| 1. |
- Marouli, Eirini, et al.
(författare)
-
Rare and low-frequency coding variants alter human adult height
- 2017
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
-
Tidskriftsartikel (refereegranskat)abstract
- Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
|
|
| 2. |
- Pascual, Unai, et al.
(författare)
-
Off-stage ecosystem service burdens : A blind spot for global sustainability
- 2017
-
Ingår i: Environmental Research Letters. - : IOP Publishing. - 1748-9326. ; 12:7
-
Tidskriftsartikel (refereegranskat)abstract
- The connected nature of social-ecological systems has never been more apparent than in today's globalized world. The ecosystem service framework and associated ecosystem assessments aim to better inform the science-policy response to sustainability challenges. Such assessments, however, often overlook distant, diffuse and delayed impacts that are critical for global sustainability. Ecosystem-services science must better recognise the off-stage impacts on biodiversity and ecosystem services of place-based ecosystem management, which we term 'ecosystem service burdens'. These are particularly important since they are often negative, and have a potentially significant effect on ecosystem management decisions. Ecosystem-services research can better recognise these off-stage burdens through integration with other analytical approaches, such as life cycle analysis and risk-based approaches that better account for the uncertainties involved. We argue that off-stage ecosystem service burdens should be incorporated in ecosystem assessments such as those led by the Intergovernmental Platform on Biodiversity and Ecosystem Services and the Intergovernmental Panel on Climate Change. Taking better account of these off-stage burdens is essential to achieve a more comprehensive understanding of cross-scale interactions, a prerequisite for any sustainability transition.
|
|
| 3. |
- De Groot, Rudolf S., et al.
(författare)
-
Benefits of Investing in Ecosystem Restoration
- 2013
-
Ingår i: Conservation Biology. - : Wiley. - 0888-8892 .- 1523-1739. ; 27:6, s. 1286-1293
-
Tidskriftsartikel (refereegranskat)abstract
- Measures aimed at conservation or restoration of ecosystems are often seen as net-cost projects by governments and businesses because they are based on incomplete and often faulty cost-benefit analyses. After screening over 200 studies, we examined the costs (94 studies) and benefits (225 studies) of ecosystem restoration projects that had sufficient reliable data in 9 different biomes ranging from coral reefs to tropical forests. Costs included capital investment and maintenance of the restoration project, and benefits were based on the monetary value of the total bundle of ecosystem services provided by the restored ecosystem. Assuming restoration is always imperfect and benefits attain only 75% of the maximum value of the reference systems over 20 years, we calculated the net present value at the social discount rates of 2% and 8%. We also conducted 2 threshold cum sensitivity analyses. Benefit-cost ratios ranged from about 0.05:1 (coral reefs and coastal systems, worst-case scenario) to as much as 35:1 (grasslands, best-case scenario). Our results provide only partial estimates of benefits at one point in time and reflect the lower limit of the welfare benefits of ecosystem restoration because both scarcity of and demand for ecosystem services is increasing and new benefits of natural ecosystems and biological diversity are being discovered. Nonetheless, when accounting for even the incomplete range of known benefits through the use of static estimates that fail to capture rising values, the majority of the restoration projects we analyzed provided net benefits and should be considered not only as profitable but also as high-yielding investments.
|
|
| 4. |
- Klionsky, Daniel J., et al.
(författare)
-
Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
-
Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
-
Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
|
|
| 5. |
- Pichler, T, et al.
(författare)
-
Proof for trivalent Sc ions in Sc-2 @ C-84 from high-energy spectroscopy
- 2000
-
Ingår i: PHYSICAL REVIEW B. - : AMERICAN PHYSICAL SOC. - 0163-1829. ; 62:19, s. 13196-13201
-
Tidskriftsartikel (refereegranskat)abstract
- The electronic structure and the valency of the Sc ions in the endohedral dimetallofullerene Sc-2 @ C-84 with D-2d symmetry are probed using high-energy spectroscopy. Comparison of the Sc 2p --> 3d x-ray-absorption spectrum with calculated ionic multiplet
|
|
