Short-term Osteoclastic Activity Induced by Locally High Concentrations of Recombinant Human Bone Morphogenetic Protein–2 in a Cancellous Bone Environment

Study Design. An experimental study investigating osteoclastic activity induced by rhBMP-2 in sheep. Objective. To examine the effects of increasing local rhBMP-2 concentration on osteoclastic response and peri-implant bone resorption. Summary of Background Data. Level I clinical studies have established the safe and effective volume and concentration of rhBMP-2 delivered on an absorbable collagen sponge. However, peri-implant bone resorption appearing as decreased mineral density has been observed radiographically in rare instances after implantation of rhBMP-2 on an absorbable collagen sponge (rhBMP-2/ACS). Methods. Bilateral corticocancellous defects were created in the distal femora of 30 adult sheep. Combinations of rhBMP-2/ACS implant volume (V) (1V = normal fill or 2V = overfilled) and rhBMP-2 solution concentration (⤫) (1 ⤫ normal concentration or 3.5 ⤫ = hyperconcentrated) resulted in local rhBMP-2 concentrations of 0⤫, 1⤫, 2⤫, 3.5⤫, and 7⤫ the estimated effective concentration for this model. Faxitron radiography, quantitative CT, histology, and quantitative histomorphometry were conducted in a blinded fashion to analyze the effect of the treatments. Results. At 1 week, the normal fill-normal concentration implants (1⤫) produced the least transient osteoclastic activity resulting in limited peri-implant resorption. Overfilledhyperconcentrated implants (2⤫, 3.5⤫) demonstrated moderate resorption zones. Overfilled-hyperconcentrated implants (7⤫) demonstrated extensive osteoclastic activity and marked resorption. Results at 4 and 8 weeks revealed dense osteoid and bone in the voids with progressive bony healing. Control defects showed no osteoclastic activity with little to no bony healing. Conclusion. Increasing the local rhBMP-2 concentration by overfilling the defect with rhBMP-2/ACS or hyper-concentrating the rhBMP-2 solution on the absorbable collagen sponge led to a concentration-dependent osteoclastic resorption of peri-implant bone. The osteoclastic effect was transient, and progressive healing took place over the 8-week survival period

CONVERT: A program to evaluate hardwood sawmill conversion efficiency

CONVERT is a computer program that allows users to evaluate the conversion efficiency of hardwood sawmills. Users can consider six factors that influence conversion efficiency. Four of the factors reflect characteristics of hardwood sawmill machines: headrig kerf, headrig type, resaw kerf, and rough green size. The other factors reflect characteristics of the mill\u27s raw material inputs: average log length and average log diameter

Expression and functional analysis of TaASY1 during meiosis of bread wheat (Triticum aestivum)

Background: Pairing and synapsis of homologous chromosomes is required for normal chromosome segregation and the exchange of genetic material via recombination during meiosis. Synapsis is complete at pachytene following the formation of a tri-partite proteinaceous structure known as the synaptonemal complex (SC). In yeast, HOP1 is essential for formation of the SC, and localises along chromosome axes during prophase I. Homologues in Arabidopsis (AtASY1), Brassica (BoASY1) and rice (OsPAIR2) have been isolated through analysis of mutants that display decreased fertility due to severely reduced synapsis of homologous chromosomes. Analysis of these genes has indicated that they play a similar role to HOP1 in pairing and formation of the SC through localisation to axial/lateral elements of the SC. Results: The full length wheat cDNA and genomic clone, TaASY1, has been isolated, sequenced and characterised. TaASY1 is located on chromosome Group 5 and the open reading frame displays significant nucleotide sequence identity to OsPAIR2 (84%) and AtASY1 (63%). Transcript and protein analysis showed that expression is largely restricted to meiotic tissue, with elevated levels during the stages of prophase I when pairing and synapsis of homologous chromosomes occur. Immunolocalisation using transmission electron microscopy showed TaASY1 interacts with chromatin that is associated with both axial elements before SC formation as well as lateral elements of formed SCs. Conclusion: TaASY1 is a homologue of ScHOP1, AtASY1 and OsPAIR2 and is the first gene to be isolated from bread wheat that is involved in pairing and synapsis of homologous chromosomes.Scott A Boden, Nadim Shadiac, Elise J Tucker, Peter Langridge and Jason A Abl

The impact of four common lumbar spine diagnoses upon overall health status

Background Context: The SF-36 health survey has been shown to be a valid instrument when used to measure the self-reported physical and mental health of patients. The impact of lumbar spinal disorders can be assessed as the difference between the SF-36 scale scores and age-and-gender specific population norms. Purpose: To establish the impact upon the self-reported health status of patients with one of four common lumbar spinal diagnoses. Study Design: A cross-sectional, observational assessment of the health status of spine patients. Methods: Data from patients presenting to the participating centers of the National Spine Network with low back pain and/or leg pain, was collected prospectively using the Health Status Questionnaire 2.0. A database search identified patients with either herniated nucleus pulposus with radicular pain (HNP), lumbar spinal stenosis without deformity (SPS), degenerative spondylolisthesis (DS), and painful disc degeneration/spondylosis (DDD). The mean SF-36 scale scores were generated for each of the diagnostic groups. The impact of these diagnoses on health status was determined as the calculated difference from the age-and-gender specific population norms for each of the eight health scale scores. These scores, usually negative in this population, represent how far below normal these patients are. The analysis was stratified according to the age of the patients (\u3c40 yrs, 40-60 yrs, \u3e60 yrs). Analysis of variance and pair-wise comparison with Bonferroni correction were used to assess the significance of differences across diagnosis and age groups. Results: Data from a total of 4,442 patients was available for this study. All four diagnostic groups had large, negative impact scores for the eight general health scales with the greatest impact upon the three scales that best measure physical health. The greatest impact on these physical health scales (physical functioning, role-physical, and bodily pain) was seen in the HNP diagnostic group. The younger age groups (\u3c40 yrs and 40-60 yrs) had the greatest physical impairment when compared to the age-and-gender specific population norms. Analysis of variance showed a significant relationship between diagnosis and SF-36 scores, and between age groups and SF-36 scores. Conclusions: All four lumbar spine disorders have a significant negative impact on all eight of the SF-36 scales. The greatest negative impact was seen in those scales that measure physical health (RP, PF, and BP). The HNP diagnostic group experienced a significantly greater impact upon these three scales. This diagnostic group had the youngest patients, whose baseline physical functional status would be expected to be the most optimal. When we stratified by age in all the diagnostic groups, the greatest negative impact scores for physical health were seen in the \u3c 40 yrs and 40-60 yrs age groups. These patients were also more likely to perceive their health as poor, experience decreased energy, and have more social impairment when compared to their age/gender norms

A synthetic compound that potentiates bone morphogenetic protein-2-induced transdifferentiation of myoblasts into the osteoblastic phenotype

金沢大学附属病院リハビリテーション部There is an urgent need to develop methods that lower costs of using recombinant human bone morphogenetic proteins (BMPs) to promote bone induction. In this study, we demonstrate the osteogenic effect of a low-molecular weight compound, SVAK-12, that potentiated the effects of BMP-2 in inducing transdifferentiation of C2C12 myoblasts into the osteoblastic phenotype. Here, we report a specific compound, SVAK-12, which was selected based on in silico screenings of small-molecule databases using the homology modeled interaction motif of Smurf1-WW2 domain. The enhancement of BMP-2 activity by SVAK-12 was characterized by evaluating a BMP-specific reporter activity and by monitoring the BMP-2-induced expression of mRNA for osteocalcin and alkaline phosphatase (ALP), which are widely accepted marker genes of osteoblast differentiation. Finally, we confirmed these results by also measuring the enhancement of BMP-2-induced activity of ALP. Smurf1 is an E3 ligase that targets osteogenic Smads for ubiquitin-mediated proteasomal degradation. Smurf1 is an interesting potential target to enhance bone formation based on the positive effects on bone of proteins that block Smurf1-binding to Smad targets or in Smurf1-/- knockout mice. Since Smads bind Smurf1 via its WW2 domain, we performed in silico screening to identify compounds that might interact with the Smurf1-WW2 domain. We recently reported the activity of a compound, SVAK-3. However, SVAK-3, while exhibiting BMP-potentiating activity, was not stable and thus warranted a new search for a more stable and efficacious compound among a selected group of candidates. In addition to being more stable, SVAK-12 exhibited a dose-dependent activity in inducing osteoblastic differentiation of myoblastic C2C12 cells even when multiple markers of the osteoblastic phenotype were parallelly monitored. © 2010 Springer Science+Business Media, LLC

Reclassification of Thiomicrospira hydrogeniphila (Watsuji et al. 2016) to Thiomicrorhabdus hydrogenophila comb. nov., with emended description of Thiomicrorhabdus (Boden et al., 2017)

The genus Thiomicrorhabdus (Tmr) in the Piskirickettsiaceae in the Thiotrichales of the Gammaproteobacteria contains four species of sulfur-oxidising obligate chemolithoautotroph with validly published names, all previously classified as Thiomicrospira (Tms) species. Here we demonstrate that Thiomicrospira hydrogeniphila , a recently published hydrogen-utilising chemolithoautotroph closely related to Thiomicrorhabdus frisia (type species of Thiomicrorhabdus ) should be classified as a member of the genus Thiomicrorhabdus and not Thiomicrospira , as Thiomicrorhabdus hydrogeniphila comb. nov., on the basis of comparative physiology and morphology as well as 16S rRNA (rrs) gene identity of Tms. hydrogeniphila MAS2T being closer to that of Tmr. frisia JB-A2T (99.1 %) than to Tms. pelophila DSM 1534T (90.5 %) or Hydrogenovibrio marinus MH-110T (94.1 %), and on the basis of the topology of 16S rRNA gene maximum likelihood trees, which clearly place Tms. hydrogeniphila within the genus Thiomicrorhabdus . It was also noted that thiosulfate-grown Thiomicrorhabdus spp. can be distinguished from Thiomicrospira spp. or Hydrogenovibrio spp. on the basis of the 3 dominant fatty acids (C16 : 1, C18 : 1 and C16 : 0), and from other Thiomicrorhabdus spp. on the basis of the fourth dominant fatty acid, which varies between the species of this genus – which could provide a useful diagnostic method. We provide an emended description of Thiomicrorhabdus (Boden R, Scott KM, Williams J, Russel S, Antonen K et al. Int J Syst Evol Microbiol 2017;67:1140–1151) to take into account the properties of Thiomicrorhabdus hydrogeniphila comb. nov.c