Profiling for novel proteomics biomarkers in neurodevelopmental disorders

Protein biomarker discovery from biological fluids, such as serum, has been widely applied to disorders such as cancer and has more recently also been utilized in neuro-psychiatric disorders with relatively clear biological causes, such as Alzheimer's disease and schizophrenia. The application of the associated technologies for the identification of protein biomarker signatures in neurodevelopmental disorders, such as autism spectrum disorder and attention deficit hyperactivity disorder, is comparatively less well established. The aim of this article is to provide an overview of the various protocols available for such analysis, discuss reports in which these techniques have been previously applied in biomarker discovery/validation in neurodevelopmental disorders, and consider the future development of this area of research.     

Recent advances in the fight against leishmaniasis with natural products

The active compounds obtained from some medicinal plants used traditionally worldwide for the treatment of leishmaniasis are reviewed. Among these active molecules, described in recent literature are quinoline alkaloids such as alkyl-2 quinoline and aryl-2 quinoline from Galipea longiflora, isoquinoline alkaloids such as isoguattouregidine from Guatteria foliosa, indole alkaloids such as conodurine and gabunine from Pescheiera van heurkii, terpenes such as jatrogrossidione from Jatropha grossidentata, acetogenins such as senegalene from Annona senegalensis and lignans such as (+)nyasol from Asparagus africanus. Other natural compounds with antileishmanial activity are coumarins, chalcones, lactones, tetralones and saponins. Some of them are known antiprotozoal natural products. These compounds could be used as templates to discover new and effective drugs against leishmaniasis.     

Derivatization of carbohydrates for analysis by chromatography; electrophoresis and mass spectrometry

Carbohydrates display a large diversity of structures and their analysis presents many obstacles as the result of properties such as isomeric diversity, existence of branched structures and the lack of chromophores or fluorophores. Consequently, many analytical approaches depend on the application of chemical modifications such as hydrolysis or derivative formation. This review covers various aspects of derivatization that are used for such approaches as improving thermal stability and volatility for gas-phase analyses, introduction of fluorophores for optical detectors, introduction of charge for mass spectral analyses and attachment of bioaffinity tags for bioactivity studies. Reducing carbohydrates contain, in addition to multiple hydroxyl groups, several other sites for derivatization such as the single anomeric site that has been used in numerous methods for attaching various property-enhancing tags. Other sites are restricted to specific carbohydrates but include carboxy groups in sialic acids and amino groups in glycosylamines. All of these groups have been the targets of derivatization and this review attempts to summarise the main methods used for these various functional groups.     

Activation of protein kinase C by ganglioside GM3 in the presence of calcium and 12-O-tetradecanoylphorbol-13-acetate

Ganglioside GM3 and 12-O-tetradecanoylphorbol-13-acetate activated protein kinase C as substitutes for phosphatidylserine and diacylglycerol. Hydrophobic gangliosides such as GM4 and GM3 were rather more potent activators of protein kinase C than hydrophilic ones such as GD1a and GT1b. Active tumor promoters such as teleocidin, mezerein, phorbol 12,13-acetate and phorbol 12,13-dibenzoate also activated protein kinase C, but not inactive tumor promoters such as phorbol and 4-alpha-phorbol 12,13-didecanoate.     

On the rotational brownian motion of a bacterial idle motor. I. Theory of time-dependent fluorescence depolarization

A rotational diffusion equation and its Green's function for a spheroidal particle such as a bacterial body, to which an actively driving but idle motor is attached, are presented. As an application of the theory, general expressions for the time-dependent fluorescence depolarization caused by such a particle have been obtained. Measurement of such depolarizalion should provide a useful tool for determination of the rate of revolution of the rotating motor attached to cell bodies such as bacteria under various solution conditions, if a fluorescent (or phosphorescent) label is attached to the motor shaft.     

Primate and feline lentivirus vector RNA packaging and propagation by heterologous lentivirus virions

Development of safe and effective gene transfer systems is critical to the success of gene therapy protocols for human diseases. Currently, several primate lentivirus-based gene transfer systems, such as those based on human and simian immunodeficiency viruses (HIV/SIV), are being tested; however, their use in humans raises safety concerns, such as the generation of replication-competent viruses through recombination with related endogenous retroviruses or retrovirus-like elements. Due to the greater phylogenetic distance from primate lentiviruses, feline immunodeficiency virus (FIV) is becoming the lentivirus of choice for human gene transfer systems. However, the safety of FIV-based vector systems has not been tested experimentally. Since lentiviruses such as HIV-1 and SIV have been shown to cross-package their RNA genomes, we tested the ability of FIV RNA to get cross-packaged into primate lentivirus particles such as HIV-1 and SIV, as well as a nonlentiviral retrovirus such as Mason-Pfizer monkey virus (MPMV), and vice versa. Our results reveal that FIV RNA can be cross-packaged by primate lentivirus particles such as HIV-1 and SIV and vice versa; however, a nonlentivirus particle such as MPMV is unable to package FIV RNA. Interestingly, FIV particles can package MPMV RNA but cannot propagate the vector RNA further for other steps of the retrovirus life cycle. These findings reveal that diverse retroviruses are functionally more similar than originally thought and suggest that upon coinfection of the same host, cross- or copackaging may allow distinct retroviruses to generate chimeric variants with unknown pathogenic potential.     

Correct samples for diagnostic tests in sexually transmitted diseases: which sample for which test?

Amplified DNA technology such as the polymerase chain reaction (PCR) and ligase chain reaction (LCR) are new techniques for the diagnosis of genital chlamydial infections in both men and women. These tests are highly sensitive and specific in detecting chlamydial genes in different specimen types such as genital samples as well as in non-invasive specimens such as urine and vulval smears. Due to the advantage of a high reliability of these techniques even when they are performed on non-invasive specimen types, amplification tests allow chlamydial diagnosis for screening especially high risk persons as the basis of chlamydia control programs.     

Synthetic peptide and protein domain arrays prepared by the SPOT technology

The SPOT(trade mark) technology for highly parallel synthesis of peptides on flat surfaces in array type format has evolved into a versatile toolbox for a variety of applications in proteomics such as mapping protein-protein interactions and profiling the substrate specificity of enzymes such as kinases and proteases. Originally developed for the synthesis of short overlapping peptide sequences for mapping antibody epitopes this technology has recently been extended to the synthesis of functional protein domains. This opens up a variety of future applications such as target identification and protein expression profiling.     

Are genetically modified plants useful and safe?

So far, plants have been genetically modified essentially to achieve resistance to herbicides, or to pathogens (mainly insects, or viruses), but resistance to abiotic stresses (such as cold, heat, drought, or salt) is also being studied. Genetically modified (GM) plants with improved nutritional qualities have more recently been developed, such as plants containing higher proportions of unsaturated fatty acids (omega-3 and omega-6) in their oil (to prevent cardio-vascular diseases), or containing beta-carotene as in the golden rice (to prevent vitamin A deficiency). Possible risks for human health (such as the production of allergenic proteins), or for the environment (such as the appearance of superweeds as a result from gene flow), should be carefully studied, and a science-based assessment of benefits vs. risks should be made on a case by case basis, both for GM plants and for plants obtained by conventional breeding methods.     

Nutrient influences on toxicity and carcinogenicity

Essential nutrients and toxicants often coexist in the diet of humans and animals. Interactions among nutrients and chemicals in the diet may alter the toxicity of the chemical or the requirement for or availability of specific nutrients. Such interactions have been demonstrated among toxins and dietary protein, trace elements, and vitamins. Certain nutrients may also alter the response to certain drugs, and some drugs, such as oral contraceptives, may alter the availability of some nutrients. The carcinogenicity of some compounds and the subsequent promotion of tumor growth are affected by nutrients such as fat, vitamins, and lipotropes and by such minor dietary constituents as naturally occurring indoles and synthetic preservatives. In this paper we review such interactions as well as the mechanisms responsible for them.     

Phytoremediation of Organic Contaminants: A Review of Phytoremediation Research at the University of Washington

As overwhelmingly positive results have become available regarding the ability of plants to degrade compounds such as trichloroethylene, phytoremediation studies are expanding. Studies to determine the potential for phytoremediation of fully chlorinated compounds, such as carbon tetrachloride and tetrachloroethylene, brominated compounds, such as ethylene dibromide and dibromochloropropane, and nonhalogenated compounds, such as methyl-t-butyl ether (MTBE), are underway. When using phytoremediation, it is important to select not only a plant that is capable of degrading the pollutant in question, but also one that will grow well in that specific environment. In ecologically sensitive areas, such as the Hawaiian Islands, only plants native to the area can be used. One way to supplement the arsenal of plants available for remedial actions is to utilize genetic engineering tools to insert into plants those genes that will enable the plant to metabolize a particular pollutant. Hybrid technologies, such as using plants in pumping and irrigation systems, also enable plants to be used as a remedial method when the source of the pollutant is beyond the reach of plant roots, or when planting space directly over the pollutant is unavailable or restricted. Thus, the potential uses of phytoremediation are expanding as the technology continues to offer new, low-cost remediation options.     

Directed evolution of enzymes for applied biocatalysis

Directed evolution has rapidly emerged as a powerful new strategy for improving the characteristics of enzymes in a targeted manner. By coupling various protocols for generating large variant libraries of genes, together with high-throughput screens that select for specific properties of an enzyme, such as thermostability, catalytic activity and substrate specificity, it is now possible to optimize biocatalysts for specific applications. However, further work is required to broaden the range of screens that can be used, particularly in terms of reaction type, such as hydroxylation and carbon-carbon bond formation, and functional characteristics, such as enantioselectivity and regioselectivity, so that directed evolution can be used in a routine manner for biocatalyst development.     

Nanoparticles for bioanalysis

This review covers the emerging field of nanobiotechnology, in which nanoparticles are applied to the analysis of biomolecules. Nanoparticles can be used in a variety of bioanalytical formats, and this review discusses four classes of use. First, nanoparticles as quantitation tags, such as the optical detection of quantum dots and the electrochemical detection of metallic nanoparticles. Second, encoded nanoparticles as substrates for multiplexed bioassays, such as striped metallic nanoparticles. Third, nanoparticles that leverage signal transduction, for example in colloidal gold-based aggregation assays. Fourth, functional nanoparticles that exploit specific physical or chemical properties of nanoparticles to carry out novel functions, such as the catalysis of a biological reaction. In addition, the review discusses the next generation of nanoparticles that will be utilized in the life sciences, such as nanodots and carbon nanotubes.     

Production of renewable polymers from crop plants

Plants produce a range of biopolymers for purposes such as maintenance of structural integrity, carbon storage, and defense against pathogens and desiccation. Several of these natural polymers are used by humans as food and materials, and increasingly as an energy carrier. In this review, we focus on plant biopolymers that are used as materials in bulk applications, such as plastics and elastomers, in the context of depleting resources and climate change, and consider technical and scientific bottlenecks in the production of novel or improved materials in transgenic or alternative crop plants. The biopolymers discussed are natural rubber and several polymers that are not naturally produced in plants, such as polyhydroxyalkanoates, fibrous proteins and poly-amino acids. In addition, monomers or precursors for the chemical synthesis of biopolymers, such as 4-hydroxybenzoate, itaconic acid, fructose and sorbitol, are discussed briefly.     

Antivirals and antiviral strategies

In recent years, the demand for new antiviral strategies has increased markedly. There are many contributing factors to this increased demand, including the ever-increasing prevalence of chronic viral infections such as HIV and hepatitis B and C, and the emergence of new viruses such as the SARS coronavirus. The potential danger of haemorrhagic fever viruses and eradicated viruses such as variola virus being used as bioterrorist weapons has also increased the profile of antiviral drug discovery. Here, the virus infections for which antiviral therapy is needed and the compounds that are available, or are being developed, for the treatment of these infections are described.     

An interesting diagnosis for a presacral mass: case report

A presacral mass can present a diagnostic dilemma for the surgical oncologist. Differential diagnoses include congenital causes such as teratoma or chordoma, neurological causes such as neurilemoma or neurofibroma or other malignancies such as lymphoma or sarcoma. Diagnosis usually requires imaging such as CT and MRI and tissue biopsy. We present an unusual cause of a presacral mass being extramedullary haematopoiesis, found incidentally in a 71 year old female. Extramedullary haematopoiesis is defined as the production of myeloid and erythroid elements outside of the bone-marrow. This diagnosis is extremely rare in the presacral area especially in a patient with no haematological abnormalities. A review of the literature is presented.     

The doctor's dilemma: opiate analgesics and chronic pain

Opiates are utilized routinely and effectively as a short-term analgesic treatment for a variety of acute pain conditions such as occur following trauma, and for patients with painful terminal diseases such as cancer. Because opiate analgesics are highly addictive substances, their use in the treatment of chronic nonmalignant pain remains controversial.     

The biomarkers of fetal growth in intrauterine growth retardation and large for gestational age cases: from adipocytokines to a metabolomic all-in-one tool

Adipose tissue is no longer considered as inert; the literature describes the role it plays in the production of many substances, such as adiponectin, visfatin, ghrelin, S100B, apelin, TNF, IL-6 and leptin. These molecules have specific roles in humans and their potential as biomarkers useful for identifying alterations related to intrauterine growth retardation and large for gestational age neonates is emerging. Infants born in such conditions have undergone metabolic changes, such as fetal hypo- or hyperinsulinemia, which may lead to development of dysmetabolic syndrome and other chronic diseases in adulthood. In this review, these biomarkers are analyzed specifically and it is discussed how metabolomics may be an advantageous tool for detection, discrimination and prediction of metabolic alterations and diseases. Thus, a holistic approach, such as metabolomics, could help the prevention and early diagnosis of metabolic syndrome.     

Equation discovery for systems biology: finding the structure and dynamics of biological networks from time course data

Reconstructing biological networks, such as metabolic and signaling networks, is at the heart of systems biology. Although many approaches exist for reconstructing network structure, few approaches recover the full dynamic behavior of a network. We survey such approaches that originate from computational scientific discovery, a subfield of machine learning. These take as input measured time course data, as well as existing domain knowledge, such as partial knowledge of the network structure. We demonstrate the use of these approaches on illustrative tasks of finding the complete dynamics of biological networks, which include examples of rediscovering known networks and their dynamics, as well as examples of proposing models for unknown networks.     

Insect reactions to light and its applications to pest management

Insects are able to see ultraviolet (UV) radiation. Nocturnal insects are often attracted to light sources that emit large amounts of UV radiation, and devices that exploit this behavior, such as light traps for forecasting pest outbreaks, and electric insect killers, have been developed. Some diurnal species are attracted to yellow; yellow pan traps are used for conducting surveys for pest outbreaks and yellow sticky plates are used for pest control. Lamps that give off yellow illumination have been used effectively to control the activity of nocturnal moths and thus reduce damage to fruit, vegetables, and flowers. Covering cultivation facilities with film that filters out near-UV radiation reduces the invasion of pests such as whiteflies and thrips into the facilities, thus reducing damage. Reflective material placed on cultivated land can control the approach of flying insects such as aphids. Future development and use of new light sources such as light-emitting diodes is anticipated for promoting integrated pest management.