the peptides in the primary structure of HSA. However, the combined use of three enzyme digests based on trypsin, endoproteinase Lys-C, and endoproteinase Glu-C increased this sequence coverage to 72.8%. The use of a ZipTip column to fractionate peptides in these digests prior to analysis increased the sequence coverage to 97.4%. These conditions made it possible to examine unique peptides from nearly all of the structure of HSA and to identify specific modifications to this protein (e.g., glycation sites). For instance, Lys199 was confirmed as a glycation site on normal HSA, whereas Lys536 and Lys389 were identified as additional modification sites on minimally glycated HSA.     

Technological trends,global market,and challenges of bio-ethanol production

Ethanol use as a fuel additive or directly as a fuel source has grown in popularity due to governmental regulations and in some cases economic incentives based on environmental concerns as well as a desire to reduce oil dependency. As a consequence, several countries are interested in developing their internal market for use of this biofuel. Currently, almost all bio-ethanol is produced from grain or sugarcane. However, as this kind of feedstock is essentially food, other efficient and economically viable technologies for ethanol production have been evaluated. This article reviews some current and promising technologies for ethanol production considering aspects related to the raw materials, processes, and engineered strains development. The main producer and consumer nations and future perspectives for the ethanol market are also presented. Finally, technological trends to expand this market are discussed focusing on promising strategies like the use of microalgae and continuous systems with immobilized cells.     

Strigolactones, signals for parasitic plants and arbuscular mycorrhizal fungi

Although strigolactones play a critical role as rhizospheric signaling molecules for the establishment of arbuscular mycorrhizal (AM) symbiosis and for seed germination of parasitic weeds, scarce data are available about interactions between AM fungi and strigolactones. In the present work, we present background data on strigolactones from studies on their seed germination activity on the parasitic weeds Orobanche and Striga, the importance of nitrogen and phosphorus for this seed germination activity, and what this could mean for AM fungi. We also present results on the susceptibility of plants to AM fungi and the possible involvement of strigolactones in this AM susceptibility and discuss the role of strigolactones for the formation and the regulation of the AM symbiosis as well as the possible implication of these compounds as plant signals in other soil-borne plant–microbe interactions.     

Low-frequency sonophoresis: a noninvasive method of drug delivery and diagnostics

Transdermal drug delivery offers an attractive alternative to injections and oral medications. However, applications of transdermal drug delivery are limited to only a few drugs as a result of low skin permeability. Application of low-frequency ultrasound enhances skin permeability, a phenomenon referred to as low-frequency sonophoresis. In this method, a short application of ultrasound is used to permeabilize skin for a prolonged period of time. During this period, ultrasonically permeabilized skin may be utilized for drug delivery. In addition, a sample of interstitial fluid or its components may be extracted through permeabilized skin for diagnostic applications. In this paper, we report our in vivo studies that demonstrate the principles of both of these concepts. Detailed studies on drug delivery are performed using inulin and mannitol as model drugs. Studies on diagnostics are performed using glucose as a model analyte. Applications of this technology to drug delivery and diagnostics are discussed.     

Soil structure formation and management effects on gas emission

The aim of this paper is to clarify the effect of soil management and thus also of soil aggregation on physical and chemical properties of structured soils both on a bulk soil scale, for single aggregates, as well as for homogenized material. Aggregate formation and aggregate strength depend on swelling and shrinkage processes and on biological activity and kinds of organic exudates as well as on the intensity, number and time of swelling and drying events. Thus, soil management like conventional or conservation tillage alter not only the mechanical strength but also the pore continuity and the hydraulic, gas and heat fluxes, and also alter the accessibility of exchange places for nutrients and for carbon storage (global change aspects). The possibility to predict physical properties on these various scales depends on the rigidity of the pore system. In general this rigidity depends on the above-mentioned physical and chemical processes both with respect to intensity and frequency, which again are linked to the soil management systems.     

La chronologie du Néolithique ancien cardial du nord-est de la péninsule Ibérique. Datations, problématique et méthodologie

In this work, we make a compilation of all radiocarbonical data existing for the cardial Neolithic culture in the northwest of the Iberian Peninsula with the aim to delimit as much as possible the chronological range attributed for this period. For this reason calibration of all data is presented on the same curve, taking into account the critical process for all of them based on stratigraphical, taphonomical and radiometrical concepts. Finally, is shown that chronological range of cardial Neolithic culture could be focused on the 2nd half of the VI millennium cal. BC.     

An ATP-binding cassette multidrug-resistance transporter is necessary for tolerance of Gibberella pulicaris to phytoalexins and virulence on potato tubers

The necrotrophic pathogen Gibberella pulicaris infects potato tubers through wounds that contain fungitoxic secondary metabolites such as the phytoalexins rishitin and lubimin. In order to colonize tuber tissue, the fungus must possess a mechanism to tolerate potato defense compounds. In this paper, we show that a gene, Gpabc1, that codes an ATP-binding cassette (ABC) transporter is required for tolerance to these phytoalexins and for virulence on potato. The Gpabc1 gene, isolated in the course of a differential cDNA screen, shares high sequence homology with the ABC1 gene of Magnaporthe grisea. G. pulicaris mutants deficient in Gpabc1 were still able to metabolize rishitin but lost their tolerance to this phytoalexin as well as their virulence on potato. These results strongly suggest that the Gpabc1-encoded ABC transporter is necessary for tolerance of G. pulicaris to rishitin and that this tolerance is required for virulence on potato.     

Assessing the capabilities of a 4kx4k CCD camera for electron cryo-microscopy at 300kV

CCD cameras have numerous advantages over photographic film for detecting electrons; however the point spread function of these cameras has not been sufficient for single particle data collection to subnanometer resolution with 300kV microscopes. We have adopted spectral signal to noise ratio (SNR) as a parameter for assessing detector quality for single particle imaging. The robustness of this parameter is confirmed under a variety of experimental conditions. Using this parameter, we demonstrate that the SNR of images of either amorphous carbon film or ice embedded virus particles collected on a new commercially available 4kx4k CCD camera are slightly better than photographic film at low spatial frequency (<1/5 Nyquist frequency), and as good as photographic film out to half of the Nyquist frequency. In addition it is slightly easier to visualize ice embedded particles on this CCD camera than on photographic film. Based on this analysis it is realistic to collect images containing subnanometer resolution data (6-9A) using this CCD camera at an effective magnification of approximately 112000x on a 300kV electron microscope.     

Curvature in hand movements as a result of visual misjudgements of direction

The path that our hand takes when moving from one position to another is often slightly curved. Part of this curvature is caused by perceptual errors. We examine here whether this is so for the influence that a surface's orientation has on the approaching hand's path. When moving our hand towards a point on a surface we tend to follow a path that makes the final approach more orthogonal to the surface at that point. Doing so makes us less sensitive to imperfections in controlling our movements. Here we show that this tendency is also present when moving towards a point along an edge of a drawing of an oriented bar. The influence of the bar's orientation is no smaller when people are explicitly asked to move as straight as possible, than when they are instructed to move as fast as possible. The bar's orientation also influences perceptual judgements of a straight path, but this influence is only as large as it is on the curvature of the hand's path for judgements of the direction from the hand's initial position to the target. We conclude that the influence of the bar's orientation on the curvature of the hand's path is caused by a misperception of the initial direction in which the hand has to move to reach the target.     

A novel view of ferritin in cancer

Since its discovery more than 85 years ago, ferritin has principally been known as an iron storage protein. However, new roles, beyond iron storage, are being uncovered. Novel processes involving ferritin such as ferritinophagy and ferroptosis and as a cellular iron delivery protein not only expand our thinking on the range of contributions of this protein but present an opportunity to target these pathways in cancers. The key question we focus on within this review is whether ferritin modulation represents a useful approach for treating cancers. We discussed novel functions and processes of this protein in cancers. We are not limiting this review to cell intrinsic modulation of ferritin in cancers, but also focus on its utility in the trojan horse approach in cancer therapeutics. The novel functions of ferritin as discussed herein realize the multiple roles of ferritin in cell biology that can be probed for therapeutic opportunities and further research.     

Size-exclusion chromatography with evaporative light scattering detection: Method for determination of polydimethylsiloxanes. I. Testing dependence of molecular weight of polydimethylsiloxanes and injected mass upon the detector signal

In recent years the evaporative light scattering detector has become a promising device in the analysis of variable chemical compounds using liquid chromatography. Due to the detection specificity, based on the scattering of the laser light on non-volatile analyte particles, this detector is considered a most universal one. Many authors consider detector signal as a mass signal and subsequently, evaporative light scattering detector has been regarded as a mass detector. Although the scientists pinpoint to many advantages of this device, many of its drawbacks were also noticed. Due to variable examinations carried out some scientist characterised the detector response as a non-linear, seeing in fact a significant limitation of this detector for the purposes of quantitative tests. The author of the present study researched, in many ways, for the solution to this problem, by carrying out tests on polydimethylsiloxanes (PDMS) of a linear structure. The aim of this study was to test the dependence of the evaporative light scattering detector signal upon the molecular weight of PDMS of a linear structure and viscosity ranging from 10 to 60,000 cSt and the injected mass. The evaluation of function monotonicity of the detector response and determination of the function for particular analytes referred to the mass ranges of 8.9-149.0 microg. In order to find the dependence of the integrated signal value of the detector signal intensity, expressed as a surface area in mug, upon analyte mass for particular PDMS, several analytical functions and formulas were used. Parameters of regression equations were calculated for linear and non-linear functions as well as their logarithmic transformations. The aim of the research for the optimal regression equation could mean increased reliability of results obtained from analyses of PDMS.     

Sulfoximines as potent RORγ inverse agonists

Progress in the identification of suitable RORγ inverse agonists as clinical candidates has been hampered by the high lipophilicity that seems required for high potency on this nuclear receptor. In this context, we decided to focus on the replacement of the hydroxymethyl group found on known modulators to determine if more polarity could be tolerated in this position. SAR of the replacement of this moiety is presented in this article leading to the identification of sulfoximine derivatives as potent modulators with pharmacological activity in the in vivo mouse Imiquimod psoriasis model.     

Polymerase chain reaction assay specific for pathogenic Leptospira based on the gene hap1 encoding the hemolysis-associated protein-1

In this study, we used Southern hybridization of genomic DNA with the integral hap1 gene as a probe to show that this gene is only present in pathogenic Leptospira strains. We then selected PCR primers based on the hap1 gene, and tested them on several Leptospira strains and biological samples. Specific amplification was obtained for all pathogenic strains tested. Negative PCR results were observed with all saprophytic leptospire strains used as well as with other spirochetes and bacteria commonly found in biological samples. The results of direct PCR performed on biological samples, such as blood, urine or kidneys correlated with the results obtained with the classical Leptospira tests (culture and MAT). A PCR assay based on this gene would be a very useful tool for the rapid, sensitive and specific identification of pathogenic leptospires in samples for diagnosis or epidemiological survey.