Evolution of population genetic structure of the British roe deer by natural and anthropogenic processes (Capreolus capreolus)

Human influence typically impacts on natural populations of conservation interest. These interactions are varied and sometimes complex, and may be negative and unintended or associated with conservation and management strategy. Understanding the details of how these interactions influence and are influenced by natural evolutionary processes is essential to the development of effective conservation strategies. In this study, we investigate a species in Britain that has experienced both negative impact through overhunting in historical times and management efforts through culls and translocations. At the same time, there are regional populations that have been less affected by human influence. We use mtDNA and nuclear microsatellite DNA markers to investigate patterns of connectivity and diversity and find multiple insular populations in Britain that probably evolved within the Holocene (when the habitat was free of ice). We identify three concurrent processes. First, surviving indigenous populations show highly provincial patterns of philopatry, maintaining and generating population structure on a small geographic scale. Second, founder populations into habitat extirpated of native populations have expanded, but remained largely insular. Third, introductions into established populations generate some admixture. We discuss the implications for the evolution of diversity of the integration of natural processes with anthropogenic influences on population size and distribution.     

C5b-9 terminal complex protects oligodendrocytes from apoptotic cell death by inhibiting caspase-8 processing and up-regulating FLIP

Activation of the terminal complement cascade involving C5 to C9 proteins has a beneficial role for oligodendrocytes (OLG) in experimental allergic encephalomyelitis, an animal model of multiple sclerosis, by protecting them from apoptotic cell death. We have previously shown that sublytic C5b-9 complexes, through posttranslational regulation of Bad, inhibit the mitochondrial pathway of apoptosis induced by serum deprivation. In the present study, we examined the possible involvement of the caspase-8 and Fas pathway in OLG apoptosis and the role of C5b-9 in this process. In a serum-free defined medium, OLG undergo apoptosis and differentiation concomitantly. Under this condition, we found that caspase-8 processing was increased in association with Bid cleavage and markedly reduced expression of cellular FLIP long isoform protein. The caspase-8 inhibitor Z-IETD-FMK inhibited cell death associated with differentiation in a dose-dependent manner. Exposure to C5b-9 induced an inhibition of caspase-8 activation, Bid cleavage, and a significant increase in expression of cellular FLIP long isoform. These C5b-9 effects were reversed by PI3K inhibitor LY294002. C5b-9 also down-regulated the expression of FasL and the Fas-induced apoptosis. These data suggest that C5b-9 through PI3K signaling can rescue OLG from Fas-mediated apoptosis by regulating caspase-8 processing.     

RGC-32 increases p34CDC2 kinase activity and entry of aortic smooth muscle cells into S-phase.

Proliferation of aortic smooth muscle cells contributes to atherogenesis and neointima formation. Sublytic activation of complement, particularly C5b-9, induces cell cycle progression in aortic smooth muscle cells. RGC-32 is a novel protein that may promote cell cycle progression in response to complement activation. We cloned human RGC-32 cDNA from a human fetal brain cDNA library. The human RGC-32 cDNA encodes a 117-amino acid protein with 92% similarity to the rat and mouse protein. Human RGC-32 maps to chromosome 13 and is expressed in most tissues. Sublytic complement activation enhanced RGC-32 mRNA expression in human aortic smooth muscle cells and induced nuclear translocation of the protein. RGC-32 was physically associated with cyclin-dependent kinase p34CDC2 and increased the kinase activity in vivo and in vitro. In addition, RGC-32 was phosphorylated by p34CDC2-cyclin B1 in vitro. Mutation of RGC-32 protein at Thr-91 prevented the p34CDC2-mediated phosphorylation and resulted in loss of p34CDC2 kinase enhancing activity. Overexpression of RGC-32 induced quiescent aortic smooth muscle cells to enter S-phase. These data indicate that cell cycle activation by C5b-9 may involve p34CDC2 activity through RGC-32. RGC-32 appears to be a cell cycle regulatory factor that mediates cell proliferation, both as an activator and substrate of p34CDC2.     

Historical sketch of Slovak Haban (Hutterite) population based on autosomal STR analysis

According to the Hutterite chronicles, the Habans arrived from Austrian Tyrol, Switzerland, and northernmost Italy and stayed in four regions of Slovakia (Soboti?te, Vel'ké Leváre, Moravsky Sv?ty Ján, Tren?ín). There are some communities in western Slovakia that retained their Haban cultural identity and still identify themselves as descendents of the Hutterite population with their own specific customs. Slovak Habans are typical founder population with significant social isolation for which high degree of inbreeding is typical. Present study investigated STR polymorphisms as a powerful genetic tool for population genetic studies. The aim was to perform a comparative, population genetic study based on 15 STR loci widely used in forensic genetics, of the Haban population, the Slovak majority population and the population of Tyrol. We analyzed allele frequencies and other statistical parameters in three selected populations in order to identify groups of specific ethnic origin and establish their genetic relationship. The data set included 110 unrelated Habans and 201 unrelated individuals from the Slovak majority population, as well as allelic frequencies for the population of Austrian Tyrol available in the literature. Population pairwise FST values used as a short term genetic distance between populations showed significant differentiation between the Habans and both reference populations (FST=0.0025 and 0.0042 for comparison with the Slovaks and Austrians, respectively; p<10(-3)). The Slovak Hutterites were demonstrated to be genetically distinct and more closely related to their geographic neighbors than to their historical ancestral population, which may be at least partially explained by gene flow between neighboring Haban and Slovak populations.     

Short-term hypoxia/reoxygenation activates the angiogenic pathway in rat caudate putamen

In response to hypoxia, tissues have to implement numerous mechanisms to enhance oxygen delivery, including the activation of angiogenesis. This work investigates the angiogenic response of the hypoxic caudate putamen after several recovery times. Adult Wistar rats were submitted to acute hypoxia and analysed after 0 h, 24 h and 5 days of reoxygenation. Expression of hypoxia-inducible factor-1 alfa (HIF-1α) and angiogenesis-related genes including vascular endothelial growth factor (VEGF), adrenomedullin (ADM) and transforming growth factor-beta 1 (TGF-β1) was determined by both RT-PCR and ELISA. For vessel labelling, lectin location and expression were analysed using histochemical and image processing techniques (fractal dimension). Expression of Hif-1α, Vegf, Adm and Tgf-β1 mRNA rose immediately after hypoxia and this increase persisted in some cases after 5 days post-hypoxia. While VEGF and TGF-β1 protein levels increased parallel to mRNA expression, ADM remained unaltered. The quantification of the striatal vessel network showed a significant augmentation at 24 h of reoxygenation. These results reveal that not only short-term hypoxia, but also the subsequent reoxygenation period, up-regulate the angiogenic pathway in the rat caudate putamen as a neuroprotective mechanism to hypoxia that seeks to maintain a proper blood supply to the hypoxic tissue, thereby minimizing the adverse effects of oxygen deprivation.     

Rapid evolution of a heteroplasmic repetitive sequence in the mitochondrial DNA control region of carnivores

We describe a repetitive DNA region at the 3 end of the mitochondrial DNA (mtDNA) control region and compare it in 21 carnivore species representing eight carnivore families. The sequence and organization of the repetitive motifs can differ extensively between arrays; however, all motifs appear to be derived from the core motif ACGT. Sequence data and Southern blot analysis demonstrate extensive heteroplasmy. The general form of the array is similar between heteroplasmic variants within an individual and between individuals within a species (varying primarily in the length of the array, though two clones from the northern elephant seal are exceptional). Within certain families, notably ursids, the array structure is also similar between species. Similarity between species was not apparent in other carnivore families, such as the mustelids, suggesting rapid changes in the organization and sequence of some arrays. The pattern of change seen within and between species suggests that a dominant mechanism involved in the evolution of these arrays is DNA slippage. A comparative analysis shows that the motifs that are being reiterated or deleted vary within and between arrays, suggesting a varying rate of DNA turnover. We discuss the evolutionary implications of the observed patterns of variation and extreme levels of heteroplasmy.By acceptance of this article, the publisher acknowledges the right of the US Government to retain non-exclusive, royalty-free license in and to any copyright covering the article. Correspondence to: A.R. Hoetzel     

Cross‐sectional serum metabolomic study of multiple forms of muscular dystrophy

Muscular dystrophies are characterized by a progressive loss of muscle tissue and/or muscle function. While metabolic alterations have been described in patients’‐derived muscle biopsies, non‐invasive readouts able to describe these alterations are needed in order to objectively monitor muscle condition and response to treatment targeting metabolic abnormalities. We used a metabolomic approach to study metabolites concentration in serum of patients affected by multiple forms of muscular dystrophy such as Duchenne and Becker muscular dystrophies, limb‐girdle muscular dystrophies type 2A and 2B, myotonic dystrophy type 1 and facioscapulohumeral muscular dystrophy. We show that 15 metabolites involved in energy production, amino acid metabolism, testosterone metabolism and response to treatment with glucocorticoids were differentially expressed between healthy controls and Duchenne patients. Five metabolites were also able to discriminate other forms of muscular dystrophy. In particular, creatinine and the creatine/creatinine ratio were significantly associated with Duchenne patients performance as assessed by the 6‐minute walk test and north star ambulatory assessment. The obtained results provide evidence that metabolomics analysis of serum samples can provide useful information regarding muscle condition and response to treatment, such as to glucocorticoids treatment.     

Mummified and skeletal southern elephant seals (Mirounga leonina) from the Victoria Land Coast,Ross Sea,Antarctica

We report on an accumulation of mummified southern elephant seals (Mirounga leonina) from Inexpressible Island on the Victoria Land Coast (VLC), western Ross Sea, Antarctica. This accumulation is unusual, as elephant seals typically breed and molt on sub‐Antarctic islands further north and do not currently occupy the VLC. Prior ancient DNA analyses revealed that these seals were part of a large, Antarctic breeding population that crashed ~1,000 yr ago. Radiocarbon dates for Inexpressible Island mummies range from 380 to 3,270 yr before present, too old to have been created by Scott's Northern Party in 1912 and varying too widely in age to represent a catastrophic death assemblage. Skeletal measurements reveal that most Inexpressible Island mummies are adult or subadult males. The presence of male elephant seals on Inexpressible Island until several hundred years ago suggests that, at a minimum, it served as a haul‐out site for the large Antarctic population and may have hosted a breeding colony. The conditions that allowed this Antarctic population to use the Ross Sea, the factors spurring its decline, and the implications for the adaptability and sensitivity of the species to environmental change all merit further study.