“Arte et Labore”—A Blackburn Rovers fan's legacy in human complex trait genetics

Through his own research contributions on the modelling and genetic analysis of quantitative traits and through his former students and postdocs, Robin Thompson has indirectly left a major legacy in human genetics. In this short note, we highlight examples of the long‐lasting relevance and impact of Robin's work in human genetics. A lone early study of marker‐assisted selection developed many of the tools and approaches later exploited (often after reinvention) by the human genetics community in GWAS studies and for prediction. Furthermore, a particularly clear example of the pervasive impact of Robin's work is that REML has become the default method to estimate variance components and that genetic predictions exploiting linkage disequilibrium in the population are starting to become used in precision medicine applications.     

Hemoxygenase-2 is an oxygen sensor for a calcium-sensitive potassium channel

Modulation of calcium-sensitive potassium (BK) channels by oxygen is important in several mammalian tissues, and in the carotid body it is crucial to respiratory control. However, the identity of the oxygen sensor remains unknown. We demonstrate that hemoxygenase-2 (HO-2) is part of the BK channel complex and enhances channel activity in normoxia. Knockdown of HO-2 expression reduced channel activity, and carbon monoxide, a product of HO-2 activity, rescued this loss of function. Inhibition of BK channels by hypoxia was dependent on HO-2 expression and was augmented by HO-2 stimulation. Furthermore, carotid body cells demonstrated HO-2-dependent hypoxic BK channel inhibition, which indicates that HO-2 is an oxygen sensor that controls channel activity during oxygen deprivation.     

Homoploid hybrid speciation in an extreme habitat

According to theory, homoploid hybrid speciation, which is hybrid speciation without a change in chromosome number, is facilitated by adaptation to a novel or extreme habitat. Using molecular and ecological data, we found that the alpine-adapted butterflies in the genus Lycaeides are the product of hybrid speciation. The alpine populations possess a mosaic genome derived from both L. melissa and L. idas and are differentiated from and younger than their putative parental species. As predicted, adaptive traits may allow for persistence in the environmentally extreme alpine habitat and reproductively isolate these populations from their parental species.     

The geologically recent giant impact basins at Vesta's south pole

Dawn's global mapping of Vesta reveals that its observed south polar depression is composed of two overlapping giant impact features. These large basins provide exceptional windows into impact processes at planetary scales. The youngest, Rheasilvia, is 500 kilometers wide and 19 kilometers deep and finds its nearest morphologic analog among large basins on low-gravity icy satellites. Extensive ejecta deposits occur, but impact melt volume is low, exposing an unusual spiral fracture pattern that is likely related to faulting during uplift and convergence of the basin floor. Rheasilvia obliterated half of another 400-kilometer-wide impact basin, Veneneia. Both basins are unexpectedly young, roughly 1 to 2 billion years, and their formation substantially reset Vestan geology and excavated sufficient volumes of older compositionally heterogeneous crustal material to have created the Vestoids and howardite-eucrite-diogenite meteorites.     

The influence of cutting cycle and stocking level on the structure and composition of managed old-growth northern hardwoods

Forest management approaches are increasingly being focused on restoring or retaining structurally complex old forest conditions. Evaluations of the long-term impacts of different management regimes on the maintenance and restoration of these conditions are critical for informing and refining current management approaches. To this end, we examined the long-term effects of differing intensities of single-tree selection harvest on stand structural attributes within northern hardwood forests in the Upper Peninsula of Michigan, USA. Stands in this study were classified as old growth at the onset of the experiment and were repeatedly treated and maintained at three residual stocking levels (11.5, 16.1, and 20.7 m² ha⁻¹ in trees greater than 24 cm DBH) with three different cutting cycle lengths (5, 10, and 15 years) over a 57-year period. Conditions within an adjacent, unmanaged old-growth system were used as a benchmark for comparing stand structural attributes, including abundance of downed woody debris (DWD), regeneration, and large diameter trees.     

Subtotal pericardectomy and epicardial excision for treatment of coccidioidomycosis-induced effusive-constrictive pericarditis in dogs: 17 cases (1999-2003)

OBJECTIVE: To determine the history, clinicopathologic findings, and results of surgery for effusive-constrictive pericarditis associated with Coccidioides immitis infection in dogs. DESIGN: Retrospective study. ANIMALS: 17 client-owned dogs that underwent a subtotal pericardectomy and epicardial excision. PROCEDURE: Hospital records from May 1999 to June 2003 were reviewed. Data collected included history, clinicopathologic findings, treatments, and outcome. Follow-up information was obtained via recheck examination and by use of standardized telephone interviews with referring veterinarians and owners. RESULTS: All dogs were of large breeds, and most were male (mean age, 4.66 years). Ten dogs had no prior history of C. immitis infection, and 7 dogs had chronic infection with C. immitis. Having a chronic C. immitis infection reduced the odds of survival, compared with no previous infection. All dogs had clinical signs of right-sided heart failure. All dogs had serum titers (range, 1:8 to 1:256) for antibodies against C. immitis prior to surgery, and titers were not significantly associated with outcome. Predominant echocardiographic findings were thickened pericardium, reduced right ventricular filling, and pleural or pericardial effusion. All dogs underwent a subtotal pericardectomy and epicardial excision and had fibrosing pyogranulomatous pericarditis in biopsy specimens obtained during surgery. The perioperative mortality rate was 23.5%, and the 2-year postdischarge survival rate was 82%. CONCLUSIONS AND CLINICAL RELEVANCE: Surgical treatment via subtotal pericardectomy and epicardial excision is successful at relieving right-sided heart failure in dogs with effusive-constrictive pericarditis secondary to C. immitis infection, but long-term treatment with antifungal agents may still be required.     

Biochemical analysis of the articular cartilage and subchondral and trabecular bone of the metacarpophalangeal joint of horses with early osteoarthritis

OBJECTIVE: To assess whether site-related changes in biochemical composition are present in the cartilage and subchondral and trabecular bone of the metacarpophalangeal joint of horses with early osteoarthritis. SAMPLE POPULATION: Right metacarpophalangeal joints from 59 mature warmblood horses. PROCEDURE: Biochemical data (cross-link, amino acid, DNA, and ash contents; denatured collagen and glycosaminoglycan [GAG] concentrations; bone mineral density; and mineral composition) were obtained from 2 differently loaded sites of phalanx I cartilage and subchondral and trabecular bone samples; data were compared with previously published values from nonosteoarthritic equine joints. RESULTS: Compared with findings in nonosteoarthritic joints, GAG concentration was lower in cartilage from osteoarthritic joints and there was a loss of site differences in cellularity and lysylpyridinoline (LP) cross-link content. In subchondral bone, LP cross-link content was decreased overall and there was a loss of site differences in osteoarthritic joints; ash content was higher in the osteoarthritic joints. Hydroxyproline content in trabecular bone from osteoarthritic joints was greater than that in nonosteoarthritic trabecular bone. In all 3 layers and at both sites, the linear increase of the pentosidine cross-link content with age had diminished or was not apparent in the horses with osteoarthritic joints. CONCLUSIONS AND CLINICAL RELEVANCE: In equine metacarpophalangeal joints with early osteoarthritis, distinct biochemical changes were detected in the cartilage and subchondral and trabecular bone. The dissimilarity in response of the different tissues and differences between the sites that are affected may be related to differences in biomechanical loading and transmission and dissipation of force.     

Accuracy and optimization of force platform gait analysis in Labradors with cranial cruciate disease evaluated at a walking gait

OBJECTIVE: To determine the combination of ground reaction forces (GRFs) that best discriminates between lame and non-lame dogs. To compare the sensitivity of force platform gait analysis and visual observation at detecting gait abnormalities in Labradors after surgery for rupture of the cranial cruciate ligament (CCL). ANIMALS: All dogs were adult Labrador Retrievers: 17 free of orthopedic and neurologic abnormalities, 100 with unilateral CCL rupture, and 131 studied 6 months after surgery for unilateral CCL injury, 15 with observable lameness. PROCEDURE: Dogs were walked over a force platform with GRF recorded during the stance phase. Analytic properties of force platform gait analysis were calculated for several combinations of forces. The probability of visual observation detecting a gait abnormality was compared with that of force platform gait analysis. RESULTS: We determined that a combination of peak vertical force (PVF) and falling slope were optimal for discriminating sound and lame Labradors. After surgery, many dogs (75%) with no observable lameness failed to achieve GRFs consistent with sound Labradors. CONCLUSION: A force platform is an accurate method of assessing lameness in Labradors with CCL rupture and is more sensitive than visual observation. Assessing lameness with a combination of GRFs is better than using univariate GRFs. CLINICAL RELEVANCE: Therapies for stifle lameness can be accurately and objectively evaluated using 2 vertical ground reaction forces obtained from a force platform.     

Canine sacroiliac luxation: anatomic study of dorsoventral articular surface angulation and safe corridor for placement of screws used for lag fixation

OBJECTIVE: To define a safe corridor in the dorsoventral plane to facilitate placement of screws inserted in lag fashion within the sacral body for fixation of sacroiliac fracture-luxation injuries in dogs. STUDY DESIGN: Anatomic study. SAMPLE POPULATION: Cadaveric canine sacra. METHODS: Canine sacra (n=45) were used for a radiographic study to define a safe corridor in the dorsoventral plane for placement of screws inserted in lag fashion for fixation of sacroiliac luxation in the dog. The defined safe corridor allowed drilling to a depth of 65% of the sacral width to ensure screw purchase of > or =60%. Effects of positioning and measurement techniques were evaluated. RESULTS: Eighty-seven safe corridors were measured. The mean articular surface was 100+/-4.52 degrees from horizontal. Mean maximum, optimum, and minimum safe corridor drill angles were 111+/- 4.57 degrees, 100+/-4.70 degrees, and 89+/-5.17 degrees, respectively, from the articular surface. Predicted surgeon error of +/-4 degrees was used to define the safe corridor for use clinically. CONCLUSIONS: In 91% of sacra, a drill angle of 100+/-4 degrees would remain ventral to the vertebral canal. Twelve sacra (14%) were at risk of penetration of the pelvic canal. A drill angle of 97+/-4 degrees avoids penetration of the vertebral canal in all sacra measured but risks ventral exit from the body in 30% of sacra studied. CLINICAL RELEVANCE: A drill angle of 97 degrees from the articular surface is recommended for insertion of screws for lag fixation of canine sacroiliac luxation.     

山羊甘肃棘豆中毒睾丸、附睾的病理学研究

山羊甘肃棘豆中毒睾丸、附睾的病理学研究丁伯良，王建辰，薛登民，贾维真，王淑娥（西北农业大学兽医系，杨陵７１２１００）马远莉（陕西省农科院农业测试中心）摘要对６只１０月龄西农莎能奶山羊公羊每日按１０ｇ／ｋｇ剂量单笼饲喂甘肃棘豆粉，４只同龄公羊作对照。１...