Dynamic regulation of extracellular superoxide production by the coccolithophore Emiliania huxleyi (CCMP 374)

© The Author(s), 2019. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Plummeer, S., Taylor, A. E., Harvey, E. L., Hansel, C. M., & Diaz, J. M. Dynamic regulation of extracellular superoxide production by the coccolithophore Emiliania huxleyi (CCMP 374). Frontiers in Microbiology, 10, (2019): 1546, doi: 10.3389/fmicb.2019.01546.In marine waters, ubiquitous reactive oxygen species (ROS) drive biogeochemical cycling of metals and carbon. Marine phytoplankton produce the ROS superoxide (O2−) extracellularly and can be a dominant source of O2− in natural aquatic systems. However, the cellular regulation, biological functioning, and broader ecological impacts of extracellular O2− production by marine phytoplankton remain mysterious. Here, we explored the regulation and potential roles of extracellular O2− production by a noncalcifying strain of the cosmopolitan coccolithophorid Emiliania huxleyi, a key species of marine phytoplankton that has not been examined for extracellular O2− production previously. Cell-normalized extracellular O2− production was the highest under presumably low-stress conditions during active proliferation and inversely related to cell density during exponential growth phase. Removal of extracellular O2− through addition of the O2− scavenger superoxide dismutase (SOD), however, increased growth rates, growth yields, cell biovolume, and photosynthetic efficiency (Fv/Fm) indicating an overall physiological improvement. Thus, the presence of extracellular O2− does not directly stimulate E. huxleyi proliferation, as previously suggested for other phytoplankton, bacteria, fungi, and protists. Extracellular O2− production decreased in the dark, suggesting a connection with photosynthetic processes. Taken together, the tight regulation of this stress independent production of extracellular O2− by E. huxleyi suggests that it could be involved in fundamental photophysiological processes.This research was supported by a Junior Faculty Seed Grant from the University of Georgia Research Foundation (JD), a National Science Foundation (NSF) Graduate Research Fellowship (SP), and NSF grant OCE-1355720 (CH). The FlowCam® and FIRe were purchased through a NSF Equipment Improvement Grant (1624593)

Implementing the Flinders Model of self-management support with Aboriginal people who have diabetes: findings from a pilot study

Programs to increase patients' capacity to manage their chronic disease are growing in popularity with policy makers, health professionals and the general public. However, until this pilot in regional South Australia, Indigenous people rarely participated in such programs. The pilot included extensive consultations with the Indigenous community, ownership of the program by an Aboriginal community-controlled health service, and a key role for Aboriginal and Torres Strait Islander Health Workers as the main coordinators of self-management support. The result was that 60 Aboriginal people participated and achieved notable improvements in health outcomes and personal goals. This pilot demonstrates that mainstream programs are relevant for Aboriginal communities as long as Aboriginal people lead the adaptation process

On-unit CT measures as tools for artificial intelligence to identify random vs. systematic anatomical changes in radiotherapy patients

Background: Although head and neck (H&N) cancer survival is steadily increasing, the close proximity of tumor volumes to organs at risk (OARs) makes radiotherapy planning and delivery challenging for these patients. Changes in patient anatomy (i.e. weight-loss, tumor shrinkage) over 7 weeks of daily radiotherapy may result in increased dosages of radiation to OARs relative to the original treatment plan, consequently hindering post-treatment quality of life. Artificial intelligence-based approaches can improve prediction and monitoring of these effects through identification of systematic changes. Objective: To collect and perform an analysis of on-unit CT measurements as surrogate measures of dose changes. Correlations among CT measures may indicate random vs. systematic changes in dose deposition (i.e. dosimetry) and further improve artificial intelligence-based approaches that determine which patients benefit most from treatment re-planning. Methods: 250 H&N cancer patients treated with curative chemo-radiotherapy were retrospectively analyzed. Five CT measures including face and neck diameter, chin and shoulder position, and head shift were calculated motivated by current literature. Dosimetric changes were calculated for OARs (pharyngeal constrictor, brainstem, parotid and submandibular glands) and tumour volumes. Conventional correlation analysis and hierarchical clustering were performed to assess group-wise correlations. K-medoid clustering and principal components analysis were conducted to infer groupings of the patients as random or systematic. Results: There is a positive correlation between increased dosages to central-axis anatomical structures (spinal cord, pharyngeal constrictor, submandibular glands) and systematic weight-loss effects (change in BMI and weight loss through the face and neck). In line with current literature, clustering indicated that 30.4% of the cohort exhibited systematic anatomical changes, potentially correctable by re-planning. MANOVA confirmed that the systematic anatomical changes corresponded to the spinal cord and brain stem (p<0.005), and Mann-Whitney U tests confirmed that the measures could identify systematic dose increases to the pharyngeal constrictor (p<0.05). Further statistical analyses will be conducted. Conclusions: On-unit CT measures appear to be able to distinguish random and systematic dosimetric effects, correlated with changes in dose as expected. These measures can be utilized to improve artificial intelligence-based patient monitoring and intervention techniques

Chronic disease self-management in Aboriginal communities: towards a sustainable program of care in rural communities

Bundoora, VI

A multiscale predictive digital twin for neurocardiac modulation

Cardiac function is tightly regulated by the autonomic nervous system (ANS). Activation of the sympathetic nervous system increases cardiac output by increasing heart rate and stroke volume, while parasympathetic nerve stimulation instantly slows heart rate. Importantly, imbalance in autonomic control of the heart has been implicated in the development of arrhythmias and heart failure. Understanding of the mechanisms and effects of autonomic stimulation is a major challenge because synapses in different regions of the heart result in multiple changes to heart function. For example, nerve synapses on the sinoatrial node (SAN) impact pacemaking, while synapses on contractile cells alter contraction and arrhythmia vulnerability. Here, we present a multiscale neurocardiac modelling and simulator tool that predicts the effect of efferent stimulation of the sympathetic and parasympathetic branches of the ANS on the cardiac SAN and ventricular myocardium. The model includes a layered representation of the ANS and reproduces firing properties measured experimentally. Model parameters are derived from experiments and atomistic simulations. The model is a first prototype of a digital twin that is applied to make predictions across all system scales, from subcellular signalling to pacemaker frequency to tissue level responses. We predict conditions under which autonomic imbalance induces proarrhythmia and can be modified to prevent or inhibit arrhythmia. In summary, the multiscale model constitutes a predictive digital twin framework to test and guide high-throughput prediction of novel neuromodulatory therapy. KEY POINTS: A multi-layered model representation of the autonomic nervous system that includes sympathetic and parasympathetic branches, each with sparse random intralayer connectivity, synaptic dynamics and conductance based integrate-and-fire neurons generates firing patterns in close agreement with experiment. A key feature of the neurocardiac computational model is the connection between the autonomic nervous system and both pacemaker and contractile cells, where modification to pacemaker frequency drives initiation of electrical signals in the contractile cells. We utilized atomic-scale molecular dynamics simulations to predict the association and dissociation rates of noradrenaline with the β-adrenergic receptor. Multiscale predictions demonstrate how autonomic imbalance may increase proclivity to arrhythmias or be used to terminate arrhythmias. The model serves as a first step towards a digital twin for predicting neuromodulation to prevent or reduce disease

Perifosine plus lenalidomide and dexamethasone in relapsed and relapsed/refractory multiple myeloma: a Phase I Multiple Myeloma Research Consortium study

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/92443/1/bjh9173.pd

DIAGNOSTIC REPORT

The final report on the first phase (2013) of the “Development of the strategic directions for education reform in Kazakh- stan for 2015-2020” project was implemented by the Graduate School of Education at Nazarbayev University on behalf of the Ministry of Education and Science of the Republic of Kazakhstan. The purpose of this research is to conduct a diagnosis of the education system of the Republic of Kazakhstan in order to identify the strengths and weaknesses of the educational system and the subsequent identification of areas for further modernization at each level

DIAGNOSTIC REPORT

The final report on the first phase (2013) of the “Development of the strategic directions for education reform in Kazakh- stan for 2015-2020” project was implemented by the Graduate School of Education at Nazarbayev University on behalf of the Ministry of Education and Science of the Republic of Kazakhstan. The purpose of this research is to conduct a diagnosis of the education system of the Republic of Kazakhstan in order to identify the strengths and weaknesses of the educational system and the subsequent identification of areas for further modernization at each level