Transmembrane Protein Oxygen Content and Compartmentalization of Cells

Recently, there was a report that explored the oxygen content of transmembrane proteins over macroevolutionary time scales where the authors observed a correlation between the geological time of appearance of compartmentalized cells with atmospheric oxygen concentration. The authors predicted, characterized and correlated the differences in the structure and composition of transmembrane proteins from the three kingdoms of life with atmospheric oxygen concentrations in geological timescale. They hypothesized that transmembrane proteins in ancient taxa were selectively excluding oxygen and as this constraint relaxed over time with increase in the levels of atmospheric oxygen the size and number of communication-related transmembrane proteins increased. In summary, they concluded that compartmentalized and non-compartmentalized cells can be distinguished by how oxygen is partitioned at the proteome level. They derived this conclusion from an analysis of 19 taxa. We extended their analysis on a larger sample of taxa comprising 309 eubacterial, 34 archaeal, and 30 eukaryotic complete proteomes and observed that one can not absolutely separate the two groups of cells based on partition of oxygen in their membrane proteins. In addition, the origin of compartmentalized cells is likely to have been driven by an innovation than happened 2700 million years ago in the membrane composition of cells that led to the evolution of endocytosis and exocytosis rather than due to the rise in concentration of atmospheric oxygen

Transcriptional profiling of the effects of 25-hydroxycholesterol on human hepatocyte metabolism and the antiviral state it conveys against the hepatitis C virus

<p>Abstract</p> <p>Background</p> <p>Hepatitis C virus (HCV) infection is a global health problem. A number of studies have implicated a direct role of cellular lipid metabolism in the HCV life cycle and inhibitors of the mevalonate pathway have been demonstrated to result in an antiviral state within the host cell. Transcriptome profiling was conducted on Huh-7 human hepatoma cells bearing subgenomic HCV replicons with and without treatment with 25-hydroxycholesterol (25-HC), an inhibitor of the mevalonate pathway that alters lipid metabolism, to assess metabolic determinants of pro- and antiviral states within the host cell. These data were compared with gene expression profiles from HCV-infected chimpanzees.</p> <p>Results</p> <p>Transcriptome profiling of Huh-7 cells treated with 25-HC gave 47 downregulated genes, 16 of which are clearly related to the mevalonate pathway. Fewer genes were observed to be upregulated (22) in the presence of 25-HC and 5 genes were uniquely upregulated in the HCV replicon bearing cells. Comparison of these gene expression profiles with data collected during the initial rise in viremia in 4 previously characterized HCV-infected chimpanzees yielded 54 overlapping genes, 4 of which showed interesting differential regulation at the mRNA level in both systems. These genes are PROX1, INSIG-1, NK4, and UBD. The expression of these genes was perturbed with siRNAs and with overexpression vectors in HCV replicon cells, and the effect on HCV replication and translation was assessed. Both PROX1 and NK4 regulated HCV replication in conjunction with an antiviral state induced by 25-hydroxycholesterol.</p> <p>Conclusion</p> <p>Treatment of Huh-7 cells bearing HCV replicons with 25-HC leads to the downregulation of many key genes involved in the mevalonate pathway leading to an antiviral state within the host cell. Furthermore, dysregulation of a larger subset of genes not directly related to the mevalonate pathway occurs both in 25-HC-treated HCV replicon harbouring cells as well as during the initial rise in viremia in infected chimpanzees. Functional studies of 3 of these genes demonstrates that they do not directly act as antiviral gene products but that they indirectly contribute to the antiviral state in the host cell. These genes may also represent novel biomarkers for HCV infection, since they demonstrate an outcome-specific expression profile.</p

Astrobiological Complexity with Probabilistic Cellular Automata

Search for extraterrestrial life and intelligence constitutes one of the major endeavors in science, but has yet been quantitatively modeled only rarely and in a cursory and superficial fashion. We argue that probabilistic cellular automata (PCA) represent the best quantitative framework for modeling astrobiological history of the Milky Way and its Galactic Habitable Zone. The relevant astrobiological parameters are to be modeled as the elements of the input probability matrix for the PCA kernel. With the underlying simplicity of the cellular automata constructs, this approach enables a quick analysis of large and ambiguous input parameters' space. We perform a simple clustering analysis of typical astrobiological histories and discuss the relevant boundary conditions of practical importance for planning and guiding actual empirical astrobiological and SETI projects. In addition to showing how the present framework is adaptable to more complex situations and updated observational databases from current and near-future space missions, we demonstrate how numerical results could offer a cautious rationale for continuation of practical SETI searches.Comment: 37 pages, 11 figures, 2 tables; added journal reference belo

Skin color-specific and spectrally-selective naked-eye dosimetry of UVA, B and C radiations

Spectrally–selective monitoring of ultraviolet radiations (UVR) is of paramount importance across diverse fields, including effective monitoring of excessive solar exposure. Current UV sensors cannot differentiate between UVA, B, and C, each of which has a remarkably different impact on human health. Here we show spectrally selective colorimetric monitoring of UVR by developing a photoelectrochromic ink that consists of a multi-redox polyoxometalate and an e− donor. We combine this ink with simple components such as filter paper and transparency sheets to fabricate low-cost sensors that provide naked-eye monitoring of UVR, even at low doses typically encountered during solar exposure. Importantly, the diverse UV tolerance of different skin colors demands personalized sensors. In this spirit, we demonstrate the customized design of robust real-time solar UV dosimeters to meet the specific need of different skin phototypes. These spectrally–selective UV sensors offer remarkable potential in managing the impact of UVR in our day-to-day life

Highlights of the Fourth Canadian Symposium on Hepatitis C: Moving towards a National Action Plan

Hepatitis C virus (HCV) affects at least 268,000 Canadians and causes greater disease burden than any other infectious disease in the country. The Canadian Institutes of Health Research (CIHR) and the Public Health Agency of Canada (PHAC) have identified HCV-related liver disease as a priority. In 2015, the release of well-tolerated, short course treatments (12 weeks) able to cure the majority of treated HCV patients revolutionized HCV therapy. However, treatment is extremely costly and puts a significant burden on the Canadian healthcare system. Thus, managing treatment costs and improving treatment engagement in those most in need will be a key challenge. Diagnosis and treatment uptake are currently poor in Canada due to financial, geographical, cultural, and social barriers. The United States, Australia, and Scotland all have National Action Plans to prevent, diagnose, and treat HCV in order to efficiently reduce the burden and costs associated with HCV-related liver disease. The theme of the 4th annual symposium held on Feb 27, 2015, "Strategies to Manage HCV Infection in Canada: Moving towards a National Action Plan," was aimed at identifying strategies to maximize the impact of highly effective therapies to reduce HCV disease burden and ultimately eliminate HCV in Canada