An equine chromosome 3 inversion is associated with the tobiano spotting pattern in German horse breeds

The tobiano white-spotting pattern is one of several known depigmentation phenotypes in horses and is desired by many horse breeders and owners. The tobiano spotting phenotype is inherited as an autosomal dominant trait. Horses that are heterozygous or homozygous for the tobiano allele (To) are phenotypically indistinguishable. A SNP associated with To had previously been identified in intron 13 of the equine KIT gene and was used for an indirect gene test. The test was useful in several horse breeds. However, genotyping this sequence variant in the Lewitzer horse breed revealed that 14% of horses with the tobiano pattern did not show the polymorphism in intron 13 and consequently the test was not useful to identify putative homozygotes for To within this breed. Speculations were raised that an independent mutation might cause the tobiano spotting pattern in this breed. Recently, the putative causative mutation for To was described as a large chromosomal inversion on equine chromosome 3. One of the inversion breakpoints is approximately 70 kb downstream of the KIT gene and probably disrupts a regulatory element of the KIT gene. We obtained genotypes for the intron 13 SNP and the chromosomal inversion for 204 tobiano spotted horses and 24 control animals of several breeds. The genotyping data confirmed that the chromosomal inversion was perfectly associated with the To allele in all investigated horses. Therefore, the new test is suitable to discriminate heterozygous To/+ and homozygous To/To horses in the investigated breeds.

Natural and anthropogenic methane fluxes in Eurasia: a mesoscale quantification by generalized atmospheric inversion

Eight surface observation sites providing quasi-continuous measurements of atmospheric methane mixingratios have been operated since the mid-2000’s in Siberia. For the first time in a single work, we assimilate 1 year of these in situ observations in an atmospheric inversion. Our objective is to quantify methane surface fluxes from anthropogenic and wetland sources at the mesoscale in the Siberian lowlands for the year 2010. To do so, we first inquire about the way the inversion uses the observations and the way the fluxes are constrained by the observation sites. As atmospheric inver- sions at the mesoscale suffer from mis-quantified sources of uncertainties, we follow recent innovations in inversion techniques and use a new inversion approach which quantifies the uncertainties more objectively than the previous inversion systems. We find that, due to errors in the representation of the atmospheric transport and redundant pieces of information, only one observation every few days is found valuable by the inversion. The remaining high-resolution quasi-continuous signal is representative of very local emission patterns difficult to analyse with a mesoscale system. An analysis of the use of information by the inversion also reveals that the observation sites constrain methane emissions within a radius of 500 km. More observation sites than the ones currently in operation are then necessary to constrain the whole Siberian lowlands. Still, the fluxes within the constrained areas are quantified with objectified uncertainties. Finally, the tolerance intervals for posterior methane fluxes are of roughly 20 % (resp. 50 %) of the fluxes for anthropogenic (resp. wetland) sources. About 50–70 % of Siberian lowlands emissions are constrained by the inversion on average on an annual basis. Extrapolating the figures on the constrained areas to the whole Siberian lowlands, we find a regional methane budget of 5–28 TgCH4 for the year 2010, i.e. 1–5 % of the global methane emissions. As very few in situ observations are available in the region of interest, observations of methane total columns from the Greenhouse Gas Observing SATellite (GOSAT) are tentatively used for the evaluation of the inversion results, but they exhibit only a marginal signal from the fluxes within the region of interest.

Evaluating atmospheric methane inversion model results for Pallas, northern Finland

A state-of-the-art inverse model, CarbonTracker Data Assimilation Shell (CTDAS), was used to optimize estimates of methane (CH4) surface fluxes using atmospheric observations of CH4 as a constraint. The model consists of the latest version of the TM5 atmospheric chemistry-transport model and an ensemble Kalman filter based data assimilation system. The model was constrained by atmospheric methane surface concentrations, obtained from the World Data Centre for Greenhouse Gases (WDCGG). Prior methane emissions were specified for five sources: biosphere, anthropogenic, fire, termites and ocean, of which bio-sphere and anthropogenic emissions were optimized. Atmospheric CH 4 mole fractions for 2007 from northern Finland calculated from prior and optimized emissions were compared with observations. It was found that the root mean squared errors of the posterior esti - mates were more than halved. Furthermore, inclusion of NOAA observations of CH 4 from weekly discrete air samples collected at Pallas improved agreement between posterior CH 4 mole fraction estimates and continuous observations, and resulted in reducing optimized biosphere emissions and their uncertainties in northern Finland.

Inversion, Obviation, and Animacy in Native Languages of the Americas: Elements for a Cross-linguistic Survey

Native languages of the Americas whose predicate and clause structure reflect nominal hierarchies show an interesting range of structural diversity not only with respect to morphological makeup of their predicates and arguments but also with respect to the factors governing obviation status. The present article maps part of such diversity. The sample surveyed here includes languages with some sort of nonlocal (third person acting on third person) direction-marking system.

Percutaneous screw fixation of the iliosacral joint: optimal screw pathways are frequently not completely intraosseous

INTRODUCTION In iliosacral screw fixation, the dimensions of solely intraosseous (secure) pathways, perpendicular to the ilio-sacral articulation (optimal) with corresponding entry (EP) and aiming points (AP) on lateral fluoroscopic projections, and the factors (demographic, anatomic) influencing these have not yet been described. METHODS In 100 CTs of normal pelvises, the height and width of the secure and optimal pathways were measured on axial and coronal views bilaterally (total measurements: n=200). Corresponding EP and AP were defined as either the location of the screw head or tip at the crossing of lateral innominate bones' cortices (EP) and sacral midlines (AP) within the centre of the pathway, respectively. EP and AP were transferred to the sagittal pelvic view using a coordinate system with the zero-point in the centre of the posterior cortex of the S1 vertebral body (x-axis parallel to upper S1 endplate). Distances are expressed in relation to the anteroposterior distance of the S1 upper endplate (in %). The influence of demographic (age, gender, side) and/or anatomic (PIA=pelvic incidence angle; TCA=transversal curvature angle, PID-Index=pelvic incidence distance-index; USW=unilateral sacral width-index) parameters on pathway dimensions and positions of EP and AP were assessed (multivariate analysis). RESULTS The width, height or both factors of the pathways were at least 7mm or more in 32% and 53% or 20%, respectively. The EP was on average 14±24% behind the centre of the posterior S1 cortex and 41±14% below it. The AP was on average 53±7% in the front of the centre of the posterior S1 cortex and 11±7% above it. PIA influenced the width, TCA, PID-Index the height of the pathways. PIA, PID-Index, and USW-Index significantly influenced EP and AP. Age, gender, and TCA significantly influenced EP. CONCLUSION Secure and optimal placement of screws of at least 7mm in diameter will be unfeasible in the majority of patients. Thoughtful preoperative planning of screw placement on CT scans is advisable to identify secure pathways with an optimal direction. For this purpose, the presented methodology of determining and transferring EPs and APs of corresponding pathways to the sagittal pelvic view using a coordinate system may be useful.

Evaluation of a Novel Screw Position in a Type III Distal Phalanx Fracture Model: An Ex Vivo Study

OBJECTIVE: Mechanical evaluation of a novel screw position used for repair in a type III distal phalanx fracture model and assessment of solar canal penetration (SCP). STUDY DESIGN: Experimental study. SAMPLE POPULATION: Disarticulated equine hooves (n = 24) and 24 isolated distal phalanges. METHODS: Hooves/distal phalanges cut in a sagittal plane were repaired with 1 of 2 different cortical screw placements in lag fashion. In group 1 (conventional screw placement), the screw was inserted halfway between the proximal border of the solar canal (SC) and the subchondral bone surface on a line parallel to the dorsal cortex, whereas in group 2, the screw was inserted more palmar/plantar, where a perpendicular line drawn from the group 1 position reached the palmar/plantar cortex. Construct strength was evaluated by 3-point bending to failure. SCP was assessed by CT imaging and macroscopically. RESULTS: Screws were significantly longer in group 2 and in forelimbs. Group 2 isolated distal phalanges had a significantly more rigid fixation compared with the conventional screw position (maximum point at failure 31%, bending stiffness 41% higher). Lumen reduction of the SC was observed in 13/52 specimens (all from group 2), of which 9 were forelimbs. CONCLUSIONS: More distal screw positioning compared with the conventionally recommended screw position for internal fixation of type III distal phalangeal fractures allows placement of a longer screw and renders a more rigid fracture fixation. The novel screw position, however, carries a higher risk of SCP

Cheek Tooth Extraction Via a Minimally Invasive Transbuccal Approach and Intradental Screw Placement in 54 Equids

OBJECTIVE: To describe (1) preoperative findings and surgical technique, (2) intraoperative difficulties, and (3) postoperative complications and long-term outcome of equine cheek tooth extraction using a minimally invasive transbuccal screw extraction (MITSE) technique. STUDY DESIGN: Retrospective case series. ANIMALS: Fifty-four equids; 50 horses, 3 ponies, and 1 mule. METHODS: Fifty-eight MITSE procedures were performed to extract cheek teeth in 54 equids. Peri- and intraoperative difficulties, as well as short- (<1 month) and long-term (>6 months) postoperative complications were recorded. Followup information was obtained through telephone interviews, making specific inquiries about nasal discharge, facial asymmetry, and findings consistent with surgical site infection. RESULTS: Preoperative findings that prompted exodontia included 50 cheek teeth with apical infections, 48 fractures, 4 neoplasia, 2 displacements, and 1 supernumerary tooth. Previous oral extraction was attempted but had failed in 55/58 (95%) animals because of cheek tooth fracture in 28, or insufficient clinical crown for extraction with forceps in 27. MITSE was successful in removing the entire targeted dental structure in 47/58 (81%) procedures. However, MITSE failed to remove the entire targeted dental structure in 11/58 (19%) procedures and was followed by repulsion in 10/11 (91%). Short-term postoperative complications included bleeding (4/58 procedures, 7%) and transient facial nerve paralysis (4/58 procedures, 7%). Owners were satisfied with the functional and cosmetic outcome for 40/41 (98%) animals with followup. CONCLUSION: MITSE offers an alternate for cheek tooth extraction in equids, where conventional oral extraction is not possible or has failed. Overall, there was low morbidity, which compares favorably with invasive buccotomy or repulsion techniques

In vivo degradation of magnesium plate/screw osteosynthesis implant systems: Soft and hard tissue response in a calvarial model in miniature pigs.

Biodegradable magnesium plate/screw osteosynthesis systems were implanted on the frontal bone of adult miniature pigs. The chosen implant geometries were based on existing titanium systems used for the treatment of facial fractures. The aim of this study was to evaluate the in vivo degradation and tissue response of the magnesium alloy WE43 with and without a plasma electrolytic surface coating. Of 14 animals, 6 received magnesium implants with surface modification (coated), 6 without surface modification (uncoated), and 2 titanium implants. Radiological examination of the skull was performed at 1, 4, and 8 weeks post-implantation. After euthanasia at 12 and 24 weeks, X-ray, computed tomography, and microfocus computed tomography analyses and histological and histomorphological examinations of the bone/implant blocks were performed. The results showed a good tolerance of the plate/screw system without wound healing disturbance. In the radiological examination, gas pocket formation was found mainly around the uncoated plates 4 weeks after surgery. The micro-CT and histological analyses showed significantly lower corrosion rates and increased bone density and bone implant contact area around the coated screws compared to the uncoated screws at both endpoints. This study shows promising results for the further development of coated magnesium implants for the osteosynthesis of the facial skeleton.

Effect of an intervertebral disk spacer on stiffness after monocortical screw/polymethylmethacrylate fixation in simulated and cadaveric canine cervical vertebral columns.

OBJECTIVE To determine the biomechanical effect of an intervertebral spacer on construct stiffness in a PVC model and cadaveric canine cervical vertebral columns stabilized with monocortical screws/polymethylmethacrylate (PMMA). STUDY DESIGN Biomechanical study. SAMPLE POPULATION PVC pipe; cadaveric canine vertebral columns. METHODS PVC model-PVC pipe was used to create a gap model mimicking vertebral endplate orientation and disk space width of large-breed canine cervical vertebrae; 6 models had a 4-mm gap with no spacer (PVC group 1); 6 had a PVC pipe ring spacer filling the gap (PCV group 2). Animals-large breed cadaveric canine cervical vertebral columns (C2-C7) from skeletally mature dogs without (cadaveric group 1, n = 6, historical data) and with an intervertebral disk spacer (cadaveric group 2, n = 6) were used. All PVC models and cadaver specimens were instrumented with monocortical titanium screws/PMMA. Stiffness of the 2 PVC groups was compared in extension, flexion, and lateral bending using non-destructive 4-point bend testing. Stiffness testing in all 3 directions was performed of the unaltered C4-C5 vertebral motion unit in cadaveric spines and repeated after placement of an intervertebral cortical allograft ring and instrumentation. Data were compared using a linear mixed model approach that also incorporated data from previously tested spines with the same screw/PMMA construct but without disk spacer (cadaveric group 1). RESULTS Addition of a spacer increased construct stiffness in both the PVC model (P < .001) and cadaveric vertebral columns (P < .001) compared to fixation without a spacer. CONCLUSIONS Addition of an intervertebral spacer significantly increased construct stiffness of monocortical screw/PMMA fixation.

Biomechanical comparison between bicortical pin and monocortical screw/polymethylmethacrylate constructs in the cadaveric canine cervical vertebral column.

OBJECTIVE To compare biomechanical stiffness of cadaveric canine cervical spine constructs stabilized with bicortical stainless steel pins and polymethylmethacrylate (PMMA), monocortical stainless steel screws with PMMA, or monocortical titanium screws with PMMA. STUDY DESIGN Biomechanical cadaver study. ANIMALS Eighteen canine cervical vertebral columns (C2-C7) were collected from skeletally mature dogs (weighing 22-32 kg). METHODS Specimens were radiographed and examined by dual energy X-ray absorptiometry. Stiffness of the unaltered C4-C5 intervertebral motion unit was measured in extension, flexion and lateral bending using non-destructive 4-point bend testing. Specimens were then stabilized by (1) bicortical stainless steel pins/PMMA, (2) monocortical stainless steel screws/PMMA, or (3) monocortical titanium screws/PMMA. Mechanical testing was repeated and stiffness data from unaltered specimens and the 3 treatment groups were compared. RESULTS All 3 surgical methods significantly increased stiffness of the C4-C5 motion unit compared with the unaltered specimen (P < .001 for all treatments), but stiffness was not significantly different among the 3 fixation groups (P = .578). CONCLUSIONS In this model, monocortical screw fixation (with stainless steel or titanium screws) was biomechanically equivalent to bicortical fixation.

Zirconia-Based Screw-Retained Prostheses Supported by Implants: A Retrospective Study on Technical Complications and Failures

BACKGROUND Little information is yet available on zirconia-based prostheses supported by implants. PURPOSE To evaluate technical problems and failures of implant-supported zirconia-based prostheses with exclusive screw-retention. MATERIAL AND METHODS Consecutive patients received screw-retained zirconia-based prostheses supported by implants and were followed over a time period of 5 years. The implant placement and prosthetic rehabilitation were performed in one clinical setting, and all patients participated in the maintenance program. The treatment comprised single crowns (SCs) and fixed dental prostheses (FDPs) of three to 12 units. Screw-retention of the CAD/CAM-fabricated SCs and FDPs was performed with direct connection at the implant level. The primary outcome was the complete failure of zirconia-based prostheses; outcome measures were fracture of the framework or extensive chipping resulting in the need for refabrication. A life table analysis was performed, the cumulative survival rate (CSR) calculated, and a Kaplan-Meier curve drawn. RESULTS Two hundred and ninety-four implants supported 156 zirconia-based prostheses in 95 patients (52 men, 43 women, average age 59.1 ± 11.7 years). Sixty-five SCs and 91 FDPs were identified, comprising a total of 441 units. Fractures of the zirconia framework and extensive chipping resulted in refabrication of nine prostheses. Nearly all the prostheses (94.2%) remained in situ during the observation period. The 5-year CSR was 90.5%, and 41 prostheses (14 SCs, 27 FDPs) comprising 113 units survived for an observation time of more than 5 years. Six SCs exhibited screw loosening, and polishing of minor chipping was required for five prostheses. CONCLUSIONS This study shows that zirconia-based implant-supported fixed prostheses exhibit satisfactory treatment outcomes and that screw-retention directly at the implant level is feasible.

Two distinct filopodia populations at the growth cone allow to sense nanotopographical extracellular matrix cues to guide neurite outgrowth

BACKGROUND The process of neurite outgrowth is the initial step in producing the neuronal processes that wire the brain. Current models about neurite outgrowth have been derived from classic two-dimensional (2D) cell culture systems, which do not recapitulate the topographical cues that are present in the extracellular matrix (ECM) in vivo. Here, we explore how ECM nanotopography influences neurite outgrowth. METHODOLOGY/PRINCIPAL FINDINGS We show that, when the ECM protein laminin is presented on a line pattern with nanometric size features, it leads to orientation of neurite outgrowth along the line pattern. This is also coupled with a robust increase in neurite length. The sensing mechanism that allows neurite orientation occurs through a highly stereotypical growth cone behavior involving two filopodia populations. Non-aligned filopodia on the distal part of the growth cone scan the pattern in a lateral back and forth motion and are highly unstable. Filopodia at the growth cone tip align with the line substrate, are stabilized by an F-actin rich cytoskeleton and enable steady neurite extension. This stabilization event most likely occurs by integration of signals emanating from non-aligned and aligned filopodia which sense different extent of adhesion surface on the line pattern. In contrast, on the 2D substrate only unstable filopodia are observed at the growth cone, leading to frequent neurite collapse events and less efficient outgrowth. CONCLUSIONS/SIGNIFICANCE We propose that a constant crosstalk between both filopodia populations allows stochastic sensing of nanotopographical ECM cues, leading to oriented and steady neurite outgrowth. Our work provides insight in how neuronal growth cones can sense geometric ECM cues. This has not been accessible previously using routine 2D culture systems.