| 1. |
- Dilliott, Allison A., et al.
(författare)
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Clinical testing panels for ALS : global distribution, consistency, and challenges
- 2023
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Ingår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. - : Taylor & Francis. - 2167-8421 .- 2167-9223. ; 24:5-6, s. 420-435
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Tidskriftsartikel (refereegranskat)abstract
- Objective: In 2021, the Clinical Genome Resource (ClinGen) amyotrophic lateral sclerosis (ALS) spectrum disorders Gene Curation Expert Panel (GCEP) was established to evaluate the strength of evidence for genes previously reported to be associated with ALS. Through this endeavor, we will provide standardized guidance to laboratories on which genes should be included in clinical genetic testing panels for ALS. In this manuscript, we aimed to assess the heterogeneity in the current global landscape of clinical genetic testing for ALS.Methods: We reviewed the National Institutes of Health (NIH) Genetic Testing Registry (GTR) and members of the ALS GCEP to source frequently used testing panels and compare the genes included on the tests.Results: 14 clinical panels specific to ALS from 14 laboratories covered 4 to 54 genes. All panels report on ANG, SOD1, TARDBP, and VAPB; 50% included or offered the option of including C9orf72 hexanucleotide repeat expansion (HRE) analysis. Of the 91 genes included in at least one of the panels, 40 (44.0%) were included on only a single panel. We could not find a direct link to ALS in the literature for 14 (15.4%) included genes.Conclusions: The variability across the surveyed clinical genetic panels is concerning due to the possibility of reduced diagnostic yields in clinical practice and risk of a missed diagnoses for patients. Our results highlight the necessity for consensus regarding the appropriateness of gene inclusions in clinical genetic ALS tests to improve its application for patients living with ALS and their families.
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| 2. |
- Kattge, Jens, et al.
(författare)
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TRY plant trait database - enhanced coverage and open access
- 2020
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Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
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Tidskriftsartikel (refereegranskat)abstract
- Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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| 3. |
- Magaldi, Fernanda M., et al.
(författare)
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Resistance Exercise Evokes Changes on Urinary Bladder Function and Morphology in Hypoestrogen Rats
- 2020
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Ingår i: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Serum levels of estrogen decrease at climacterium and directly interfere with the urogenital tract. Urinary bladder (UB) is responsive to hormonal changes, especially estrogen. Resistance exercise elicits benefits on severe chronic diseases. Nevertheless, it is still unclear whether the resistance exercise directly affects the UB in ovariectomized (OVx) rats. This study focused on investigating the effects of resistance exercise on UB function and morphology in OVx and control rats. Adult female Wistar rats (∼250-300 g, 14-16 weeks old) [control (n = 20) and OVx (n = 20)] were divided in the following groups: sedentary (SED), and trained over 1 week (acute), 3 weeks (intermediate), and 10 weeks (chronic). Training was carried out in a ladder, with six bouts in alternate days with 75% of body weight load attached to the tail of the animal. Afterward, the animals were isoflurane anesthetized for evaluation of intravesical pressure (IP) changes upon topical administration of acetylcholine (Ach) and noradrenaline (NE) on the UB. At the end of the experiment, the UB was harvested for histological analysis and stained with hematoxylin-eosin and picrosirius red. Ach increased the IP in both OVx and control rats, whereas NE decreased the IP. However, the acute and intermediate groups showed attenuated responses to Ach and NE, while the chronic groups recovered the responses to Ach and NE close to those observed in SED groups. Acute and intermediate groups also showed decreased thickness of the muscular layer, with a reversal of the process with chronic training. In the OVx groups, the acute training reduced the thickness of the smooth muscle and mucosal layers, whereas chronic training increased it. Urothelium thickness decreased in the OVx SED and acute groups. Collagen type I fibers (CI-F) reduced in OVx SED acute and intermediate groups, while collagen type III fibers (CIII-F) increased in the OVx acute group. In the mucosal layer, the volume density of CFs reduced in OVx rats compared to control groups and chronic training resulted in their recovery. Our data suggest that chronic resistance exercise for 10 weeks reversed the functional and morphological changes caused by hypoestrogenism.
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| 4. |
- Moreno, Roberta B., et al.
(författare)
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Structure and antinociceptive effects of beta-D-glucans from Cookeina tricholoma
- 2016
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Ingår i: Carbohydrate Polymers. - : Elsevier. - 0144-8617 .- 1879-1344. ; 141, s. 220-228
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Tidskriftsartikel (refereegranskat)abstract
- Structurally different water-insoluble (1 -> 3),(1 -> 6) beta-D-glucans were isolated from aqueous and alkaline extracts of the mushroom-forming ascomycete Cookeina tricholoma, a wild edible mushroom found in Brazilian Amazon forest. The structures showed different substitution patterns, which may influence their extractability and consequently their conformation in solution, and different M-w (4.3 x 10(5) Da, 3.7 x 10(5) Da and 8.2 x 10(5) Da, for ICW-Ct, IHW-Ct and IK2-ct, respectively). The main-chains are composed of (1 -> 3) -linked beta-D-Glcp units 0-6 substituted by side chains with different lengths of (1 -> 6)-linked beta-D-Glcp units (ICW-Ct and IHW-Ct) or by a combination of (1 -> 6) -linked beta-D-Glcp units and single units of beta-D-Glcp (IK2-ct). beta-D-glucans with similar Mw and showing only (1 6) -linked beta-D-Glcp units as side chains (ICW-Ct and IHW-Ct) showed significant inhibition of neurogenic pain, 69 +/- 11 and 57 +/- 11% at the dose of 10 mg kg(-1), respectively, in the model of nociception induced by intraplantar injection of formalin.
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| 5. |
- Nicolas, Aude, et al.
(författare)
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Genome-wide Analyses Identify KIF5A as a Novel ALS Gene
- 2018
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Ingår i: Neuron. - : Cell Press. - 0896-6273 .- 1097-4199. ; 97:6, s. 1268-1283.e6
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Tidskriftsartikel (refereegranskat)abstract
- To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.
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