Cardiac mitochondria exhibit dynamic functional clustering

Multi-oscillatory behavior of mitochondrial inner membrane potential ΔΨm in self-organized cardiac mitochondrial networks can be triggered by metabolic or oxidative stress. Spatio-temporal analyses of cardiac mitochondrial networks have shown that mitochondria are heterogeneously organized in synchronously oscillating clusters in which the mean cluster frequency and size are inversely correlated, thus suggesting a modulation of cluster frequency through local inter-mitochondrial coupling. In this study, we propose a method to examine the mitochondrial network's topology through quantification of its dynamic local clustering coefficients. Individual mitochondrial ΔΨm oscillation signals were identified for each cardiac myocyte and cross-correlated with all network mitochondria using previously described methods (Kurz et al., 2010a). Time-varying inter-mitochondrial connectivity, defined for mitochondria in the whole network whose signals are at least 90% correlated at any given time point, allowed considering functional local clustering coefficients. It is shown that mitochondrial clustering in isolated cardiac myocytes changes dynamically and is significantly higher than for random mitochondrial networks that are constructed using the Erdös–Rényi model based on the same sets of vertices. The network's time-averaged clustering coefficient for cardiac myocytes was found to be 0.500 ± 0.051 (N = 9) vs. 0.061 ± 0.020 for random networks, respectively. Our results demonstrate that cardiac mitochondria constitute a network with dynamically connected constituents whose topological organization is prone to clustering. Cluster partitioning in networks of coupled oscillators has been observed in scale-free and chaotic systems and is therefore in good agreement with previous models of cardiac mitochondrial networks

Systemic NK cell ablation attenuates intra‐abdominal adipose tissue macrophage infiltration in murine obesity

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/108606/1/oby20823.pd

The Alliance for Cellular Signaling Plasmid Collection: A Flexible Resource for Protein Localization Studies and Signaling Pathway Analysis

Cellular responses to inputs that vary both temporally and spatially are determined by complex relationships between the components of cell signaling networks. Analysis of these relationships requires access to a wide range of experimental reagents and techniques, including the ability to express the protein components of the model cells in a variety of contexts. As part of the Alliance for Cellular Signaling, we developed a robust method for cloning large numbers of signaling ORFs into Gateway® entry vectors, and we created a wide range of compatible expression platforms for proteomics applications. To date, we have generated over 3000 plasmids that are available to the scientific community via the American Type Culture Collection. We have established a website at www.signaling-gateway.org/data/plasmid/ that allows users to browse, search, and blast Alliance for Cellular Signaling plasmids. The collection primarily contains murine signaling ORFs with an emphasis on kinases and G protein signaling genes. Here we describe the cloning, databasing, and application of this proteomics resource for large scale subcellular localization screens in mammalian cell lines

Experimental Philosophy of Science and Philosophical Differences across the Sciences

This paper contributes to the underdeveloped field of experimental philosophy of science. We examine variability in the philosophical views of scientists. Using data from Toolbox Dialogue Initiative, we analyze scientists’ responses to prompts on philosophical issues (methodology, confirmation, values, reality, reductionism, and motivation for scientific research) to assess variance in the philosophical views of physical scientists, life scientists, and social and behavioral scientists. We find six prompts about which differences arose, with several more that look promising for future research. We then evaluate the difference between the natural and social sciences and the challenge of interdisciplinary integration across scientific branches

Experimental Philosophy of Science and Philosophical Differences across the Sciences

This paper contributes to the underdeveloped field of experimental philosophy of science. We examine variability in the philosophical views of scientists. Using data from Toolbox Dialogue Initiative, we analyze scientists’ responses to prompts on philosophical issues (methodology, confirmation, values, reality, reductionism, and motivation for scientific research) to assess variance in the philosophical views of physical scientists, life scientists, and social and behavioral scientists. We find six prompts about which differences arose, with several more that look promising for future research. We then evaluate the difference between the natural and social sciences and the challenge of interdisciplinary integration across scientific branches

Urinary thrombomodulin levels were significantly higher following occupational exposure to chemicals, in the presence of dipstick protein, but not in the presence of dipstick blood

Currently, there are no biomarkers which can identify patients with an increased risk of developing urothelial cancer as a result of occupational chemical exposure. The aim of this study was to evaluate the relationships between final diagnosis and 22 biomarkers measured in urine, serum and plasma collected from 156 hematuric patients. Fourteen of the 80 patients (17.5%) with urothelial cancer and 13/76 (17.1%) of the controls were deemed to have a history of chemical exposure. We applied Fisher's exact tests to explore associations between chemical exposure and final diagnosis, and tumor stage and grade, where applicable; ANOVA and t-test to compare age across patients with and without chemical exposure; and Zelen's exact test to evaluate relationships across final diagnosis, chemical exposure and smoking. Following pre-selection of biomarkers using Lasso, we identified biomarkers with differential levels across patients with and without chemical exposure using Welch's t-test. Using a one-sided t-test and considering multiple testing using FDR, we observed that TM levels in urine were significantly higher in samples from patients with a history of chemical exposure regardless of their diagnosis as control or urothelial cancer (one-sided t-test, pUC = 0.014 and pCTL = 0.043); in the presence of dipstick protein and when urinary pH levels ≤ 6 (p = 0.003), but not in the presence of dipstick blood (p = 0.115). Urothelial cancer patients with a history of chemical exposure were significantly younger (64.1 years) than those without chemical exposure (70.2 years) (one-sided t-test p-value = 0.012); and their tumors were higher grade (Fisher's exact test; p = 0.008). There was a strong association between a history of chemical exposure and smoking in urothelial cancer patients (Zelen's exact test; p = 0.025). Elevated urinary thrombomodulin levels could have the potential to identify chemical exposure in hematuric patients at high risk of developing urothelial cancer.</p

Experimental Philosophy of Science and Philosophical Differences across the Sciences

This paper contributes to the underdeveloped field of experimental philosophy of science. We examine variability in the philosophical views of scientists. Using data from Toolbox Dialogue Initiative, we analyze scientists’ responses to prompts on philosophical issues (methodology, confirmation, values, reality, reductionism, and motivation for scientific research) to assess variance in the philosophical views of physical scientists, life scientists, and social and behavioral scientists. We find six prompts about which differences arose, with several more that look promising for future research. We then evaluate the difference between the natural and social sciences and the challenge of interdisciplinary integration across scientific branches

Experimental Philosophy of Science and Philosophical Differences across the Sciences

This paper contributes to the underdeveloped field of experimental philosophy of science. We examine variability in the philosophical views of scientists. Using data from Toolbox Dialogue Initiative, we analyze scientists’ responses to prompts on philosophical issues (methodology, confirmation, values, reality, reductionism, and motivation for scientific research) to assess variance in the philosophical views of physical scientists, life scientists, and social and behavioral scientists. We find six prompts about which differences arose, with several more that look promising for future research. We then evaluate the difference between the natural and social sciences and the challenge of interdisciplinary integration across scientific branches