The assessment of circulating 25(OH)D and 1,25(OH)2D: where we are and where we are going

The field of Vitamin D assay technology has progressed significantly over the past 4 decades. Further, the clinical utility of these measurements has moved from esoteric into mainstream clinical diagnosis. This movement has been fueled by the realization that Vitamin D is involved in bodily systems beyond skeletal integrity. The clinical assay techniques for circulating 25(OH)D and 1,25(OH)₂D have progressed away from competitive protein binding assay (CPBAs) that utilize tritium reporters to radioimmunoassay (RIAs) that utilize both I¹²⁵ and chemiluminescent reporters. These advances have allowed direct serum analysis of 25(OH)D in an automated format that provides a huge sample throughput. Detection of circulating 25(OH)D can also be achieved utilizing direct high-performance liquid chromatographic (HPLC) or liquid chromatography coupled with mass spectrometry (LC–MS) techniques. These methods are accurate, however, they require expensive equipment and restrict sample throughput in the large clinical laboratory. Direct serum detection of 1,25(OH)₂D is unlikely to occur for many reasons as a sample pre-purification will always be required. However, a semi-automated chemiluminescent detection system with automated sample preparation is in final development for the determination of circulating 1,25(OH)₂D. These advances will allow both 25(OH)D and 1,25(OH)₂D to be detected in an accurate, rapid fashion to meet the clinical demands we see emerging.     

Anticipation in lynch syndrome: where we are where we go

Lynch syndrome (LS) is the most common form of inherited predisposition to develop cancer mainly in the colon and endometrium but also in other organ sites. Germline mutations in DNA mismatch repair (MMR) gene cause the transmission of the syndrome in an autosomal dominant manner. The management of LS patients is complicated by the large variation in age at cancer diagnosis which requires these patients to be enrolled in surveillance protocol starting as early as in their second decade of life. Several environmental and genetic factors have been proposed to explain this phenotypic heterogeneity, but the molecular mechanisms remain unknown. Although the presence of genetic anticipation in Lynch syndrome has been suspected since 15 years, only recently the phenomenon has been increasingly reported to be present in different cancer genetic syndromes including LS. While the biological basis of earlier cancer onset in successive generations remains poorly known, recent findings point to telomere dynamics as a mechanism significantly contributing to genetic anticipation in Lynch syndrome and in other familial cancers. In this review, we summarize the clinical and molecular features of Lynch syndrome, with a particular focus on the latest studies that have investigated the molecular mechanisms of genetic anticipation.     

Glycosaminoglycanomics: where we are

Glycosaminoglycans regulate numerous physiopathological processes such as development, angiogenesis, innate immunity, cancer and neurodegenerative diseases. Cell surface GAGs are involved in cell-cell and cell-matrix interactions, cell adhesion and signaling, and host-pathogen interactions. GAGs contribute to the assembly of the extracellular matrix and heparan sulfate chains are able to sequester growth factors in the ECM. Their biological activities are regulated by their interactions with proteins. The structural heterogeneity of GAGs, mostly due to chemical modifications occurring during and after their synthesis, makes the development of analytical techniques for their profiling in cells, tissues, and biological fluids, and of computational tools for mining GAG-protein interaction data very challenging. We give here an overview of the experimental approaches used in glycosaminoglycomics, of the major GAG-protein interactomes characterized so far, and of the computational tools and databases available to analyze and store GAG structures and interactions.     

The current state of microbial proteomics: where we are and where we want to go

Proteomics allows the assessment of cellular processes in an unprecedented scale by providing a comprehensive quantitative and qualitative overview of the protein content of a cell. Consequently, proteomics has been employed to investigate a multitude of bacterial processes ranging from the analysis of environmental communities, identification of virulence factors to the proteome-guided optimization of production strains. Proteomics has, in short, become an indispensable tool for the global analysis of bacterial physiology. Nonetheless, challenges exist, especially in the accurate prediction of phenotypic consequences based on any given proteome composition. In this review, we will give an overview of current highlights in the area of microbial proteomics, discuss some current challenges and present new developments that may help in overcoming them.     

Birdlife International: who we are and where we have come from

Rands, M. 2000. Birdlife International: who we are and where we have come from. Ostrich 71 (1 & 2): 148–149.

The International Council for Bird Preservation (ICBP)—the forerunner of BirdLife International—was founded in 1922 by a small and dedicated group of individuals. It has grown into a world-wide network of Partner organisations and individuals committed to achieving the conservation of the world's birds and other biological diversity. The evolution and some major achievements of the organisation are outlined, from the early days of ICBP, to the current status of BirdLife International, actively represented in 80 countries world-wide. The BirdLife Vision, the mission of the Partnership, the regional structures and some of the personalities behind the conservation action are presented as the organisation looks forward to the challenge of conserving the world's birds in the 21st century.     

The assessment of circulating 25(OH)D and 1,25(OH)2D: Where we are and where we are going

The field of Vitamin D assay technology has progressed significantly over the past 4 decades. Further, the clinical utility of these measurements has moved from esoteric into mainstream clinical diagnosis. This movement has been fueled by the realization that Vitamin D is involved in bodily systems beyond skeletal integrity. The clinical assay techniques for circulating 25(OH)D and 1,25(OH)₂D have progressed away from competitive protein binding assay (CPBAs) that utilize tritium reporters to radioimmunoassay (RIAs) that utilize both I¹²⁵ and chemiluminescent reporters. These advances have allowed direct serum analysis of 25(OH)D in an automated format that provides a huge sample throughput. Detection of circulating 25(OH)D can also be achieved utilizing direct high-performance liquid chromatographic (HPLC) or liquid chromatography coupled with mass spectrometry (LC–MS) techniques. These methods are accurate, however, they require expensive equipment and restrict sample throughput in the large clinical laboratory. Direct serum detection of 1,25(OH)₂D is unlikely to occur for many reasons as a sample pre-purification will always be required. However, a semi-automated chemiluminescent detection system with automated sample preparation is in final development for the determination of circulating 1,25(OH)₂D. These advances will allow both 25(OH)D and 1,25(OH)₂D to be detected in an accurate, rapid fashion to meet the clinical demands we see emerging.     

Biological AFM: where we come from--where we are--where we may go

Biological atomic force microscopy (AFM) is a fast growing and advancing field. This review's objective is to overview the state of the art and to retrace achievements of biological AFM as presented by past and present research, and wishes to give a (subjective) outlook where AFM may go in the upcoming years. The following areas of interest are discussed: High-resolution imaging, cell imaging, single molecule force spectroscopy, cell mechanical measurements, combined AFM instrumentation, and AFM instrumentation. Of all these topics, particular representative examples are shown, each of them standing for a variety of achievements by many research groups.     

The conservation of non-marine molluscs in South America: where we are and how to move forward

Biodiversity and Conservation - South America is a high biodiversity continent with five out of 13 countries considered megadiverse. Many major groups within this fauna exhibit high diversity,...     

Embryonic stem cells for basic research and potential clinical applications in cardiology

Embryonic stem (ES) cells are pluripotent, possessing the unique property to differentiate into any somatic cell type while retaining the ability to proliferate indefinitely. Due to their ability to recapitulate embryonic differentiation, ES cells are an ideal tool to study the process of early embryogenesis in vitro. Signalling cascades and genes involved in differentiation can be easily studied, and functional genomics approaches aim to identify the regulatory networks underlying lineage commitment. Their unique ability to differentiate into any cell type make ES cells a prime candidate for cell replacement therapy (CRT) of various degenerative disorders. Results from various disease models are promising and have demonstrated their principal suitability as a therapeutic agent in diseases such as myocardial infarctions, diabetes mellitus and Parkinson's disease. Prior to clinical trials in humans, two issues remain to be solved: due to their high proliferative potential, ES cells can form teratocarcinomas in the recipient, and depending on the source of the cells, ES cell grafts may be rejected by the host organism. This review discusses the current state of basic ES cell research with a focus on cardiac differentiation and gives an overview of their use in CRT approaches.     

Optimizing stem cells for cardiac repair: Current status and new frontiers in regenerative cardiology

Cell therapy has the potential to improve healing of ischemic heart, repopulate injured myocardium and restore cardiac function. The tremendous hope and potential of stem cell therapy is well understood, yet recent trials involving cell therapy for cardiovascular diseases have yielded mixed results with inconsistent data thereby readdressing controversies and unresolved questions regarding stem cell efficacy for ischemic cardiac disease treatment. These controversies are believed to arise by the lack of uniformity of the clinical trial methodologies, uncertainty regarding the underlying reparative mechanisms of stem cells, questions concerning the most appropriate cell population to use, the proper delivery method and timing in relation to the moment of infarction, as well as the poor stem cell survival and engraftment especially in a diseased microenvironment which is collectively acknowledged as a major hindrance to any form of cell therapy. Indeed, the microenvironment of the failing heart exhibits pathological hypoxic, oxidative and inflammatory stressors impairing the survival of transplanted cells. Therefore, in order to observe any significant therapeutic benefit there is a need to increase resilience of stem cells to death in the transplant microenvironment while preserving or better yet improving their reparative functionality. Although stem cell differentiation into cardiomyocytes has been observed in some instance, the prevailing reparative benefits are afforded through paracrine mechanisms that promote angiogenesis, cell survival, transdifferentiate host cells and modulate immune responses. Therefore, to maximize their reparative functionality, ex vivo manipulation of stem cells through physical, genetic and pharmacological means have shown promise to enable cells to thrive in the postischemic transplant microenvironment. In the present work, we will overview the current status of stem cell therapy for ischemic heart disease, discuss the most recurring cell populations employed, the mechanisms by which stem cells deliver a therapeutic benefit andstrategies that have been used to optimize and increase survival and functionality of stem cells including ex vivo preconditioning with drugs and a novel pharmacooptimizer as well as genetic modifications.     

Human diversity: our genes tell where we live

A detailed genetic analysis of more than a thousand human subjects clusters them into five groups corresponding to major geographical regions. This new study shows that self-reported ancestry is a good predictor of one's genetic make-up.     

Hydatid control in Australia: where it began, what we have achieved and where to from here

Echinococcus granulosus was imported into Australia with domestic livestock about 200 years ago. It spread rapidly through domestic animals and quickly became a public health problem in the new colony. Control was hampered by ignorance of the transmission pattern. The association between metacestodes and tapeworms was not elucidated until 63 years after the arrival of the First Fleet. Australian wildlife were highly susceptible to infection with E. granulosus and wildlife/domestic animal interaction facilated rapid infiltration of wildlife by E. granulosus. The wildlife reservoir has hampered hydatid control campaigns on mainland Australia but successful eradication has been achieved in the island state of Tasmania where there was no wildlife reservoir. The application of a new recombinant vaccine for sheep in control campaigns and the use of praziquantel baits for controlling infection in dingoes around bush campsites and picnic areas is discussed.