Affinity proteomics reveals elevated muscle proteins in plasma of children with cerebral malaria

Systemic inflammation and sequestration of parasitized erythrocytes are central processes in the pathophysiology of severe Plasmodium falciparum childhood malaria. However, it is still not understood why some children are more at risks to develop malaria complications than others. To identify human proteins in plasma related to childhood malaria syndromes, multiplex antibody suspension bead arrays were employed. Out of the 1,015 proteins analyzed in plasma from more than 700 children, 41 differed between malaria infected children and community controls, whereas 13 discriminated uncomplicated malaria from severe malaria syndromes. Markers of oxidative stress were found related to severe malaria anemia while markers of endothelial activation, platelet adhesion and muscular damage were identified in relation to children with cerebral malaria. These findings suggest the presence of generalized vascular inflammation, vascular wall modulations, activation of endothelium and unbalanced glucose metabolism in severe malaria. The increased levels of specific muscle proteins in plasma implicate potential muscle damage and microvasculature lesions during the course of cerebral malaria

Adipocyte ACLY Facilitates Dietary Carbohydrate Handling to Maintain Metabolic Homeostasis in Females

Sugars and refined carbohydrates are major components of the modern diet. ATP-citrate lyase (ACLY) is upregulated in adipocytes in response to carbohydrate consumption and generates acetyl-coenzyme A (CoA) for both lipid synthesis and acetylation reactions. Here, we investigate the role of ACLY in the metabolic and transcriptional responses to carbohydrates in adipocytes and unexpectedly uncover a sexually dimorphic function in maintaining systemic metabolic homeostasis. When fed a high-sucrose diet, Acly(FAT-/-) females exhibit a lipodystrophy-like phenotype, with minimal fat accumulation, insulin resistance, and hepatic lipid accumulation, whereas Acly(FAT-/-) males have only mild metabolic phenotypes. We find that ACLY is crucial for nutrient-dependent carbohydrate response element-binding protein (ChREBP) activation in adipocytes and plays a key role, particularly in females, in the storage of newly synthesized fatty acids in adipose tissue. The data indicate that adipocyte ACLY is important in females for the systemic handling of dietary carbohydrates and for the preservation of metabolic homeostasis

Severe childhood malaria syndromes defined by plasma proteome profiles

BACKGROUND Cerebral malaria (CM) and severe malarial anemia (SMA) are the most serious life-threatening clinical syndromes of Plasmodium falciparum infection in childhood. Therefore it is important to understand the pathology underlying the development of CM and SMA, as opposed to uncomplicated malaria (UM). Different host responses to infection are likely to be reflected in plasma proteome-patterns that associate with clinical status and therefore provide indicators of the pathogenesis of these syndromes. METHODS AND FINDINGS Plasma and comprehensive clinical data for discovery and validation cohorts were obtained as part of a prospective case-control study of severe childhood malaria at the main tertiary hospital of the city of Ibadan, an urban and densely populated holoendemic malaria area in Nigeria. A total of 946 children participated in this study. Plasma was subjected to high-throughput proteomic profiling. Statistical pattern-recognition methods were used to find proteome-patterns that defined disease groups. Plasma proteome-patterns accurately distinguished children with CM and with SMA from those with UM, and from healthy or severely ill malaria-negative children. CONCLUSIONS We report that an accurate definition of the major childhood malaria syndromes can be achieved using plasma proteome-patterns. Our proteomic data can be exploited to understand the pathogenesis of the different childhood severe malaria syndromes

Elevated levels of diesel range organic compounds in groundwater near Marcellus gas operations are derived from surface activities

Author Posting. © The Author(s), 2015. This is the author's version of the work. It is posted here by permission of National Academy of Sciences for personal use, not for redistribution. The definitive version was published in Proceedings of the National Academy of Sciences of the United States of American 112 (2015): 13184-13189, doi: 10.1073/pnas.1511474112 .Hundreds of organic chemicals are utilized during natural gas extraction via high volume hydraulic fracturing (HVHF). However, it is unclear if these chemicals, injected into deep shale horizons, reach shallow groundwater aquifers and impact local water quality, either from deep underground injection sites or from the surface or shallow subsurface. Here, we report detectable levels of organic compounds in shallow groundwater samples from private residential wells overlying the Marcellus Shale in northeastern Pennsylvania. Analyses of purgeable and extractable organic compounds from 64 groundwater samples revealed trace levels of volatile organic compounds, well below the Environmental Protection Agency’s maximum contaminant levels, and low levels of both gasoline range (GRO; 0-8 ppb) and diesel range organic compounds (DRO; 0-157 ppb). A compound-specific analysis revealed the presence of bis(2-ethylhexyl)phthalate, which is a disclosed HVHF additive, that was notably absent in a representative geogenic water sample and field blanks. Pairing these analyses with 1) inorganic chemical fingerprinting of deep saline groundwater, 2) characteristic noble gas isotopes, and 3) spatial relationships between active shale gas extraction wells and wells with disclosed environmental health and safety (EHS) violations, we differentiate between a chemical signature associated with naturally occurring saline groundwater and a one associated with alternative anthropogenic routes from the surface (e.g., accidental spills or leaks). The data support a transport mechanism of DRO to groundwater via accidental release of fracturing fluid chemicals derived from the surface rather than subsurface flow of these fluids from the underlying shale formation.The authors thank Duke University’s Pratt School of Engineering and the National Science Foundation’s CBET Grant Number 1336702 and NSF EAGER (EAR-1249255) for financial support.2016-04-1

Explaining Cold-Pulse Dynamics in Tokamak Plasmas Using Local Turbulent Transport Models

A long-standing enigma in plasma transport has been resolved by modeling of cold-pulse experiments conducted on the Alcator C-Mod tokamak. Controlled edge cooling of fusion plasmas triggers core electron heating on time scales faster than an energy confinement time, which has long been interpreted as strong evidence of nonlocal transport. This Letter shows that the steady-state profiles, the cold-pulse rise time, and disappearance at higher density as measured in these experiments are successfully captured by a recent local quasilinear turbulent transport model, demonstrating that the existence of nonlocal transport phenomena is not necessary for explaining the behavior and time scales of cold-pulse experiments in tokamak plasmas.United States. Department of Energy (Award DE-FC02-99ER54512)United States. Department of Energy (Grant DESC0014264

Real-Time and Post-Processed Orbit Determination and Positioning

Novel methods and systems for the accurate and efficient processing of real-time and latent global navigation satellite systems (GNSS) data are described. Such methods and systems can perform orbit determination of GNSS satellites, orbit determination of satellites carrying GNSS receivers, positioning of GNSS receivers, and environmental monitoring with GNSS data

Enhancing the impact of implementation strategies in healthcare: a research agenda

The field of implementation science was developed to better understand the factors that facilitate or impede implementation and generate evidence for implementation strategies. In this article, we briefly review progress in implementation science, and suggest five priorities for enhancing the impact of implementation strategies. Specifically, we suggest the need to: 1) enhance methods for designing and tailoring implementation strategies; 2) specify and test mechanisms of change; 3) conduct more effectiveness research on discrete, multi-faceted, and tailored implementation strategies; 4) increase economic evaluations of implementation strategies; and 5) improve the tracking and reporting of implementation strategies. We believe that pursuing these priorities will advance implementation science by helping us to understand when, where, why, and how implementation strategies improve implementation effectiveness and subsequent health outcomes

Enhancing the Impact of Implementation Strategies in Healthcare: A Research Agenda

The field of implementation science was developed to better understand the factors that facilitate or impede implementation and generate evidence for implementation strategies. In this article, we briefly review progress in implementation science, and suggest five priorities for enhancing the impact of implementation strategies. Specifically, we suggest the need to: (1) enhance methods for designing and tailoring implementation strategies; (2) specify and test mechanisms of change; (3) conduct more effectiveness research on discrete, multi-faceted, and tailored implementation strategies; (4) increase economic evaluations of implementation strategies; and (5) improve the tracking and reporting of implementation strategies. We believe that pursuing these priorities will advance implementation science by helping us to understand when, where, why, and how implementation strategies improve implementation effectiveness and subsequent health outcomes

Balanced Synaptic Input Shapes the Correlation between Neural Spike Trains

Stimulus properties, attention, and behavioral context influence correlations between the spike times produced by a pair of neurons. However, the biophysical mechanisms that modulate these correlations are poorly understood. With a combined theoretical and experimental approach, we show that the rate of balanced excitatory and inhibitory synaptic input modulates the magnitude and timescale of pairwise spike train correlation. High rate synaptic inputs promote spike time synchrony rather than long timescale spike rate correlations, while low rate synaptic inputs produce opposite results. This correlation shaping is due to a combination of enhanced high frequency input transfer and reduced firing rate gain in the high input rate state compared to the low state. Our study extends neural modulation from single neuron responses to population activity, a necessary step in understanding how the dynamics and processing of neural activity change across distinct brain states