John W.

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Changes in cardiac metabolism typically precede cardiac dysfunction and therefore represent an important target for diagnosis and treatment designed to prevent progression to heart failure, a leading cause of death. Profound changes in pyruvate metabolism, including reduced expression of the mitochondrial pyruvate carrier (MPC), are increasingly recognized as early maladaptive alterations in cardiomyopathies, but no methods currently exist to determine MPC expression in vivo. We exposed mice to doxorubicin (DOX), an anthracycline chemotherapeutic known to perturb pyruvate metabolism, and demonstrated that cardiac tissue levels of MPC decrease within 4 weeks of initial DOX exposure. Using a combination of stable isotope tracing metabolomics, hyperpolarized [1-13C]pyruvate magnetic resonance imaging (MRI), and [3-11C]pyruvate positron emission tomography (PET), we found that loss of MPC and monocarboxylate transporter 1 (MCT1) resulted in decreased utilization of pyruvate for mitochondrial oxidative metabolism and resulted in decreased cardiac carbon-11 clearance. Despite recovery of expression levels of pyruvate transporters, including MPC, 16 weeks after initial DOX exposure, cardiac carbon-11 clearance still trends towards differences between control mice and the mice exposed to this chemotherapeutic. [3-11C]Pyruvate PET is therefore a promising approach to imaging cardiac pyruvate transport with potential applications to the identification of early maladaptive changes in pyruvate metabolism and monitoring response to therapy.

To manage and protect marine ecosystems, we first need a spatialised knowledge of the seascape-scale processes surrounding them. However, we lack spatially explicit understanding of how regional processes influence biological patterns in many marine systems. This is especially true of remote marine ecosystems, such as those in the deep sea. Here, we conceptualise potential seascape-scale environmental influences on deep-sea hydrothermal vent ecosystems, guided by experts and literature. We propose environmental characteristics that may shape local biodiversity patterns, such as community structure, habitat availability, and temporal stability. Next, we develop pipelines from data extraction to analysis to improve spatial data accessibility and investigate which variables can be used to draw similarities among vent fields. Finally, we group vents from different regions according to shared environmental characteristics. We show that vents that are spatially isolated and have different species pools can share similar environmental characteristics across ocean basins, including geological, oceanographic, and biological dynamics. We thus illustrate how large-scale environmental data can be used to compare seascape attributes across remote, island-like vent ecosystems. We suggest that looking beyond local scales to consider how seascapes both influence and distinguish different vent systems within a global setting is important for conservation and macroecological contexts.

Capnometry is a cost-efficient method of monitoring carbon dioxide (CO2) in healthcare settings, especially during mechanical ventilation and cardiopulmonary bypass. However, the utility of capnometers for studying CO2 elimination in a longer-duration, clinical extracorporeal membrane oxygenation (ECMO) has been poorly characterized. This report presents data from 10 venovenous ECMO patients at Vanderbilt University Medical Center between April and June 2021. Exhaust CO2 was intermittently measured from a membrane oxygenator’s gas outlet, and arterial blood samples were simultaneously drawn from the patient. Clinical variables including ECMO and ventilator management, patient demographics, and outcomes were recorded. Exhaust CO2 and other study variables were recorded at 233 discrete time points from the 10 patients. The median duration of ECMO support was 9 days. Sweep gas flow rate demonstrated a strong, negative correlation with exhaust CO2 concentration, from both univariate and multivariate regression analyses (adjusted β = − 5.556 for sweep < 4 L/min, p < 0.001). Blood flow, oxygenator duration of use, and arterial CO2 demonstrated weaker relationships with exhaust CO2 (adjusted β = 2.341, − 0.258, 0.175, respectively), which agrees with the clinical understanding about CO2 management during ECMO. This descriptive study provides foundation for future research to precisely define the clinical role of ECMO exhaust capnometry in the management of the sweep gas flow and the overall therapy.

This study describes a novel mechanism of calcium control of metabolism found in the mitochondrial intermembrane space that is entirely independent of matrix Ca2+ uptake.

As advanced nuclear reactor designs move towards higher operating temperatures, rapid nuclear material creep research has become increasingly important. Research of irradiated materials has been limited by space constraints inside research reactors. To mitigate these constraints, the utilization of sub-sized specimens has seen growing popularity to produce more irradiated material samples. However, the impact of using sub-sized specimens for creep research is not currently well understood. To address this issue, this paper aims to provide a comprehensive dataset from various sources that will include creep properties, material composition, treatment conditions, irradiation conditions, and specimen dimensions. A dataset has been curated from 54 peer-reviewed sources, resulting in a total of 1,583 different specimens. The dataset focuses on materials relevant to nuclear reactor applications, including austenitic stainless steels, reactor pressure vessel steels, Inconel alloys, Zircaloy, and ferritic-martensitic steels. This paper also provides a concise summary of creep tests for interpreting the dataset as well as discussing recent studies that used machine learning models to predict creep rupture life. The primary focus of this paper is to provide a comprehensive dataset to enable researchers to perform studies on the influences of specimen size on creep properties.

Every year, the panel overseeing the trust fund for Social Security and Medicare publishes its annual financial report.

Background Pediatric ureteropelvic junction obstruction (UPJO) is the leading cause of congenital obstructive uropathy. Experimental models have identified local urothelial remodeling in UPJO and implicated this remodeling as a protective adaptation to preserve kidney structural integrity and function. We investigated the expression of urothelial proteins in human urine and resected tissue specimens from children with UPJO in a pilot study. Methods Children undergoing pyeloplasty for clinically significant UPJO and healthy age- and sex-matched controls were included. Bladder urine samples were evaluated by ELISA for urothelial proteins (KRT5, KRT14, KRT20, UPK2, UPK3A) and normalized to creatinine (Cr). When available, kidney urine collected at pyeloplasty was compared to bladder urine from the same subject. Urothelial proteins were localized by immunofluorescence microscopy in surgically resected kidney pelvises proximal to the obstruction. Results Twenty-three UPJO and 14 control urines were evaluated. KRT14/Cr, KRT20/Cr, and UPK2/Cr levels were significantly higher in UPJO urine compared to controls (p < 0.05; Mann–Whitney U test). Levels of urothelial proteins were as high or higher in urine obtained from the obstructed kidney when compared to paired bladder urine. Immunofluorescence microscopy of obstructed urothelium identified basal KRT14+ cells, pan-urothelial UPK+ cells, and superficial KRT20 + cells, with nuclear localization of two transcription factors implicated in obstructive urothelial remodeling, GRHL3 and PPARγ. Conclusions We provide evidence of increased urothelial proteins in urine from children with UPJO in this pilot study, along with evidence of their local expression by obstructed urothelium. Graphical abstract