| 1. |
- Azevedo, Flavio, et al.
(författare)
-
Social and moral psychology of COVID-19 across 69 countries
- 2023
-
Ingår i: Scientific Data. - : NATURE PORTFOLIO. - 2052-4463. ; 10:1
-
Tidskriftsartikel (refereegranskat)abstract
- The COVID-19 pandemic has affected all domains of human life, including the economic and social fabric of societies. One of the central strategies for managing public health throughout the pandemic has been through persuasive messaging and collective behaviour change. To help scholars better understand the social and moral psychology behind public health behaviour, we present a dataset comprising of 51,404 individuals from 69 countries. This dataset was collected for the International Collaboration on Social & Moral Psychology of COVID-19 project (ICSMP COVID-19). This social science survey invited participants around the world to complete a series of moral and psychological measures and public health attitudes about COVID-19 during an early phase of the COVID-19 pandemic (between April and June 2020). The survey included seven broad categories of questions: COVID-19 beliefs and compliance behaviours; identity and social attitudes; ideology; health and well-being; moral beliefs and motivation; personality traits; and demographic variables. We report both raw and cleaned data, along with all survey materials, data visualisations, and psychometric evaluations of key variables.
|
|
| 2. |
- Van Bavel, Jay J., et al.
(författare)
-
National identity predicts public health support during a global pandemic
- 2022
-
Ingår i: Nature Communications. - : Nature Portfolio. - 2041-1723. ; 13:1
-
Tidskriftsartikel (refereegranskat)abstract
- Understanding collective behaviour is an important aspect of managing the pandemic response. Here the authors show in a large global study that participants that reported identifying more strongly with their nation reported greater engagement in public health behaviours and support for public health policies in the context of the pandemic. Changing collective behaviour and supporting non-pharmaceutical interventions is an important component in mitigating virus transmission during a pandemic. In a large international collaboration (Study 1, N = 49,968 across 67 countries), we investigated self-reported factors associated with public health behaviours (e.g., spatial distancing and stricter hygiene) and endorsed public policy interventions (e.g., closing bars and restaurants) during the early stage of the COVID-19 pandemic (April-May 2020). Respondents who reported identifying more strongly with their nation consistently reported greater engagement in public health behaviours and support for public health policies. Results were similar for representative and non-representative national samples. Study 2 (N = 42 countries) conceptually replicated the central finding using aggregate indices of national identity (obtained using the World Values Survey) and a measure of actual behaviour change during the pandemic (obtained from Google mobility reports). Higher levels of national identification prior to the pandemic predicted lower mobility during the early stage of the pandemic (r = -0.40). We discuss the potential implications of links between national identity, leadership, and public health for managing COVID-19 and future pandemics.
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
- Jones, Benedict C, et al.
(författare)
-
To which world regions does the valence-dominance model of social perception apply?
- 2021
-
Ingår i: Nature Human Behaviour. - : Springer Science and Business Media LLC. - 2397-3374. ; 5:1, s. 159-169
-
Tidskriftsartikel (refereegranskat)abstract
- Over the past 10 years, Oosterhof and Todorov's valence-dominance model has emerged as the most prominent account of how people evaluate faces on social dimensions. In this model, two dimensions (valence and dominance) underpin social judgements of faces. Because this model has primarily been developed and tested in Western regions, it is unclear whether these findings apply to other regions. We addressed this question by replicating Oosterhof and Todorov's methodology across 11 world regions, 41 countries and 11,570 participants. When we used Oosterhof and Todorov's original analysis strategy, the valence-dominance model generalized across regions. When we used an alternative methodology to allow for correlated dimensions, we observed much less generalization. Collectively, these results suggest that, while the valence-dominance model generalizes very well across regions when dimensions are forced to be orthogonal, regional differences are revealed when we use different extraction methods and correlate and rotate the dimension reduction solution. PROTOCOL REGISTRATION: The stage 1 protocol for this Registered Report was accepted in principle on 5 November 2018. The protocol, as accepted by the journal, can be found at https://doi.org/10.6084/m9.figshare.7611443.v1 .
|
|
| 6. |
- Mesa, D., et al.
(författare)
-
Upper limits for mass and radius of objects around Proxima Cen from SPHERE/VLT
- 2017
-
Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966 .- 1745-3925 .- 1745-3933. ; 466:1, s. l118-L122
-
Tidskriftsartikel (refereegranskat)abstract
- The recent discovery of an earth-like planet around Proxima Centauri has drawn much attention to this star and its environment. We performed a series of observations of Proxima Centauri using Spectro-Polarimetric High-contrast Exoplanet REsearch (SPHERE), the planet-finder instrument installed at the European Southern Observatory (ESO) Very Large Telescope (VLT) UT3, using its near-infrared modules, InfraRed Dual-band Imager and Spectrograph (IRDIS) and IFS. No planet was detected directly, but we set upper limits on the mass up to 7 au by exploiting the AMES-COND models. Our IFS observations reveal that no planet more massive than similar to 6-7 M-Jup can be present within 1 au. The dual-band imaging camera IRDIS also enables us to probe larger separations than other techniques such as radial velocity or astrometry. We obtained mass limits of the order of 4 M-Jup at separations of 2 au or larger, representing the most stringent mass limits at separations larger than 5 au available at the moment. We also made an attempt to estimate the radius of possible planets around Proxima using the reflected light. Since the residual noise for the observations is dominated by photon noise and thermal background, longer exposures in good observing conditions could improve the achievable contrast limit further.
|
|
| 7. |
- Žliobaitė, Indrė, et al.
(författare)
-
The NOW Database of Fossil Mammals
- 2023
-
Ingår i: Evolution of Cenozoic Land Mammal Faunas and Ecosystems: 25 years of the NOW database of fossil mammals. - : Springer. ; , s. 33-42
-
Bokkapitel (refereegranskat)abstract
- NOW (New and Old Worlds) is a global database of fossil mammal occurrences, currently containing around 68,000 locality-species entries. The database spans the last 66 million years, with its primary focus on the last 23 million years. Whereas the database contains records from all continents, the main focus and coverage of the database historically has been on Eurasia. The database includes primarily, but not exclusively, terrestrial mammals. It covers a large part of the currently known mammalian fossil record, focusing on classical and actively researched fossil localities. The database is managed in collaboration with an international advisory board of experts. Rather than a static archive, it emphasizes the continuous integration of new knowledge of the community, data curation, and consistency of scientific interpretations. The database records species occurrences at localities worldwide, as well as ecological characteristics of fossil species, geological contexts of localities and more. The NOW database is primarily used for two purposes: (1) queries about occurrences of particular taxa, their characteristics and properties of localities in the spirit of an encyclopedia; and (2) large scale research and quantitative analyses of evolutionary processes, patterns, reconstructing past environments, as well as interpreting evolutionary contexts. The data are fully open, no logging in or community membership is necessary for using the data for any purpose.
|
|
| 8. |
- Almén, Markus Sällman, et al.
(författare)
-
Genome-wide analysis reveals DNA methylation markers that vary with both age and obesity
- 2014
-
Ingår i: Gene. - : Elsevier BV. - 0378-1119 .- 1879-0038. ; 548:1, s. 61-67
-
Tidskriftsartikel (refereegranskat)abstract
- The combination of the obesity epidemic and an aging population presents growing challenges for the healthcare system. Obesity and aging are major risk factors for a diverse number of diseases and it is of importance to understand their interaction and the underlying molecular mechanisms. Herein the authors examined the methylation levels of 27578 CpG sites in 46 samples from adult peripheral blood. The effect of obesity and aging was ascertained with general linear models. More than one hundred probes were correlated to aging, nine of which belonged to the KEGG group map04080. Additionally, 10 CpG sites had diverse methylation profiles in obese and lean individuals, one of which was the telomerase catalytic subunit (TERT). In eight of ten cases the methylation change was reverted between obese and lean individuals. One region proved to be differentially methylated with obesity (LINC00304) independent of age. This study provides evidence that obesity influences age driven epigenetic changes, which provides a molecular link between aging and obesity. This link and the identified markers may prove to be valuable biomarkers for the understanding of the molecular basis of aging, obesity and associated diseases.
|
|
| 9. |
- Brem, Jürgen, et al.
(författare)
-
Imitation of β-lactam binding enables broad-spectrum metallo-β-lactamase inhibitors
- 2022
-
Ingår i: Nature Chemistry. - : Springer Nature. - 1755-4330 .- 1755-4349. ; 14:1, s. 15-24
-
Tidskriftsartikel (refereegranskat)abstract
- Carbapenems are vital antibiotics, but their efficacy is increasingly compromised by metallo-β-lactamases (MBLs). Here we report the discovery and optimization of potent broad-spectrum MBL inhibitors. A high-throughput screen for NDM-1 inhibitors identified indole-2-carboxylates (InCs) as potential β-lactamase stable β-lactam mimics. Subsequent structure-activity relationship studies revealed InCs as a new class of potent MBL inhibitor, active against all MBL classes of major clinical relevance. Crystallographic studies revealed a binding mode of the InCs to MBLs that, in some regards, mimics that predicted for intact carbapenems, including with respect to maintenance of the Zn(II)-bound hydroxyl, and in other regards mimics binding observed in MBL-carbapenem product complexes. InCs restore carbapenem activity against multiple drug-resistant Gram-negative bacteria and have a low frequency of resistance. InCs also have a good in vivo safety profile, and when combined with meropenem show a strong in vivo efficacy in peritonitis and thigh mouse infection models.
|
|
| 10. |
|
|
| 11. |
- Ciganoka, Darja, et al.
(författare)
-
Identification of somatostatin receptor type 5 gene polymorphisms associated with acromegaly
- 2011
-
Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 165:4, s. 517-525
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this study was to characterize the genetic variance of somatostatin receptor 5 (SSTR5) and investigate the possible correlation of such variants with acromegaly risk and different disease characteristics. Design and methods: The SSTR5 gene coding region and 2000 bp upstream region was sequenced in 48 patients with acromegaly and 96 control subjects. Further, three single nucleotide polymorphisms (SNPs) were analyzed in the same group of acromegaly patients and in an additional group of 475 age- and sex-matched controls. Results: In total, 19 SNPs were identified in the SSTR5 gene locus by direct sequencing. Three SNPs (rs34037914, rs169068, and rs642249) were significantly associated with the presence of acromegaly using the initial controls. The allele frequencies were significantly (P<0.01) different between the acromegaly patients and the additional large control group. rs34037914 and rs642249 remained significantly associated with acromegaly after Bonferroni correction and permutation tests (odds ratio (OR) = 3.38; 95% confidence interval (CI), 1.78-6.42; P=0.00016 and OR=2.41; 95% CI, 1.41-4.13; P=0.0014 respectively). Haplotype reconstruction revealed two possible risk haplotypes determined by rs34037914 (633T) and rs642249 (1044A) alleles. Both haplotypes were found in significantly higher frequency in acromegaly patients compared with controls (P=0.001). In addition, the 663T allele was significantly associated with a younger age of acromegaly diagnosis (unstandardized regression coefficient beta=-10.4; P=0.002), increased body mass index (beta=4.1; P=0.004), higher number of adenoma resection (P<0.001) and lack of observable tumor shrinkage after somatostatin analog treatment (P=0.014). Conclusions: Our results demonstrate a previously undetected strong association of two SSTR5 SNPs with acromegaly. The data also suggest a possible involvement of SSTR5 variants in decreased suppression of GH production and increased tumor proliferation.
|
|
| 12. |
- Dambrova, Maija, et al.
(författare)
-
Acylcarnitines : Nomenclature, Biomarkers, Therapeutic Potential, Drug Targets, and Clinical Trials
- 2022
-
Ingår i: Pharmacological Reviews. - : AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS. - 0031-6997 .- 1521-0081. ; 74:3, s. 506-551
-
Forskningsöversikt (refereegranskat)abstract
- Acylcarnitines are fatty acid metabolites that play important roles in many cellular energy metabolism pathways. They have historically been used as important diagnostic markers for inborn errors of fatty acid oxidation and are being intensively studied as markers of energy metabolism, deficits in mitochondrial and peroxisomal b-oxidation activity, insulin resistance, and physical activity. Acylcarnitines are increasingly being identified as important indicators in metabolic studies of many diseases, including metabolic disorders, cardiovascular diseases, diabetes, depression, neurologic disorders, and certain cancers. The US Food and Drug Administration-approved drug L-carnitine, along with short-chain acylcarnitines (acetylcarnitine and propionylcarnitine), is now widely used as a dietary supplement. In light of their growing importance, we have undertaken an extensive review of acylcarnitines and provided a detailed description of their identity, nomenclature, classification, biochemistry, pathophysiology, supplementary use, potential drug targets, and clinical trials. We also summarize these updates in the Human Metabo lome Database, which now includes information on the structures, chemical formulae, chemical/spectral properties, descriptions, and pathways for 1240 acylcarnitines. This work lays a solid foundation for identifying, characterizing, and understanding acylcarnitines in human biosamples. We also discuss the emerging opportunities for using acylcarnitines as biomarkers and as dietary interventions or supplements for many wide-ranging indications. The opportunity to identify new drug targets involved in controlling acylcarnitine levels is also discussed. Significance Statement--This review provides a comprehensive overview of acylcarnitines, including their nomenclature, structure and biochemistry, and use as disease biomarkers and pharmaceutical agents. We present updated information contained in the Human Metabolome Database website as well as substantial mapping of the known biochemical pathways associated with acylcarnitines, thereby providing a strong foundation for further clarification of their physiological roles.
|
|
| 13. |
- Elbere, Ilze, et al.
(författare)
-
Significantly altered peripheral blood cell DNA methylation profile as a result of immediate effect of metformin use in healthy individuals
- 2018
-
Ingår i: Clinical Epigenetics. - : Springer Science and Business Media LLC. - 1868-7083 .- 1868-7075. ; 10
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Metformin is a widely prescribed antihyperglycemic agent that has been also associated with multiple therapeutic effects in various diseases, including several types of malignancies. There is growing evidence regarding the contribution of the epigenetic mechanisms in reaching metformin's therapeutic goals; however, the effect of metformin on human cells in vivo is not comprehensively studied. The aim of our study was to examine metformin-induced alterations of DNA methylation profiles in white blood cells of healthy volunteers, employing a longitudinal study design.Results: Twelve healthy metformin-naive individuals where enrolled in the study. Genome-wide DNA methylation pattern was estimated at baseline, 10h and 7days after the start of metformin administration. The whole-genome DNA methylation analysis in total revealed 125 differentially methylated CpGs, of which 11 CpGs and their associated genes with the most consistent changes in the DNA methylation profile were selected: POFUT2, CAMKK1, EML3, KIAA1614, UPF1, MUC4, LOC727982, SIX3, ADAM8, SNORD12B, VPS8, and several differentially methylated regions as novel potential epigenetic targets of metformin. The main functions of the majority of top-ranked differentially methylated loci and their representative cell signaling pathways were linked to the well-known metformin therapy targets: regulatory processes of energy homeostasis, inflammatory responses, tumorigenesis, and neurodegenerative diseases.Conclusions: Here we demonstrate for the first time the immediate effect of short-term metformin administration at therapeutic doses on epigenetic regulation in human white blood cells. These findings suggest the DNA methylation process as one of the mechanisms involved in the action of metformin, thereby revealing novel targets and directions of the molecular mechanisms underlying the various beneficial effects of metformin.Trial registrationEU Clinical Trials Register, 2016-001092-74. Registered 23 March 2017, https://www.clinicaltrialsregister.eu/ctr-search/trial/2016-001092-74/LV.
|
|
| 14. |
- Fridmanis, Davids, et al.
(författare)
-
Formation of new genes explains lower intron density in mammalian Rhodopsin G protein-coupled receptors
- 2007
-
Ingår i: Molecular Phylogenetics and Evolution. - : Elsevier BV. - 1055-7903 .- 1095-9513. ; 43:3, s. 864-880
-
Tidskriftsartikel (refereegranskat)abstract
- Mammalian G protein-coupled receptor (GPCR) genes are characterised by a large proportion of intronless genes or a lower density of introns when compared with GPCRs of invertebrates. It is unclear which mechanisms have influenced intron density in this protein family, which is one of the largest in the mammalian genomes. We used a combination of Hidden Markov Models (HMM) and BLAST searches to establish the comprehensive repertoire of Rhodopsin GPCRs from seven species and performed overall alignments and phylogenetic analysis using the maximum parsimony method for over 1400 receptors in 12 subgroups. We identified 14 different Ancestral Receptor Groups (ARGs) that have members in both vertebrate and invertebrate species. We found that there exists a remarkable difference in the intron density among ancestral and new Rhodopsin GPCRs. The intron density among ARGs members was more than 3.5-fold higher than that within non-ARG members and more than 2-fold higher when considering only the 7TM region. This suggests that the new GPCR genes have been predominantly formed intronless while the ancestral receptors likely accumulated introns during their evolution. Many of the intron positions found in mammalian ARG receptor sequences were found to be present in orthologue invertebrate receptors suggesting that these intron positions are ancient. This analysis also revealed that one intron position is much more frequent than any other position and it is common for a number of phylogenetically different Rhodopsin GPCR groups. This intron position lies within a functionally important, conserved, DRY motif which may form a proto-splice site that could contribute to positional intron insertion. Moreover, we have found that other receptor motifs, similar to DRY, also contain introns between the second and third nucleotide of the arginine codon which also forms a proto-splice site. Our analysis presents compelling evidence that there was not a major loss of introns in mammalian GPCRs and formation of new GPCRs among mammals explains why these have fewer introns compared to invertebrate GPCRs. We also discuss and speculate about the possible role of different RNA- and DNA-based mechanisms of intron insertion and loss.
|
|
| 15. |
- Fridmanis, Davids, et al.
(författare)
-
Identification of domains responsible for specific membrane transport and ligand specificity of the ACTH receptor (MC2R)
- 2010
-
Ingår i: Molecular and Cellular Endocrinology. - : Elsevier BV. - 0303-7207 .- 1872-8057. ; 321:2, s. 175-183
-
Tidskriftsartikel (refereegranskat)abstract
- The adrenocorticotropic hormone (ACTH) receptor has highly specific membrane expression that is limited to adrenal cells; in other cell types the polypeptide fails to be transported to the cell surface. Unlike other evolutionarily related members of the melanocortin receptor family (MC1R-MC5R) that recognize different melanocortin peptides, ACTHR (MC2R) binds only ACTH. We used a mutagenesis approach involving systematic construction of chimeric ACTHR/MC4R receptors to identify the domains determining the selectivity of ACTHR membrane transport and ACTH binding. In total 15 chimeric receptors were created by replacement of selected domains of human ACTHR with the corresponding regions of human MC4R. We developed an analytical method to accurately quantify cell-membrane localization of recombinant receptors fused with enhanced green fluorescent protein by confocal fluorescence microscopy. The chimeric receptors were also tested for their ability to bind ACTH (1-24) and the melanocyte-stimulating hormone (MSH) analog, Nle4, DPhe7-alpha-MSH, and to induce a cAMP response. Our results indicate that substitution of the MC4R N-terminal segment with the homologous segment of ACTHR significantly decreased membrane transport. We also identified another signal localized in the third and fourth transmembrane regions as the main determinant of ACTHR intracellular retention. In addition, we found that the fourth and fifth transmembrane domains of the ACTHR are involved in ACTH binding selectivity. We discuss the mechanisms involved in bypassing these arrest signals via an interaction with melanocortin 2 receptor accessory protein (MRAP) and the possible mechanisms that determine the high ligand-binding specificity of ACTHR.
|
|
| 16. |
- Fridmanis, Davids, et al.
(författare)
-
Replacement of short segments within transmembrane domains of MC2R disrupts retention signal
- 2014
-
Ingår i: Journal of Molecular Endocrinology. - 0952-5041 .- 1479-6813. ; 53:2, s. 201-215
-
Tidskriftsartikel (refereegranskat)abstract
- The proteolysis of the pro-opiomelanocortin precursor results in the formation of melanocortins (MCs), a group of peptides that share the conserved -H-F-R-W- sequence, which acts as a pharmacophore for five subtypes of MC receptors (MCRs). MC type 2 receptor (MC2R; also known as ACTHR) is the most specialized of all the MCRs. It is predominantly expressed in the adrenal cortex and specifically binds ACTH. Unlike other MCRs, it requires melanocortin receptor accessory protein 1 (MRAP) for formation of active receptor and for its transport to the cell membrane. The molecular mechanisms underlying this specificity remain poorly understood. In this study, we used directed mutagenesis to investigate the role of various short MC2R sequence segments in receptor membrane trafficking and specific activation upon stimulation with ligands. The strategy of the study was to replace two to five amino acid residues within one MC2R segment with the corresponding residues of MC4R. In total, 20 recombinant receptors C-terminally fused to enhanced green fluorescent protein were generated and their membrane trafficking efficiencies and cAMP response upon stimulation with α-MSH and ACTH(1-24) were estimated during their stand-alone expression and coexpression with MRAP. Our results indicate that both the motif that determines the ligand-recognition specificity and the intracellular retention signal are formed by a specific extracellular structure, which is supported by the correct alignment of the transmembrane domains. Our results also indicate that the aromatic-residue-rich segment of the second extracellular loop is involved in the effects mediated by the second ACTH pharmacophore (-K-K-R-R-).
|
|
| 17. |
- Gorasso, Vanessa, et al.
(författare)
-
Burden of disease attributable to risk factors in European countries: a scoping literature review
- 2023
-
Ingår i: Archives of Public Health. - 0778-7367 .- 2049-3258. ; 81:1
-
Forskningsöversikt (refereegranskat)abstract
- Objectives: Within the framework of the burden of disease (BoD) approach, disease and injury burden estimates attributable to risk factors are a useful guide for policy formulation and priority setting in disease prevention. Considering the important differences in methods, and their impact on burden estimates, we conducted a scoping literature review to: (1) map the BoD assessments including risk factors performed across Europe; and (2) identify the methodological choices in comparative risk assessment (CRA) and risk assessment methods. Methods: We searched multiple literature databases, including grey literature websites and targeted public health agencies websites. Results: A total of 113 studies were included in the synthesis and further divided into independent BoD assessments (54 studies) and studies linked to the Global Burden of Disease (59 papers). Our results showed that the methods used to perform CRA varied substantially across independent European BoD studies. While there were some methodological choices that were more common than others, we did not observe patterns in terms of country, year or risk factor. Each methodological choice can affect the comparability of estimates between and within countries and/or risk factors, since they might significantly influence the quantification of the attributable burden. From our analysis we observed that the use of CRA was less common for some types of risk factors and outcomes. These included environmental and occupational risk factors, which are more likely to use bottom-up approaches for health outcomes where disease envelopes may not be available. Conclusions: Our review also highlighted misreporting, the lack of uncertainty analysis and the under-investigation of causal relationships in BoD studies. Development and use of guidelines for performing and reporting BoD studies will help understand differences, avoid misinterpretations thus improving comparability among estimates.
|
|
| 18. |
- Haitina, Tatjana, et al.
(författare)
-
Cloning, tissue distribution, pharmacology and three-dimensional modelling of melanocortin receptors 4 and 5 in rainbow trout suggest close evolutionary relationship of these subtypes
- 2004
-
Ingår i: Biochemical Journal. - 0264-6021 .- 1470-8728. ; 380:2, s. 475-486
-
Tidskriftsartikel (refereegranskat)abstract
- The rainbow trout (Oncorhynchus mykiss) is one of the most widely used fish species in aquaculture and physiological research. In the present paper, we report the first cloning, 3D (three-dimensional) modelling, pharmacological characterization and tissue distribution of two melanocortin (MC) receptors in rainbow trout. Phylogenetic analysis indicates that these receptors are orthologues of the human MC4 and MC5 receptors. We created 3D molecular models of these rainbow trout receptors and their human counterparts. These models suggest greater divergence between the two human receptors than between their rainbow trout counterparts. The pharmacological analyses demonstrated that ACTH (adrenocorticotropic hormone) had surprisingly high affinity for the rainbow trout MC4 and MC5 receptors, whereas alpha-, beta- and gamma-MSH (melanocyte-stimulating hormone) had lower affinity. In second-messenger studies, the cyclic MSH analogues MTII and SHU9119 acted as potent agonist and antagonist respectively at the rainbow trout MC4 receptor, indicating that these ligands are suitable for physiological studies in rainbow trout. Interestingly, we found that the rainbow trout MC4 receptor has a natural high-affinity binding site for zinc ions (0.5 microM) indicating that zinc may play an evolutionary conserved role at this receptor. Reverse transcription PCR indicates that the rainbow trout receptors are expressed both in peripheral tissues and in the central nervous system, including the telencephalon, optic tectum and hypothalamus. Overall, this analysis indicates that the rainbow trout MC4 and MC5 receptors have more in common than their mammalian counterparts, which may suggest that these two receptors have a closer evolutionary relationship than the other MC receptor subtypes.
|
|
| 19. |
- Haitina, Tatjana, et al.
(författare)
-
Functional characterization of two melanocortin (MC) receptors in lamprey showing orthology to the MC1 and MC4 receptor subtypes
- 2007
-
Ingår i: BMC Evolutionary Biology. - : Springer Science and Business Media LLC. - 1471-2148. ; 7, s. 101-
-
Tidskriftsartikel (refereegranskat)abstract
- Background The melanocortin (MC) receptors have a key role in regulating body weight and pigmentation. They belong to the rhodopsin family of G protein-coupled receptors (GPCRs). The purpose of this study was to identify ancestral MC receptors in agnathan, river lamprey. Results We report cloning of two MC receptors from river lamprey. The lamprey receptors, designated MCa and MCb, showed orthology to the MC1 and MC4 receptor subtypes, respectively. The molecular clock analysis suggested that lamprey MC receptor genes were not duplicated recently and diverged from each other more than 400 MYR ago. Expression and pharmacological characterization showed that the lamprey MCa receptor was able to bind and be activated by both lamprey and human MSH peptides. The lamprey MCa receptor had relatively high affinity for ACTH derived peptides similarly to the fish MC receptors. We found that both of the lamprey MC receptors were expressed in skin, while the MCb receptor was also found in liver, heart and skeletal muscle. Conclusion This study shows presence of MC receptors in agnathans indicating early signs of specific functions of melanocortin receptor subtypes.
|
|
| 20. |
- Haitina, Tatjana, et al.
(författare)
-
Pharmacological characterization of melanocortin receptors in fish suggests an important role for ACTH
- 2005
-
Ingår i: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923 .- 1749-6632. ; 1040:Apr, s. 337-9
-
Tidskriftsartikel (refereegranskat)abstract
- Abstract: The melanocortin (MC) receptor subtypes have distinctive characteristic binding profiles. We found that the trout and Fugu MC4 receptors have similar affinity for α-MSH and β-MSH and a much higher affinity for ACTH than does the human MC4 receptor. The Fugu MC1 and the trout and Fugu MC5 receptors also have higher affinity for ACTH-derived peptides than α-, β-, or γ-MSH. It is tempting to speculate that ACTH-derived peptides may have played an important role as “original” ligands at the MC receptors, while the specificity of the different subtypes for the α-, β-, and γ-MSH peptides may have appeared at later stages during vertebrate evolution.
|
|
| 21. |
- Hood, Michael E, et al.
(författare)
-
Distribution of the anther-smut pathogen Microbotryum on species of the Caryophyllaceae.
- 2010
-
Ingår i: The New phytologist. - : Wiley. - 1469-8137 .- 0028-646X. ; 187:1, s. 217-29
-
Tidskriftsartikel (refereegranskat)abstract
- *Understanding disease distributions is of fundamental and applied importance, yet few studies benefit from integrating broad sampling with ecological and phylogenetic data. Here, anther-smut disease, caused by the fungus Microbotryum, was assessed using herbarium specimens of Silene and allied genera of the Caryophyllaceae. *A total of 42,000 herbarium specimens were examined, and plant geographical distributions and morphological and life history characteristics were tested as correlates of disease occurrence. Phylogenetic comparative methods were used to determine the association between disease and plant life-span. *Disease was found on 391 herbarium specimens from 114 species and all continents with native Silene. Anther smut occurred exclusively on perennial plants, consistent with the pathogen requiring living hosts to overwinter. The disease was estimated to occur in 80% of perennial species of Silene and allied genera. The correlation between plant life-span and disease was highly significant while controlling for the plant phylogeny, but the disease was not correlated with differences in floral morphology. *Using resources available in natural history collections, this study illustrates how disease distribution can be determined, not by restriction to a clade of susceptible hosts or to a limited geographical region, but by association with host life-span, a trait that has undergone frequent evolutionary transitions.
|
|
| 22. |
- Ignatovica, Vita, et al.
(författare)
-
Identification and analysis of functionally important amino acids in human purinergic 12 receptor using a Saccharomyces cerevisiae expression system
- 2012
-
Ingår i: The FEBS Journal. - : Wiley. - 1742-464X .- 1742-4658. ; 279:1, s. 180-191
-
Tidskriftsartikel (refereegranskat)abstract
- The purinergic 12 receptor (P2Y12) is a major drug target for anticoagulant therapies, but little is known about the regions involved in ligand binding and activation of this receptor. We generated four randomized P2Y12 libraries and investigated their ligand binding characteristics. P2Y12 was expressed in a Saccharomyces cerevisiae model system. Four libraries were generated with randomized amino acids at positions 181, 256, 265 and 280. Mutant variants were screened for functional activity in yeast using the natural P2Y12 ligand ADP. Activation results were investigated using quantitative structure-activity relationship (QSAR) models and ligand-receptor docking. We screened four positions in P2Y12 for functional activity by substitution with amino acids with diverse physiochemical properties. This analysis revealed that positions E181, R256 and R265 alter the functional activity of P2Y12 in a specific manner. QSAR models for E181 and R256 mutant libraries strongly supported the experimental data. All substitutions of amino acid K280 were completely inactive, highlighting the crucial role of this residue in P2Y12 function. Ligand-receptor docking revealed that K280 is likely to be a key element in the ligand-binding pocket of P2Y12. The results of this study demonstrate that positions 181, 256, 265 and 280 of P2Y12 are important for the functional integrity of the receptor. Moreover, K280 appears to be a crucial feature of the P2Y12 ligand-binding pocket. These results are important for rational design of novel antiplatelet agents.
|
|
| 23. |
- Ignatovica, Vita, et al.
(författare)
-
Single nucleotide polymorphisms of the purinergic 1 receptor are not associated with myocardial infarction in a Latvian population
- 2012
-
Ingår i: Molecular Biology Reports. - : Springer Science and Business Media LLC. - 0301-4851 .- 1573-4978. ; 39:2, s. 1917-1925
-
Tidskriftsartikel (refereegranskat)abstract
- The purinergic 1 receptor (P2RY1) has been implicated in development of heart disease and in individual pharmacodynamic response to anticoagulant therapies. However, the association of polymorphisms in the P2RY1 gene with myocardial infarction (MI), and its associated conditions, has yet to be reported in the literature. We evaluated seven known SNPs in P2RY1 for association with MI in a Latvian population. Seven independent parameters that are related to MI [body mass index (BMI), type 2 diabetes (T2D), angina pectoris, hypertension, hyperlipidemia, atrial fibrillation and heart failure] were investigated. No significant association with MI was observed for any of the polymorphisms. Those SNPs for which the P value was close to significance were located in coding or promoter regions. Intriguingly, carriers of the minor allele in the P2RY1 gene locus showed a tendency towards higher onset age for MI, suggesting a possible protective effect of these SNPs against MI or their contribution in progression as opposed to onset. Finally, a linkage disequilibrium (LD) plot was generated for these polymorphisms in the Latvian population. The results of this study suggest that the role of P2RY1 in individuals from Latvian population is likely to be principally involved in platelet aggregation and thromboembolic diseases, and not as a significant contributing factor to the global metabolic syndrome.
|
|
| 24. |
- Jacobsson, Josefin A., et al.
(författare)
-
Major gender difference in association of FTO gene variant among severely obese children with obesity and obesity related phenotypes.
- 2008
-
Ingår i: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 368:3, s. 476-482
-
Tidskriftsartikel (refereegranskat)abstract
- Recent studies have shown that SNPs in the FTO gene predispose to childhood and adult obesity. In this study, we examined the association between variants in FTO and KIAA1005, a gene that maps closely to FTO, and obesity, as well as obesity related traits among 450 well characterised severely obese children and 512 normal weight controls. FTO showed significant association with several obesity related traits while SNPs in KIAA1005 did not. When stratified by gender, the FTO variant rs9939609 showed association with obesity and BMI among girls (P=0.006 and 0.004, respectively) but not among boys. Gender differences were also found in the associations of the FTO rs9939609 with obesity related traits such as insulin sensitivity and plasma glucose. This study suggests that FTO may have an important role for gender specific development of severe obesity and insulin resistance in children.
|
|
| 25. |
- Jacobsson, J. A., et al.
(författare)
-
Novel genetic variant in FTO influences insulin levels and insulin resistance in severely obese children and adolescents.
- 2008
-
Ingår i: International Journal of Obesity. - : Springer Science and Business Media LLC. - 0307-0565 .- 1476-5497. ; 32:11, s. 1730-1735
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND The global prevalence of obesity and overweight is increasing rapidly among adults as well as among children and adolescents. Recent genome-wide association studies have provided strong support for association between variants in the FTO gene and obesity. We sequenced regions of the FTO gene to identify novel variants that are associated with obesity and related metabolic traits. RESULTS We screened exons 3 and 4 including exon-intron boundaries in FTO in 48 obese children and adolescents and identified three novel single nucleotide polymorphism in the fourth intronic region, (c.896+37A>G, c.896+117C>G and c.896+223A>G). We further genotyped c.896+223A>G in 962 subjects, 450 well-characterized obese children and adolescents and 512 adolescents with normal weight. Evidence for differences in genotype frequencies were not detected for the c.896+223A>G variant between extremely obese children and adolescents and normal weight adolescents (P=0.406, OR=1.154 (0.768-1.736)). Obese subjects with the GG genotype, however, had 30% increased fasting serum insulin levels (P=0.017) and increased degree of insulin resistance (P=0.025). There were in addition no differences in body mass index (BMI) or BMI standard deviation score (SDS) levels among the obese subjects according to genotype and the associations with insulin levels and insulin resistance remained significant when adjusting for BMI SDS. CONCLUSION These findings suggest that this novel variant in FTO is affecting metabolic phenotypes such as insulin resistance, which are not mediated through differences in BMI levels.
|
|
| 26. |
- Kalnina, Ineta, et al.
(författare)
-
Association between a rare SNP in the second intron of human Agouti related protein gene and increased BMI
- 2009
-
Ingår i: BMC Medical Genetics. - : Springer Science and Business Media LLC. - 1471-2350. ; 10, s. 63-
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The agouti related protein (AGRP) is an endogenous antagonist of the melanocortin 4 receptor and is one of the most potent orexigenic factors. The aim of the present study was to assess the genetic variability of AGRP gene and investigate whether the previously reported SNP rs5030980 and the rs11575892, a SNP that so far has not been studied with respect to obesity is associated with increased body mass index (BMI). METHODS: We determined the complete sequence of the AGRP gene and upstream promoter region in 95 patients with severe obesity (BMI > 35 kg/m2). Three polymorphisms were identified: silent mutation c.123G>A (rs34123523) in the second exon, non-synonymous mutation c.199G>A (rs5030980) and c.131-42C>T (rs11575892) located in the second intron. We further screened rs11575892 in a selected group of 1135 and rs5030980 in group of 789 participants from the Genome Database of Latvian Population and Latvian State Research Program Database. RESULTS: The CT heterozygotes of rs11575892 had significantly higher mean BMI value (p = 0.027). After adjustment for age, gender and other significant non-genetic factors (presence of diseases), the BMI levels remained significantly higher in carriers of the rs11575892 T allele (p = 0.001). The adjusted mean BMI value of CC genotype was 27.92 +/- 1.01 kg/m2 (mean, SE) as compared to 30.97 +/- 1.03 kg/m2 for the CT genotype. No association was found between rs5030980 and BMI. CONCLUSION: This study presents an association of rare allele of AGRP polymorphism in heterozygous state with increased BMI. The possible functional effects of this polymorphism are unclear but may relate to splicing defects.
|
|
| 27. |
- Kalnina, Ineta, et al.
(författare)
-
Polymorphisms in FTO and near TMEM18 associate with type 2 diabetes and predispose to younger age at diagnosis of diabetes
- 2013
-
Ingår i: Gene. - : Elsevier BV. - 0378-1119 .- 1879-0038. ; 527:2, s. 462-468
-
Tidskriftsartikel (refereegranskat)abstract
- Variations in the FTO gene and near the TMEM18 gene are risk factors for common form of obesity, but have also been linked with type 2 diabetes (T2D). Our aim was to investigate the contribution of these variants to risk of T2D in a population in Latvia. Four single nucleotide polymorphisms (SNP) in the first and fourth intronic regions of FTO and one close to TMEM18 were genotyped in 987 patients with T2D and 1080 controls selected from the Latvian Genome Data Base (LGDB). We confirmed association of SNPs in the first intron (rs11642015, rs62048402 and rs9939609) of FTO and rs7561317 representing the TMEM18 locus with T2D. Association between SNP in FTO and T2D remained significant after correction for body mass index (BMI). The rs57103849 located in the fourth intron of FTO and rs7561317 in TMEM18 showed BMI independent association with younger age at diagnosis of T2D. Our results add to the evidence that BMI related variants in and near FTO and TMEM18 may increase the risk for T2D not only through secondary effects of obesity. The influence of variants in the fourth intron of the FTO gene on development of T2D may be mediated by mechanisms other than those manifested by SNPs in the first intron of the same gene.
|
|
| 28. |
- Klovins, Janis, et al.
(författare)
-
Cloning of two melanocortin (MC) receptors in spiny dogfish : MC3 receptor in cartilaginous fish shows high affinity to ACTH-derived peptides while it has lower preference to gamma-MSH
- 2004
-
Ingår i: European Journal of Biochemistry. - : Wiley. - 0014-2956 .- 1432-1033. ; 271:21, s. 4320-4331
-
Tidskriftsartikel (refereegranskat)abstract
- We report the cloning and characterization of two melanocortin receptors (MCRs) from the spiny dogfish (Squalus acanthias) (Sac). Phylogenetic analysis shows that these shark receptors are orthologues of the MC3R and MC5R subtypes, sharing 65% and 70% overall amino acid identity with the human counterparts, respectively. The SacMC3R was expressed and pharmacologically characterized in HEK293 cells. The radioligand binding results show that this receptor has high affinity for adrenocorticotropic hormone (ACTH)-derived peptides while it has comparable affinity for alpha- and beta-melanocyte stimulating hormone (MSH), and slightly lower affinity for gamma-MSH when compared with the human orthologue. ACTH(1-24) has high potency in a second-messenger cAMP assay while alpha- and gamma-MSH had slightly lower potency in cells expressing the SacMC3R. We used receptor-enhanced green fluorescence protein (EGFP) fusion to show the presence of SacMC3R in plasma membrane of Chinese hamster ovary and HEK293 cells but the SacMC5R was retained in intracellular compartments of these cells hindering pharmacological characterization. The anatomical distribution of the receptors were determined using reverse transcription PCR. The results showed that the SacMC3R is expressed in the hypothalamus, brain stem and telencephalon, optic tectum and olfactory bulbs, but not in the cerebellum of the spiny dogfish while the SacMC5R was found only in the same central regions. This report describes the first molecular characterization of a MC3R in fish. The study indicates that many of the important elements of the MC system existed before radiation of gnathostomes, early in vertebrate evolution, at least 450 million years ago.
|
|
| 29. |
- Koenig, Julian, et al.
(författare)
-
Cortical thickness and resting-state cardiac function across the lifespan : A cross-sectional pooled mega-analysis
- 2021
-
Ingår i: Psychophysiology. - : Wiley. - 0048-5772 .- 1469-8986 .- 1540-5958. ; 58:7
-
Tidskriftsartikel (refereegranskat)abstract
- Understanding the association between autonomic nervous system [ANS] function and brain morphology across the lifespan provides important insights into neurovisceral mechanisms underlying health and disease. Resting-state ANS activity, indexed by measures of heart rate [HR] and its variability [HRV] has been associated with brain morphology, particularly cortical thickness [CT]. While findings have been mixed regarding the anatomical distribution and direction of the associations, these inconsistencies may be due to sex and age differences in HR/HRV and CT. Previous studies have been limited by small sample sizes, which impede the assessment of sex differences and aging effects on the association between ANS function and CT. To overcome these limitations, 20 groups worldwide contributed data collected under similar protocols of CT assessment and HR/HRV recording to be pooled in a mega-analysis (N = 1,218 (50.5% female), mean age 36.7 years (range: 12–87)). Findings suggest a decline in HRV as well as CT with increasing age. CT, particularly in the orbitofrontal cortex, explained additional variance in HRV, beyond the effects of aging. This pattern of results may suggest that the decline in HRV with increasing age is related to a decline in orbitofrontal CT. These effects were independent of sex and specific to HRV; with no significant association between CT and HR. Greater CT across the adult lifespan may be vital for the maintenance of healthy cardiac regulation via the ANS—or greater cardiac vagal activity as indirectly reflected in HRV may slow brain atrophy. Findings reveal an important association between CT and cardiac parasympathetic activity with implications for healthy aging and longevity that should be studied further in longitudinal research.
|
|
| 30. |
- Lagerström, Malin C., et al.
(författare)
-
High affinity agonistic metal ion binding sites within the melanocortin 4 receptor illustrate conformational change of transmembrane region 3
- 2003
-
Ingår i: Journal of Biological Chemistry. - : American Society for Biochemistry and Molecular Biology. - 0021-9258 .- 1083-351X. ; 278:51, s. 51521-51526
-
Tidskriftsartikel (refereegranskat)abstract
- We created a molecular model of the human melanocortin 4 receptor (MC4R) and introduced a series of His residues into the receptor protein to form metal ion binding sites. We were able to insert micromolar affinity binding sites for zinc between transmembrane region (TM) 2 and TM3 where the metal ion alone was able to activate this peptide binding G-protein-coupled receptor. The exact conformation of the metal ion interactions allowed us to predict the orientation of the helices, and remodeling of the receptor protein indicated that Glu100 and Ile104 in TM2 and Asp122 and Ile125 in TM3 are directed toward a putative area of activation of the receptor. The molecular model suggests that a rotation of TM3 may be important for activation of the MC4R. Previous models of G-protein-coupled receptors have suggested that unlocking of a stabilizing interaction between the DRY motif, in the cytosolic part of TM3, and TM6 is important for the activation process. We suggest that this unlocking process may be facilitated through creation of a new interaction between TM3 and TM2 in the MC4R.
|
|
| 31. |
- Lagerström, Malin C., et al.
(författare)
-
The evolutionary history and tissue mapping of GPR123 : specific CNS expression pattern predominantly in thalamic nuclei and regions containing large pyramidal cells
- 2007
-
Ingår i: Journal of Neurochemistry. - : Wiley. - 0022-3042 .- 1471-4159. ; 100:4, s. 1129-1142
-
Tidskriftsartikel (refereegranskat)abstract
- The Adhesion family of G protein-coupled receptors (GPCRs) includes 33 receptors and is the second largest GPCR family. Most of these proteins are still orphans and fairly little is known of their tissue distribution and evolutionary context. We report the evolutionary history of the Adhesion family protein GPR123 as well as mapping of GPR123 mRNA expression in mouse and rat using in situ hybridization and real-time PCR, respectively. GPR123 was found to be well conserved within the vertebrate lineage, especially within the transmembrane regions and in the distal part of the cytoplasmic tail, containing a potential PDZ binding domain. The real-time PCR data indicates that GPR123 is predominantly expressed in CNS. The in situ data show high expression in thalamic nuclei and regions containing large pyramidal cells like cortex layers 5 and 6 and subiculum. Moreover, we found distinct expression in amygdala, hypothalamus, inferior olive and spinal cord. The CNS specific expression, together with the high sequence conservation between the vertebrate sequences investigated, indicate that GPR123 may have an important role in the regulation of neuronal signal transduction.
|
|
| 32. |
- Niehaves, B., et al.
(författare)
-
Participative enterprise modelling for balanced scorecard implementation
- 2006
-
Ingår i: Proc. Eur. Conf. Inf. Syst., ECIS.
-
Konferensbidrag (refereegranskat)abstract
- Balanced Scorecards (BSC) have been established as a valuable and practicable instrument addressing major management problems in organisations. BSC are commonly IT-supported and found a conceptual basis for management information systems. They are often applied to IT-Controlling, and they are also repeatedly applied to specify requirements towards the corporate IT architecture. However, BSC implementation often struggles when it comes to discovering and documenting organisational knowledge that is not easily accessible or not of sufficient quality. On the other hand, Enterprise modelling (EM) seeks to solve organisational design problems in, for instance, business process reengineering, strategy planning, enterprise integration, and information systems development. Here, participative EM methods lead to improved quality as well as to consensus and to increased acceptance of the business decisions. At this juncture, participative EM can support BSC implementation projects that comprise activities requiring the discovery and documentation of organisational knowledge that is not easily accessible or not of sufficient quality. For that reason, the aim of this paper is to integrate participative EM approaches, taking Enterprise Knowledge Development (EKD) as an example, and BSC implementation. In order to operationalise this conceptual improvement, we will perform a stepwise analysis of BSC implementation processes and identify shortcomings that are able to be addressed with the help of participative enterprise modelling.
|
|
| 33. |
|
|
| 34. |
|
|
| 35. |
- Ringholm, Aneta, et al.
(författare)
-
Pharmacological characterization of loss of function mutations of the human melanocortin 1 receptor that are associated with red hair
- 2004
-
Ingår i: Journal of Investigative Dermatology. - 0022-202X .- 1523-1747. ; 123:5, s. 917-923
-
Tidskriftsartikel (refereegranskat)abstract
- Variation in skin color is the major host risk factor for melanoma and other forms of skin cancer. Individuals with red hair show an increased ratio of phaeomelanin to eumelanin in both hair and skin. This ratio is regulated by the melanocortin (MC) 1 receptor. There are several common point mutations in the human MC1 receptor that are overrepresented in North European red-heads, and in individuals with pale skin. In order to determine the functional significance of these mutations, we expressed the Asp84Glu, Val92Met, Arg163Gln, and Asp294His variants of the human MC1 receptors in eukaryotic cells and determined their ability to bind alpha-melanocyte stimulating hormone (MSH) peptides and increase intracellular cAMP. The mutants Asp84Glu and Asp294His showed a much lower response to alpha-MSH in cAMP and a slightly impaired ability to bind alpha-MSH, and the Val92Met mutant bound alpha-MSH with 100-fold lower affinity as compared with the wild-type. The Arg163Gln variant, widely found in some Asian populations, reached normal level of cAMP response but had just slightly lower potency for alpha-MSH in binding and second messenger studies. The results provide important pharmacological characterization of common MC1 receptor variants in various world populations.
|
|
| 36. |
|
|
| 37. |
- Rovite, Vita, et al.
(författare)
-
The role of common and rare MC4R variants and FTO polymorphisms in extreme form of obesity
- 2014
-
Ingår i: Molecular Biology Reports. - : Springer Science and Business Media LLC. - 0301-4851 .- 1573-4978. ; 41:3, s. 1491-500
-
Tidskriftsartikel (refereegranskat)abstract
- Melanocortin 4 receptor (MC4R) is an important regulator of food intake and number of studies report genetic variations influencing the risk of obesity. Here we explored the role of common genetic variation from MC4R locus comparing with SNPs from gene FTO locus, as well as the frequency and functionality of rare MC4R mutations in cohort of 380 severely obese individuals (BMI > 39 kg/m(2)) and 380 lean subjects from the Genome Database of Latvian Population (LGDB). We found correlation for two SNPs-rs11642015 and rs62048402 in the fat mass and obesity-associated protein (FTO) with obesity but no association was detected for rs17782313 located in the MC4R locus in these severely obese individuals. We sequenced the whole gene MC4R coding region in all study subjects and found five previously known heterozygous non-synonymous substitutions V103I, I121T, S127L, V166I and I251L. Expression in mammalian cells showed that the S127L, V166I and double V103I/S127L mutant receptors had significantly decreased quantity at the cell surface compared to the wild type MC4R. We carried out detailed functional analysis of V166I that demonstrated that, despite low abundance in plasma membrane, the V166I variant has lower EC50 value upon αMSH activation than the wild type receptor, while the level of AGRP inhibition was decreased, implying that V166I cause hyperactive satiety signalling. Overall, this study suggest that S127L may be the most frequent functional MC4R mutation leading to the severe obesity in general population and provides new insight into the functionality of population based variants of the MC4R.
|
|
| 38. |
- Schiöth, Helgi B, et al.
(författare)
-
Evolutionary conservation of the structural, pharmacological, and genomic characteristics of the melanocortin receptor subtypes
- 2005
-
Ingår i: Peptides. - : Elsevier BV. - 0196-9781 .- 1873-5169. ; 26:10, s. 1886-1900
-
Tidskriftsartikel (refereegranskat)abstract
- We have cloned melanocortin receptors (MCRs) from several species of fish. The MC4R and MC5R subtypes arose early in vertebrate evolution and their primary structure is remarkably conserved. Expression and pharmacological characterization of the MCRs in fish has revealed that they bind and respond to melanocortin peptides with high potency. Detailed characterization of the binding properties of the different subtypes suggests that MCRs in early vertebrates had preference for adrenocorticotropic hormone (ACTH) peptides, while the high sensitivity for the shorter proopiomelanocortin (POMC) products, such as the α-, β-, and γ-melanocyte-stimulating hormone (MSH), has appeared later, perhaps as the MCR subtypes gained more specialized functions. The MCR repertoire shows in general high similarities in their primary structures, while they are however not similar in terms of functional roles. The MCRs serve therefore as an interesting model family to understand the molecular mechanisms of how functions of the genes can diverge during evolution. In this review, we provide an overview of our recent studies on the cloning, expression, pharmacology, 3D modeling, and genomic studies of the MCRs in non-mammalian species.
|
|
| 39. |
- Schiöth, Helgi B., et al.
(författare)
-
Unusual genomic structure : melanocortin receptors in fugu
- 2005
-
Ingår i: Annals of the New York Academy of Sciences. - : New York Academy of Sciences. - 0077-8923 .- 1749-6632. ; 1040, s. 460-463
-
Tidskriftsartikel (refereegranskat)abstract
- The melanocortin (MC) receptors are found in five subtypes in mammals and chicken, while recent studies have shown that the Fugu (Takifugu rubripes) genome has only four MC receptors and the zebrafish genome has six subtypes. The MC3 receptor seems to be missing from the two closely related pufferfishes, Fugu and Tetraodon (Tetraodon nigroviridis). The MC2 and MC5 receptors in the pufferfish have introns. Moreover, these two receptors are found in a tandem that is remarkably conserved in several vertebrate species. Here, we speculate about the genomic origin of the MC receptors.
|
|
| 40. |
|
|
| 41. |
|
|
| 42. |
|
|
| 43. |
- Tafoya, Daniel, 1981, et al.
(författare)
-
First Images of the Molecular Gas around a Born-again Star Revealed by ALMA
- 2022
-
Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 925:1
-
Tidskriftsartikel (refereegranskat)abstract
- Born-again stars allow probing stellar evolution in human timescales and provide the most promising path for the formation of hydrogen-deficient post-asymptotic giant branch objects, but their cold and molecular components remain poorly explored. Here we present ALMA observations of V 605 Aql that unveil for the first time the spatio-kinematic distribution of the molecular material associated with a born-again star. Both the continuum and molecular line emission exhibit a clumpy ring-like structure with a total extent of approximate to 1 '' in diameter. The bulk of the molecular emission is interpreted as being produced in a radially expanding disk-like structure with an expansion velocity v(exp) similar to 90 km s(-1) and an inclination i approximate to 60 degrees with respect to the line of sight. The observations also reveal a compact high-velocity component, v(exp) similar to 280 km s(-1), that is aligned perpendicularly to the expanding disk. This component is interpreted as a bipolar outflow with a kinematical age tau less than or similar to 20 yr, which could either be material that is currently being ejected from V 605 Aql, or is being dragged from the inner parts of the disk by a stellar wind. The dust mass of the disk is in the range M-dust similar to 0.2-8 x 10(-3) M-circle dot, depending on the dust absorption coefficient. The mass of the CO is MCO approximate to 1.1 x 10(-5) M-circle dot, which is more than three orders of magnitude larger than the mass of the other detected molecules. We estimate a C-12/C-13 ratio of 5.6 +/- 0.6, which is consistent with the single stellar evolution scenario in which the star experienced a very late thermal pulse instead of a nova-like event as previously suggested.
|
|
| 44. |
- Voisin, Sarah, et al.
(författare)
-
Many obesity-associated SNPs strongly associate with DNA methylation changes at proximal promoters and enhancers
- 2015
-
Ingår i: Genome Medicine. - : Springer Science and Business Media LLC. - 1756-994X. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The mechanisms by which genetic variants, such as single nucleotide polymorphisms (SNPs), identified in genome-wide association studies act to influence body mass remain unknown for most of these SNPs, which continue to puzzle the scientific community. Recent evidence points to the epigenetic and chromatin states of the genome as having important roles. Methods: We genotyped 355 healthy young individuals for 52 known obesity-associated SNPs and obtained DNA methylation levels in their blood using the Illumina 450 K BeadChip. Associations between alleles and methylation at proximal cytosine residues were tested using a linear model adjusted for age, sex, weight category, and a proxy for blood cell type counts. For replication in other tissues, we used two open-access datasets (skin fibroblasts, n = 62; four brain regions, n = 121-133) and an additional dataset in subcutaneous and visceral fat (n = 149). Results: We found that alleles at 28 of these obesity-associated SNPs associate with methylation levels at 107 proximal CpG sites. Out of 107 CpG sites, 38 are located in gene promoters, including genes strongly implicated in obesity (MIR148A, BDNF, PTPMT1, NR1H3, MGAT1, SCGB3A1, HOXC12, PMAIP1, PSIP1, RPS10-NUDT3, RPS10, SKOR1, MAP2K5, SIX5, AGRN, IMMP1L, ELP4, ITIH4, SEMA3G, POMC, ADCY3, SSPN, LGR4, TUFM, MIR4721, SULT1A1, SULT1A2, APOBR, CLN3, SPNS1, SH2B1, ATXN2L, and IL27). Interestingly, the associated SNPs are in known eQTLs for some of these genes. We also found that the 107 CpGs are enriched in enhancers in peripheral blood mononuclear cells. Finally, our results indicate that some of these associations are not blood-specific as we successfully replicated four associations in skin fibroblasts. Conclusions: Our results strongly suggest that many obesity-associated SNPs are associated with proximal gene regulation, which was reflected by association of obesity risk allele genotypes with differential DNA methylation. This study highlights the importance of DNA methylation and other chromatin marks as a way to understand the molecular basis of genetic variants associated with human diseases and traits.
|
|
