The effect of electromagnetic fields on postoperative pain and locomotor recovery in dogs with acute, severe thoracolumbar intervertebral disc extrusion: a randomized placebo-controlled, prospective clinical trial.

Spinal cord injury (SCI) due to acute intervertebral disc extrusions (IVDE) is common in dogs and is treated by surgical decompression. Dogs with sensorimotor complete injuries have an incomplete recovery. Pulsed electromagnetic fields (PEMF) reduce postoperative pain through anti-inflammatory effects and there is growing evidence for neuroprotective effects. This randomized, controlled clinical trial evaluated the effect of PEMF on post-operative pain and neurologic recovery in dogs with surgically treated sensorimotor complete SCI due to acute IVDE. Sixteen dogs with surgically treated complete thoracolumbar SCI were randomized to receive PEMF (15 minutes every 2 hours for 2 weeks then twice daily for 4 weeks) or placebo starting immediately after diagnosis. The primary outcome was gait score at 2 weeks. Secondary measures of gait, pain perception and proprioceptive function were evaluated at 2 and 6 weeks. Plasma GFAP concentration was measured as a SCI biomarker. Post-operative pain was quantified by measuring mechanical sensory thresholds (MST) at control and surgical sites. There was no significant difference in demographics or GFAP concentration between the 2 groups at trial entry. There was no difference in primary outcome or in secondary measures of gait, but proprioceptive placing was significantly better at 6 weeks and GFAP concentrations were significantly lower at 2 weeks in the PEMF group. MSTs were significantly higher in the PEMF treated group. We conclude that PEMF reduced incision-associated pain in dogs following surgery for IVDE and may reduce extent of spinal cord injury and enhance proprioceptive placing. Larger clinical trials are warranted

Genes in the postgenomic era

We outline three very different concepts of the gene - 'instrumental', 'nominal', and 'postgenomic'. The instrumental gene has a critical role in the construction and interpretation of experiments in which the relationship between genotype and phenotype is explored via hybridization between organisms or directly between nucleic acid molecules. It also plays an important theoretical role in the foundations of disciplines such as quantitative genetics and population genetics. The nominal gene is a critical practical tool, allowing stable communication between bioscientists in a wide range of fields grounded in well-defined sequences of nucleotides, but this concept does not embody major theoretical insights into genome structure or function. The post-genomic gene embodies the continuing project of understanding how genome structure supports genome function, but with a deflationary picture of the gene as a structural unit. This final concept of the gene poses a significant challenge to conventional assumptions about the relationship between genome structure and function, and between genotype and phenotype

Sensory Ataxic Neuropathy in Golden Retriever Dogs Is Caused by a Deletion in the Mitochondrial tRNATyr Gene

Sensory ataxic neuropathy (SAN) is a recently identified neurological disorder in golden retrievers. Pedigree analysis revealed that all affected dogs belong to one maternal lineage, and a statistical analysis showed that the disorder has a mitochondrial origin. A one base pair deletion in the mitochondrial tRNATyr gene was identified at position 5304 in affected dogs after re-sequencing the complete mitochondrial genome of seven individuals. The deletion was not found among dogs representing 18 different breeds or in six wolves, ruling out this as a common polymorphism. The mutation could be traced back to a common ancestor of all affected dogs that lived in the 1970s. We used a quantitative oligonucleotide ligation assay to establish the degree of heteroplasmy in blood and tissue samples from affected dogs and controls. Affected dogs and their first to fourth degree relatives had 0–11% wild-type (wt) sequence, while more distant relatives ranged between 5% and 60% wt sequence and all unrelated golden retrievers had 100% wt sequence. Northern blot analysis showed that tRNATyr had a 10-fold lower steady-state level in affected dogs compared with controls. Four out of five affected dogs showed decreases in mitochondrial ATP production rates and respiratory chain enzyme activities together with morphological alterations in muscle tissue, resembling the changes reported in human mitochondrial pathology. Altogether, these results provide conclusive evidence that the deletion in the mitochondrial tRNATyr gene is the causative mutation for SAN

Syndromics: A Bioinformatics Approach for Neurotrauma Research

Substantial scientific progress has been made in the past 50 years in delineating many of the biological mechanisms involved in the primary and secondary injuries following trauma to the spinal cord and brain. These advances have highlighted numerous potential therapeutic approaches that may help restore function after injury. Despite these advances, bench-to-bedside translation has remained elusive. Translational testing of novel therapies requires standardized measures of function for comparison across different laboratories, paradigms, and species. Although numerous functional assessments have been developed in animal models, it remains unclear how to best integrate this information to describe the complete translational “syndrome” produced by neurotrauma. The present paper describes a multivariate statistical framework for integrating diverse neurotrauma data and reviews the few papers to date that have taken an information-intensive approach for basic neurotrauma research. We argue that these papers can be described as the seminal works of a new field that we call “syndromics”, which aim to apply informatics tools to disease models to characterize the full set of mechanistic inter-relationships from multi-scale data. In the future, centralized databases of raw neurotrauma data will enable better syndromic approaches and aid future translational research, leading to more efficient testing regimens and more clinically relevant findings

The production of a physiological puzzle: how Cytisus adami confused and inspired a century’s botanists, gardeners, and evolutionists

‘Adam’s laburnum’ (or Cytisus adami), produced by accident in 1825 by Jean-Louis Adam, a nurseryman in Vitry, became a commercial success within the plant trade for its striking mix of yellow and purple flowers. After it came to the attention of members of La Société d’Horticulture de Paris, the tree gained enormous fame as a potential instance of the much sought-after ‘graft hybrid’, a hypothetical idea that by grafting one plant onto another, a mixture of the two could be produced. As I show in this paper, many eminent botanists and gardeners, including Charles Darwin, both experimented with Adam’s laburnum and argued over how it might have been produced and what light, if any, it shed on the laws of heredity. Despite Jean-Louis Adam’s position and status as a nurseryman active within the Parisian plant trade, a surprising degree of doubt and scepticism was attached to his testimony on how the tree had been produced in his nursery. This doubt, I argue, helps us to trace the complex negotiations of authority that constituted debates over plant heredity in the early 19th century and that were introduced with a new generation of gardening and horticultural periodicals