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- Shepherd, L., et al.
(författare)
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Infection-related and -unrelated malignancies, HIV and the aging population
- 2016
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Ingår i: HIV Medicine. - : Wiley. - 1464-2662 .- 1468-1293. ; 17:8, s. 590-600
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: HIV-positive people have increased risk of infection-related malignancies (IRMs) and infection-unrelated malignancies (IURMs). The aim of the study was to determine the impact of aging on future IRM and IURM incidence. Methods: People enrolled in EuroSIDA and followed from the latest of the first visit or 1 January 2001 until the last visit or death were included in the study. Poisson regression was used to investigate the impact of aging on the incidence of IRMs and IURMs, adjusting for demographic, clinical and laboratory confounders. Linear exponential smoothing models forecasted future incidence. Results: A total of 15 648 people contributed 95 033 person-years of follow-up, of whom 610 developed 643 malignancies [IRMs: 388 (60%); IURMs: 255 (40%)]. After adjustment, a higher IRM incidence was associated with a lower CD4 count [adjusted incidence rate ratio (aIRR) CD4 count < 200 cells/μL: 3.77; 95% confidence interval (CI) 2.59, 5.51; compared with ≥ 500 cells/μL], independent of age, while a CD4 count < 200 cells/μL was associated with IURMs in people aged < 50 years only (aIRR: 2.51; 95% CI 1.40–4.54). Smoking was associated with IURMs (aIRR: 1.75; 95% CI 1.23, 2.49) compared with never smokers in people aged ≥ 50 years only, and not with IRMs. The incidences of both IURMs and IRMs increased with older age. It was projected that the incidence of IRMs would decrease by 29% over a 5-year period from 3.1 (95% CI 1.5–5.9) per 1000 person-years in 2011, whereas the IURM incidence would increase by 44% from 4.1 (95% CI 2.2–7.2) per 1000 person-years over the same period. Conclusions: Demographic and HIV-related risk factors for IURMs (aging and smoking) and IRMs (immunodeficiency and ongoing viral replication) differ markedly and the contribution from IURMs relative to IRMs will continue to increase as a result of aging of the HIV-infected population, high smoking and lung cancer prevalence and a low prevalence of untreated HIV infection. These findings suggest the need for targeted preventive measures and evaluation of the cost−benefit of screening for IURMs in HIV-infected populations.
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- Birney, Ewan, et al.
(författare)
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Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
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Tidskriftsartikel (refereegranskat)abstract
- We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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- Richards, Stephen, et al.
(författare)
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Genome Sequence of the Pea Aphid Acyrthosiphon pisum
- 2010
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Ingår i: PLoS biology. - : Public Library of Science (PLoS). - 1544-9173 .- 1545-7885. ; 8:2, s. e1000313-
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Tidskriftsartikel (refereegranskat)abstract
- Aphids are important agricultural pests and also biological models for studies of insect-plant interactions, symbiosis, virus vectoring, and the developmental causes of extreme phenotypic plasticity. Here we present the 464 Mb draft genome assembly of the pea aphid Acyrthosiphon pisum. This first published whole genome sequence of a basal hemimetabolous insect provides an outgroup to the multiple published genomes of holometabolous insects. Pea aphids are host-plant specialists, they can reproduce both sexually and asexually, and they have coevolved with an obligate bacterial symbiont. Here we highlight findings from whole genome analysis that may be related to these unusual biological features. These findings include discovery of extensive gene duplication in more than 2000 gene families as well as loss of evolutionarily conserved genes. Gene family expansions relative to other published genomes include genes involved in chromatin modification, miRNA synthesis, and sugar transport. Gene losses include genes central to the IMD immune pathway, selenoprotein utilization, purine salvage, and the entire urea cycle. The pea aphid genome reveals that only a limited number of genes have been acquired from bacteria; thus the reduced gene count of Buchnera does not reflect gene transfer to the host genome. The inventory of metabolic genes in the pea aphid genome suggests that there is extensive metabolite exchange between the aphid and Buchnera, including sharing of amino acid biosynthesis between the aphid and Buchnera. The pea aphid genome provides a foundation for post-genomic studies of fundamental biological questions and applied agricultural problems.
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| 5. |
- Raack, J., et al.
(författare)
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Present-day gully activity in Sisyphi Cavi, Mars - Flow-like features and block movements
- 2020
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Ingår i: Icarus. - : Elsevier BV. - 0019-1035. ; 350
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Tidskriftsartikel (refereegranskat)abstract
- The continuously increasing number of multi-temporal high-resolution images from the surface of Mars offers the possibility for detailed studies of present-day surface activity. In this study we investigated all gullies in the Sisyphi Cavi region (355 degrees E, 71 degrees S) of the south polar region of Mars. This region is influenced by the seasonal deposition of a decimeters-thick translucent slab ice in late autumn/winter and its subsequent sublimation in spring. We mapped all gullies (n = 17.760) and measured their orientations. We also identified gullies with contemporary activity (n = 35) using multi-temporal HiRISE images for martian years (MY) 28 to 34. We observed two different kinds of activity: (1) dark flow-like features, and (2) movement of blocks. For both, sediment was transported from the source region (alcove and/or flanks of channels) down the gully. Using image data from HRSC, CTX, and HiRISE, we monitored the general defrosting of the study region. We also analyzed the maximum daytime surface temperatures of the complete study region based on TES data from MYs 24 to 26. To identify the origin and triggering mechanism of the observed activity, we used: (1) detailed topographic investigations (e.g., slope angles) of two extensively gullied slopes based on two HiRISE-DTMs, (2) identification of small scale displacements with Digital Image Correlation (DIC), and (3) orientation measurements of active gullies and comparison to non-active gullies. We found that for the active gullies studied, activity happens at the end of spring between L-S similar to 225 degrees and similar to 250 degrees. This is consistent with the timing of final stages of defrosting in the region. At this time, some surfaces are already defrosted while others still host the seasonal slab ice cover. For the surfaces with slab ice, dark defrosting spots (and flows, if the surface is inclined) are observed on dark dunes as well as on gully aprons and in gully channels. These spots form when, triggered by basal sublimation generated overpressure, sediment entrained in CO2-gas is transported through cracks within the ice and redeposited onto the frosted surface. We compared and linked both morphologic features (dark dune spots and dark flow-like features) and concluded that these features have comparable or even the same triggering mechanisms. Based on this extensive study, the most plausible mechanism for ongoing gully activity can be divided into two steps: 1) accumulation of material within gully channels via small dry flows on top of the slab ice (comparable to dark dune spots/flows), 2) when a critical mass is reached, the sediment flows down the still frosted gully on top of the sublimating ice or as a mixture of dry material and ice in a catastrophic flow. The triggering factor for the movement of blocks remains unclear, as their timing could not be constrained with the available data. We identified headwall erosion in one gully in the study region, whereas a discrete source could not be identified for the other sites, suggesting multiple failure mechanisms could be active in such gullies. Finally, through volume balance calculations we show that active gullies in Sisyphi Cavi could have been formed within decades to several tens of thousands of MY, but gully-morphology indicates a much-longer period for formation of the entire gully-landform.
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