The influence of parasitic water mites on the instantaneous death rate of their hosts

Summary The effect of 2 species of water mites on the instantaneous death rate of their hosts was measured on the basis of laboratory experiments. In both parasite-host association — the parasitic water mite Hydryphantes tenuabilis on the aquatic insect host Hydrometra australis and the parasitic water mite Arrenurus pseudotenuicollis on the mosquito Anopheles crucians — the effect of mite load on the instantaneous death rate of the host appeared to be linear. Also, the impact of a single parasite on the host's death rate was apparently related to the ratio of parasite to host body weight. The results of this study are in general agreement with recent theoretical investigations of the regulation of host populations by parasites.     

HIV-1 Tat regulates endothelial cell cycle progression via activation of the Ras/ERK MAPK signaling pathway

Tat, the transactivator of HIV-1 gene expression, is released by acutely HIV-1-infected T-cells and promotes adhesion, migration, and growth of inflammatory cytokine-activated endothelial and Kaposi's sarcoma cells. It has been previously demonstrated that these effects of Tat are due to its ability to bind through its arginine-glycine-aspartic (RGD) region to the alpha5beta1 and alphavbeta3 integrins. However, the signaling pathways linking Tat to the regulation of cellular functions are incompletely understood. Here, we report that Tat ligation on human endothelial cells results in the activation of the small GTPases Ras and Rac and the mitogen-activated protein kinase ERK, specifically through its RGD region. In addition, we demonstrated that Tat activation of Ras, but not of Rac, induces ERK phosphorylation. We also found that the receptor proximal events accompanying Tat-induced Ras activation are mediated by tyrosine phosphorylation of Shc and recruitment of Grb2. Moreover, Tat enabled endothelial cells to progress through the G1 phase in response to bFGF, and the process is linked to ERK activation. Taken together, these data provide novel evidence about the ability of Tat to activate the Ras-ERK cascade which may be relevant for endothelial cell proliferation and for Kaposi's sarcoma progression.     

The Holocene treeline in the northern Andes (Ecuador): First evidence from soil charcoal

Indications for the speed and timing of past altitudinal treeline shifts are often contradictory. Partly, this may be due to interpretation difficulties of pollen records, which are generally regional rather than local proxies. We used pedoanthracology, the identification and dating of macroscopic soil charcoal, to study vegetation history around the treeline in the northern Ecuadorian Andes. Pedoanthracology offers a complementary method to pollen-based vegetation reconstructions by providing records with high spatial detail on a local scale. The modern vegetation is tussock grass páramo (tropical alpine vegetation) and upper montane cloud forest, and the treeline is located at ca. 3600 m. Charcoal was collected from soils in the páramo (at 3890 and 3810 m) and in the forest (at 3540 m), and represents a sequence for the entire Holocene.The presence of páramo taxa throughout all three soil profiles, especially in combination with the absence of forest taxa, shows that the treeline in the study area has moved up to its present position only late in the Holocene (after ca. 5850 cal years BP). The treeline may have been situated between 3600 m and 3800 m at some time after ca. 4900 cal years BP, or it may never have been higher than it is today. The presence of charcoal throughout the profiles also shows that fires have occurred in this area at least since the beginning of the Holocene.These results contradict interpretations of palaeological data from Colombia, which suggest a rapid treeline rise at the Pleistocene–Holocene transition. They also contradict the hypothesis that man-made fires have destroyed large extents of forest above the modern treeline. Instead, páramo fires have probably contributed to the slowness of treeline rise during the Holocene.     

Lysosomal fusion and SNARE function are impaired by cholesterol accumulation in lysosomal storage disorders

The function of lysosomes relies on the ability of the lysosomal membrane to fuse with several target membranes in the cell. It is known that in lysosomal storage disorders (LSDs), lysosomal accumulation of several types of substrates is associated with lysosomal dysfunction and impairment of endocytic membrane traffic. By analysing cells from two severe neurodegenerative LSDs, we observed that cholesterol abnormally accumulates in the endolysosomal membrane of LSD cells, thereby reducing the ability of lysosomes to efficiently fuse with endocytic and autophagic vesicles. Furthermore, we discovered that soluble N‐ethylmaleimide‐sensitive factor attachment protein (SNAP) receptors (SNAREs), which are key components of the cellular membrane fusion machinery are aberrantly sequestered in cholesterol‐enriched regions of LSD endolysosomal membranes. This abnormal spatial organization locks SNAREs in complexes and impairs their sorting and recycling. Importantly, reducing membrane cholesterol levels in LSD cells restores normal SNARE function and efficient lysosomal fusion. Our results support a model by which cholesterol abnormalities determine lysosomal dysfunction and endocytic traffic jam in LSDs by impairing the membrane fusion machinery, thus suggesting new therapeutic targets for the treatment of these disorders.     

The multiple forms of bovine seminal ribonuclease: Structure and stability of a C-terminal swapped dimer

Bovine seminal ribonuclease (BS-RNase) acquires an interesting anti-tumor activity associated with the swapping on the N-terminal. The first direct experimental evidence on the formation of a C-terminal swapped dimer (C-dimer) obtained from the monomeric derivative of BS-RNase, although under non-native conditions, is here reported. The X-ray model of this dimer reveals a quaternary structure different from that of the C-dimer of RNase A, due to the presence of three mutations in the hinge peptide 111–116. The mutations increase the hinge peptide flexibility and decrease the stability of the C-dimer against dissociation. The biological implications of the structural data are also discussed.     

Drosophila serpin 27A is a likely target for immune suppression of the blood cell-mediated melanotic encapsulation response

Avirulent strains of the endoparasitoid Leptopilina boulardi succumb to a blood cell-mediated melanotic encapsulation response in host larvae of Drosophila melanogaster. Virulent wasp strains effectively abrogate the cellular response with substances introduced into the host that specifically target and effectively suppress one or more immune signaling pathways, including elements that control phenoloxidase-mediated melanotic encapsulation. The present study implicates involvement of the Drosophila Toll pathway in cellular innate immunity by regulating the serine protease inhibitor Serpin 27A (Spn27A), which normally functions as a negative regulator of phenoloxidase. The introduction of Spn27A into normally highly immune competent D. melanogaster larvae significantly reduced their ability to form melanotic capsules around eggs of L. boulardi. This study confirms the role of Spn27A in the melanization cascade and establishes that this pathway and associated blood cell responses can be activated by parasitization. The activation of phenoloxidase and the site-specific localization of the ensuing melanotic response are such critical components of the blood cell response that Spn27A and the signaling elements mediating its activity are likely to represent prime targets for immune suppression by L. boulardi.     

HPLC analysis of fusaric acid, 9,10-dehydrofusaric acid and their methyl esters,toxic metabolites from weed pathogenic Fusarium species

A simple and rapid HPLC method, using a high-density C18 column, has been developed for the quantitative analysis of fusaric and dehydrofusaric acids and their methyl esters in the methanol extract of lyophilised culture filtrates of species of Fusarium. The method has been used to determine the content of these metabolites in two strains of Fusarium oxysporum and in strains of F. nygamai and F. udum. Fusaric acid has been isolated and identified from a strain of F. udum for the first time.     

Impact of diffused versus vasculature targeted DNA damage on the heart of mice depleted of telomeric factor Ft1

DNA damage is emerging as a driver of heart disease, although the cascade of events, its timing, and the cell types involved are yet to be fully clarified. In this context, the implication of cardiomyocytes has been highlighted, while that of vasculature smooth muscle cells has been implicated but not explored exhaustively. In our previous work we characterized a factor called Ft1 in mice and AKTIP in humans whose depletion generates telomere instability and DNA damage. Herein, we explored the effect of the reduction of Ft1 on the heart with the goal of comparatively defining the impact of DNA damage targeted to vasculature smooth muscle cells to that of diffuse damage. Using two newly generated mouse models, Ft1 constitutively knocked out (Ft1ko) mice, and mice in which we targeted the Ft1 depletion to the smooth muscle cells (Ft1sm22ko), it is shown that both genetic models display cardiac defects but with differences. Both Ft1ko and Ft1sm22ko mice display hypertrophy, fibrosis, and functional heart defects. Interestingly, Ft1sm22ko mice have early milder pathological traits that become manifest with age. Significantly, the defects of Ft1ko mice, including the alteration of the left ventricle and functional heart defects, are rescued by depletion of the DNA damage sensor p53. These results point to Ft1 deficiency as a driver of cardiac disease and show that Ft1 deficiency targeted to vasculature smooth muscle cells generates a pre-pathological profile exacerbated by age.