Effect of Levels of Acetate on the Mevalonate Pathway of Borrelia burgdorferi

Borrelia burgdorferi, the agent of Lyme disease, is a spirochetal pathogen with limited metabolic capabilities that survives under highly disparate host-specific conditions. However, the borrelial genome encodes several proteins of the mevalonate pathway (MP) that utilizes acetyl-CoA as a substrate leading to intermediate metabolites critical for biogenesis of peptidoglycan and post-translational modifications of proteins. In this study, we analyzed the MP and contributions of acetate in modulation of adaptive responses in B. burgdorferi. Reverse-transcription PCR revealed that components of the MP are transcribed as individual open reading frames. Immunoblot analysis using monospecific sera confirmed synthesis of members of the MP in B. burgdorferi. The rate-limiting step of the MP is mediated by HMG-CoA reductase (HMGR) via conversion of HMG-CoA to mevalonate. Recombinant borrelial HMGR exhibited a Km value of 132 µM with a Vmax of 1.94 µmol NADPH oxidized minute−1 (mg protein)−1 and was inhibited by statins. Total protein lysates from two different infectious, clonal isolates of B. burgdorferi grown under conditions that mimicked fed-ticks (pH 6.8/37°C) exhibited increased levels of HMGR while other members of the MP were elevated under unfed-tick (pH 7.6/23°C) conditions. Increased extra-cellular acetate gave rise to elevated levels of MP proteins along with RpoS, CsrABb and their respective regulons responsible for mediating vertebrate host-specific adaptation. Both lactone and acid forms of two different statins inhibited growth of B. burgdorferi strain B31, while overexpression of HMGR was able to partially overcome that inhibition. In summary, these studies on MP and contributions of acetate to host-specific adaptation have helped identify potential metabolic targets that can be manipulated to reduce the incidence of Lyme disease

Embedded Hyperchaotic Lorenz Generator for Secure Communications

11th IEEE International New Circuits and Systems Conference (NEWCAS), Inst Mines Telecom, Paris, FRANCE, JUN 16-19, 2013International audienceWe propose in this paper a new hardware architecture for implementing the hyperchaotic Lorenz generator using FPGA technology. The goal is to design a new complex chaotic system which can be used as an unidentifiable key generator in embedded cryptosystems. The proposed architecture provides good performances in terms of throughput and resources cost required for highly secure communications between embedded systems

Digital synthesis architecture for modulation and demodulation

25th International Conference on Microelectronics (ICM), Beirut, LEBANON, DEC 15-18, 2013International audienceNowadays, the current challenge in the wireless digital systems is to design new digital, generic and "universal" architectures, take charge of functionalities previously managed by different circuits. Moreover, these ones must be sufficiently flexible to support multiple transmission standards and easily adaptable for future evolutions. In this work, we propose a digital architecture for modulation and demodulation using LFSR registers. The architecture was implemented on Xilinx Virtex series field programmable gate arrays (FPGA). The implementations demonstrate that our proposed architecture can deliver a high reduction of the FPGA logic requirements and consumption power when compared with the Velcro architecture

Reliable Router for accurate Online Error Detection in Dynamic Network on Chip

25th International Conference on Microelectronics (ICM), Beirut, LEBANON, DEC 15-18, 2013International audienceThis paper proposes a new reliable router allowing accurate online error detections in dynamic Network on Chip (NoC). The proposed router has the capability to detect and localize accurately inner or outer data packet errors of the router while distinguish between temporary and permanently errors. The error detection mechanisms of the proposed switches and advantages with regards to the other main already proposed router approaches are detailed while proving the feasibility and efficiency through several simulations online detection cases. Performance evaluation and FPGA implementation results are also given

Local or global commons? Application of framework for analysing SES for soil biodiversity at EU level

Defect in apoptosis has been implicated as a major cause of resistance to chemotherapy observed in B cell chronic lymphocytic leukaemia (B CLL). This study evaluated the pro-apoptotic effect of an anthocyanin-rich dietary bilberry extract (Antho 50) on B CLL cells from 30 patients and on peripheral blood mononuclear cells (PBMCs) from healthy subjects, and determined the underlying mechanism. Antho 50 induced concentration- and time-dependent pro-apoptotic effects in B CLL cells but little or no effect in PBMCs. Among the main phenolic compounds of the bilberry extract, delphinidin-3-O-glucoside and delphinidin-3-O-rutinoside induced a pro-apoptotic effect. Antho 50-induced apoptosis is associated with activation of caspase 3, down-regulation of UHRF1, a rapid dephosphorylation of Akt and Bad, and down-regulation of Bcl-2. Antho 50 significantly induced PEG-catalase-sensitive formation of reactive oxygen species in B CLL cells. PEG-catalase prevented the Antho 50-induced induction of apoptosis and related signaling. The present findings indicate that Antho 50 exhibits strong pro-apoptotic activity through redox-sensitive caspase 3 activation-related mechanism in B CLL cells involving dysregulation of the Bad/Bcl-2 pathway. This activity of Antho 50 involves the glucoside and rutinoside derivatives of delphinidin. They further suggest that Antho 50 has chemotherapeutic potential by targeting selectively B CLL cells