Sequence‐independent processing site of the C‐terminal domain (CTD) influences maturation of the RgpB protease from Porphyromonas gingivalis

The Gram‐negative periodontal pathogen Porphyromonas gingivalis produces a family of outer membrane‐anchored proteases, the gingipains, shown to play an essential role in virulence of the organism. The C‐terminal domain (CTD) of gingipains and other secreted proteins is known to be the targeting signal for maturation and translocation of the protein through the outer membrane. The CTD is subsequently cleaved during the secretion process. Multiple alignment of various CTDs failed to define a consensus sequence at the putative CTD processing site. Using mutagenesis, we were able to show that cleavage at the site is not dependent on a specific residue and that recognition of the site is independent of local sequence. Interestingly, length of the junction between the CTD and adjacent Ig‐like subdomain has a critical influence on post‐translational glycan modification of the protein, whereby insertion of additional residues immediately N‐terminal to the cleavage site results in failure of glycan modification and release of soluble protease into the culture medium. Various hypotheses are presented to explain these phenomena. Knowledge of the role CTDs play in maturation of gingipains has broader application for understanding maturation of CTD homologues expressed by bacteria of the Bacteriodetes phylum.     

Scots pine growing on forested mires in Abernethy Forest,Strathspey, Scotland

Summary

A substantial proportion of the Abernethy Forest Reserve has Scots pine (Pinus sylvestris) growing on the surfaces of a variety of mires. The hydrology of the mires has been affected by drainage and peat cutting but this area is unusual in having had a long period of protection from grazing by domestic stock. There are three main types of pine populations found on these mires. Woodland bog comprises predominantly bog vegetation with abundant pine seedlings due to the heavy seed rain from the surrounding woodland. Only a few very small trees survive, which are stunted, heavily diseased and have very low seed production. Wooded bog also comprises predominately bog vegetation but there are scattered mature trees of a moderate height with an open canopy. The trees are fertile and can form uneven aged stands with regeneration. Bog woodland is a predominantly woodland vegetation with tall, dense tree cover on deep peat. The trees are well grown with a dense canopy. A few remnants of bog vegetation remain in the ground flora although most have been replaced by woodland bryophytes and shrubs. Each of these three types is described and their development is discussed.     

Neutering Dogs: Effects on Joint Disorders and Cancers in Golden Retrievers

In contrast to European countries, the overwhelming majority of dogs in the U.S. are neutered (including spaying), usually done before one year of age. Given the importance of gonadal hormones in growth and development, this cultural contrast invites an analysis of the multiple organ systems that may be adversely affected by neutering. Using a single breed-specific dataset, the objective was to examine the variables of gender and age at the time of neutering versus leaving dogs gonadally intact, on all diseases occurring with sufficient frequency for statistical analyses. Given its popularity and vulnerability to various cancers and joint disorders, the Golden Retriever was chosen for this study. Veterinary hospital records of 759 client-owned, intact and neutered female and male dogs, 1–8 years old, were examined for diagnoses of hip dysplasia (HD), cranial cruciate ligament tear (CCL), lymphosarcoma (LSA), hemangiosarcoma (HSA), and mast cell tumor (MCT). Patients were classified as intact, or neutered early (<12 mo) or late (≥12 mo). Statistical analyses involved survival analyses and incidence rate comparisons. Outcomes at the 5 percent level of significance are reported. Of early-neutered males, 10 percent were diagnosed with HD, double the occurrence in intact males. There were no cases of CCL diagnosed in intact males or females, but in early-neutered males and females the occurrences were 5 percent and 8 percent, respectively. Almost 10 percent of early-neutered males were diagnosed with LSA, 3 times more than intact males. The percentage of HSA cases in late-neutered females (about 8 percent) was 4 times more than intact and early-neutered females. There were no cases of MCT in intact females, but the occurrence was nearly 6 percent in late-neutered females. The results have health implications for Golden Retriever companion and service dogs, and for oncologists using dogs as models of cancers that occur in humans.     

The Role of Task-Related Learned Representations in Explaining Asymmetries in Task Switching

Task switch costs often show an asymmetry, with switch costs being larger when switching from a difficult task to an easier task. This asymmetry has been explained by difficult tasks being represented more strongly and consequently requiring more inhibition prior to switching to the easier task. The present study shows that switch cost asymmetries observed in arithmetic tasks (addition vs. subtraction) do not depend on task difficulty: Switch costs of similar magnitudes were obtained when participants were presented with unsolvable pseudo-equations that did not differ in task difficulty. Further experiments showed that neither task switch costs nor switch cost asymmetries were due to perceptual factors (e.g., perceptual priming effects). These findings suggest that asymmetrical switch costs can be brought about by the association of some tasks with greater difficulty than others. Moreover, the finding that asymmetrical switch costs were observed (1) in the absence of a task switch proper and (2) without differences in task difficulty, suggests that present theories of task switch costs and switch cost asymmetries are in important ways incomplete and need to be modified.     

Alirocumab,a Therapeutic Human Antibody to PCSK9, Does Not Affect CD81 Levels or Hepatitis C Virus Entry and Replication into Hepatocytes

BackgroundProprotein convertase subtilisin/kexin type 9 (PSCK9) is secreted mainly from the liver and binds to the low-density lipoprotein receptor (LDLR), reducing LDLR availability and thus resulting in an increase in LDL-cholesterol. While the LDLR has been implicated in the cell entry process of the hepatitis C virus (HCV), overexpression of an artificial non-secreted, cell membrane-bound form of PCSK9 has also been shown to reduce surface expression of CD81, a major component of the HCV entry complex, leading to concerns that pharmacological inhibition of PCSK9 may increase susceptibility to HCV infection by increasing either CD81 or LDLR availability. Here, we evaluated effects of PCSK9 and PCSK9 blockade on CD81 levels and HCV entry with a physiologically relevant model using native secreted PCSK9 and a monoclonal antibody to PCSK9, alirocumab.ConclusionThese results suggest that inhibition of PCSK9 with alirocumab has no effect on CD81 and does not result in increased susceptibility to HCV entry.     

Seasonal nutritional status in Norway lobsters,Nephrops norvegicus (L.): are females nutritionally compromised over the winter?

Norway lobsters, Nephrops norvegicus, are sediment-dwelling decapod crustaceans that excavate burrows from which they make short excursions to feed by predation and scavenging. The females of this species are known to reside within their burrows for an extended period of time over the winter while brooding their eggs. The aim of this study was to assess the likelihood of these females being able to feed during this brooding period. Biophysical and biochemical measurements that had previously been shown to change with starvation under laboratory conditions in male N. norvegicus were taken for female N. norvegicus under similar conditions. These measurements were also compared in both sexes obtained from monthly trawl samples from the Clyde Sea Area, Scotland, UK, together with trawl composition data. The laboratory study showed that the hepatosomatic index, and the copper, lipid and water content of the hepatopancreas can be used as indicators of the state of starvation in females, as in males. In the wild, both sexes have reduced nutritional status during the winter, but not to the degree seen in animals starved for 20 weeks in aquarium trials. This study does not support the hypothesis that females cease feeding over winter, during their brooding period. Firstly, some females were unable to sustain ovary development during starvation under controlled conditions, contrary to field observations. Secondly, field data suggest that there is no sex-specific reduction in nutritional status.