| 1. |
|
|
| 2. |
- 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.
|
|
| 3. |
- Edwards, Ceiridwen J., et al.
(författare)
-
Ancient Hybridization and an Irish Origin for the Modern Polar Bear Matriline
- 2011
-
Ingår i: Current Biology. - : Elsevier BV. - 0960-9822 .- 1879-0445. ; 21:15, s. 1251-1258
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Polar bears (Ursus maritimus) are among those species most susceptible to the rapidly changing arctic climate, and their survival is of global concern. Despite this, little is known about polar bear species history. Future conservation strategies would significantly benefit from an understanding of basic evolutionary information, such as the timing and conditions of their initial divergence from brown bears (U. arctos) or their response to previous environmental change. Results: We used a spatially explicit phylogeographic model to estimate the dynamics of 242 brown bear and polar bear matrilines sampled throughout the last 120,000 years and across their present and past geographic ranges. Our results show that the present distribution of these matrilines was shaped by a combination of regional stability and rapid, long-distance dispersal from ice-age refugia. In addition, hybridization between polar bears and brown bears may have occurred multiple times throughout the Late Pleistocene. Conclusions: The reconstructed matrilineal history of brown and polar bears has two striking features. First, it is punctuated by dramatic and discrete climate-driven dispersal events. Second, opportunistic mating between these two species as their ranges overlapped has left a strong genetic imprint. In particular, a likely genetic exchange with extinct Irish brown bears forms the origin of the modern polar bear matriline. This suggests that interspecific hybridization not only may be more common than previously considered but may be a mechanism by which species deal with marginal habitats during periods of environmental deterioration.
|
|
| 4. |
- Westerberg, Ida, et al.
(författare)
-
Response to discussion by Ertsen on Westerberg et al. “Perceptual models of uncertainty for socio-hydrological systems".
- 2018
-
Ingår i: Hydrological Sciences Journal. - : Informa UK Limited. - 0262-6667 .- 2150-3435. ; :63, s. 13–14-
-
Tidskriftsartikel (refereegranskat)abstract
- Ertsen discusses the representation of reality and uncertainty in our paper, raising three critical points. In response to the first, we agree that discussion of different interpretations of the concept of uncertainty is important when developing perceptual models – making different uncertainty interpretations explicit was a key motivation behind our method. Secondly, we do not, as Ertsen suggests, deny anyone who is not a “certified” scientist to have relevant knowledge. The elicitation of diverse views by discussing perceptual models is a basis for open discussion and decision making. Thirdly, Ertsen suggests that it is not useful to treat socio-hydrological systems as if they exist. We argue that we act as “pragmatic realists” in most practical applications by treating socio-hydrological systems as an external reality that can be known. But the uncertainty that arises from our knowledge limitations needs to be recognized, as it may impact on practical decision making and associated costs.
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- Stattin, Eva-Lena, et al.
(författare)
-
SNX10 gene mutation leading to osteopetrosis with dysfunctional osteoclasts
- 2017
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1
-
Tidskriftsartikel (refereegranskat)abstract
- Autosomal recessive osteopetrosis (ARO) is a heterogeneous disorder, characterized by defective osteoclastic resorption of bone that results in increased bone density. We have studied nine individuals with an intermediate form of ARO, from the county of Vasterbotten in Northern Sweden. All afflicted individuals had an onset in early infancy with optic atrophy, and in four patients anemia was present at diagnosis. Tonsillar herniation, foramen magnum stenosis, and severe osteomyelitis of the jaw were common clinical features. Whole exome sequencing, verified by Sanger sequencing, identified a splice site mutation c.212 + 1 G > T in the SNX10 gene encoding sorting nexin 10. Sequence analysis of the SNX10 transcript in patients revealed activation of a cryptic splice site in intron 4 resulting in a frame shift and a premature stop (p.S66Nfs * 15). Haplotype analysis showed that all cases originated from a single mutational event, and the age of the mutation was estimated to be approximately 950 years. Functional analysis of osteoclast progenitors isolated from peripheral blood of patients revealed that stimulation with receptor activator of nuclear factor kappa-B ligand (RANKL) resulted in a robust formation of large, multinucleated osteoclasts which generated sealing zones; however these osteoclasts exhibited defective ruffled borders and were unable to resorb bone in vitro.
|
|
| 9. |
- Van Loon, Anne F., et al.
(författare)
-
Streamflow droughts aggravated by human activities despite management
- 2022
-
Ingår i: Environmental Research Letters. - : IOP Publishing. - 1748-9326. ; 17:4
-
Tidskriftsartikel (refereegranskat)abstract
- Human activities both aggravate and alleviate streamflow drought. Here we show that aggravation is dominant in contrasting cases around the world analysed with a consistent methodology. Our 28 cases included different combinations of human-water interactions. We found that water abstraction aggravated all drought characteristics, with increases of 20%-305% in total time in drought found across the case studies, and increases in total deficit of up to almost 3000%. Water transfers reduced drought time and deficit by up to 97%. In cases with both abstraction and water transfers into the catchment or augmenting streamflow from groundwater, the water inputs could not compensate for the aggravation of droughts due to abstraction and only shift the effects in space or time. Reservoir releases for downstream water use alleviated droughts in the dry season, but also led to deficits in the wet season by changing flow seasonality. This led to minor changes in average drought duration (-26 to +38%) and moderate changes in average drought deficit (-86 to +369%). Land use showed a smaller impact on streamflow drought, also with both increases and decreases observed (-48 to +98%). Sewage return flows and pipe leakage possibly counteracted the effects of increased imperviousness in urban areas; however, untangling the effects of land use change on streamflow drought is challenging. This synthesis of diverse global cases highlights the complexity of the human influence on streamflow drought and the added value of empirical comparative studies. Results indicate both intended and unintended consequences of water management and infrastructure on downstream society and ecosystems.
|
|
| 10. |
- Westerberg, Ida, et al.
(författare)
-
A comparison of methods for streamflow uncertainty estimation.
- 2018
-
Ingår i: Water resources research. - 0043-1397 .- 1944-7973. ; :54, s. 7149–7176-
-
Tidskriftsartikel (refereegranskat)abstract
- Streamflow time series are commonly derived from stage‐discharge rating curves, but the uncertainty of the rating curve and resulting streamflow series are poorly understood. While different methods to quantify uncertainty in the stage‐discharge relationship exist, there is limited understanding of how uncertainty estimates differ between methods due to different assumptions and methodological choices. We compared uncertainty estimates and stage‐discharge rating curves from seven methods at three river locations of varying hydraulic complexity. Comparison of the estimated uncertainties revealed a wide range of estimates, particularly for high and low flows. At the simplest site on the Isère River (France), full width 95% uncertainties for the different methods ranged from 3 to 17% for median flows. In contrast, uncertainties were much higher and ranged from 41 to 200% for high flows in an extrapolated section of the rating curve at the Mahurangi River (New Zealand) and 28 to 101% for low flows at the Taf River (United Kingdom), where the hydraulic control is unstable at low flows. Differences between methods result from differences in the sources of uncertainty considered, differences in the handling of the time‐varying nature of rating curves, differences in the extent of hydraulic knowledge assumed, and differences in assumptions when extrapolating rating curves above or below the observed gaugings. Ultimately, the selection of an uncertainty method requires a match between user requirements and the assumptions made by the uncertainty method. Given the significant differences in uncertainty estimates between methods, we suggest that a clear statement of uncertainty assumptions be presented alongside streamflow uncertainty estimates.
|
|
