| 11. |
- Wedding, Lisa M., et al.
(författare)
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Advancing the integration of spatial data to map human and natural drivers on coral reefs
- 2018
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 13:3
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Tidskriftsartikel (refereegranskat)abstract
- A major challenge for coral reef conservation and management is understanding how a wide range of interacting human and natural drivers cumulatively impact and shape these ecosystems. Despite the importance of understanding these interactions, a methodological framework to synthesize spatially explicit data of such drivers is lacking. To fill this gap, we established a transferable data synthesis methodology to integrate spatial data on environmental and anthropogenic drivers of coral reefs, and applied this methodology to a case study location-the Main Hawaiian Islands (MHI). Environmental drivers were derived from time series (2002-2013) of climatological ranges and anomalies of remotely sensed sea surface temperature, chlorophyll-a, irradiance, and wave power. Anthropogenic drivers were characterized using empirically derived and modeled datasets of spatial fisheries catch, sedimentation, nutrient input, new development, habitat modification, and invasive species. Within our case study system, resulting driver maps showed high spatial heterogeneity across the MHI, with anthropogenic drivers generally greatest and most widespread on O'ahu, where 70% of the state's population resides, while sedimentation and nutrients were dominant in less populated islands. Together, the spatial integration of environmental and anthropogenic driver data described here provides a first-ever synthetic approach to visualize how the drivers of coral reef state vary in space and demonstrates a methodological framework for implementation of this approach in other regions of the world. By quantifying and synthesizing spatial drivers of change on coral reefs, we provide an avenue for further research to understand how drivers determine reef diversity and resilience, which can ultimately inform policies to protect coral reefs.
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| 12. |
- Abrandt Dahlgren, M., et al.
(författare)
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Why This Book?
- 2019
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Ingår i: Interprofessional Simulation in Health Care. Professional and Practice-based Learning, vol 26. Abrandt Dahlgren M., Rystedt H., Felländer-Tsai L., Nyström S. (eds). - Cham : Springer. - 2210-5549. - 9783030195410 ; , s. 3-8
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- The introductory chapter provides a backdrop to and problematization of simulation as a pedagogical technology for interprofessional learning in health care education and practice. The chapter also discusses the relation to the changing views on professional learning and the current discourses on the increasing complexity of future health care. The dominating scientific, technical rationalities of professional practice as simply the application of theoretical knowledge, possessed by individuals, are being challenged. Recent theorizations of practice instead suggest alternative views of knowledge as being embodied and relational, intertwined with ethical reasoning and materiality. There is a global call for health care education reform and interprofessional learning to resolve patient safety issues. However, there is a lack of research with a particular view on interprofessional simulation, and hence a need of scrutiny and development the pedagogy for simulation practice. © 2019, Springer Nature Switzerland AG.
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| 13. |
- Anthony, Kenneth R. N., et al.
(författare)
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Operationalizing resilience for adaptive coral reef management under global environmental change
- 2015
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Ingår i: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 21:1, s. 48-61
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Forskningsöversikt (refereegranskat)abstract
- Cumulative pressures from global climate and ocean change combined with multiple regional and local-scale stressors pose fundamental challenges to coral reef managers worldwide. Understanding how cumulative stressors affect coral reef vulnerability is critical for successful reef conservation now and in the future. In this review, we present the case that strategically managing for increased ecological resilience (capacity for stress resistance and recovery) can reduce coral reef vulnerability (risk of net decline) up to a point. Specifically, we propose an operational framework for identifying effective management levers to enhance resilience and support management decisions that reduce reef vulnerability. Building on a system understanding of biological and ecological processes that drive resilience of coral reefs in different environmental and socio-economic settings, we present an Adaptive Resilience-Based management (ARBM) framework and suggest a set of guidelines for how and where resilience can be enhanced via management interventions. We argue that press-type stressors (pollution, sedimentation, overfishing, ocean warming and acidification) are key threats to coral reef resilience by affecting processes underpinning resistance and recovery, while pulse-type (acute) stressors (e.g. storms, bleaching events, crown-of-thorns starfish outbreaks) increase the demand for resilience. We apply the framework to a set of example problems for Caribbean and Indo-Pacific reefs. A combined strategy of active risk reduction and resilience support is needed, informed by key management objectives, knowledge of reef ecosystem processes and consideration of environmental and social drivers. As climate change and ocean acidification erode the resilience and increase the vulnerability of coral reefs globally, successful adaptive management of coral reefs will become increasingly difficult. Given limited resources, on-the-ground solutions are likely to focus increasingly on actions that support resilience at finer spatial scales, and that are tightly linked to ecosystem goods and services.
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| 14. |
- Babazadeh, Roja, et al.
(författare)
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Syntaxin 5 Is Required for the Formation and Clearance of Protein Inclusions during Proteostatic Stress
- 2019
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 28:8
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Tidskriftsartikel (refereegranskat)abstract
- Spatial sorting to discrete quality control sites in the cell is a process harnessing the toxicity of aberrant proteins. We show that the yeast t-snare phosphoprotein syntaxin5 (Sed5) acts as a key factor in mitigating proteotoxicity and the spatial deposition and clearance of IPOD (insoluble protein deposit) inclusions associates with the disaggregase Hsp104. Sed5 phosphorylation promotes dynamic movement of COPII-associated Hsp104 and boosts disaggregation by favoring anterograde ER-to-Golgi trafficking. Hsp104-associated aggregates co-localize with Sed5 as well as components of the ER, trans Golgi network, and endocytic vesicles, transiently during proteostatic stress, explaining mechanistically how misfolded and aggregated proteins formed at the vicinity of the ER can hitchhike toward vacuolar IPOD sites. Many inclusions become associated with mitochondria in a HOPS/vCLAMP-dependent manner and co-localize with Vps39 (HOPS/vCLAMP) and Vps13, which are proteins providing contacts between vacuole and mitochondria. Both Vps39 and Vps13 are required also for efficient Sed5-dependent clearance of aggregates.
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| 15. |
- Birchenough, George M. H., et al.
(författare)
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A sentinel goblet cell guards the colonic crypt by triggering Nlrp6-dependent Muc2 secretion
- 2016
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 352:6293, s. 1535-1542
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Tidskriftsartikel (refereegranskat)abstract
- Innate immune signaling pathways contribute to the protection of host tissue when bacterially challenged. Colonic goblet cells are responsible for generating the two mucus layers that physically separate the luminalmicrobiota from the host epithelium. Analysis of colonic tissues from multiple mouse strains allowed us to identify a "sentinel" goblet cell (senGC) localized to the colonic crypt entrance. This cell nonspecifically endocytoses and reacts to the TLR2/1, TLR4, and TLR5 ligands by activating the Nlrp6 inflammasome downstream of TLR-and MyD88-dependent Nox/Duox reactive oxygen species synthesis. This triggers calcium ion-dependent compound exocytosis ofMuc2 mucin fromthe senGC and generates an intercellular gap junction signal; in turn, this signal induces Muc2 secretion from adjacent goblet cells in the upper crypt, which expels bacteria. Thus, senGCs guard and protect the colonic crypt from bacterial intruders that have penetrated the inner mucus layer.
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| 16. |
- Birkeland, Kare I., et al.
(författare)
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Cardiovascular mortality and morbidity in patients with type 2 diabetes following initiation of sodium-glucose co-transporter-2 inhibitors versus other glucose-lowering drugs (CVD-REAL Nordic) : A Multinational Observational Analysis
- 2017
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Ingår i: The Lancet Diabetes and Endocrinology. - New York : Elsevier. - 2213-8587 .- 2213-8595. ; 5:9, s. 709-717
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Tidskriftsartikel (refereegranskat)abstract
- Background In patients with type 2 diabetes and a high cardiovascular risk profile, the sodium-glucose co-transporter-2 (SGLT2) inhibitors empagliflozin and canagliflozin have been shown to lower cardiovascular morbidity and mortality. Using real-world data from clinical practice, we aimed to compare cardiovascular mortality and morbidity in new users of SGLT2 inhibitors versus new users of other glucose-lowering drugs, in a population with a broad cardiovascular risk profile. Methods CVD-REAL Nordic was an observational analysis of individual patient-level data from the Prescribed Drug Registers, Cause of Death Registers, and National Patient Registers in Denmark, Norway, and Sweden. All patients who filled a prescription for glucose-lowering drugs between 2012 and 2015 were included and followed up until Dec 31, 2015. Patients were divided into new users of SGLT2 inhibitors and new users of other glucose-lowering drugs. Each SGLT2 inhibitor user was matched with three users of other glucose-lowering drugs by use of propensity scores. Hazard ratios (HRs) were estimated by country (Cox survival model) and weighted averages were calculated. Cardiovascular outcomes investigated were cardiovascular mortality, major adverse cardiovascular events (cardiovascular mortality, myocardial infarction, and ischaemic or haemorrhagic stroke), hospital events for heart failure (inpatient or outpatient visit with a primary diagnosis of heart failure), non-fatal myocardial infarction, non-fatal stroke, and atrial fibrillation. We also assessed incidence of severe hypoglycaemia. Findings Matched SGLT2 inhibitor (n=22 830) and other glucose-lowering drug (n=68 490) groups were well balanced at baseline, with a mean follow-up of 0.9 (SD 4.1) years (80 669 patient-years) and mean age of 61 (12.0) years; 40% (36 362 of 91 320) were women and prevalence of cardiovascular disease was 25% (22 686 of 91 320). 94% of the total SGLT2 inhibitor exposure time was for use of dapagliflozin, with 5% for empagliflozin, and 1% for canagliflozin. Compared with other glucose-lowering drugs, use of SGLT2 inhibitors was associated with decreased risk of cardiovascular mortality (HR 0.53 [95% CI 0.40-0.71]), major adverse cardiovascular events (0.78 [0.69-0.87]), and hospital events for heart failure (0.70 [0.61-0.81]; p<0.0001 for all). We did not identify significant differences between use of SGLT2 inhibitors and use of other glucose-lowering drugs for non-fatal myocardial infarction, non-fatal stroke, or atrial fibrillation. Compared with other glucose-lowering drugs, use of SGLT2 inhibitors was associated with a decreased risk of severe hypoglycaemia (HR 0.76 [0.65-0.90]; p=0.001). For cardiovascular mortality, the differences were similar for the 25% of individuals with cardiovascular disease at baseline and those without (HR 0.60 [0.42-0.85] vs 0.55 [0.34-0.90]), while for major adverse cardiovascular events the HR in the group with cardiovascular disease at baseline was 0.70 (0.59-0.83) versus 0.90 (0.76-1.07) in the group without. Interpretation In a population of patients with type 2 diabetes and a broad cardiovascular risk profile, SGLT2 inhibitor use was associated with reduced cardiovascular disease and cardiovascular mortality compared with use of other glucose-lowering drugs-a finding consistent with the results of clinical trials in patients at high cardiovascular risk.
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| 17. |
- Borestrom, C., et al.
(författare)
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A CRISP(e)R view on kidney organoids allows generation of an induced pluripotent stem cell-derived kidney model for drug discovery
- 2018
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Ingår i: Kidney International. - : Elsevier BV. - 0085-2538 .- 1523-1755. ; 94:6, s. 1099-1110
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Tidskriftsartikel (refereegranskat)abstract
- Development of physiologically relevant cellular models with strong translatability to human pathophysiology is critical for identification and validation of novel therapeutic targets. Herein we describe a detailed protocol for generation of an advanced 3-dimensional kidney cellular model using induced pluripotent stem cells, where differentiation and maturation of kidney progenitors and podocytes can be monitored in live cells due to CRISPR/Cas9-mediated fluorescent tagging of kidney lineage markers (SIX2 and NPHS1). Utilizing these cell lines, we have refined the previously published procedures to generate a new, higher throughput protocol suitable for drug discovery. Using paraffin-embedded sectioning and whole-mount immunostaining, we demonstrated that organoids grown in suspension culture express key markers of kidney biology (WT1, ECAD, LTL, nephrin) and vasculature (CD31) within renal cortical structures with microvilli, tight junctions and podocyte foot processes visualized by electron microscopy. Additionally, the organoids resemble the adult kidney transcriptomics profile, thereby strengthening the translatability of our in vitro model. Thus, development of human nephron-like structures in vitro fills a major gap in our ability to assess the effect of potential treatment on key kidney structures, opening up a wide range of possibilities to improve clinical translation.
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| 18. |
- Bosmans, J W A M, et al.
(författare)
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Functional mucous layer and healing of proximal colonic anastomoses in an experimental model.
- 2017
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Ingår i: The British journal of surgery. - : Oxford University Press (OUP). - 1365-2168 .- 0007-1323. ; 104:5, s. 619-630
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Tidskriftsartikel (refereegranskat)abstract
- Anastomotic leakage (AL) is the most dreaded complication after colorectal surgery, causing high morbidity and mortality. Mucus is a first line of defence against external factors in the gastrointestinal tract. In this study, the structural mucus protein Muc2 was depleted in genetically engineered mice and the effect on healing of colonic anastomoses studied in an experimental model.Mice of different Muc2 genotypes were used in a proximal colonic AL model. Tissues were scored histologically for inflammation, bacterial translocation was determined by quantitative PCR of bacterial 16S ribosomal DNA, and epithelial cell damage was determined by assessing serum levels of intestinal fatty acid-binding protein.Of 22 Muc2-deficient (Muc2(-/-) ) mice, 20 developed AL, compared with seven of 22 control animals (P <0·001). Control mice showed normal healing, whereas Muc2(-/-) mice had more inflammation with less collagen deposition and neoangiogenesis. A tendency towards higher bacterial translocation was seen in mesenteric lymph nodes and spleen in Muc2(-/-) mice. Intestinal fatty acid-binding protein levels were significantly higher in Muc2(-/-) mice compared with controls (P = 0·011).A functional mucous layer facilitates the healing of colonic anastomoses. Clinical relevance Colorectal anastomotic leakage remains the most dreaded complication after colorectal surgery. It is known that the aetiology of anastomotic leakage is multifactorial, and a role is suggested for the interaction between intraluminal content and mucosa. In this murine model of proximal colonic anastomotic leakage, the authors investigated the mucous layer at the intestinal mucosa, as the first line of defence, and found that a normal, functioning mucous layer is essential in the healing process of colonic anastomoses. Further research on anastomotic healing should focus on positively influencing the mucous layer to promote better postoperative recovery.
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| 19. |
- Chaffin, Brian C., et al.
(författare)
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Biological invasions, ecological resilience and adaptive governance
- 2016
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Ingår i: Journal of Environmental Management. - : Elsevier BV. - 0301-4797 .- 1095-8630. ; 183, s. 399-407
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Tidskriftsartikel (refereegranskat)abstract
- In a world of increasing interconnections in global trade as well as rapid change in climate and land cover, the accelerating introduction and spread of invasive species is a critical concern due to associated negative social and ecological impacts, both real and perceived. Much of the societal response to invasive species to date has been associated with negative economic consequences of invasions. This response has shaped a war-like approach to addressing invasions, one with an agenda of eradications and intense ecological restoration efforts towards prior or more desirable ecological regimes. This trajectory often ignores the concept of ecological resilience and associated approaches of resilience-based governance. We argue that the relationship between ecological resilience and invasive species has been understudied to the detriment of attempts to govern invasions, and that most management actions fail, primarily because they do not incorporate adaptive, learning-based approaches. Invasive species can decrease resilience by reducing the biodiversity that underpins ecological functions and processes, making ecosystems more prone to regime shifts. However, invasions do not always result in a shift to an alternative regime; invasions can also increase resilience by introducing novelty, replacing lost ecological functions or adding redundancy that strengthens already existing structures and processes in an ecosystem. This paper examines the potential impacts of species invasions on the resilience of ecosystems and suggests that resilience-based approaches can inform policy by linking the governance of biological invasions to the negotiation of tradeoffs between ecosystem services.
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| 20. |
- Cvjetkovic, Aleksander, et al.
(författare)
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Extracellular vesicles in motion
- 2017
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Ingår i: Science Matters. - : Sciencematters. - 2297-8240 .- 2297-9239.
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Tidskriftsartikel (refereegranskat)abstract
- By secreting extracellular vesicles (EVs), including exosomes and microvesicles, into the extracellular milieu, cells can convey complex biological messages between each other. These vesicles are generally thought to be static packages lacking the flexibility of their parental cells in terms of motility and the ability to change shape. However, cryo-electron micrographs reveal the presence of actin-like filaments in a subpopulation of EVs, raising the question if these vesicles could possess motile capabilities similar to that produced by actin in cells. We here show that fluorescently labeled EVs change their shape in a matter of minutes, regardless of whether they are isolated from human body fluids, mouse tissue or cell culture of human cells or yeast. Our findings therefore cast doubt on movement being confined to cells, suggesting that some EVs indeed have an intrinsic capacity to move. This novel observation showing morphological plasticity among EVs adds another level of complexity to the already multifaceted vesicular secretome, and may lead to new ways in which we perceive these nano-carriers of intercellular signals.
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