| 1. |
- Abarenkov, Kessy, et al.
(author)
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Annotating public fungal ITS sequences from the built environment according to the MIxS-Built Environment standard – a report from a May 23-24, 2016 workshop (Gothenburg, Sweden)
- 2016
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In: MycoKeys. - : Pensoft Publishers. - 1314-4057 .- 1314-4049. ; 16, s. 1-15
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Journal article (peer-reviewed)abstract
- Recent molecular studies have identified substantial fungal diversity in indoor environments. Fungi and fungal particles have been linked to a range of potentially unwanted effects in the built environment, including asthma, decay of building materials, and food spoilage. The study of the built mycobiome is hampered by a number of constraints, one of which is the poor state of the metadata annotation of fungal DNA sequences from the built environment in public databases. In order to enable precise interrogation of such data – for example, “retrieve all fungal sequences recovered from bathrooms” – a workshop was organized at the University of Gothenburg (May 23-24, 2016) to annotate public fungal barcode (ITS) sequences according to the MIxS-Built Environment annotation standard (http://gensc.org/mixs/). The 36 participants assembled a total of 45,488 data points from the published literature, including the addition of 8,430 instances of countries of collection from a total of 83 countries, 5,801 instances of building types, and 3,876 instances of surface-air contaminants. The results were implemented in the UNITE database for molecular identification of fungi (http://unite.ut.ee) and were shared with other online resources. Data obtained from human/animal pathogenic fungi will furthermore be verified on culture based metadata for subsequent inclusion in the ISHAM-ITS database (http://its.mycologylab.org).
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| 2. |
- Engström-Ruud, Linda, et al.
(author)
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Activation of GFRAL+ neurons induces hypothermia and glucoregulatory responses associated with nausea and torpor.
- 2024
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In: Cell reports. - 2211-1247. ; 43:4
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Journal article (peer-reviewed)abstract
- GFRAL-expressing neurons actuate aversion and nausea, are targets for obesity treatment, and may mediate metformin effects by long-term GDF15-GFRAL agonism. Whether GFRAL+ neurons acutely regulate glucose and energy homeostasis is, however, underexplored. Here, we report that cell-specific activation of GFRAL+ neurons using a variety of techniques causes a torpor-like state, including hypothermia, the release of stress hormones, a shift from glucose to lipid oxidation, and impaired insulin sensitivity, glucose tolerance, and skeletal muscle glucose uptake but augmented glucose uptake in visceral fat. Metabolomic analysis of blood and transcriptomics of muscle and fat indicate alterations in ketogenesis, insulin signaling, adipose tissue differentiation and mitogenesis, and energy fluxes. Our findings indicate that acute GFRAL+ neuron activation induces endocrine and gluco- and thermoregulatory responses associated with nausea and torpor. While chronic activation of GFRAL signaling promotes weight loss in obesity, these results show that acute activation of GFRAL+ neurons causes hypothermia and hyperglycemia.
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| 3. |
- Xia, Ying, et al.
(author)
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Knockout of STE20-type kinase TAOK3 does not attenuate diet-induced NAFLD development in mice
- 2023
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In: Molecular Medicine. - 1076-1551. ; 29:1
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Journal article (peer-reviewed)abstract
- ObjectiveNon-alcoholic fatty liver disease (NAFLD), the primary hepatic consequence of obesity, is affecting about 25% of the global adult population. The aim of this study was to examine the in vivo role of STE20-type protein kinase TAOK3, which has been previously reported to regulate hepatocellular lipotoxicity in vitro, in the development of NAFLD and systemic insulin resistance in the context of obesity.MethodsTaok3 knockout mice and wild-type littermates were challenged with a high-fat diet. Various in vivo tests were performed to characterize the whole-body metabolism. NAFLD progression in the liver, and lipotoxic damage in adipose tissue, kidney, and skeletal muscle were compared between the genotypes by histological assessment, immunofluorescence microscopy, protein and gene expression profiling, and biochemical assays. Intracellular lipid accumulation and oxidative/ER stress were analyzed in cultured human and mouse hepatocytes where TAOK3 was knocked down by small interfering RNA. The expression of TAOK3-related STE20-type kinases was quantified in different organs from high-fat diet-fed Taok3-/- and wild-type mice.ResultsTAOK3 deficiency had no impact on body weight or composition, food consumption, locomotor activity, or systemic glucose or insulin homeostasis in obese mice. Consistently, Taok3-/- mice and wild-type littermates developed a similar degree of high-fat diet-induced liver steatosis, inflammation, and fibrosis, and we detected no difference in lipotoxic damage of adipose tissue, kidney, or skeletal muscle when comparing the two genotypes. In contrast, the silencing of TAOK3 in vitro markedly suppressed ectopic lipid accumulation and metabolic stress in mouse and human hepatocytes. Interestingly, the hepatic mRNA abundance of several TAOK3-related kinases, which have been previously implicated to increase the risk of NAFLD susceptibility, was significantly elevated in Taok3-/-vs. wild-type mice.ConclusionsIn contrast to the in vitro observations, genetic deficiency of TAOK3 in mice failed to mitigate the detrimental metabolic consequences of chronic exposure to dietary lipids, which may be partly attributable to the activation of liver-specific compensation response for the genetic loss of TAOK3 by related STE20-type kinases.
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| 4. |
- Ruud, Johan, 1978-
(author)
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Central Nervous System and Innate Immune Mechanisms for Inflammation- and Cancer-induced Anorexia
- 2012
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Doctoral thesis (other academic/artistic)abstract
- Anyone who has experienced influenza or a bacterial infection knows what it means to be ill. Apart from feeling feverish, experiencing aching joints and muscles, you lose the desire to eat. Anorexia, defined as loss of appetite or persistent satiety leading to reduced energy intake, is a hallmark of acute inflammatory disease. The anorexia is part of the acute phase response, triggered as the result of activation of the innate immune system with concomitant release of inflammatory mediators, which interact with the central nervous system. A chronic condition, and a severe medical problem, that resembles inflammation-induced anorexia is cachexia. Cachexia, which is commonly associated with malignant cancer, is typified as a cytokine-associated metabolic derangement leading to weight loss, mediated by activation of the immune system. Paradoxically, weight loss in cancer patients is often associated with reduced food intake, indicating that the normal coupling of energy intake to body weight is disarranged. Accumulating evidence indicates that inflammation- and cancer-induced anorexia are associated with Toll-like receptor and cycloxygenase (Cox) activation. However, the nature of these pathways is far from understood, and a series of experiments addressing this issue was therefore undertaken.In paper I, we injected Morris hepatoma 7777 cells or vehicle into rats, and we analyzed the distribution pattern of the transcription factor Fos, an index of neuronal activity, in the brainstem. We found that the anorexia and weight loss in tumor-bearing rats were associated with extensive expression of Fos in the area postrema and the general visceral region of the nucleus of the solitary tract in the medulla oblongata, as well as in the external lateral pontine parabrachial nucleus, and that the magnitude of the Fos expression correlated positively with tumor weight and negatively with body weight development, respectively. The Fos expression occurred without any obvious signs of peripheral or central inflammation, and was not secondary to alterations in body weight or reduced food intake. Thus, in paper I, we found a tumor-elicited activation of three interconnected autonomic structures, which integrate and transmit afferent visceral and sensory information, and which are known to play vital roles for energy homeostasis.In paper II we evaluated the effects of tumor growth on feeding behaviour in mice as well as the role of Cox-1 and Cox-2, and prostaglandin E2 (PGE2) for the decreased appetite. We implanted mice with a MCG 101 tumor, which resulted in decreased meal frequency but not decreased meal size or meal duration. We found that indomethacin, a non-selective Cox-inhibitor, attenuated the anorexia as well as the tumor growth. When given acutely at manifest anorexia, Cox-inhibitors rescued the loss of appetite and prevented body weight loss without affecting tumor weight. Despite Cox-2 gene induction in the brain and Cox-2 protein induction in cells associated to the blood-brain barrier in tumor-bearing mice, a Cox-2 inhibitor had no impact on tumor-induced anorexia. By contrast, manipulating Cox-1 activity with a selective Cox-1 inhibitor delayed the onset of the anorexic response. Tumor growth was associated with large elevations in plasma PGE2, a response that was prevented by indomethacin. In contrast, however, PGE2 levels in liquor were largely unaffected, in line with tumor-bearing mice being afebrile. Neutralisation of peripheral PGE2 with anti-PGE2 antibodies did not temper the anorexia, and deletion of host mPGES-1 did not affect the anorexia or tumor growth. Furthermore, we found that tumor-bearing mice lacking EP4 receptors in the nervous system, created by Cre-LoxP-targeted mutagenesis, developed anorexia. The most important conclusions from paper II are that decreased meal frequency caused the anorexia, and that Cox-enzymes, most likely Cox-1, are critical for cancer-elicited anorexia and weight loss and that these changes occur independently of host mPGES-1, PGE2 and neuronal EP4 receptor signaling.In paper III, we investigated whether the inflammatory response critical for tumor-induced anorexia (paper II) was a result of innate immune signaling mechanisms. In paper IV, we also included measurements of food intake in mice injected with bacterial endotoxin, lipopolysaccharide (LPS; a Toll-like receptor 4 ligand), and aimed at identifying at which site(s) the activation of the innate immune system occurs during acute (LPS) as well as chronic (tumor) inflammation. To do so we examined the anorexic response in mice ubiquitously lacking (born without the gene in every cell) MyD88, the intracellular adaptor for Toll-like receptor and IL-1/18 receptor signalling, or lacking MyD88 in specific cell types. We found that a ubiquitous null deletion conferred complete resistance to LPS- and tumor-induced anorexia, as well as protected against weight loss. MyD88 knock-out mice, which had been subjected to whole-body irradiation to delete hematopoietic cells, and then transplanted with wild-type bone-marrow, developed anorexia when challenged with LPS. In line with this, mice lacking MyD88 in hematopoietic cells were largely protected against LPS-induced anorexia. Similarly, inactivation of MyD88 in hematopoietic cells attenuated the tumor-induced anorexia development and protected from body weight loss. In contrast, genetic disruption of MyD88 signaling in neural cells or cerebrovascular endothelial cells affected neither LPS- or tumor-induced anorexia, nor weight loss. Thus, the key findings in paper III and IV are that genetic inactivation of MyD88 protects mice from developing cancer- and LPS-induced anorexia, indicating that innate immune signaling mechanisms are critical for this response. The findings also identify hematopoietic cells, but not neural cells or cerebrovascular endothelial cells, as a critical nexus for inflammatory driven anorexia and weight loss associated with acute (LPS) and chronic (malignant) disease.
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| 5. |
- Ruud, Johan, 1978-, et al.
(author)
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Identification of rat brainstem neuronal structures activated during cancer-induced anorexia
- 2007
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In: Journal of Comparative Neurology. - : Wiley. - 0021-9967 .- 1096-9861. ; 504:3, s. 275-286
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Journal article (peer-reviewed)abstract
- In cancer-related anorexia, body weight loss is paradoxically associated with reduced appetite, which is contrary to the situation during starvation, implying that the normal coupling of food intake to energy expenditure is disarranged. Here we examined brainstem mechanisms that may underlie suppression of food intake in a rat model of cancer anorexia. Cultured Morris 7777 hepatoma cells were injected subcutaneously in Buffalo rats, resulting in slowly growing tumor and reduced food intake and body weight loss after about 10 days. The brainstem was examined for induced expression of the transcription factors Fos and FosB as signs of neuronal activation. The results showed that anorexia and retarded body weight growth were associated with Fos protein expression in the area postrema, the general visceral region of the nucleus of the solitary tract, and the external lateral parabrachial nucleus, structures that also display Fos after peripheral administration of satiating or anorexigenic stimuli. The magnitude of the Fos expression was specifically related to the size of induced tumor, and not associated with weight loss per se, because it was not present in pair-fed or food-deprived rats. It also appeared to be independent of proinflammatory cytokines, as determined by the absence of increased cytokine levels in plasma and induced cytokine and cyclooxygenase expression in the brain. The findings thus provide evidence that cancer-associated anorexia and weight loss in this model is associated with activation of brainstem circuits involved in the suppression of food intake, and suggest that this occurs by inflammatory-independent mechanisms. © 2007 Wiley-Liss, Inc.
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| 6. |
- Zlatkovic, Jovana, 1992, et al.
(author)
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Reduction of body weight by increased loading is associated with activation of norepinephrine neurones in the medial nucleus of the solitary tract.
- 2023
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In: Journal of neuroendocrinology. - 1365-2826. ; 35:12
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Journal article (peer-reviewed)abstract
- We previously provided evidence supporting the existence of a novel leptin-independent body weight homeostat ("the gravitostat") that senses body weight and then initiates a homeostatic feed-back regulation of body weight. We, herein, hypothesize that this feed-back regulation involves a CNS mechanism. To identify populations of neurones of importance for the putative feed-back signal induced by increased loading, high-fat diet-fed rats or mice were implanted intraperitoneally or subcutaneously with capsules weighing ∼15% (Load) or ∼2.5% (Control) of body weight. At 3-5days after implantation, neuronal activation was assessed in different parts of the brain/brainstem by immunohistochemical detection of FosB. Implantation of weighted capsules, both subcutaneous and intraperitoneal, induced FosB in specific neurones in the medial nucleus of the solitary tract (mNTS), known to integrate information about the metabolic status of the body. These neurones also expressed tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DbH), a pattern typical of norepinephrine neurones. In functional studies, we specifically ablated norepinephrine neurones in mNTS, which attenuated the feed-back regulation of increased load on body weight and food intake. In conclusion, increased load appears to reduce body weight and food intake via activation of norepinephrine neurones in the mNTS.
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