Chemoproteomics reveals Toll-like receptor fatty acylation

Partial funding for Open Access provided by The Ohio State University Open Access Fund.Background: Palmitoylation is a 16-carbon lipid post-translational modification that increases protein hydrophobicity. This form of protein fatty acylation is emerging as a critical regulatory modification for multiple aspects of cellular interactions and signaling. Despite recent advances in the development of chemical tools for the rapid identification and visualization of palmitoylated proteins, the palmitoyl proteome has not been fully defined. Here we sought to identify and compare the palmitoylated proteins in murine fibroblasts and dendritic cells. Results: A total of 563 putative palmitoylation substrates were identified, more than 200 of which have not been previously suggested to be palmitoylated in past proteomic studies. Here we validate the palmitoylation of several new proteins including Toll-like receptors (TLRs) 2, 5 and 10, CD80, CD86, and NEDD4. Palmitoylation of TLR2, which was uniquely identified in dendritic cells, was mapped to a transmembrane domain-proximal cysteine. Inhibition of TLR2 S-palmitoylation pharmacologically or by cysteine mutagenesis led to decreased cell surface expression and a decreased inflammatory response to microbial ligands. Conclusions: This work identifies many fatty acylated proteins involved in fundamental cellular processes as well as cell type-specific functions, highlighting the value of examining the palmitoyl proteomes of multiple cell types. Spalmitoylation of TLR2 is a previously unknown immunoregulatory mechanism that represents an entirely novel avenue for modulation of TLR2 inflammatory activity.This work was supported by funding from the NIH/NIAID (grant R00AI095348 to J.S.Y.), the NIH/NIGMS (R01GM087544 to HCH), and the Ohio State University Public Health Preparedness for Infectious Diseases (PHPID) program. NMC is supported by the Ohio State University Systems and Integrative Biology Training Program (NIH/NIGMS grant T32GM068412). BWZ is a fellow of the National Science Foundation Graduate Research Fellowship Program (DGE-0937362)

Perbedaan MBSR dan Terapi Musik untuk Menurunkan Stres pada Pasien Kanker Payudara di Era Pandemi COVID-19

This study aims to determine the differences in the effectiveness of MBSR and music therapy in reducing the stress level of breast cancer patients in the COVID-19 pandemic era. The method used is a systematic review using the Scopus, ScienceDirect, Web of Science, PubMed and CINAHL databases. The JBI critical assessment checklist was used to assess the methodological quality of the included randomized controlled trials. The results showed that the MBSR intervention was carried out in 4-12 weeks, while music therapy was carried out in 12-40 minutes. MBSR and music therapy can reduce stress in breast cancer patients, but MBR therapy is more effective in the long term. In conclusion, MBSR and music therapy can be used as psychological therapy for breast cancer patients during the COVID-19 pandemic.  Keywords: Breast Cancer, MBSR, Stress, Music Therap

The impact of socioeconomic position on stage at diagnosis and survival in colorectal cancer patients in Switzerland

Studies outside of Switzerland have reported socioeconomic inequalities in colorectal cancer (CRC) stage at diagnosis and survival. Aim : To investigate the impact of socioeconomic position (SEP) and further demographic characteristics on colorectal cancer (CRC) stage at diagnosis on CRC-specific survival ; To investigate whether potential survival inequalities can be explained by differences in stage at diagnosis and/or sociodemographic factors

Influence of Pore Size in Benzoin Condensation of Furfural Using Heterogenized Benzimidazole Organocatalysts

A designed N-heterocyclic carbene (NHC) catalyst was covalently anchored on a range of mesoporous and hierarchical supports, to study the influence of pore size in the benzoin condensation of furfural. The structural and spectroscopic characteristics of the anchored catalysts were investigated, also with the help of molecular dynamics simulations, in order to rationalize the degree of stability and recyclability of the heterogenized organocatalysts. Quantitative yields (99 %) and complete recyclability were maintained after several cycles, vindicating the design rationale

Pleural Mesothelioma: forecasts of the death toll in the area of Casale Monferrato, Italy

In the city of Casale Monferrato, the largest Italian factory that produced asbestos cement goods was active from 1907 to 1985. As a consequence, asbestos fibers scattered in the surrounding area and caused an enormous number of pleural mesotheliomas. Due to the very long latency of this disease, many subjects have not exhibited its symptoms yet. The aim of this paper is to model and predict the future evolution of the number of deaths due to this disease among residents in the area around that city. The model used here is based on a Cellular Automata that is assumed to pass through three steps: exposure, contamination, diagnosis. In that way, forecasts of the future evolution take into account the environmental conditions that changed in time during the last century because of different levels in plant activity. The model is fitted to annual diagnosis data starting from 1954 to 2009. Results show that deaths will not end until 2033, and that in the next two decades, at least 479 more subjects will be diagnosed with this disease

La propensi\uf3n al uso del coche compartido y sus bases decisionales. Resultados de una investigaci\uf3n en cuatro ciudades italianas

This article aims to further understand the factors that lead to the choice of car sharing, with respect to the attitude towards the use of private cars; we will analyze the role of the (non) perception of the costs associated with car ownership over consumption and alternative mobility practices. The study is based on the results of a CATI that we carry out in this little explored market area in four urban metropolitan cities in Italy (Rome, Milan, Turin and Genova). For this purpose, we first did an exploratory factor analysis to determine the key dimensions of private car behavior. Then we perform a logistic regression model to analyze what factors can affect the dependent variable. According to our analysis, awareness of the costs associated with the use and ownership of the car is of no importance since many of the interviewed car users tend to underestimate the cost of owning and using a car.Este art\uedculo tiene el objetivo de avanzar en el conocimiento de los factores que conducen a la elecci\uf3n del coche compartido (car sharing), en relaci\uf3n al uso del coche privado. En particular, analizaremos el rol de la (no) percepci\uf3n de los costos asociados a la propiedad del coche sobre las pr\ue1cticas de consumo y de movilidad alternativa. El estudio se basa en los resultados de un CATI que llevamos a cabo en esta \ue1rea de mercado poco explorada en cuatro ciudades metropolitanas urbanas en Italia (Roma, Mil\ue1n, Tur\uedn y G\ue9nova). Para este prop\uf3sito, primero hicimos un an\ue1lisis factorial exploratorio para determinar las dimensiones clave del comportamiento del coche privado. Luego realizamos un modelo de regresi\uf3n log\uedstica para analizar qu\ue9 factores pueden afectar a la variable dependiente. Seg\ufan nuestro an\ue1lisis, el conocimiento de los costos asociados con el uso y la propiedad del coche no tiene importancia determinante ya que muchos de los usuarios de coche entrevistados tienden a subestimar el costo de poseer y de usar el autom\uf3vi

Simultaneous measurement of ion ratios by inductively coupled plasma - mass spectrometry with a twin quadrupole instrument

The ion beam from the inductively coupled plasma (ICP) is split into two parts by a device comprised of two electrostatic sectors in a back-to-back arrangement. Each ion beam is then monitored by a separate quadrupole mass analyzer and electron multiplier. Thus, ion ratios can be measured simultaneously without scanning. Isotope ratios for copper are measured with a precision of 0.14% relative standard deviation (RSD). Internal standard ratios for (Co+ signal)/(La+ signal) are measured with a precision of 1% RSD. Ion signals in the two channels are highly correlated, and the magnitude of flicker noise is reduced in the resulting ratios. Bias in the measured isotope ratios is substantial but can be corrected by calibration

Genetic susceptibility to malignant pleural mesothelioma and other asbestos-associated diseases.

Exposure to asbestos fibers is a major risk factor for malignant pleuralmesothelioma (MPM), lung cancer, and other non-neoplastic conditions, such as asbestosis and pleural plaques. However, in the last decade many studies have shown that polymorphism in the genes involved in xenobiotic and oxidative metabolism or in DNA repair processes may play an important role in the etiology and pathogenesis of these diseases. To evaluate the association between diseases linked to asbestos and genetic variability we performed a review of studies on this topic included in the PubMed database. One hundred fifty-nine citations were retrieved; 24 of them met the inclusion criteria and were evaluated in the review. The most commonly studied GSTM1 polymorphism showed for all asbestos-linked diseases an increased risk in association with the null genotype, possibly linked to its role in the conjugation of reactive oxygen species. Studies focused on GSTT1 null and SOD2 Ala16Val polymorphisms gave conflicting results, while promising results came from studies on a1-antitrypsin in asbestosis and MPO in lung cancer. Among genetic polymorphisms associated to the risk of MPM, the GSTM1 null genotype and two variant alleles of XRCC1 and XRCC3 showed increased risks in a subset of studies. Results for the NAT2 acetylator status, SOD2 polymorphism and EPHX activity were conflicting. Major limitations in the study design, including the small size of study groups, affected the reliability of these studies. Technical improvements such as the use of high-throughput techniques will help to identify molecular pathways regulated by candidate genes