| 1. |
- Guerreiro, Rita, et al.
(författare)
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Genome-wide analysis of genetic correlation in dementia with Lewy bodies, Parkinson's and Alzheimer's diseases.
- 2016
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 1558-1497 .- 0197-4580. ; 38, s. 7-214
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Tidskriftsartikel (refereegranskat)abstract
- The similarities between dementia with Lewy bodies (DLB) and both Parkinson's disease (PD) and Alzheimer's disease (AD) are many and range from clinical presentation, to neuropathological characteristics, to more recently identified, genetic determinants of risk. Because of these overlapping features, diagnosing DLB is challenging and has clinical implications since some therapeutic agents that are applicable in other diseases have adverse effects in DLB. Having shown that DLB shares some genetic risk with PD and AD, we have now quantified the amount of sharing through the application of genetic correlation estimates, and show that, from a purely genetic perspective, and excluding the strong association at the APOE locus, DLB is equally correlated to AD and PD.
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| 2. |
- Kun-Rodrigues, Celia, et al.
(författare)
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A comprehensive screening of copy number variability in dementia with Lewy bodies.
- 2019
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Ingår i: Neurobiology of aging. - : Elsevier BV. - 1558-1497 .- 0197-4580. ; 75
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Tidskriftsartikel (refereegranskat)abstract
- The role of genetic variability in dementia with Lewy bodies (DLB) is now indisputable; however, data regarding copy number variation (CNV) in this disease has been lacking. Here, we used whole-genome genotyping of 1454 DLB cases and 1525 controls to assess copy number variability. We used 2 algorithms to confidently detect CNVs, performed a case-control association analysis, screened for candidate CNVs previously associated with DLB-related diseases, and performed a candidate gene approach to fully explore the data. We identified 5 CNV regions with a significant genome-wide association to DLB; 2 of these were only present in cases and absent from publicly available databases: one of the regions overlapped LAPTM4B, a known lysosomal protein, whereas the other overlapped the NME1 locus and SPAG9. We also identified DLB cases presenting rare CNVs in genes previously associated with DLB or related neurodegenerative diseases, such as SNCA, APP, and MAPT. To our knowledge, this is the first study reporting genome-wide CNVs in a large DLB cohort. These results provide preliminary evidence for the contribution of CNVs in DLB risk.
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| 3. |
- Kun-Rodrigues, Celia, et al.
(författare)
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Analysis of C9orf72 repeat expansions in a large international cohort of dementia with Lewy bodies
- 2017
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 49
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Tidskriftsartikel (refereegranskat)abstract
- . C9orf72 repeat expansions are a common cause of amyotrophic lateral sclerosis and frontotemporal dementia. To date, no large-scale study of dementia with Lewy bodies (DLB) has been undertaken to assess the role of . C9orf72 repeat expansions in the disease. Here, we investigated the prevalence of . C9orf72 repeat expansions in a large cohort of DLB cases and identified no pathogenic repeat expansions in neuropathologically or clinically defined cases, showing that . C9orf72 repeat expansions are not causally associated with DLB.
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| 4. |
- Mann, Andrew W., et al.
(författare)
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Zodiacal Exoplanets In Time (Zeit). III. A Short-Period Planet Orbiting A Pre-Main-Sequence Star In The Upper Scorpius Ob Association
- 2016
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Ingår i: Astronomical Journal. - : American Astronomical Society. - 0004-6256 .- 1538-3881. ; 152:3
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Tidskriftsartikel (refereegranskat)abstract
- We confirm and characterize a close-in (P-orb = 5.425 days), super-Neptune sized (5.04(-0.37)(+0.34) R-circle plus) planet transiting K2-33 (2MASS J16101473-1919095), a late-type (M3) pre-main-sequence (11 Myr old) star in the Upper Scorpius subgroup of the Scorpius-Centaurus OB association. The host star has the kinematics of a member of the Upper Scorpius OB association, and its spectrum contains lithium absorption, an unambiguous sign of youth (<20 Myr) in late-type dwarfs. We combine photometry from K2 and the ground-based MEarth project to refine the planet's properties and constrain the host star's density. We determine K2-33's bolometric flux and effective temperature from moderate-resolution spectra. By utilizing isochrones that include the effects of magnetic fields, we derive a precise radius (6%-7%) and mass (16%) for the host star, and a stellar age consistent with the established value for Upper Scorpius. Follow-up high-resolution imaging and Doppler spectroscopy confirm that the transiting object is not a stellar companion or a background eclipsing binary blended with the target. The shape of the transit, the constancy of the transit depth and periodicity over 1.5 yr, and the independence with wavelength rule out stellar variability or a dust cloud or debris disk partially occulting the star as the source of the signal; we conclude that it must instead be planetary in origin. The existence of K2-33b suggests that close-in planets can form in situ or migrate within similar to 10 Myr, e.g., via interactions with a disk, and that long-timescale dynamical migration such as by Lidov-Kozai or planet-planet scattering is not responsible for all short-period planets.
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| 5. |
- Muirhead, Philip S., et al.
(författare)
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Kepler-445, Kepler-446 and the Occurrence of Compact Multiples Orbiting mid-M Dwarf Stars
- 2015
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 801:1
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Tidskriftsartikel (refereegranskat)abstract
- We confirm and characterize the exoplanetary systems Kepler-445 and Kepler-446: two mid-M dwarf stars, each with multiple, small, short-period transiting planets. Kepler-445 is a metal-rich ([ Fe/H] = + 0.25 0.10) M4 dwarf with three transiting planets, and Kepler-446 is a metal-poor ([ Fe/H] = -0.30 0.10) M4 dwarf also with three transiting planets. Kepler-445c is similar toGJ 1214b: both in planetary radius and the properties of the host star. The Kepler-446 system is similar to the Kepler-42 system: both are metal-poor with large galactic space velocities and three short-period, likely rocky transiting planets that were initially assigned erroneously large planet-to-star radius ratios. We independently determined stellar parameters from spectroscopy and searched for and fitted the transit light curves for the planets, imposing a strict prior on stellar density in order to remove correlations between the fitted impact parameter and planet-to-star radius ratio for short-duration transits. Combining Kepler-445, Kepler-446, and Kepler-42, and isolating all mid-M dwarf stars observed by Kepler with the precision necessary to detect similar systems, we calculate that 21+ 7 -5 % of mid-M dwarf stars host compact multiples ( multiple planets with periods of less than 10 days) for a wide range of metallicities. We suggest that the inferred planet masses for these systems support highly efficient accretion of protoplanetary disk metals by mid-M dwarf protoplanets.
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| 6. |
- Zamora, Juan Carlos, et al.
(författare)
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Considerations and consequences of allowing DNA sequence data as types of fungal taxa
- 2018
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Ingår i: IMA Fungus. - : INT MYCOLOGICAL ASSOC. - 2210-6340 .- 2210-6359. ; 9:1, s. 167-185
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Tidskriftsartikel (refereegranskat)abstract
- Nomenclatural type definitions are one of the most important concepts in biological nomenclature. Being physical objects that can be re-studied by other researchers, types permanently link taxonomy (an artificial agreement to classify biological diversity) with nomenclature (an artificial agreement to name biological diversity). Two proposals to amend the International Code of Nomenclature for algae, fungi, and plants (ICN), allowing DNA sequences alone (of any region and extent) to serve as types of taxon names for voucherless fungi (mainly putative taxa from environmental DNA sequences), have been submitted to be voted on at the 11th International Mycological Congress (Puerto Rico, July 2018). We consider various genetic processes affecting the distribution of alleles among taxa and find that alleles may not consistently and uniquely represent the species within which they are contained. Should the proposals be accepted, the meaning of nomenclatural types would change in a fundamental way from physical objects as sources of data to the data themselves. Such changes are conducive to irreproducible science, the potential typification on artefactual data, and massive creation of names with low information content, ultimately causing nomenclatural instability and unnecessary work for future researchers that would stall future explorations of fungal diversity. We conclude that the acceptance of DNA sequences alone as types of names of taxa, under the terms used in the current proposals, is unnecessary and would not solve the problem of naming putative taxa known only from DNA sequences in a scientifically defensible way. As an alternative, we highlight the use of formulas for naming putative taxa (candidate taxa) that do not require any modification of the ICN.
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| 7. |
- Aoude, Lauren G, et al.
(författare)
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Nonsense Mutations in the Shelterin Complex Genes ACD and TERF2IP in Familial Melanoma.
- 2015
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 107:2, s. 408-408
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Tidskriftsartikel (refereegranskat)abstract
- The shelterin complex protects chromosomal ends by regulating how the telomerase complex interacts with telomeres. Following the recent finding in familial melanoma of inactivating germline mutations in POT1, encoding a member of the shelterin complex, we searched for mutations in the other five components of the shelterin complex in melanoma families.
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| 8. |
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| 9. |
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| 10. |
- Evans, Andrew, et al.
(författare)
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Breast ultrasound : recommendations for information to women and referring physicians by the European Society of Breast Imaging
- 2018
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Ingår i: Insights into Imaging. - : Springer Science and Business Media LLC. - 1869-4101. ; 9:4, s. 449-461
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Tidskriftsartikel (refereegranskat)abstract
- Abstract: This article summarises the information that should be provided to women and referring physicians about breast ultrasound (US). After explaining the physical principles, technical procedure and safety of US, information is given about its ability to make a correct diagnosis, depending on the setting in which it is applied. The following definite indications for breast US in female subjects are proposed: palpable lump; axillary adenopathy; first diagnostic approach for clinical abnormalities under 40 and in pregnant or lactating women; suspicious abnormalities at mammography or magnetic resonance imaging (MRI); suspicious nipple discharge; recent nipple inversion; skin retraction; breast inflammation; abnormalities in the area of the surgical scar after breast conserving surgery or mastectomy; abnormalities in the presence of breast implants; screening high-risk women, especially when MRI is not performed; loco-regional staging of a known breast cancer, when MRI is not performed; guidance for percutaneous interventions (needle biopsy, pre-surgical localisation, fluid collection drainage); monitoring patients with breast cancer receiving neo-adjuvant therapy, when MRI is not performed. Possible indications such as supplemental screening after mammography for women aged 40–74 with dense breasts are also listed. Moreover, inappropriate indications include screening for breast cancer as a stand-alone alternative to mammography. The structure and organisation of the breast US report and of classification systems such as the BI-RADS and consequent management recommendations are illustrated. Information about additional or new US technologies (colour-Doppler, elastography, and automated whole breast US) is also provided. Finally, five frequently asked questions are answered. Teaching Points: • US is an established tool for suspected cancers at all ages and also the method of choice under 40. • For US-visible suspicious lesions, US-guided biopsy is preferred, even for palpable findings. • High-risk women can be screened with US, especially when MRI cannot be performed. • Supplemental US increases cancer detection but also false positives, biopsy rate and follow-up exams. • Breast US is inappropriate as a stand-alone screening method.
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| 11. |
- Malavelle, Florent F., et al.
(författare)
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Strong constraints on aerosol-cloud interactions from volcanic eruptions
- 2017
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 546:7659, s. 485-491
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Tidskriftsartikel (refereegranskat)abstract
- Aerosols have a potentially large effect on climate, particularly through their interactions with clouds, but the magnitude of this effect is highly uncertain. Large volcanic eruptions produce sulfur dioxide, which in turn produces aerosols; these eruptions thus represent a natural experiment through which to quantify aerosol-cloud interactions. Here we show that the massive 2014-2015 fissure eruption in Holuhraun, Iceland, reduced the size of liquid cloud droplets-consistent with expectations-but had no discernible effect on other cloud properties. The reduction in droplet size led to cloud brightening and global-mean radiative forcing of around -0.2 watts per square metre for September to October 2014. Changes in cloud amount or cloud liquid water path, however, were undetectable, indicating that these indirect effects, and cloud systems in general, are well buffered against aerosol changes. This result will reduce uncertainties in future climate projections, because we are now able to reject results from climate models with an excessive liquid-water-path response.
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| 12. |
- Mann, Andrew, et al.
(författare)
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How to Constrain Your M Dwarf : Measuring Effective Temperature, Bolometric Luminosity, Mass, and Radius
- 2015
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 804
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Tidskriftsartikel (refereegranskat)abstract
- Precise and accurate parameters for late-type (late K and M) dwarf stars are important for characterization of any orbiting planets, but such determinations have been hampered by these stars' complex spectra and dissimilarity to the Sun. We exploit an empirically calibrated method to estimate spectroscopic effective temperature (Teff) and the Stefan--Boltzmann law to determine radii of 183 nearby K7--M7 single stars with a precision of 2%--5%. Our improved stellar parameters enable us to develop model-independent relations between Teff or absolute magnitude and radius, as well as between color and Teff. The derived Teff--radius relation depends strongly on [Fe/H], as predicted by theory. The relation between absolute KS magnitude and radius can predict radii accurate to ~= 3%. We derive bolometric corrections to the V{{R}C}{{I}C}grizJH{{K}S} and Gaia passbands as a function of color, accurate to 1%--3%. We confront the reliability of predictions from Dartmouth stellar evolution models using a Markov chain Monte Carlo to find the values of unobservable model parameters (mass, age) that best reproduce the observed effective temperature and bolometric flux while satisfying constraints on distance and metallicity as Bayesian priors. With the inferred masses we derive a semi-empirical mass--absolute magnitude relation with a scatter of 2% in mass. The best-agreement models overpredict stellar Teff values by an average of 2.2% and underpredict stellar radii by 4.6%, similar to differences with values from low-mass eclipsing binaries. These differences are not correlated with metallicity, mass, or indicators of activity, suggesting issues with the underlying model assumptions, e.g., opacities or convective mixing length.
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| 13. |
- Newell, Felicity, et al.
(författare)
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Whole-genome landscape of mucosal melanoma reveals diverse drivers and therapeutic targets
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Knowledge of key drivers and therapeutic targets in mucosal melanoma is limited due to the paucity of comprehensive mutation data on this rare tumor type. To better understand the genomic landscape of mucosal melanoma, here we describe whole genome sequencing analysis of 67 tumors and validation of driver gene mutations by exome sequencing of 45 tumors. Tumors have a low point mutation burden and high numbers of structural variants, including recurrent structural rearrangements targeting TERT, CDK4 and MDM2. Significantly mutated genes are NRAS, BRAF, NF1, KIT, SF3B1, TP53, SPRED1, ATRX, HLA-A and CHD8. SF3B1 mutations occur more commonly in female genital and anorectal melanomas and CTNNB1 mutations implicate a role for WNT signaling defects in the genesis of some mucosal melanomas. TERT aberrations and ATRX mutations are associated with alterations in telomere length. Mutation profiles of the majority of mucosal melanomas suggest potential susceptibility to CDK4/6 and/or MEK inhibitors.
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| 14. |
- van Leeuwen, F., et al.
(författare)
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Gaia Data Release 1 : Open cluster astrometry: Performance, limitations, and future prospects
- 2017
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 601
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Tidskriftsartikel (refereegranskat)abstract
- Context. The first Gaia Data Release contains the Tycho-Gaia Astrometric Solution (TGAS). This is a subset of about 2 million stars for which, besides the position and photometry, the proper motion and parallax are calculated using Hipparcos and Tycho-2 positions in 1991.25 as prior information. Aims. We investigate the scientific potential and limitations of the TGAS component by means of the astrometric data for open clusters. Methods. Mean cluster parallax and proper motion values are derived taking into account the error correlations within the astrometric solutions for individual stars, an estimate of the internal velocity dispersion in the cluster, and, where relevant, the effects of the depth of the cluster along the line of sight. Internal consistency of the TGAS data is assessed. Results. Values given for standard uncertainties are still inaccurate and may lead to unrealistic unit-weight standard deviations of least squares solutions for cluster parameters. Reconstructed mean cluster parallax and proper motion values are generally in very good agreement with earlier Hipparcos-based determination, although the Gaia mean parallax for the Pleiades is a significant exception. We have no current explanation for that discrepancy. Most clusters are observed to extend to nearly 15 pc from the cluster centre, and it will be up to future Gaia releases to establish whether those potential cluster-member stars are still dynamically bound to the clusters. Conclusions. The Gaia DR1 provides the means to examine open clusters far beyond their more easily visible cores, and can provide membership assessments based on proper motions and parallaxes. A combined HR diagram shows the same features as observed before using the Hipparcos data, with clearly increased luminosities for older A and F dwarfs.
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| 15. |
- Wilson, Susan, et al.
(författare)
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The XMM Cluster Survey : evolution of the velocity dispersion-temperature relation over half a Hubble time
- 2016
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Ingår i: Montly notices of the royal astronomical society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 463:1, s. 413-428
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Tidskriftsartikel (refereegranskat)abstract
- We measure the evolution of the velocity dispersion–temperature (σv–TX) relation up to z = 1 using a sample of 38 galaxy clusters drawn from the XMM Cluster Survey. This work improves upon previous studies by the use of a homogeneous cluster sample and in terms of the number of high-redshift clusters included. We present here new redshift and velocity dispersion measurements for 12 z > 0.5 clusters observed with the Gemini Multi Object Spectographs instruments on the Gemini telescopes. Using an orthogonal regression method, we find that the slope of the relation is steeper than that expected if clusters were self-similar, and that the evolution of the normalization is slightly negative, but not significantly different from zero (σv ∝ T0.86±0.14E(z)−0.37±0.33). We verify our results by applying our methods to cosmological hydrodynamical simulations. The lack of evolution seen in our data is consistent with simulations that include both feedback and radiative cooling.
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