| 1. |
- Chen, Ruoqing, et al.
(författare)
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Childhood injury after a parental cancer diagnosis
- 2015
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Ingår i: eLIFE. - Stockholm : eLife Sciences Publications Ltd. - 2050-084X. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- A parental cancer diagnosis is psychologically straining for the whole family. We investigated whether a parental cancer diagnosis is associated with a higher-than-expected risk of injury among children by using a Swedish nationwide register-based cohort study. Compared to children without parental cancer, children with parental cancer had a higher rate of hospital contact for injury during the first year after parental cancer diagnosis (hazard ratio [HR]=1.27, 95% confidence interval [CI]=1.22-1.33), especially when the parent had a comorbid psychiatric disorder after cancer diagnosis (HR=1.41, 95% CI=1.08-1.85). The rate increment declined during the second and third year after parental cancer diagnosis (HR=1.10, 95% CI=1.07-1.14) and became null afterwards (HR=1.01, 95% CI=0.99-1.03). Children with parental cancer also had a higher rate of repeated injuries than the other children (HR=1.13, 95% CI= 1.12-1.15). Given the high rate of injury among children in the general population, our findings may have important public health implications.
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| 4. |
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| 5. |
- Aczel, Balazs, et al.
(författare)
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Consensus-based guidance for conducting and reporting multi-analyst studies
- 2021
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Ingår i: eLIFE. - : eLife Sciences Publications. - 2050-084X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Any large dataset can be analyzed in a number of ways, and it is possible that the use of different analysis strategies will lead to different results and conclusions. One way to assess whether the results obtained depend on the analysis strategy chosen is to employ multiple analysts and leave each of them free to follow their own approach. Here, we present consensus-based guidance for conducting and reporting such multi-analyst studies, and we discuss how broader adoption of the multi-analyst approach has the potential to strengthen the robustness of results and conclusions obtained from analyses of datasets in basic and applied research.
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| 6. |
- Agrawal, Ritvija, et al.
(författare)
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The KASH5 protein involved in meiotic chromosomal movements is a novel dynein activating adaptor
- 2022
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Ingår i: eLife. - 2050-084X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Dynein harnesses ATP hydrolysis to move cargo on microtubules in multiple biological contexts. Dynein meets a unique challenge in meiosis by moving chromosomes tethered to the nuclear envelope to facilitate homolog pairing essential for gametogenesis. Though processive dynein motility requires binding to an activating adaptor, the identity of the activating adaptor required for dynein to move meiotic chromosomes is unknown. We show that the meiosis-specific nuclear-envelope protein KASH5 is a dynein activating adaptor: KASH5 directly binds dynein using a mechanism conserved among activating adaptors and converts dynein into a processive motor. We map the dynein-binding surface of KASH5, identifying mutations that abrogate dynein binding in vitro and disrupt recruitment of the dynein machinery to the nuclear envelope in cultured cells and mouse spermatocytes in vivo. Our study identifies KASH5 as the first transmembrane dynein activating adaptor and provides molecular insights into how it activates dynein during meiosis.
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| 7. |
- Aibara, Shintaro, et al.
(författare)
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Structural basis of mitochondrial translation
- 2020
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Ingår i: eLIFE. - 2050-084X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Translation of mitochondrial messenger RNA (mt-mRNA) is performed by distinct mitoribosomes comprising at least 36 mitochondria-specific proteins. How these mitoribosomal proteins assist in the binding of mt-mRNA and to what extent they are involved in the translocation of transfer RNA (mt-tRNA) is unclear. To visualize the process of translation in human mitochondria, we report similar to 3.0 angstrom resolution structure of the human mitoribosome, including the L7/L12 stalk, and eight structures of its functional complexes with mt-mRNA, mt-tRNAs, recycling factor and additional trans factors. The study reveals a transacting protein module LRPPRC-SLIRP that delivers mt-mRNA to the mitoribosomal small subunit through a dedicated platform formed by the mitochondria-specific protein mS39. Mitoribosomal proteins of the large subunit mL40, mL48, and mL64 coordinate translocation of mt-tRNA. The comparison between those structures shows dynamic interactions between the mitoribosome and its ligands, suggesting a sequential mechanism of conformational changes.
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| 8. |
- Alanio, Cécile, et al.
(författare)
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Bystander hyperactivation of preimmune CD8(+) T cells in chronic HCV patients
- 2015
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Ingår i: eLife. - 2050-084X. ; 2015:4
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Tidskriftsartikel (refereegranskat)abstract
- Chronic infection perturbs immune homeostasis. While prior studies have reported dysregulation of effector and memory cells, little is known about the effects on naïve T cell populations. We performed a cross-sectional study of chronic hepatitis C (cHCV) patients using tetramer-associated magnetic enrichment to study antigen-specific inexperienced CD8(+) T cells (i.e., tumor or unrelated virus-specific populations in tumor-free and sero-negative individuals). cHCV showed normal precursor frequencies, but increased proportions of memory-phenotype inexperienced cells, as compared to healthy donors or cured HCV patients. These observations could be explained by low surface expression of CD5, a negative regulator of TCR signaling. Accordingly, we demonstrated TCR hyperactivation and generation of potent CD8(+) T cell responses from the altered T cell repertoire of cHCV patients. In sum, we provide the first evidence that naïve CD8(+) T cells are dysregulated during cHCV infection, and establish a new mechanism of immune perturbation secondary to chronic infection.
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| 9. |
- Alex, Amal, et al.
(författare)
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Electroporated recombinant proteins as tools for in vivo functional complementation, imaging and chemical biology
- 2019
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Ingår i: eLIFE. - : ELIFE SCIENCES PUBLICATIONS LTD. - 2050-084X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Delivery of native or chemically modified recombinant proteins into mammalian cells shows promise for functional investigations and various technological applications, but concerns that sub-cellular localization and functional integrity of delivered proteins may be affected remain high. Here, we surveyed batch electroporation as a delivery tool for single polypeptides and multi-subunit protein assemblies of the kinetochore, a spatially confined and well-studied subcellular structure. After electroporation into human cells, recombinant fluorescent Ndc80 and Mis12 multi-subunit complexes exhibited native localization, physically interacted with endogenous binding partners, and functionally complemented depleted endogenous counterparts to promote mitotic checkpoint signaling and chromosome segregation. Farnesylation is required for kinetochore localization of the Dynein adaptor Spindly. In cells with chronically inhibited farnesyl transferase activity, in vitro farnesylation and electroporation of recombinant Spindly faithfully resulted in robust kinetochore localization. Our data show that electroporation is well-suited to deliver synthetic and chemically modified versions of functional proteins, and, therefore, constitutes a promising tool for applications in chemical and synthetic biology.
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