Botulinum toxin D ADP-ribosylates a 22-24 KDa membrane protein in platelets and HL-60 cells that is distinct from p21N-ras

Botulinum toxin D ADP-ribosylates a 22-24 KDa protein in platelets, GH3 and HL-60 cells, and a mouse T-cell line CTLL. In platelet homogenates the protein is localized to the membrane fraction, and ADP-ribosylation can also be produced in saponin-permeabilized and intact cells. In the latter, the toxin also potentiates secretion caused by a variety of agonists. In platelets and HL-60 cells the toxin substrate is shown, by use of anti-ras monoclonal antibody, to be distinct from the ras family of proteins. This toxin substrate may represent an additional class of proteins involved in stimulus-response coupling.     

Inhibition of Host Vacuolar H+-ATPase Activity by a Legionella pneumophila Effector

Legionella pneumophila is an intracellular pathogen responsible for Legionnaires'' disease. This bacterium uses the Dot/Icm type IV secretion system to inject a large number of bacterial proteins into host cells to facilitate the biogenesis of a phagosome permissive for its intracellular growth. Like many highly adapted intravacuolar pathogens, L. pneumophila is able to maintain a neutral pH in the lumen of its phagosome, particularly in the early phase of infection. However, in all cases, the molecular mechanisms underlying this observation remain unknown. In this report, we describe the identification and characterization of a Legionella protein termed SidK that specifically targets host v-ATPase, the multi-subunit machinery primarily responsible for organelle acidification in eukaryotic cells. Our results indicate that after being injected into infected cells by the Dot/Icm secretion system, SidK interacts with VatA, a key component of the proton pump. Such binding leads to the inhibition of ATP hydrolysis and proton translocation. When delivered into macrophages, SidK inhibits vacuole acidification and impairs the ability of the cells to digest non-pathogenic E. coli. We also show that a domain located in the N-terminal portion of SidK is responsible for its interactions with VatA. Furthermore, expression of sidK is highly induced when bacteria begin to enter new growth cycle, correlating well with the potential temporal requirement of its activity during infection. Our results indicate that direct targeting of v-ATPase by secreted proteins constitutes a virulence strategy for L. pneumophila, a vacuolar pathogen of macrophages and amoebae.     

An analysis of the genetic relationship between udder health and udder conformation traits in South African Jersey cows

A multi-trait animal model was used to estimate genetic parameters among lactation somatic cell score (SCS) and udder-type traits in South African Jersey cattle, through restricted maximum likelihood (REML) procedures. Data comprised records on 18 321 Jersey cows in 470 herds, collected through the National Milk Recording Scheme from 1996 to 2002. Average SCS in the first three lactations (SCS1, SCS2 and SCS3) were considered as different traits and the udder-type traits were fore udder attachment (FUA), rear udder height (RUH), rear udder width (RUW), udder cleft (UC), udder depth (UD), fore teat placement (FTP), rear teat placement (RTP) and fore teat length (FTL). Heritability estimates for the respective lactation SCS were 0.07 ± 0.01, 0.11 ± 0.01 and 0.11 ± 0.02. Udder-type traits had heritability estimates ranging from 0.14 ± 0.01 for UD to 0.30 ± 0.02 for FTL. Genetic correlations between SCS and udder-type traits ranged from -0.003 ± 0.07 between FUA and SCS3 to -0.50 ± 0.07 between UD and SCS3. Slow genetic progress is expected when selection is applied independently on SCS and udder-type traits, due to the generally low heritabilities. Tightly attached shallow udders with narrowly placed rear teats are associated with low SCS in the Jersey population.     

Stabilization of inhomogeneous patterns in a diffusion-reaction system under structural and parametric uncertainties

Many phenomena such as neuron firing in the brain, the travelling waves which produce the heartbeat, arrythmia and fibrillation in the heart, catalytic reactions or cellular organization activities, among others, can be described by a unifying paradigm based on a class of nonlinear reaction-diffusion mechanisms. The FitzHugh-Nagumo (FHN) model is a simplified version of such class which is known to capture most of the qualitative dynamic features found in the spatiotemporal signals. In this paper, we take advantage of the dissipative nature of diffusion-reaction systems and results in finite dimensional nonlinear control theory to develop a class of nonlinear feedback controllers which is able to ensure stabilization of moving fronts for the FHN system, despite structural or parametric uncertainty. In the context of heart or neuron activity, this class of control laws is expected to prevent cardiac or neurological disorders connected with spatiotemporal wave disruptions. In the same way, biochemical or cellular organization related with certain functional aspects of life could also be influenced or controlled by the same feedback logic. The stability and robustness properties of the controller will be proved theoretically and illustrated on simulation experiments.