| 1. |
- 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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| 2. |
- Jin, S. C., et al.
(författare)
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Mutations disrupting neuritogenesis genes confer risk for cerebral palsy
- 2020
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 52:10
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Tidskriftsartikel (refereegranskat)abstract
- Whole-exome sequencing of 250 parent-offspring trios identifies an enrichment of rare damaging de novo mutations in individuals with cerebral palsy and implicates genetically mediated dysregulation of early neuronal connectivity in the etiology of this disorder. In addition to commonly associated environmental factors, genomic factors may cause cerebral palsy. We performed whole-exome sequencing of 250 parent-offspring trios, and observed enrichment of damaging de novo mutations in cerebral palsy cases. Eight genes had multiple damaging de novo mutations; of these, two (TUBA1AandCTNNB1) met genome-wide significance. We identified two novel monogenic etiologies,FBXO31andRHOB, and showed that theRHOBmutation enhances active-state Rho effector binding while theFBXO31mutation diminishes cyclin D levels. Candidate cerebral palsy risk genes overlapped with neurodevelopmental disorder genes. Network analyses identified enrichment of Rho GTPase, extracellular matrix, focal adhesion and cytoskeleton pathways. Cerebral palsy risk genes in enriched pathways were shown to regulate neuromotor function in aDrosophilareverse genetics screen. We estimate that 14% of cases could be attributed to an excess of damaging de novo or recessive variants. These findings provide evidence for genetically mediated dysregulation of early neuronal connectivity in cerebral palsy.
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| 3. |
- Aebersold, Ruedi, et al.
(författare)
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How many human proteoforms are there?
- 2018
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Ingår i: Nature Chemical Biology. - : NATURE PUBLISHING GROUP. - 1552-4450 .- 1552-4469. ; 14:3, s. 206-214
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Tidskriftsartikel (refereegranskat)abstract
- Despite decades of accumulated knowledge about proteins and their post-translational modifications (PTMs), numerous questions remain regarding their molecular composition and biological function. One of the most fundamental queries is the extent to which the combinations of DNA-, RNA-and PTM-level variations explode the complexity of the human proteome. Here, we outline what we know from current databases and measurement strategies including mass spectrometry-based proteomics. In doing so, we examine prevailing notions about the number of modifications displayed on human proteins and how they combine to generate the protein diversity underlying health and disease. We frame central issues regarding determination of protein-level variation and PTMs, including some paradoxes present in the field today. We use this framework to assess existing data and to ask the question, "How many distinct primary structures of proteins (proteoforms) are created from the 20,300 human genes?" We also explore prospects for improving measurements to better regularize protein-level biology and efficiently associate PTMs to function and phenotype.
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| 4. |
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| 5. |
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| 6. |
- MacLennan, Alastair H, et al.
(författare)
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Genetic or Other Causation Should Not Change the Clinical Diagnosis of Cerebral Palsy.
- 2019
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Ingår i: Journal of child neurology. - : SAGE Publications. - 1708-8283 .- 0883-0738. ; 38:4, s. 472-6
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Tidskriftsartikel (refereegranskat)abstract
- High throughput sequencing is discovering many likely causative genetic variants in individuals with cerebral palsy. Some investigators have suggested that this changes the clinical diagnosis of cerebral palsy and that these individuals should be removed from this diagnostic category. Cerebral palsy is a neurodevelopmental disorder diagnosed on clinical signs, not etiology. All nonprogressive permanent disorders of movement and posture attributed to disturbances that occurred in the developing fetal and infant brain can be described as "cerebral palsy." This definition of cerebral palsy should not be changed, whatever the cause. Reasons include stability, utility and accuracy of cerebral palsy registers, direct access to services, financial and social support specifically offered to families with cerebral palsy, and community understanding of the clinical diagnosis. Other neurodevelopmental disorders, for example, epilepsy, have not changed the diagnosis when genomic causes are found. The clinical diagnosis of cerebral palsy should remain, should prompt appropriate genetic studies and can subsequently be subclassified by etiology.
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| 7. |
- Zhu, Youjian, et al.
(författare)
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Cogasification of Australian Brown Coal with Algae in a Fluidized Bed Reactor
- 2015
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Ingår i: Energy & Fuels. - : American Chemical Society (ACS). - 0887-0624 .- 1520-5029. ; 29:3, s. 1686-1700
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Tidskriftsartikel (refereegranskat)abstract
- Recently, the use of algae for CO2 abatement, wastewater treatment, and energy production has increasingly gained attention worldwide. In order to explore the potential of using algae as an alternative fuel as well as the possible challenges related to the algae gasification process, two species of macroalgae, Derbesia tenuissima and Oedogonium sp., and one type of microalgae, Scenedesmus sp. were studied in this research. In this work, Oedogonium sp. was cultivated with two protocols: producing biomass with both high and low levels of nitrogen content. Cogasification of 10 wt % algae with an Australian brown coal was performed in a fluidized bed reactor, and the effects of algae addition on syngas yield, ash composition, and bed agglomeration were investigated. It was found that CO and H-2 yield increased and CO2 yield decreased after adding three types of macroalgae in the coal, with a slight increase of carbon conversion rate, compared to the coal alone experiment. In the case of coal/Scenedesmus sp, the carbon conversion rate decreased with lower CO/CO2/H-2 yield as compared to coal alone. Samples of fly ash, bed ash, and bed material agglomerates were analyzed using scanning electron microscopy combined with an energy dispersive X-ray detector (SEM-EDX) and X-ray diffraction (XRD). It was observed that both the fly ash and bed ash samples from all coal/macroalgae tests contained more Na and K as compared to the coal test. High Ca and Fe contents were also found in the fly ash and bed ash from the coal/Scenedesmus sp. test. Significant differences in the characteristics and compositions of the ash layer on the bed particles were observed from the different tests. Agglomerates were found in the bed material samples after the cogasification tests of coal/Oedogonium N+ and coal/Oedogonium N. The formation of liquid alkalisilicates on the sand particles was considered to be the main reason for agglomeration for the coal/Oedogonium N+ and coal/Oedogonium N tests. Agglomerates of fused ash and tiny silica sand particles were also found in the coal/Scenedesmus sp. test. In this case, however, the formation of a Fe-Al silicate eutectic mixture was proposed to be the main reason for agglomeration. Debersia was suggested to be a potential alternative fuel, which can be cogasified with brown coal without any significant operating problems under the current experimental conditions. However, for the other algae types, appropriate countermeasures are needed to avoid agglomeration and defluidization in the cogasification process.
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| 8. |
- Omenn, G. S., et al.
(författare)
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Progress on Identifying and Characterizing the Human Proteome : 2019 Metrics from the HUPO Human Proteome Project
- 2019
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Ingår i: Journal of Proteome Research. - : American Chemical Society. - 1535-3893 .- 1535-3907. ; 18:12, s. 4098-4107
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Tidskriftsartikel (refereegranskat)abstract
- The Human Proteome Project (HPP) annually reports on progress made throughout the field in credibly identifying and characterizing the complete human protein parts list and making proteomics an integral part of multiomics studies in medicine and the life sciences. NeXtProt release 2019-01-11 contains 17 694 proteins with strong protein-level evidence (PE1), compliant with HPP Guidelines for Interpretation of MS Data v2.1; these represent 89% of all 19 823 neXtProt predicted coding genes (all PE1,2,3,4 proteins), up from 17 470 one year earlier. Conversely, the number of neXtProt PE2,3,4 proteins, termed the "missing proteins" (MPs), has been reduced from 2949 to 2129 since 2016 through efforts throughout the community, including the chromosome-centric HPP. PeptideAtlas is the source of uniformly reanalyzed raw mass spectrometry data for neXtProt; PeptideAtlas added 495 canonical proteins between 2018 and 2019, especially from studies designed to detect hard-to-identify proteins. Meanwhile, the Human Protein Atlas has released version 18.1 with immunohistochemical evidence of expression of 17 000 proteins and survival plots as part of the Pathology Atlas. Many investigators apply multiplexed SRM-targeted proteomics for quantitation of organ-specific popular proteins in studies of various human diseases. The 19 teams of the Biology and Disease-driven B/D-HPP published a total of 160 publications in 2018, bringing proteomics to a broad array of biomedical research.
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| 9. |
- Ruiz-Romero, Cristina, et al.
(författare)
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Mining the Proteome Associated with Rheumatic and Autoimmune Diseases
- 2019
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 18:12, s. 4231-4239
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Tidskriftsartikel (refereegranskat)abstract
- A steady increase in the incidence of osteoarthritis and other rheumatic diseases has been observed in recent decades, including autoimmune conditions such as rheumatoid arthritis, spondyloarthropathies, systemic lupus erythematosus, systemic sclerosis, and Sjogren's syndrome. Rheumatic and autoimmune diseases (RADs) are characterized by the inflammation of joints, muscles, or other connective tissues. In addition to often experiencing debilitating mobility and pain, RAD patients are also at a higher risk of suffering comorbidities such as cardiovascular or infectious events. Given the socioeconomic impact of RADs, broad research efforts have been dedicated to these diseases worldwide. In the present work, we applied literature mining platforms to identify "popular" proteins closely related to RADs. The platform is based on publicly available literature. The results not only will enable the systematic prioritization of candidates to perform targeted proteomics studies but also may lead to a greater insight into the key pathogenic processes of these disorders.
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| 10. |
- Zhu, Youjian, et al.
(författare)
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Fluidized bed co-gasification of algae and wood pellets : gas yields and bed agglomeration analysis
- 2016
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Ingår i: Energy & Fuels. - : American Chemical Society (ACS). - 0887-0624 .- 1520-5029. ; 30:3, s. 1800-1809
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Tidskriftsartikel (refereegranskat)abstract
- Algae utilization in energy production has gained increasing attention as a result of its characteristics, such as high productivity, rapid growth rate, and flexible cultivation environment. In this paper, three species of algae, including a fresh water macroalgae, Oedogonium sp., a saltwater macroalgae, Derbersia tenuissima, and a microalgae species, Scenedesmus sp., were studied to explore the potential of using smaller amounts of algae fuels in blends with traditional woody biomasses in the gasification processes. Co-gasification of 10 wt % algae and 90 wt % Swedish wood pellets was performed in a fluidized bed reactor. The effects of algae addition on the syngas yield and carbon conversion rate were investigated. The addition of 10 wt % algae in wood increased the CO, H2, and CH4 yields by 3–20, 6–31, and 9–20%, respectively. At the same time, it decreased the CO2 yield by 3–18%. The carbon conversion rates were slightly increased with the addition of 10 wt % macroalgae in wood, but the microalgae addition resulted in a decrease of the carbon conversion rate by 8%. Meanwhile, the collected fly ash and bed material samples were analyzed using scanning electron microscopy combined with an energy-dispersive X-ray detector (SEM–EDX) and X-ray diffraction (XRD) technique. The fly ashes of wood/marcoalgae tests showed a higher Na content with lower Si and Ca contents compared to the wood test. The gasification tests were scheduled to last 4 h; however, only wood and wood/Derbersia gasification experiments were carried out without significant operational problems. The gasification of 10 wt % Oedogonium N+ and Oedogonium N– led to defluidization of the bed in less than 1 h, and the wood/Scenedesmus (WD/SA) test was stopped after 1.8 h as a result of severe agglomeration. It was found that the algae addition had a remarkable influence on the characteristics and compositions of the coating layer. The coating layer formation and bed agglomeration mechanism of wood/macroalgae was initiated by the reaction of alkali compounds with the bed particles to form low-temperature melting silicates (inner layer). For the WD/SA test, the agglomeration was influenced by both the composition of the original algae fuel as well as the external mineral contaminations. In summary, the operational problems experienced during the co-gasification tests of different algae–wood mixtures were assigned to the specific ash compositions of the different fuel mixtures. This showed the need for countermeasures, specifically to balance the high alkali content, to reach stable operation in a fluidized bed gasifier.
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