What can we do about osteoarthritis?

Osteoarthritis is complex in genetics, pathogenesis, monitoring and treatment. Current treatment of osteoarthritis does not influence progression. Much could be gained by more effective 'low-tech-low-cost' treatment. However, many patients have rapidly progressive disease, multiple joint involvement, and severe disease. We need to clarify the genetics of osteoarthritis, identify those at risk for progression and severe disease, and identify molecular processes critical for joint survival and failure. Will saving the cartilage improve patient pain and function? Effective outcome measures are needed to accelerate testing of new treatments. Further improvement is needed in joint implant technology to decrease costs, wear and loosening.     

What do we know about serotonin?

The present review focuses on what is known of basic serotonin physiology in the human body. Here, we describe serotonin biochemistry and metabolism and summarize the results of studies that have contributed significantly to our understanding of serotonin physiology. We report the well-established role of serotonin in cardiovascular, gastrointestinal, and circulatory physiology. Emphasis is placed on the role of serotonin in peripheral physiological systems rather than in the central nervous system. A brief overview is provided on the emerging role of serotonin in novel areas such as bone pathways and glucose uptake. We also report a select few animal studies and animal models that have provided worthwhile contributions to the understanding of serotonin in human physiology. In addition, we summarize the results of large-scale genetic studies on serotonin and serotonin transporter genes, performed in relation to behavioral and mood disorders.     

What do we need to know about speciation?

Speciation has been a major focus of evolutionary biology research in recent years, with many important advances. However, some of the traditional organising principles of the subject area no longer provide a satisfactory framework, such as the classification of speciation mechanisms by geographical context into allopatric, parapatric and sympatry classes. Therefore, we have asked where speciation research should be directed in the coming years. Here, we present a distillation of questions about the mechanisms of speciation, the genetic basis of speciation and the relationship between speciation and diversity. Our list of topics is not exhaustive; rather we aim to promote discussion on research priorities and on the common themes that underlie disparate speciation processes.     

What have we learnt about microarray analyses of atherogenesis?

PURPOSE OF REVIEW: This review covers recent developments in microarray studies in the field of atherogenesis research. RECENT FINDINGS: During the past year microarrays have been applied to the analysis of pathogenic mechanisms of several atherosclerosis risk factors, including ageing, hypertension, obesity, and cytomegalovirus infection. In addition, gene expression patterns during the development of in-stent restenosis have been examined. Several studies have also explored the pleiotropic effects of statin therapy. As a technical improvement, the combination of laser microdissection with microarrays in human samples has been reported. SUMMARY: Microarray analyses have given important new information about atherogenesis. It is anticipated that microarray studies will significantly contribute to further discoveries in the field.     

What do we know about salt stress in bryophytes?

Bryophytes are among the first plants that faced the terrestrial way of life. They settled almost all terrestrial habitats, but no extant seawater representatives are known. It is not widely documented how bryophytes cope with salt stress, but there are species inhabiting salty environments. Here, we present the current state of knowledge on salt stress biology in bryophytes.     

What do we know about gliotransmitter release from astrocytes?

Astrocytes participate in information processing by actively modulating synaptic properties via gliotransmitter release. Various mechanisms of astrocytic release have been reported, including release from storage organelles via exocytosis and release from the cytosol via plasma membrane ion channels and pumps. It is still not fully clear which mechanisms operate under which conditions, but some of them, being Ca²⁺-regulated, may be physiologically relevant. The properties of Ca²⁺-dependent transmitter release via exocytosis or via ion channels are different and expected to produce different extracellular transmitter concentrations over time and to have distinct functional consequences. The molecular aspects of these two release pathways are still under active investigation. Here, we discuss the existing morphological and functional evidence in support of either of them. Transgenic mouse models, specific antagonists and localization studies have provided insight into regulated exocytosis, albeit not in a systematic fashion. Even more remains to be uncovered about the details of channel-mediated release. Better functional tools and improved ultrastructural approaches are needed in order fully to define specific modalities and effects of astrocytic gliotransmitter release pathways.     

Donor vigilance: What are we doing about it?

Donor vigilance is the systematic monitoring of adverse reactions and incidents in blood donor care with a view to improving quality and safety for blood donors. Standard international definitions are available for surveillance purposes. In recent years advances have been made in determining risk factors for vasovagal and other adverse reactions to blood donation as well as in evaluating preventive measures. Blood establishments should record all adverse reactions in blood donors. Besides its use for individual donor care, this information can be reviewed within and between organisations to guide policy decisions and research for improving donor care.     

What do we know about Hawaiian ferns and lycophytes?

The Hawaiian Islands are home to one of the most distinctive fern and lycophyte floras in the world. Of the 144 native fern species, 76% are endemic and, including subspecies and varieties, 84% of the 167 native fern taxa are endemic. There are 15 native lycophyte species, 47% of which are endemic, and 16 taxa, 50% of which are endemic. I review here most of the available literature on Hawaiian ferns and lycophytes. Few species of ferns or lycophytes have been studied in any kind of detail and, for most, we only know basic classification and general ecological information. Although the total number of studies reviewed here is not large, research has been conducted on a wide range of topics including systematics, floristics, dispersal, phylogeny, biogeography, ecology, form and function, population genetics, microevolution, fern-animal and fern-fungi associations, reproductive biology, demography, ethnobotany, and conservation.     

What do we know about mechanical strain in lung alveoli?

The pulmonary alveolus, terminal gas-exchange unit of the lung, is composed of alveolar epithelial and endothelial cells separated by a thin basement membrane and interstitial space. These cells participate in the maintenance of a delicate system regulated not only by biological factors but also by the mechanical environment of the lung, which undergoes dynamic deformation during breathing. Clinical and animal studies as well as cell culture studies point toward a strong influence of mechanical forces on lung cells and tissues including effects on growth and repair, surfactant release, injury, and inflammation. However, despite substantial advances in our understanding of lung mechanics over the last half century, there are still many unanswered questions regarding the micromechanics of the alveolus and how it deforms during lung inflation. Therefore, the aims of this review are to draw a multidisciplinary account of the mechanics of the alveolus on the basis of its structure, biology, and chemistry and to compare estimates of alveolar deformation from previous studies.     

What can we learn about protein folding from Ising-like models?

Ising-like models have been remarkably successful in reproducing all the experimental data available on the equilibrium and kinetics of secondary structure formation in short peptides. Over the past two years, very similar models have been used to predict the folding of complete proteins, with encouraging results. Although Ising-like models are probably too simple to describe all aspects of protein folding, the results obtained so far indicate that they can play a critical role in the study of protein folding by bridging the gap between experiment and more detailed theoretical approaches.     

How much do we know about the current extinction rate?

Since about J600, 486 animal species have been recorded extinct. This represents about 0.04% of all animal species so far described. In the same period, 600 plant species are known to have disappeared, about 0.25% of the total. These figures are much smaller than those of the Permian/ Triassic and Cretaceous/Tertiary mass extinctions. One might therefore conclude that at present life on earth is at comparatively little risk of extinction. However, there is a growing body of data to show that the converse is true.     

Dying with dementia: what do we know about it?

Death with dementia is increasingly common, yet research on end of life with dementia and end-of-life care for such patients has been sparse. This article reviews recent studies in this area, most of which were done in US nursing homes. Research focused on five domains: prognosis, decision making, treatment, patient's health and suffering, and family's circumstances and satisfaction with care. Prognostication focused on developing risk scores for mortality within 6 months or a year, and while decision making was usually studied qualitatively, the other three domains were largely covered by a series of small, retrospective studies. Future direction in research is discussed, including the ongoing CASCADE project in Boston and the Dutch End of Life with Dementia Study (DEOLD). Both of these prospective studies in nursing home residents assess decision making, as well as factors associated with family's satisfaction and patient suffering. These studies will provide insight into interventions that are most likely to improve end of life care of patients with dementia in the respective countries and elsewhere.     

What do we know about the mechanisms of aromatase inhibitor resistance?

Clinical trials have demonstrated the importance of aromatase inhibitor (AI) therapy in the effective treatment of hormone-dependent breast cancers. Yet, as with all prolonged drug therapy, resistance to aromatase inhibitors does develop. To date, the precise mechanism responsible for resistance to aromatase inhibitors is not completely understood. In this paper, several mechanisms of de novo/intrinsic resistance and acquired resistance to AIs are discussed. These mechanisms are hypothesized based on important findings from a number of laboratories.

To better understand this question, our lab has generated, in vitro, breast cancer cell lines that are resistant to aromatase inhibitors. Resistant cell lines were generated over a prolonged period of time using the MCF-7aro (aromatase overexpressed) breast cancer line. These cell lines are resistant to the aromatase inhibitors letrozole, anastrozole and exemestane and the anti-estrogen tamoxifen, for comparison. Two types of resistant cell lines have been generated, those that grow in the presence of testosterone (T) which is needed for cell growth, and resistant lines that are cultured in the presence of inhibitor only (no T). In addition to functional characterization of aromatase and ER in these resistant cell lines, microarray analysis has been employed in order to determine differential gene expression within the aromatase inhibitor resistant cell lines versus tamoxifen, in order to better understand the mechanism responsible for AI resistance on a genome-wide scale. We anticipate that our studies will generate important information on the mechanisms of AI resistance. Such information can be valuable for the development of treatment strategies against AI-resistant breast cancers.