Mitochondrial Uncoupling Protein-2 (UCP2) Mediates Leptin Protection Against MPP+ Toxicity in Neuronal Cells

Mitochondrial dysfunction is involved in the pathogenesis of neurodegenerative diseases, including Parkinson’s disease (PD). Uncoupling proteins (UCPs) delink ATP production from biofuel oxidation in mitochondria to reduce oxidative stress. UCP2 is expressed in brain, and has neuroprotective effects under various toxic insults. We observed induction of UCP2 expression by leptin in neuronal cultures, and hypothesize that leptin may preserve neuronal survival via UCP2. We showed that leptin preserved cell survival in neuronal SH-SY5Y cells against MPP+ toxicity (widely used in experimental Parkinsonian models) by maintaining ATP levels and mitochondrial membrane potential (MMP); these effects were accompanied by increased UCP2 expression. Leptin had no effect in modulating reactive oxygen species levels. Stable knockdown of UCP2 expression reduced ATP levels, and abolished leptin protection against MPP+-induced mitochondrial depolarization, ATP deficiency, and cell death, indicating that UCP2 is critical in mediating these neuroprotective effects of leptin against MPP+ toxicity. Interestingly, UCP2 knockdown increased UCP4 expression, but not of UCP5. Our findings show that leptin preserves cell survival by maintaining MMP and ATP levels mediated through UCP2 in MPP+-induced toxicity

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Towards a cryptographic treatment of publish/subscribe systems

Publish/subscribe mechanism is a typical many-to-many messaging paradigm when multiple applications want to receive the same message or when a group of applications would like to notify each other. Nonetheless, there exist only a few works that address the security issues for content-based publish/subscribe systems formally. Although the security requirements have been partially addressed by Wang et al., there is no formal definition for all of these security requirements in the literature. As a result, most of the existing schemes do not have any security proof and it is difficult to justify whether those schemes are really secure in practice. Furthermore, there is no comprehensive scheme that satisfies the most essential security requirements at the same time. In this paper, we introduce the first security model for important security requirements of content-based publish/subscribe systems. We also give a new security requirement for publisher authenticity, which means that the publisher is authenticated to publish certain types of notification only, and cannot publish other types of notification. We then exhibit a new scheme which fulfills most of the security requirements. Furthermore, we also provide a comprehensive proof for our concrete construction according to the new model. 2014 IOS Press

Sanitizable Signatures Revisited

A sanitizable signature scheme is a signature scheme which allows a sanitizer to hide parts of the original message after the message is signed, without interacting with the signer. There exists many security models, properties and constructions for sanitizable signatures, which are useful in different scenarios. The aim of this paper is twofold.Firstly, we summarize different properties in the literature and gives some generic conversions between them. We propose a security model to capture most of these properties.Secondly, we present the first concrete construction of sanitizable signatures which is proven secure in the standard model

Characterization of Erythrocytic Uptake and Release and Disposition Pathways of Nitrite, Nitrate, Methemoglobin, and Iron-Nitrosyl Hemoglobin in the Human Circulation

Nitrite-hemoglobin reactions have been studied extensively in vitro, but there is a lack of information on the kinetics of nitrite and its metabolites in humans. In this study, we developed a nine-compartment physiological pharmacokinetic model to describe the in vivo erythrocytic uptake and release and disposition pathways of nitrite, nitrate, methemoglobin, and iron-nitrosyl hemoglobin in the human circulation. Our model revealed that nitrite entered erythrocytes rapidly with a rate constant of 0.256 min−1 (i.e., half-life = 2.71 min). The formation of iron-nitrosyl hemoglobin from nitrite, which involves the reduction of nitrite by deoxyhemoglobin to generate nitric oxide (NO) and reaction of NO with deoxyhemoglobin to form iron-nitrosyl hemoglobin, occurred rapidly as well (k = 2.02 min−1; half-life = 0.343 min = 21 s). The disposition kinetics of methemoglobin was complex. Nitrate formation occurred primarily in erythrocytes through the nitrite-oxyhemoglobin reaction and was higher when nitrite was administered intra-arterially than intravenously. Nitrate reduction was an insignificant metabolic pathway. This study is the first to comprehensively evaluate the kinetics of nitrite and its metabolites in humans and provides unique insights into the rapid equilibrium of nitrite into erythrocytes and conversion to NO in the red cell, which is kinetically associated with vasodilation