Future prospects and constraints of olive mill wastewaters use and treatment: A review

There has been an increasing number of biotechnical processes for use or treatment of olive mill wastewaters (OMW) over the last twenty years, both at laboratory size and on pilot scale. This paper reviews the methods described in the literature emphasizing the most important features and constraints of each of these processes.     

Ultrasound absorption and entropy production in biological tissue: a novel approach to anticancer therapy

Leiomyosarcoma is a malignant mesenchymal tumor originating from smooth muscle cells, which most frequently develops in the myometrium and in the gastro-intestinal tract. Reviewing the international literature, radiation-induced sarcoma arise in 0.035 to 0.2 % of all irradiated patients. Especially in the head and neck region, radiation-induced leiomyosarcoma is an extremely rare lesion. The authors report a case of a radiation-induced leiomyosarcoma of the tonsillar region of the oropharynx in a 51-year-old male patient, who had undergone radiation therapy of this region 38 years before. The lesion was treated by radical surgery. Diagnostic steps, histological presentation and therapy are described in detail and the literature concerning radiation induced malignancies in general as well as radiation induced leiomyosarcoma in particular is reviewed. The highlights of this case are an extremely uncommon location and a rare pathological entity of radiation induced malignancies.     

Segmental bone defects: from cellular and molecular pathways to the development of novel biological treatments

Several conditions in clinical orthopaedic practice can lead to the development of a diaphyseal segmental bone defect, which cannot heal without intervention. Segmental bone defects have been traditionally treated with bone grafting and/or distraction osteogenesis, methods that have many advantages, but also major drawbacks, such as limited availability, risk of disease transmission and prolonged treatment. In order to overcome such limitations, biological treatments have been developed based on specific pathways of bone physiology and healing. Bone tissue engineering is a dynamic field of research, combining osteogenic cells, osteoinductive factors, such as bone morphogenetic proteins, and scaffolds with osteoconductive and osteoinductive attributes, to produce constructs that could be used as bone graft substitutes for the treatment of segmental bone defects. Scaffolds are usually made of ceramic or polymeric biomaterials, or combinations of both in composite materials. The purpose of the present review is to discuss in detail the molecular and cellular basis for the development of bone tissue engineering constructs.     

Universal digital high-resolution melt: a novel approach to broad-based profiling of heterogeneous biological samples

Comprehensive profiling of nucleic acids in genetically heterogeneous samples is important for clinical and basic research applications. Universal digital high-resolution melt (U-dHRM) is a new approach to broad-based PCR diagnostics and profiling technologies that can overcome issues of poor sensitivity due to contaminating nucleic acids and poor specificity due to primer or probe hybridization inaccuracies for single nucleotide variations. The U-dHRM approach uses broad-based primers or ligated adapter sequences to universally amplify all nucleic acid molecules in a heterogeneous sample, which have been partitioned, as in digital PCR. Extensive assay optimization enables direct sequence identification by algorithm-based matching of melt curve shape and Tm to a database of known sequence-specific melt curves. We show that single-molecule detection and single nucleotide sensitivity is possible. The feasibility and utility of U-dHRM is demonstrated through detection of bacteria associated with polymicrobial blood infection and microRNAs (miRNAs) associated with host response to infection. U-dHRM using broad-based 16S rRNA gene primers demonstrates universal single cell detection of bacterial pathogens, even in the presence of larger amounts of contaminating bacteria; U-dHRM using universally adapted Lethal-7 miRNAs in a heterogeneous mixture showcases the single copy sensitivity and single nucleotide specificity of this approach.     

Turning food waste to energy and resources towards a great environmental and economic sustainability: An innovative integrated biological approach

Food waste (FW) management is a global conundrum because of the rapid population growth and growing economic activity. Currently, incineration and landfill are still the main means for FW management, while their environmental sustainability and economic viability have been in question. Recently, the biological processes including anaerobic digestion, aerobic composting, bioethanol fermentation, feed fermentation etc. have attracted increasing interest with the aims for energy and resource recovery from FW. However, these biological approaches have inherent drawbacks, and cannot provide a comprehensive solution for future FW management. Therefore, this review attempts to offer a critical and holistic analysis of current biotechnologies for FW management with the focus on the challenges and solutions forward. The biological approaches towards future FW management should be able to achieve both environmental sustainability and economic viability. In this instance, the concept of zero solid discharge-driven resource recovery has thus been put forward. According to which, several innovative biological processes for FW management are further elucidated with critical analysis on their engineering feasibility and environmental sustainability. It turns out that is an urgent need for turning current single task-orientated bioprocess to an integrated biological process with multiple tasks of concurrent recovery of water, resource and energy together with zero-solid discharge.     

Application of zero valent iron coupling with biological process for wastewater treatment: a review

As a promising technology, zero valent iron (ZVI) coupling with microorganisms has attracted extensive attention for contaminants removal from wastewater. The current paper provides a comprehensive review on recent developments in: (1) the chemical behavior of ZVI and potential mechanisms of integrated bio-ZVI technology in contaminants removal; (2) synergistic effects of bio-ZVI towards various common environmental pollutants in wastewater, including inorganic oxyanions, organic compounds, heavy metals and dyes; (3) promotion effects of ZVI on the biologically anaerobic digestion of waste sludge; (4) operating factors affecting the effectiveness of bio-ZVI process; (5) measures developed to enhance the long-term performance of the bio-ZVI technology. The chemical behavior and stimulating roles of ZVI playing in the growth and diversity of microorganisms is reasonable for the synergistic effects of the combined system. It was demonstrated that combined bio-ZVI system showed appreciable removal efficiencies for several types of contaminants. Additionally, the formation of passive layer on the ZVI surface can be avoided by the means of electrochemical and microbial method. Lastly, this review highlighted the research gaps to improve the sustainability of this technology. Based on these understandings, further efforts should be made to expand the applications of this combined technology and establish some feasible strategies to provide opportunities for the engineering applications.     

Hepatic processing determines dual activity of alpha-tocopheryl succinate: a novel paradigm for a shift in biological activity due to pro-vitamin-to-vitamin conversion

Redox-silent vitamin E analogues, represented by alpha-tocopheryl succinate, are potent anti-cancer drugs with potential secondary bioactivity due to their processing in vivo. Here we verified the hypothesis that hepatic processing of these agents determines the secondary effect. Mice were repeatedly injected with alpha-tocopheryl succinate, and their systemic and hepatic vein blood was assessed for alpha-tocopheryl succinate and its hydrolysis product, vitamin E (alpha-tocopherol). While levels of alpha-tocopherol doubled compared to control mice and alpha-tocopheryl succinate accumulated in the systemic blood, no alpha-tocopheryl succinate was detected in blood draining the liver. We conclude that hepatic processing endows compounds like alpha-tocopheryl succinate with a secondary, anti-oxidant/anti-inflammatory activity due to converting it to the redox-active alpha-tocopherol. Our finding epitomises a novel, general paradigm, according to which a drug can be converted in the liver into a product that has a different beneficial bioactivity.     

Differential volatile signatures from skin, naevi and melanoma: a novel approach to detect a pathological process

Background

Early detection of melanoma is of great importance to reduce mortality. Discovering new melanoma biomarkers would improve early detection and diagnosis. Here, we present a novel approach to detect volatile compounds from skin.

Methods and Findings

We used Head Space Solid Phase Micro-Extraction (HS-SPME) and gas chromatography/mass spectrometry (GC/MS) to identify volatile signatures from melanoma, naevi and skin samples. We hypothesized that the metabolic state of tissue alters the profile of volatile compounds. Volatiles released from fresh biopsy tissue of melanoma and benign naevus were compared based on their difference in frequency distribution and their expression level. We also analyzed volatile profiles from frozen tissue, including skin and melanoma.

Conclusions

Three volatiles, 4-methyl decane, dodecane and undecane were preferentially expressed in both fresh and frozen melanoma, indicating that they are candidate biomarkers. Twelve candidate biomarkers evaluated by fuzzy logic analysis of frozen samples distinguished melanoma from skin with 89% sensitivity and 90% specificity. Our results demonstrate proof-of-principle that there is differential expression of volatiles in melanoma. Our volatile metabolomic approach will lead to a better understanding of melanoma and can enable development of new diagnostic and treatment strategies based on altered metabolism.     

Development of a novel process for the biological conversion of H2S and methanethiol to elemental sulfur

The feasibility of anaerobic treatment of wastewater containing methanethiol (MT), an extremely volatile and malodorous sulfur compound, was investigated in lab-scale bioreactors. Inoculum biomass originating from full-scale anaerobic wastewater treatment facilities was used. Several sludges, tested for their ability to degrade MT, revealed the presence of organisms capable of metabolizing MT as their sole source of energy. Furthermore, batch tests were executed to gain a better understanding of the inhibition potential of MT. It was found that increasing MT concentrations affected acetotrophic organisms more dramatically than methylotrophic organisms. Continuous reactor experiments, using two lab-scale upflow anaerobic sludge bed (UASB) reactors (R1 and R2), aimed to determine the maximal MT load and the effect of elevated sulfide concentrations on MT conversion. Both reactors were operated at a hydraulic retention time (HRT) of about 7 hours, a temperature of 30 degrees C, and a pH of between 7.3 and 7.6. At the highest influent MT concentration applied, 14 mM in R1, corresponding to a volumetric loading rate of about 50 mM MT per day, 87% of the organic sulfur was recovered as hydrogen sulfide (12.2 mM) and the remainder as volatile organic sulfur compounds (VOSCs). Upon decreasing the HRT to 3.5 to 4.0 h at a constant MT loading rate, the sulfide concentration in the reactor decreased to 8 mM and MT conversion efficiency increased to values near 100%. MT conversion was apparently inhibited by the high sulfide concentrations in the reactor. The specific MT degradation rate, as determined after 120 days of operation in R1, was 2.83 +/- 0.27 mmol MT g VSS(-1) day(-1). During biological desulfurization of liquid hydrocarbon phases, such as with liquefied petroleum gas (LPG), the combined removal of hydrogen sulfide and MT is desired. In R2, the simultaneous addition of sodium sulfide and MT was therefore studied and the effect of elevated sulfide concentrations was investigated. The addition of sodium sulfide resulted in enhanced disintegration of sludge granules, causing significant washout of biomass. Additional acetate, added to stimulate growth of methanogenic bacteria to promote granulation, was hardly converted at the termination of the experimental period.     

When and where of auditory spatial processing in cortex: a novel approach using electrotomography

The modulation of brain activity as a function of auditory location was investigated using electro-encephalography in combination with standardized low-resolution brain electromagnetic tomography. Auditory stimuli were presented at various positions under anechoic conditions in free-field space, thus providing the complete set of natural spatial cues. Variation of electrical activity in cortical areas depending on sound location was analyzed by contrasts between sound locations at the time of the N1 and P2 responses of the auditory evoked potential. A clear-cut double dissociation with respect to the cortical locations and the points in time was found, indicating spatial processing (1) in the primary auditory cortex and posterodorsal auditory cortical pathway at the time of the N1, and (2) in the anteroventral pathway regions about 100 ms later at the time of the P2. Thus, it seems as if both auditory pathways are involved in spatial analysis but at different points in time. It is possible that the late processing in the anteroventral auditory network reflected the sharing of this region by analysis of object-feature information and spectral localization cues or even the integration of spatial and non-spatial sound features.     

Analytical methods for biological monitoring of exposure to pesticides: a review

Synthetic pesticides have been used since in the early to mid twentieth century. In the US alone, over 800 pesticide active ingredients are formulated in about 21,000 different commercial products. Although many public health benefits have been realized by the use of pesticides, their potential impact on the environment and public health is substantial. For risk assessment studies, exposure assessment is an integral component, which has unfortunately, often been weak or missing. In the past several decades, researchers have proposed to fill these missing data gaps using biological monitoring of specific markers related to exposures. In this paper, we present a review of existing analytical methodology for the biological monitoring of exposure to pesticides. We also present a critical assessment of the existing methodology and explore areas in which more research is needed.     

Lipoprotein oxidation and its significance for atherosclerosis: a mathematical approach

Atherosclerosis is a chronic disease which involves the build up of cholesterol and fatty deposits within the arterial wall. This results in the narrowing of the vessel lumen, which eventually restricts blood flow to vital organs such as the heart and lungs. These events may culminate in a heart attack or stroke, the commonest causes of death in the U.K. population. In this paper we study the early stages of atherosclerosis which include the build up of cholesterol within subendothelial cells to form what is known as a fatty streak, the earliest identifiable evidence of atherosclerosis. The deposition of cholesterol is believed to be a consequence of oxidation of circulating cholesterol-rich lipoproteins, in particular low density lipoproteins (LDLs). Via a mathematical model we investigate this process of oxidation within the context of an in vitro framework. We first recreate existing experimental results and then extend the model to investigate phenomenon not studied by current experimental protocols. We find that the model displays hysteresis which reveals some interesting insights into possible in vivo events. Mathematical analysis of this behaviour predicts that vitamin E supplementation is not as beneficial as high density lipoproteins (HDLs) and vitamin C. Furthermore, the scavenging of oxidants by HDL can provide an important first line of defence against LDL oxidation.     

Organic nanofibers containing insect pheromone disruptants: a novel technical approach to controlled release dispensers with potential for process mechanization

Beginning fifty years ago, the search for suitable dispensers containing insect pheromones grew with the availability of these synthetic biotechnical tools. Many economic entomologists and application engineers dearly wish they had the "smart, intelligent and ideal dispenser". More or less suitable approximations are available commercially, but none so far meets all demands. Under economic strictures, novel inexpensive systems would be advantageous with release characteristics tailored to the specific life histories of pest insects, the plants considered and the numerous requirements of growers alike. Simultaneously, their field distribution should be mechanizable and be accomplished by one (or very few) application runs. The dispensers should be biodegradable, biocompatible, sustainably applicable, and they should be based on renewable resources. This report presents first results of a novel organic, electrospun nanofiber dispenser with dimensions in the upper nanometer range. Its load of pheromone can be adjusted to be sufficient for 7 weeks of constant disruptive action in vineyards and can be directed against the European Grape Vine Moth Lobesia botrana (Lepidoptera: Tortricidae) which here serves as a readily available model. Mating disruption in L. botrana and the related Eupoecilia ambiguella is a well studied and developed engineering process. Equally, nanofiber production by electrospinning (for a comprehensive review see Greiner and Wendorff, 2007A, B) is well known and already has numerous applications in filtration technology, air conditioning, and medical wound dressing. Our goal was to bring together and successfully mate these (partly incompatible) technologies via technical tricks of a proprietary nature. Even though the lifetime and effectiveness of currently available nanofibers still must be doubled, the rather complicated system of their production and analysis is known well enough to identify the parameters that need future adjustment. Another challenge is the mechanical distribution of the fibers in the vineyards by suitable machinery. Also, in this respect, certain technical leads are available for future development.     

A novel method for detecting intramolecular coevolution: adding a further dimension to selective constraints analyses

Protein evolution depends on intramolecular coevolutionary networks whose complexity is proportional to the underlying functional and structural interactions among sites. Here we present a novel approach that vastly improves the sensitivity of previous methods for detecting coevolution through a weighted comparison of divergence between amino acid sites. The analysis of the HIV-1 Gag protein detected convergent adaptive coevolutionary events responsible for the selective variability emerging between subtypes. Coevolution analysis and functional data for heat-shock proteins, Hsp90 and GroEL, highlight that almost all detected coevolving sites are functionally or structurally important. The results support previous suggestions pinpointing the complex interdomain functional interactions within these proteins and we propose new amino acid sites as important for interdomain functional communication. Three-dimensional information sheds light on the functional and structural constraints governing the coevolution between sites. Our covariation analyses propose two types of coevolving sites in agreement with previous reports: pairs of sites spatially proximal, where compensatory mutations could maintain the local structure stability, and clusters of distant sites located in functional domains, suggesting a functional dependency between them. All sites detected under adaptive evolution in these proteins belong to coevolution groups, further underlining the importance of testing for coevolution in selective constraints analyses.     

The role of the dielectric barrier in narrow biological channels: a novel composite approach to modeling single-channel currents

A composite continuum theory for calculating ion current through a protein channel of known structure is proposed, which incorporates information about the channel dynamics. The approach is utilized to predict current through the Gramicidin A ion channel, a narrow pore in which the applicability of conventional continuum theories is questionable. The proposed approach utilizes a modified version of Poisson-Nernst-Planck (PNP) theory, termed Potential-of-Mean-Force-Poisson-Nernst-Planck theory (PMFPNP), to compute ion currents. As in standard PNP, ion permeation is modeled as a continuum drift-diffusion process in a self-consistent electrostatic potential. In PMFPNP, however, information about the dynamic relaxation of the protein and the surrounding medium is incorporated into the model of ion permeation by including the free energy of inserting a single ion into the channel, i.e., the potential of mean force along the permeation pathway. In this way the dynamic flexibility of the channel environment is approximately accounted for. The PMF profile of the ion along the Gramicidin A channel is obtained by combining an equilibrium molecular dynamics (MD) simulation that samples dynamic protein configurations when an ion resides at a particular location in the channel with a continuum electrostatics calculation of the free energy. The diffusion coefficient of a potassium ion within the channel is also calculated using the MD trajectory. Therefore, except for a reasonable choice of dielectric constants, no direct fitting parameters enter into this model. The results of our study reveal that the channel response to the permeating ion produces significant electrostatic stabilization of the ion inside the channel. The dielectric self-energy of the ion remains essentially unchanged in the course of the MD simulation, indicating that no substantial changes in the protein geometry occur as the ion passes through it. Also, the model accounts for the experimentally observed saturation of ion current with increase of the electrolyte concentration, in contrast to the predictions of standard PNP theory.     

Thematic review series: systems biology approaches to metabolic and cardiovascular disorders. Lipidomics: a global approach to lipid analysis in biological systems

Lipids are water-insoluble molecules that have a wide variety of functions within cells, including: 1) maintenance of electrochemical gradients; 2) subcellular partitioning; 3) first- and second-messenger cell signaling; 4) energy storage; and 5) protein trafficking and membrane anchoring. The physiological importance of lipids is illustrated by the numerous diseases to which lipid abnormalities contribute, including atherosclerosis, diabetes, obesity, and Alzheimer's disease. Lipidomics, a branch of metabolomics, is a systems-based study of all lipids, the molecules with which they interact, and their function within the cell. Recent advances in soft-ionization mass spectrometry, combined with established separation techniques, have allowed the rapid and sensitive detection of a variety of lipid species with minimal sample preparation. A "lipid profile" from a crude lipid extract is a mass spectrum of the composition and abundance of the lipids it contains, which can be used to monitor changes over time and in response to particular stimuli. Lipidomics, integrated with genomics, proteomics, and metabolomics, will contribute toward understanding how lipids function in a biological system and will provide a powerful tool for elucidating the mechanism of lipid-based disease, for biomarker screening, and for monitoring pharmacologic therapy.     

Compounds that bind APP and inhibit Abeta processing in vitro suggest a novel approach to Alzheimer disease therapeutics

Extracellular deposits of aggregated amyloid-beta (Abeta) peptides are a hallmark of Alzheimer disease; thus, inhibition of Abeta production and/or aggregation is an appealing strategy to thwart the onset and progression of this disease. The release of Abeta requires processing of the amyloid precursor protein (APP) by both beta- and gamma-secretase. Using an assay that incorporates full-length recombinant APP as a substrate for beta-secretase (BACE), we have identified a series of compounds that inhibit APP processing, but do not affect the cleavage of peptide substrates by BACE1. These molecules also inhibit the processing of APP and Abeta by BACE2 and selectively inhibit the production of Abeta(42) species by gamma-secretase in assays using CTF99. The compounds bind directly to APP, likely within the Abeta domain, and therefore, unlike previously described inhibitors of the secretase enzymes, their mechanism of action is mediated through APP. These studies demonstrate that APP binding agents can affect its processing through multiple pathways, providing proof of concept for novel strategies aimed at selectively modulating Abeta production.