TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disorder characterized pathologically by ubiquitinated TAR DNA binding protein (TDP-43) inclusions. The function of TDP-43 in the nervous system is uncertain, and a mechanistic role in neurodegeneration remains speculative. We identified neighboring mutations in a highly conserved region of TARDBP in sporadic and familial ALS cases. TARDBPM337V segregated with disease within one kindred and a genome-wide scan confirmed that linkage was restricted to chromosome 1p36, which contains the TARDBP locus. Mutant forms of TDP-43 fragmented in vitro more readily than wild type and, in vivo, caused neural apoptosis and developmental delay in the chick embryo. Our evidence suggests a pathophysiological link between TDP-43 and ALS.     

Comparative Efficacy of Anesthetics for the Freshwater Prawn Macrobrachiurn rosenbergii

Abstract— The freshwater prawn Macrobrachiurn rosenbergii is a commercially important culture species in the South Central United States. Two major constraints in the commercial culture of the freshwater prawn in the U.S. are poor survival during live transportation of seed‐stock to growout ponds, and live transportation of pond harvested prawn to distant live markets due to the territorial and cannibalistic nature of prawn. The use of anesthetics could possibly improve transport survival; however, to date anesthetic agents have not been evaluated for use with prawn. Two trials were conducted with juvenile freshwater prawn to compare the efficacy of anesthetics commonly used on fish. The first trial was designed to identify the most promising candidates. In Study 1, tricaine methanesulfonate (MS‐222), 2‐phenoxyethanol, quinaldine sulfate (quinaldine), clove oil, and Aqui‐S^TM were evaluated at 25 and 100 mg/L for 1 h in three replicate 10‐L glass containers, containing five juvenile prawn each. Relative sedation level was determined every 3 min for 1 h, then recovery time and survival were measured. In Study 1, MS‐222 and 2‐phenoxyethanol were determined to be ineffective on prawn at all rates tested. Based on their performance in Study 1, quinaldine, clove oil, and AquiS^TM were evaluated at 100, 200, and 300 mg/L in Study 2. Observations were determined as in Study 1. Clove oil and Aqui‐S^TM induced anesthesia faster and at lower concentrations than quinaldine. At the highest treatment rate (300 mg/L) prawn suffered 60% mortality in the Aqui‐S^TM treatment, 13% mortality in the quinaldine treatment, and 0% mortality in the clove oil treatment and control following a 1‐h exposure to these concentrations. Based on these data, Aqui‐S^TM and clove oil applied at 100 mg/L may be suitable anesthetic treatments for prawn. Additional research is needed to determine optimal time and dose relationships to minimize stress during holding, handling, and transportation of prawn.     

Eel acetylcholinesterase inhibition studies with heteroarylphosphinates

The inhibition of eel acetylcholinesterase by the 4-nitrophenyl esters of 2-furyl(methyl)-, methyl(2-thienyl)-, di-2-furyl-, and di-2-thienylphosphinic acid (I, II, III, and IV, respectively) was investigated at pH 6.90 in 0.067 M phosphate buffer (25.0°C) using stopped-flow instrumentation and automated data processing. Our evaluation of the dissociation constant, K_d, the unimolecular bonding rate constant, k₂, and the bimolecular reaction constant, k_i, are the first reported values for these constants for alkyl/heteroaryl and diheteroaryl esters of phosphinic acids. The largest k_i value (19,330 M^?1 sec^?1) was observed for the reaction of I with the enzyme. The order for the remaining three is II > IV > III. There is no direct relationship between the hydrolysis rates of the esters and their anticholinesterase activities on eel acetylcholinesterase. Likewise, there is no direct relationship between their anticholinesterase activities and the LD₅₀ values in rats.     

Glomerular capillary endotheliosis in sow kidney

A high incidence of proliferative renal glomerular lesions was found in sows from a breeding herd. All the sows had a very similar lesion, which was characterised by swelling of endothelial cells, with varying degrees of obstruction of the capillary lumina, and an increase in the number of mesangial cells. By differential diagnosis the condition was found to conform most closely with the renal lesion of human pregnancy toxaemia (pre-eclampsia syndrome). It is suggested that this nephropathy may play a part in limiting the useful breeding life of affected sows.     

The exploitation of the genome in the search for determinants of virulence in Streptococcus uberis

Despite much success in the control of mastitis in dairy cattle, intramammary infection with Streptococcus uberis remains a threat to herd health. This organism is a frequent cause of mastitis worldwide. Recent advances in the ability to genetically manipulate this bacterium, coupled to the determination of a representative genome sequence have already enabled the investigation of certain aspects of disease pathogenesis. Further use of such technology coupled to reliable models of disease and post-genomic analysis will permit the elucidation of further interactions between pathogen and host. This additional information can be usefully targeted at identification of candidates for inclusion in effective vaccines. This communication reviews the current, reported progress using this technology for S. uberis.     

Physiologic VDD versus nonphysiologic VVI pacing in canine 3rd-degree atrioventricular block

Historically, ventricular demand, nonphysiologic (VVI) pacing has been the most commonly used modality to treat 3rd-degree atrioventricular (AV) block. The goal of this study was to determine the feasibility of using a commercial, single-lead, physiologic (VDD) pacemaker in dogs with 3rd-degree AV block. Furthermore, we hoped to characterize and identify differences in the radiographic, echocardiographic, neurohormonal, and quality of life consequences of physiologic versus nonphysiologic pacing. We evaluated 10 dogs during a 12-week crossover study. Acutely, rate-matched physiologic pacing reduced pulmonary capillary wedge pressure by 19% compared with nonphysiologic pacing. VDD pacing significantly reduced left atrial size normalized to body weight, left atrial-to-aortic root ratio, and left ventricular end-systolic dimension and increased fractional shortening, aortic Doppler velocity, cardiac output, and stroke volume compared with VVI pacing. Variable rate VDD pacing resulted in a significantly slower heart rate (HR) during echocardiography than fixed-rate (100 bpm) VVI pacing. AV synchronous pacing reduced circulating N-terminal proatrial natriuretic peptide (ANP), norepinephrine (NOR), and epinephrine (EPI) concentrations compared with asynchronous pacing. There were no significant differences in systemic blood pressure, thoracic radiographs, or owner-perceived quality of life. The median percentage of AV synchronous pacing during the VDD modality was 99.8% (range, 1.2 to 99.9%). This study confirms the potential to achieve physiologic pacing with a commercial, single-lead system in dogs. VDD pacing improved hemodynamics and neurohormonal profiles over asynchronous pacing although the long-term clinical benefits of these changes remain to be determined.     

Quantitative and qualitative assessment of the demand for veterinarians and animal health technologists in western Canada

A manpower survey of veterinary practices in western Canada found that there were potentially 314 full-time equivalent veterinary vacancies. However, only 8% of the respondents were in urgent need of another veterinarian. The results underscore that hiring intentions are best viewed as a continuum and not as a simple dichotomous variable: “Looking to hire? (Yes/No)”.