The adaptor protein PID1 regulates receptor-dependent endocytosis of postprandial triglyceride-rich lipoproteins.

ObjectiveInsulin resistance is associated with impaired receptor dependent hepatic uptake of triglyceride-rich lipoproteins (TRL), promoting hypertriglyceridemia and atherosclerosis. Next to low-density lipoprotein (LDL) receptor (LDLR) and syndecan-1, the LDLR-related protein 1 (LRP1) stimulated by insulin action contributes to the rapid clearance of TRL in the postprandial state. Here, we investigated the hypothesis that the adaptor protein phosphotyrosine interacting domain-containing protein 1 (PID1) regulates LRP1 function, thereby controlling hepatic endocytosis of postprandial lipoproteins.MethodsLocalization and interaction of PID1 and LRP1 in cultured hepatocytes was studied by confocal microscopy of fluorescent tagged proteins, by indirect immunohistochemistry of endogenous proteins, by GST-based pull down and by immunoprecipitation experiments. The in vivo relevance of PID1 was assessed using whole body as well as liver-specific Pid1-deficient mice on a wild type or Ldlr-deficient (Ldlr-/-) background. Intravital microscopy was used to study LRP1 translocation in the liver. Lipoprotein metabolism was investigated by lipoprotein profiling, gene and protein expression as well as organ-specific uptake of radiolabelled TRL.ResultsPID1 co-localized in perinuclear endosomes and was found associated with LRP1 under fasting conditions. We identified the distal NPxY motif of the intracellular C-terminal domain (ICD) of LRP1 as the site critical for the interaction with PID1. Insulin-mediated NPxY-phosphorylation caused the dissociation of PID1 from the ICD, causing LRP1 translocation to the plasma membrane. PID1 deletion resulted in higher LRP1 abundance at the cell surface, higher LDLR protein levels and, paradoxically, reduced total LRP1. The latter can be explained by higher receptor shedding, which we observed in cultured Pid1-deficient hepatocytes. Consistently, PID1 deficiency alone led to increased LDLR-dependent endocytosis of postprandial lipoproteins and lower plasma triglycerides. In contrast, hepatic PID1 deletion on an Ldlr-/- background reduced lipoprotein uptake into liver and caused plasma TRL accumulation.ConclusionsBy acting as an insulin-dependent retention adaptor, PID1 serves as a regulator of LRP1 function controlling the disposal of postprandial lipoproteins. PID1 inhibition provides a novel approach to lower plasma levels of pro-atherogenic TRL remnants by stimulating endocytic function of both LRP1 and LDLR in the liver

Psychophysiological processes of stress in chronic physical illness: a theoretical perspective

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75576/1/j.1365-2648.1990.tb01843.x.pd

Distribution of methane in the water column of the Baltic Sea

The distribution of dissolved methane in the water column of the Baltic Sea was extensively investigated. A strong correlation between the vertical density stratification, the distribution of oxygen, hydrogen sulfide, and methane has been identified. A widespread release of methane from the seafloor is indicated by increasing methane concentrations with water depth. The deep basins in the central Baltic Sea show the strongest methane enrichments in stagnant anoxic water bodies (max. 1086 nM and 504 nM, respectively), with a pronounced decrease towards the pelagic redoxcline and slightly elevated surface water concentrations (saturation values of 206% and 120%, respectively). In general the more limnic basins in the northern part of the Baltic are characterized by lower water column methane concentrations and surface water saturation values close to the atmospheric equilibrium (between 106% and 116%). In contrast, the shallow Western Baltic Sea is characterized by high saturation values up to 746%

Coordinated Sampling of Microorganisms Over Freshwater and Saltwater Environments Using an Unmanned Surface Vehicle (USV) and a Small Unmanned Aircraft System (sUAS)

Biological aerosols (bioaerosols) are ubiquitous in terrestrial and aquatic environments and may influence cloud formation and precipitation processes. Little is known about the aerosolization and transport of bioaerosols from aquatic environments. We designed and deployed a bioaerosol-sampling system onboard an unmanned surface vehicle (USV; a remotely operated boat) to collect microbes and monitor particle sizes in the atmosphere above a salt pond in Falmouth, MA, United States and a freshwater lake in Dublin, VA, United States. The bioaerosol-sampling system included a series of 3D-printed impingers, two different optical particle counters, and a weather station. A small unmanned aircraft system (sUAS; a remotely operated airplane) was used in a coordinated effort with the USV to collect microorganisms on agar media 50 m above the surface of the water. Samples from the USV and sUAS were cultured on selective media to estimate concentrations of culturable microorganisms (bacteria and fungi). Concentrations of microbes from the sUAS ranged from 6 to 9 CFU/m3 over saltwater, and 12 to 16 CFU/m3 over freshwater (over 10-min sampling intervals) at 50 m above ground level (AGL). Concentrations from the USV ranged from 0 (LOD) to 42,411 CFU/m3 over saltwater, and 0 (LOD) to 56,809 CFU/m3 over freshwater (over 30-min sampling intervals) in air near the water surface. Particle concentrations recorded onboard the USV ranged from 0 (LOD) to 288 μg/m3 for PM1, 1 to 290 μg/m3 for PM2.5, and 1 to 290 μg/m3 for PM10. A general trend of increasing concentration with an increase in particle size was recorded by each sensor. Through laboratory testing, the collection efficiency of the 3D-printed impingers was determined to be 75% for 1 μm beads and 99% for 3 μm beads. Additional laboratory tests were conducted to determine the accuracy of the miniaturized optical particle counters used onboard the USV. Future work aims to understand the distribution of bioaerosols above aquatic environments and their potential association with cloud formation and precipitation processes

Coordinated Unmanned Aircraft System (UAS) and Ground-Based Weather Measurements to Predict Lagrangian Coherent Structures (LCSs)

Concentrations of airborne chemical and biological agents from a hazardous release are not spread uniformly. Instead, there are regions of higher concentration, in part due to local atmospheric flow conditions which can attract agents. We equipped a ground station and two rotary-wing unmanned aircraft systems (UASs) with ultrasonic anemometers. Flights reported here were conducted 10 to 15 m above ground level (AGL) at the Leach Airfield in the San Luis Valley, Colorado as part of the Lower Atmospheric Process Studies at Elevation—a Remotely-Piloted Aircraft Team Experiment (LAPSE-RATE) campaign in 2018. The ultrasonic anemometers were used to collect simultaneous measurements of wind speed, wind direction, and temperature in a fixed triangle pattern; each sensor was located at one apex of a triangle with ∼100 to 200 m on each side, depending on the experiment. A WRF-LES model was used to determine the wind field across the sampling domain. Data from the ground-based sensors and the two UASs were used to detect attracting regions (also known as Lagrangian Coherent Structures, or LCSs), which have the potential to transport high concentrations of agents. This unique framework for detection of high concentration regions is based on estimates of the horizontal wind gradient tensor. To our knowledge, our work represents the first direct measurement of an LCS indicator in the atmosphere using a team of sensors. Our ultimate goal is to use environmental data from swarms of sensors to drive transport models of hazardous agents that can lead to real-time proper decisions regarding rapid emergency responses. The integration of real-time data from unmanned assets, advanced mathematical techniques for transport analysis, and predictive models can help assist in emergency response decisions in the future

A low frequency multibeam assessment: Spatial mapping of shallow gas by enhanced penetration and angular response anomaly

This study highlights the potential of using a low frequency multibeam echosounder for detection and visualization of shallow gas occurring several meters beneath the seafloor. The presence of shallow gas was verified in the Bornholm Basin, Baltic Sea, at 80 m water depth with standard geochemical core analysis and hydroacoustic subbottom profiling. Successively, this area was surveyed with a 95 kHz and a 12 kHz multibeam echosounder (MBES). The bathymetric measurements with 12 kHz provided depth values systematically deeper by several meters compared to 95 kHz data. This observation was attributed to enhanced penetration of the low frequency signal energy into soft sediments. Consequently, the subbottom geoacoustic properties contributed highly to the measured backscattered signals. Those appeared up to 17 dB higher inside the shallow gas area compared to reference measurements outside and could be clearly linked to the shallow gas front depth down to 5 meter below seafloor. No elevated backscatter was visible in 95 kHz MBES data, which in turn highlights the superior potential of low frequency MBES to image shallow sub-seafloor features. Small gas pockets could be resolved even on the outer swath (up to 65°). Strongly elevated backscattering from gassy areas occurred at large incidence angles and a high gas sensitivity of the MBES is further supported by an angular response analysis presented in this study. We conclude that the MBES together with subbottom profiling can be used as an efficient tool for spatial subbottom mapping in soft sediment environments

A novel deletion mutation of the EXT2 gene in a large Chinese pedigree with hereditary multiple exostosis

Hereditary multiple exostoses (EXT) is an autosomal dominant disease characterized by the formation of cartilage-capped prominences (exostoses) that develop from the juxta-epiphyseal regions of the long bones. 3 genes are known to be involved in the formation of exostoses. Among them, EXT1 and EXT2, which encode enzymes that catalyse the biosynthesis of heparan sulfate, an important component of the extracellular matrix, are responsible for over 70% of the EXT cases. A large Chinese family with hereditary multiple exostoses has been analysed and the disease-causing mutation has been found. Blood samples were obtained from 69 family members, including 23 affected individuals. The EXT phenotype was shown to be linked to the EXT2 gene by using 2-point linkage analysis. After polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) analysis and DNA sequencing, a previously unreported deletion of a G in exon 3 of EXT2 gene was observed. This deletion co-segregated with the disease phenotype, suggesting that it is the disease-causing mutation in this family. Furthermore, in at least 4 members chondrosarcoma occurred after either an operation or injury of the exostosis and 3 of them died of the malignance in the family. Whether the operation or injury was responsible for the malignant transformation still needs further study. © 2001 Cancer Research Campaign http://www.bjcancer.co

Data Generated during the 2018 LAPSE-RATE Campaign: An Introduction and Overview

Unmanned aircraft systems (UASs) offer innovative capabilities for providing new perspectives on the atmosphere, and therefore atmospheric scientists are rapidly expanding their use, particularly for studying the planetary boundary layer. In support of this expansion, from 14 to 20 July 2018 the International Society for Atmospheric Research using Remotely piloted Aircraft (ISARRA) hosted a community flight week, dubbed the Lower Atmospheric Profiling Studies at Elevation – a Remotely-piloted Aircraft Team Experiment (LAPSE-RATE; de Boer et al., 2020a). This field campaign spanned a 1-week deployment to Colorado\u27s San Luis Valley, involving over 100 students, scientists, engineers, pilots, and outreach coordinators. These groups conducted intensive field operations using unmanned aircraft and ground-based assets to develop comprehensive datasets spanning a variety of scientific objectives, including a total of nearly 1300 research flights totaling over 250 flight hours. This article introduces this campaign and lays the groundwork for a special issue on the LAPSE-RATE project. The remainder of the special issue provides detailed overviews of the datasets collected and the platforms used to collect them. All of the datasets covered by this special issue have been uploaded to a LAPSE-RATE community set up at the Zenodo data archive (https://zenodo.org/communities/lapse-rate/, last access: 3 December 2020)