| 1. |
- El-Sayed, Najib M., et al.
(författare)
-
The genome sequence of Trypanosoma cruzi, etiologic agent of Chagas disease.
- 2005
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 309:5733, s. 409-15
-
Tidskriftsartikel (refereegranskat)abstract
- Whole-genome sequencing of the protozoan pathogen Trypanosoma cruzi revealed that the diploid genome contains a predicted 22,570 proteins encoded by genes, of which 12,570 represent allelic pairs. Over 50% of the genome consists of repeated sequences, such as retrotransposons and genes for large families of surface molecules, which include trans-sialidases, mucins, gp63s, and a large novel family (>1300 copies) of mucin-associated surface protein (MASP) genes. Analyses of the T. cruzi, T. brucei, and Leishmania major (Tritryp) genomes imply differences from other eukaryotes in DNA repair and initiation of replication and reflect their unusual mitochondrial DNA. Although the Tritryp lack several classes of signaling molecules, their kinomes contain a large and diverse set of protein kinases and phosphatases; their size and diversity imply previously unknown interactions and regulatory processes, which may be targets for intervention.
|
|
| 2. |
- Beven, Keith, et al.
(författare)
-
Epistemic uncertainties and natural hazard risk assessment - Part 1 : A review of different natural hazard areas
- 2018
-
Ingår i: Natural hazards and earth system sciences. - : COPERNICUS GESELLSCHAFT MBH. - 1561-8633 .- 1684-9981. ; 18:10, s. 2741-2768
-
Forskningsöversikt (refereegranskat)abstract
- This paper discusses how epistemic uncertainties are currently considered in the most widely occurring natural hazard areas, including floods, landslides and debris flows, dam safety, droughts, earthquakes, tsunamis, volcanic ash clouds and pyroclastic flows, and wind storms. Our aim is to provide an overview of the types of epistemic uncertainty in the analysis of these natural hazards and to discuss how they have been treated so far to bring out some commonalities and differences. The breadth of our study makes it difficult to go into great detail on each aspect covered here; hence the focus lies on providing an overview and on citing key literature. We find that in current probabilistic approaches to the problem, uncertainties are all too often treated as if, at some fundamental level, they are aleatory in nature. This can be a tempting choice when knowledge of more complex structures is difficult to determine but not acknowledging the epistemic nature of many sources of uncertainty will compromise any risk analysis. We do not imply that probabilistic uncertainty estimation necessarily ignores the epistemic nature of uncertainties in natural hazards; expert elicitation for example can be set within a probabilistic framework to do just that. However, we suggest that the use of simple aleatory distributional models, common in current practice, will underestimate the potential variability in assessing hazards, consequences, and risks. A commonality across all approaches is that every analysis is necessarily conditional on the assumptions made about the nature of the sources of epistemic uncertainty. It is therefore important to record the assumptions made and to evaluate their impact on the uncertainty estimate. Additional guidelines for good practice based on this review are suggested in the companion paper (Part 2).
|
|
| 3. |
- Beven, Keith, et al.
(författare)
-
Epistemic uncertainties and natural hazard risk assessment - Part 2 : What should constitute good practice?
- 2018
-
Ingår i: Natural hazards and earth system sciences. - : COPERNICUS GESELLSCHAFT MBH. - 1561-8633 .- 1684-9981. ; 18:10, s. 2769-2783
-
Tidskriftsartikel (refereegranskat)abstract
- Part 1 of this paper has discussed the uncertainties arising from gaps in knowledge or limited understanding of the processes involved in different natural hazard areas. Such deficits may include uncertainties about frequencies, process representations, parameters, present and future boundary conditions, consequences and impacts, and the meaning of observations in evaluating simulation models. These are the epistemic uncertainties that can be difficult to constrain, especially in terms of event or scenario probabilities, even as elicited probabilities rationalized on the basis of expert judgements. This paper reviews the issues raised by trying to quantify the effects of epistemic uncertainties. Such scientific uncertainties might have significant influence on decisions made, say, for risk management, so it is important to examine the sensitivity of such decisions to different feasible sets of assumptions, to communicate the meaning of associated uncertainty estimates, and to provide an audit trail for the analysis. A conceptual framework for good practice in dealing with epistemic uncertainties is outlined and the implications of applying the principles to natural hazard assessments are discussed. Six stages are recognized, with recommendations at each stage as follows: (1) framing the analysis, preferably with input from potential users; (2) evaluating the available data for epistemic uncertainties, especially when they might lead to inconsistencies; (3) eliciting information on sources of uncertainty from experts; (4) defining a workflow that will give reliable and accurate results; (5) assessing robustness to uncertainty, including the impact on any decisions that are dependent on the analysis; and (6) communicating the findings and meaning of the analysis to potential users, stakeholders, and decision makers. Visualizations are helpful in conveying the nature of the uncertainty outputs, while recognizing that the deeper epistemic uncertainties might not be readily amenable to visualizations.
|
|
| 4. |
- Carville, N. Craig, et al.
(författare)
-
Biocompatibility of ferroelectric lithium niobate and the influence of polarization charge on osteoblast proliferation and function
- 2015
-
Ingår i: Journal of Biomedical Materials Research. Part A. - : John Wiley and Sons. - 1549-3296 .- 1552-4965. ; 103:8, s. 2540-2548
-
Tidskriftsartikel (refereegranskat)abstract
- In this work, the influence of substrate surface charge on in vitro osteoblast cell proliferation on ferroelectric lithium niobate (LN) crystal surfaces is investigated. LN has a spontaneous polarization along the z-axis and is thus characterized by positive and negative bound polarization charge at the +z and -z surfaces. Biocompatibility of LN was demonstrated via culturing and fluorescence imaging of MC3T3 osteoblast cells for up to 11 days. The cells showed enhanced proliferation rates and improved osteoblast function through mineral formation on the positively and negatively charged LN surfaces compared to electrostatically neutral x-cut LN and a glass cover slip control. These results highlight the potential of LN as a template for investigating the role of charge on cellular processes.
|
|
| 5. |
- Constantinidis, Ioannis, et al.
(författare)
-
Non-invasive evaluation of alginate/poly-L-lysine/alginate microcapsules by magnetic resonance microscopy
- 2007
-
Ingår i: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 28:15, s. 2438-2445
-
Tidskriftsartikel (refereegranskat)abstract
- In this report, we present data to demonstrate the utility of H-1 MR microscopy to non-invasively examine alginate/poly-L-lysine/ alginate (APA) microcapsules. Specifically, high-resolution images were used to visualize and quantify the poly-L-lysine (PLL) layer, and monitor temporal changes in the alginate gel microstructure during a month long in vitro culture. The thickness of the alginate/PLL layer was quantified to be 40.6 +/- 6.2 mu m regardless of the alginate composition used to generate the beads or the time of alginate/PLL interaction (2, 6, or 20 min). However, there was a notable difference in the contrast of the PLL layer that depended upon the guluronic content of the alginate and the alginate/PLL interaction time. The T-2 relaxation time and the apparent diffusion coefficient (ADC) of the alginate matrix were measured periodically throughout the month long culture period. Alginate beads generated with a high guluronic content alginate demonstrated a temporal decrease in T-2 over the duration of the experiment, while ADC was unaffected. This decrease in T-2 is attributed to a reorganization of the alginate microstructure due to periodic media exchanges that mimicked a regular feeding regiment for cultured cells. In beads coated with a PLL layer, this temporal decrease in T-2 was less pronounced suggesting that the PLL layer helped maintain the integrity of the initial alginate microstructure. Conversely, alginate beads generated with a high mannuronic content alginate (with or without a PLL layer) did not display temporal changes in either T-2 or ADC. This observation suggests that the microstructure of high mannuronic content alginate beads is less susceptible to culture conditions.
|
|
| 6. |
- Simpson, Jeremy C, et al.
(författare)
-
Biogenesis of tubular ER-to-Golgi transport intermediates.
- 2006
-
Ingår i: Molecular biology of the cell. - 1059-1524. ; 17:2, s. 723-37
-
Tidskriftsartikel (refereegranskat)abstract
- Tubular transport intermediates (TTIs) have been described as one class of transport carriers in endoplasmic reticulum (ER)-to-Golgi transport. In contrast to vesicle budding and fusion, little is known about the molecular regulation of TTI synthesis, transport and fusion with target membranes. Here we have used in vivo imaging of various kinds of GFP-tagged proteins to start to address these questions. We demonstrate that under steady-state conditions TTIs represent approximately 20% of all moving transport carriers. They increase in number and length when more transport cargo becomes available at the donor membrane, which we induced by either temperature-related transport blocks or increased expression of the respective GFP-tagged transport markers. The formation and motility of TTIs is strongly dependent on the presence of intact microtubules. Microinjection of GTPgammaS increases the frequency of TTI synthesis and the length of these carriers. When Rab proteins are removed from membranes by microinjection of recombinant Rab-GDI, the synthesis of TTIs is completely blocked. Microinjection of the cytoplasmic tails of the p23 and p24 membrane proteins also abolishes formation of p24-containing TTIs. Our data suggest that TTIs are ER-to-Golgi transport intermediates that form preferentially when transport-competent cargo exists in excess at the donor membrane. We propose a model where the interaction of the cytoplasmic tails of membrane proteins with microtubules are key determinants for TTI synthesis and may also serve as a so far unappreciated model for aspects of transport carrier formation.
|
|
| 7. |
- Stadler, Charlotte, et al.
(författare)
-
Immunofluorescence and fluorescent protein-tagging are complementary techniques with high correlation for subcellular investigation of the human proteome in mammalian cells
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Imaging techniques such as immunofluorescence (IF) and expression of fluorescent protein (FP) fusions are widely used to investigate the subcellular distribution of proteins. Due to potential steric hindrance with FPs and fixation artifacts obtained during IF, the reliability of these two fundamental methods is often discussed. Here we report a systematic study of over 500 human proteins where the localizations obtained in live versus fixed cells using FPs and IF respectively have been compared. The results indicate that 80% of the analyzed proteins yield the same subcellular distribution, which is as high as that seen for FP tagging at either the N- and C-terminal. The localizations of 250 proteins, with no previous experimental data, were determined by the overlap of the two methods as applied here. The fraction of proteins located to multiple organelles is approximately 60% for both methods, indicating a complex subcellular protein organization. The result shows that IF and FP tagging are reliable techniques, both needed for a complete investigation of the subcellular human proteome.
|
|
| 8. |
- Stadler, Charlotte, et al.
(författare)
-
Immunofluorescence and fluorescent-protein tagging show high correlation for protein localization in mammalian cells
- 2013
-
Ingår i: Nature Methods. - 1548-7091 .- 1548-7105. ; 10:4, s. 315-323
-
Tidskriftsartikel (refereegranskat)abstract
- Imaging techniques such as immunofluorescence (IF) and the expression of fluorescent protein (FP) fusions are widely used to investigate the subcellular distribution of proteins. Here we report a systematic analysis of >500 human proteins comparing the localizations obtained in live versus fixed cells using FPs and IF, respectively. We identify systematic discrepancies between IF and FPs as well as between FP tagging at the N and C termini. The analysis shows that for 80% of the proteins, IF and FPs yield the same subcellular distribution, and the locations of 250 previously unlocalized proteins were determined by the overlap between the two methods. Approximately 60% of proteins localize to multiple organelles for both methods, indicating a complex subcellular protein organization. These results show that both IF and FP tagging are reliable techniques and demonstrate the usefulness of an integrative approach for a complete investigation of the subcellular human proteome.
|
|
| 9. |
- Stephens, Lucas, et al.
(författare)
-
Archaeological assessment reveals Earth’s early transformation through land use
- 2019
-
Ingår i: Science. - : American Association for the Advancement of Science. - 0036-8075 .- 1095-9203. ; 365:6456, s. 897-902
-
Tidskriftsartikel (refereegranskat)abstract
- Humans began to leave lasting impacts on Earth’s surface starting 10,000 to 8000 years ago. Through a synthetic collaboration with archaeologists around the globe, Stephens et al. compiled a comprehensive picture of the trajectory of human land use worldwide during the Holocene (see the Perspective by Roberts). Hunter-gatherers, farmers, and pastoralists transformed the face of Earth earlier and to a greater extent than has been widely appreciated, a transformation that was essentially global by 3000 years before the present.Science, this issue p. 897; see also p. 865Environmentally transformative human use of land accelerated with the emergence of agriculture, but the extent, trajectory, and implications of these early changes are not well understood. An empirical global assessment of land use from 10,000 years before the present (yr B.P.) to 1850 CE reveals a planet largely transformed by hunter-gatherers, farmers, and pastoralists by 3000 years ago, considerably earlier than the dates in the land-use reconstructions commonly used by Earth scientists. Synthesis of knowledge contributed by more than 250 archaeologists highlighted gaps in archaeological expertise and data quality, which peaked for 2000 yr B.P. and in traditionally studied and wealthier regions. Archaeological reconstruction of global land-use history illuminates the deep roots of Earth’s transformation and challenges the emerging Anthropocene paradigm that large-scale anthropogenic global environmental change is mostly a recent phenomenon.
|
|
