When HIPAA finally comes, will clinical engineering be ready?

We live in interesting times. Recognize that HIPAA will impact nearly everyone in every health care organization and fundamentally change the health care industry. Implementation of HIPAA standards as well as ongoing developments in telemedicine, e-health and the Internet will continue to have a synergistic effect and further transform our industry. Biomedical technology will evolve and combine into ever-larger integrated networks. These networks will extend not only throughout the hospitals but also into the clinics, doctors' offices, and even patients' homes and workplaces. As clinical engineers, we need to stay ahead of the curve, anticipate and be prepared for these developments. We need to understand HIPAA and the implications it has for the technology we manage. We must ensure that the organizations we represent are prepared for what will undoubtedly be an exciting future.     

Recent progress in the study of G protein-coupled receptors with molecular dynamics computer simulations

G protein-coupled receptors (GPCRs) are a large, biomedically important family of proteins, and the recent explosion of new high-resolution structural information about them has provided an enormous opportunity for computational modeling to make major contributions. In particular, molecular dynamics simulations have become a driving factor in many areas of GPCR biophysics, improving our understanding of lipid-protein interaction, activation mechanisms, and internal hydration. Given that computers will continue to get faster and more structures will be solved, the importance of computational methods will only continue to grow, particularly as simulation research is more closely coupled to experiment.     

Structural gymnastics of multifunctional metamorphic proteins

The classic structure–function paradigm holds that a protein exhibits a single well-defined native state that gives rise to its biological function. Nonetheless, over the past few decades, numerous examples of proteins exhibiting biological function arising from multiple structural states of varying disorder have been identified. Most recently, several examples of ‘metamorphic proteins’, able to interconvert between vastly different native-like topologies under physiological conditions, have been characterised with multiple functions. In this review, we look at the concept of protein metamorphosis in relation to the current understanding of the protein structure–function landscape. Although structural dynamism observed for metamorphic proteins provides a novel source of functional versatility, the dynamic nature of the metamorphic proteins generally makes them difficult to identify and probe using conventional protein structure determination methods. However, as the existence of metamorphic proteins has now been established and techniques enabling the analysis of multiple protein conformers are improving, it is likely that this class will continue to grow in number.     

The chorion defect of the ocelliless mutation caused by abnormal follicle cell function

Homozygous Drosophila females bearing the ocelliless mutation are sterile and produce oocytes with abnormal chorions. It has been possible to determine in which tissues these defects reside by generating ovarian chimeras. Pole cells from ocelliless female embryos can give rise to functional oocytes surrounded by normal chorions when placed in a wild-type environment. Conversely, when wild-type pole cells are placed in homozygous ocelliless females, the oocytes that form from them have abnormal chorions and never give rise to progeny. Thus the chorion defect and sterility of the ocelliless mutation are not germ-line autonomous. Homozygous ocelliless ovaries will attach to the uterus when placed in a wild-type third instar larva, but few eggs are ever laid, and the chorions of stage 14 oocytes remain ocelliless in morphology. Wild-type ovaries continue to produce oocytes with normal chorion morphology when placed into ocelliless hosts, indicating that the ocelliless chorion defect is ovary autonomous. Thus the chorion defect of the ocelliless mutation resides in the ovarian somatic tissue, presumably the follicle cells.     

Revolution in mitochondrial medicine.

A revolution in chemical pathology occurred about 40 years ago with the discovery of a patient with mitochondrial dysfunction. The field of mitochondrial medicine has experienced explosive growth during the last decade. More than 50 mtDNA mutations and several nuclear gene mutations have been identified in affected patients. The recent development of animal models will continue the revolution in mitochondrial medicine by facilitating in depth studies of the molecular pathogenesis and development of novel drug and gene therapy strategies for mitochondrial dysfunction. As we enter the next millennium, we can expect mitochondrial medicine to remain a dynamic and rapidly developing field.     

Systems biology of lactic acid bacteria: a critical review

Understanding the properties of a system as emerging from the interaction of well described parts is the most important goal of Systems Biology. Although in the practice of Lactic Acid Bacteria (LAB) physiology we most often think of the parts as the proteins and metabolites, a wider interpretation of what a part is can be useful. For example, different strains or species can be the parts of a community, or we could study only the chemical reactions as the parts of metabolism (and forgetting about the enzymes that catalyze them), as is done in flux balance analysis. As long as we have some understanding of the properties of these parts, we can investigate whether their interaction leads to novel or unanticipated behaviour of the system that they constitute. There has been a tendency in the Systems Biology community to think that the collection and integration of data should continue ad infinitum, or that we will otherwise not be able to understand the systems that we study in their details. However, it may sometimes be useful to take a step back and consider whether the knowledge that we already have may not explain the system behaviour that we find so intriguing. Reasoning about systems can be difficult, and may require the application of mathematical techniques. The reward is sometimes the realization of unexpected conclusions, or in the worst case, that we still do not know enough details of the parts, or of the interactions between them. We will discuss a number of cases, with a focus on LAB-related work, where a typical systems approach has brought new knowledge or perspective, often counterintuitive, and clashing with conclusions from simpler approaches. Also novel types of testable hypotheses may be generated by the systems approach, which we will illustrate. Finally we will give an outlook on the fields of research where the systems approach may point the way for the near future.     

Manufacturing of recombinant therapeutic proteins in microbial systems

Recombinant therapeutic proteins have gained enormous importance for clinical applications. The first recombinant products have been produced in E. coli more than 20 years ago. Although with the advent of antibody-based therapeutics mammalian expression systems have experienced a major boost, microbial expression systems continue to be widely used in industry. Their intrinsic advantages, such as rapid growth, high yields and ease of manipulation, make them the premier choice for expression of non-glycosylated peptides and proteins. Innovative product classes such as antibody fragments or alternative binding molecules will further expand the use of microbial systems. Even more, novel, engineered production hosts and integrated technology platforms hold enormous potential for future applications. This review summarizes current applications and trends for development, production and analytical characterization of recombinant therapeutic proteins in microbial systems.     

Trust: The Missing Dimension in the Food Retail Transition in Thailand

Thailand has experienced dramatic growth of large national and international modern food retailers, such as supermarkets, hypermarkets and convenience stores in large cities and regional centres in the last two decades. Nevertheless, Thai consumers continue to purchase perishables (fruits, vegetables and animal products) from fresh markets (wet markets, talat sot) contradicting predictions from analysts that modern food retail chains will rapidly replace fresh markets as the preferred venue for purchasing all types of foods. This paper examines trust in food retail systems as an under-explored dimension lying behind the continued patronage by Thais of fresh markets to purchase perishable items. It derives from a research program commenced in 2005 that includes fieldwork visits, interviews and questionnaires. In the context of the Thai food retail transition, we propose that trust affects relationships between consumers and (1) individual fresh market-based vendors, (2) the food products sold at fresh markets and (3) the food retail system more broadly. If fresh markets can be maintained in the face of sustained pressure from modern national and international food retailers, Thais will continue to use them. Meanwhile, trust is a relatively unrecognised dimension that is supporting the continued existence of traditional food retail formats.     

Life‐history innovation to climate change: can single‐brooded migrant birds become multiple breeders?

When climatic conditions change and become outside the range experienced in the past, species may show life‐history innovations allowing them to adapt in new ways. We report such an innovation for pied flycatchers Ficedula hypoleuca. Decades of breeding biological studies on pied flycatchers have rarely reported multiple breeding in this long‐distance migrant. In two populations, we found 12 recent incidents of females with second broods, all produced by extremely early laying females in warm springs. As such early first broods are a recent phenomenon, because laying dates have gradually advanced over time, this innovation now allows individual females to enhance their reproductive success considerably. If laying dates continue advancing, potentially more females may become multiple breeders and selection for early (and multiple) breeding phenotypes increases, which may accelerate adaptation to climatic change.     

Bone marrow endothelial progenitors in atherosclerotic plaque resolution

Atherosclerosis is a major cause of morbidity and mortality in the United States. Persistently elevated circulating low-density lipoprotein, or hypercholesterolemia, and deposition of low-density lipoprotein in the vascular wall are the main inducers of atherosclerosis, which manifests itself as arterial lesions or plaques. Some plaques become thrombosis-prone and rupture, causing acute myocardial infarction or stroke. Lowering plasma cholesterol through the use of statins is the primary intervention against atherosclerosis. Treatment with statins slows progression of atherosclerosis but can only support limited plaque regression. Partially regressed plaques continue to pose a serious threat due to their remaining potential to rupture. Thus, new interventions inducing complete reversal of atherosclerosis are being sought. Implementation of new therapies will require clear understanding of the mechanisms driving plaque resolution. In this Commentary, we highlight the role of bone marrow endothelial progenitors in atherosclerotic plaque regression and discuss how regenerative cell-based interventions could be used in combination with plasma lipid-lowering to induce plaque reversal in order to prevent and/or reduce adverse cardiovascular events.     

Context-dependent misclassification of masquerading prey

Masquerading prey resemble inedible objects such as leaves, twigs, stones and bird-droppings; and benefit because their predators misclassify them as the objects that they appear to resemble. From previous work on the importance of context cues in animal learning, we predict that predators will be less likely to misclassify masquerading prey as their models when they are found in a context in which predators have never before experienced the model. Here, we test this prediction using domestic chicks Gallus gallus domesticus as predators and twig-mimicking larvae of the Early Thorn moth Selenia dentaria as masquerading prey. We found that the benefit of masquerade was significantly larger when the twig-mimicking caterpillar was found in the context in which birds had previously experienced twigs. This suggests that masqueraders may have to pay opportunity costs associated with matching their models in position and microhabitat; and that predators’ classification decisions are complex and multi-factorial.     

Antiapoptotic effects of Phe140Asn,a novel human granulocyte colony-stimulating factor mutant in H9c2 rat cardiomyocytes

Granulocyte colony-stimulating factor (G-CSF) is used for heart failure therapy and promotes myocardial regeneration by inducing mobilization of bone marrow stem cells to the injured heart after myocardial infarction; however, this treatment has one weakness in that its biological effect is transient. In our previous report, we generated 5 mutants harboring N-linked glycosylation to improve its antiapoptotic activities. Among them, one mutant (Phe140Asn) had higher cell viability than wild-type hG-CSF in rat cardiomyocytes, even after treatment with an apoptotic agent (H₂O₂). Cells treated with this mutant significantly upregulated the antiapoptotic proteins, and experienced reductions in caspase 3 activity and PARP cleavage. Moreover, the total number of apoptotic cells was dramatically lower in cultures treated with mutant hG-CSF. Taken together, these results suggest that the addition of an N-linked glycosylation was successful in improving the antiapoptotic activity of hG-CSF, and that this mutated product will be a feasible therapy for patients who have experienced heart failure. [BMB Reports 2012; 45(12): 742-747]     

Generations of sequencing technologies

Advancements in the field of DNA sequencing are changing the scientific horizon and promising an era of personalized medicine for elevated human health. Although platforms are improving at the rate of Moore's Law, thereby reducing the sequencing costs by a factor of two or three each year, we find ourselves at a point in history where individual genomes are starting to appear but where the cost is still too high for routine sequencing of whole genomes. These needs will be met by miniaturized and parallelized platforms that allow a lower sample and template consumption thereby increasing speed and reducing costs. Current massively parallel, state-of-the-art systems are providing significantly improved throughput over Sanger systems and future single-molecule approaches will continue the exponential improvements in the field.     

Application of LCA in German industry

This article summarises the findings of a survey on the application of LCA in German industry. It elaborates on the objectives and the considered products of LCAs in different industrial branches. Positively answered questionnaires have primarily been received from the automobile industry, followed by the chemical and paper and print industries. In general, German industry has become more experienced with LCA and will continue to apply this instrument in the near future. The evaluation reveals that the prevailing objective is product and process optimisation, while the utilisation for procurement, for example, is not yet wide spread. Furthermore, LCA is used for information purposes, while the major target groups are customers and consumers. Companies, however, especially those in the automobile industry, do not always make these studies available to the public. It appears that food companies use LCAs in a more offensive fashion, while chemical industry applies these instruments for more defensive reasons. Few LCAs have been conducted by industrial associations. For them, they more often serve external purposes, i.e. information of interest groups is more important than product optimisation.     

Expert status and performance

Expert judgements are essential when time and resources are stretched or we face novel dilemmas requiring fast solutions. Good advice can save lives and large sums of money. Typically, experts are defined by their qualifications, track record and experience. The social expectation hypothesis argues that more highly regarded and more experienced experts will give better advice. We asked experts to predict how they will perform, and how their peers will perform, on sets of questions. The results indicate that the way experts regard each other is consistent, but unfortunately, ranks are a poor guide to actual performance. Expert advice will be more accurate if technical decisions routinely use broadly-defined expert groups, structured question protocols and feedback.     

Microbe Hunting

Summary: Platforms for pathogen discovery have improved since the days of Koch and Pasteur; nonetheless, the challenges of proving causation are at least as daunting as they were in the late 1800s. Although we will almost certainly continue to accumulate low-hanging fruit, where simple relationships will be found between the presence of a cultivatable agent and a disease, these successes will be increasingly infrequent. The future of the field rests instead in our ability to follow footprints of infectious agents that cannot be characterized using classical microbiological techniques and to develop the laboratory and computational infrastructure required to dissect complex host-microbe interactions. I have tried to refine the criteria used by Koch and successors to prove linkage to disease. These refinements are working constructs that will continue to evolve in light of new technologies, new models, and new insights. What will endure is the excitement of the chase. Happy hunting!     

The evolutionary fate of recently duplicated retrogenes in mice

Inferences about the evolutionary impact of gene duplications often rely on the analysis of their long-term outcome. The fate of the majority of them must, however, be decided shortly after duplication. Here we analysed the evolutionary pattern of 10 mouse genes very recently duplicated by retrotransposition, by sequencing the retroposed copy in five to 10 closely related mouse species. In all cases the retroposed copy experienced accelerated nonsynonymous evolution whereas the divergence pattern of the source copy appeared unaffected by the duplication, consistent with the neofunctionalization model. The analysis further revealed that most retrogenes, including pseudogenes, did not experience a period of relaxed neutral evolution, but have been submitted to purifying selection ever since their retroposition. We propose that these duplicates play a biochemical role but are not indispensable. Purifying selection prevents them from acquiring a negative role until they are lost or silenced. This period of unnecessary redundancy could in rare cases give the time for new functions to evolve.     

On the origin of the term "stem cell"

Stem cells have fascinated both biologists and clinicians for over a century. Here, we discuss the origin of the term "stem cell," which can be traced back to the late 19th century. The term stem cell originated in the context of two major embryological questions of that time: the continuity of the germ-plasm and the origin of the hematopoietic system. Theodor Boveri and Valentin H?cker used the term stem cell to describe cells committed to give rise to the germline. In parallel, Artur Pappenheim, Alexander Maximow, Ernst Neumann, and others used it to describe a proposed progenitor of the blood system. The original meanings of the term stem cell, rather than being historical relics, continue to capture important aspects of the biology of stem cells as we see them today.     

Synaesthetic colours do not camouflage form in visual search

One of the major issues in synaesthesia research is to identify the level of processing involved in the formation of the subjective colours experienced by synaesthetes: are they perceptual phenomena or are they due to memory and association learning? To address this question, we tested whether the colours reported by a group of grapheme-colour synaesthetes (previously studied in an functional magnetic resonance imaging experiment) influenced them in a visual search task. As well as using a condition where synaesthetic colours should have aided visual search, we introduced a condition where the colours experienced by synaesthetes would be expected to make them worse than controls. We found no evidence for differences between synaesthetes and normal controls, either when colours should have helped them or where they should have hindered. We conclude that the colours reported by our population of synaesthetes are not equivalent to perceptual signals, but arise at a cognitive level where they are unable to affect visual search.     

The European Research Council--a new opportunity for European science

The long-awaited European Research Council (ERC), which receives money from the research budget of the European Union and will finance fundamental science for Europe's scientists, has finally been established. With a focus on excellence, calls for both young and experienced scientists and an average budget of \[euro]1 billion per year, the ERC will have the opportunity to give basic research in Europe a significant boost.