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- Al-Khawaja, Khadija, et al.
(författare)
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Palestinian women of Syria mobilising to influence knowledge production
- 2023
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Ingår i: Forced Migration Review. - United Kingdom : Refugees Studies Centre. - 1460-9819 .- 2051-3070. ; :June, s. 5-7
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Tidskriftsartikel (refereegranskat)abstract
- The voices of Palestinian women of Syria are often silenced in knowledge produced in humanitarian research and practice. ‘Speaking back’ sessions provide crucial insights into these women’s experiences and their relevance for discussions on rights mobilisation.Forced migrants are often asked to share parts of their lives with journalists, researchers and humanitarian professionals. Knowledge production is part and parcel of humanitarian practice: humanitarian actors endlessly collect, share and analyse testimonies from marginalised peoples in order to access funding and distribute aid. However, research participants’ wider stories and experiences are often silenced. They are seldom asked to take part in these processes and have little influence over how their words, voices and images are framed. Few researchers have actively engaged in how to empower participants from marginalised communities to act as consultants and experts that inform dialogues on knowledge production about their own communities.
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| 3. |
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| 4. |
- Chelban, V., et al.
(författare)
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PDXK mutations cause polyneuropathy responsive to pyridoxal 5′-phosphate supplementation
- 2019
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Ingår i: Annals of Neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 86:2, s. 225-240
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To identify disease-causing variants in autosomal recessive axonal polyneuropathy with optic atrophy and provide targeted replacement therapy. Methods: We performed genome-wide sequencing, homozygosity mapping, and segregation analysis for novel disease-causing gene discovery. We used circular dichroism to show secondary structure changes and isothermal titration calorimetry to investigate the impact of variants on adenosine triphosphate (ATP) binding. Pathogenicity was further supported by enzymatic assays and mass spectroscopy on recombinant protein, patient-derived fibroblasts, plasma, and erythrocytes. Response to supplementation was measured with clinical validated rating scales, electrophysiology, and biochemical quantification. Results: We identified biallelic mutations in PDXK in 5 individuals from 2 unrelated families with primary axonal polyneuropathy and optic atrophy. The natural history of this disorder suggests that untreated, affected individuals become wheelchair-bound and blind. We identified conformational rearrangement in the mutant enzyme around the ATP-binding pocket. Low PDXK ATP binding resulted in decreased erythrocyte PDXK activity and low pyridoxal 5′-phosphate (PLP) concentrations. We rescued the clinical and biochemical profile with PLP supplementation in 1 family, improvement in power, pain, and fatigue contributing to patients regaining their ability to walk independently during the first year of PLP normalization. Interpretation: We show that mutations in PDXK cause autosomal recessive axonal peripheral polyneuropathy leading to disease via reduced PDXK enzymatic activity and low PLP. We show that the biochemical profile can be rescued with PLP supplementation associated with clinical improvement. As B6 is a cofactor in diverse essential biological pathways, our findings may have direct implications for neuropathies of unknown etiology characterized by reduced PLP levels. ANN NEUROL 2019;86:225–240. © 2019 The Authors. Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.
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| 5. |
- Cipullo, M, et al.
(författare)
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Structural basis for late maturation steps of the human mitoribosomal large subunit
- 2021
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 3673-
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Tidskriftsartikel (refereegranskat)abstract
- Mitochondrial ribosomes (mitoribosomes) synthesize a critical set of proteins essential for oxidative phosphorylation. Therefore, mitoribosomal function is vital to the cellular energy supply. Mitoribosome biogenesis follows distinct molecular pathways that remain poorly understood. Here, we determine the cryo-EM structures of mitoribosomes isolated from human cell lines with either depleted or overexpressed mitoribosome assembly factor GTPBP5, allowing us to capture consecutive steps during mitoribosomal large subunit (mt-LSU) biogenesis. Our structures provide essential insights into the last steps of 16S rRNA folding, methylation and peptidyl transferase centre (PTC) completion, which require the coordinated action of nine assembly factors. We show that mammalian-specific MTERF4 contributes to the folding of 16S rRNA, allowing 16 S rRNA methylation by MRM2, while GTPBP5 and NSUN4 promote fine-tuning rRNA rearrangements leading to PTC formation. Moreover, our data reveal an unexpected involvement of the elongation factor mtEF-Tu in mt-LSU assembly, where mtEF-Tu interacts with GTPBP5, similar to its interaction with tRNA during translational elongation.
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| 7. |
- Gennery, A. R., et al.
(författare)
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Treatment of CD40 ligand deficiency by hematopoietic stem cell transplantation: a survey of the European experience, 1993-2002
- 2004
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 103:3, s. 1152-7
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Tidskriftsartikel (refereegranskat)abstract
- CD40 ligand (CD40L) deficiency causes recurrent sinopulmonary infection, Pneumocystis carinii pneumonia, and Cryptosporidium parvum infection. Approximately 40% to 50% of patients survive to the third decade: long-term survival is unclear. Hematopoietic stem cell transplantation (HSCT) is curative. We present a retrospective analysis of 38 European patients undergoing HSCT for CD40L deficiency in 8 European countries between 1993 and 2002. Donor stem cell source included 14 HLA-identical siblings, 22 unrelated donors, and 2 phenotypically matched parental stem cells (12 T-cell depleted). Of the patients, 34 engrafted and 26 (68%) survived; 3 had autologous reconstitution, 22 (58%) were cured, and 1 engrafted but has poor T-cell immune reconstitution. There were 18 evaluated patients who responded to vaccination. Of the patients, 12 (32%) died from infection-related complications, with severe cryptosporidiosis in 6. Grades 2 to 4 graft-versus-host disease (GvHD) associated with infection occurred in 6 of 12 fatal cases. HSCT cured 58% of patients, 72% of those without hepatic disease. Early T-cell function following whole marrow HSCT may limit cryptosporidial disease, but survival was similar after T-cell-depleted HSCT. Preexisting lung damage was the most important adverse risk factor. Further studies will determine optimal timing and type of HSCT.
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| 8. |
- Habibi, Mojtaba, et al.
(författare)
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University Student Depression Inventory: Measurement model and psychometric properties
- 2014
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Ingår i: Australian journal of psychology. - : Australian Psychological Society. - 0004-9530 .- 1742-9536. ; 66:3, s. 149-157
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Tidskriftsartikel (refereegranskat)abstract
- University Student Depression Inventory (USDI) was developed to assess the symptoms of depression among the university students. Considering the debilitating nature of depression among university students globally, USDI was translated in Persian and validated using university students from Iran. A battery including the Persian version of USDI and scales measuring suicide, depression, and stress was administered to a normative sample of 359 undergraduate students, and an additional clinical sample of 150 students referred to the universitys mental health centre. The results supported the factor structure and the psychometric properties of the translated version. Confirmatory factor analysis upheld the previously reported three-factor first-order and one-factor second-order structure. The internal consistency, test-retest reliability, and concurrent and discriminant validity of the Persian version were supported. Cut-off points using receiver operating characteristic curve analysis were established to identify students at risk. Gender differences on the symptoms of depression were evident only in the normative sample, where male participants, compared with female students, had higher mean scores in lethargy, cognitive/emotion, and academic motivation subscales. The translated scale can be used with Persian-speaking students in Iran and the neighbouring countries as well as those settled in the West to identify symptoms of depression for further evaluation and management.
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| 9. |
- Itoh, Yuzuru, et al.
(författare)
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Mechanism of mitoribosomal small subunit biogenesis and preinitiation
- 2022
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 606, s. 603-608
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Tidskriftsartikel (refereegranskat)abstract
- Mitoribosomes are essential for the synthesis and maintenance of bioenergetic proteins. Here we use cryo-electron microscopy to determine a series of the small mitoribosomal subunit (SSU) intermediates in complex with auxiliary factors, revealing a sequential assembly mechanism. The methyltransferase TFB1M binds to partially unfolded rRNA h45 that is promoted by RBFA, while the mRNA channel is blocked. This enables binding of METTL15 that promotes further rRNA maturation and a large conformational change of RBFA. The new conformation allows initiation factor mtIF3 to already occupy the subunit interface during the assembly. Finally, the mitochondria-specific ribosomal protein mS37 (ref. 1) outcompetes RBFA to complete the assembly with the SSU–mS37–mtIF3 complex2 that proceeds towards mtIF2 binding and translation initiation. Our results explain how the action of step-specific factors modulate the dynamic assembly of the SSU, and adaptation of a unique protein, mS37, links the assembly to initiation to establish the catalytic human mitoribosome.
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| 10. |
- Itoh, Yuzuru, et al.
(författare)
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Structure of the mitoribosomal small subunit with streptomycin reveals Fe-S clusters and physiological molecules
- 2022
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Ingår i: eLIFE. - 2050-084X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- The mitoribosome regulates cellular energy production, and its dysfunction is associated with aging. Inhibition of the mitoribosome can be caused by off-target binding of antimicrobial drugs and was shown to be coupled with a bilateral decreased visual acuity. Previously, we reported mitochondria-specific protein aspects of the mitoribosome, and in this article we present a 2.4-Å resolution structure of the small subunit in a complex with the anti-tuberculosis drug streptomycin that reveals roles of non-protein components. We found iron–sulfur clusters that are coordinated by different mitoribosomal proteins, nicotinamide adenine dinucleotide (NAD) associated with rRNA insertion, and posttranslational modifications. This is the first evidence of inter-protein coordination of iron–sulfur, and the finding of iron–sulfur clusters and NAD as fundamental building blocks of the mitoribosome directly links to mitochondrial disease and aging. We also report details of streptomycin interactions, suggesting that the mitoribosome-bound streptomycin is likely to be in hydrated gem-diol form and can be subjected to other modifications by the cellular milieu. The presented approach of adding antibiotics to cultured cells can be used to define their native structures in a bound form under more physiological conditions, and since streptomycin is a widely used drug for treatment, the newly resolved features can serve as determinants for targeting.
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