| 1. |
- Brownstein, Catherine A., et al.
(författare)
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An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge
- 2014
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Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 15:3, s. R53-
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. Results: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. Conclusions: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups.
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| 2. |
- Metcalfe, Daniel B., et al.
(författare)
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Impacts of experimentally imposed drought on leaf respiration and morphology in an Amazon rain forest
- 2010
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Ingår i: Functional Ecology. - : Wiley. - 0269-8463 .- 1365-2435. ; 24:3, s. 524-533
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Tidskriftsartikel (refereegranskat)abstract
- P>1. The Amazon region may experience increasing moisture limitation over this century. Leaf dark respiration (R) is a key component of the Amazon rain forest carbon (C) cycle, but relatively little is known about its sensitivity to drought. 2. Here, we present measurements of R standardized to 25 degrees C and leaf morphology from different canopy heights over 5 years at a rain forest subject to a large-scale through-fall reduction (TFR) experiment, and nearby, unmodified Control forest, at the Caxiuana reserve in the eastern Amazon. 3. In all five post-treatment measurement campaigns, mean R at 25 degrees C was elevated in the TFR forest compared to the Control forest experiencing normal rainfall. After 5 years of the TFR treatment, R per unit leaf area and mass had increased by 65% and 42%, respectively, relative to pre-treatment means. In contrast, leaf area index (L) in the TFR forest was consistently lower than the Control, falling by 23% compared to the pre-treatment mean, largely because of a decline in specific leaf area (S). 4. The consistent and significant effects of the TFR treatment on R, L and S suggest that severe drought events in the Amazon, of the kind that may occur more frequently in future, could cause a substantial increase in canopy carbon dioxide emissions from this ecosystem to the atmosphere.
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| 3. |
- Alves, G.R., et al.
(författare)
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Using VISIR in a large undergraduate course : Preliminary assessment results
- 2011
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Konferensbidrag (refereegranskat)abstract
- The use of remote labs in undergraduate courses has been reported in literature several times since the mid 90's. Nevertheless, very few articles present results about the learning gains obtained by students using them, especially with a large number of students, thus suggesting a lack of data concerning their pedagogical effectiveness. This paper addresses such a gap by presenting some preliminary results concerning the use of a remote laboratory, known as VISIR, in a large undergraduate course on Applied Physics, with over 500 students enrolled.
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| 4. |
- Bjork, J., et al.
(författare)
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STM fingerprint of molecule-adatom interactions in a self-assembled metal-organic surface coordination network on Cu(111)
- 2010
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Ingår i: Physical Chemistry Chemical Physics. - : Royal Society of Chemistry (RSC). - 1463-9084 .- 1463-9076. ; 12:31, s. 8815-8821
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Tidskriftsartikel (refereegranskat)abstract
- A novel approach of identifying metal atoms within a metal-organic surface coordination network using scanning tunnelling microscopy (STM) is presented. The Cu adatoms coordinated in the porous surface network of 1,3,8,10-tetraazaperopyrene (TAPP) molecules on a Cu(111) surface give rise to a characteristic electronic resonance in STM experiments. Using density functional theory calculations, we provide strong evidence that this resonance is a fingerprint of the interaction between the molecules and the Cu adatoms. We also show that the bonding of the Cu adatoms to the organic exodentate ligands is characterised by both the mixing of the nitrogen lone-pair orbitals of TAPP with states on the Cu adatoms and the partial filling of the lowest unoccupied molecular orbital (LUMO) of the TAPP molecule. Furthermore, the key interactions determining the surface unit cell of the network are discussed.
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| 5. |
- Hill, M. S., et al.
(författare)
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Reconstruction of Family-Level Phylogenetic Relationships within Demospongiae (Porifera) Using Nuclear Encoded Housekeeping Genes
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:1, s. e50437-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Demosponges are challenging for phylogenetic systematics because of their plastic and relatively simple morphologies and many deep divergences between major clades. To improve understanding of the phylogenetic relationships within Demospongiae, we sequenced and analyzed seven nuclear housekeeping genes involved in a variety of cellular functions from a diverse group of sponges. Methodology/Principal Findings: We generated data from each of the four sponge classes (i.e., Calcarea, Demospongiae, Hexactinellida, and Homoscleromorpha), but focused on family-level relationships within demosponges. With data for 21 newly sampled families, our Maximum Likelihood and Bayesian-based approaches recovered previously phylogenetically defined taxa: Keratosap, Myxospongiaep, Spongillidap, Haploscleromorphap (the marine haplosclerids) and Democlaviap. We found conflicting results concerning the relationships of Keratosap and Myxospongiaep to the remaining demosponges, but our results strongly supported a clade of Haploscleromorphap+Spongillidap+Democlaviap. In contrast to hypotheses based on mitochondrial genome and ribosomal data, nuclear housekeeping gene data suggested that freshwater sponges (Spongillidap) are sister to Haploscleromorphap rather than part of Democlaviap. Within Keratosap, we found equivocal results as to the monophyly of Dictyoceratida. Within Myxospongiaep, Chondrosida and Verongida were monophyletic. A well-supported clade within Democlaviap, Tetractinellidap, composed of all sampled members of Astrophorina and Spirophorina (including the only lithistid in our analysis), was consistently revealed as the sister group to all other members of Democlaviap. Within Tetractinellidap, we did not recover monophyletic Astrophorina or Spirophorina. Our results also reaffirmed the monophyly of order Poecilosclerida (excluding Desmacellidae and Raspailiidae), and polyphyly of Hadromerida and Halichondrida. Conclusions/Significance: These results, using an independent nuclear gene set, confirmed many hypotheses based on ribosomal and/or mitochondrial genes, and they also identified clades with low statistical support or clades that conflicted with traditional morphological classification. Our results will serve as a basis for future exploration of these outstanding questions using more taxon- and gene-rich datasets.
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| 6. |
- Kimlicka, L., et al.
(författare)
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The Cardiac Ryanodine Receptor N-Terminal Region Contains an Anion Binding Site that Is Targeted by Disease Mutations
- 2013
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Ingår i: Structure. - : Elsevier BV. - 0969-2126. ; 21:8, s. 1440-1449
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Tidskriftsartikel (refereegranskat)abstract
- Ryanodine receptors (RyRs) are calcium release channels located in the membrane of the endoplasmic and sarcoplasmic reticulum and play a major role in muscle excitation-contraction coupling. The cardiac isoform (RyR2) is the target for >150 mutations that cause catecholaminergic polymorphic ventricular tachycardia (CPVT) and other conditions. Here, we present the crystal structure of the N-terminal region of RyR2 (1-547), an area encompassing 29 distinct disease mutations. The protein folds up in three individual domains, which are held together via a central chloride anion that shields repulsive positive charges. Several disease mutant versions of the construct drastically destabilize the protein. The R420Q disease mutant causes CPVT and ablates chloride binding. The mutation results in reorientations of the first two domains relative to the third domain. These conformational changes likely activate the channel by destabilizing intersubunit interactions that are disrupted upon channel opening.
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