Uniformity in the biochemical properties of Renibacterium salmoninarum isolates obtained from several sources

Abstract A marked similarity in the biochemical properties of 26 Renibacterium salmoninarum cultures was found. Properties not previously recorded for this bacterium include haemolytic and proteolytic activity, DNase and the presence of glycogen in cells, and negative reactions in tests for nitrates, Tween-80 hydrolysis, amylase, bile solubility, arginine hydrolysis and phosphatase. Selected properties enabled bacteria morphologically similar to R. salmoninarum to be identified.     

Pulmonary hypertension and fenfluramine

Pulmonary hypertension developed in two women who had been taking fenfluramine for over eight months for weight reduction. On withdrawing the drug symptoms and electrocardiographic evidence of pulmonary hypertension disappeared in both cases. In one patient, however, the evidence recurred after rechallenge with fenfluramine.These findings are strong evidence that fenfluramine may cause pulmonary hypertension. Hence any patient taking the drug should report immediately any deterioration in exercise tolerance.     

Seasonality and heterogeneity of live fish movements in Scottish fish farms

Movement of live animals is a key contributor to disease spread. Farmed Atlantic salmon Salmo salar, rainbow trout Onchorynchus mykiss and brown/sea trout Salmo trutta are initially raised in freshwater (FW) farms; all the salmon and some of the trout are subsequently moved to seawater (SW) farms. Frequently, fish are moved between farms during their FW stage and sometimes during their SW stage. Seasonality and differences in contact patterns across production phases have been shown to influence the course of an epidemic in livestock; however, these parameters have not been included in previous network models studying disease transmission in salmonids. In Scotland, farmers are required to register fish movements onto and off their farms; these records were used in the present study to investigate seasonality and heterogeneity of movements for each production phase separately for farmed salmon, rainbow trout and brown/sea trout. Salmon FW-FW and FW-SW movements showed a higher degree of heterogeneity in number of contacts and different seasonal patterns compared with SW-SW movements. FW-FW movements peaked from May to July and FW-SW movements peaked from March to April and from October to November. Salmon SW-SW movements occurred more consistently over the year and showed fewer connections and number of repeated connections between farms. Therefore, the salmon SW-SW network might be treated as homogeneous regarding the number of connections between farms and without seasonality. However, seasonality and production phase should be included in simulation models concerning FW-FW and FW-SW movements specifically. The number of rainbow trout FW-FW and brown/sea trout FW-FW movements were different from random. However, movements from other production phases were too low to discern a seasonal pattern or differences in contact pattern.     

E2F-1 regulation by an unusual DNA damage-responsive DP partner subunit

E2F activity is negatively regulated by retinoblastoma protein (pRb) through binding to the E2F-1 subunit. Within the E2F heterodimer, DP proteins are E2F partner subunits that allow proper cell cycle progression. In contrast to the other DP proteins, the newest member of the family, DP-4, downregulates E2F activity. In this study we report an unexpected role for DP-4 in regulating E2F-1 activity during the DNA damage response. Specifically, DP-4 is induced in DNA-damaged cells, upon which it binds to E2F-1 as a non-DNA-binding E2F-1/DP-4 complex. Consequently, depleting DP-4 in cells re-instates E2F-1 activity that coincides with increased levels of chromatin-bound E2F-1, E2F-1 target gene expression and associated apoptosis. Mutational analysis of DP-4 highlighted a C-terminal region, outside the DNA-binding domain, required for the negative control of E2F-1 activity. Our results define a new pathway, which acts independently of pRb and through a biochemically distinct mechanism, involved in negative regulation of E2F-1 activity.     

Luciferase-expressing Leishmania infantum allows the monitoring of amastigote population size, in vivo, ex vivo and in vitro

Here we engineered transgenic Leishmania infantum that express luciferase, the objectives being to more easily monitor in real time their establishment either in BALB/c mice--the liver and spleen being mainly studied-or in vitro. Whatever stationary phase L. infantum promastigotes population--wild type or engineered to express luciferase-the parasite burden was similar in the liver and the spleen at day 30 post the intravenous inoculation of BALB/c mice. Imaging of L. infantum hosting BALB/C mice provided sensitivity in the range of 20,000 to 40,000 amastigotes/mg tissue, two tissues-liver and spleen-being monitored. Once sampled and processed ex vivo for their luciferin-dependent bioluminescence the threshold sensitivity was shown to range from 1,000 to 6,000 amastigotes/mg tissue. This model further proved to be valuable for in vivo measurement of the efficiency of drugs such as miltefosine and may, therefore, additionally be used to evaluate vaccine-induced protection.     

Bridging the gap: Facilities and technologies for development of early stage therapeutic mAb candidates

Therapeutic monoclonal antibodies (mAbs) currently dominate the biologics marketplace. Development of a new therapeutic mAb candidate is a complex, multistep process and early stages of development typically begin in an academic research environment. Recently, a number of facilities and initiatives have been launched to aid researchers along this difficult path and facilitate progression of the next mAb blockbuster. Complementing this, there has been a renewed interest from the pharmaceutical industry to reconnect with academia in order to boost dwindling pipelines and encourage innovation. In this review, we examine the steps required to take a therapeutic mAb from discovery through early stage preclinical development and toward becoming a feasible clinical candidate. Discussion of the technologies used for mAb discovery, production in mammalian cells and innovations in single-use bioprocessing is included. We also examine regulatory requirements for product quality and characterization that should be considered at the earliest stages of mAb development. We provide details on the facilities available to help researchers and small-biotech build value into early stage product development, and include examples from within our own facility of how technologies are utilized and an analysis of our client base.Key words: monoclonal antibody, preclinical development, biologics, CHO cells, cell culture     

Effects of Hunting on Response Behaviors of Wild Reindeer

ABSTRACT Because wild reindeer (Rangifer tarandus) are hunted in southern Norway, reindeer may perceive all recreationists as threats. Potential adverse effects of hunting on reindeer behavior may be exacerbated by other forms of recreation because the number of skiers and hikers in areas inhabited by reindeer has also increased. The Norefjell-Reinsjøfjell wild reindeer area is used extensively for recreation and tourism. Reindeer hunting was introduced in the area in 1992, and harvest rate has been stable at about 38% of winter herd size. We recorded behavioral responses of reindeer to a person approaching directly on foot or skis during 1992 and again in 2002–2006. Compared to 1992, flight-initiation distance increased and fewer groups assessed the observer before taking flight during 2002–2006. In winter, when reindeer are usually comparably more vigilant than in other seasons, flight-initiation distance increased from only 60 m to 115 m and escape distance decreased from 400 m to 210 m. Neither alert distance, calf carcass weights (23.6 ± 0.7 [SE] kg to 22.4 ± 0.2 kg), nor reindeer herd size (661 ± 73 to 579 ± 15) changed during the 15 years of our study. Reindeer appeared to habituate to the observer because they initiated flight at shorter distances as the number of approaches on the same day increased. In Norefjell-Reinsjøfjell, encounters with a person on foot or skis did not result in behavioral responses likely to entail substantial energy costs for reindeer; therefore, hunting at current levels appears compatible with other recreational activities.     

The Simulium vernum group (Diptera: Simuliidae) in Europe: multiple character sets for assessing species status

The value of using characters from multiple sources – chromosomes, ecology, gene sequences, and morphology – to evaluate the species status of closely related black flies is demonstrated for three European members of the Simulium vernum group: Simulium crenobium (Knoz, 1961), Simulium juxtacrenobium Bass & Brockhouse, 1990, and Simulium vernum s.s. Macquart, 1826. Simulium juxtacrenobium is a chromosomally, molecularly, and morphologically distinct species that diverged from S. crenobium and S. vernum s.s. about 2 Mya. It is specialized for intermittent streams, is univoltine, and is recorded for the first time from northern Europe, based on collections from Finland and Sweden, representing a range extension of about 1800 km. In contrast, S. crenobium, although confirmed as a distinct species, differs from S. vernum s.s. by only a few larval and chromosomal characters, and by a breeding habitat restricted to mountain spring brooks. Whereas all four character sets independently support the specific distinctness of S. juxtacrenobium and S. vernum s.s., multiple character sets are required to establish the specific validity of S. crenobium.