SIRT2 deficiency modulates macrophage polarization and susceptibility to experimental colitis

BACKGROUND SIRT2 belongs to a highly conserved family of NAD+-dependent deacylases, consisting of seven members (SIRT1-SIRT7), which vary in subcellular localizations and have substrates ranging from histones to transcription factors and enzymes. Recently SIRT2 was revealed to play an important role in inflammation, directly binding, deacetylating, and inhibiting the p65 subunit of NF-κB. METHODS A Sirt2 deficient mouse line (Sirt2-/-) was generated by deleting exons 5-7, encoding part of the SIRT2 deacetylase domain, by homologous recombination. Age- and sex-matched Sirt2-/- and Sirt2+/+ littermate mice were subjected to dextran sulfate sodium (DSS)-induced colitis and analyzed for colitis susceptibility. RESULTS Sirt2-/- mice displayed more severe clinical and histological manifestations after DSS colitis compared to wild type littermates. Notably, under basal condition, Sirt2 deficiency does not affect the basal phenotype and intestinal morphology Sirt2 deficiency, however, affects macrophage polarization, creating a pro-inflammatory milieu in the immune cells compartment. CONCLUSION These data confirm a protective role for SIRT2 against the development of inflammatory processes, pointing out a potential role for this sirtuin as a suppressor of colitis. In fact, SIRT2 deletion promotes inflammatory responses by increasing NF-κB acetylation and by reducing the M2-associated anti-inflammatory pathway. Finally, we speculate that the activation of SIRT2 may be a potential approach for the treatment of inflammatory bowel disease.

Variables affecting the stability of multiple cloning sites and hairpin structures in retroviral vectors

Retroviruses are RNA viruses that replicate through a double-stranded DNA intermediate. The viral enzyme reverse transcriptase copies the retroviral genomic RNA into this DNA intermediate through the process of reverse transcription. Many variables can affect the fidelity of reverse transcriptase during reverse transcription, including specific sequences within the retroviral genome. ^ Previous studies have observed that multiple cloning sites (MCS) and sequences predicted to form stable hairpin structures are hotspots for deletion during retroviral replication. The studies described in this dissertation were performed to elucidate the variables that affect the stability of MCS and hairpin structures in retroviral vectors. Two series of retroviral vectors were constructed and characterized in these studies. ^ Spleen necrosis virus-based vectors were constructed containing separate MCS insertions of varying length, orientation, and symmetry. The only MCS that was a hotspot for deletion formed a stable hairpin structure. Upon more detailed study, the MCS previously reported as a hotspot for deletion was found to contain a tandem linker insertion that formed a hairpin structure. Murine leukemia virus-based vectors were constructed containing separate sequence insertions of either inverted repeat symmetry (122IR) that could form a hairpin structure, or little symmetry (122c) that would form a less stable structure. These insertions were made into either the neomycin resistance marker ( neo) or the hygromycin resistance marker (hyg) of the vector. 122c was stable in both neo and hyg, while 122IR was preferentially deleted in neo and was remarkably unstable in hyg. ^ These results suggest that MCS are hotspots for deletion in retroviral vectors if they can form hairpin structures, and that hairpin structures can be highly unstable at certain locations in retroviral vectors. This information may contribute to improved design of retroviral vectors for such uses as human gene therapy, and will contribute to a greater understanding of the basic science of retroviral reverse transcription. ^

Splitsville: A Study of Income Inequality and Political Polarization in the United States House of Representatives

The study compares a measure of income inequality with polarization scores of U.S. Representatives from the 104th to the 109th Congresses. It attempts to explain the link, on the abstract level, between high inequality and high polarization. The end findings indicate that inequality increases a Representative's likelihood to act liberally.

The Moderating Role of Electoral Pressure on Congressional Ideological Polarization: A Cross-Sectional Time-Series Analysis

Reelection and self-interest are recurring themes in the study of our congressional leaders. To date, many studies have already been done on the trends between elections, party affiliation, and voting behavior in Congress. However, because a plethora of data has been collected on both elections and congressional voting, the ability to draw a connection between the two provides a very reasonable prospect. This project analyzes whether voting shifts in congressional elections have an effect on congressional voting. Will a congressman become ideologically more polarized when his electoral margins increase? Essentially, this paper assumes that all congressmen are ideologically polarized, and it is elections which serve to reel congressmen back toward the ideological middle. The election and ideological data for this study, which spans from the 56th to the 107th Congress, finds statistically significant relationships between these two variables. In fact, congressman pay attention to election returns when voting in Congress. When broken down by party, Democrats are more exhibitive of this phenomenon, which suggest that Democrats may be more likely to intrinsically follow the popular model of representation. Meanwhile, it can be hypothesized that insignificant results for Republicans indicate that Republicans may follow a trustee model of representation.

Cellular Trafficking of Single and Multistage Vectors

Nanomedicine is an innovative field of science which has recently generated many drug delivery platforms with exciting results. The great potential of these strategies rely on the unique characteristics of the devices at the nano-scale in terms of long time circulation in the blood stream, selective accumulation at the lesions sites, increased solubility in aqueous solutions, etc. Herein we report on a new drug delivery system known as a multistage system which is comprised of non-spherical, mesoporous silicon particles loaded with second stage nanoparticles. The rationally designed particle shape, the possibility to modulate the surface properties and the degree of porosity allow these carriers to be optimized for vascular targeting and to overcome the numerous biological barriers found in drug delivery. In this study we investigated the intra and inter cellular trafficking of the multistage system in endothelial cells bringing evidence of its bio-compatibility as well as its ability to perform multiple intra and inter cellular tasks. Once internalized in cells, the multi-particle construct is able to dissociate, localizing in different subcellular compartments which can be targeted for exocytosis. In particular the second stage nanoparticles were found to be secreted in microvesicles which can act as mediators of transfer of particles across the endothelium and between different endothelial and cancer cells.

Spatio-temporal dynamics of viruses are differentially affected by parasitoids depending on the mode of transmission by their insect vectors.

Relationships between agents in multitrophic systems are complex and very specific. Insect-transmitted plant viruses are completely dependent on the behaviour and distribution patterns of their vectors. The presence of natural enemies may directly affect aphid behaviour and spread of plant viruses, as the escape response of aphids might cause a potential risk for virus dispersal. The spatio-temporal dynamics of Cucumber mosaic virus (CMV) and Cucurbit aphid-borne yellows virus (CABYV), transmitted by Aphis gossypii in a non-persistent and persistent manner, respectively, were evaluated at short and long term in the presence and absence of the aphid parasitoid, Aphidius colemani. SADIE methodology was used to study the distribution patterns of both the virus and its vector, and their degree of association. Results suggested that parasitoids promoted aphid dispersion at short term, which enhanced CMV spread, though consequences of parasitism suggest potential benefits for disease control at long term. Furthermore, A. colemani significantly limited the spread and incidence of the persistent virus CABYV at long term. The impact of aphid parasitoids on the dispersal of plant viruses with different transmission modes is discussed.

Phonotactic language recognition using i-vectors and phoneme posteriogram counts

This paper describes a novel approach to phonotactic LID, where instead of using soft-counts based on phoneme lattices, we use posteriogram to obtain n-gram counts. The high-dimensional vectors of counts are reduced to low-dimensional units for which we adapted the commonly used term i-vectors. The reduction is based on multinomial subspace modeling and is designed to work in the total-variability space. The proposed technique was tested on the NIST 2009 LRE set with better results to a system based on using soft-counts (Cavg on 30s: 3.15% vs 3.43%), and with very good results when fused with an acoustic i-vector LID system (Cavg on 30s acoustic 2.4% vs 1.25%). The proposed technique is also compared with another low dimensional projection system based on PCA. In comparison with the original soft-counts, the proposed technique provides better results, reduces the problems due to sparse counts, and avoids the process of using pruning techniques when creating the lattices.

Experimental measurements of the scattered-light polarization from different liquid flows

An experimental system designed to measure very low optical powers, of the order of a few picowatts, is presented. Its main aid is to detect the polarisation state of scattered light from a fluid flow, in different angular directions with respect to the longitudinal axis of the flow. A laser beam incident linearly polarized crosses the fluid flow orthogonally. The scattered light is detected by means of a photodetector situated behind a lineal polarizer whose orientation can be rotated. The outgoing electrical signal is amplified by means of a Mode-lockin amplifier and is digitally processed.

Low-resource language recognition using a fusion of phoneme posteriorgram counts, acoustic and glottal-based i-vectors

This paper presents a description of our system for the Albayzin 2012 LRE competition. One of the main characteristics of this evaluation was the reduced number of available files for training the system, especially for the empty condition where no training data set was provided but only a development set. In addition, the whole database was created from online videos and around one third of the training data was labeled as noisy files. Our primary system was the fusion of three different i-vector based systems: one acoustic system based on MFCCs, a phonotactic system using trigrams of phone-posteriorgram counts, and another acoustic system based on RPLPs that improved robustness against noise. A contrastive system that included new features based on the glottal source was also presented. Official and postevaluation results for all the conditions using the proposed metrics for the evaluation and the Cavg metric are presented in the paper.