| 1. |
- 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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| 2. |
- Bondesson, Maria, et al.
(författare)
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Estrogen receptor signaling during vertebrate development
- 2015
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Ingår i: Biochimica et Biophysica Acta. Gene Regulatory Mechanisms. - : Elsevier BV. - 1874-9399 .- 1876-4320. ; 1849:2, s. 142-151
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Forskningsöversikt (refereegranskat)abstract
- Estrogen receptors are expressed and their cognate ligands produced in all vertebrates, indicative of important and conserved functions. Through evolution estrogen has been involved in controlling reproduction, affecting both the development of reproductive organs and reproductive behavior. This review broadly describes the synthesis of estrogens and the expression patterns of aromatase and the estrogen receptors, in relation to estrogen functions in the developing fetus and child. We focus on the role of estrogens for the development of reproductive tissues, as well as non-reproductive effects on the developing brain. We collate data from human, rodent, bird and fish studies and highlight common and species-specific effects of estrogen signaling on fetal development. Morphological malformations originating from perturbed estrogen signaling in estrogen receptor and aromatase knockout mice are discussed, as well as the clinical manifestations of rare estrogen receptor alpha and aromatase gene mutations in humans.
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| 3. |
- Gustafsson, Johan, et al.
(författare)
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Future trends for patient-specific dosimetry methodology in molecular radiotherapy
- 2023
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Ingår i: Physica Medica. - 1120-1797. ; 115
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Forskningsöversikt (refereegranskat)abstract
- Molecular radiotherapy is rapidly expanding, and new radiotherapeutics are emerging. The majority of treatments is still performed using empirical fixed activities and not tailored for individual patients. Molecular radiotherapy dosimetry is often seen as a promising candidate that would allow personalisation of treatments as outcome should ultimately depend on the absorbed doses delivered and not the activities administered. The field of molecular radiotherapy dosimetry has made considerable progress towards the feasibility of routine clinical dosimetry with reasonably accurate absorbed-dose estimates for a range of molecular radiotherapy dosimetry applications. A range of challenges remain with respect to the accurate quantification, assessment of time-integrated activity and absorbed dose estimation. In this review, we summarise a range of technological and methodological advancements, mainly focussed on beta-emitting molecular radiotherapeutics, that aim to improve molecular radiotherapy dosimetry to achieve accurate, reproducible, and streamlined dosimetry. We describe how these new technologies can potentially improve the often time-consuming considered process of dosimetry and provide suggestions as to what further developments might be required.
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| 4. |
- Gustafsson, Jan
(författare)
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Neonatal energy substrate production
- 2009
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Ingår i: Indian Journal of Medical Research (IJMR). - 0971-5916. ; 130:5, s. 618-623
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Forskningsöversikt (refereegranskat)abstract
- Glucose is the most important foetal energy substrate. At birth the transplacental transfer of substrates is terminated. Before the start of breastfeeding the newborn infant must produce its own glucose particularly for the need of the central nervous system. Neonatal hypoglycaemia commonly occurs in risk groups such as immature and low birth weight infants, infants of mothers with diabetes and infants born large for gestational age. Our data show that extremely immature infants can also produce their own glucose during the first day of postnatal life. Although their stores of depot fat are limited, they also have a capacity for lipolysis. Infants of diabetic mothers have unimpaired lipolysis in spite of hyperinsulinaemia. This may represent a mechanism to compensate for the reduced rate of glucose production in these infants. The number of infants born large for gestational age is increasing in several countries partly consequent to increases in maternal weight. We have shown that foetal weight depends on maternal glucose production, which in turn is related to parameters associated with maternal fat mass. Like infants born small for gestational age, those born large for gestational age are at risk for metabolic disease later in life. Owing to a high fat mass these infants have a high rate of lipolysis, which can be one reason underlying the reduced insulin sensitivity seen already during the first day of life.
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| 5. |
- Heverin, Maura, et al.
(författare)
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On the regulatory importance of 27-hydroxycholesterol in mouse liver
- 2017
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Ingår i: Journal of Steroid Biochemistry and Molecular Biology. - : Elsevier. - 0960-0760 .- 1879-1220. ; 169, s. 10-21
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Forskningsöversikt (refereegranskat)abstract
- 27-Hydroxycholesterol (27OH) is a strong suppressor of cholesterol synthesis and a weak activator of LXR in vitro. The regulatory importance of 27OH in vivo is controversial. Here we utilized male mice with increased levels of 27OH either due to increased production (CYP27A1 transgenic mice) or reduced metabolism (Cyp7b1-/- mice). We also used mice lacking 27OH due to a knockout of Cyp27a1. The latter mice were treated with cholic acid to compensate for reduced bile acid synthesis. The effects of the different levels of 27OH on Srebp- and other LXR-regulated genes in the liver were investigated. In the liver of CYP27tg mice we found a modest increase of the mRNA levels corresponding to the LXR target genes Cyp7b1 and Abca1. A number of other LXR-regulated genes were not affected. The effect on Abca1 mRNA was not seen in the liver of Cyp7b1-/- mice. There were little or no effects on cholesterol synthesis. In the liver of the Cyp27-/- mice treated with 0.025% cholic acid there was no significant effect of the knockout on the LXR target genes. In a previous work triple-knockout mice deficient in the biosynthesis of 24S-hydroxycholesterol, 25-hydroxycholesterol and 27OH were shown to have impaired response to dietary cholesterol, suggesting side-chain oxidized oxysterols to be mediators in cholesterol-induced effects on LXR target genes at a transcriptional level (Chen W. et al., Cell Metab. 5 (2007) 73-79). The hydroxylated oxysterol responsible for the effect was not defined. We show here that treatment of wildtype mice with dietary cholesterol under the same conditions as in the above study induced the LXR target genes Lpl, Abcg8 and Srebp1c in wild type mice but failed to activate the same genes in mice lacking 27-hydroxycholesterol due to a knockout of Cyp27. We failed to demonstrate the above effects at the protein level (Abcg8) or at the activity level (Lpl). The results suggest that 27OH is not an important regulator of Srebp- or LXR regulated genes under basal conditions in mouse liver. On the other hand 27OH appears to mediate cholesterol-induced effects on some LXR target genes at a transcriptional level under some in vivo conditions.
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| 6. |
- Leijon, Mats, et al.
(författare)
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Wave Energy from the North Sea : Experiences from the Lysekil Research Site
- 2008
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Ingår i: Surveys in geophysics. - : Springer Science and Business Media LLC. - 0169-3298 .- 1573-0956. ; 29:3, s. 221-240
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Forskningsöversikt (refereegranskat)abstract
- This paper provides a status update on the development of the Swedish wave energy research area located close to Lysekil on the Swedish West coast. The Lysekil project is run by the Centre for Renewable Electric Energy Conversion at Uppsala University. The project was started in 2004 and currently has permission to run until the end of 2013. During this time period 10 grid-connected wave energy converters, 30 buoys for studies on environmental impact, and a surveillance tower for monitoring the interaction between waves and converters will be installed and studied. To date the research area holds one complete wave energy converter connected to a measuring station on shore via a sea cable, a Wave Rider™ buoy for wave measurements, 25 buoys for studies on environmental impact, and a surveillance tower. The wave energy converter is based on a linear synchronous generator which is placed on the sea bed and driven by a heaving point absorber at the ocean surface. The converter is directly driven, i.e. it has no gearbox or other mechanical or hydraulic conversion system. This results in a simple and robust mechanical system, but also in a somewhat more complicated electrical system.
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| 7. |
- Nunez, Julio, et al.
(författare)
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Congestion in heart failure: a circulating biomarker-based perspective. A review from the Biomarkers Working Group of the Heart Failure Association, European Society of Cardiology
- 2022
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Ingår i: European Journal of Heart Failure. - : WILEY. - 1388-9842 .- 1879-0844. ; 24:10, s. 1751-1766
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Forskningsöversikt (refereegranskat)abstract
- Congestion is a cardinal sign of heart failure (HF). In the past, it was seen as a homogeneous epiphenomenon that identified patients with advanced HF. However, current evidence shows that congestion in HF varies in quantity and distribution. This updated view advocates for a congestive-driven classification of HF according to onset (acute vs. chronic), regional distribution (systemic vs. pulmonary), compartment of distribution (intravascular vs. extravascular), and clinical vs. subclinical. Thus, this review will focus on the utility of circulating biomarkers for assessing and managing the different fluid overload phenotypes. This discussion focused on the clinical utility of the natriuretic peptides, carbohydrate antigen 125 (also called mucin 16), bio-adrenomedullin and mid-regional pro-adrenomedullin, ST2 (also known as interleukin-1 receptor-like 1), cluster of differentiation 146, troponin, C-terminal pro-endothelin-1, and parameters of haemoconcentration. The utility of circulation biomarkers on top of clinical evaluation, haemodynamics, and imaging needs to be better determined by dedicated studies. Some multiparametric frameworks in which these tools contribute to management are proposed.
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| 8. |
- Proos, Lemm A., 1943-, et al.
(författare)
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Is Early Puberty Triggered by Catch-Up Growth Following Undernutrition?
- 2012
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1661-7827 .- 1660-4601. ; 9:5, s. 1791-1809
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Forskningsöversikt (refereegranskat)abstract
- Undernutrition during fetal and postnatal life is still a major problem in many low- and middle-income countries. Even in high-income countries malnutrition may exist in cases of intrauterine growth retardation, as well as in chronic conditions such as anorexia nervosa and inflammatory bowel disease. Children adopted from developing countries are often chronically malnourished. Nutritional rehabilitation, resulting in catch-up growth, is often complicated by influences originating in fetal life as well as during postnatal growth. This may result in hormonal and metabolic changes as well as alterations in pubertal development. The present review focuses on fetal, postnatal and fetal-postnatal undernutrition and subsequent catch-up growth as well as catch-up growth in relation to pubertal development. Catch-up growth in children can be associated with early puberty following fetal or combined fetal-postnatal undernutrition. However, early puberty does not seem to occur following catch-up growth after isolated postnatal undernutrition. Gonadotropins have been reported to be elevated in prepubertal adopted girls as well as during catch-up growth in animals. Even if other factors may contribute, linear catch-up growth seems to be associated with the timing of pubertal development. The mechanisms behind this are still unknown. Future research may elucidate how to carry out nutritional rehabilitation without risk for early pubertal development.
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| 9. |
- Ridefelt, Peter, et al.
(författare)
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Estimating reliable paediatric reference intervals in clinical chemistry and haematology
- 2014
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Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 103:1, s. 10-15
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Forskningsöversikt (refereegranskat)abstract
- Very few high-quality studies on paediatric reference intervals for general clinical chemistry and haematology analytes have been performed. Three recent prospective community-based projects utilising blood samples from healthy children in Sweden, Denmark and Canada have substantially improved the situation. ConclusionThe present review summarises current reference interval studies for common clinical chemistry and haematology analyses.
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| 10. |
- Williams, Cecilia, et al.
(författare)
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Estrogen receptor beta as target for colorectal cancer prevention
- 2016
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Ingår i: Cancer Letters. - : Elsevier. - 0304-3835 .- 1872-7980. ; 372:1, s. 48-56
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Forskningsöversikt (refereegranskat)abstract
- Colorectal cancer (CRC) is a leading cause of death in the United States. Despite its slow development and the capacity for early diagnosis, current preventive approaches are not sufficient. However, a role for estrogen has been demonstrated in multiple epidemiologic studies, which may benefit CRC prevention. A large body of evidence from preclinical studies indicates that expression of the estrogen receptor beta (ER beta/ESR2) demonstrates an inverse relationship with the presence of colorectal polyps and stage of tumors, and can mediate a protective response. Natural compounds, including phytoestrogens, or synthetic ER beta selective agonists, can activate or upregulate ER beta in the colon and promote apoptosis in preclinical models and in clinical experience. Importantly, this activity has been associated with a reduction in polyp formation and, in rodent models of CRC, has been shown to lower incidence of colon adenocarcinoma. Collectively, these findings indicate that targeted activation of ER beta may represent a novel clinical approach for management of colorectal adenomatous polyps and prevention of colorectal carcinoma in patients at risk for this condition. In this review, we discuss the potential of new chemopreventive or dietary approaches based on estrogen signaling.
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