An empirical approach towards the efficient and optimal production of influenza-neutralizing ovine polyclonal antibodies demonstrates that the novel adjuvant CoVaccine HT(TM) is functionally superior to Freund's adjuvant

Passive immunotherapies utilising polyclonal antibodies could have a valuable role in preventing and treating infectious diseases such as influenza, particularly in pandemic situations but also in immunocompromised populations such as the elderly, the chronically immunosuppressed, pregnant women, infants and those with chronic diseases. The aim of this study was to optimise current methods used to generate ovine polyclonal antibodies. Polyclonal antibodies to baculovirus-expressed recombinant influenza haemagglutinin from A/Puerto Rico/8/1934 H1N1 (PR8) were elicited in sheep using various immunisation regimens designed to investigate the priming immunisation route, adjuvant formulation, sheep age, and antigen dose, and to empirically ascertain which combination maximised antibody output. The novel adjuvant CoVaccine HT™ was compared to Freund’s adjuvant which is currently the adjuvant of choice for commercial production of ovine polyclonal Fab therapies. CoVaccine HT™ induced significantly higher titres of functional ovine anti-haemagglutinin IgG than Freund’s adjuvant but with fewer side effects, including reduced site reactions. Polyclonal hyperimmune sheep sera effectively neutralised influenza virus in vitro and, when given before or after influenza virus challenge, prevented the death of infected mice. Neither the age of the sheep nor the route of antigen administration appeared to influence antibody titre. Moreover, reducing the administrated dose of haemagglutinin antigen minimally affected antibody titre. Together, these results suggest a cost effective way of producing high and sustained yields of functional ovine polyclonal antibodies specifically for the prevention and treatment of globally significant diseases.Natalie E. Stevens, Cara K. Fraser, Mohammed Alsharifi, Michael P. Brown, Kerrilyn R. Diener, John D. Haybal

Novel survey method finds dramatic decline of wild cotton-top tamarin population

For conservation purposes, accurate methods are required to track cotton-top tamarins in their natural habitat. As existing census methods are not appropriate for surveying these monkeys, a lure-transect method combined with playback vocalization was used here to allow accurate counting of the animals

Overview of homocysteine and folate metabolism. With special references to cardiovascular disease and neural tube defects

This overview addresses homocysteine and folate metabolism. Its functions and complexity are described, leading to explanations why disturbed homocysteine and folate metabolism is implicated in many different diseases, including congenital birth defects like congenital heart disease, cleft lip and palate, late pregnancy complications, different kinds of neurodegenerative and psychiatric diseases, osteoporosis and cancer. In addition, the inborn errors leading to hyperhomocysteinemia and homocystinuria are described. These extreme human hyperhomocysteinemia models provide knowledge about which part of the homocysteine and folate pathways are linked to which disease. For example, the very high risk for arterial and venous occlusive disease in patients with severe hyperhomocysteinemia irrespective of the location of the defect in remethylation or transsulphuration indicates that homocysteine itself or one of its “direct” derivatives is considered toxic for the cardiovascular system. Finally, common diseases associated with elevated homocysteine are discussed with the focus on cardiovascular disease and neural tube defects

The Effects of Tail Biopsy for Genotyping on Behavioral Responses to Nociceptive Stimuli

Removal of a small segment of tail at weaning is a common method used to obtain tissue for the isolation of genomic DNA to identify genetically modified mice. When genetically manipulated mice are used for pain research, this practice could result in confounding changes to the animals' responses to noxious stimuli. In this study, we sought to systematically investigate whether tail biopsy representative of that used in standard genotyping methods affects behavioral responses to a battery of tests of nociception. Wild-type littermate C57BL/6J and 129S6 female and male mice received either tail biopsies or control procedural handling at Day 21 after birth and were then tested at 6–9 weeks for mechanical and thermal sensitivity. C57BL/6J mice were also tested in the formalin model of inflammatory pain. In all tests performed (von Frey, Hargreaves, modified Randall Selitto, and formalin), C57BL/6J tail-biopsied animals' behavioral responses were not significantly different from control animals. In 129S6 animals, tail biopsy did not have a significant effect on behavioral responses in either sex to the von Frey and the modified Randall-Selitto tests of mechanical sensitivity. Interestingly, however, both sexes exhibited small but significant differences between tail biopsied and control responses to a radiant heat stimulus. These results indicate that tail biopsy for genotyping purposes has no effect on nocifensive behavioral responses of C57BL/6J mice, and in 129S6 mice, causes only a minor alteration in response to a radiant heat stimulus while other nocifensive behavioral responses are unchanged. The small effect seen is modality- and strain-specific

Bacterial diversity in snow on North Pole ice floes

The microbial abundance and diversity in snow on ice floes at three sites near the North Pole was assessed using quantitative PCR and 454 pyrosequencing. Abundance of 16S rRNA genes in the samples ranged between 43 and 248 gene copies per millilitre of melted snow. A total of 291,331 sequences were obtained through 454 pyrosequencing of 16S rRNA genes, resulting in 984 OTUs at 97 % identity. Two sites were dominated by Cyanobacteria (72 and 61 %, respectively), including chloroplasts. The third site differed by consisting of 95 % Proteobacteria. Principal component analysis showed that the three sites clustered together when compared to the underlying environments of sea ice and ocean water. The Shannon indices ranged from 2.226 to 3.758, and the Chao1 indices showed species richness between 293 and 353 for the three samples. The relatively low abundances and diversity found in the samples indicate a lower rate of microbial input to this snow habitat compared to snow in the proximity of terrestrial and anthropogenic sources of microorganisms. The differences in species composition and diversity between the sites show that apparently similar snow habitats contain a large variation in biodiversity, although the differences were smaller than the differences to the underlying environment. The results support the idea that a globally distributed community exists in snow and that the global snow community can in part be attributed to microbial input from the atmosphere. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00792-014-0660-y) contains supplementary material, which is available to authorized users

Theorizing Institutional Scandal and the Regulatory State

One by one, UK public institutions are being scandalised for corruption, immorality or incompetence and subjected to trial by media and criminal prosecution. The state?s historic response to public sector scandal ? denial and neutralisation ? has been replaced with acknowledgement and regulation in the form of the re-vamped public inquiry. Public institutions are being cut adrift and left to account in isolation for their scandalous failures. Yet the state?s attempts to distance itself from its scandalised institutions, while extending its regulatory control over them, are risky. Both the regulatory state and its public inquiries risk being consumed by the scandal they are trying to manage

The influence of a pre-exercise sports drink (PRX) on factors related to maximal aerobic performance

<p>Abstract</p> <p>Background</p> <p>Pre-exercise sports drinks (PRX) are commonly used as ergogenic aids in athletic competitions requiring aerobic power. However, in most cases, claims regarding their effectiveness have not been substantiated. In addition, the ingredients in PRX products must be deemed acceptable by the athletic governing bodies that regulate their use in training and competition. The purpose of this study was to examine the effects of a modified PRX formulation (known as EM·PACT™) from earlier investigations on factors related to maximal aerobic performance during a graded exercise test. The modification consisted of removing creatine to meet the compliance standards set forth by various athletic organizations that regulate the use of nutritional supplements.</p> <p>Methods</p> <p>Twenty-nine male and female college students varying in levels of aerobic fitness participated in a randomized crossover administration of PRX (containing 14 g/serving of fructose, medium-chain triglycerides, and amino acids mixed with 8 oz. of water) and placebo (PL) 30 minutes prior to performing a treadmill test with approximately one week separation between the trials. VO₂max, maximal heart rate (HR), time to exhaustion (Time), and percentage estimated non-protein fat substrate utilization (FA) during two <it>a priori </it>submaximal stages of a graded exercise testing were evaluated.</p> <p>Results</p> <p>The VO₂max mean value of the PRX trial was significantly greater than the PL trial (P < 0.01). The mean value for Time was also observed to be greater for the PRX trial compared to PL (P < 0.05). Additionally, percentage of FA during submaximal stages of the exercise test was greater for PRX trial in comparison to PL (P < 0.01).</p> <p>Conclusions</p> <p>The modified PRX formulation utilized in this investigation supports the findings of the previous investigation and its efficacy for enhancing indices of aerobic performance (specifically VO₂max, Time, & FA) during graded exercise testing.</p

Paternal and Maternal History of Myocardial Infarction and Cardiovascular Diseases Incidence in a Dutch Cohort of Middle-Aged Persons

Background - A positive parental history of myocardial infarction (MI) is an independent risk factor for cardiovascular diseases (CVD). However, different definitions of parental history have been used. We evaluated the impact of parental gender and age of onset of MI on CVD incidence. Methods - Baseline data were collected between 1993 and 1997 in 10¿524 respondents aged 40–65 years. CVD events were obtained from the National Hospital Discharge Register and Statistics Netherlands. We used proportional hazard models to calculate hazard ratios (HR) and 95% confidence intervals (CI) for CVD incidence and adjusted for lifestyle and biological risk factors. Results - At baseline, 36% had a parental history of MI. During 10-year follow-up, 914 CVD events occurred. The age and gender adjusted HR was 1.3 (95% CI 1.1–1.5) for those with a paternal MI, 1.5 (1.2–1.8) for those with a maternal MI and 1.6 (1.2–2.2) for those with both parents with an MI. With decreasing parental age of MI, HR increased from 1.2 (1.0–1.6) for age =70 years to 1.5 (1.2–1.8) for ag