| 1. |
- Ludvigsson, Jonas F., 1969-, et al.
(författare)
-
Diagnosis and management of adult coeliac disease : guidelines from the British Society of Gastroenterology
- 2014
-
Ingår i: Gut. - : BMJ Publishing Group Ltd. - 0017-5749 .- 1468-3288. ; 63:8, s. 1210-1228
-
Tidskriftsartikel (refereegranskat)abstract
- A multidisciplinary panel of 18 physicians and 3 non-physicians from eight countries (Sweden, UK, Argentina, Australia, Italy, Finland, Norway and the USA) reviewed the literature on diagnosis and management of adult coeliac disease (CD). This paper presents the recommendations of the British Society of Gastroenterology. Areas of controversies were explored through phone meetings and web surveys. Nine working groups examined the following areas of CD diagnosis and management: classification of CD; genetics and immunology; diagnostics; serology and endoscopy; follow-up; gluten-free diet; refractory CD and malignancies; quality of life; novel treatments; patient support; and screening for CD.
|
|
| 2. |
- Barbero-Palacios, Laura, et al.
(författare)
-
Herbivore diversity effects on Arctic tundra ecosystems : a systematic review
- 2024
-
Ingår i: Environmental Evidence. - : BioMed Central (BMC). - 2047-2382. ; 13:1
-
Forskningsöversikt (refereegranskat)abstract
- Background: Northern ecosystems are strongly influenced by herbivores that differ in their impacts on the ecosystem. Yet the role of herbivore diversity in shaping the structure and functioning of tundra ecosystems has been overlooked. With climate and land-use changes causing rapid shifts in Arctic species assemblages, a better understanding of the consequences of herbivore diversity changes for tundra ecosystem functioning is urgently needed. This systematic review synthesizes available evidence on the effects of herbivore diversity on different processes, functions, and properties of tundra ecosystems.Methods: Following a published protocol, our systematic review combined primary field studies retrieved from bibliographic databases, search engines and specialist websites that compared tundra ecosystem responses to different levels of vertebrate and invertebrate herbivore diversity. We used the number of functional groups of herbivores (i.e., functional group richness) as a measure of the diversity of the herbivore assemblage. We screened titles, abstracts, and full texts of studies using pre-defined eligibility criteria. We critically appraised the validity of the studies, tested the influence of different moderators, and conducted sensitivity analyses. Quantitative synthesis (i.e., calculation of effect sizes) was performed for ecosystem responses reported by at least five articles and meta-regressions including the effects of potential modifiers for those reported by at least 10 articles.Review findings: The literature searches retrieved 5944 articles. After screening titles, abstracts, and full texts, 201 articles including 3713 studies (i.e., individual comparisons) were deemed relevant for the systematic review, with 2844 of these studies included in quantitative syntheses. The available evidence base on the effects of herbivore diversity on tundra ecosystems is concentrated around well-established research locations and focuses mainly on the impacts of vertebrate herbivores on vegetation. Overall, greater herbivore diversity led to increased abundance of feeding marks by herbivores and soil temperature, and to reduced total abundance of plants, graminoids, forbs, and litter, plant leaf size, plant height, and moss depth, but the effects of herbivore diversity were difficult to tease apart from those of excluding vertebrate herbivores. The effects of different functional groups of herbivores on graminoid and lichen abundance compensated each other, leading to no net effects when herbivore effects were combined. In turn, smaller herbivores and large-bodied herbivores only reduced plant height when occurring together but not when occurring separately. Greater herbivore diversity increased plant diversity in graminoid tundra but not in other habitat types.Conclusions: This systematic review underscores the importance of herbivore diversity in shaping the structure and function of Arctic ecosystems, with different functional groups of herbivores exerting additive or compensatory effects that can be modulated by environmental conditions. Still, many challenges remain to fully understand the complex impacts of herbivore diversity on tundra ecosystems. Future studies should explicitly address the role of herbivore diversity beyond presence-absence, targeting a broader range of ecosystem responses and explicitly including invertebrate herbivores. A better understanding of the role of herbivore diversity will enhance our ability to predict whether and where shifts in herbivore assemblages might mitigate or further amplify the impacts of environmental change on Arctic ecosystems.
|
|
| 3. |
- Boza-Serrano, Antonio, et al.
(författare)
-
Galectin-3, a novel endogenous TREM2 ligand, detrimentally regulates inflammatory response in Alzheimer’s disease
- 2019
-
Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 138:2, s. 251-273
-
Tidskriftsartikel (refereegranskat)abstract
- Alzheimer’s disease (AD) is a progressive neurodegenerative disease in which the formation of extracellular aggregates of amyloid beta (Aβ) peptide, fibrillary tangles of intraneuronal tau and microglial activation are major pathological hallmarks. One of the key molecules involved in microglial activation is galectin-3 (gal3), and we demonstrate here for the first time a key role of gal3 in AD pathology. Gal3 was highly upregulated in the brains of AD patients and 5xFAD (familial Alzheimer’s disease) mice and found specifically expressed in microglia associated with Aβ plaques. Single-nucleotide polymorphisms in the LGALS3 gene, which encodes gal3, were associated with an increased risk of AD. Gal3 deletion in 5xFAD mice attenuated microglia-associated immune responses, particularly those associated with TLR and TREM2/DAP12 signaling. In vitro data revealed that gal3 was required to fully activate microglia in response to fibrillar Aβ. Gal3 deletion decreased the Aβ burden in 5xFAD mice and improved cognitive behavior. Interestingly, a single intrahippocampal injection of gal3 along with Aβ monomers in WT mice was sufficient to induce the formation of long-lasting (2 months) insoluble Aβ aggregates, which were absent when gal3 was lacking. High-resolution microscopy (stochastic optical reconstruction microscopy) demonstrated close colocalization of gal3 and TREM2 in microglial processes, and a direct interaction was shown by a fluorescence anisotropy assay involving the gal3 carbohydrate recognition domain. Furthermore, gal3 was shown to stimulate TREM2–DAP12 signaling in a reporter cell line. Overall, our data support the view that gal3 inhibition may be a potential pharmacological approach to counteract AD.
|
|
| 4. |
- Carlsson, Susanne, et al.
(författare)
-
Affinity of galectin-8 and its carbohydrate recognition domains for ligands in solution and at the cell surface.
- 2007
-
Ingår i: Glycobiology. - : Oxford University Press (OUP). - 0959-6658 .- 1460-2423. ; 17:6, s. 663-76
-
Tidskriftsartikel (refereegranskat)abstract
- Galectin-8 has two different carbohydrate recognition domains (CRDs), the N-terminal Gal-8N and the C-terminal Gal-8C linked by a peptide, and has various effects on cell adhesion and signaling. To understand the mechanism for these effects further, we compared the binding activities of galectin-8 in solution with its binding and activation of cells. We used glycan array analysis to broaden the specificity profile of the two galectin-8 CRDs, as well as intact galectin-8s (short and long linker), confirming the unique preference for sulfated and sialylated glycans of Gal-8N. Using a fluorescence anisotropy assay, we examined the solution affinities for a subset of these glycans, the highest being 50 nM for NeuAcalpha2,3Lac by Gal-8N. Thus, carbohydrate-protein interactions can be of high affinity without requiring multivalency. More importantly, using fluorescence polarization, we also gained information on how the affinity is built by multiple weak interactions between different fragments of the glycan and its carrier molecule and the galectin CRD subsites (A-E). In intact galectin-8 proteins, the two domains act independently of each other in solution, whereas at a surface they act together. Ligands with moderate or weak affinity for the isolated CRDs on the array are bound strongly by intact galectin-8s. Also galectin-8 binding and signaling at cell surfaces can be explained by combined binding of the two CRDs to low or medium affinity ligands, and their highest affinity ligands, such as sialylated galactosides, are not required.
|
|
| 5. |
- Cebecauer, Matej, et al.
(författare)
-
Integrating Demand Responsive Services into Public Transport Disruption Management
- 2021
-
Ingår i: IEEE Open Journal of Intelligent Transportation Systems. - : Institute of Electrical and Electronics Engineers (IEEE). - 2687-7813. ; 2, s. 24-36
-
Tidskriftsartikel (refereegranskat)abstract
- High-capacity public transport services such as metro and commuter trains are efficient during normal operations but are vulnerable to disruptions. To manage disruptions, bridging buses are commonly called in to replace the rail-based service along the disrupted lines. These often take significant time to arrive and are costly to keep stand-by. Demand-responsive transport such as taxi can respond to demand almost immediately but is costly and must usually be arranged by the individual travelers. This study examines the integration and potential role of demand-responsive transport in disruption management. The analysis considers the impacts of limiting the serving area, varying the number of available vehicles, pursuing ride-sharing, as well as a system-of-systems approach with collaboration between taxis and bridging buses. Results of computational experiments on the case study of Stockholm, Sweden reveal that integration of demand-responsive transport in the disruption management can bring large positive benefits in terms of average and maximum waiting times for travelers. This is especially the case for strategies including ridesharing. It is also shown that appropriate trade-offs between desired waiting times and costs can be achieved by collaboration of both bridging buses and demand-responsive transport. Additionally, more robust public transport with increased reliability during disruptions can increase sustainability as more people may choose public transport instead of private cars.
|
|
| 6. |
- Cebecauer, Matej, et al.
(författare)
-
Public transport disruption management by collaboration with demand responsive services
- 2020
-
Konferensbidrag (refereegranskat)abstract
- For large cities, public transport represents the backbone for commuters and thus plays a crucial role for society and for the economy. High-capacity public transport services such as metro and commuter trains are efficient during normal operations but are vulnerable to disruptions. Metro and commuter train disruptions can be handled in several ways. Very common are bridging buses that are called in to replace the rail-based service along the disrupted lines. These often take significant time to arrive and are costly to keep stand-by. Demand-responsive transport such as taxi can respond to demand almost immediately but is costly and must usually be arranged by the individual travelers. This study examines the integration and potential role of demand-responsive transport in disruption management. The analysis considers the impacts of limiting the serving area, varying the number of available vehicles, pursuing ridesharing, as well as a system-of-systems approach with collaboration between taxis and bridging buses. Results of computational experiments on the case study of Stockholm, Sweden reveal that integration of demand-responsive transport in the disruption management can bring large positive benefits in terms of average and maximum waiting times for travelers. This is especially the case for strategies including ridesharing. It is also shown that appropriate trade-offs between desired waiting times and costs can be achieved by collaboration of both bridging buses and demand-responsive transport. Additionally, it is expected that more robust public transport with increased reliability during disruptions can increase sustainability as more people may choose public transport instead of private cars.
|
|
| 7. |
- Gunnarsson, David, et al.
(författare)
-
Mono-(2-ethylhexyl) phthalate stimulates basal steroidogenesis by a cAMP-independent mechanism in mouse gonadal cells of both sexes
- 2008
-
Ingår i: Reproduction. - 1470-1626 .- 1476-3990. ; 135:5, s. 693-703
-
Tidskriftsartikel (refereegranskat)abstract
- Phthalates are widely used as plasticizers in a number of daily-life products. In this study, we investigated the influence of mono-(2-ethylhexyl) phthalate (MEHP), the active metabolite of the frequently used plasticizer di-(2-ethylhexyl) phthalate (DEHP), on gonadal steroidogenesis in vitro. MEHP (25–100 µM) stimulated basal steroid synthesis in a concentration-dependent manner in immortalized mouse Leydig tumor cells (MLTC-1). The stimulatory effect was also detected in KK-1 granulosa tumor cells. MEHP exposure did not influence cAMP or StAR protein levels and induced a gene expression profile of key steroidogenic proteins different from the one induced by human chorionic gonadotropin (hCG). Simultaneous treatment with MEHP and a p450scc inhibitor (aminoglutethimide) indicated that MEHP exerts its main stimulatory effect prior to pregnenolone formation. MEHP (10–100 µM) up-regulated hormone-sensitive lipase and 3-hydroxy-3-methylglutaryl coenzyme A reductase, suggesting that MEHP increases the amount of cholesterol available for steroidogenesis. Our data suggest that MEHP, besides its known inhibitory effect on hCG action, can directly stimulate gonadal steroidogenesis in both sexes through a cAMP- and StAR-independent mechanism. The anti-steroidogenic effect of DEHP has been proposed to cause developmental disorders such as hypospadias and cryptorchidism, whereas a stimulation of steroid synthesis may prematurely initiate the onset of puberty and theoretically affect the hypothalamic–pituitary–gonadal axis.
|
|
| 8. |
- Gunnarsson, David, 1975-
(författare)
-
Reproductive toxicology of endocrine disruptors : effects of cadmium, phthalates and phytoestrogens on testicular steroidogenesis
- 2008
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- A number of investigations during the last two decades describe adverse trends in male reproductive health, which have been proposed to be caused by environmental factors with endocrine disrupting properties. In contrast to many other toxicants, endocrine disruptors often do not show linear dose-response relationships typical of those found in traditional toxicological studies. For many compounds, low-dose exposure causes effects opposite to the ones seen after high-dose exposure. In addition, the timing of exposure has been found to be critical. Hence, to correctly assess the impact of endocrine disruptors on reproductive health requires in-depth knowledge of their mechanisms of action. This thesis aimed at identifying the mechanisms underlying the effects of cadmium (Cd), phthalates and phytoestrogens on testicular steroidogenesis. For this purpose, in vitro as well as in vivo models were used. Cd was found to inhibit testosterone synthesis in vivo by down-regulating LH receptor gene expression and reducing the testicular levels of cAMP and StAR protein. In addition, Cd caused a pronounced increase in testicular prostaglandin F2ɑ (PGF2ɑ), suggesting that Cd exerts its suppressive effect on steroidogenesis also by inducing the inhibitory PKC pathway. Pre-treatment with zinc (Zn) protected completely against Cd-induced effects on testosterone and PGF2ɑ. Furthermore, we observed that Cd exposure increased glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA expression in the testis. GAPDH is a potent coactivator of androgen receptor-mediated transcription and the up-regulation found in our study is probably a compensatory response to reduced testosterone concentrations. This finding is interesting since GAPDH has been proposed to have an important role in the regulation of apoptosis as well as sperm motility. We discovered that mono-(2-ethylhexyl) phthalate (MEHP), the active metabolite of the frequently used phthalate di-(2-ethylhexyl) phthalate (DEHP), stimulates Leydig cell steroidogenesis in vitro, by a cAMP- and StAR-independent mechanism. MEHP exposure caused a similar effect in granulosa cells. Gene expression analysis revealed that MEHP is likely to stimulate steroidogenesis by increasing the amount of cholesterol available for steroid synthesis. In the last investigation, we examined the effects of low-dose phytoestrogen exposure on testosterone synthesis during puberty in male goats. Isoflavones present in clover increased plasma concentrations of testosterone and free as well as total triiodothyronine (T3). T3 has previously been shown to induce testosterone synthesis and it is possible that an elevated T3 secretion underlies the increased plasma testosterone levels. Reduced fertility and reproductive tract malformations affect both the individual and the society. Hence, a sound knowledge of reproductive toxicants is of crucial importance. The findings presented in this thesis provide new insights into the reproductive toxicology of endocrine disruptors and may be valuable for risk assessment purposes.
|
|
| 9. |
- Heinälä, Milla, et al.
(författare)
-
Survey on methodologies in the risk assessment of chemical exposures in emergency response situations in Europe
- 2013
-
Ingår i: Journal of Hazardous Materials. - : Elsevier. - 0304-3894 .- 1873-3336. ; 244, s. 545-554
-
Tidskriftsartikel (refereegranskat)abstract
- A scientifically sound assessment of the risk to human health resulting from acute chemical releases is the cornerstone for chemical incident prevention, preparedness and response. Although the general methodology to identify acute toxicity of chemicals has not substantially changed in the last decades, there is ongoing debate on the current approaches for human health risk assessment in scenarios involving acute chemical releases.A survey was conducted to identify 1) the most important present and potential future chemical incident scenarios and anticipated changes in chemical incidents or their management; 2) information, tools and guidance used in different countries to assess health risks from acute chemical releases; and 3) needs for new information, tools, guidance and expertise to enable the valid and rapid health risk assessment of acute chemical exposures.According to the results, there is an obvious variability in risk assessment practices within Europe. The multiplicity of acute exposure reference values appears to result in variable practices. There is a need for training especially on the practical application of acute exposure reference values. Although acutely toxic and irritating/corrosive chemicals will remain serious risks also in future the development of plausible scenarios for potential emerging risks is also needed. This includes risks from new mixtures and chemicals (e.g. nanoparticles).
|
|
| 10. |
- Leffler, David, et al.
(författare)
-
An adaptive route choice model for integrated fixed and flexible transit systems
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Over the past decade, there has been a surge of interest in the transport community in the application of agent-based simulation models to evaluate flexible transit solutions characterized by different degrees of short-term flexibility in routing and scheduling. A central modeling decision in the development of an agent-based simulation model for the evaluation of flexible transit is how one chooses to represent the mode- and route-choices of travelers. The real-time adaptive behavior of travelers is intuitively important to model in the presence of a flexible transit service, where the routing and scheduling of vehicles is highly dependent on supply-demand dynamics at a closer to real-time temporal resolution. We propose a utility-based transit route-choice model with representation of within-day adaptive travel behavior and between-day learning where station-based fixed-transit, flexible-transit, and active-mode alternatives may be dynamically combined in a single path. To enable experimentation, this route-choice model is implemented within an agent-based dynamic public transit simulation framework. Model properties are first explored in a choice between fixed- and flexible-transit modes for a toy network. The framework is then applied to illustrate level-of-service trade-offs and analyze traveler mode choices within a mixed fixed- and flexible transit system in a case study based on a real-life branched transit service in Stockholm, Sweden.
|
|
