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| 2. |
- Liu, DJ, et al.
(författare)
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Schizophrenia risk conferred by rare protein-truncating variants is conserved across diverse human populations
- 2023
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 55:3, s. 369-
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Tidskriftsartikel (refereegranskat)abstract
- Schizophrenia (SCZ) is a chronic mental illness and among the most debilitating conditions encountered in medical practice. A recent landmark SCZ study of the protein-coding regions of the genome identified a causal role for ten genes and a concentration of rare variant signals in evolutionarily constrained genes1. This recent study—and most other large-scale human genetics studies—was mainly composed of individuals of European (EUR) ancestry, and the generalizability of the findings in non-EUR populations remains unclear. To address this gap, we designed a custom sequencing panel of 161 genes selected based on the current knowledge of SCZ genetics and sequenced a new cohort of 11,580 SCZ cases and 10,555 controls of diverse ancestries. Replicating earlier work, we found that cases carried a significantly higher burden of rare protein-truncating variants (PTVs) among evolutionarily constrained genes (odds ratio = 1.48; P = 5.4 × 10−6). In meta-analyses with existing datasets totaling up to 35,828 cases and 107,877 controls, this excess burden was largely consistent across five ancestral populations. Two genes (SRRM2 and AKAP11) were newly implicated as SCZ risk genes, and one gene (PCLO) was identified as shared by individuals with SCZ and those with autism. Overall, our results lend robust support to the rare allelic spectrum of the genetic architecture of SCZ being conserved across diverse human populations.
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| 4. |
- Brawand, David, et al.
(författare)
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The genomic substrate for adaptive radiation in African cichlid fish
- 2014
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 513:7518, s. 375-381
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Tidskriftsartikel (refereegranskat)abstract
- Cichlid fishes are famous for large, diverse and replicated adaptive radiations in the Great Lakes of East Africa. To understand themolecular mechanisms underlying cichlid phenotypic diversity, we sequenced the genomes and transcriptomes of five lineages of African cichlids: the Nile tilapia (Oreochromis niloticus), an ancestral lineage with low diversity; and four members of the East African lineage: Neolamprologus brichardi/pulcher (older radiation, Lake Tanganyika), Metriaclima zebra (recent radiation, Lake Malawi), Pundamilia nyererei (very recent radiation, Lake Victoria), and Astatotilapia burtoni (riverine species around Lake Tanganyika). We found an excess of gene duplications in the East African lineage compared to tilapia and other teleosts, an abundance of non-coding element divergence, accelerated coding sequence evolution, expression divergence associated with transposable element insertions, and regulation by novel microRNAs. In addition, we analysed sequence data from sixty individuals representing six closely related species from Lake Victoria, and show genome-wide diversifying selection on coding and regulatory variants, some of which were recruited from ancient polymorphisms. We conclude that a number of molecular mechanisms shaped East African cichlid genomes, and that amassing of standing variation during periods of relaxed purifying selection may have been important in facilitating subsequent evolutionary diversification.
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| 5. |
- Hasan, A, et al.
(författare)
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World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Schizophrenia : Part 1: Update 2012 on the acute treatment of schizophrenia and the management of treatment resistance.
- 2012
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Ingår i: The World Journal of Biological Psychiatry. - : Informa UK Limited. - 1562-2975 .- 1814-1412. ; 13:5, s. 318-378
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Tidskriftsartikel (refereegranskat)abstract
- These updated guidelines are based on a first edition of the World Federation of Societies of Biological Psychiatry Guidelines for Biological Treatment of Schizophrenia published in 2005. For this 2012 revision, all available publications pertaining to the biological treatment of schizophrenia were reviewed systematically to allow for an evidence-based update. These guidelines provide evidence-based practice recommendations that are clinically and scientifically meaningful and these guidelines are intended to be used by all physicians diagnosing and treating people suffering from schizophrenia. Based on the first version of these guidelines, a systematic review of the MEDLINE/PUBMED database and the Cochrane Library, in addition to data extraction from national treatment guidelines, has been performed for this update. The identified literature was evaluated with respect to the strength of evidence for its efficacy and then categorised into six levels of evidence (A–F; Bandelow et al. 2008b, World J Biol Psychiatry 9:242). This first part of the updated guidelines covers the general descriptions of antipsychotics and their side effects, the biological treatment of acute schizophrenia and the management of treatment-resistant schizophrenia.
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| 6. |
- Ade, Peter, et al.
(författare)
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The Simons Observatory : science goals and forecasts
- 2019
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Ingår i: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :2
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Tidskriftsartikel (refereegranskat)abstract
- The Simons Observatory (SO) is a new cosmic microwave background experiment being built on Cerro Toco in Chile, due to begin observations in the early 2020s. We describe the scientific goals of the experiment, motivate the design, and forecast its performance. SO will measure the temperature and polarization anisotropy of the cosmic microwave background in six frequency bands centered at: 27, 39, 93, 145, 225 and 280 GHz. The initial con figuration of SO will have three small-aperture 0.5-m telescopes and one large-aperture 6-m telescope, with a total of 60,000 cryogenic bolometers. Our key science goals are to characterize the primordial perturbations, measure the number of relativistic species and the mass of neutrinos, test for deviations from a cosmological constant, improve our understanding of galaxy evolution, and constrain the duration of reionization. The small aperture telescopes will target the largest angular scales observable from Chile, mapping approximate to 10% of the sky to a white noise level of 2 mu K-arcmin in combined 93 and 145 GHz bands, to measure the primordial tensor-to-scalar ratio, r, at a target level of sigma(r) = 0.003. The large aperture telescope will map approximate to 40% of the sky at arcminute angular resolution to an expected white noise level of 6 mu K-arcmin in combined 93 and 145 GHz bands, overlapping with the majority of the Large Synoptic Survey Telescope sky region and partially with the Dark Energy Spectroscopic Instrument. With up to an order of magnitude lower polarization noise than maps from the Planck satellite, the high-resolution sky maps will constrain cosmological parameters derived from the damping tail, gravitational lensing of the microwave background, the primordial bispectrum, and the thermal and kinematic Sunyaev-Zel'dovich effects, and will aid in delensing the large-angle polarization signal to measure the tensor-to-scalar ratio. The survey will also provide a legacy catalog of 16,000 galaxy clusters and more than 20,000 extragalactic sources.
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| 8. |
- Olvegård, Maja, et al.
(författare)
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Performance of parabolic and diffusive OTR screens at the CLIC Test Facility 3
- 2011
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Ingår i: Proceedings of DIPAC2011, Hamburg, Germany. ; , s. 413-415
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- At the CLIC Test Facility 3, OTR screens are commonly used in beam imaging systems for energy and energy spread characterization in dedicated spectrometer lines. In these lines the horizontal beam size is typically of the order of one centimeter. Already in 2005 a limitation was observed resulting from a strong dependence of the intensity of the light captured by the camera, on the positionon the screen (vignetting). The severity of this effect increases with the electron energy, as the aperture of the optical system is finite and the OTR photons are emitted in asmall cone of 1/γ angle. To mitigate this effect, different shapes and surface polishing of the screens were investigated. Parabolic and diffusive OTR radiators were tested in several spectrometer lines all along the CTF3 complex.The results are presented in this paper.
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| 9. |
- Sukuru, Sai Chetan K, et al.
(författare)
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Discovering new classes of Brugia malayi asparaginyl-tRNA synthetase inhibitors and relating specificity to conformational change.
- 2006
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Ingår i: Journal of computer-aided molecular design. - : Springer Science and Business Media LLC. - 0920-654X .- 1573-4951. ; 20:3, s. 159-78
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Tidskriftsartikel (refereegranskat)abstract
- SLIDE software, which models the flexibility of protein and ligand side chains while docking, was used to screen several large databases to identify inhibitors of Brugia malayi asparaginyl-tRNA synthetase (AsnRS), a target for anti-parasitic drug design. Seven classes of compounds identified by SLIDE were confirmed as micromolar inhibitors of the enzyme. Analogs of one of these classes of inhibitors, the long side-chain variolins, cannot bind to the adenosyl pocket of the closed conformation of AsnRS due to steric clashes, though the short side-chain variolins identified by SLIDE apparently bind isosterically with adenosine. We hypothesized that an open conformation of the motif 2 loop also permits the long side-chain variolins to bind in the adenosine pocket and that their selectivity for Brugia relative to human AsnRS can be explained by differences in the sequence and conformation of this loop. Loop flexibility sampling using Rigidity Optimized Conformational Kinetics (ROCK) confirms this possibility, while scoring of the relative affinities of the different ligands by SLIDE correlates well with the compounds' ranks in inhibition assays. Combining ROCK and SLIDE provides a promising approach for exploiting conformational flexibility in structure-based screening and design of species selective inhibitors.
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| 10. |
- Zelinka, Samuel L., et al.
(författare)
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Interlaboratory study of the operational stability of automated sorption balances
- 2024
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Ingår i: Adsorption. - 0929-5607.
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Tidskriftsartikel (refereegranskat)abstract
- Automated sorption balances are widely used for characterizing the interaction of water vapor with hygroscopic materials. These instruments provide an efficient way to collect sorption isotherm data and kinetic data. A typical method for defining equilibrium after a step change in relative humidity (RH) is using a particular threshold value for the rate of change in mass with time. Recent studies indicate that commonly used threshold values yield substantial errors and that further measurements are needed at extended hold times as a basis to assess the accuracy of abbreviated equilibration criteria. However, the mass measurement accuracy at extended times depends on the operational stability of the instrument. Published data on the stability of automated sorption balances are rare. An interlaboratory study was undertaken to investigate equilibration criteria for automated sorption balances. This paper focuses on the mass, temperature, and RH stability and includes data from 25 laboratories throughout the world. An initial target for instrument mass stability was met on the first attempt in many cases, but several instruments were found to have unexpectedly large instabilities. The sources of these instabilities were investigated and greatly reduced. This paper highlights the importance of verifying operational mass stability of automated sorption balances, gives a method to perform stability checks, and provides guidance on identifying and correcting common sources of mass instability.
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