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The article offers information on the changes in the pasture based dairy systems that may impact the health of cattle in New Zealand and Australia. It is stated that the increased intensification of milk production can increase the risk if of mastitis and culling of udder health, which, can be decreased through increased milking frequency. The intensive grazing patterns linked with higher grass yields using better cultivars and fertilizers favor nematodes and there is a reported evidence of anthelmintic resistance in nematodes and liver fluke that the veterinarians are suggested to be aware of. Though pasture fed cattle are better addressed in the control of milk fever, hypomagnesaemia and trace element deficiencies, they reportedly show higher prevalence of acidosis.

Importance: Psoriasis is associated with increased cardiovascular risk, but the underlying pathogenic mechanisms remain unclear. Elucidating these mechanisms can help develop treatment strategies and enhance understanding of the link between peripheral inflammation, such as psoriatic skin lesions, and cardiovascular disease (CVD)., Objective: To explore whether systemic inflammation is a mediator of the association between psoriasis skin disease severity and CVD., Design, Setting, and Participants: This cohort study used data from cross-sectional study (Psoriasis Atherosclerosis and Cardiometabolic Disease Initiative [PACI]), which enrolled patients from January 2013 to February 2022, and an inception cohort study (Stockholm Psoriasis Cohort [SPC]), which enrolled patients from January 2000 to December 2005. The PACI enrolled consecutive patients referred by dermatologists in Maryland, and the SPC enrolled consecutive patients referred from a wide range of practices in Sweden. Patients with prevalent psoriasis from the PACI and patients with incident psoriasis from the SPC were included. Data were analyzed from October 2023 to January 2024., Exposures: Psoriasis skin disease severity was measured using the Psoriasis Area and Severity Index (PASI), and systemic inflammation was measured using glycan biomarker of N-acetyl side chains of acute-phase proteins (GlycA). Mediation analysis was performed by evaluating the associations between exposure, mediator, and outcome in patients with first-tertile and third-tertile PASI scores when GlycA level was set at the level observed in patients with first-tertile PASI., Main Outcomes and Measures: Noncalcified coronary burden (NCB) measured using coronary computed tomography angiography in the PACI and hospitalization for CVD or cardiovascular death in the SPC., Results: Of 260 eligible patients from the PACI, 162 (62.3%) were male, and the median (IQR) age was 51 (41-60) years; of 509 eligible patients from the SPC, 237 (46.6%) were male, and the median (IQR) age was 43 (30-57) years. In both studies, PASI was associated with GlycA level and CVD, and GlycA level was associated with CVD. The direct and indirect (through GlycA) effects of PASI on NCB were estimated at 0.94 (95% CI, 0.26-1.74) and 0.19 (95% CI, 0.02-0.47), respectively. The odds ratios for the direct and indirect effects of PASI on cardiovascular events were estimated at 1.23 (95% CI, 0.70-1.92) and 1.16 (95% CI, 1.04-1.42), respectively., Conclusions and Relevance: In this study, skin disease severity measured using PASI was associated with systemic inflammation, and both PASI and systemic inflammation, measured using GlycA levels, were associated with CVD. The association between PASI and CVD may be mediated by systemic inflammation.

Background and Aims: Vitamin D binding protein (DBP) serves a dual function as a vitamin D carrier and actin scavenger. Free DBP is present in high concentrations in serum, while a smaller pool is bound to lipoproteins like HDL and VLDL. The role of DBP's interaction with lipoproteins remains unclear. Given that HDL has been proposed to have both atheroprotective and anti-inflammatory properties, we sought to compare whether HDL-associated DBP and/or total serum DBP could serve as useful biomarkers for assessing disease severity in psoriasis and cardiovascular disease., Methods: Psoriasis (PSO) patients (N = 83), which were part of a prospective, observational cohort and non-psoriasis (non-PSO) subjects (n = 35) underwent blood collection for HDL purification by liquid chromatography and CCTA scans to assess coronary plaque burden. Serum and HDL-bound DBP levels were measured by ELISA., Results: The psoriasis cohort was middle-aged (mean ± IQR: 50 (38-59), predominantly male (n = 55, 66 %) and had moderate-to-severe skin disease [psoriasis area severity index score, PASI score, med (IQR): 9.6 (6-18.3)]. Consistent with our previous reports, PSO patients had significantly higher Framingham Risk Score (FRS), high sensitivity C-reactive protein (hs-CRP), Body Mass Index (BMI), insulin resistance (HOMA-IR) and total coronary plaque burden, driven by the rupture-prone non-calcified necrotic core. However, while the concentration of serum DBP (S-DBP) between PSO and non-PSO was unchanged (PSO: 177.80 (125.77-250.99) vs non-PSO: 177.74 (104.32-254.04), the concentration of DBP associated with HDL (HDL-DBP) was decreased in psoriatics (PSO μg/ml: 1.38 (0.64-2.75) vs non-PSO: 1.72 (1.18-3.90). Although both S-DBP and HDL-DBP levels showed inverse correlations with a measure of skin disease severity (PASI) (S-DBP, Rho = -0.022 vs HDL-DBP, Rho = -113), only HDL-DBP exhibited an inverse relationship with necrotic plaque burden [Rho -0.226, p = 0.085 vs S-DBP (0.041, p = 0.76)]. This relationship was strengthened after adjusting for traditional cardiovascular risk factors such as age and sex (β = -0.237, p = 0.045), FRS (β = -0.295, p = 0.033) and including biological treatment and HDL-cholesterol (β = -0.213, p = 0.048)., Conclusions: In conclusion, we found HDL-DBP levels may better capture the severity of psoriatic disease and association with cardiovascular risk factors than S-DBP., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Mehta is a full-time US government employee and has served as a consultant for Amgen, Eli Lilly, and Leo Pharma receiving grants/other payments; as a principal investigator and/or investigator for AbbVie, Celgene, Janssen Pharmaceuticals, Inc, and Novartis receiving grants and/or research funding; and as a principal investigator for the National Institute of Health receiving grants and/or research funding.

This review summarises up-to-date research on the diagnosis of gastrointestinal nematode (GIN) infection in livestock and anthelmintic resistance in GIN. It was commissioned to assist funding bodies to prioritise and guide research and extension efforts to improve the health, welfare and productivity of grazing ruminants in the face of challenge with GIN. A comprehensive review of published articles from journals, books and websites was undertaken, with a focus on peer-reviewed articles published between 2000 and 2024 involving genera of GIN in grazing sheep and cattle with economic importance to New Zealand. Suggestions for articles to include were received from 14 experts in GIN diagnostics. This review is a summary of a longer report submitted to the sponsoring organisation. Clinical signs of GIN infection in grazing ruminants in temperate grazing systems are inadequate as triggers for management interventions including anthelmintic treatment as they are visible only after economically significant pathological changes have occurred. Livestock producers benefit from monitoring GIN burdens using faecal egg counts (FEC) or associated signals such as weight gain. In future, they may use remote monitoring devices for activity in animals, as well as estimating pasture larval contamination. Methods of diagnosing GIN infections using automated FEC devices have improved the convenience of monitoring parasite burdens compared with traditional laboratory methods. However, a lack of quality control measures and a gap in training of skilled technicians for larval differentiation may lead to a shortage of diagnostic capability. Current methods of diagnosing anthelmintic resistance, particularly FEC reduction tests, are not likely to be replaced by laboratory assays in the near future and attention should be focused on facilitating application of new FEC technologies for both animal monitoring and resistance diagnosis. Extension and application of currently available methods and technology will improve animal health and productivity in ruminant grazing systems in the short term. Adoption of novel technologies for remote animal monitoring, practical tools for estimating pasture larval contamination and promoting genetic selection for immunity and resilience to GIN in both sheep and cattle will further enhance productivity in the long term.

Background: Beta-defensins (BDs) are antimicrobial peptides secreted upon epithelial injury. Both chemotactic and antimicrobial properties of BDs function as initial steps in host defense and prime the adaptive immune system in the body. Psoriasis, a chronic immune-mediated inflammatory disease, has both visible cutaneous manifestations as well as known associations with higher incidence of cardiometabolic complications and vascular inflammation., Objectives: We aimed to investigate the circulating expression of beta-defensin-2 (BD2) in psoriasis at baseline compared to control subjects, along with changes in BD2 levels following biologic treatment at one-year. The contribution of BD2 to subclinical atherosclerosis is also assessed. In addition, we have sought to unravel signaling mechanisms linking inflammation with BD2 expression., Methods: Multimodality imaging as well inflammatory biomarker assays were performed in biologic naïve psoriasis (n=71) and non-psoriasis (n=53) subjects. A subset of psoriasis patients were followed for one-year after biological intervention (anti-Tumor Necrosis Factor-α (TNFα), n=30; anti-Interleukin17A (IL17A), n=21). Measurements of circulating BD2 were completed by Enzyme-Linked Immunosorbent Assay (ELISA). Using HaCaT transformed keratinocytes, expression of BD2 upon cytokine treatment was assessed by quantitative polymerase chain reaction (qPCR) and ELISA., Results: Herein, we confirm that human circulating BD2 levels associate with psoriasis, which attenuate upon biologic interventions (anti-TNFα, anti-IL-17A). A link between circulating BD2 and sub-clinical atherosclerosis markers was not observed. Furthermore, we demonstrate that IL-17A-driven BD2 expression occurs in a Phosphatidylinositol 3-kinase (PI3-kinase) and Rac1 GTPase-dependent manner., Conclusions: Our findings expand on the potential role of BD2 as a tractable biomarker in psoriasis patients and describes the role of an IL-17A-PI3-kinase/Rac signaling axis in regulating BD2 levels in keratinocytes., Competing Interests: Conflicts of Interest Disclosures Nehal Mehta has received research grants from Abbvie, Janssen, Novartis Corp, and Celgene, outside the submitted work. All other authors report no conflicts of interest.

Background: To identify any universal impact of strongyle parasite burden on the growth rate of young cattle., Methods: A meta-analysis and meta-regression of the relationship between differences in strongyle parasite burden between cohorts and average daily weight gain was conducted. Publications were identified from a search of databases applying PRISMA 2020 principles. Eligible studies had at least two groups of growing cattle on the same farm that were identical in composition, management and diet except for parasite exposure and were subject to body weight gain or average daily gain and faecal egg count measurements across the common growing period. The reference group had the lowest growth-period faecal egg count. A meta-regression estimated the impact of strongyle parasitism. The dependent variable was the log of the ratio of average daily gain between comparison groups and the reference group with the predictor variable as the common logarithm of the difference in average faecal egg count (plus 1) between the comparison and the reference groups., Results: 26 publications containing 85 groups and 59 comparison ratios were analysed. Papers included representatives from dairy and beef industries and from pasture and feedlot production systems and from all cattle-producing continents. The comparison group average daily growth rate was 0.89 (95%CI 0.81-0.97) that of the reference group. Meta-regression identified a 0.131 linear reduction in average daily weight gain ratio for every log 10 increase in the difference between comparison and reference group faecal egg count. Direction of effect was consistent across all subset analyses (continent, class of stock and production system). Whilst small faecal egg count differences between the comparison and reference groups often provided similar rates of daily weight gain, the trend was negative with most comparison groups having lower daily weight gains than their reference group., Conclusions: Strongyle parasitism of growing cattle as measured by faecal egg count is associated with reduced growth across all production systems, geographies and classes of cattle., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Objectives: Psoriasis is a heterogeneous inflammatory disease that involves the skin, joints, liver, heart, and other organs. Psoriatic arthritis (PsA) is associated with cardiovascular disease (CVD), but the relative contributions of inflammatory and metabolic dysregulation to CVD are incompletely understood. We set out to discover novel potential contributors to CVD in PsA patients by comprehensively phenotyping a cohort of PsA patients using these advanced technologies., Methods: In this cross-sectional analysis of a cohort study, we investigated associations of systemic inflammation and metabolic dysregulation with Coronary CT angiography (CCTA)-proven coronary artery disease (CAD) in 39 subjects with PsA. We measured traditional CVD risk factors [blood pressure, Body Mass Index (BMI), diabetes, age, sex, smoking], serum markers of systemic inflammation (hsCRP, GlycA) and metabolic dysfunction (cholesterol efflux capacity), and inflammatory cytokines (IL-1β, IL-6, IL-12/IL-23, IL-17A, TNF-α, IFN-γ). We also incorporated radiographic measures of metabolic dysfunction (visceral and subcutaneous adipose volume) and tissue-specific inflammation (positron emission tomography-computed tomography, PET-CT). To quantify relative contributions of FDG (fluorodeoxyglucose) uptake and adiposity to coronary plaque, we performed multiple linear regression, controlling for Framingham risk score (FRS) and FRS + visceral adiposity., Results: Compared with non-psoriatic volunteers, subjects with PsA had elevated markers of metabolic and inflammatory disease, which was more pronounced in subjects with moderate-to-severe skin disease. This included visceral (p = 0.005) and subcutaneous (p = 0.004) adiposity, BMI (p = 0.001), hemoglobin A1C (p = 0.037), high sensitivity C-reactive protein (p = 0.005), IL-6 (p = 0.003), IFN-γ (p = 0.006), and liver FDG uptake (p = 0.03). In subjects with PsA, visceral adiposity correlated significantly with subclinical CAD (standardized β = 0.681, p = 0.002), as did FDG uptake in bone marrow (standardized β = 0.488, p = 0.008), liver (standardized β = 0.619, p < 0.001), spleen (standardized β = 0.523, p = 0.004), and subcutaneous adipose (standardized β = 0.524, p = 0.003)., Interpretation: Together, these findings reveal inflammatory and metabolic potential contributors to subclinical CAD in PsA, including adipose inflammation, and suggesting novel targets for CVD prevention and treatment in PsA., Competing Interests: NM has served as a consultant for Amgen, Eli Lilly, and Leo Pharma, receiving grants and other payments. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Schwartz, Parel, Li, Sorokin, Berg, Chen, Dey, Hong, Playford, Sylvester, Teague, Siegel and Mehta.)

Chronic inflammation is a critical component of atherogenesis, however, reliable human translational models aimed at characterizing these mechanisms are lacking. Psoriasis, a chronic inflammatory skin disease associated with increased susceptibility to atherosclerosis, provides a clinical human model that can be utilized to investigate the links between chronic inflammation and atherosclerosis development. We sought to investigate key biological processes in psoriasis skin and human vascular tissue to identify biological components that may promote atherosclerosis in chronic inflammatory conditions. Using a bioinformatics approach of human skin and vascular tissue, we determined IFN-γ and TNF-α are the dominant pro-inflammatory signals linking atherosclerosis and psoriasis. We then stimulated primary aortic endothelial cells and ex-vivo atherosclerotic tissue with IFN-γ and TNF-α and found they synergistically increased monocyte and T-cell chemoattractants, expression of adhesion molecules on the endothelial cell surface, and decreased endothelial barrier integrity in vitro, therefore increasing permeability. Our data provide strong evidence of synergism between IFN-γ and TNF- α in inflammatory atherogenesis and provide rationale for dual cytokine antagonism in future studies.

Objective: To study the effects of oral contraceptive pills (OCP), the first-line treatment for PCOS, on high-density lipoprotein cholesterol (HDL-C) function (reverse cholesterol efflux capacity) and lipoprotein particles measured using nuclear magnetic resonance spectroscopy in obese women., Design: Secondary analysis of a randomized controlled trial (OWL-PCOS) of OCP or Lifestyle (intensive Lifestyle modification) or Combined (OCP + Lifestyle) treatment groups for 16 weeks., Patients: Eighty-seven overweight/obese women with PCOS at two academic centres., Measurements: Change in HDL-C efflux capacity and lipoprotein particles., Results: High-density lipoprotein cholesterol efflux capacity increased significantly at 16 weeks in the OCP group [0·11; 95% confidence interval (CI) 0·03, 0·18, P = 0·008] but not in the Lifestyle (P = 0·39) or Combined group (P = 0·18). After adjusting for HDL-C and TG levels, there was significant mean change in efflux in the Combined group (0·09; 95% CI 0·01, 0·15; P = 0·01). Change in HDL-C efflux correlated inversely with change in serum testosterone (r s = -0·21; P = 0·05). In contrast, OCP use induced an atherogenic low-density lipoprotein cholesterol (LDL-C) profile with increase in small (P = 0·006) and large LDL-particles (P = 0·002). Change in small LDL-particles correlated with change in serum testosterone (r s = -0·31, P = 0·009) and insulin sensitivity index (ISI; r s = -0·31, P = 0·02). Both Lifestyle and Combined groups did not show significant changes in the atherogenic LDL particles., Conclusions: Oral contraceptive pills use is associated with improved HDL-C function and a concomitant atherogenic LDL-C profile. Combination of a Lifestyle program with OCP use improved HDL-C function and mitigated adverse effects of OCP on lipoproteins. Our study provides evidence for use of OCP in overweight/obese women with PCOS when combined with Lifestyle changes., (© 2017 John Wiley & Sons Ltd.)

Objective: To report anthelmintic resistance in gastrointestinal nematode parasites of cattle on commercial dairy farms in the Macalister Irrigation District of Gippsland, Victoria., Methods: Faecal egg count reduction tests (FECRTs) were used to assess anthelmintic resistance on 20 Macalister Irrigation District dairy farms between May 2013 and June 2014. All three currently available anthelmintic classes for cattle nematodes in Australia were tested. Faecal samples were collected 10-14 days post-treatment for individual faecal egg counts (FEC) and larval differentiation. The arithmetic mean FEC for each treatment group was compared with an untreated control post-treatment. Resistance was defined as <95% reduction in FEC, with a lower 95% confidence interval <90% when the mean FEC of the control group, differentiated by genus, was greater than 25 eggs/g., Results: Anthelmintic resistance was present on all 20 dairy farms involved in this study. Resistance to doramectin in at least one species was detected on 15/20 (70%) farms, fenbendazole on 16/20 (80%) farms and levamisole on 5/20 (25%) farms. On three farms, resistance by Ostertagia ostertagi to all three anthelmintic classes was detected., Conclusion: This is the first report of anthelmintic-resistant O. ostertagi on Australian dairy farms. Resistance to all three available anthelmintic classes is of concern, given the high pathogenicity of this species. The study highlights the need for veterinarians and dairy farmers to be aware of the risks posed by anthelmintic resistance., (© 2016 Australian Veterinary Association.)

Background: Infectious diseases in dairy cows often follow a time of nutritional or physiological stress and the subsequent altered immune system function. This study aimed to determine if the immunomodulatory effects of a feed additive previously observed in experimental animals and housed cattle fed total mixed rations could be reproduced in pasture-fed dairy cattle under Australian conditions., Methods: The study included 34 pasture-fed dairy cattle given the treatment (n = 17) or placebo (bentonite, n = 17) for an acclimation period of 15 days followed by 60 days of supplementation. Blood tests were taken pre-trial and then 30, 60 and 90 days after acclimation. Blood samples were extracted and preserved in Trizol and analysed for immune markers., Results: Pasture-fed dairy cows in the treatment group had significantly higher levels of the immune markers interleukin-8R and L-selectin in comparison with placebo-fed cows at 60 days after the start of supplementation., Conclusion: The immunomodulatory effects of the additive observed in the current study and the associated enhanced neutrophil function demonstrated by other studies suggest a role in decreasing the rates of mastitis and other infectious diseases of dairy cattle, particularly during times of nutritional or physiological stress., (© 2014 Australian Veterinary Association.)

Objective: This study aimed to provide an indication of the prevalence and severity of anthelmintic resistance (AR) in the Australian sheep industry by compiling the results of faecal worm egg count reduction tests (FECRTs)., Methods: Government and private parasitology laboratories, pharmaceutical companies and veterinarians known to have conducted FECRTs were asked to provide results that conformed to Australian and New Zealand standard diagnostic procedures., Results: Data were available from a total of 390 tests, with larval differentiation conducted in 222 cases. Pooled results from all states for the macrocyclic lactone (ML) class showed a lower prevalence of AR against combined species for moxidectin (54%) compared with abamectin (77%) and ivermectin (87%). Analysis by state revealed higher levels of ML-resistant Teladorsagia sp. in Tasmania and Western Australia than in other states and ML-resistant Haemonchus sp. was more frequently detected in New South Wales., Conclusion: This compilation of results of FECRTs conducted by Australian parasitology laboratories in 2009-12 showed widespread AR of the common sheep nematodes (Teladorsagia, Trichostrongylus and Haemonchus) to all broad-spectrum anthelmintics, with the exception of monepantel, whether used singly or in combination., (© 2014 Australian Veterinary Association.)

Context: Women with polycystic ovary syndrome (PCOS) have a high prevalence of cardiovascular disease (CVD) risk factors including dyslipidemia. Lipoproteins are heterogeneous, and measurement of serum lipids provides only the size of the pool and does not predict their function or composition. Recently, high-density lipoprotein cholesterol (HDL-C) function, as determined by cholesterol efflux capacity from macrophages, has been shown to be an independent predictor of subclinical CVD., Objective: The aim of the study was to comprehensively evaluate lipoprotein profile including lipid particle size and number and cholesterol efflux capacity in PCOS to better define CVD risk., Design and Setting: A case control study was performed at an academic PCOS center., Patients: Women with PCOS (n = 124) and geographically matched controls (n = 67) were included in the study., Main Outcome Measures: The primary outcome was to measure HDL-C efflux capacity by an ex vivo system involving the incubation of macrophages with apolipoprotein (Apo) B-depleted serum from subjects, and the secondary outcome was to measure lipid particle size and number using nuclear magnetic resonance spectroscopy., Results: Women with PCOS had significantly higher body mass index and blood pressure but similar HDL-C and low-density lipoprotein cholesterol levels compared to controls. The mean ApoA1 levels were lower, and the ApoB/ApoA1 ratio was higher in PCOS subjects compared to controls (P < .01). There were no differences in ApoB levels. Women with PCOS had an 7% decrease in normalized cholesterol efflux capacity compared to controls (P < .003). Cholesterol efflux capacity in PCOS correlated with body mass index, ApoA1, HDL-C, and the presence of metabolic syndrome. In a multivariable regression model, PCOS was significantly associated with diminished cholesterol efflux. PCOS was also associated with an atherogenic profile including an increase in large very low-density lipoprotein particles, very low-density lipoprotein (VLDL) size, and small low-density lipoprotein cholesterol particles (P < .01)., Conclusions: Our novel findings of decreased cholesterol efflux and an atherogenic lipid particle number and size pattern in women with PCOS, independent of obesity, further substantiate the increased risk of CVD in this population.

Objective:  To assess the effects of application of occlusive polypropylene clips to lambs on body weight, breech bare area measurements and scores, wrinkle scores, and faecal and urine stain scores., Procedures:  A randomised controlled trial using 32,028 lambs was conducted on 208 properties across Australia. Polypropylene clips were applied at lamb marking. At each site, 160 lambs were weighed, measured for breech bare area and scored for bare area, wrinkle, dag and urine staining, and skin type and thickness. Lambs were allocated to a control (no clips) or treatment (breech and tail clips) group. Lambs were assessed on days 14 (range 10-19) and 55 (range 34-129) after clip application for body weight, breech bare area measurements and scores. On day 55 the operators also scored wrinkling and urine staining., Results:  At an average of 55 days after treatment, treated ewe and wether lambs had 16% and 21% greater horizontal bare area measurements, and 31.7% and 32.7% higher bare area scores than control lambs, respectively. The ewes and wether lambs also had lower wrinkle (6.8% and 5.8%, respectively) and dag scores (12% and 12.3%, respectively) than controls. Treated ewes had lower urine stain scores (18.8%) than controls. However, body weight was slightly lower in clip-treated lambs compared with controls by 0.320 kg (1.2%) and 0.430 kg (1.6%) for ewes and wethers, respectively., Conclusion:  Polypropylene clips applied to the breech and tail of lambs increased breech bare area and reduced dag, urine and wrinkle scores. Improvements in these measures of factors that predispose to blowfly strike suggest that the application of clips may reduce the risk of breech flystrike., (© 2012 The Authors. Australian Veterinary Journal © 2012 Australian Veterinary Association.)

Objective: A multivariate analysis approach was used to evaluate both the effects of application of occlusive polypropylene clips to the breech on bare area measurements and scores of lambs, and the influence of operator, region, sheep, farm and environmental factors on outcomes., Procedures: A randomised controlled trial using 32,028 lambs was conducted on 208 commercial wool-growing properties across Australia. Differences in bare area measurements and scores between groups were estimated and analysed using a mixed model to investigate the effects of operator differences, farm and environmental factors and the interactions among these factors., Results: Clip-treated lambs with higher body weight at visit 1 had higher bare area measures and scores, but lower changes in dag and urine scores. Lambs with tight skin showed improved response in bare area scores and measurements after clip treatment, but lambs with a high wrinkle score at visit 1 showed less response to the treatment in their urine, dag and wrinkle and bare area scores. These effects of the clip treatment were not significantly influenced by estimated fleece fibre diameter, operator or region, but were significantly influenced by farm., Conclusions: The effect of occlusive clips on breech measurements and scores was significantly influenced by body weight, skin type and thickness, wrinkle score and sex of the lamb, but not by region, operator or estimated fibre diameter. The clip treatment significantly improved characteristics that influence the susceptibility of lambs to flystrike under most conditions., (© 2012 The Authors. Australian Veterinary Journal © 2012 Australian Veterinary Association.)

Theileria parasites cause a benign infection of cattle in parts of Australia where they are endemic, but have, in recent years, been suspected of being responsible for a number of outbreaks of disease in cattle near the coast of New South Wales. The objective of this study was to identify and characterize the species of Theileria in cattle on six farms in New South Wales where disease outbreaks have occurred, and compare with Theileria from three disease-free farms in Queensland that is endemic for Theileria. Special reference was made to sub-typing of T. orientalis by type-specific PCR and sequencing of the small subunit (SSU) rRNA gene, and sequence analysis of the gene encoding a polymorphic merozoite/piroplasm surface protein (MPSP) that may be under immune selection. Nucleotide sequencing of SSU rRNA and MPSP genes revealed the presence of four Theileria genotypes: T. orientalis (buffeli), T. orientalis (ikeda), T. orientalis (chitose) and T. orientalis type 4 (MPSP) or type C (SSU rRNA). The majority of animals showed mixed infections while a few showed single infection. When MPSP nucleotide sequences were translated into amino acids, base transition did not change amino acid composition of the protein product, suggesting possible silent polymorphism. The occurrence of ikeda and type 4 (type C) previously not reported to occur and silent mutation is thought to have enhanced parasite evasion of the host immune response causing the outbreak.

Adherens junctions are calcium-dependent cell-cell contacts that link neighboring cells through cadherin receptors. Coordinated regulation of the actin cytoskeleton by the Rho GTPases is required for the formation and dissolution of adherens junctions. However, the pathways that link cadherin signaling to cytoskeletal regulation remain poorly defined. Here we identify the Abl family kinases as critical mediators of cadherin-mediated adhesion. Endogenous Abl family kinases, Abl and Arg, are activated and required for Rac activation after cadherin engagement and regulate the formation and maintenance of adherens junctions in mammalian cells. Significantly, we show that Abl-dependent regulation of the Rho-ROCK-myosin signaling pathway is critical for the maintenance of adherens junctions. Inhibition of the Abl kinases in epithelial sheets results in the activation of Rho and its downstream target ROCK, leading to enhanced phosphorylation of the myosin regulatory light chain. These signaling events result in enhanced stress fiber formation and increased actomyosin contractility, thereby disrupting adherens junctions. Conversely, Arg gain of function promotes adherens junction formation through a Crk-dependent pathway in cells with weak junctions. These data identify the Abl kinases as a regulatory link between the cadherin-catenin adhesion complex and the actin cytoskeleton through regulation of Rac and Rho during adherens junction formation, and also reveal a functional link between Abl and Rho that is essential for adherens junction stability.

The Abl-interactor (Abi) family of adaptor proteins has been linked to signaling pathways involving the Abl tyrosine kinases and the Rac GTPase. Abi proteins localize to sites of actin polymerization in protrusive membrane structures and regulate actin dynamics in vitro. Here we demonstrate that Abi2 modulates cell morphogenesis and migration in vivo. Homozygous deletion of murine abi2 produced abnormal phenotypes in the eye and brain, the tissues with the highest Abi2 expression. In the absence of Abi2, secondary lens fiber orientation and migration were defective in the eye, without detectable defects in proliferation, differentiation, or apoptosis. These phenotypes were consistent with the localization of Abi2 at adherens junctions in the developing lens and at nascent epithelial cell adherens junctions in vitro. Downregulation of Abi expression by RNA interference impaired adherens junction formation and correlated with downregulation of the Wave actin-nucleation promoting factor. Loss of Abi2 also resulted in cell migration defects in the neocortex and hippocampus, abnormal dendritic spine morphology and density, and severe deficits in short- and long-term memory. These findings support a role for Abi2 in the regulation of cytoskeletal dynamics at adherens junctions and dendritic spines, which is critical for intercellular connectivity, cell morphogenesis, and cognitive functions.

The insulin-like growth factor (IGF) type 1 receptor is required for growth, transformation, and protection from apoptosis. IGFs can enhance cell migration, which is known to be influenced via regulation of the E-cadherin/beta-catenin complex. We sought to investigate whether IGF-1 modulated the interaction between E-cadherin and beta-catenin in human colorectal cancer cells. We used the C10 cell line, which we established and have previously shown to lack adenomatous polyposis coli, E-cadherin, or beta-catenin mutations. We found that IGF-1 stimulation enhanced tyrosine phosphorylation of two proteins, beta-catenin and insulin-receptor substrate 1, which formed a complex with E-cadherin. Tyrosine phosphorylation of beta-catenin was accompanied by rapid (<1 min) dissociation from E-cadherin at the plasma membrane, followed by relocation to the cellular cytoplasm. IGF-1 also enhanced the stability of beta-catenin protein. Despite this, we observed no enhancement of transcriptional activity in complex with T-cell factor 4 (Tcf-4) in human embryonic kidney 293 cells treated with IGF-1 or insulin alone. IGF-1 did, however, enhance transcriptional activity in combination with lithium chloride, an inhibitor of glycogen synthase kinase 3 beta, which also stabilizes beta-catenin. In conclusion, we have shown that IGF-1 causes tyrosine phosphorylation and stabilization of beta-catenin. These effects may contribute to transformation, cell migration, and a propensity for metastasis in vivo.

The recent advances in the understanding of the pathogenesis of ovarian cancer have been helpful in addressing issues in diagnosis, prognosis and management. The study of ovarian tumours by novel techniques such as immunohistochemistry, fluorescent in situ hybridisation, comparative genomic hybridisation, polymerase chain reaction and new tumour markers have aided the evaluation and application of new concepts into clinical practice. The correlation of novel surrogate tumour specific features with response to treatment and outcome in patients has defined prognostic factors which may allow the future design of tailored therapy based on a molecular profile of the tumour. These have also been used to design new approaches to therapy such as antibody targeting and gene therapy. The delineation of roles of c-erbB2, c-fms and other novel receptor kinases in the pathogenesis of ovarian cancer has led initially to the development of anti-c-erbB2 monoclonal antibody therapy. The discovery of BRCA1 and BRCA2 genes will have an impact in the diagnosis and the prevention of familial ovarian cancer. The important role played by recessive genes such as p53 in cancer has raised the possibility of restoration of gene function by gene therapy. Although the pathological diagnosis of ovarian cancer is still confirmed principally on morphological features, addition of newer investigations will increasingly be useful in addressing difficult diagnostic problems. The increasingly rapid pace of discovery of genes important in disease, makes it imperative that the evaluation of their contribution in the pathogenesis of ovarian cancer is undertaken swiftly, thus improving the overall management of patients and their outcome.

The human X chromosome is associated with a large number of disease phenotypes, principally because of its unique mode of inheritance that tends to reveal all recessive disorders in males. With the longer term goal of identifying and characterizing most of these genes, we have adopted a chromosome-wide strategy to establish a YAC contig map. We have performed > 3250 inter Alu-PCR product hybridizations to identify overlaps between YAC clones. Positional information associated with many of these YAC clones has been derived from our Reference Library Database and a variety of other public sources. We have constructed a YAC contig map of the X chromosome covering 125 Mb of DNA in 25 contigs and containing 906 YAC clones. These contigs have been verified extensively by FISH and by gel and hybridization fingerprinting techniques. This independently derived map exceeds the coverage of recently reported X chromosome maps built as part of whole-genome YAC maps.

The discoidin domain receptor (DDR) is a new class of receptor tyrosine kinase that is distinguished by a unique extracellular domain homologous to the lectin Discoidin I found Dictyostelium discoideum. A cosmid was isolated from a human chromosome 6 cosmid library containing the DDR gene. A complete genomic contig of the DDR gene was constructed from seven subclones of the cosmid. The cosmid fragments were analyzed by PCR, sequencing, and comparison of genomic/cDNA sequence. The DDR gene is composed of 17 exons, ranging in size from 96 to 1014 bp, distributed along approximately 12 kb of genomic DNA. The extracellular domain is encoded by 8 exons of which three code for the discoidin domain. The transmembrane domain is encoded by 1 exon, the juxtamembrane by 3 exons, and the catalytic domain by 5 exons. The generation of the two splice variants of DDR, EDDR1 and EDDR2 are explained by the genomic structure. Exon 11 (111 bp in the juxtamembrane domain) is present in DDR and absent in the splice variant EDDR1. An inverted repeat of 20 bp was identified at the 3' exon-intron junction of exon 11, which results in a lariat loop-like secondary structure. EDDR2 is generated because of a cryptic splice acceptor site that results in an extra 18 bp (6 amino acids) inserted 5' of exon 14 in the catalytic domain. A polymorphic (GT)17 repeat was identified in intron 5 with a heterozygosity of 0.71. The exon-intron structure of the DDR gene will be helpful in further understanding of its function and explains the possible structural basis for the two splice variants.

Parenteral strobilation of Echinococcus multilocularis was observed in acid (severe combined immuno-deficient) mice after intracerebral, subcutaneous and intraperitoneal inoculation with protoscoleces. Evaginated protoscoleces and segmented worms were obtained at the inoculated sites. Most worms recovered from peritoneal cavity of scid mice were encapsulated by connective tissue and granulocytes but showed a maximum of 3 proglottids, elongation of genital primordia and vesiculation. Viability of worms recovered from the subcutaneous tissue and peritoneal cavity of scid mice were higher (69.1-91.4%) than those from the immunologically normal C.B-17 (4.0-48.0%) control mice. However, viabilities of worms from the cerebrum of both scid and C.B-17 were almost the same (87.7-94.4%). Worms recovered from scid mice showed further development of reproductive organs when transplanted into the small intestine of prednisolone treated golden hamster. These findings suggest that the parenteral milieu of scid mice allows adult development of E. multilocularis protoscoleces.

Severe combined immune-deficient (scid) mice, which lack functional B- and T-lymphocytes, were infected with Echinococcus multilocularis larval tissue before or after reconstitution with lymphoid cells from immunocompetent donor mice. Untreated scid mice were highly susceptible to E. multilocularis infection, while scid mice reconstituted with purified lymphocytes derived from either infected or uninfected normal donor mice were capable of almost totally suppressing the growth of the larval cyst mass. The somatic development of the larval parasite varied according to the infection status of the cell donor, with protoscolices forming in scid mice reconstituted with cells from uninfected normal mice but not in those receiving cells from infected normal mice. These results confirm earlier findings that lymphocytes are important in suppressing the growth of E. multilocularis cysts in the intermediate host and also indicate that protoscolex development is influenced by lymphocytes or their products.

E. multilocularis infection was suppressed in C.B-17 mice after intraperitoneal inoculation of protoscoleces, with larval cysts weighing no more than 1.0 g. In scid mice, which are genetically identical to C.B-17 except for a deficiency in functional lymphocytes, infection progressed and larval cysts reached a mass of 17.5 g at 15 weeks post-infection. The growth of the larval cyst mass in scid mice was similar to that in other susceptible mouse strains, with a biphasic pattern. Histological observations revealed giant cells and granulomatous inflammation in the C.B-17, but not in the scid mice. These results led to the conclusion that suppression of the growth of the larval cyst mass in the initial stage of infection in susceptible mice strains is caused by factors other than the host's lymphocytic immune response.

Echinococcus multilocularis is a cestode helminth which, along with E. granulosus, E. oligarthus and E. vogeli is a causative agent of hydatid disease in man. In the intermediate host (including man), cysts formed by the metacestode (larval stage) develop in the internal organs, causing functional impairment which often leads to the death of the host. In this review larval E. multilocularis infection in mice, the most popular experimental intermediate host, is examined, and the immune response to the organism is described in detail. Evidence is presented which suggests that cell-mediated immunity (CMI) plays a large role in suppression of larval growth. Congenitally athymic nude mice, and mice treated to remove thymocytes had high susceptibility to infection, while mice strains assessed as having high helper T lymphocyte function showed resistance to infection. The degree of antibody response shown by the host does not correlate with the susceptibility to E. multilocularis. Infection with E. multilocularis is accompanied by immunosuppression, manifested by inhibition of effector cell chemotaxis and receptor expression, suppressor macrophage and lymphocyte activity, decline in helper T-lymphocyte activity and immune-complex deposition.