Porphyromonas gingivalis–dendritic cell interactions: consequences for coronary artery disease

An estimated 80 million US adults have one or more types of cardiovascular diseases. Atherosclerosis is the single most important contributor to cardiovascular diseases; however, only 50% of atherosclerosis patients have currently identified risk factors. Chronic periodontitis, a common inflammatory disease, is linked to an increased cardiovascular risk. Dendritic cells (DCs) are potent antigen presenting cells that infiltrate arterial walls and may destabilize atherosclerotic plaques in cardiovascular disease. While the source of these DCs in atherosclerotic plaques is presently unclear, we propose that dermal DCs from peripheral inflamed sites such as CP tissues are a potential source. This review will examine the role of the opportunistic oral pathogen Porphyromonas gingivalis in invading DCs and stimulating their mobilization and misdirection through the bloodstream. Based on our published observations, combined with some new data, as well as a focused review of the literature we will propose a model for how P. gingivalis may exploit DCs to gain access to systemic circulation and contribute to coronary artery disease. Our published evidence supports a significant role for P. gingivalis in subverting normal DC function, promoting a semimature, highly migratory, and immunosuppressive DC phenotype that contributes to the inflammatory development of atherosclerosis and, eventually, plaque rupture

In Vitro Identification of Novel Plasminogen-Binding Receptors of the Pathogen Leptospira interrogans

Background: Leptospirosis is a multisystem disease caused by pathogenic strains of the genus Leptospira. We have reported that Leptospira are able to bind plasminogen (PLG), to generate active plasmin in the presence of activator, and to degrade purified extracellular matrix fibronectin. Methodology/Principal Findings: We have now cloned, expressed and purified 14 leptospiral recombinant proteins. The proteins were confirmed to be surface exposed by immunofluorescence microscopy and were evaluated for their ability to bind plasminogen (PLG). We identified eight as PLG-binding proteins, including the major outer membrane protein LipL32, the previously published rLIC12730, rLIC10494, Lp29, Lp49, LipL40 and MPL36, and one novel leptospiral protein, rLIC12238. Bound PLG could be converted to plasmin by the addition of urokinase-type PLG activator (uPA), showing specific proteolytic activity, as assessed by its reaction with the chromogenic plasmin substrate, D-Val-Leu-Lys 4-nitroanilide dihydrochloride. The addition of the lysine analog 6-aminocaproic acid (ACA) inhibited the protein-PLG interaction, thus strongly suggesting the involvement of lysine residues in plasminogen binding. The binding of leptospiral surface proteins to PLG was specific, dose-dependent and saturable. PLG and collagen type IV competed with LipL32 protein for the same binding site, whereas separate binding sites were observed for plasma fibronectin. Conclusions/Significance: PLG-binding/activation through the proteins/receptors on the surface of Leptospira could help the bacteria to specifically overcome tissue barriers, facilitating its spread throughout the host.FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo)CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico)Fundacao Butantan, BrazilFAPESP (Brazil

Low input voltage and high step-up integrated regulator for thermoelectric energy harvesting

This paper presents a low input voltage and high step-up fully integrated DC-DC regulator in 0.18 mu m standard CMOS technology for thermoelectric micro-power generation. The circuit avoids off-chip components, non-standard processes, and is thus suitable for ultra-low voltage low profile system-on-chip applications. The proposed system can deliver a regulated output voltage of 1.5 V at 31 mu W output power with an input voltage as low as 0.2 V. The maximum simulated efficiency is 22% at the given step-up range. The design methodology of an integrated inductor layout and oscillator has been reported in detail for the standard process. At the ultra-low voltage range of interest, the regulator is estimated to have lower cost, higher integration, and improved efficiency compared to the alternatives reported in literature, including the 90 nm and 0.18 mu m two-stage charge pump designs previously reported by our team

An on-die ultra-low voltage DC-DC step-up converter with voltage doubling LC-tank

In this paper we report the design, characterization and verification of a novel on-die ultra-low voltage DC-DC converter circuit for energy harvester applications in 0.18 mu m complementary metal oxide semiconductor (CMOS) technology. The circuit self-starts, does not use off-chip components, and is thus suitable for use in highly integrated low cost systems. The first version of the design has a five-stage charge-pump stimulated by an oscillator with two center-tap inductors. It is validated on a test chip that this converter can boost 0.25 V-1.7 V for a 60 k Omega load with 15.5% maximum efficiency. The center-tap implementation leads to a 38% area reduction compared to the conventional four planar inductors. The proposed second version of the DC-DC design has a modified LC-tank with center-tap and planar hybrid inductors, which leads to a simulated step up from 0.2 V input to 1.65 V output for a 45 k Omega load with 35% maximum efficiency. The new boost implementation is hence expected to improve both power efficiency and output power capacity significantly compared to the first design, at a cost of a 31% layout area growth. The second revision in addition provides a 15% chip area reduction compared to the conventional four planar-inductor approach

Fully Integrated Ultra-Low Voltage Step-up Converter with Voltage Doubling LC-Tank for Energy Harvesting Applications

This paper reports the design, fabrication, and validation of a novel integrated interface circuit for ultra-low voltage step up converter in 0.18 mu m CMOS technology. The circuit does not use off-chip components. Fully integrated centre-tap differential inductors are introduced in the proposed LC oscillator design to achieve 38% area reduction compared to the use of four separate inductors. The efficiency of the system is hence enhanced through the elimination of clock buffer circuits traditionally utilized to drive the step-up converter. The experimental results prove that the system can self-start, and step 0.25 V up to 1.7 V to supply a 46 mu W load with 15.5% efficiency. The minimum validated input voltage is 0.15 V, which is boosted up to 1.2 V under open circuit conditions