Phytochemicals: the good, the bad and the ugly?

Phytochemicals are constitutive metabolites that enable plants to overcome temporary or continuous threats integral to their environment, while also controlling essential functions of growth and reproduction. All of these roles are generally advantageous to the producing organisms but the inherent biological activity of such constituents often causes dramatic adverse consequences in other organisms that may be exposed to them. Nevertheless, such effects may be the essential indicator of desirable properties, such as therapeutic potential, especially when the mechanism of bioactivity can be delineated. Careful observation of cause and effect, followed by a coordinated approach to identify the responsible entities, has proved extremely fruitful in discovering roles for phytochemical constituents. The process is illustrated by selected examples of plants poisonous to animals and include the steroidal alkaloid toxin of Veratrum californicum (Western false hellebore), piperidine alkaloids of Lupinus species (lupines), and polyhydroxy indolizidine, pyrrolizidine and nortropane alkaloids of Astragalus and Oxytropis species (locoweeds), Castanospermum australe (Moreton Bay chestnut) and Ipomoea species (morning glories).     

Is proteomics the new genomics?

Mass spectrometry (MS)-based proteomics has become a formidable tool for the investigation of posttranslational modifications to proteins, protein interactions, and organelles. Is it now ready to tackle comprehensive protein expression analysis?     

Which came first, the lung or the breath?

Lungs are the characteristic air-filled organs (AO) of the Polypteriformes, lungfish and tetrapods, whereas the swimbladder is ancestral in all other bony fish. Lungs are paired ventral derivatives of the pharynx posterior to the gills. Their respiratory blood supply is the sixth branchial artery and the venous outflow enters the heart separately from systemic and portal blood at the sinus venosus (Polypteriformes) or the atrium (lungfish), or is delivered to a separate left atrium (tetrapods). The swimbladder, on the other hand, is unpaired, and arises dorsally from the posterior pharynx. It is employed in breathing in Ginglymodi (gars), Halecomorphi (bowfin) and in basal teleosts. In most cases, its respiratory blood supply is homologous to that of the lung, but the vein drains to the cardinal veins. Separate intercardiac channels for oxygenated and deoxygenated blood are lacking. The question of the homology of lungs and swimbladders and of breathing mechanisms remains open. On the whole, air ventilatory mechanisms in the actinopterygian lineage are similar among different groups, including Polypteriformes, but are distinct from those of lungfish and tetrapods. However, there is extreme variation within this apparent dichotomy. Furthermore, the possible separate origin of air breathing in actinopterygian and 'sarcopterygian' lines is in conflict with the postulated much more ancient origin of vertebrate air-breathing organs. New studies on the isolated brainstem preparation of the gar (Lepisosteus osseus) show a pattern of efferent activity associated with a glottal opening that is remarkably similar to that seen in the in-vitro brainstem preparation of frogs and tadpoles. Given the complete lack of evidence for AO in chondrichthyans, and the isolated position of placoderms for which buoyancy organs of uncertain homology have been demonstrated, it is likely that homologous pharyngeal AO arose in the ancestors of early bony fish, and was pre-dated by behavioral mechanisms for surface (water) breathing. The primitive AO may have been the posterior gill pouches or even the modified gills themselves, served by the sixth branchial artery. Further development of the dorsal part may have led to the respiratory swimbladder, whereas the paired ventral parts evolved into lungs.     

Does antiperspirant use increase the risk of aluminium-related disease,including Alzheimer's disease?

Aluminium salts are the major constituent of many widely used antiperspirant products. The use of such antiperspirants has been linked with the systemic accumulation of aluminium and an increased risk of Alzheimer's disease. But can the frequent use of aluminium-based antiperspirants lead to the accumulation of toxic levels of aluminium? And are there measures that we can take to reduce such accumulation without reducing the effectiveness of antiperspirants?     

Tired of the same old grind in the new genomics and proteomics era?

New discoveries in life sciences depend on accurate analysis of biomolecules, which in turn depends on the extraction of high-quality molecules in high quantities from the tissues of plants, animals or microorganisms. The extraction process for hard-to-lyse cells and tissues has been a bottleneck in the path to discovery for many years. This review describes extraction methods currently in use, and compares them to a newly developed, automated process involving patented pressure cycling technology (PCT). The PCT sample preparation system (SPS) uses an instrument capable of rapid, temperature-controlled pressure cycling between ambient and high pressures, and single-use sample tubes containing a ram and a lysis disk. The quality and quantity of nucleic acid and protein prepared by the PCT SPS method are comparable to the older methods, whereas ease and safety of processing, reproducibility, speed and control are enhanced.     

Mottled Duck introductions to South Carolina: The ugly,the bad,and the good?

Translocations or other movements of wildlife sometimes accomplish their intended objectives, but unforeseen consequences may arise and disrupt locally adapted ecological communities, restructure or dilute genetic integrity of populations or subspecies of the moved organism, and otherwise negatively influences a species’ long‐term fitness. Two historical populations of Mottled Ducks (Anas fulvigula) exist and are endemic to (1) Mexico and the West‐Gulf Coast (A. f. maculosa) regions of the United States and (2) Florida (A. f. fulvigula). From 1975 to 1983, 1285 Mottled Ducks from Florida, Louisiana, and Texas were released to coastal South Carolina, primarily to ultimately establish a legally harvestable population. This movement stirred mixed reactions amid the conservation community. Contemporary information suggests an increasing Mottled Duck population in South Carolina and possibly dispersing into Georgia. Herein, I objectively discuss the potential consequences of this new population per the birds’ evolution, ecology, and management. Ultimately, I suggest that this translocation is a long‐term benefit to the species.     

Cellular plasticity: the good, the bad, and the ugly? Microenvironmental influences on progenitor cell therapy

Progenitor cell based therapies have emerged for the treatment of ischemic cardiovascular diseases where there is insufficient endogenous repair. However, clinical success has been limited, which challenges the original premise that transplanted progenitor cells would orchestrate repair. In this review, we discuss the basics of endothelial progenitor cell therapy and describe how microenvironmental changes (i.e., trophic and mechano-structural factors) in the damaged myocardium influence progenitor cell plasticity and hamper beneficial therapeutic outcome. Further understanding of these microenvironmental clues will enable optimization of cell therapy at all levels. We discuss current concepts and provide future perspectives for the enhancement of progenitor cell therapy, and merge these advances into a combined approach for ischemic tissue repair.     

Unraveling the resistance of microbial biofilms: has proteomics been helpful?

Biofilms are surface-attached, matrix-encased, structured microbial communities which display phenotypic features that are dramatically different from those of their free-floating, or planktonic, counterparts. Biofilms seem to be the preferred mode of growth of microorganisms in nature, and at least 65% of all human infections are associated with biofilms. The most notable and clinically relevant property of biofilms is their greater resistance to antimicrobials compared with their planktonic counterparts. Although both bacterial and fungal biofilms display this phenotypic feature, the exact mechanisms underlying their increased drug resistance are yet to be determined. Advances in proteomics techniques during the past decade have facilitated in-depth analysis of the possible mechanisms underpinning increased drug resistance in biofilms. These studies have demonstrated the ability of proteomics techniques to unravel new targets for combating microbial biofilms. In this review, we discuss the putative drug resistance mechanisms of microbial biofilms that have been uncovered by proteomics and critically evaluate the possible contribution of the new knowledge to future development in the field. We also summarize strategic uses of novel proteomics technologies in studies related to drug resistance mechanisms of microbial biofilms.     

Is proteomics heading in the wrong direction?

Proteomics is now considered to be one of the most important 'post-genome' approaches to help us understand gene function. In fact, several genomics companies have launched large-scale proteomics projects, and have started to annotate the entire human proteome. The 'holistic view' painted by a human proteome project is seductive, but is it realistic?     

Inhibition of neutrophil apoptosis by acrolein: a mechanism of tobacco-related lung disease?

Cigarette smoking is known to contribute to inflammatory diseases of the respiratory tract by promoting recruitment of inflammatory-immune cells such as neutrophils and perhaps by altering neutrophil functional properties. We investigated whether acrolein, a toxic unsaturated aldehyde found in cigarette smoke, could directly affect neutrophil function. Exposure of freshly isolated human neutrophils to acrolein markedly inhibited spontaneous neutrophil apoptosis as indicated by loss of membrane asymmetry and DNA fragmentation and induced increased neutrophil production of the chemokine interleukin-8 (IL-8). Acrolein (1--50 microM) was found to induce marked activation of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinases (MAPKs), and inhibition of p38 MAPK activation by SB-203580 prevented acrolein-induced IL-8 release. However, inhibition of either ERK or p38 MAPK did not affect acrolein-dependent inhibition of apoptosis. Acrolein exposure prevented the activation of caspase-3, a crucial step in the execution of neutrophil apoptosis, presumably by direct inhibition of the enzyme. Our results indicate that acrolein may contribute to smoke-induced inflammatory processes in the lung by increasing neutrophil recruitment and reducing neutrophil clearance by apoptosis.     

Gel-based proteomics in disease research: Is it still valuable?

Gel electrophoresis had been the primary method in proteomics. In the early era of proteomics, gel electrophoresis was a dominant technique of sample preparation for mass spectrometry analysis. Particularly, two-dimensional electrophoresis provided high-resolution proteome separation, and was regarded as the standard methodology for the separation of wide-range proteomes. However, gel electrophoresis turned downwards due to the progress of other separations including liquid chromatography and ionization techniques, resulting gel-free proteomics finally becoming dominant players at present. There are numerous advantages in gel-free approach in aspects of current trends of disease research. Interestingly, gel-free approaches are still advanced, it seems that gel electrophoresis will not be disappeared. The unique features of gel electrophoresis can be complementary for gel-free and it is suitable for the new wave of top-down functional proteomics.     

Can correcting the ΔF508-CFTR proteostasis-defect rescue CF lung disease?

Protein homeostasis (proteostasis) generates and maintains individual proteins in their folded and functional-competent states. The components of the cellular proteostasis machinery also dictate the functional lifetime of a protein by constantly regulating its conformation, concentration and subcellular location. The autosomal recessive disease cystic fibrosis (CF) is caused by a proteostasis-defect in CF transmembrane conductance regulator (CFTR). The most common CF mutation leading to this proteostasis-defect is the deletion of a phenylalanine residue at position 508 (ΔF508) of the CFTR protein. This ΔF508-CFTR protein is prone to aberrant folding, increased ER-associated degradation, atypical intracellular trafficking and reduced stability at the apical membrane. This ΔF508-CF proteostasis-defect leads to an obstructive lung disease characterized by impaired ion transport in airway epithelial cells, mucus buildup in air space and chronic airway inflammation. We assess here whether correcting the underlying defect in ΔF508-CFTR protein processing using therapeutic proteostasis regulators can treat chronic CF lung disease. As a proof of concept, recent studies support that the selective modulation of mutant-CFTR proteostasis may offer promising therapies to reverse chronic CF lung disease.