| 1. |
- Reinthaler, Eva M., et al.
(författare)
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TPP2 mutation associated with sterile brain inflammation mimicking MS
- 2018
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Ingår i: NEUROLOGY-GENETICS. - 2376-7839. ; 4:6
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Tidskriftsartikel (refereegranskat)abstract
- Objective To ascertain the genetic cause of a consanguineous family from Syria suffering from a sterile brain inflammation mimicking a mild nonprogressive form of MS.Methods We used homozygosity mapping and next-generation sequencing to detect the disease-causing gene in the affected siblings. In addition, we performed RNA and protein expression studies, enzymatic activity assays, immunohistochemistry, and targeted sequencing of further MS cases from Austria, Germany, Canada and Jordan.Results In this study, we describe the identification of a homozygous missense mutation (c.82T>G, p.Cys28Gly) in the tripeptidyl peptidase II (TPP2) gene in all 3 affected siblings of the family. Sequencing of all TPP2-coding exons in 826 MS cases identified one further homozygous missense variant (c.2027C>T, p.Thr676Ile) in a Jordanian MS patient. TPP2 protein expression in whole blood was reduced in the affected siblings. In contrast, TPP2 protein expression in postmortem brain tissue from MS patients without TPP2 mutations was highly upregulated.Conclusions The homozygous TPP2 mutation (p.Cys28Gly) is likely responsible for the inflammation phenotype in this family. TPP2 is an ubiquitously expressed serine peptidase that removes tripeptides from the N-terminal end of longer peptides. TPP2 is involved in various biological processes including the destruction of major histocompatibility complex Class I epitopes. Recessive loss-of-function mutations in TPP2 were described in patients with Evans syndrome, a rare autoimmune disease affecting the hematopoietic system. Based on the gene expression results in our MS autopsy brain samples, we further suggest that TPP2 may play a broader role in the inflammatory process in MS.
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| 2. |
- Baltar, Federico, et al.
(författare)
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Significance of non-sinking particulate organic carbon and dark CO2 fixation to heterotrophic carbon demand in the mesopelagic Atlantic
- 2010
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Ingår i: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 37, s. L09602-
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Tidskriftsartikel (refereegranskat)abstract
- It is generally assumed that sinking particulate organic carbon (POC) constitutes the main source of organic carbon supply to the deep ocean's food webs. However, a major discrepancy between the rates of sinking POC supply (collected with sediment traps) and the prokaryotic organic carbon demand (the total amount of carbon required to sustain the heterotrophic metabolism of the prokaryotes; i.e., production plus respiration, PCD) of deep-water communities has been consistently reported for the dark realm of the global ocean. While the amount of sinking POC flux declines exponentially with depth, the concentration of suspended, buoyant non-sinking POC (nsPOC; obtained with oceanographic bottles) exhibits only small variations with depth in the (sub) tropical Northeast Atlantic. Based on available data for the North Atlantic we show here that the sinking POC flux would contribute only 4-12% of the PCD in the mesopelagic realm (depending on the primary production rate in surface waters). The amount of nsPOC potentially available to heterotrophic prokaryotes in the mesopelagic realm can be partly replenished by dark dissolved inorganic carbon fixation contributing between 12% to 72% to the PCD daily. Taken together, there is evidence that the mesopelagic microheterotrophic biota is more dependent on the nsPOC pool than on the sinking POC supply. Hence, the enigmatic major mismatch between the organic carbon demand of the deep-water heterotrophic microbiota and the POC supply rates might be substantially smaller by including the potentially available nsPOC and its autochthonous production in oceanic carbon cycling models. Citation: Baltar, F., J. Aristegui, E. Sintes, J. M. Gasol, T. Reinthaler, and G. J. Herndl (2010), Significance of non-sinking particulate organic carbon and dark CO2 fixation to heterotrophic carbon demand in the mesopelagic northeast Atlantic.
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| 3. |
- Herndl, Gerhard J., et al.
(författare)
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Regulation of aquatic microbial processes: the ‘microbial loop’ of the sunlit surface waters and the dark ocean dissected
- 2008
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Ingår i: Aquatic Microbial Ecology. - : Inter-Research Science Center. - 0948-3055 .- 1616-1564. ; 53:Sp. Iss. 1, s. 59-68
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Tidskriftsartikel (refereegranskat)abstract
- Our understanding of microbial food web interactions in the ocean is essentially based on research performed in the euphotic layer, where the interactions between phytoplankton and prokaryotic plankton, mainly heterotrophic Bacteria, are well established. In the euphotic layer, particularly in meso- and eutrophic waters, prokaryotic plankton are mainly top-down controlled by bacterivorous flagellates and viruses, affecting metabolically active, fast growing populations more than dormant stages. In the meso- and bathypelagic realm of the ocean, however, prokaryotic plankton are thought to be mainly bottom-up controlled, because the heterotrophic component of the prokaryotic community is limited by the availability of organic carbon. However, deep-water prokaryotes exhibit a number of peculiarities compared to prokaryotes in the euphotic layer, among which are a large genome size and a gene repertoire indicative of a predominately surface-attached mode of life. This indicates that deep-water prokaryotic activity might be primarily associated with particles. Our present knowledge indicates that the microbial communities and their interactions in the deep ocean are likely very different from those known from surface waters. Increasing efforts to shed light on the microbial biota of the ocean's interior will likely lead to the discovery of novel metabolic pathways in prokaryotes and to the resolution of the current discrepancy between the geochemical evidence of remineralization rates of organic matter and actual measurements.
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