Are we ready for back-to-nature crop breeding?

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Durable power of attorney for health care. Are we ready for it?

Health care professionals need to be well informed about advance directives for medical care in the event a patient becomes incapacitated. The Patient Self-Determination Act requires that all patients be advised of their options at the time of hospital admission. Hospitals and health care professionals will need to work together to plan for implementing this law. We surveyed 215 physicians, nurses, and social workers at a Veterans Affairs Medical Center about the California advance directive, the Durable Power of Attorney for Health Care. Attitudes were generally positive. All of the social workers had heard of the durable power of attorney directive, but 36% of physicians and nurses had never heard of it and an additional 20% had no experience with one. For respondents who had heard of the directive, the mean knowledge score was 6.35 of a possible 10 (5 predicted by chance). Respondents brought up the issue of durable power of attorney with patients before a crisis only 19% of the time and determined whether one had been signed for only 16% of older patients in hospital. The most commonly cited reasons for failure to discuss this with patients were lack of proper forms, pamphlets, or a place to refer a patient. Of those who had ever seen such a document in use, 42% were aware of a problem with it at some time. Whereas attitudes toward advance directives are positive, many physicians and nurses had little knowledge of the Durable Power of Attorney for Health Care and were poorly equipped to discuss it with patients. We encourage educating hospital staff to prepare for the enactment of the Patient Self-Determination Act. We also recommend that the concerns raised by professionals about the use of a durable power of attorney be addressed.     

Scoring functions for protein–protein interactions

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Systems for the detection and analysis of protein–protein interactions

The analysis of protein–protein interactions is important for developing a better understanding of the functional annotations of proteins that are involved in various biochemical reactions in vivo. The discovery that a protein with an unknown function binds to a protein with a known function could provide a significant clue to the cellular pathway concerning the unknown protein. Therefore, information on protein–protein interactions obtained by the comprehensive analysis of all gene products is available for the construction of interactive networks consisting of individual protein–protein interactions, which, in turn, permit elaborate biological phenomena to be understood. Systems for detecting protein–protein interactions in vitro and in vivo have been developed, and have been modified to compensate for limitations. Using these novel approaches, comprehensive and reliable information on protein–protein interactions can be determined. Systems that permit this to be achieved are described in this review.K. Kuroda, M. Kato and J. Mima contributed equally to this work.     

Data mining for protein–protein interactions in invertebrate model organisms

Well-annotated genome databases are available for many invertebrate species, notably the fruitfly, Drosophila melanogaster, and the nematode, Caenorhabditis elegans. An adequate interpretation of this information at the biological level requires the exploration of the interactions between the gene products. Knowledge of protein interactions and the components of cell signalling pathways in the fly and worm are particularly valuable as hypotheses can be rapidly tested using the powerful genetic toolkits available. Invertebrates offer additional experimental advantages when attempting to characterise protein–protein interactions (PPIs). Their relatively small genome size compared to mammals helps to reduce missed interactions due to redundancy, and their function can be addressed using forward (mutants) and reverse (RNA interference) genetics. However, the researcher looking for evidence of PPIs for a protein of interest is faced with the challenge of extracting interaction data from sources that are highly varied, such as the results of microarray experiments in the unstructured text of research papers. This challenge is greatly reduced by a range of public databases of curated information, as well as publicly available, enhanced search engines, which can provide either direct experimental evidence for a PPI, or valuable clues for generating new hypotheses.     

Are we ready for therapeutic drug monitoring of biologic therapeutics?

In the previous issue of Arthritis Research & Therapy, Ducourau and colleagues report that they retrospectively detected anti-infliximab antibodies in 21% of patients with rheumatic diseases. Patients with anti-infliximab antibodies had lower serum drug concentrations. These findings contribute to the existing evidence of immunogenicity of biologicals and its clinical relevance. We argue for therapeutic drug monitoring to optimize treatment response.     

Are we ready for a natural history of motor learning?

Here we argue that general principles with regard to the contributions of the cerebellum, basal ganglia, and primary motor cortex to motor learning can begin to be inferred from explicit comparison across model systems and consideration of phylogeny. Both the cerebellum and the basal ganglia have highly conserved circuit architecture in vertebrates. The cerebellum has consistently been shown to be necessary for adaptation of eye and limb movements. The precise contribution of the basal ganglia to motor learning remains unclear but one consistent finding is that they are necessary for early acquisition of novel sequential actions. The primary motor cortex allows independent control of joints and construction of new movement synergies. We suggest that this capacity of the motor cortex implies that it is a necessary locus for motor skill learning, which we argue is the ability to execute selected actions with increasing speed and precision.     

Genome editing in livestock: Are we ready for a revolution in animal breeding industry?

Genome editing is a powerful technology that can efficiently alter the genome of organisms to achieve targeted modification of endogenous genes and targeted integration of exogenous genes. Current genome-editing tools mainly include ZFN, TALEN and CRISPR/Cas9, which have been successfully applied to all species tested including zebrafish, humans, mice, rats, monkeys, pigs, cattle, sheep, goats and others. The application of genome editing has quickly swept through the entire biomedical field, including livestock breeding. Traditional livestock breeding is associated with rate limiting issues such as long breeding cycle and limitations of genetic resources. Genome editing tools offer solutions to these problems at affordable costs. Generation of gene-edited livestock with improved traits has proven feasible and valuable. For example, the CD163 gene-edited pig is resistant to porcine reproductive and respiratory syndrome (PRRS, also referred to as “blue ear disease”), and a SP110 gene knock-in cow less susceptible to tuberculosis. Given the high efficiency and low cost of genome editing tools, particularly CRISPR/Cas9, it is foreseeable that a significant number of genome edited livestock animals will be produced in the near future; hence it is imperative to comprehensively evaluate the pros and cons they will bring to the livestock breeding industry. Only with these considerations in mind, we will be able to fully take the advantage of the genome editing era in livestock breeding.     

Protein–protein interactions of huntingtin in the hippocampus

Molecular Biology - Huntingtin (HTT) occurs in the neuronal cytoplasm and can interact with structural elements of synapses. Huntington’s disease (HD) results from pathological expansion of a...     

Are we stuck in the standards?

To avoid duplication of effort, slow adoption and inefficiency in development, those developing biological standards need to communicate more with each other, attract help from experts in the ontology/standards communities and keep focused on needs of users.     

Novel therapeutic approaches in utilizing platelet lysate in regenerative medicine: Are we ready for clinical use?

Hemoderivative materials are used to treat different diseases. These derivatives include platelet-rich plasma, serum, platelet gel, and platelet lysate (PL). Among them, PL contains more growth factors than the others and its production is inexpensive and easy. PL is one of the proper sources of platelet release factors. It is used in cells growth and proliferation and is a good alternative to fetal bovine serum. In recent years, the clinical use of PL has gained more appeal by scientists. PL is a solution saturated by growth factors, proteins, cytokines, and chemokines and is administered to treat different diseases such as wound healing, bone regeneration, alopecia, oral mucositis, radicular pain, osteoarthritis, and ocular diseases. In addition, it can be used in cell culture for cell therapy and tissue transplantation purposes. Platelet-derived growth factor, fibroblast growth factor, insulin-like growth factor, transforming growth factor β, and vascular endothelial growth factor are key PL growth factors playing a major role in cell proliferation, wound healing, and angiogenesis. In this paper, we scrutinized recent advances in using PL and PL-derived growth factors to treat diseases and in regenerative medicine, and the ability to replace PL with other hemoderivative materials.     

Are competing intermolecular and intramolecular interactions of PERIOD protein important for the regulation of circadian rhythms in Drosophila?

Genetic analysis is revealing molecular components of circadian rhythms. The gene products of the period gene in Drosophila and the frequency gene in Neurospora oscillate with a circadian rhythm. A recent paper⁽¹⁾ has shown that the PERIOD protein can undergo both intermolecular and intramolecular interactions in vitro. The effects of temperature and two period mutations on these molecular interactions were compared to the effects of the mutations and temperature on the in vivo period length of circadian rhythms. The results suggest that the molecular interactions may compete to maintain a rhythm with a constant period over a wide temperature range.     

Split focal adhesion kinase for probing protein–protein interactions

Since protein–protein interactions (PPIs) regulate a variety of cellular processes, the detection of PPIs is crucial for elucidating the underlying molecular mechanisms as well as developing therapeutics. In this study, we propose a novel system to detect PPIs using the distinct domains of focal adhesion kinase (FAK). In this system named “split FAK”, the linker and kinase domains in native FAK are tethered separately to two target proteins of interest. The interaction between the target proteins brings the linker and kinase domains into proximity, which leads to phosphorylation at Y397 of the linker domain, recruitment of another tyrosine kinase Src, and phosphorylation at Y576 of the kinase domain. PPIs are readily detected by probing phosphorylation at Y397 and Y576 of these domains. To demonstrate this system, we designed a series of split FAK chimeras with different domain structures. Consequently, dimerizer-induced interaction between FK506-binding protein 12 (FKBP) and the T2098L mutant of FKBP12-rapamycin binding domain (FRB) was clearly detected by probing phosphorylation at the specific tyrosine residues of most of the split FAK chimeras. This is a novel PPI detection system based on a mechanism-inspired design of a trans-activated split kinase.