Genetic and functional characterization of disease associations explains comorbidity

Understanding relationships between diseases, such as comorbidities, has important socio-economic implications, ranging from clinical study design to health care planning. Most studies characterize disease comorbidity using shared genetic origins, ignoring pathway-based commonalities between diseases. In this study, we define the disease pathways using an interactome-based extension of known disease-genes and introduce several measures of functional overlap. The analysis reveals 206 significant links among 94 diseases, giving rise to a highly clustered disease association network. We observe that around 95% of the links in the disease network, though not identified by genetic overlap, are discovered by functional overlap. This disease network portraits rheumatoid arthritis, asthma, atherosclerosis, pulmonary diseases and Crohn's disease as hubs and thus pointing to common inflammatory processes underlying disease pathophysiology. We identify several described associations such as the inverse comorbidity relationship between Alzheimer's disease and neoplasms. Furthermore, we investigate the disruptions in protein interactions by mapping mutations onto the domains involved in the interaction, suggesting hypotheses on the causal link between diseases. Finally, we provide several proof-of-principle examples in which we model the effect of the mutation and the change of the association strength, which could explain the observed comorbidity between diseases caused by the same genetic alterations

Data_Sheet_1_A temperature-based model of biomass accumulation in humid forests of the world.docx

Forests benefit humans in numerous ways. Many of these benefits are greater from forests with large trees and high biomass (i.e., above-ground biomass) than from young forests with small trees. Understanding how the biomass accumulation rate depends on climate is therefore important. According to a classic theory, the biomass accumulation rate first increases until canopy closure, as leaf area and gross primary productivity increase, and decreases thereafter because leaf area cannot increase further and maintaining larger biomass is energetically costlier as living tissue increases even though its proportion of all biomass decreases. We based our modeling on this classic theory and defined relative productivity, pr indicating productivity, and relative maintenance cost, cr, signaling the expense of sustaining a unit of biomass in humid climates of the world. The biomass accumulation rate of low biomass forests is determined by pr − cr and maximal biomass by pr/cr. We then compiled a global data set from the literature, with 3,177 records to fit a parameter for the efficiency of converting surplus carbon into accumulated biomass and another parameter determining biomass at canopy closure. Based on the parameterized models, a constant temperature of 22.3°C leads to the most rapid biomass accumulation in low biomass forests, whereas 16.4°C results in greatest maximal biomass. Our parameterized model can be applied to both climate change adaptation and mitigation by optimizing land use.</p

Table_1_A temperature-based model of biomass accumulation in humid forests of the world.XLSX

Forests benefit humans in numerous ways. Many of these benefits are greater from forests with large trees and high biomass (i.e., above-ground biomass) than from young forests with small trees. Understanding how the biomass accumulation rate depends on climate is therefore important. According to a classic theory, the biomass accumulation rate first increases until canopy closure, as leaf area and gross primary productivity increase, and decreases thereafter because leaf area cannot increase further and maintaining larger biomass is energetically costlier as living tissue increases even though its proportion of all biomass decreases. We based our modeling on this classic theory and defined relative productivity, pr indicating productivity, and relative maintenance cost, cr, signaling the expense of sustaining a unit of biomass in humid climates of the world. The biomass accumulation rate of low biomass forests is determined by pr − cr and maximal biomass by pr/cr. We then compiled a global data set from the literature, with 3,177 records to fit a parameter for the efficiency of converting surplus carbon into accumulated biomass and another parameter determining biomass at canopy closure. Based on the parameterized models, a constant temperature of 22.3°C leads to the most rapid biomass accumulation in low biomass forests, whereas 16.4°C results in greatest maximal biomass. Our parameterized model can be applied to both climate change adaptation and mitigation by optimizing land use.</p

Simulation results with multivariate controls.

<p>In this type of analysis, we can seek to observe changes in the overall level of social morality while modifying two or more variables simultaneously.</p

Silver(I)-Catalyzed Oxidative Cyclopropanation of 1,6-Enynes: Synthesis of 3‑Aza-bicyclo[3.1.0]hexane Derivatives

A simple Ag(I)-catalyzed oxidative cyclopropanation of heteroatom-tethered 1,6-enynes for the establishment of valuable functionalized 3-aza-bicyclo[3.1.0]hexane is presented, which allows the formation of multiple chemical bonds in one step under 20 mol % silver(I) catalysts and air conditions. This approach is highly atom economical, easy to perform, and free of external oxidants and features good to excellent yields and gram-scale synthesis. The preliminary study showed that an uncommon silver carbenoid intermediate might be involved in this process

Simulation results with univariate controls.

<p>In this type of analysis, we can observe the effects of the changes in the overall social moral level by adjustments of one variable parameter value. Critical state parameter values are found after repeated experiments. Some results consistent with other research conclusions. Such as incentives are an expensive means of management <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0079852#pone.0079852-Daniel1" target="_blank">[31]</a> and psychological research on rewards and punishments <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0079852#pone.0079852-Chen1" target="_blank">[32]</a>.</p

Model Parameters and Initial Values.

<p>Model Parameters and Initial Values.</p

NetLogo interface of the simulation mode.

<p>NetLogo is a multi-agent programmable modeling environment. Here is the simulation interface that was developed by authors. This model includes the command area, parameters area, chart area and image area. Command area is responsible for the control of initialization parameters and operating procedures. Parameters area allows to dynamically adjust the parameters. The chart area display the simulation results. Image area can be dynamically displays the status of agents.</p

Highly efficient Brønsted acid and Lewis acid catalysis systems for the Friedländer Quinoline synthesis

<p>The efficient and green Brønsted acid or Lewis acid catalysis systems for the Friedländer synthesis of 2,3,4-trisubstituted quinolines from the condensation of 2-aminoarylketones and β-ketoesters/ketones had been developed. The results confirmed that 4-toluenesulfonic acid, magnesium chloride, and cupric nitrate were the desired catalyst independently. This protocol had the advantages of mild conditions, operational simplicity, and excellent yields.</p

Primary DG donor cells are the only cell type that contains a subpopulation of NeuN/Prox1+ cells before transplantation.

<p>Examples of cultured DG cells stained for (A) the proliferation maker Ki67, (B–C) the progenitor cell markers Nestin and Sox2, (D–F) the neuronal cell markers DCX, NeuN and Prox1 and (G–H) glial-related markers S100β and GFAP. (I–J) Percentages of cultured or primary DG and vSVZ cells expressing different markers (mean ± SEM, n = 3), *p<0.05. Scale bar  = 50 µm.</p