Bovine Malignant Catarrhal Fever

Malignant catarrhal fever (MCF) or malignant head catarrh has been recognized for over 125 years as a fatal disease of cattle and some wild ruminants. Found world wide, it is prevalent in Australia, the British Isles, Canada, the United States and Africa. The causative agent is believed to be a herpesvirus, but it is thought that tissue damage is the result of hypersensitivity to viral antigens and not direct effects of the virus

A Novel Mutation in the Upstream Open Reading Frame of the CDKN1B Gene Causes a MEN4 Phenotype

PubMed ID: 23555276This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Claw and limb disorders in 12 Norwegian beef-cow herds

<p>Abstract</p> <p>Background</p> <p>The main aim of the study was to assess the prevalence of claw and limb disorders in Norwegian beef-cow herds.</p> <p>Methods</p> <p>Twenty-six herds with ≥15 cow-years were selected by computerized systematic assignment from the three most beef cattle-dense regions of Norway. The study population consisted of 12 herds with 28 heifers and 334 cows. The animals were trimmed and examined once by claw trimmers during the late winter and spring of 2003. The seven claw trimmers had been taught diagnosing and recording of claw lesions. Environment, feeding and management routines, age and breed, culling and carcass characteristics were also recorded.</p> <p>Results</p> <p>Lameness was recorded in 1.1% of the animals, and only in hind claws. Pericarpal swellings were recorded in one animal and peritarsal lesions in none. In total, claw and limb disorders including lameness were recorded in 29.6% of the animals, 4.1% with front and 28.2% with hind limb disorders, respectively. Most lesions were mild. Laminitis-related claw lesions were recorded in 18.0% of the animals and infectious lesions in 16.6%. The average claw length was 84 mm in front claws and 89 mm in hind claw. Both laminitis-related and infectious claw lesions were more prevalent with increasing age. Carcasses from animals with claw and limb disorders were on average 34 kg heavier than carcasses from animals without such disorders (p = 0.02). Our results also indicate association between some management factors and claw lesions.</p> <p>Conclusion</p> <p>The study shows that the prevalence of lameness was low in 12 Norwegian beef-cow herds compared to beef-cattle herds in other countries and also that there were less claw and limb disorders in these herds compared to foreign dairy-cattle herds. The prevalence of lameness and white-line fissures was approximately the same as in Norwegian dairy herds whereas less dermatitis, heel-horn erosions, haemorrhages of the sole and the white line and sole ulcers were recorded.</p

A Chemical Genetic Screen for Modulators of Asymmetrical 2,2′-Dimeric Naphthoquinones Cytotoxicity in Yeast

BACKGROUND: Dimeric naphthoquinones (BiQ) were originally synthesized as a new class of HIV integrase inhibitors but have shown integrase-independent cytotoxicity in acute lymphoblastic leukemia cell lines suggesting their use as potential anti-neoplastic agents. The mechanism of this cytotoxicity is unknown. In order to gain insight into the mode of action of binaphthoquinones we performed a systematic high-throughput screen in a yeast isogenic deletion mutant array for enhanced or suppressed growth in the presence of binaphthoquinones. METHODOLOGY/PRINCIPAL FINDINGS: Exposure of wild type yeast strains to various BiQs demonstrated inhibition of yeast growth with IC(50)s in the microM range. Drug sensitivity and resistance screens were performed by exposing arrays of a haploid yeast deletion mutant library to BiQs at concentrations near their IC(50). Sensitivity screens identified yeast with deletions affecting mitochondrial function and cellular respiration as having increased sensitivity to BiQs. Corresponding to this, wild type yeast grown in the absence of a fermentable carbon source were particularly sensitive to BiQs, and treatment with BiQs was shown to disrupt the mitochondrial membrane potential and lead to the generation of reactive oxygen species (ROS). Furthermore, baseline ROS production in BiQ sensitive mutant strains was increased compared to wild type and could be further augmented by the presence of BiQ. Screens for resistance to BiQ action identified the mitochondrial external NAD(P)H dehydrogenase, NDE1, as critical to BiQ toxicity and over-expression of this gene resulted in increased ROS production and increased sensitivity of wild type yeast to BiQ. CONCLUSIONS/SIGNIFICANCE: In yeast, binaphthoquinone cytotoxicity is likely mediated through NAD(P)H:quonine oxidoreductases leading to ROS production and dysfunctional mitochondria. Further studies are required to validate this mechanism in mammalian cells

A search for structurally similar cellular internal ribosome entry sites

Internal ribosome entry sites (IRES) allow ribosomes to be recruited to mRNA in a cap-independent manner. Some viruses that impair cap-dependent translation initiation utilize IRES to ensure that the viral RNA will efficiently compete for the translation machinery. IRES are also employed for the translation of a subset of cellular messages during conditions that inhibit cap-dependent translation initiation. IRES from viruses like Hepatitis C and Classical Swine Fever virus share a similar structure/function without sharing primary sequence similarity. Of the cellular IRES structures derived so far, none were shown to share an overall structural similarity. Therefore, we undertook a genome-wide search of human 5′UTRs (untranslated regions) with an empirically derived structure of the IRES from the key inhibitor of apoptosis, X-linked inhibitor of apoptosis protein (XIAP), to identify novel IRES that share structure/function similarity. Three of the top matches identified by this search that exhibit IRES activity are the 5′UTRs of Aquaporin 4, ELG1 and NF-kappaB repressing factor (NRF). The structures of AQP4 and ELG1 IRES have limited similarity to the XIAP IRES; however, they share trans-acting factors that bind the XIAP IRES. We therefore propose that cellular IRES are not defined by overall structure, as viral IRES, but are instead dependent upon short motifs and trans-acting factors for their function

Stat1 Phosphorylation Determines Ras Oncogenicity by Regulating p27Kip1

Inactivation of p27Kip1 is implicated in tumorigenesis and has both prognostic and treatment-predictive values for many types of human cancer. The transcription factor Stat1 is essential for innate immunity and tumor immunosurveillance through its ability to act downstream of interferons. Herein, we demonstrate that Stat1 functions as a suppressor of Ras transformation independently of an interferon response. Inhibition of Ras transformation and tumorigenesis requires the phosphorylation of Stat1 at tyrosine 701 but is independent of Stat1 phosphorylation at serine 727. Stat1 induces p27Kip1 expression in Ras transformed cells at the transcriptional level through mechanisms that depend on Stat1 phosphorylation at tyrosine 701 and activation of Stat3. The tumor suppressor properties of Stat1 in Ras transformation are reversed by the inactivation of p27Kip1. Our work reveals a novel functional link between Stat1 and p27Kip1, which act in coordination to suppress the oncogenic properties of activated Ras. It also supports the notion that evaluation of Stat1 phosphorylation in human tumors may prove a reliable prognostic factor for patient outcome and a predictor of treatment response to anticancer therapies aimed at activating Stat1 and its downstream effectors

Design of a multicentered randomized controlled trial on the clinical and cost effectiveness of schema therapy for personality disorders

<p>Abstract</p> <p>Background</p> <p>Despite international guidelines describing psychotherapy as first choice for people with personality disorders (PDs), well-designed research on the effectiveness and cost-effectiveness of psychotherapy for PD is scarce. Schema therapy (ST) is a specific form of psychological treatment that proved to be effective for borderline PD. Randomized controlled studies on the effectiveness of ST for other PDs are lacking. Another not yet tested new specialized treatment is Clarification Oriented Psychotherapy (COP). The aim of this project is to perform an effectiveness study as well as an economic evaluation study (cost effectiveness as well as cost-utility) comparing ST versus COP versus treatment as usual (TAU). In this study, we focus on avoidant, dependent, obsessive-compulsive, paranoid, histrionic and narcissistic PD.</p> <p>Methods/Design</p> <p>In a multicentered randomized controlled trial, ST, and COP as an extra experimental condition, are compared to TAU. Minimal 300 patients are recruited in 12 mental health institutes throughout the Netherlands, and receive an extensive screening prior to enrolment in the study. When eligible, they are randomly assigned to one of the intervention groups. An economic evaluation and a qualitative research study on patient and therapist perspectives on ST are embedded in this trial. Outcome assessments (both for clinical effectiveness and economic evaluation) take place at 6,12,18,24 and 36 months after start of treatment. Primary outcome is recovery from PD; secondary measures include general psychopathological complaints, social functioning and quality of life. Data for the cost-effectiveness and cost-utility analyses are collected by using a retrospective cost interview. Information on patient and therapist perspectives is gathered using in-depth interviews and focus groups, and focuses on possible helpful and impeding aspects of ST.</p> <p>Discussion</p> <p>This trial is the first to compare ST and COP head-to-head with TAU for people with a cluster C, paranoid, histrionic and/or narcissistic PD. By combining clinical effectiveness data with an economic evaluation and with direct information from primary stakeholders, this trial offers a complete and thorough view on ST as a contribution to the improvement of treatment for this PD patient group.</p> <p>Trial registration</p> <p>Netherlands Trial Register (NTR): <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=566">NTR566</a></p