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| 2. |
- Béthermin, Matthieu, et al.
(författare)
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CONCERTO: High-fidelity simulation of millimeter line emissions of galaxies and [CII] intensity mapping
- 2022
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 667
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Tidskriftsartikel (refereegranskat)abstract
- The intensity mapping of the [CII] 158-μm line redshifted to the submillimeter window is a promising probe of the za>4 star formation and its spatial distribution into large-scale structures. To prepare the first-generation experiments (e.g., CONCERTO), we need realistic simulations of the submillimeter extragalactic sky in spectroscopy. We present a new version of the simulated infrared dusty extragalactic sky (SIDES) model including the main submillimeter lines around 1 mm (CO, [CII], [CI]). This approach successfully reproduces the observed line luminosity functions. We then use our simulation to generate CONCERTO-like cubes (125-305 GHz) and forecast the power spectra of the fluctuations caused by the various astrophysical components at those frequencies. Depending on our assumptions on the relation between the star formation rate and [CII] luminosity, and the star formation history, our predictions of the za∼6 [CII] power spectrum vary by two orders of magnitude. This highlights how uncertain the predictions are and how important future measurements will be to improve our understanding of this early epoch. SIDES can reproduce the CO shot noise recently measured at a4;100 GHz by the millimeter-wavelength intensity mapping experiment (mmIME). Finally, we compare the contribution of the different astrophysical components at various redshifts to the power spectra. The continuum is by far the brightest, by a factor of three to 100, depending on the frequency. At 300 GHz, the CO foreground power spectrum is higher than the [CII] one for our base scenario. At lower frequencies, the contrast between [CII] and extragalactic foregrounds is even worse. Masking the known galaxies from deep surveys should allow us to reduce the foregrounds to 20% of the [CII] power spectrum up to z∼ 6.5. However, this masking method will not be sufficient at higher redshifts. The code and the products of our simulation are released publicly, and can be used for both intensity mapping experiments and submillimeter continuum and line surveys.
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| 3. |
- Van Cuyck, M., et al.
(författare)
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CONCERTO : Extracting the power spectrum of the [CII] emission line
- 2023
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Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 676
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Tidskriftsartikel (refereegranskat)abstract
- Context. CONCERTO is the first experiment to perform a [CII] line intensity mapping (LIM) survey on the COSMOS field to target z > 5.2. Measuring the [CII] angular power spectrum allows us to study the role of dusty star-forming galaxies in the star formation history during the epochs of Reionization and post-Reionization. The main obstacle to this measurement is the contamination by bright foregrounds: the dust continuum emission and atomic and molecular lines from foreground galaxies at z ≲ 3.Aims. We evaluate our ability to retrieve the [CII] signal in mock observations of the sky using the Simulated Infrared Dusty Extragalactic Sky (SIDES), which covers the mid-infrared to millimetre range. We also measure the impact of field-to-field variance on the residual foreground contamination.Methods. We compared two methods for dealing with the dust continuum emission from galaxies (i.e. the cosmic infrared background fluctuations): the standard principal component analysis (PCA) and the asymmetric re-weighted penalized least-squares (arPLS) method. For line interlopers, the strategy relies on masking low-redshift galaxies using the instrumental beam profile and external catalogues. As we do not have observations of CO or deep-enough classical CO proxies (such as LIR), we relied on the COSMOS stellar mass catalogue, which we demonstrate to be a reliable CO proxy for masking. To measure the angular power spectrum of masked data, we adapted the P of K EstimatoR (POKER) from cosmic infrared background studies and discuss its use on LIM data.Results. The arPLS method achieves a reduction in the cosmic infrared background fluctuations to a sub-dominant level of the [CII] power at z ∼ 7, a factor of > 70 below our fiducial [CII] model. When using the standard PCA, this factor is only 0.7 at this redshift. The masking lowers the power amplitude of line contamination down to 2 × 10−2 Jy2 sr−1. This residual level is dominated by faint undetected sources that are not clustered around the detected (and masked) sources. For our [CII] model, this results in a detection at z = 5.2 with a power ratio [CII]/(residual interlopers) = 62 ± 32 for a 22% area survey loss. However, at z = 7, [CII]/(residual interlopers) = 2.0 ± 1.4, due to the weak contrast between [CII] and the residual line contamination. Thanks to the large area covered by SIDES-Uchuu, we show that the power amplitude of line residuals varies by 12–15% for z = 5.2 − 7, which is less than the field-to-field variance affecting [CII] power spectra.Conclusions. We present an end-to-end simulation of the extragalactic foreground removal that we ran to detect the [CII] at high redshift via its angular power spectrum. We show that cosmic infrared background fluctuations are not a limiting foreground for [CII] LIM. On the contrary, the CO and [CI] line contamination severely limits our ability to accurately measure the [CII] angular power spectrum at z ≳ 7.
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| 4. |
- Gkogkou, A., et al.
(författare)
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CONCERTO: Simulating the CO, [CII], and [CI] line emission of galaxies in a 117 deg2 field and the impact of field-to-field variance
- 2023
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 670
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Tidskriftsartikel (refereegranskat)abstract
- In the submillimeter regime, spectral line scans and line intensity mapping (LIM) are new promising probes for the cold gas content and star formation rate of galaxies across cosmic time. However, both of these two measurements suffer from field-to-field variance. We study the effect of field-to-field variance on the predicted CO and [CII] power spectra from future LIM experiments such as CONCERTO, as well as on the line luminosity functions (LFs) and the cosmic molecular gas mass density that are currently derived from spectral line scans. We combined a 117 deg2 dark matter lightcone from the Uchuu cosmological simulation with the simulated infrared dusty extragalactic sky (SIDES) approach. The clustering of the dusty galaxies in the SIDES-Uchuu product is validated by reproducing the cosmic infrared background anisotropies measured by Herschel and Planck. We find that in order to constrain the CO LF with an uncertainty below 20%, we need survey sizes of at least 0.1 deg2. Furthermore, accounting for the field-to-field variance using only the Poisson variance can underestimate the total variance by up to 80%. The lower the luminosity is and the larger the survey size is, the higher the level of underestimate. At z < 3, the impact of field-to-field variance on the cosmic molecular gas density can be as high as 40% for the 4.6 arcmin2 field, but drops below 10% for areas larger than 0.2 deg2. However, at z > 3 the variance decreases more slowly with survey size and for example drops below 10% for 1 deg2 fields. Finally, we find that the CO and [CII] LIM power spectra can vary by up to 50% in 1 deg2 fields. This limits the accuracy of the constraints provided by the first 1 deg2 surveys. In addition the level of the shot noise power is always dominated by the sources that are just below the detection thresholds, which limits its potential for deriving number densities of faint [CII] emitters. We provide an analytical formula to estimate the field-to-field variance of current or future LIM experiments given their observed frequency and survey size. The underlying code to derive the field-to-field variance and the full SIDES-Uchuu products (catalogs, cubes, and maps) are publicly available.
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| 10. |
- Fasano, A., et al.
(författare)
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Gaps, Controversies, and Proposed Roadmap for Research in Normal Pressure Hydrocephalus
- 2020
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Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 35:11, s. 1945-1954
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Tidskriftsartikel (refereegranskat)abstract
- Idiopathic normal pressure hydrocephalus is considered common but remains underinvestigated. There are no uniformly accepted diagnostic criteria and therapeutic guidelines. We summarize the accumulated evidence regarding the definition, pathophysiology, diagnosis, and treatment of idiopathic normal pressure hydrocephalus, highlighting the many gaps and controversies, including diagnostic challenges, the frequent association with neurodegeneration and vascular disease, and the many unknowns regarding patient selection and outcome predictors. A roadmap to fill these gaps and solve the controversies around this condition is also proposed. More evidence is required with respect to diagnostic criteria, the value of ancillary testing, prospective population-based studies and novel trial designs. Furthermore, a need exists to develop new advanced options in shunt technology. (c) 2020 International Parkinson and Movement Disorder Society
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| 11. |
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| 12. |
- Landegren, N, et al.
(författare)
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AIREing out autoimmunity
- 2015
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Ingår i: SCIENCE TRANSLATIONAL MEDICINE. - 1946-6234. ; 7:292
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 13. |
- Lang, Anthony E, et al.
(författare)
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Integrated Safety of Levodopa-Carbidopa Intestinal Gel From Prospective Clinical Trials.
- 2016
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Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 31:4, s. 538-546
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Tidskriftsartikel (refereegranskat)abstract
- Continuous administration of levodopa-carbidopa intestinal gel (carbidopa-levodopa enteral suspension) through a percutaneous endoscopic gastrojejunostomy is a treatment option for advanced Parkinson disease (PD) patients with motor fluctuations resistant to standard oral medications. Safety data from 4 prospective studies were integrated to assess the safety of this therapy.
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| 14. |
- Ludvigsson, Jonas F., et al.
(författare)
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The Oslo definitions for coeliac disease and related terms
- 2013
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Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 62:1, s. 43-52
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Tidskriftsartikel (refereegranskat)abstract
- Objective The literature suggests a lack of consensus on the use of terms related to coeliac disease (CD) and gluten. Design A multidisciplinary task force of 16 physicians from seven countries used the electronic database PubMed to review the literature for CD-related terms up to January 2011. Teams of physicians then suggested a definition for each term, followed by feedback of these definitions through a web survey on definitions, discussions during a meeting in Oslo and phone conferences. In addition to 'CD', the following descriptors of CD were evaluated (in alphabetical order): asymptomatic, atypical, classical, latent, non-classical, overt, paediatric classical, potential, refractory, silent, subclinical, symptomatic, typical, CD serology, CD autoimmunity, genetically at risk of CD, dermatitis herpetiformis, gluten, gluten ataxia, gluten intolerance, gluten sensitivity and gliadin-specific antibodies. Results CD was defined as 'a chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary gluten in genetically predisposed individuals'. Classical CD was defined as 'CD presenting with signs and symptoms of malabsorption. Diarrhoea, steatorrhoea, weight loss or growth failure is required.' 'Gluten-related disorders' is the suggested umbrella term for all diseases triggered by gluten and the term gluten intolerance should not to be used. Other definitions are presented in the paper. Conclusion This paper presents the Oslo definitions for CD-related terms.
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| 18. |
- Andreoli, María F, et al.
(författare)
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Pre-prandial plasma liver-expressed antimicrobial peptide 2 (LEAP2) concentration in humans is inversely associated with hunger sensation in a ghrelin independent manner.
- 2023
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Ingår i: European Journal of Nutrition. - 1436-6207 .- 1436-6215.
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The liver-expressed antimicrobial peptide 2 (LEAP2) is a newly recognized peptide hormone that acts via the growth hormone secretagogue receptor (GHSR) blunting the effects of ghrelin and displaying ghrelin-independent actions. Since the implications of LEAP2 are beginning to be elucidated, we investigated if plasma LEAP2 concentration varies with feeding status or sex and whether it is associated with glucose metabolism and appetite sensations.METHODS: We performed a single test meal study, in which plasma concentrations of LEAP2, ghrelin, insulin and glucose as well as visual analogue scales for hunger, desire to eat, prospective food consumption, fullness were assessed before and 60 min after breakfast in 44 participants (n = 21 females) with normal weight (NW) or overweight/obesity (OW/OB).RESULTS: Pre-prandial plasma LEAP2 concentration was ~ 1.6-fold higher whereas ghrelin was ~ 2.0-fold lower in individuals with OW/OB (p < 0.001) independently of sex. After adjusting for body mass index (BMI) and sex, pre-prandial plasma LEAP2 concentration displayed a direct relationship with BMI (β: 0.09; 95%CI: 0.05, 0.13; p < 0.001), fat mass (β: 0.05; 95%CI: 0.01, 0.09; p = 0.010) and glycemia (β: 0.24; 95%CI: 0.05, 0.43; p = 0.021), whereas plasma ghrelin concentration displayed an inverse relationship with BMI and fat mass but not with glycemia. Postprandial plasma LEAP2 concentration increased ~ 58% in females with OW/OB (p = 0.045) but not in females with NW or in males. Pre-prandial plasma LEAP2 concentration displayed an inverse relationship with hunger score (β: - 11.16; 95% CI: - 18.52, - 3.79; p = 0.004), in a BMI-, sex- and ghrelin-independent manner.CONCLUSIONS: LEAP2 emerges as a key hormone implicated in the regulation of metabolism and appetite in humans.TRIAL REGISTRATION: The study was retrospectively registered in clinicaltrials.gov (April 2023).CLINICALTRIALS: gov Identifier: NCT05815641.
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| 19. |
- Bastide, Matthieu F, et al.
(författare)
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Pathophysiology of L-dopa-induced motor and non-motor complications in Parkinson's disease.
- 2015
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Ingår i: Progress in Neurobiology. - : Elsevier BV. - 1873-5118 .- 0301-0082. ; 132:Jul 21, s. 96-168
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Forskningsöversikt (refereegranskat)abstract
- Involuntary movements, or dyskinesia, represent a debilitating complication of levodopa (L-dopa) therapy for Parkinson's disease (PD). L-dopa-induced dyskinesia (LID) are ultimately experienced by the vast majority of patients. In addition, psychiatric conditions often manifested as compulsive behaviours, are emerging as a serious problem in the management of L-dopa therapy. The present review attempts to provide an overview of our current understanding of dyskinesia and other L-dopa-induced dysfunctions, a field that dramatically evolved in the past twenty years. In view of the extensive literature on LID, there appeared a critical need to re-frame the concepts, to highlight the most suitable models, to review the central nervous system (CNS) circuitry that may be involved, and to propose a pathophysiological framework was timely and necessary. An updated review to clarify our understanding of LID and other L-dopa-related side effects was therefore timely and necessary. This review should help in the development of novel therapeutic strategies aimed at preventing the generation of dyskinetic symptoms.
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| 20. |
- Fasano, Andrea, et al.
(författare)
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Kinetic Modeling of the Reversible or Irreversible Electrochemical Responses of FeFe-Hydrogenases
- 2024
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 146:2, s. 1455-1466
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Tidskriftsartikel (refereegranskat)abstract
- The enzyme FeFe-hydrogenase catalyzes H2 evolution and oxidation at an active site that consists of a [4Fe-4S] cluster bridged to a [Fe2(CO)3(CN)2(azadithiolate)] subsite. Previous investigations of its mechanism were mostly conducted on a few “prototypical” FeFe-hydrogenases, such as that from Chlamydomonas reinhardtii(Cr HydA1), but atypical hydrogenases have recently been characterized in an effort to explore the diversity of this class of enzymes. We aim at understanding why prototypical hydrogenases are active in either direction of the reaction in response to a small deviation from equilibrium, whereas the homologous enzyme from Thermoanaerobacter mathranii (Tam HydS) shows activity only under conditions of very high driving force, a behavior that was referred to as “irreversible catalysis”. We follow up on previous spectroscopic studies and recent developments in the kinetic modeling of bidirectional reactions to investigate and compare the catalytic cycles of Cr HydA1 and Tam HydS under conditions of direct electron transfer with an electrode. We compare the hypothetical catalytic cycles described in the literature, and we show that the observed changes in catalytic activity as a function of potential, pH, and H2 concentration can be explained with the assumption that the same catalytic mechanism applies. This helps us identify which variations in properties of the catalytic intermediates give rise to the distinct “reversible” or “irreversible” catalytic behaviors.
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| 21. |
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| 22. |
- Fasano, M., et al.
(författare)
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Towards a functional definition of the mitochondrial human proteome
- 2016
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Ingår i: EuPA Open Proteomics. - : Elsevier. - 2212-9685. ; 10, s. 24-27
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Tidskriftsartikel (refereegranskat)abstract
- The mitochondrial human proteome project (mt-HPP) was initiated by the Italian HPP group as a part of both the chromosome-centric initiative (C-HPP) and the "biology and disease driven" initiative (B/D-HPP). In recent years several reports highlighted how mitochondrial biology and disease are regulated by specific interactions with non-mitochondrial proteins. Thus, it is of great relevance to extend our present view of the mitochondrial proteome not only to those proteins that are encoded by or transported to mitochondria, but also to their interactors that take part in mitochondria functionality. Here, we propose a graphical representation of the functional mitochondrial proteome by retrieving mitochondrial proteins from the NeXtProt database and adding to the network their interactors as annotated in the IntAct database. Notably, the network may represent a reference to map all the proteins that are currently being identified in mitochondrial proteomics studies.
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| 23. |
- Furman, David, et al.
(författare)
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Chronic inflammation in the etiology of disease across the life span
- 2019
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 25:12, s. 1822-1832
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Tidskriftsartikel (refereegranskat)abstract
- Although intermittent increases in inflammation are critical for survival during physical injury and infection, recent research has revealed that certain social, environmental and lifestyle factors can promote systemic chronic inflammation (SCI) that can, in turn, lead to several diseases that collectively represent the leading causes of disability and mortality worldwide, such as cardiovascular disease, cancer, diabetes mellitus, chronic kidney disease, non-alcoholic fatty liver disease and autoimmune and neurodegenerative disorders. In the present Perspective we describe the multi-level mechanisms underlying SCI and several risk factors that promote this health-damaging phenotype, including infections, physical inactivity, poor diet, environmental and industrial toxicants and psychological stress. Furthermore, we suggest potential strategies for advancing the early diagnosis, prevention and treatment of SCI.
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| 24. |
- Johnson, Calvin W., et al.
(författare)
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White paper: From bound states to the continuum
- 2020
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Ingår i: Journal of Physics G: Nuclear and Particle Physics. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 47:12
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Forskningsöversikt (refereegranskat)abstract
- This white paper reports on the discussions of the 2018 Facility for Rare Isotope Beams Theory Alliance (FRIB-TA) topical program ‘From bound states to the continuum: Connecting bound state calculations with scattering and reaction theory’. One of the biggest and most important frontiers in nuclear theory today is to construct better and stronger bridges between bound state calculations and calculations in the continuum, especially scattering and reaction theory, as well as teasing out the influence of the continuum on states near threshold. This is particularly challenging as many-body structure calculations typically use a bound state basis, while reaction calculations more commonly utilize few-body continuum approaches. The many-body bound state and few-body continuum methods use different language and emphasize different properties. To build better foundations for these bridges, we present an overview of several bound state and continuum methods and, where possible, point to current and possible future connections.
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| 27. |
- Parenti, Marco Daniele, et al.
(författare)
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Discovery of the 4-aminopiperidine-based compound EM127 for the site-specific covalent inhibition of SMYD3
- 2022
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Ingår i: European Journal of Medicinal Chemistry. - : Elsevier. - 0223-5234 .- 1768-3254. ; 243
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Tidskriftsartikel (refereegranskat)abstract
- Recent findings support the hypothesis that inhibition of SMYD3 methyltransferase may be a therapeutic avenue for some of the deadliest cancer types. Herein, active site-selective covalent SMYD3 inhibitors were designed by introducing an appropriate reactive cysteine trap into reversible first-generation SMYD3 inhibitors. The 4-amino-piperidine derivative EM127 (11C) bearing a 2-chloroethanoyl group as reactive warhead showed selectivity for Cys186, located in the substrate/histone binding pocket. Selectivity towards Cys186 was retained even at high inhibitor/enzyme ratio, as shown by mass spectrometry. The mode of interaction with the SMYD3 substrate/ histone binding pocket was revealed by crystallographic studies. In enzymatic assays, 11C showed a stronger SMYD3 inhibitory effect compared to the reference inhibitor EPZ031686. Remarkably, 11C attenuated the proliferation of MDA-MB-231 breast cancer cell line at the same low micromolar range of concentrations that reduced SMYD3 mediated ERK signaling in HCT116 colorectal cancer and MDA-MB-231 breast cancer cells. Furthermore, 11C (5 mu M) strongly decreased the steady-state mRNA levels of genes important for tumor biology such as cyclin dependent kinase 2, c-MET, N-cadherin and fibronectin 1, all known to be regulated, at least in part, by SMYD3. Thus, 11C is as a first example of second generation SMYD3 inhibitors; this agent represents a covalent and a site specific SMYD3 binder capable of potent and prolonged attenuation of methyltransferase activity.
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