| 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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| 2. |
- 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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| 3. |
- Anderl, Ines, et al.
(författare)
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New ways to make a blood cell
- 2015
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Ingår i: eLIFE. - 2050-084X. ; 4
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 4. |
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| 5. |
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| 6. |
- Dijk, Wieneke, et al.
(författare)
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ANGPTL4 mediates shuttling of lipid fuel to brown adipose tissue during sustained cold exposure
- 2015
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Ingår i: eLIFE. - : eLife Sciences Publications. - 2050-084X. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- Brown adipose tissue (BAT) activation via cold exposure is increasingly scrutinized as a potential approach to ameliorate cardio-metabolic risk. Transition to cold temperatures requires changes in the partitioning of energy substrates, re-routing fatty acids to BAT to fuel non-shivering thermogenesis. However, the mechanisms behind the redistribution of energy substrates to BAT remain largely unknown. Angiopoietin-like 4 (ANGPTL4), a protein that inhibits lipoprotein lipase (LPL) activity, is highly expressed in BAT. Here, we demonstrate that ANGPTL4 is part of a shuttling mechanism that directs fatty acids derived from circulating triglyceride-rich lipoproteins to BAT during cold. Specifically, we show that cold markedly down-regulates ANGPTL4 in BAT, likely via activation of AMPK, enhancing LPL activity and uptake of plasma triglyceride-derived fatty acids. In contrast, cold up-regulates ANGPTL4 in WAT, abolishing a cold-induced increase in LPL activity. Together, our data indicate that ANGPTL4 is an important regulator of plasma lipid partitioning during sustained cold.
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| 7. |
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| 8. |
- Duncan, S., et al.
(författare)
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Seasonal shift in timing of vernalization as an adaptation to extreme winter
- 2015
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Ingår i: eLIFE. - 2050-084X. ; 4:JULY
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Tidskriftsartikel (refereegranskat)abstract
- The requirement for vernalization, a need for prolonged cold to trigger flowering, aligns reproductive development with favorable spring conditions. In Arabidopsis thaliana vernalization depends on the cold-induced epigenetic silencing of the floral repressor locus FLC. Extensive natural variation in vernalization response is associated with A. thaliana accessions collected from different geographical regions. Here, we analyse natural variation for vernalization temperature requirement in accessions, including those from the northern limit of the A. thaliana range. Vernalization required temperatures above 0°C and was still relatively effective at 14°C in all the accessions. The different accessions had characteristic vernalization temperature profiles. One Northern Swedish accession showed maximum vernalization at 8°C, both at the level of flowering time and FLC chromatin silencing. Historical temperature records predicted all accessions would vernalize in autumn in N. Sweden, a prediction we validated in field transplantation experiments. The vernalization response of the different accessions was monitored over three intervals in the field and found to match that when the average field temperature was given as a constant condition. The vernalization temperature range of 0–14°C meant all accessions fully vernalized before snowfall in N. Sweden. These findings have important implications for understanding the molecular basis of adaptation and for predicting the consequences of climate change on flowering time.
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| 9. |
- Guan, Jikui, et al.
(författare)
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FAM150A and FAM150B are activating ligands for anaplastic lymphoma kinase
- 2015
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Ingår i: eLIFE. - Cambridge : eLife Sciences Publications. - 2050-084X. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- Aberrant activation of anaplastic lymphoma kinase (ALK) has been described in a range of human cancers, including non-small cell lung cancer and neuroblastoma (Hallberg and Palmer, 2013). Vertebrate ALK has been considered to be an orphan receptor and the identity of the ALK ligand(s) is a critical issue. Here we show that FAM150A and FAM150B are potent ligands for human ALK that bind to the extracellular domain of ALK and in addition to activation of wild-type ALK are able to drive 'superactivation' of activated ALK mutants from neuroblastoma. In conclusion, our data show that ALK is robustly activated by the FAM150A/B ligands and provide an opportunity to develop ALK-targeted therapies in situations where ALK is overexpressed/activated or mutated in the context of the full length receptor.
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| 10. |
- Laurent, Patrick, et al.
(författare)
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Decoding a neural circuit controlling global animal state in C. elegans.
- 2015
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Ingår i: eLIFE. - : eLife Sciences Publications. - 2050-084X. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- Brains organize behavior and physiology to optimize the response to threats or opportunities. We dissect how 21% O2, an indicator of surface exposure, reprograms C. elegans' global state, inducing sustained locomotory arousal and altering expression of neuropeptides, metabolic enzymes, and other non-neural genes. The URX O2-sensing neurons drive arousal at 21% O2 by tonically activating the RMG interneurons. Stimulating RMG is sufficient to switch behavioral state. Ablating the ASH, ADL, or ASK sensory neurons connected to RMG by gap junctions does not disrupt arousal. However, disrupting cation currents in these neurons curtails RMG neurosecretion and arousal. RMG signals high O2 by peptidergic secretion. Neuropeptide reporters reveal neural circuit state, as neurosecretion stimulates neuropeptide expression. Neural imaging in unrestrained animals shows that URX and RMG encode O2 concentration rather than behavior, while the activity of downstream interneurons such as AVB and AIY reflect both O2 levels and the behavior being executed.
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