Thiazolidinediones address underlying causes of type 2 diabetes, although their mechanism of action is not clearly understood. The compounds are thought to function as direct activators of the ...nuclear receptor PPAR{gamma} (peroxisome proliferator-activated receptor-{gamma}), although pioglitazone, the weaker agonist of the two thiazolidinediones now in clinical use, seems to have more useful effects on circulating lipids. We have used tritiated pioglitazone and a photoaffinity cross-linker to identify a novel binding site in mitochondria. A saturable binding site for 3Hpioglitazone was solubilized from the membranes with CHAPS and migrated as a large complex by size exclusion chromatography. The binding correlated with a <17-kDa protein (m17), marked by a photoaffinity cross-linker, in both subcellular location and selectivity of competition by analogs. The protein was isolated and identified by mass spectrometry analysis and NH2-terminal sequencing. Three synthetic peptides with potential antigenic properties were synthesized from the predicted nontransmembrane sequence to generate antibodies in rabbits. Western blots show that this protein, which we have termed "mitoNEET," is located in the mitochondrial fraction of rodent brain, liver, and skeletal muscle, showing the identical subcellular location and migration on SDS-PAGE as the protein cross-linked specifically by the thiazolidinedione photoprobe. The protein exists in low levels in preadipocytes, and expression increases exponentially in differentiated adipocytes. The synthetic protein bound to solid phase associated with a complex of solubilized mitochondrial proteins, including the trifunctional {beta}-oxidation protein. It is possible that thiazolidinedione modification of the function of the mitochondrial target may contribute to lipid lowering and/or antidiabetic actions. PUBLICATION ABSTRACT
Nanowire surface conduction channels have been fabricated and tested based on self-assembled Si nanowires (SiNWs) synthesized via VLS processing. Conduction channel formation utilized W and Ni ...silicidation. SiNWs were directly grown on silicon substrates via vapor-liquid-solid (VLS) growth process. The diameters of the SiNW templates ranged from approximately 5 to 120 nm. Nanowire synthesis via VLS growth was carried out using a SiH 4 /Ar mixture at 500°C. TEM analysis confirmed crystalline VLS SiNWs. Ni evaporation and Ni and W atomic layer deposition (ALD) and post-deposition thermal processing were carried out for silicide formation. TEM-EDS results showed that ALD W was conformally deposited on the surface of SiNWs. In contrast, e-beam evaporated Ni was asymmetrically deposited on the template nanowire although the resultant silicide was nearly symmetric. Conformal Ni deposition and silicidation was successfully performed, however, using Ni ALD processing. Silicide nanowires were dispensed on Au-patterned Si wafers for electrical characterization and exhibited an improvement in electrical conductivity of eight orders of magnitude compared with that of as-grown VLS silicon nanowires.
Tooth replacement rate is an important contributor to feeding ecology for polyphyodont animals. Dinosaurs exhibit a wide range of tooth replacement rates, mirroring their diverse craniofacial ...specializations, but little is known about broad-scale allometric or evolutionary patterns within the group. In the current broad but sparse dinosaurian sample, only three non-avian theropod tooth replacement rates have been estimated. We estimated tooth formation and replacement rates in three additional non-avian theropod dinosaurs, the derived latest Cretaceous abelisaurid Majungasaurus and the more generalized Late Jurassic Allosaurus and Ceratosaurus. We created the largest dental histological and CT dataset for any theropod dinosaur, sectioning and scanning over a dozen toothed elements of Majungasaurus and several additional elements from the other two genera. Using this large sample, we created models of tooth formation time that allow for theropod replacement rates to be estimated non-destructively. In contrast to previous results for theropods, we found high tooth replacement rates in all three genera, with Allosaurus and Ceratosaurus rates of ~100 days and 56 days for Majungasaurus. The latter rate is on par with those of derived herbivorous dinosaurs including some neosauropods, hadrosaurids, and ceratopsians. This elevated rate may be a response to high rates of tooth wear in Majungasaurus. Within Dinosauria, there is no relationship between body mass and tooth replacement rate and no trends in replacement rate over time. Rather, tooth replacement rate is clade-specific, with elevated rates in abelisaurids and diplodocoids and lower rates in coelurosaurs.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Glucagon is released from pancreatic α-cells to activate pathways that raise blood glucose. Its secretion is regulated by α-cell-intrinsic glucose sensing and paracrine control through insulin and ...somatostatin. To understand the inadequately high glucagon levels that contribute to hyperglycemia in type-2 diabetes (T2D), we analyzed granule behavior, exocytosis and membrane excitability in α-cells of 68 non-diabetic and 21 T2D human donors. We report that exocytosis is moderately reduced in α-cells of T2D donors, without changes in voltage-dependent ion currents or granule trafficking. Dispersed α-cells have a non-physiological V-shaped dose response to glucose, with maximal exocytosis at hyperglycemia. Within intact islets, hyperglycemia instead inhibits α-cell exocytosis, but not in T2D or when paracrine inhibition by insulin or somatostatin is blocked. Surface expression of somatostatin-receptor-2 is reduced in T2D, suggesting a mechanism for the observed somatostatin resistance. Thus, elevated glucagon in human T2D may reflect α-cell insensitivity to paracrine inhibition at hyperglycemia.
In 2021, two guidelines were introduced with the purpose of increasing cities’ tree canopy coverage (TCC): Konijnendijk’s 3–30–300 rule, where 30 represents the goal to achieve at least 30 % TCC, and ...the Swedish Environmental Protection Agency’s (SEPA) guideline, aiming for all Swedish cities to increase their TCC by two percentage points (%pts) within a period of 10 years. While these ambitious goals are positive, not least from a sustainability perspective, there is a lack of research on whether these goals are feasible and how to reach them in practice. The overall TCC in Uppsala, Sweden’s fourth largest city, is 28 %, with considerably lower TCC in the eastern parts of the city. In this study, we will investigate, and visualise, how a 2 %pts increase as well as 30 % TCC could be achieved in two areas in eastern Uppsala: Fålhagen, a residential area, and Boländerna, a commercial and industrial area. We used geographical information systems (GIS) and a scenario approach to calculate the number of trees needed, and possible locations for them, to achieve a 2 %pts increase or the 30 % TCC goal. The results show that an increase of 2 %pts seems possible in both areas, particularly if the municipality and private property owners collaborate. However, it is difficult to estimate the time needed until the canopies of the proposed trees have become large enough to reach the 2 %pts increase. It does not seem likely to reach 30 % TCC in eastern Uppsala with today’s land use. To be able to reach the goals presented in this paper, it seems necessary to include them in municipality policies. Perhaps Konijnendijk’s and SEPA’s guidelines can be starting points for such policies and applied as rules-of-thumb rather than applicable planning tools.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Transplantation of pancreatic islet cells derived from human pluripotent stem cells is a promising treatment for diabetes. Despite progress in the generation of stem-cell-derived islets (SC-islets), ...no detailed characterization of their functional properties has been conducted. Here, we generated functionally mature SC-islets using an optimized protocol and benchmarked them comprehensively against primary adult islets. Biphasic glucose-stimulated insulin secretion developed during in vitro maturation, associated with cytoarchitectural reorganization and the increasing presence of alpha cells. Electrophysiology, signaling and exocytosis of SC-islets were similar to those of adult islets. Glucose-responsive insulin secretion was achieved despite differences in glycolytic and mitochondrial glucose metabolism. Single-cell transcriptomics of SC-islets in vitro and throughout 6 months of engraftment in mice revealed a continuous maturation trajectory culminating in a transcriptional landscape closely resembling that of primary islets. Our thorough evaluation of SC-islet maturation highlights their advanced degree of functionality and supports their use in further efforts to understand and combat diabetes.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
This review article presents a description of contemporary developments and findings related to the different elements needed in future 4th generation district heating systems (4GDH). Unlike the ...first three generations of district heating, the development of 4GDH involves meeting the challenge of more energy efficient buildings as well as the integration of district heating into a future smart energy system based on renewable energy sources. Following a review of recent 4GDH research, the article quantifies the costs and benefits of 4GDH in future sustainable energy systems. Costs involve an upgrade of heating systems and of the operation of the distribution grids, while benefits are lower grid losses, a better utilization of low-temperature heat sources and improved efficiency in the production compared to previous district heating systems. It is quantified how benefits exceed costs by a safe margin with the benefits of systems integration being the most important.
•Provides a review of 4th Generation District Heating (4GDH) in scientific papers.•Shows how 4GDH is an important integrated part of future sustainable energy systems.•Quantifies costs and benefits of 4GDH in a future sustainable energy system.•Shows how benefits exceed costs by a safe margin.•Shows the significant benefits of systems integration.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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