| 1. |
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| 2. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 3. |
- Breznau, Nate, et al.
(författare)
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Observing many researchers using the same data and hypothesis reveals a hidden universe of uncertainty
- 2022
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 119:44
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Tidskriftsartikel (refereegranskat)abstract
- This study explores how researchers analytical choices affect the reliability of scientific findings. Most discussions of reliability problems in science focus on systematic biases. We broaden the lens to emphasize the idiosyncrasy of conscious and unconscious decisions that researchers make during data analysis. We coordinated 161 researchers in 73 research teams and observed their research decisions as they used the same data to independently test the same prominent social science hypothesis: that greater immigration reduces support for social policies among the public. In this typical case of social science research, research teams reported both widely diverging numerical findings and substantive conclusions despite identical start conditions. Researchers expertise, prior beliefs, and expectations barely predict the wide variation in research outcomes. More than 95% of the total variance in numerical results remains unexplained even after qualitative coding of all identifiable decisions in each teams workflow. This reveals a universe of uncertainty that remains hidden when considering a single study in isolation. The idiosyncratic nature of how researchers results and conclusions varied is a previously underappreciated explanation for why many scientific hypotheses remain contested. These results call for greater epistemic humility and clarity in reporting scientific findings.
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| 4. |
- Kehoe, Laura, et al.
(författare)
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Make EU trade with Brazil sustainable
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 5. |
- Palsdottir, Vilborg, 1979, et al.
(författare)
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Interactions Between the Gravitostat and the Fibroblast Growth Factor System for the Regulation of Body Weight
- 2019
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Ingår i: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 160:5, s. 1057-1064
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Tidskriftsartikel (refereegranskat)abstract
- Both fibroblast growth factors (FGFs), by binding to FGF receptors (FGFRs), and activation of the gravitostat, by artificial loading, decrease the body weight (BW). Previous studies demonstrate that both the FGF system and loading have the capacity to regulate BW independently of leptin. The aim of the current study was to determine the possible interactions between the effect of increased loading and the FGF system for the regulation of BW. We observed that the BW-reducing effect of increased loading was abolished in mice treated with a monoclonal antibody directed against FGFR1c, suggesting interactions between the two systems. As serum levels of endocrine FGF21 and hepatic FGF21 mRNA were increased in the loaded mice compared with the control mice, we first evaluated the loading response in FGF21 over expressing mice with constant high FGF21 levels. Leptin treatment, but not increased loading, decreased the BW in the FGF21-overexpressing mice, demonstrating that specifically the loading effect is attenuated in the presence of high activity in the FGF system. However, as FGF21 knockout mice displayed a normal loading response on BW, FGF21 is neither mediating nor essential for the loading response. In conclusion, the BW-reducing effect of increased loading but not of leptin treatment is blocked by high activity in the FGF system. We propose that both the gravitostat and the FGF system regulate BW independently of leptin and that pharmacologically enhanced activity in the FGF system reduces the sensitivity of the grayitostat.
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| 6. |
- Albuquerque, Daniel, et al.
(författare)
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LES simulation of oscillating natural ventilation driven by vortex shedding in isolated buildings
- 2020
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Ingår i: Proceedings of Building Simulation 2019: 16th Conference of IBPSA. - : IBPSA. - 9781775052012 ; , s. 644-649
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Konferensbidrag (refereegranskat)abstract
- A recently published study presented a new type of natural ventilation (NV) flow, named pumping ventilation. The oscilatory mechanism of vortex shedding that occurs at the wake region of an isolated building drives this new type of ventilation in rooms with two (or more) openings facing the leeward or windward side of an isolated building. This paper presents a validated Large Eddy Simulation (LES) study of oscillating/pumping NV in an isolated building using three different separations (s') between its two windows. LES is validated using an experimental database from measurements performed at the University of Gavle boundary layer wind tunnel (WT). The measurements use a cubic model with 0.45m side representing a three-story building at a 1/20 scale that allows the use of bottom-hung windows. LES results show a good agreement with the measured non-dimensional ventilation rates. A dimensionless analysis shows the dominant frequencies of the pumping flow, are close to the Strouhal frequency.
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| 7. |
- Albuquerque, Daniel P., et al.
(författare)
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Experimental and numerical investigation of pumping ventilation on the leeward side of a cubic building
- 2020
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Ingår i: Building and Environment. - : Elsevier. - 0360-1323 .- 1873-684X. ; 179
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Tidskriftsartikel (refereegranskat)abstract
- Unstable interaction between shear layers that form in the wake of an isolated building exposed to wind can drive natural pumping ventilation in windward and leeward facing rooms with two or more horizontally separated openings. This paper presents an experimental and numerical study of pumping ventilation in a three-story cubic building with two leeward openings in its middle floor. Reduced-scaled measurements were performed in the University of Gävle atmospheric-boundary-layer wind tunnel. The ventilation mechanism was investigated using smoke visualization, hot wire anemometry and particle image velocimetry. Effective ventilation rates were obtained using a tracer gas decay method. Experimental results confirmed that pumping ventilation is a 3D oscillatory unstable phenomenon with periodic behavior over several oscillation cycles. Measured flowrates show a linear relation between the effective ventilation rate and window separation. The numerical simulations used two turbulence modeling approaches: unsteady Reynolds-averaged Navier-Stokes (URANS) and large eddy simulation (LES). Both URANS and LES could predict vortex shedding frequency with an error below 5%. LES showed a good agreement with the measured ventilation rates, with an error below 10%, while URANS underestimated ventilation rates by at least 40%. The ventilation efficiency, obtained by LES, ranged between 0.60 and 0.75 (for the case with larger window separation). The results show that LES may be a suitable simulation approach for pumping ventilation. In contrast, URANS cannot simulate pumping ventilation.
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| 8. |
- Améen, Caroline, 1975, et al.
(författare)
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Activation of peroxisome proliferator-activated receptor alpha increases the expression and activity of microsomal triglyceride transfer protein in the liver
- 2005
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Ingår i: J Biol Chem. ; 280:2, s. 1224-9
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Tidskriftsartikel (refereegranskat)abstract
- Microsomal triglyceride transfer protein (MTP) is rate-limiting in the assembly and secretion of lipoproteins containing apolipoprotein (apo) B. Previously we demonstrated that Wy 14,643 (Wy), a peroxisome proliferator-activated receptor (PPAR) alpha agonist, increases apoB-100 secretion despite decreased triglyceride synthesis. In this study, we sought to determine whether PPARalpha activation increases MTP expression and activity. Treatment with Wy increased hepatic MTP expression and activity in rats and mice and increased MTP expression in primary cultures of rat and mouse hepatocytes. Addition of actinomycin D blocked this increase and the MTP promoter (-136 to +67) containing a conserved DR1 element was activated by Wy, showing that PPARalpha activates transcription of the gene. Wy did not affect MTP expression in the intestine or in cultured hepatocytes from PPARalpha-null mice. A retinoid X receptor agonist (9-cis-retinoic acid), but not a PPARgamma agonist (rosiglitazone), increased MTP mRNA expression in cultured hepatocytes from both wild type and PPARalpha-null mice. In rat hepatocytes incubated with Wy, MTP mRNA levels increased between 6 and 24 h, and MTP protein expression and apoB-100 secretion increased between 24 and 72 h. In conclusion, PPARalpha activation stimulates hepatic MTP expression via increased transcription of the Mtp gene. This effect is paralleled by a change in apoB-100 secretion, indicating that the effect of Wy on apoB-100 secretion is mediated by increased expression of MTP.
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| 9. |
- Améen, Caroline, 1975, et al.
(författare)
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Effects of gender and GH secretory pattern on sterol regulatory element-binding protein-1c and its target genes in rat liver.
- 2004
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Ingår i: American journal of physiology. Endocrinology and metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 287:6
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Tidskriftsartikel (refereegranskat)abstract
- We investigated whether the sexually dimorphic secretory pattern of growth hormone (GH) in the rat regulates hepatic gene expression of sterol regulatory element-binding protein-1c (SREBP-1c) and its target genes. SREBP-1c, fatty acid synthase (FAS), and glycerol-3-phosphate acyltransferase (GPAT) mRNA were more abundant in female than in male livers, whereas acetyl-CoA carboxylase-1 (ACC1) and stearoyl-CoA desaturase-1 (SCD-1) were similarly expressed in both sexes. Hypophysectomized female rats were given GH as a continuous infusion or as two daily injections for 7 days to mimic the female- and male-specific GH secretory patterns, respectively. The female pattern of GH administration increased the expression of SREBP-1c, ACC1, FAS, SCD-1, and GPAT mRNA, whereas the male pattern of GH administration increased only SCD-1 mRNA. FAS and SCD-1 protein levels were regulated in a similar manner by GH. Incubation of primary rat hepatocytes with GH increased SCD-1 mRNA levels and decreased FAS and GPAT mRNA levels but had no effect on SREBP-1c mRNA. GH decreased hepatic liver X receptor-alpha (LXRalpha) mRNA levels both in vivo and in vitro. Feminization of the GH plasma pattern in male rats by administration of GH as a continuous infusion decreased insulin sensitivity and increased expression of FAS and GPAT mRNA but had no effect on SREBP-1c, ACC1, SCD-1, or LXRalpha mRNA. In conclusion, FAS and GPAT are specifically upregulated by the female secretory pattern of GH. This regulation is not a direct effect of GH on hepatocytes and does not involve changed expression of SREBP-1c or LXRalpha mRNA but is associated with decreased insulin sensitivity.
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| 10. |
- Azzu, V., et al.
(författare)
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Suppression of insulin-induced gene 1 (INSIG1) function promotes hepatic lipid remodelling and restrains NASH progression
- 2021
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Ingår i: Molecular Metabolism. - : Elsevier BV. - 2212-8778. ; 48
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Non-alcoholic fatty liver disease (NAFLD) is a silent pandemic associated with obesity and the metabolic syndrome, and also increases cardiovascular- and cirrhosis-related morbidity and mortality. A complete understanding of adaptive compensatory metabolic programmes that modulate non-alcoholic steatohepatitis (NASH) progression is lacking. Methods and results: Transcriptomic analysis of liver biopsies in patients with NASH revealed that NASH progression is associated with rewiring of metabolic pathways, including upregulation of de novo lipid/cholesterol synthesis and fatty acid remodelling. The modulation of these metabolic programmes was achieved by activating sterol regulatory element-binding protein (SREBP) transcriptional networks; however, it is still debated whether, in the context of NASH, activation of SREBPs acts as a pathogenic driver of lipotoxicity, or rather promotes the biosynthesis of protective lipids that buffer excessive lipid accumulation, preventing inflammation and fibrosis. To elucidate the pathophysiological role of SCAP/SREBP in NASH and wound-healing response, we used an Insig1 deficient (with hyper-efficient SREBPs) murine model challenged with a NASH-inducing diet. Despite enhanced lipid and cholesterol biosynthesis, Insig1 KO mice had similar systemic metabolism and insulin sensitivity to Het/WT littermates. Moreover, activating SREBPs resulted in remodelling the lipidome, decreased hepatocellular damage, and improved wound-healing responses. Conclusions: Our study provides actionable knowledge about the pathways and mechanisms involved in NAFLD pathogenesis, which may prove useful for developing new therapeutic strategies. Our results also suggest that the SCAP/SREBP/INSIG1 trio governs transcriptional programmes aimed at protecting the liver from lipotoxic insults in NASH. (C) 2021 Published by Elsevier GmbH. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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| 11. |
- Bjursell, Mikael, 1977, et al.
(författare)
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Opposing effects of adiponectin receptors 1 and 2 on energy metabolism
- 2007
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Ingår i: DIABETES. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 56:3, s. 583-593
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Tidskriftsartikel (refereegranskat)abstract
- The adipocyte-derived hormone adiponectin regulates glucose and lipid metabolism and influences the risk for developing obesity, type 2 diabetes, and cardiovascular disease. Adiponectin binds to two different seven-transmembrane domain receptors termed AdipoR1 and AdipoR2. To study the physiological importance of these receptors, AdipoR1 gene knockout mice (AdipoR1−/−) and AdipoR2 gene knockout mice (AdipoR2−/−) were generated. AdipoR1−/− mice showed increased adiposity associated with decreased glucose tolerance, spontaneous locomotor activity, and energy expenditure. However, AdipoR2−/− mice were lean and resistant to high-fat diet–induced obesity associated with improved glucose tolerance and higher spontaneous locomotor activity and energy expenditure and reduced plasma cholesterol levels. Thus, AdipoR1 and AdipoR2 are clearly involved in energy metabolism but have opposing effects.
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| 12. |
- Bohlooly-Yeganeh, Mohammad, 1966, et al.
(författare)
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Growth hormone overexpression in the central nervous system results in hyperphagia-induced obesity associated with insulin resistance and dyslipidemia.
- 2005
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Ingår i: Diabetes. - 0012-1797 .- 1939-327X. ; 54:1, s. 51-62
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Tidskriftsartikel (refereegranskat)abstract
- It is well known that peripherally administered growth hormone (GH) results in decreased body fat mass. However, GH-deficient patients increase their food intake when substituted with GH, suggesting that GH also has an appetite stimulating effect. Transgenic mice with an overexpression of bovine GH in the central nervous system (CNS) were created to investigate the role of GH in CNS. This study shows that overexpression of GH in the CNS differentiates the effect of GH on body fat mass from that on appetite. The transgenic mice were not GH-deficient but were obese and showed increased food intake as well as increased hypothalamic expression of agouti-related protein and neuropeptide Y. GH also had an acute effect on food intake following intracerebroventricular injection of C57BL/6 mice. The transgenic mice were severely hyperinsulinemic and showed a marked hyperplasia of the islets of Langerhans. In addition, the transgenic mice displayed alterations in serum lipid and lipoprotein levels and hepatic gene expression. In conclusion, GH overexpression in the CNS results in hyperphagia-induced obesity indicating a dual effect of GH with a central stimulation of appetite and a peripheral lipolytic effect.
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| 13. |
- Bortolini, Giacomo, 1996-, et al.
(författare)
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The spatially resolved star formation history of the dwarf spiral galaxy NGC 5474
- 2024
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Ingår i: Monthly notices of the Royal Astronomical Society. - 0035-8711 .- 1365-2966. ; 527:3, s. 5339-5355
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Tidskriftsartikel (refereegranskat)abstract
- We study the resolved stellar populations and derive the star formation history of NGC 5474, a peculiar star-forming dwarf galaxy at a distance of ∼7 Mpc, using Hubble Space Telescope Advanced Camera for Surveys data from the Legacy Extragalactic UV Survey (LEGUS) programme. We apply an improved colour–magnitude diagram fitting technique based on the code SFERA and use the latest PARSEC–COLIBRI stellar models. Our results are the following. The off-centre bulge-like structure, suggested to constitute the bulge of the galaxy, is dominated by star formation (SF) activity initiated 14 Gyr ago and lasted at least up to 1 Gyr ago. Nevertheless, this component shows clear evidence of prolonged SF activity (lasting until ∼10 Myr ago). We estimate the total stellar mass of the bulge-like structure to be (5.0 ± 0.3) × 108 M⊙. Such a mass is consistent with published suggestions that this structure is in fact an independent system orbiting around and not within NGC 5474’s disc. The stellar overdensity located to the South–West of the bulge-like structure shows a significant SF event older than 1 Gyr, while it is characterized by two recent peaks of SF, around ∼10 and ∼100 Myr ago. In the last Gyr, the behaviour of the stellar disc is consistent with what is known in the literature as ‘gasping’. The synchronized burst at 10–35 Myr in all components might hint to the recent gravitational interaction between the stellar bulge-like structure and the disc of NGC 5474.
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| 14. |
- Calzetti, Daniela, et al.
(författare)
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Revisiting Attenuation Curves : The Case of NGC 3351
- 2021
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 913:1
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Tidskriftsartikel (refereegranskat)abstract
- Multiwavelength images from the far-UV (similar to 0.15 mu m) to the submillimeter of the central region of the galaxy NGC 3351 are analyzed to constrain its stellar populations and dust attenuation. Despite hosting a similar to 1 kpc circumnuclear starburst ring, NGC 3351 deviates from the IRX-beta relation, the relation between the infrared-to-UV luminosity ratio and the UV continuum slope beta that other starburst galaxies follow. To understand the reason for the deviation, we leverage the high angular resolution of archival near-UV-to-near-IR Hubble Space Telescope images to divide the ring into similar to 60-180 pc size regions and model each individually. We find that the UV slope of the combined intrinsic (dust-free) stellar populations in the central region is redder than what is expected for a young model population. This is due to the region's complex star formation history, which boosts the near-UV emission relative to the far-UV. The resulting net attenuation curve has a UV slope that lies between those of the starburst attenuation curve (Calzetti et al. 2000) and the Small Magellanic Cloud extinction curve; the total-to-selective attenuation value, R'(V) = 4.93, is larger than both. As found for other star-forming galaxies, the stellar continuum of NGC 3351 is less attenuated than the ionized gas, with E(B - V)(star) = 0.40 E(B - V)(gas). The combination of the red intrinsic stellar population and the new attenuation curve fully accounts for the location of the central region of NGC 3351 on the IRX-beta diagram. Thus, the observed characteristics result from the complex mixture of stellar populations and dust column densities in the circumnuclear region. Despite being a sample of one, these findings highlight the difficulty of defining attenuation curves of general applicability outside the regime of centrally concentrated starbursts.
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| 15. |
- Carlsson, Björn, et al.
(författare)
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Review article: the emerging role of genetics in precision medicine for patients with non-alcoholic steatohepatitis.
- 2020
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Ingår i: Alimentary pharmacology & therapeutics. - : Wiley. - 1365-2036 .- 0269-2813. ; 51:12, s. 1305-1320
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Forskningsöversikt (refereegranskat)abstract
- Non-alcoholic steatohepatitis (NASH) is a severe form of non-alcoholic fatty liver disease (NAFLD) characterised by liver fat accumulation, inflammation and progressive fibrosis. Emerging data indicate that genetic susceptibility increases risks of NAFLD, NASH and NASH-related cirrhosis.To review NASH genetics and discuss the potential for precision medicine approaches to treatment.PubMed search and inclusion of relevant literature.Single-nucleotide polymorphisms in PNPLA3, TM6SF2, GCKR, MBOAT7 and HSD17B13 are clearly associated with NASH development or progression. These genetic variants are common and have moderate-to-large effect sizes for development of NAFLD, NASH and hepatocellular carcinoma (HCC). The genes play roles in lipid remodelling in lipid droplets, hepatic very low-density lipoprotein (VLDL) secretion and de novo lipogenesis. The PNPLA3 I148M variant (rs738409) has large effects, with approximately twofold increased odds of NAFLD and threefold increased odds of NASH and HCC per allele. Obesity interacts with PNPLA3 I148M to elevate liver fat content and increase rates of NASH. Although the isoleucine-to-methionine substitution at amino acid position 148 of the PNPLA3 enzyme inactivates its lipid remodelling activity, the effect of PNPLA3 I148M results from trans-repression of another lipase (ATGL/PNPLA2) by sequestration of a shared cofactor (CGI-58/ABHD5), leading to decreased hepatic lipolysis and VLDL secretion. In homozygous Pnpla3 I148M knock-in rodent models of NAFLD, targeted PNPLA3 mRNA knockdown reduces hepatic steatosis, inflammation and fibrosis.The emerging genetic and molecular understanding of NASH paves the way for novel interventions, including precision medicines that can modulate the activity of specific genes associated with NASH.
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| 16. |
- Carrilho da Graça, Guilherme, et al.
(författare)
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Pumping ventilation of corner and single sided rooms with two openings
- 2021
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Ingår i: Building and Environment. - : Elsevier. - 0360-1323 .- 1873-684X. ; 205
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Tidskriftsartikel (refereegranskat)abstract
- Corner rooms with two or more open windows in perpendicular facades can be naturally ventilated in cross-ventilation or pumping ventilation. These two airflow regimes also occur in rooms with two openings in the same façade, in the form of single sided pumping or cross sided ventilation. This paper presents an experimental and numerical simulation study of the scale and occurrence of these two flow regimes for rooms in a rectangular building exposed to wind. Flow visualization and tracer gas measurement of effective airflow were performed in an atmospheric boundary layer wind tunnel using a rectangular model of a three-story building (1/20 scale) with a ventilated middle floor. Experimental results show that pumping ventilation occurs when the wind is perpendicular to the façade (single sided rooms) or aligned with the building corner (corner rooms). In addition to these two perfectly aligned wind directions, pumping also occurs for a range of incoming wind angles: ±19° for single sided; and ±9° for corner rooms. As a result, for isolated rectangular buildings that have, at least, one single sided and two corner rooms in each facade, pumping ventilation can potentially occur in two or more rooms for 62 % of incoming wind directions. To investigate the transition between steady cross-ventilation and unsteady pumping ventilation, three-dimensional computational fluid dynamics large eddy simulations were performed to obtain wind generated pressures in the ventilation openings. Results show that the transition from cross-ventilation to pumping occurs when the steady pressure becomes smaller than the unsteady component. These results are used to develop a pressure based simplified model for corner ventilation that can predict effective airflow from external wind generated pressures with an average error below 10.2 %. © 2021 Elsevier Ltd
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| 17. |
- de Bem, Andreza Fabro, et al.
(författare)
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Animal Models of Metabolic Disorders in the Study of Neurodegenerative Diseases : An Overview
- 2021
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Ingår i: Frontiers in Neuroscience. - : Frontiers Media SA. - 1662-4548 .- 1662-453X. ; 14
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Forskningsöversikt (refereegranskat)abstract
- The incidence of metabolic disorders, as well as of neurodegenerative diseases—mainly the sporadic forms of Alzheimer’s and Parkinson’s disease—are increasing worldwide. Notably, obesity, diabetes, and hypercholesterolemia have been indicated as early risk factors for sporadic forms of Alzheimer’s and Parkinson’s disease. These conditions share a range of molecular and cellular features, including protein aggregation, oxidative stress, neuroinflammation, and blood-brain barrier dysfunction, all of which contribute to neuronal death and cognitive impairment. Rodent models of obesity, diabetes, and hypercholesterolemia exhibit all the hallmarks of these degenerative diseases, and represent an interesting approach to the study of the phenotypic features and pathogenic mechanisms of neurodegenerative disorders. We review the main pathological aspects of Alzheimer’s and Parkinson’s disease as summarized in rodent models of obesity, diabetes, and hypercholesterolemia.
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| 18. |
- Disney-Hogg, Linden, et al.
(författare)
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Impact of atopy on risk of glioma : a Mendelian randomisation study
- 2018
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Ingår i: BMC Medicine. - : BioMed Central. - 1741-7015. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- Background: An inverse relationship between allergies with glioma risk has been reported in several but not all epidemiological observational studies. We performed an analysis of genetic variants associated with atopy to assess the relationship with glioma risk using Mendelian randomisation (MR), an approach unaffected by biases from temporal variability and reverse causation that might have affected earlier investigations.Methods: Two-sample MR was undertaken using genome-wide association study data. We used single nucleotide polymorphisms (SNPs) associated with atopic dermatitis, asthma and hay fever, IgE levels, and self-reported allergy as instrumental variables. We calculated MR estimates for the odds ratio (OR) for each risk factor with glioma using SNP-glioma estimates from 12,488 cases and 18,169 controls, using inverse-variance weighting (IVW), maximum likelihood estimation (MLE), weighted median estimate (WME) and mode-based estimate (MBE) methods. Violation of MR assumptions due to directional pleiotropy were sought using MR-Egger regression and HEIDI-outlier analysis.Results: Under IVW, MLE, WME and MBE methods, associations between glioma risk with asthma and hay fever, self-reported allergy and IgE levels were non-significant. An inverse relationship between atopic dermatitis and glioma risk was found by IVW (OR 0.96, 95% confidence interval (CI) 0.93-1.00, P = 0.041) and MLE (OR 0.96, 95% CI 0.94-0.99, P = 0.003), but not by WME (OR 0.96, 95% CI 0.91-1.01, P = 0.114) or MBE (OR 0.97, 95% CI 0.92-1.02, P = 0.194).Conclusions: Our investigation does not provide strong evidence for relationship between atopy and the risk of developing glioma, but findings do not preclude a small effect in relation to atopic dermatitis. Our analysis also serves to illustrate the value of using several MR methods to derive robust conclusions.
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| 19. |
- Du, Jiaying, et al.
(författare)
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Perception of Delay in Computer Input Devices Establishing a Baseline for Signal Processing of Motion Sensor Systems
- 2016
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Ingår i: The 3rd EAI International Conference on IoT Technologies for HealthCare HealthyIoT'16. - Västeraås, Sweden : Springer International Publishing. ; , s. 107-112
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Konferensbidrag (refereegranskat)abstract
- New computer input devices in healthcare applications using small embedded sensors need firmware filters to run smoothly and to provide a better user experience. Therefore, it has to be investigated how much delay can be tolerated for signal processing before the users perceive a delay when using a computer input device. This paper is aimed to find out a threshold of unperceived delay by performing user tests with 25 participants. A communication retarder was used to create delays from 0 to 100 ms between a receiving computer and three different USB-connected computer input devices. A wired mouse, a wifi mouse and a head-mounted mouse were used as input devices. The results of the user tests show that delays up to 50ms could be tolerated and are not perceived as delay, or depending on the used device still perceived as acceptable.
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| 20. |
- Du, Jiaying, et al.
(författare)
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The effects of perceived USB-delay for sensor and embedded system development
- 2016
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Ingår i: Proceedings of the Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBSVolume 2016. - 9781457702204 ; , s. 2492-2495
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Konferensbidrag (refereegranskat)abstract
- Perceiving delay in computer input devices is a problem which gets even more eminent when being used in healthcare applications and/or in small, embedded systems. Therefore, the amount of delay found as acceptable when using computer input devices was investigated in this paper. A device was developed to perform a benchmark test for the perception of delay. The delay can be set from 0 to 999 milliseconds (ms) between a receiving computer and an available USB-device. The USB-device can be a mouse, a keyboard or some other type of USB-connected input device. Feedback from performed user tests with 36 people form the basis for the determination of time limitations for the USB data processing in microprocessors and embedded systems without users' noticing the delay. For this paper, tests were performed with a personal computer and a common computer mouse, testing the perception of delays between 0 and 500 ms. The results of our user tests show that perceived delays up to 150 ms were acceptable and delays larger than 300 ms were not acceptable at all.
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| 21. |
- Dutta, Tanmoy, 1998, et al.
(författare)
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Mitochondrial amidoxime-reducing component 1 p.Ala165Thr increases protein degradation mediated by the proteasome.
- 2024
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Ingår i: Liver international : official journal of the International Association for the Study of the Liver. - 1478-3223 .- 1478-3231. ; 44:5, s. 1219-1232
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Tidskriftsartikel (refereegranskat)abstract
- Metabolic dysfunction-associated steatotic liver disease (MASLD) is a global health concern with no effective and specific drug treatment available. The rs2642438 minor allele in mitochondrial amidoxime-reducing component 1 (MARC1) results in an aminoacidic substitution (p.Ala165Thr) and associates with protection against MASLD. However, the mechanisms behind this protective effect are unknown. In this study, we examined the consequences of this aminoacidic substitution on protein stability and subcellular localization.We overexpressed the human MARC1 A165 (wild-type) or 165T (mutant) invivo in mice and invitro in human hepatoma cells (HepG2 and HuH-7), generated several mutants at position 165 by insitu mutagenesis and then examined protein levels. We also generated HepG2 cells stably overexpressing MARC1 A165 or 165T to test the effect of this substitution on MARC1 subcellular localization.MARC1 165T overexpression resulted in lower protein levels than A165 both invivo and invitro. Similarly, any mutant at position 165 showed lower protein levels compared to the wild-type protein. We showed that the 165T mutant protein is polyubiquitinated and its degradation is accelerated through lysine-48 ubiquitin-mediated proteasomal degradation. We also showed that the 165T substitution does not affect the MARC1 subcellular localization.This study shows that alanine at position 165 in MARC1 is crucial for protein stability, and the threonine substitution at this position leads to a hypomorphic protein variant due to lower protein levels. Our result supports the notion that lowering hepatic MARC1 protein level may be a successful therapeutic strategy for treating MASLD.
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| 23. |
- Dutton, Edward, 1980-, et al.
(författare)
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The myth of the stupid believer : The negative religiousness-IQ nexus is not on general intelligence (g) and is likely a product of the relations between IQ and Autism Spectrum traits
- 2020
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Ingår i: Journal of religion and health. - : Springer. - 0022-4197 .- 1573-6571. ; 59:3, s. 1567-1579
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Tidskriftsartikel (refereegranskat)abstract
- Numerous studies have found a negative relationship between religiousness and IQ. It is in the region of - 0.2, according to meta-analyses. The reasons for this relationship are, however, unknown. It has been suggested that higher intelligence leads to greater attraction to science, or that it helps to override evolved cognitive dispositions such as for religiousness. Either way, such explanations assume that the religion-IQ nexus is on general intelligence (g), rather than some subset of specialized cognitive abilities. In other words, they assume it is a Jensen effect. Two large datasets comparing groups with different levels of religiousness show that their IQ differences are not on g and must, therefore, be attributed to specialized abilities. An analysis of the specialized abilities on which the religious and non-religious groups differ reveals no clear pattern. We cautiously suggest that this may be explicable in terms of autism spectrum disorder traits among people with high IQ scores, because such traits are negatively associated with religiousness.
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| 24. |
- Edvardsson, Ulrika, 1967, et al.
(författare)
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PPARalpha activation increases triglyceride mass and adipose differentiation-related protein in hepatocytes.
- 2006
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Ingår i: Journal of lipid research. - 0022-2275. ; 47:2, s. 329-40
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Tidskriftsartikel (refereegranskat)abstract
- Adipose differentiation-related protein (ADRP) is a lipid droplet-associated protein that is expressed in various tissues. In mice treated with the peroxisome proliferator-activated receptor alpha (PPARalpha) agonist Wy14,643 (Wy), hepatic mRNA and protein levels of ADRP as well as hepatic triglyceride content increased. Also in primary mouse hepatocytes, Wy increased ADRP expression and intracellular triglyceride mass. The triglyceride mass increased in spite of unchanged triglyceride biosynthesis and increased palmitic acid oxidation. However, Wy incubation decreased the secretion of newly synthesized triglycerides, whereas apolipoprotein B secretion increased. Thus, decreased availability of triglycerides for VLDL assembly could help to explain the cellular accumulation of triglycerides after Wy treatment. We hypothesized that this effect could be mediated by increased ADRP expression. Similar to PPARalpha activation, adenovirus-mediated ADRP overexpression in mouse hepatocytes enhanced cellular triglyceride mass and decreased the secretion of newly synthesized triglycerides. In ADRP-overexpressing cells, Wy incubation resulted in a further decrease in triglyceride secretion. This effect of Wy was not attributable to decreased cellular triglycerides after increased fatty acid oxidation because the triglyceride mass in Wy-treated ADRP-overexpressing cells was unchanged. In summary, PPARalpha activation prevents the availability of triglycerides for VLDL assembly and increases hepatic triglyceride content in part by increasing the expression of ADRP.
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