A survey of ovary-, testis-, and soma-biased gene expression in Drosophila melanogaster adults

BACKGROUND: Sexual dimorphism results in the formation of two types of individuals with specialized reproductive roles and is most evident in the germ cells and gonads. RESULTS: We have undertaken a global analysis of transcription between the sexes using a 31,464 element FlyGEM microarray to determine what fraction of the genome shows sex-biased expression, what tissues express these genes, the predicted functions of these genes, and where these genes map onto the genome. Females and males (both with and without gonads), dissected testis and ovary, females and males with genetically ablated germlines, and sex-transformed flies were sampled. CONCLUSIONS: Using any of a number of criteria, we find extensive sex-biased expression in adults. The majority of cases of sex differential gene expression are attributable to the germ cells. There is also a large class of genes with soma-biased expression. There is little germline-biased expression indicating that nearly all genes with germline expression also show sex-bias. Monte Carlo simulations show that some genes with sex-biased expression are non-randomly distributed in the genome

Short‐term outcomes of 59 dogs treated for ilial body fractures with locking or non‐locking plates

Objective: To determine the influence of plating systems on the clinical outcomes in dogs treated for ilial fractures. Design: Retrospective study. Animals: Fifty‐nine dogs (63 hemipelves). Methods: Radiographs and medical records of dogs with ilial fractures presented to Iowa State University between 2003 and 2019 were reviewed. After fracture reduction, fractures were fixed with a locking plate system (LPS) or non‐locking plate system (NLS). Perioperative, long‐term complications, and follow‐up data were recorded. The frequency of implant failure and pelvic collapse were compared using a logistic and linear regression analysis, respectively. Where the univariate test was statistically significant, a multivariate analysis across categories was performed to identify statistically different categories. Results: LPS and NLS implants were used in 25/63 and 38/63 hemipelves, respectively. Median follow‐up time was 8 weeks (3–624 weeks). Implant failure occurred in 18/63 (29%) of fracture repairs, consisting of 17 with NLS and 1 with LPS. Revision surgery was recommended in five cases of implant failure, all with NLS. The probability of implant failure was higher when fractures were fixed with NLS (p = .0056). All other variables evaluated did not seem to influence outcome measures. Conclusion: The variable with the most influence on the outcomes of dogs treated for ilial fractures consisted of the fixation method (NLS vs. LPS). Fractures repaired with NLS were nearly 20 times more likely to fail than those repaired with LPS. Clinical Relevance: Surgeons should consider repairing ilial body fractures in dogs with LPS to reduce the risk of short‐term implant failure

Discovery and characterisation of an antibody that selectively modulates the inhibitory activity of plasminogen activator inhibitor-1.

Plasminogen activator inhibitor-1 (PAI-1) is a serine protease inhibitor (serpin) that regulates fibrinolysis, cell adhesion and cell motility via its interactions with plasminogen activators and vitronectin. PAI-1 has been shown to play a role in a number of diverse pathologies including cardiovascular diseases, obesity and cancer and is therefore an attractive therapeutic target. However the multiple patho-physiological roles of PAI-1, and understanding the relative contributions of these in any one disease setting, make the development of therapeutically relevant molecules challenging. Here we describe the identification and characterisation of fully human antibody MEDI-579, which binds with high affinity and specificity to the active form of human PAI-1. MEDI-579 specifically inhibits serine protease interactions with PAI-1 while conserving vitronectin binding. Crystallographic analysis reveals that this specificity is achieved through direct binding of MEDI-579 Fab to the reactive centre loop (RCL) of PAI-1 and at the same exosite used by both tissue and urokinase plasminogen activators (tPA and uPA). We propose that MEDI-579 acts by directly competing with proteases for RCL binding and as such is able to modulate the interaction of PAI-1 with tPA and uPA in a way not previously described for a human PAI-1 inhibitor

Evaluation of Type 1 Immune Response in Naïve and Vaccinated Animals following Challenge with Leptospira borgpetersenii Serovar Hardjo: Involvement of WC1(+) γδ and CD4 T Cells

Organisms within the Hardjo serovar of Leptospira species are harbored in cattle throughout the world, causing abortion in pregnant animals as well as being shed in the urine, thereby providing sources of zoonotic infection for humans. We recently showed that sterile immunity in vaccinated cattle is associated with induction of a type 1 (Th1) cell-mediated immune response. Here naïve and previously vaccinated pregnant cattle were challenged with a virulent strain of serovar Hardjo and subsequently evaluated for expression of a type 1 immune response. Lymphocytes that responded in a recall response to antigen by undergoing blast transformation were evident in cultures of peripheral blood mononuclear cells (PBMC) from vaccinated cattle throughout the postchallenge test period while those from naïve cattle were evident at one time point only. Nevertheless, beginning at 2 weeks after challenge, gamma interferon (IFN-γ) was measured in supernatants of antigen-stimulated PBMC cultures from nonvaccinated animals although the amount produced was always less than that in cultures of PBMC from vaccinated animals. IFN-γ(+) cells were also evident in antigen-stimulated cultures of PBMC from vaccinated but not from nonvaccinated animals throughout the postchallenge period. The IFN-γ(+) cells included CD4(+) and WC1(+) γδ T cells, and a similar proportion of these two subpopulations were found among the dividing cells in antigen-stimulated cultures as ascertained by carboxyfluorescein succinimidyl ester loading. Finally, while naïve and vaccinated animals had similar levels of antigen-specific immunoglobulin G1 (IgG1) following challenge, vaccinated animals had twofold-more IgG2. In conclusion, while infection may induce a type 1 response we suggest that it is too weak to prevent establishment of chronic infection

Radiation exposure associated with percutaneous fluoroscopically guided lag screw fixation for sacroiliac luxation in dogs

Objective: To determine radiation exposure to surgical personnel and to evaluate the accuracy of a modified percutaneous lag screw fixation technique for sacroiliac luxation (SIL) under fluoroscopic guidance in dogs. Study design: Cadaveric experimental study. Sample population: Seventeen beagle cadavers with iatrogenic SIL. Methods: Seventeen beagles with iatrogenic SIL underwent reduction and stabilization with 3.5‐mm screws. Hypodermic needles (14 gauge) and fluoroscopy were used to orient two Kirschner wires for temporary stabilization and to guide drilling of glide and pilot holes using cannulated drill bits. Duration of surgery and radiation exposure were recorded. Postoperative computed tomographic evaluation of screw position and angulation was performed. Results: Average time for fixation was 15.85 minutes (range, 6.37–33.5). Cumulative radiation doses of 0.4 mrem for the dominant arm of the assistant and 0 mrem for the primary surgeon were recorded. The mean dorsoventral and craniocaudal screw angles were 0.68° ± 3.4° (range − 5.4° to 9.5°) and 1.9° ± 3.2° (range − 4.3° to 9.1°), respectively. Sixteen of the 17 dogs had 100% sacral screw purchase, with the remaining case achieving 93.4% purchase. Conclusion: Fluoroscopy‐assisted percutaneous placement of 3.5‐mm cortical screws in lag fashion performed with 14‐gauge needles in conjunction with Kirschner wires and cannulated drill bits yielded repeatable accurate screw placement with low levels of ionizing radiation exposure to the surgical team. Clinical significance: The described technique may be a viable method for minimally invasive osteosynthesis fixation of SIL with low levels of radiation exposure to the surgical team. These results provide evidence to support further evaluation of radiation exposure in clinical cases and can aid in study design and sample size determination.This is the published version of the following article: Naiman, Jaron H., Eric M. Zellner, Brian L. Petrovsky, Thomas O. Riegel, Elizabeth M. Schmitt, Lingnan Yuan, Jonathan P. Mochel, and Karl H. Kraus. "Radiation exposure associated with percutaneous fluoroscopically guided lag screw fixation for sacroiliac luxation in dogs." Veterinary Surgery (2021). DOI: 10.1111/vsu.13613. Posted with permission.</p

Radiation exposure associated with percutaneous fluoroscopically guided lag screw fixation for sacroiliac luxation in dogs

Objective: To determine radiation exposure to surgical personnel and to evaluate the accuracy of a modified percutaneous lag screw fixation technique for sacroiliac luxation (SIL) under fluoroscopic guidance in dogs. Study design: Cadaveric experimental study. Sample population: Seventeen beagle cadavers with iatrogenic SIL. Methods: Seventeen beagles with iatrogenic SIL underwent reduction and stabilization with 3.5‐mm screws. Hypodermic needles (14 gauge) and fluoroscopy were used to orient two Kirschner wires for temporary stabilization and to guide drilling of glide and pilot holes using cannulated drill bits. Duration of surgery and radiation exposure were recorded. Postoperative computed tomographic evaluation of screw position and angulation was performed. Results: Average time for fixation was 15.85 minutes (range, 6.37–33.5). Cumulative radiation doses of 0.4 mrem for the dominant arm of the assistant and 0 mrem for the primary surgeon were recorded. The mean dorsoventral and craniocaudal screw angles were 0.68° ± 3.4° (range − 5.4° to 9.5°) and 1.9° ± 3.2° (range − 4.3° to 9.1°), respectively. Sixteen of the 17 dogs had 100% sacral screw purchase, with the remaining case achieving 93.4% purchase. Conclusion: Fluoroscopy‐assisted percutaneous placement of 3.5‐mm cortical screws in lag fashion performed with 14‐gauge needles in conjunction with Kirschner wires and cannulated drill bits yielded repeatable accurate screw placement with low levels of ionizing radiation exposure to the surgical team. Clinical significance: The described technique may be a viable method for minimally invasive osteosynthesis fixation of SIL with low levels of radiation exposure to the surgical team. These results provide evidence to support further evaluation of radiation exposure in clinical cases and can aid in study design and sample size determination.This is the published version of the following article: Naiman, Jaron H., Eric M. Zellner, Brian L. Petrovsky, Thomas O. Riegel, Elizabeth M. Schmitt, Lingnan Yuan, Jonathan P. Mochel, and Karl H. Kraus. "Radiation exposure associated with percutaneous fluoroscopically guided lag screw fixation for sacroiliac luxation in dogs." Veterinary Surgery (2021). DOI: 10.1111/vsu.13613. Posted with permission.</p

Synergistic Actions of Blocking Angiopoietin-2 and Tumor Necrosis Factor-α in Suppressing Remodeling of Blood Vessels and Lymphatics in Airway Inflammation

Remodeling of blood vessels and lymphatics are prominent features of sustained inflammation. Angiopoietin-2 (Ang2)/Tie2 receptor signaling and tumor necrosis factor-α (TNF)/TNF receptor signaling are known to contribute to these changes in airway inflammation after Mycoplasma pulmonis infection in mice. We determined whether Ang2 and TNF are both essential for the remodeling on blood vessels and lymphatics, and thereby influence the actions of one another. Their respective contributions to the initial stage of vascular remodeling and sprouting lymphangiogenesis were examined by comparing the effects of function-blocking antibodies to Ang2 or TNF, given individually or together during the first week after infection. As indices of efficacy, vascular enlargement, endothelial leakiness, venular marker expression, pericyte changes, and lymphatic vessel sprouting were assessed. Inhibition of Ang2 or TNF alone reduced the remodeling of blood vessels and lymphatics, but inhibition of both together completely prevented these changes. Genome-wide analysis of changes in gene expression revealed synergistic actions of the antibody combination over a broad range of genes and signaling pathways involved in inflammatory responses. These findings demonstrate that Ang2 and TNF are essential and synergistic drivers of remodeling of blood vessels and lymphatics during the initial stage of inflammation after infection. Inhibition of Ang2 and TNF together results in widespread suppression of the inflammatory response

Short‐term outcomes of 59 dogs treated for ilial body fractures with locking or non‐locking plates

Objective: To determine the influence of plating systems on the clinical outcomes in dogs treated for ilial fractures. Design: Retrospective study. Animals: Fifty‐nine dogs (63 hemipelves). Methods: Radiographs and medical records of dogs with ilial fractures presented to Iowa State University between 2003 and 2019 were reviewed. After fracture reduction, fractures were fixed with a locking plate system (LPS) or non‐locking plate system (NLS). Perioperative, long‐term complications, and follow‐up data were recorded. The frequency of implant failure and pelvic collapse were compared using a logistic and linear regression analysis, respectively. Where the univariate test was statistically significant, a multivariate analysis across categories was performed to identify statistically different categories. Results: LPS and NLS implants were used in 25/63 and 38/63 hemipelves, respectively. Median follow‐up time was 8 weeks (3–624 weeks). Implant failure occurred in 18/63 (29%) of fracture repairs, consisting of 17 with NLS and 1 with LPS. Revision surgery was recommended in five cases of implant failure, all with NLS. The probability of implant failure was higher when fractures were fixed with NLS (p = .0056). All other variables evaluated did not seem to influence outcome measures. Conclusion: The variable with the most influence on the outcomes of dogs treated for ilial fractures consisted of the fixation method (NLS vs. LPS). Fractures repaired with NLS were nearly 20 times more likely to fail than those repaired with LPS. Clinical Relevance: Surgeons should consider repairing ilial body fractures in dogs with LPS to reduce the risk of short‐term implant failure.This is the published version of the following article: Petrovsky, Brian, Taylor Knuth, Cristina Aponte‐Colón, William Hoefle, Karl Kraus, Jaron Naiman, Lingnan Yuan, Jonathan P. Mochel, and Eric Zellner. "Short‐term outcomes of 59 dogs treated for ilial body fractures with locking or non‐locking plates." Veterinary Surgery (2021). DOI: 10.1111/vsu.13656. Posted with permission.</p