Power to the people: a wiki-governance model for biobanks

Biobanks are adopting various modes of public engagement to close the agency gap between participants and biobank builders. We propose a wiki-governance model for biobanks that harnesses Web 2.0, and which gives citizens the ability to collaborate in biobank governance and policymaking.     

Realizing the promise of IVF in cattle--an overview

The in vitro-produced embryo could play a central role in dairy and beef production systems because of its potential role in genetic selection strategies and crossbreeding schemes, and because it can be integrated into reproductive management strategies for improving pregnancy rates in herds with low fertility. The promise attendant upon use of in vitro-produced embryos is not being fully realized, however. Indeed, there are important technical limitations to their production that reduce the desirability of in vitro-produced embryos because of increased costs, sub-optimal embryonic and fetal survival, and offspring that are occasionally abnormal. Most technical problems associated with in vitro production of embryos can be overcome through research. Among the requirements for a successful research program will be renewed emphasis on conducting embryo transfer trials to determine effects of modifications to embryo production protocols on pregnancy rates and fetal development. Given the promise of in vitro embryo technologies, there is an urgent need for a concerted and sustained investment in research to improve these technologies. Developing a consensus that the study of embryo technology is one of the most important areas of agricultural research should be both an individual and organizational priority.     

Alternative consent models for biobanks: the new Spanish law on biomedical research

This article provides an overview of recent contributions to the debate on the ethical use of previously collected biobank samples, as well as a country report about how this issue has been regulated in Spain by means of the new Biomedical Research Act, enacted in the summer of 2007. By contrasting the Spanish legal situation with the wider discourse of international bioethics, we identify and discuss a general trend moving from the traditional requirements of informed consent towards new models more favourable to research in a post-genomic context.     

Closure of population biobanks and direct-to-consumer genetic testing companies

Genetic research gained new momentum with the completion of the Human Genome Project in 2003. Formerly centered on the investigation of single-gene disorders, genetic research is increasingly targeting common complex diseases and in doing so is studying the whole genome, the environment and its impact on genomic variation. Consequently, biobanking initiatives have emerged around the world as a tool to sustain such progress. Whether they are small scale or longitudinal, public or private, commercial or non-commercial, biobanks should consider the possibility of closure. Interestingly, while raising important ethical issues, this topic has hardly been explored in the literature. Indeed, ethical issues associated with sale, insolvency, end of funding, or transfer of materials to other entities (which are all issues either related to or possible consequences of closure) are seldom the subject of discussion. In an attempt to fill this gap, this paper will discuss—using population and direct-to-consumer (DTC) genetic testing companies’ biobanks as case studies—(1) international and national normative documents addressing the issue of closure and (2) the internal policies of population biobanks and DTC genetic testing companies. The analysis will inform the debate on biobank closure and elucidate the underlying ethical issues, which include, but are not limited to informed consent, storage and privacy.     

Baciphelacin: a new eukaryotic translation inhibitor

Baciphelacin an antibiotic produced by Bacillus thiaminolyticus was a potent inhibitor of protein synthesis in HeLa cells and other mammalian cell lines. It had no effect on DNA or RNA synthesis. Concentrations of baciphelacin around 10⁻⁷ M inhibited protein synthesis by 50% in intact cells. The antibiotic had no effect on protein synthesis in Saccharomyces cerevisiae or Escherichia coli, but inhibited the protozoan Trypanosoma brucei. In vitro protein synthesis in a rabbit reticulocyte cell-free system was blocked by baciphelacin. However, translation of globin mRNA in a wheat cell-free system was not affected by this antibiotic. Baciphelacin had no activity against a number of cell-free systems used to measure different steps of translation, including binding of substrates to the ribosome, peptide bond formation and polyphenylalanine synthesis. Therefore, it is assumed that it affects the initiation of translation or the charging of tRNA. Finally, the inhibition of protein synthesis by compounds structurally related to baciphelacin was tested and their effects compared to baciphelacin.     

Engineered exosomes: A new promise for the management of musculoskeletal diseases

Background

Exosomes are nanovesicles actively secreted by potentially all cell types, including tumour cells, with the primary role of extracellular systemic communication mediators, both at autocrine and paracrine levels, at short and long distances. Recently, different studies have used exosomes as a delivery system for a plethora of different molecules, such as drugs, microRNAs and proteins. This has been made possible thanks to the simplicity in exosomes engineering, their great stability and versatility for applications in oncology as well as in regenerative medicine.

Non-kinase second-messenger signaling: new pathways with new promise

Intercellular signaling by growth factors, hormones and neurotransmitters produces second messenger molecules such as cyclic adenosine monophosphate (cAMP) and diacylglycerol (DAG). Protein Kinase A and Protein Kinase C are the principal effector proteins of these prototypical second messengers in certain cell types. Recently, novel receptors for cAMP and DAG have been identified. These proteins, designated EPAC (Exchange Protein directly Activated by cAMP) or cAMP-GEF (cAMP regulated Guanine nucleotide Exchange Factor) and CalDAG-GEF (Calcium and Diacylglycerol regulated Guanine nucleotide Exchange Factor) or RasGRP (Ras Guanine nucleotide Releasing Protein) are able to mediate some of the physiologic effects of the second messengers in a protein-kinase-independent fashion. These proteins are exchange factors for Ras family GTPases that operate in pathways that run parallel to the classic kinase-dependent pathways. The rapidly emerging recognition of the functions of these "non-kinase" effectors in diverse processes such as insulin secretion, thymocyte development, asthma and malignant transformation creates new opportunities for discovery and identifies potential new therapeutic targets.     

Human small breast epithelial mucin: the promise of a new breast tumor biomarker

Breast cancer remains one of the most frequently diagnosed cancers today. In developed countries, one in eight women is expected to present with breast cancer within her lifetime and an estimated 1,000,000 cases are detected each year worldwide (Canadian Cancer Statistics, http://www.cancer.ca/vgn/images/ portal/cit_86751114/14/33/1959864 11niw_stats2004_en.pdf). For women with recurrent disease, the median time of survival is about 2 years. Despite optimal surgery, adjuvant irradiation, hormonal treatment, and chemotherapy, approximately 30% of patients with localized breast cancer finally develop distant metastases. Early detection, which enables intervention at a localized and potentially curable stage, remains a central goal in breast cancer treatment. Indeed, the 5-year survival rate for women with breast cancer has been shown to increase dramatically when the disease is diagnosed at an early stage: from less than 25% in women with disseminated cancer to about 75% in patients with regional disease and over 95% in women with a localized tumor (Breast Cancer Facts and Figures, 2001-2002, http://www.cancer.org/downloads/STT/BrCaFF 2001.pdf). Unfortunately, only 60% of all breast cancers are diagnosed at a local stage. Any improvement in early detection through identification of tumor biomarkers would have a significant impact on reducing overall breast cancer mortality.     

The scanning model for translation: an update

The small (40S) subunit of eukaryotic ribosomes is believed to bind initially at the capped 5'-end of messenger RNA and then migrate, stopping at the first AUG codon in a favorable context for initiating translation. The first-AUG rule is not absolute, but there are rules for breaking the rule. Some anomalous observations that seemed to contradict the scanning mechanism now appear to be artifacts. A few genuine anomalies remain unexplained.     

Children and biobanks: a review of the ethical and legal discussion

The use of tissue samples from children is vital to genetic research. Collections of such tissue, in so-called biobanks, can take the form of large-scale prospective cohort studies or disease-specific studies using tissue of children with that specific disease. Collections of samples gathered in a diagnostics context, such as blood spot cards, can also be used for genetic research. Research on stored tissue samples from children poses ethical questions that are different from those posed by the use of samples from adults. Also, the ethical questions raised by the participation of children in biobanks are not analogous to those raised by the participation of children in clinical trials. In this review we first give an overview of the international ethical guidelines and legal regulations concerning biobanking and minors. Next, we review the different themes that occur in the ethical literature on this subject. Specifically we focus on questions of risk and benefit, consent and assent and the return of individual results. We also discuss the concept of solidarity, which is a relatively new concept in the context of children and biomedical research. To conclude, we discuss the gaps and questions raised by the review.     

Nucleic-acid-templated synthesis as a model system for ancient translation

The translation of nucleic acids into synthetic structures with expanded functional potential has been the subject of considerable research, with applications including small-molecule and polymer evolution, reaction discovery and sensing. Here, we review properties of nucleic-acid-templated synthesis in the context of requirements for prebiotic translation. This analysis highlights the chemical possibilities of ancient translation systems, as well as challenges that these systems may have faced.     

A model for the development of genetic translation

Several models have been advanced, both in this journal and others, for the development of the genetic code and translation apparatus. Eigen in particular has put forward a detailed model based on the hypercycle. This paper uses some of these previous ideas to develop a new model of the code and translation in which the pairs AU and GC play complementary roles, and in whichtRNAs develop from a molecule withtwo loops which stacks in repetitive patterns without the need for a messenger RNA. Thus a bridge is provided between random, (or autocatalytic) polymerization, and coded translation. In addition, alternative postulates to several of Eigen's ideas are tested by computer simulation.     

The promise and limitations of population exomics for human evolution studies

Exome sequencing is poised to yield substantial insights into human genetic variation and evolutionary history, but there are significant challenges to overcome before this becomes a reality.     

Systems vaccinology: a promise for the young and the poor

As a child, the risk of suffering and dying from infection is higher the younger you are; and higher, the less developed a region you are born in. Childhood vaccination programmes have greatly reduced mortality around the world, but least so for the very young among the very poor of the world. This appears partly owing to suboptimal vaccine effectiveness. Unfortunately, although most vaccines are administered to the newborn and very young infant (less than or equal to two months), we know the least about their host response to vaccination. We thus currently lack the knowledge to guide efforts aimed at improving vaccine effectiveness in this vulnerable population. Systems vaccinology, the study of molecular networks activated by immunization, has begun to provide unprecedented insights into mechanisms leading to vaccine-induced protection from infection or disease. However, all published reports of systems vaccinology have focused on either adults or at most children and older infants, not those most in need, i.e. newborns and very young infants. Given that the tools of systems vaccinology work perfectly well with very small sample volumes, it is time we deliver the promise that systems vaccinology holds for those most in need of vaccine-mediated protection from infection.     

Nanobiotechnology: the promise and reality of new approaches to molecular recognition

Nanobiotechnology is the convergence of engineering and molecular biology that is leading to a new class of multifunctional devices and systems for biological and chemical analysis with better sensitivity and specificity and a higher rate of recognition. Nano-objects with important analytical applications include nanotubes, nanochannels, nanoparticles, nanopores and nanocapacitors. Here, we take a critical look at the subset of recent developments in this area relevant to molecular recognition. Potential benefits of using nano-objects (nanotubes, quantum dots, nanorods and nanoprisms) and nanodevices (nanocapacitors, nanopores and nanocantilevers) leading to an expanded range of label multiplexing are described along with potential applications in future diagnostics. We also speculate on further pathways in nanotechnology development and the emergence of order in this somewhat chaotic, yet promising, new field.