| 1. |
- Egeblad, Louise, et al.
(författare)
-
Structural and functional studies of the human phosphoribosyltransferase domain containing protein 1
- 2010
-
Ingår i: The FEBS Journal. - : Wiley. - 1742-464X .- 1742-4658. ; 277:23, s. 4920-30
-
Tidskriftsartikel (refereegranskat)abstract
- Human hypoxanthine-guanine phosphoribosyltransferase (HPRT) (EC 2.4.2.8) catalyzes the conversion of hypoxanthine and guanine to their respective nucleoside monophosphates. Human HPRT deficiency as a result of genetic mutations is linked to both Lesch-Nyhan disease and gout. In the present study, we have characterized phosphoribosyltransferase domain containing protein 1 (PRTFDC1), a human HPRT homolog of unknown function. The PRTFDC1 structure has been determined at 1.7 Å resolution with bound GMP. The overall structure and GMP binding mode are very similar to that observed for HPRT. Using a thermal-melt assay, a nucleotide metabolome library was screened against PRTFDC1 and revealed that hypoxanthine and guanine specifically interacted with the enzyme. It was subsequently confirmed that PRTFDC1 could convert these two bases into their corresponding nucleoside monophosphate. However, the catalytic efficiency (k(cat)/K(m)) of PRTFDC1 towards hypoxanthine and guanine was only 0.26% and 0.09%, respectively, of that of HPRT. This low activity could be explained by the fact that PRTFDC1 has a Gly in the position of the proposed catalytic Asp of HPRT. In PRTFDC1, a water molecule at the position of the aspartic acid side chain position in HPRT might be responsible for the low activity observed by acting as a weak base. The data obtained in the present study indicate that PRTFDC1 does not have a direct catalytic role in the nucleotide salvage pathway.
|
|
| 2. |
- Envall, Ida, et al.
(författare)
-
Existing evidence related to soil retention of phosphorus from on-site wastewater treatment systems in boreal and temperate climate zones : a systematic map
- 2023
-
Ingår i: Environmental Evidence. - : Springer Nature. - 2047-2382. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: In Sweden there are nearly one million soil-based on-site wastewater treatment systems (OWTSs). OWTSs may contribute to eutrophication of surface waters, due to the discharge of phosphorus (P). Hence, in certain cases, a high P removal rate (up to 90%) of OWTSs is required by Swedish authorities. Since these requirements may have costly consequences to property owners, it is debated whether they are too strict. In this debate, it is often claimed that the soil retention of P occurring in the natural environments may be underestimated by authorities. Soil retention is the inhibition of the transport of P through the ground, due to different chemical, physical and biological processes occurring there. These processes make the P transport slower, which may reduce the unwanted impact on receiving water bodies. However, the efficiency of soil retention of P remains unclear. The objective of this systematic map was to collect, code, organise and elucidate the relevant evidence related to the topic, to be able to guide stakeholders through the evidence base, and to support future research synthesising, commissioning, and funding. The systematic map was carried out in response to needs declared by the Swedish Agency for Marine and Water Management but the conclusions should be valid for a wider range of countries across boreo-temperate regions.Methods: Searches were made for peer-reviewed and grey literature using bibliographic databases, search engines, specialist websites, and stakeholder contacts. The references were screened for relevance according to a predefined set of eligibility criteria. A detailed database of the relevant studies was compiled. Data and metadata that enable evaluation and discussion of the character and quality of the evidence base were extracted and coded. Special focus was placed on assessing if existing evidence could contribute to policy and practice decision making. Descriptive information about the evidence base was presented in tables and figures. An interactive evidence atlas and a choropleth were created, displaying the locations of all studies.Review findings: 234 articles out of 10,797 screened records fulfilled the eligibility criteria. These articles contain 256 studies, performed in the field or in the laboratory. Six different study types were identified, based on where the measurements were conducted. Most studies, including laboratory studies, lack replicates. Most field studies are observational case studies.Conclusions: It is not possible to derive valid generic measures of the efficiency of soil retention of P occurring in the natural soil environment from available research. Neither does the evidence base allow for answering the question of the magnitude of the potential impact of OWTSs on the P concentration in recipients on a general basis, or under what conditions OWTSs generally have such an impact. A compilation of groundwater studies may provide examples of how far the P may reach in x years, but the number of groundwater studies is insufficient to draw any general conclusions, given the complexity and variability of the systems. Future research should strive for replicated study designs, more elaborate reporting, and the establishment of a reporting standard.
|
|
| 3. |
- Envall, Ida, et al.
(författare)
-
What evidence exists related to soil retention of phosphorus from on-site wastewater treatment systems in boreal and temperate climate zones? : A systematic map protocol
- 2020
-
Ingår i: Environmental Evidence. - : BMC. - 2047-2382. ; 9:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background Soil-based on-site wastewater treatment systems (OWSs) are suspected to contribute to eutrophication of surface waters, due to the discharge of phosphorus (P). However, along the flow path between the facilities and surface waters, different processes contribute to delay the transport of phosphorus through the ground. This may reduce the unwanted impact on receiving water bodies. However, the strength and significance of this so-called soil retention remains unclear. In Sweden, there are nearly one million OWSs. To protect surface waters, a high P removal rate (up to 90%) is often required by the local municipalities. However, since these requirements may have costly consequences to property owners, it is debated as to whether they are too strict. In this debate, it is often claimed that the retention of P occurring in natural environments may be underestimated by authorities. Accordingly, there is a need for a scrutiny of the available evidence related to soil retention of phosphorus from OWSs. This is the objective of the planned systematic map. Focus will be on boreal and temperate climate zones. Methods Searches will be made for peer-reviewed articles and grey literature using bibliographic databases, search engines, specialist websites and stakeholder contacts. The references will be screened for relevance according to a predefined set of eligibility criteria. At stage one, after testing and clarifying the eligibility criteria, the references will be single-screened based on title and abstract. At stage two, potentially relevant references will be screened in full-text independently by two reviewers. We will compile a detailed database of the relevant studies. Moreover, a narrative report will be produced, describing the research landscape in general terms. This will be carried out with a conceptual model, describing the processes involved in P retention in natural environments, as a foundation. It will be discussed where the respective studies/study types fit into the conceptual model, and also evaluated how each study/study type can be related to the overarching question of eutrophication. Moreover, we will describe identified knowledge gaps that warrant further primary research effort, as well as identified knowledge clusters that could be suitable for systematic reviews.
|
|
| 4. |
|
|
| 5. |
- Roy, Ananya, et al.
(författare)
-
Mast Cell Infiltration in Human Brain Metastases Modulates the Microenvironment and Contributes to the Metastatic Potential
- 2017
-
Ingår i: Frontiers in Oncology. - : Frontiers Media SA. - 2234-943X. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- Metastatic brain tumors continue to be a clinical problem, despite new therapeutic advances in cancer treatment. Brain metastases (BMs) are among the most common mass lesions in the brain that are resistant to chemotherapies, have a very poor prognosis, and currently lack any efficient diagnostic tests. Predictions estimate that about 40% of lung and breast cancer patients will develop BM. Despite this, very little is known about the immunological and genetic aberrations that drive tumorigenesis in BM. In this study, we demonstrate the infiltration of mast cells (MCs) in a large cohort of human BM samples with different tissues of origin for primary cancer. We applied patient-derived BM cell models to the study of BM cell-MC interactions. BM cells when cocultured with MCs demonstrate enhanced growth and self-renewal capacity. Gene set enrichment analyses indicate increased expression of signal transduction and transmembrane proteins related genes in the cocultured BM cells. MCs exert their effect by release of mediators such as IL-8, IL-10, matrix metalloprotease 2, and vascular endothelial growth factor, thereby permitting metastasis. In conclusion, we provide evidence for a role of MCs in BM. Our findings indicate MCs' capability of modulating gene expression in BM cells and suggest that MCs can serve as a new target for drug development against metastases in the brain.
|
|
| 6. |
|
|
| 7. |
|
|
