Agouti: from mouse to man, from skin to fat

The agouti protein regulates pigmentation in the mouse hair follicle producing a black hair with a subapical yellow band. Its effect on pigmentation is achieved by antagonizing the binding of alpha-melanocyte stimulating hormone (alpha-MSH) to melanocortin 1 receptor (Mc1r), switching melanin synthesis from eumelanin (black/brown) to phaeomelanin (red/yellow). Dominant mutations in the non-coding region of mouse agouti cause yellow coat colour and ectopic expression also results in obesity, type 11 diabetes, increased somatic growth and tumourigenesis. At least some of these pleiotropic effects can be explained by antagonism of other members of the melanocortin receptor family by agouti protein. The yellow coat colour is the result of agouti chronically antagonizing the binding of alpha-MSH to Mc1r and the obese phenotype results from agouti protein antagonizing the binding of alpha-MSH to Mc3r and/or Mc4r. Despite the existence of a highly homologous agouti protein in humans, agouti signal protein (ASIP), its role has yet to be defined. However it is known that human ASIP is expressed at highest levels in adipose tissue where it may antagonize one of the melanocortin receptors. The conserved nature of the agouti protein combined with the diverse phenotypic effects of agouti mutations in mouse and the different expression patterns of human and mouse agouti, suggest ASIP may play a role in human energy homeostasis and possibly human pigmentation.     

Social Darwinism: from reality to myth and from myth to reality

Considering the variety of contradictory definitions which have been attributed to the term in the course of more than a century, one may be tempted to admit that 'Social Darwinism' can be reduced to a social myth. But it seems nevertheless necessary to answer the question: what has been called 'Social Darwinism' for more than one century and why was the expression used in a negative way to express contradictory opinions which sometimes have nothing to do with Darwin's theory. What we still call 'Social Darwinism' is the result of a misunderstanding: the theories expressed under that phrase have little to do with the Darwinian concepts of natural selection or descent with modification. They have their origin in a pre-darwinian conception of the struggle for existence, which Darwin used in a metaphorical sense. This confusion will then appear to refer clearly to the relationship we establish between biology and society, whether biological laws are directly prolonged in society, or more or less intermingle in a close network. The issue of the definition of Social Darwinism depends obviously on the possible answers to this question, and so does the issue of redefining Darwinism at large.     

Novel transaminases from thermophiles: from discovery to application

Transaminases (TAs) are promising biocatalysts for chiral amine synthesis; however, only few thermophilic TAs have been described to date. In this work, a genome mining approach was taken to seek novel TAs from nine thermophilic microorganisms. TA sequences were identified from their respective genome sequences and their Pfam were predicted confirming that TAs class I–II are the most abundant (50%), followed by class III (26%), V (16%), IV (8%) and VI (1%). The percentage of open reading frames (ORFs) that are TAs ranges from 0.689% in Thermococcus litoralis to 0.424% in Sulfolobus solfataricus. A total of 94 putative TAs were successfully cloned and expressed into E. coli, showing mostly good expression levels when using a chemical chaperone media containing d -sorbitol. Kinetic and end-point colorimetric assays with different amino donors–acceptors confirmed TAs activity allowing for initial exploration of the substrate scope. Stereoselective and non-stereoselective serine-TAs were selected for the synthesis of hydroxypyruvate (HPA). Low HPA reaction yields were observed with four non-stereoselective serine-TAs, whilst two stereoselective serine-TAs showed significantly higher yields. Coupling serine-TA reactions to a transketolase to yield l -erythrulose (Ery) substantially increased serine conversion into HPA. Combining both stereoselective serine-TAs and transketolase using the inexpensive racemic D/L-serine led to high Ery yield (82%). Thermal characterization of stereoselective serine-TAs confirmed they have excellent thermostability up to 60°C and high optimum temperatures.     

Retinoblastoma: from bench to bedside

Retinoblastoma (Rb) is the most common primary ocular malignancy of children and is caused by a mutation in the gene RB1. Approximately 40% of cases are associated with one or more constitutional mutations, and are therefore heritable, whereas the other 60% are sporadic. Rb is exclusively found in young children. In some cases, Rb tumours metastasise to extraocular organs including bone, lung and brain. Although there is no effective treatment for metastatic disease, non-metastatic cases can be cured by removal of the eye(enucleation). Newer treatment strategies emphasise salvaging the affected eye whenever possible. Animal models of Rb have been developed with xenograft and transgenic techniques. Each model has both strengths and weaknesses for exploring the mechanisms of disease development and progression and the efficacy of new treatment strategies.     

TransACTS: from science to innovation

The ACTS (Advanced Chemical Technologies for Sustainability) Symposium is a Dutch national meeting that brought together representatives of academia, industry and the Dutch government for innovation-driven research on sustainable chemical technologies. It provides an excellent network opportunity where all ACTS research programmes presented their work, focussing on their specific sustainable technologies. The ACTS symposium was held from 12 to 13 of January 2011 at De Werelt, Lunteren, The Netherlands. For more information about TransACTS, please visit .     

Anthocyanins: from plant to health

Anthocyanins are a group of natural occurring pigments responsible for the red-blue colour of many fruits and vegetables. Anthocyanins are of interest for two reasons because they cannot only be used in the technological field as natural colorants but also have important implications in the field of human health. Numerous studies indicate the potential effect that this family of flavonoids may have in reducing the incidence of cardiovascular disease, cancer, hyperlipidemias and other chronic diseases through the intake of anthocyanin-rich foods. This review examines existing literature in this area: from plant content and distribution to health implications, including the effect of agronomic and genetic modifications on the anthocyanin content of plants as well as other biotechnological factors and food processing. The bioavailability, metabolism, bioactivity, and epidemiology of anthocyanins will also be reviewed.     

Ergot: from witchcraft to biotechnology

The ergot diseases of grasses, caused by members of the genus Claviceps , have had a severe impact on human history and agriculture, causing devastating epidemics. However, ergot alkaloids, the toxic components of Claviceps sclerotia, have been used intensively (and misused) as pharmaceutical drugs, and efficient biotechnological processes have been developed for their in vitro production. Molecular genetics has provided detailed insight into the genetic basis of ergot alkaloid biosynthesis and opened up perspectives for the design of new alkaloids and the improvement of production strains; it has also revealed the refined infection strategy of this biotrophic pathogen, opening up the way for better control. Nevertheless, Claviceps remains an important pathogen worldwide, and a source for potential new drugs for central nervous system diseases.     

Cryptosporidium: from molecules to disease

The international conference, Cryptosporidium: from molecules to disease, was held 7-12 October 2001, in Fremantle, Western Australia, to discuss all aspects of Cryptosporidium and cryptosporidiosis.     

Lipoarabinomannans: from structure to biosynthesis

Mycobacterium tuberculosis, the causative agent of tuberculosis, is one of the most effective human pathogens and the molecular basis of its virulence remains poorly understood. Here, we review our current knowledge about the structure and biosynthesis of the mycobacterial cell-wall lipoglycans, lipoarabinomannans (LAM). LAM are ubiquitous of mycobacteria and appear as the most potent non-peptidic molecules to modulate the host immune response. Nevertheless, LAM structure differs according to the mycobacterial species and three types of LAM have been described: mannose-capped LAM (ManLAM), phospho-myo-inositol-capped LAM (PILAM) and non-capped LAM (AraLAM). The type of capping is a major structural feature determining the ability of LAM to modulate the immune response. ManLAM, found in slow-growing mycobacteria, such as M. tuberculosis, have been demonstrated to be powerful anti-inflammatory molecules and emerge as key virulence factors that may be relevant drug targets. LAM-like molecules are not only confined to mycobacteria but are also present in actinomycetes (including the genera Rhodococcus, Corynebacterium or Gordonia). This offers the possibility of comparative studies that should help in deciphering the structure-function relationships and biosynthesis of these complex molecules in the future.     

Hormesis: from mainstream to therapy

This issue of the Journal of Cell Communication and Cell Signaling on hormetic mechanisms represents an important step in the evolution of the hormesis dose response concept. Since its modern resurgence in the late 1970s the widespread occurrence of hormesis has been in search of its underlying mechanisms. The present integrative set of papers builds upon significant recent advances in the elucidation of hormetic mechanisms and provides the reader with a deep and extensive view of the concept of hormesis from a broad range of researcher perspectives and in many biomedical applications.     

Probiotics: from bench to market

"Probiotics: From Bench to Market" was a one-day conference convened by the New York Academy of Sciences on June 11, 2010, with the goal of stimulating discussion of the physiological effects of probiotics on the gastrointestinal, nervous, and immune systems. The program included speakers from academia, industry, and government to give conference participants a full understanding of the state of the field of probiotics. The overall goal of the program was to increase communication and collaboration among these groups to advance probiotic research and probiotic contributions to public health. The conference was divided into three sessions and included both oral and visual presentations as well as panel discussions.     

Spinophilin: from partners to functions

Spinophilin/neurabin 2 has been isolated independently by two laboratories as a protein interacting with protein phosphatase 1 (PP1) and F-actin. Gene analysis and biochemical approaches have contributed to define a number of distinct modular domains in spinophilin that govern protein-protein interactions such as two F-actin-, three potential Src homology 3 (SH3)-, a receptor- and a PP1-binding domains, a PSD95/DLG/zo-1 (PDZ) and three coiled-coil domains, and a potential leucine/isoleucine zipper (LIZ) motif. More than 30 partner proteins of spinophilin have been discovered, including cytoskeletal and cell adhesion molecules, enzymes, guanine nucleotide exchange factors (GEF) and regulator of G-protein signalling protein, membrane receptors, ion channels and others proteins like the tumour suppressor ARF. The physiological relevance of some of these interactions remains to be demonstrated. However, spinophilin structure suggests that the protein is a multifunctional protein scaffold that regulates both membrane and cytoskeletal functions. Spinophilin plays important functions in the nervous system where it is implicated in spine morphology and density regulation, synaptic plasticity and neuronal migration. Spinophilin regulates also seven-transmembrane receptor signalling and may provide a link between some of these receptors and intracellular mitogenic signalling events dependent on p70(S6) kinase and Rac G protein-GEF. Strikingly a role for spinophilin in cell growth was demonstrated and this effect was enhanced by its interaction with ARF. Here we review the current knowledge of the protein partners of spinophilin and present the available data that are contributing to the appreciation of spinophilin functions.     

Batteries: from alkaline to zinc-air

There is no perfect disposable battery--one that will sit on the shelf for 20 years, then continually provide unlimited current, at a completely constant voltage until exhausted, without producing heat. There is no perfect rechargeable battery--one with all of the above characteristics and will also withstand an infinite overcharge while providing an equally infinite cycle life. There are only compromises. Every battery selection is a compromise between the ideally required characteristics, the advantages, and the limitations of each battery type. General selection of a battery type to power a medical device is largely outside the purview of the biomed. Initially, these are engineering decisions made at the time of medical equipment design and are intended to be followed in perpetuity. However, since newer cell types evolve and the manufacturer's literature is fixed at the time of printing, some intelligent substitutions may be made as long as the biomed understands the characteristics of both the recommended cell and the replacement cell. For example, when the manufacturer recommends alkaline, it is usually because of the almost constant voltage it produces under the devices' design load. Over time, other battery types may be developed that will meet the intent of the manufacturer, at a lower cost, providing longer operational life, at a lower environmental cost, or with a combination of these advantages. In the Obstetrical Doppler cited at the beginning of this article, the user had put in carbon-zinc cells, and the biomed had unknowingly replaced them with carbonzinc cells. If the alkaline cells recommended by the manufacturer had been used, there would have been the proper output voltage at the battery terminals when the [table: see text] cells were at their half-life. Instead, the device refused to operate since the battery voltage was below presumed design voltage. While battery-type substitutions may be easily and relatively successfully made in disposable applications (for example, zinc-air for alkaline--if it is cost-effective), this is absolutely forbidden for secondary cells. Because of the differing cell voltages, charge characteristics and overcharge tolerance between different types of secondary cells, substituting a nickel-cadmium battery pack for the more expensive lithium-ion pack (if it is physically able to fit into the battery compartment), might appear to save money (e.g. $50 vs. $100) but it would be very ill advised. Since the cell characteristics are very different, it would be downright fatal to anyone within the 'kill radius' when the pack explodes. Those outside the kill radius would receive chemical burns from the electrolyte. Substitutions of secondary cell battery packs are generally not a good idea for biomeds to engage in. These are engineering decisions best left to either aftermarket battery pack manufacturers or the medical device manufacturer as a design engineering change.