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"Baker, Peter"
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Mitochondrial role in the neonatal predisposition to developing nonalcoholic fatty liver disease
Nonalcoholic fatty liver disease (NAFLD) is a global epidemic in obese children and adults, and the onset might have fetal origins. A growing body of evidence supports the role of developmental programming, whereby the maternal environment affects fetal and infant development, altering the risk profile for disease later in life. Human and nonhuman primate studies of maternal obesity demonstrate that risk factors for pediatric obesity and NAFLD begin in utero. The pathologic mechanisms for NAFLD are multifactorial but have centered on altered mitochondrial function/dysfunction that might precede insulin resistance. Compared with the adult liver, the fetal liver has fewer mitochondria, low activity of the fatty acid metabolic enzyme carnitine palmitoyl-CoA transferase-1, and little or no gluconeogenesis. Exposure to excess maternal fuels during fetal life uniquely alters hepatic fatty acid oxidation, tricarboxylic acid cycle activity, de novo lipogenesis, and mitochondrial health. These events promote increased oxidative stress and excess triglyceride storage, and, together with altered immune function and epigenetic changes, they prime the fetal liver for NAFLD and might drive the risk for nonalcoholic steatohepatitis in the next generation.
Journal Article
Enhancing green bean crop maturity and yield prediction by harnessing the power of statistical analysis, crop records and weather data
Climate change impacts require us to reexamine crop growth and yield under increasing temperatures and continuing yearly climate variability. Agronomic and agro-meteorological variables were concorded for a large number of plantings of green bean ( Phaseolus vulgaris L.) in three growing seasons over several years from semi-tropical Queensland. Using the Queensland government’s SILO meteorological database matched to sowing dates and crop phenology, we derived planting specific agro-meteorological variables. Linear and nonlinear statistical models were used to predict duration of vegetative and pod filling periods and fresh yield using agro-meteorological variables including thermal time, radiation and days of high temperature stress. High temperatures over 27.5∘C and 30∘C in the pod fill period were associated with a lower fresh bean yield. Differences between specific bean growing sites were examined using our bespoke open source software to derive agro-meteorological variables. Agronomically informed statistical models using production data were useful in predicting time of harvest. These methods can be applied to other commercial crops when crop phenology dates are collected.
Journal Article
Protein interaction landscapes revealed by advanced in vivo cross-linking–mass spectrometry
Defining protein–protein interactions (PPIs) in their native environment is crucial to understanding protein structure and function. Cross-linking–mass spectrometry (XL-MS) has proven effective in capturing PPIs in living cells; however, the proteome coverage remains limited. Here, we have developed a robust in vivo XL-MS platformto facilitate in-depth PPI mapping by integrating a multifunctional MS-cleavable cross-linker with sample preparation strategies and high-resolution MS. The advancement of click chemistry–based enrichment significantly enhanced the detection of cross-linked peptides for proteome-wide analyses. This platform enabled the identification of 13,904 unique lysine–lysine linkages from in vivo cross-linked HEK 293 cells, permitting construction of the largest in vivo PPI network to date, comprising 6,439 interactions among 2,484 proteins. These results allowed us to generate a highly detailed yet panoramic portrait of human interactomes associated with diverse cellular pathways. The strategy presented here signifies a technological advancement for in vivo PPI mapping at the systems level and can be generalized for charting protein interaction landscapes in any organisms.
Journal Article
Enhancement of the superconducting transition temperature of FeSe by intercalation of a molecular spacer layer
Altering the composition of the spacer layers present in iron-based superconductors is one strategy for increasing the temperature below which they superconduct. Now, intercalating FeSe with molecular spacer layers is also shown to enhance the superconducting transition temperature.
The discovery of high-temperature superconductivity in a layered iron arsenide
1
has led to an intensive search to optimize the superconducting properties of iron-based superconductors by changing the chemical composition of the spacer layer between adjacent anionic iron arsenide layers
2
,
3
,
4
,
5
,
6
,
7
. Superconductivity has been found in iron arsenides with cationic spacer layers consisting of metal ions (for example, Li
+
, Na
+
, K
+
, Ba
2+
) or PbO- or perovskite-type oxide layers, and also in Fe
1.01
Se (ref.
8
) with neutral layers similar in structure to those found in the iron arsenides and no spacer layer. Here we demonstrate the synthesis of Li
x
(NH
2
)
y
(NH
3
)
1−
y
Fe
2
Se
2
(
x
~0.6;
y
~0.2), with lithium ions, lithium amide and ammonia acting as the spacer layer between FeSe layers, which exhibits superconductivity at 43(1) K, higher than in any FeSe-derived compound reported so far. We have determined the crystal structure using neutron powder diffraction and used magnetometry and muon-spin rotation data to determine the superconducting properties. This new synthetic route opens up the possibility of further exploitation of related molecular intercalations in this and other systems to greatly optimize the superconducting properties in this family.
Journal Article
Disruption in glutathione metabolism and altered energy production in the liver and kidney after ischemic acute kidney injury in mice
Acute kidney injury (AKI) is a systemic disease that affects energy metabolism in various remote organs in murine models of ischemic AKI. However, AKI-mediated effects in the liver have not been comprehensively assessed. After inducing ischemic AKI in 8–10-week-old, male C57BL/6 mice, mass spectrometry metabolomics revealed that the liver had the most distinct phenotype 24 h after AKI versus 4 h and 7 days. Follow up studies with in vivo [
13
C
6
]-glucose tracing on liver and kidney 24 h after AKI revealed 4 major findings: (1) increased flux through glycolysis and the tricarboxylic (TCA) cycle in both kidney and liver; (2) depleted hepatic glutathione levels and its intermediates despite unchanged level of reactive oxygen species, suggesting glutathione consumption exceeds production due to systemic oxidative stress after AKI; (3) hepatic ATP depletion despite unchanged rate of mitochondrial respiration, suggesting increased ATP consumption relative to production; (4) increased hepatic and renal urea cycle intermediates suggesting hypercatabolism and upregulation of the urea cycle independent of impaired renal clearance of nitrogenous waste. Taken together, this is the first study to describe the hepatic metabolome after ischemic AKI in a murine model and demonstrates that there is significant liver-kidney crosstalk after AKI.
Journal Article