| 1. |
- Ali, Rabea A. M., et al.
(author)
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Neoproterozoic and Cretaceous mantle oxidation states : Controls Chock for and heterogeneity through time
- 2020
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In: Lithos. - : Elsevier BV. - 0024-4937 .- 1872-6143. ; 356
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Journal article (peer-reviewed)abstract
- To estimate the oxygen fugacity (fO(2)) of the Neoproterozoic and Cretaceous suprasubduction zone mantle, and to evaluate the possible secular changes in the upper mantle oxidation state, the compositions of spinel, olivine and orthopyroxene of Neoproterozoic (Egypt and Saudi Arabia) and late Cretaceous (Iran) mantle rocks were determined. For accurate estimation fO(2), spinel ferric iron was calculated after correcting the electron microprobe data using a set of spine! standards for which the ferric iron content was measured by Mossbauer spectroscopy. The Neoproterozoic samples record strongly heterogenous fO(2) values ranging from moderately oxidized (FMQ +0.54) to ultra-reduced (FMQ-4.73) for harzburgites, from highly oxidized (FMQ+1.49) to moderately reduced (FMQ-0.60) for dunites as well as one highly reduced (FMQ-1.61) value for chromitite. Such heterogeneity is not apparent in the late Cretaceous harzburgites that record fO(2) values ranging from slightly oxidized (FMQ +0.45) to moderately reduced (FMQ -0.85). The fO(2) of the Neoproterozoic forearc mantle is most easily explained by melt-mantle interaction and deep-mantle recycling, while that of the late Cretaceous forearc mantle can be attributed to variable degrees of melt-mantle interaction. The estimated fO(2 )values of Neoproterozoic/Cretaceous mantle unaffected by melt-rock interaction and deep-mantle recycling, and published values of Precambrian and Modern mantle suggest a consistent upper mantle oxidation state from Proterozoic to present day.
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| 2. |
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| 4. |
- Alkasalias, T, et al.
(author)
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Proof-of-principle studies on a strategy to enhance nucleotide imbalance specifically in cancer cells
- 2022
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In: Cell death discovery. - : Springer Science and Business Media LLC. - 2058-7716. ; 8:1, s. 464-
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Journal article (peer-reviewed)abstract
- Highly specific and potent inhibitors of dihydroorotate dehydrogenase (DHODH), an essential enzyme of the de novo pyrimidine ribonucleotide synthesis pathway, are in clinical trials for autoimmune diseases, viral infections and cancer. However, because DHODH inhibitors (DHODHi) are immunosuppressants they may reduce the anticancer activity of the immune system. Therefore, there may be a need to improve the therapeutic index of DHODHi in cancer patients. The aim of this study was to find strategies to protect activated T cells from DHODHi and to identify cancer types hypersensitive to these inhibitors. First, we observed that like uridine supplementation, adding cytidine to the culture medium protects T cells from DHODH blockage. Next, we identified tumor types with altered expression of pyrimidine ribonucleotide synthesis enzymes. In this regard, we detected that the expression of cytidine deaminase (CDA), which converts cytidine into uridine, is low in an important proportion of cancer cell lines and consistently low in neuroblastoma samples and in cell lines from neuroblastoma and small cell lung carcinoma. This suggested that in the presence of a DHODHi, an excess of cytidine would be deleterious for low CDA expressing cancer cell lines. We show that this was the case (as could be seen almost immediately after treatment) when cells were cultured with fetal bovine serum but, was significantly less evident when cultures contained human serum. One interesting feature of CDA is that aside from acting intracellularly, it is also present in human plasma/serum. Altogether, experiments using recombinant CDA, human serum, pharmacologic inhibition of CDA and T cell/cancer cell co-cultures suggest that the therapeutic index of DHODHi could be improved by selecting patients with low-CDA expressing cancers in combination with strategies to increase cytidine or the cytidine/uridine ratio in the extracellular environment. Collectively, this proof-of-principle study warrants the discovery of agents to deplete extracellular CDA.
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| 11. |
- Christakoudi, Sofia, et al.
(author)
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Steroid regulation : An overlooked aspect of tolerance and chronic rejection in kidney transplantation
- 2018
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In: Molecular and Cellular Endocrinology. - : ELSEVIER IRELAND LTD. - 0303-7207 .- 1872-8057. ; 473, s. 205-216
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Journal article (peer-reviewed)abstract
- Steroid conversion (HSD11B1, HSD11B2, H6PD) and receptor genes (NR3C1, NR3C2) were examined in kidney-transplant recipients with "operational tolerance" and chronic rejection (CR), independently and within the context of 88 tolerance-associated genes. Associations with cellular types were explored. Peripheral whole-blood gene-expression levels (RT-qPCR-based) and cell counts were adjusted for immunosuppressant drug intake. Tolerant (n = 17), stable (n = 190) and CR patients (n = 37) were compared. Healthy controls (n= 14) were used as reference. The anti-inflammatory glucocorticoid receptor (NR3C1) and the cortisol-activating HSD11B1 and H6PD genes were up-regulated in CR and were lowest in tolerant patients. The pro-inflammatory mineralocorticoid gene (NR3C2) was downregulated in stable and CR patients. NR3C1 was associated with neutrophils and NR3C2 with T-cells. Steroid conversion and receptor genes, alone, enabled classification of tolerant patients and were major contributors to gene-expression signatures of both, tolerance and CR, alongside known tolerance-associated genes, revealing a key role of steroid regulation and response in kidney transplantation.
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| 12. |
- Chuang, Allen, et al.
(author)
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Optimal SNR exponent for discrete-input MIMO ARQ block-fading channels
- 2007
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In: 2007 IEEE INTERNATIONAL SYMPOSIUM ON INFORMATION THEORY PROCEEDINGS, VOLS 1-7. ; , s. 2291-2295
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Conference paper (other academic/artistic)abstract
- In this paper, we consider an automatic-repeat-request (ARQ) retransmission protocol signaling over a block-fading multiple-input, multiple-output (MIMO) channel. In particular, we consider fixed rate codes constructed over discrete complex signal constellations. We show that the optimal signal-to-noise ratio (SNR) exponent is given by a modified Singleton bound, relating all the system parameters. To demonstrate the practical significance of the theoretical analysis, we present numerical results showing that practical Singleton-bound-achieving maximum distance separable codes achieve the optimal SNR exponent.
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| 13. |
- Costeira-Paulo, Joana, et al.
(author)
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Lipids Shape the Electron Acceptor-Binding Site of the Peripheral Membrane Protein Dihydroorotate Dehydrogenase
- 2018
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In: Cell Chemical Biology. - : Elsevier BV. - 2451-9456 .- 2451-9448. ; 25:3, s. 309-317
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Journal article (peer-reviewed)abstract
- The interactions between proteins and biological membranes are important for drug development, but remain notoriously refractory to structural investigation. We combine non-denaturing mass spectrometry (MS) with molecular dynamics (MD) simulations to unravel the connections among co-factor, lipid, and inhibitor binding in the peripheral membrane protein dihydroorotate dehydrogenase (DHODH), a key anticancer target. Interrogation of intact DHODH complexes by MS reveals that phospholipids bind via their charged head groups at a limited number of sites, while binding of the inhibitor brequinar involves simultaneous association with detergent molecules. MD simulations show that lipids support flexible segments in the membrane-binding domain and position the inhibitor and electron acceptor-binding site away from the membrane surface, similar to the electron acceptor-binding site in respiratory chain complex I. By complementing MS with MD simulations, we demonstrate how a peripheral membrane protein uses lipids to modulate its structure in a similar manner as integral membrane proteins.
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| 14. |
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| 15. |
- Fåhraeus, R, et al.
(author)
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Response to cAMP levels of the Epstein-Barr virus EBNA2-inducible LMP1 oncogene and EBNA2 inhibition of a PP1-like activity.
- 1994
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In: The EMBO journal. - 0261-4189. ; 13:24, s. 6041-51
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Journal article (peer-reviewed)abstract
- The expression of the Epstein-Barr virus LMP1 oncogene is regulated by viral and non-viral factors in a tissue dependent fashion. The virus encoded transcription factor EBNA2 induces its expression in human B-cells. However, this induction also requires the contribution of cellular and/or other viral factors. In nasopharyngeal carcinoma cells and in cells from Hodgkin's lymphoma, LMP1 gene transcription is independent of viral products. Here we show that the effect of a factor binding to a cAMP responsive-like element (CRE) in the LMP1 gene transcription regulatory sequence (LRS) is essential for efficient promoter activity in the DG75 B-cell line and that elevation of cAMP levels in the cells induces LRS-derived CAT activity in a CRE dependent fashion. Incubation of two EBV-immortalized B-cell lines expressing endogenous EBNA2A with 8-Br cAMP increased the levels of the latency associated 66 kDa LMP1 within 2 h. Interestingly, LMP1 expression in DG75 cells conferred resistance to the inhibitory effect of 8-Br cAMP on cell proliferation. The protein phosphatase 1 and 2A (PP1 and PP2A, respectively) inhibitor okadaic acid also stimulated LRS-CAT activity in DG75 cells. EBNA2A from an EBV-immortalized B-cell line co-immunopurified with a PP1-like protein. An EBNA2A fragment spanning residues 324-436 fused to the GST protein specifically rescued a PP1/PP2A-like component from DG75 cell extracts. This GST-EBNA2A fusion product inhibited a PP1-like activity in nuclear extracts from these cells.
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| 16. |
- Gault, Joseph, et al.
(author)
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Mass Spectrometry Reveals the Direct Action of a Chemical Chaperone
- 2018
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In: The Journal of Physical Chemistry Letters. - : American Chemical Society (ACS). - 1948-7185. ; 9:14, s. 4082-4086
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Journal article (peer-reviewed)abstract
- Despite their fundamental biological importance and therapeutic potential, the interactions between chemical chaperones and proteins remain difficult to capture due to their transient and nonspecific nature. Using a simple mass spectrometric assay, we are able to follow the interactions between proteins and the chemical chaperone trimethylamine-N-oxide (TMAO). In this manner, we directly observe that the counteraction of TMAO and the denaturant urea is driven by the exclusion of TMAO from the protein surface, whereas the surfactant lauryl dimethylamine-N-oxide cannot be displaced. Our results clearly demonstrate a direct chaperoning mechanism for TMAO, corroborating extensive computational studies, and pave the way for the use of nondenaturing mass spectrometry and related techniques to study chemical chaperones in molecular detail.
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| 17. |
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| 18. |
- Heath, Victoria, et al.
(author)
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Monitor – biology
- 2004
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In: Drug Discovery Today. - 1878-5832. ; 9:15, s. 678-681
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Journal article (peer-reviewed)abstract
- The hottest developments in the fields of cancer research, neuroscience, genomics and proteomics, anti-virals and more, with a pick of the key research papers in these areas.
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| 19. |
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| 20. |
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| 21. |
- Kapun, Martin, et al.
(author)
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Drosophila Evolution over Space and Time (DEST) : A New Population Genomics Resource
- 2021
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In: Molecular biology and evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 38:12, s. 5782-5805
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Journal article (peer-reviewed)abstract
- Drosophila melanogaster is a leading model in population genetics and genomics, and a growing number of whole-genome data sets from natural populations of this species have been published over the last years. A major challenge is the integration of disparate data sets, often generated using different sequencing technologies and bioinformatic pipelines, which hampers our ability to address questions about the evolution of this species. Here we address these issues by developing a bioinformatics pipeline that maps pooled sequencing (Pool-Seq) reads from D. melanogaster to a hologenome consisting of fly and symbiont genomes and estimates allele frequencies using either a heuristic (PoolSNP) or a probabilistic variant caller (SNAPE-pooled). We use this pipeline to generate the largest data repository of genomic data available for D. melanogaster to date, encompassing 271 previously published and unpublished population samples from over 100 locations in >20 countries on four continents. Several of these locations have been sampled at different seasons across multiple years. This data set, which we call Drosophila Evolution over Space and Time (DEST), is coupled with sampling and environmental metadata. A web-based genome browser and web portal provide easy access to the SNP data set. We further provide guidelines on how to use Pool-Seq data for model-based demographic inference. Our aim is to provide this scalable platform as a community resource which can be easily extended via future efforts for an even more extensive cosmopolitan data set. Our resource will enable population geneticists to analyze spatiotemporal genetic patterns and evolutionary dynamics of D. melanogaster populations in unprecedented detail.
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| 22. |
- Kapun, Martin, et al.
(author)
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Genomic analysis of european drosophila melanogaster populations reveals longitudinal structure, continent-wide selection, and previously unknown DNA viruses
- 2020
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In: Molecular biology and evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 37:9, s. 2661-2678
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Journal article (peer-reviewed)abstract
- Genetic variation is the fuel of evolution, with standing genetic variation especially important for short-term evolution and local adaptation. To date, studies of spatiotemporal patterns of genetic variation in natural populations have been challenging, as comprehensive sampling is logistically difficult, and sequencing of entire populations costly. Here, we address these issues using a collaborative approach, sequencing 48 pooled population samples from 32 locations, and perform the first continent-wide genomic analysis of genetic variation in European Drosophila melanogaster. Our analyses uncover longitudinal population structure, provide evidence for continent-wide selective sweeps, identify candidate genes for local climate adaptation, and document clines in chromosomal inversion and transposable element frequencies. We also characterize variation among populations in the composition of the fly microbiome, and identify five new DNA viruses in our samples.
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| 23. |
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| 24. |
- Kharaziha, Pedram, et al.
(author)
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Functional characterization of novel germline TP53 variants in Swedish families
- 2019
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In: Clinical Genetics. - : Wiley. - 0009-9163 .- 1399-0004. ; 96:3, s. 216-225
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Journal article (peer-reviewed)abstract
- Pathogenic germline TP53 variants predispose to a wide range of early onset cancers, often recognized as the Li-Fraumeni syndrome (LFS). They are also identified in 1% of families with hereditary breast cancer (HrBC) that do not fulfill the criteria for LFS. In this study, we present a total of 24 different TP53 variants identified in 31 Swedish families with LFS or HrBC. Ten of these variants, nine exonic and one splice, have previously not been described as germline pathogenic variants. The nine exonic variants were functionally characterized and demonstrated partial transactivation activity compared to wild-type p53. Some show nuclear localization similar to wild-type p53 while others possess cytoplasmic or perinuclear localization. The four frameshift variants (W91Gfs*32, L111 Wfs*12, S227 Lfs*20 and S240Kfs*25) had negligible, while F134 L and T231del had low level of p53 activity. The L111 Wfs*12 and T231del variants are also deficient for induction of apoptosis. The missense variant R110C retain p53 effects and the nonsense E349* shows at least partial transcription factor activity but has reduced ability to trigger apoptosis. This is the first functional characterization of novel germline TP53 pathogenic or likely pathogenic variants in the Swedish cohort as an attempt to understand its association with LFS and HrBC, respectively.
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| 25. |
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| 26. |
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| 27. |
- Ladds, Marcus J. G. W., et al.
(author)
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A DHODH inhibitor increases p53 synthesis and enhances tumor cell killing by p53 degradation blockage
- 2018
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9
-
Journal article (peer-reviewed)abstract
- The development of non-genotoxic therapies that activate wild-type p53 in tumors is of great interest since the discovery of p53 as a tumor suppressor. Here we report the identification of over 100 small-molecules activating p53 in cells. We elucidate the mechanism of action of a chiral tetrahydroindazole (HZ00), and through target deconvolution, we deduce that its active enantiomer (R)-HZ00, inhibits dihydroorotate dehydrogenase (DHODH). The chiral specificity of HZ05, a more potent analog, is revealed by the crystal structure of the (R)-HZ05/DHODH complex. Twelve other DHODH inhibitor chemotypes are detailed among the p53 activators, which identifies DHODH as a frequent target for structurally diverse compounds. We observe that HZ compounds accumulate cancer cells in S-phase, increase p53 synthesis, and synergize with an inhibitor of p53 degradation to reduce tumor growth in vivo. We, therefore, propose a strategy to promote cancer cell killing by p53 instead of its reversible cell cycle arresting effect.
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| 28. |
- Ladds, Marcus J. G. W., et al.
(author)
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Autophagic flux blockage by accumulation of weakly basic tenovins leads to elimination of B-Raf mutant tumour cells that survive vemurafenib
- 2018
-
In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 13:4
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Journal article (peer-reviewed)abstract
- Tenovin-6 is the most studied member of a family of small molecules with antitumour activity in vivo. Previously, it has been determined that part of the effects of tenovin-6 associate with its ability to inhibit SirT1 and activate p53. However, tenovin-6 has also been shown to modulate autophagic flux. Here we show that blockage of autophagic flux occurs in a variety of cell lines in response to certain tenovins, that autophagy blockage occurs regardless of the effect of tenovins on SirT1 or p53, and that this blockage is dependent on the aliphatic tertiary amine side chain of these molecules. Additionally, we evaluate the contribution of this tertiary amine to the elimination of proliferating melanoma cells in culture. We also demonstrate that the presence of the tertiary amine is sufficient to lead to death of tumour cells arrested in G1 phase following vemurafenib treatment. We conclude that blockage of autophagic flux by tenovins is necessary to eliminate melanoma cells that survive B-Raf inhibition and achieve total tumour cell kill and that autophagy blockage can be achieved at a lower concentration than by chloroquine. This observation is of great relevance as relapse and resistance are frequently observed in cancer patients treated with B-Raf inhibitors.
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| 29. |
- Ladds, MJGW, et al.
(author)
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Publisher Correction: A DHODH inhibitor increases p53 synthesis and enhances tumor cell killing by p53 degradation blockage
- 2018
-
In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 2071-
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Journal article (peer-reviewed)abstract
- The original PDF version of this Article listed the authors as “Marcus J.G.W. Ladds,” where it should have read “Marcus J. G. W. Ladds, Ingeborg M. M. van Leeuwen, Catherine J. Drummond et al.#”.Also in the PDF version, it was incorrectly stated that “Correspondence and requests for materials should be addressed to S. Lín.”, instead of the correct “Correspondence and requests for materials should be addressed to S. Laín.”This has been corrected in the PDF version of the Article. The HTML version was correct from the time of publication.
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| 30. |
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| 31. |
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| 32. |
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| 33. |
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| 34. |
- Lain, S
(author)
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Drug discovery in the p53 field
- 2010
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In: Seminars in cancer biology. - : Elsevier BV. - 1096-3650 .- 1044-579X. ; 20:1, s. 1-2
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Journal article (other academic/artistic)
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| 35. |
- Lain, S
(author)
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If p53 can't do it, ask p73
- 2008
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In: CELL CYCLE. - 1538-4101. ; 7:21, s. 3290-3291
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Journal article (other academic/artistic)
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| 36. |
- Lane, DP, et al.
(author)
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p53-based cancer therapy
- 2010
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In: Cold Spring Harbor perspectives in biology. - : Cold Spring Harbor Laboratory. - 1943-0264. ; 2:9, s. a001222-
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Journal article (peer-reviewed)
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| 37. |
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| 38. |
- Lin, Ci, et al.
(author)
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Direct Band Gap in Multilayer Transition Metal Dichalcogenide Nanoscrolls with Enhanced Photoluminescence
- 2022
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In: ACS Materials Letters. - : American Chemical Society (ACS). - 2639-4979. ; 4:8, s. 1547-1555
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Journal article (peer-reviewed)abstract
- A direct band gap that solely exists in monolayer semiconducting transition metal dichalcogenides (TMDs) endows strong photoluminescence (PL) features, whereas multilayer TMD structures exhibit quenched PL due to the direct-to-indirect band gap transition. We demonstrate multi-layer TMD (such as MoS2 and WS2) nanoscrolls with a preserved direct band gap fabricated by an effective and facile method of solvent-driven self-assembly. The resultant multi-layer nanoscrolls, exhibiting up to 11 times higher PL intensity than the remanent monolayer, are carefully characterized using PL spectroscopy. Significantly enlarged interlayer distances and modulated interlayer coupling in the fabricated nanostructures are unveiled by cross-sectional scanning transmission electron microscopy, atomic force microscopy, and Raman spectroscopy. The preservation of direct band gap features is further evidenced by density functional theory calculations using the simplified bilayer model with an experimentally obtained 15 & ANGS; interlayer distance. The modulation of the PL intensity as an indicator of the band gap crossover in the TMD nanoscrolls is demonstrated by removing the acetone molecules trapped inside the interlayer space. The general applicability of the method presents an opportunity for large-scale fabrication of a plethora of multilayer TMD nanoscrolls with direct band gaps.
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| 39. |
- Lundstedt, Staffan, et al.
(author)
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Sources, Fate, and Toxic Hazards of Oxygenated Polycyclic Aromatic Hydrocarbons (PAHs) at PAH- contaminated Sites
- 2007
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In: AMBIO: A Journal of the Human Environment. ; 36:6, s. 475–85-
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Journal article (peer-reviewed)abstract
- In this paper we show that oxygenated polycyclic aromatic hydrocarbons (oxy-PAHs) are important cocontaminants that should be taken into account during risk assessment and remediation of sites with high levels of PAHs. The presented data, which have been collected both from our own research and the published literature, demonstrate that oxy-PAHs are abundant but neglected contaminants at these sites. The oxy-PAHs show relatively high persistency and because they are formed through transformation of PAHs, their concentrations in the environment may even increase as the sites are remediated by methods that promote PAH degradation. Furthermore, we show that oxy-PAHs are toxic to both humans and the environment, although the toxicity seems to be manifested through other effects than those known to be important for polycyclic aromatic compounds in general, that is, mutagenicity and carcinogenicity. Finally, we present data that support the hypothesis that oxy-PAHs are more mobile in the environment than PAHs, due to their polarity, and thus have a higher tendency to spread from contaminated sites via surface water and groundwater. We believe that oxy-PAHs should be included in monitoring programs at PAH-contaminated sites, even if a number of other toxicologically relevant compounds that may also be present, such as nitro-PAHs and azaarenes, are not monitored. This is because oxy-PAH levels are difficult to predict from the PAH levels, because their environmental behavior differs substantially from that of PAHs, and oxy-PAHs may be formed as PAHs are degraded.
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| 40. |
- Ma, L, et al.
(author)
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SIRT1 and SIRT2 inhibition impairs pediatric soft tissue sarcoma growth
- 2014
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In: Cell death & disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 5, s. e1483-
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Journal article (peer-reviewed)abstract
- Sirtuins are NAD+ dependent deacetylases and/or ADP-ribosyl transferases active on histone and non-histone substrates. The first sirtuin was discovered as a transcriptional repressor of the mating-type-loci (Silent Information Regulator sir2) in the budding yeast, where it was shown to extend yeast lifespan. Seven mammalian sirtuins (SIRT1-7) have been now identified with distinct subcellular localization, enzymatic activities and substrates. These enzymes regulate cellular processes such as metabolism, cell survival, differentiation, DNA repair and they are implicated in the pathogenesis of solid tumors and leukemias. The purpose of the present study was to investigate the role of sirtuin expression, activity and inhibition in the survival of pediatric sarcoma cell lines.We have analyzed the expression of SIRT1 and SIRT2 in a series of pediatric sarcoma tumor cell lines and normal cells, and we have evaluated the activity of the sirtuin inhibitor and p53 activator tenovin-6 (Tv6) in synovial sarcoma and rhabdomyosarcoma cell lines. We show that SIRT1 is overexpressed in synovial sarcoma biopsies and cell lines in comparison with normal mesenchymal cells. Tv6 induced apoptosis as well as impaired autophagy flux. Using siRNA to knock down SIRT1 and SIRT2, we show that the expression of both proteins is crucial for the survival of rhabdomyosarcoma cells and that the loss of SIRT1 expression results in a decreased LC3II expression. Our results show that SIRT1 and SIRT2 expressions are crucial for the survival of synovial sarcomas and rhabdomyosarcomas, and demonstrate that the pharmacological inhibition of sirtuins impairs the autophagy process and induces tumor cell death.
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| 41. |
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| 42. |
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| 43. |
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| 44. |
- Malfatti, Edoardo, et al.
(author)
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A New Muscle Glycogen Storage Disease Associated with Glycogenin-1 Deficiency
- 2014
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In: Annals of Neurology. - : Wiley. - 0364-5134. ; 76:6, s. 891-898
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Journal article (peer-reviewed)abstract
- We describe a slowly progressive myopathy in 7 unrelated adult patients with storage of polyglucosan in muscle fibers. Genetic investigation revealed homozygous or compound heterozygous deleterious variants in the glycogenin-1 gene (GYG1). Most patients showed depletion of glycogenin-1 in skeletal muscle, whereas 1 showed presence of glycogenin-1 lacking the C-terminal that normally binds glycogen synthase. Our results indicate that either depletion of glycogenin-1 or impaired interaction with glycogen synthase underlies this new form of glycogen storage disease that differs from a previously reported patient with GYG1 mutations who showed profound glycogen depletion in skeletal muscle and accumulation of glycogenin-1. Ann Neurol 2014;76:891-898
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| 45. |
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| 47. |
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| 48. |
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| 49. |
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| 50. |
- Mendham, Amy, et al.
(author)
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Osteoporosis in older black South African women and relationships with body composition, dietary intake and physical activity
- 2020
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In: 13th European Nutrition Conference, FENS 2019, 15–18 October 2019, Malnutrition in an Obese World: European Perspectives. - : Cambridge University Press. ; , s. E441-E441
-
Conference paper (other academic/artistic)abstract
- Introduction: Osteoporosis was not a public health concern in black South African (SA) women, until recently when it was reported that the prevalence of vertebral fractures was 9.1% in black compared to 5.0% in white SA women. Accordingly, this study aimed to measure bone mineral density (BMD) of older black SA women and to investigate its association with risk factors for osteoporosis, including strength, muscle and fat mass, dietary intake and objectively measured physical activity (PA).Methods and materials: Older black SA women (age, 68 (range; 60–85 years) n = 122) completed sociodemographic and quantitative food frequency questionnaires (QFFQ), fasting venous blood samples (25-hydroxycholecalciferol: Vitamin D-25), 24 h urine collection (estimate protein intake), grip strength and PA monitoring (activPAL). Dual-energy x-ray absorptiometry (DXA) scans of the hip (femoral neck and total) and lumbar spine determined BMD and whole-body scans for fat and fat-free soft tissue mass (FFSTM). WHO classifications were used to determine osteopenia (t-score -2.5 to -1), and osteoporosis (t-score < -2.5).Results: At the lumbar spine 34.4% of the women (n = 42) had osteopenia and 19.7% (n = 24) had osteoporosis. Osteopenia at the left femoral neck was 32% (n = 40) and osteoporosis was 13.1% (n = 16) of participants. The total left hip BMD indicated osteopenia in 27.9% (n = 34) and osteoporosis in 13.1% (n = 16) of participants. Multinomial regression revealed no differences in age (y) or frequency of falls in the past year between all groups (p = 0.727). Compared to those with normal BMD, participants with osteoporosis at the hip neck and lumbar spine were shorter, weighed less and had a lower body mass index (BMI) (all p < 0.05). When adjusted for height, the osteoporotic group (hip neck and lumbar spine) had lower trunk fat (% whole body), FFSTM (kg) and grip strength (kg), compared to those with normal BMD (p < 0.05). Only protein intake (g; 24 h urine analyses) was lower in women with osteoporosis (all sites) compared to those with normal BMD. Fat, carbohydrate and micronutrient intakes (relative to total daily energy intake), and vitamin D concentrations were not associated with BMD (all sites). Number of daily step count and stepping time (min) were inversely associated with BMI (p < 0.05), but not with BMD (all sites; p > 0.05).Discussion: A high prevalence of osteopenia and osteoporosis was evident at the lumbar spine and hip in older black SA women. This study highlights the importance of strength, body composition, and protein intake in maintaining BMD and preventing the development of osteoporosis in older women.
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