Clustering in Cell Cycle Dynamics with General Response/Signaling Feedback

Motivated by experimental and theoretical work on autonomous oscillations in yeast, we analyze ordinary differential equations models of large populations of cells with cell-cycle dependent feedback. We assume a particular type of feedback that we call Responsive/Signaling (RS), but do not specify a functional form of the feedback. We study the dynamics and emergent behaviour of solutions, particularly temporal clustering and stability of clustered solutions. We establish the existence of certain periodic clustered solutions as well as "uniform" solutions and add to the evidence that cell-cycle dependent feedback robustly leads to cell-cycle clustering. We highlight the fundamental differences in dynamics between systems with negative and positive feedback. For positive feedback systems the most important mechanism seems to be the stability of individual isolated clusters. On the other hand we find that in negative feedback systems, clusters must interact with each other to reinforce coherence. We conclude from various details of the mathematical analysis that negative feedback is most consistent with observations in yeast experiments.Comment: To appear in J. Theoretical Biology 292 (2012), 103-11

Neuroprotective Role of Gap Junctions in a Neuron Astrocyte Network Model

A detailed biophysical model for a neuron/astrocyte network is developed to explore mechanisms responsible for the initiation and propagation of cortical spreading depolarizations and the role of astrocytes in maintaining ion homeostasis, thereby preventing these pathological waves. Simulations of the model illustrate how properties of spreading depolarizations, such as wave speed and duration of depolarization, depend on several factors, including the neuron and astrocyte Na+-K+ ATPase pump strengths. In particular, we consider the neuroprotective role of astrocyte gap junction coupling. The model demonstrates that a syncytium of electrically coupled astrocytes can maintain a physiological membrane potential in the presence of an elevated extracellular K+ concentration and efficiently distribute the excess K+ across the syncytium. This provides an effective neuroprotective mechanism for delaying or preventing the initiation of spreading depolarizations.Postprint (author's final draft

Oxidative potential and chemical characterization of ambient aerosols in a South Texas coastal city

Oxidative Potential (OP) is a valuable metric that, when quantified, better describes the cellular response to aerosol inhalation than size distribution and mass alone. Aerosol samples were collected at three different sites in Corpus Christi, TX, with varying levels of pollutant emissions. The dithiothreitol (DTT) assay was adapted to determine the OP of the samples collected. Stark variations in OP are expected between the three sampling sites. The multiple size ranges collected in this study (18-.18μm) are a unique aspect in that previous studies focus mainly on PM10 and PM2.5. Samples were extracted using sonication, and evaluated to find OP, chemical composition, and carbonic content. Plots were developed to evaluate trends between both OPmass and OPvol with ambient concentrations of carbon and metals. The Pearson correlation coefficient is reported to show any viable statically relationships between the different aspects of PM analyzed. As expected, higher traffic was found to be related with higher OP. Ambient carbon and metal concentrations were surprisingly found to have little predictable impact on OP. The most valuable information garnered stems from the carbon and metal fraction of the PM collected. These fractions consistently showed the highest correlation with the OP determined

Neuroprotective Role of Gap Junctions in a Neuron Astrocyte Network Model

A detailed biophysical model for a neuron/astrocyte network is developed to explore mechanisms responsible for the initiation and propagation of cortical spreading depolarizations and the role of astrocytes in maintaining ion homeostasis, thereby preventing these pathological waves. Simulations of the model illustrate how properties of spreading depolarizations, such as wave speed and duration of depolarization, depend on several factors, including the neuron and astrocyte Na+-K+ ATPase pump strengths. In particular, we consider the neuroprotective role of astrocyte gap junction coupling. The model demonstrates that a syncytium of electrically coupled astrocytes can maintain a physiological membrane potential in the presence of an elevated extracellular K+ concentration and efficiently distribute the excess K+ across the syncytium. This provides an effective neuroprotective mechanism for delaying or preventing the initiation of spreading depolarizations

Non–Contrast-Enhanced Computerized Tomography and Analgesic-Related Kidney Disease: Report of the National Analgesic Nephropathy Study

Previous studies suggested that the non–contrast-enhanced computerized tomography (CT) scan is a highly reliable tool for the diagnosis of analgesic-associated renal disease. However, this issue has not been addressed in the US population. A total of 221 incident patients with ESRD from different regions of the United States underwent a helical CT scan and detailed questioning about drug history. Specific renal anatomic criteria were developed to determine whether a constellation of CT findings (small indented calcified kidneys [SICK]) is linked to analgesic ingestion. For approximating use before the onset of renal disease, only analgesic ingestion at least 9 yr before starting dialysis was considered relevant. Fifteen patients met the criteria for SICK. This represented 7% of the enrolled patients and approximately 1% of the total ESRD population. There was a significant increase in the estimated risk among patients with a history of heavy aspirin ingestion (odds ratio [OR] 7.4 [95% confidence interval (CI) 1.2 to 43] for ≥1 kg lifetime; OR 8.8 [95% CI 1.2 to 66] for ≥0.3 kg/yr). Total analgesic ingestion of ≥0.3 kg/yr also was significantly associated with SICK (OR 8.2; 95% CI 1.5 to 45). These findings were accounted for largely by combination products that contained aspirin and phenacetin (used by three patients with SICK), which are no longer available. In addition, the CT finding of SICK was present only in a minority of heavy analgesic users, yielding a sensitivity of 5 to 26%. Findings of SICK are infrequent in the US ESRD population and do not occur among a sufficient proportion of heavy analgesic users to render the non–contrast-enhanced CT scan a sensitive tool to detect analgesic-associated kidney injury