| 1. |
|
|
| 2. |
- Horger, B A, et al.
(författare)
-
Neurturin exerts potent actions on survival and function of midbrain dopaminergic neurons
- 1998
-
Ingår i: The Journal of Neuroscience. - 1529-2401. ; 18:13, s. 4929-4937
-
Tidskriftsartikel (refereegranskat)abstract
- Glial cell line-derived neurotrophic factor (GDNF) exhibits potent effects on survival and function of midbrain dopaminergic (DA) neurons in a variety of models. Although other growth factors expressed in the vicinity of developing DA neurons have been reported to support survival of DA neurons in vitro, to date none of these factors duplicate the potent and selective actions of GDNF in vivo. We report here that neurturin (NTN), a homolog of GDNF, is expressed in the nigrostriatal system, and that NTN exerts potent effects on survival and function of midbrain DA neurons. Our findings indicate that NTN mRNA is sequentially expressed in the ventral midbrain and striatum during development and that NTN exhibits survival-promoting actions on both developing and mature DA neurons. In vitro, NTN supports survival of embryonic DA neurons, and in vivo, direct injection of NTN into the substantia nigra protects mature DA neurons from cell death induced by 6-OHDA. Furthermore, administration of NTN into the striatum of intact adult animals induces behavioral and biochemical changes associated with functional upregulation of nigral DA neurons. The similarity in potency and efficacy of NTN and GDNF on DA neurons in several paradigms stands in contrast to the differential distribution of the receptor components GDNF Family Receptor alpha1 (GFRalpha1) and GFRalpha2 within the ventral mesencephalon. These results suggest that NTN is an endogenous trophic factor for midbrain DA neurons and point to the possibility that GDNF and NTN may exert redundant trophic influences on nigral DA neurons acting via a receptor complex that includes GFRalpha1.
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
- Zhou, Junhua, et al.
(författare)
-
Somatic mutations of GNA11 and GNAQ in CTNNB1-mutant aldosterone-producing adenomas presenting in puberty, pregnancy or menopause
- 2021
-
Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:9, s. 1360-1372
-
Tidskriftsartikel (refereegranskat)abstract
- Sequence analysis identifies gain-of-function somatic mutations in GNA11 or GNAQ in CTNNB1-mutant aldosterone-producing adenomas. Most patients with these mutations presented during puberty, pregnancy or menopause, with elevated LHCGR expression. Most aldosterone-producing adenomas (APAs) have gain-of-function somatic mutations of ion channels or transporters. However, their frequency in aldosterone-producing cell clusters of normal adrenal gland suggests a requirement for codriver mutations in APAs. Here we identified gain-of-function mutations in both CTNNB1 and GNA11 by whole-exome sequencing of 3/41 APAs. Further sequencing of known CTNNB1-mutant APAs led to a total of 16 of 27 (59%) with a somatic p.Gln209His, p.Gln209Pro or p.Gln209Leu mutation of GNA11 or GNAQ. Solitary GNA11 mutations were found in hyperplastic zona glomerulosa adjacent to double-mutant APAs. Nine of ten patients in our UK/Irish cohort presented in puberty, pregnancy or menopause. Among multiple transcripts upregulated more than tenfold in double-mutant APAs was LHCGR, the receptor for luteinizing or pregnancy hormone (human chorionic gonadotropin). Transfections of adrenocortical cells demonstrated additive effects of GNA11 and CTNNB1 mutations on aldosterone secretion and expression of genes upregulated in double-mutant APAs. In adrenal cortex, GNA11/Q mutations appear clinically silent without a codriver mutation of CTNNB1.
|
|
| 6. |
- Babst, F., et al.
(författare)
-
When tree rings go global: Challenges and opportunities for retro- and prospective insight
- 2018
-
Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791. ; 197, s. 1-20
-
Tidskriftsartikel (refereegranskat)abstract
- The demand for large-scale and long-term information on tree growth is increasing rapidly as environmental change research strives to quantify and forecast the impacts of continued warming on forest ecosystems. This demand, combined with the now quasi-global availability of tree-ring observations, has inspired researchers to compile large tree-ring networks to address continental or even global-scale research questions. However, these emergent spatial objectives contrast with paleo-oriented research ideas that have guided the development of many existing records. A series of challenges related to how, where, and when samples have been collected is complicating the transition of tree rings from a local to a global resource on the question of tree growth. Herein, we review possibilities to scale tree-ring data (A) from the sample to the whole tree, (B) from the tree to the site, and (C) from the site to larger spatial domains. Representative tree-ring sampling supported by creative statistical approaches is thereby key to robustly capture the heterogeneity of climate-growth responses across forested landscapes. We highlight the benefits of combining the temporal information embedded in tree rings with the spatial information offered by forest inventories and earth observations to quantify tree growth and its drivers. In addition, we show how the continued development of mechanistic tree-ring models can help address some of the non-linearities and feedbacks that complicate making inference from tree-ring data. By embracing scaling issues, the discipline of dendrochronology will greatly increase its contributions to assessing climate impacts on forests and support the development of adaptation strategies. © 2018 Elsevier Ltd
|
|
| 7. |
- Björklund, J., et al.
(författare)
-
Scientific Merits and Analytical Challenges of Tree-Ring Densitometry
- 2019
-
Ingår i: Reviews of geophysics. - 8755-1209 .- 1944-9208. ; 57:4, s. 1224-1264
-
Forskningsöversikt (refereegranskat)abstract
- X-ray microdensitometry on annually resolved tree-ring samples has gained an exceptional position in last-millennium paleoclimatology through the maximum latewood density (MXD) parameter, but also increasingly through other density parameters. For 50 years, X-ray based measurement techniques have been the de facto standard. However, studies report offsets in the mean levels for MXD measurements derived from different laboratories, indicating challenges of accuracy and precision. Moreover, reflected visible light-based techniques are becoming increasingly popular, and wood anatomical techniques are emerging as a potentially powerful pathway to extract density information at the highest resolution. Here we review the current understanding and merits of wood density for tree-ring research, associated microdensitometric techniques, and analytical measurement challenges. The review is further complemented with a careful comparison of new measurements derived at 17 laboratories, using several different techniques. The new experiment allowed us to corroborate and refresh long-standing wisdom but also provide new insights. Key outcomes include (i) a demonstration of the need for mass/volume-based recalibration to accurately estimate average ring density; (ii) a substantiation of systematic differences in MXD measurements that cautions for great care when combining density data sets for climate reconstructions; and (iii) insights into the relevance of analytical measurement resolution in signals derived from tree-ring density data. Finally, we provide recommendations expected to facilitate futureinter-comparability and interpretations for global change research.
|
|
| 8. |
- Björklund, Jesper, 1979, et al.
(författare)
-
Scientific Merits and Analytical Challenges ofTree-Ring Densitometry
- 2019
-
Ingår i: Reviews of Geophysics. - : American Geophysical Union (AGU). - 8755-1209 .- 1944-9208. ; 57:4, s. 1224-1264
-
Tidskriftsartikel (refereegranskat)abstract
- X-ray microdensitometry on annually resolved tree-ring samples has gained an exceptional position in last-millennium paleoclimatology through the maximum latewood density (MXD) parameter, but also increasingly through other density parameters. For 50 years, X-ray based measurement techniques have been the de facto standard. However, studies report offsets in the mean levels for MXD measurements derived from different laboratories, indicating challenges of accuracy and precision. Moreover, reflected visible light-based techniques are becoming increasingly popular, and wood anatomical techniques are emerging as a potentially powerful pathway to extract density information at the highest resolution. Here we review the current understanding and merits of wood density for tree-ring research, associated microdensitometric techniques, and analytical measurement challenges. The review is further complemented with a careful comparison of new measurements derived at 17 laboratories, using several different techniques. The new experiment allowed us to corroborate and refresh "long-standing wisdom" but also provide new insights. Key outcomes include (i) a demonstration of the need for mass/volume-based recalibration to accurately estimate average ring density; (ii) a substantiation of systematic differences in MXD measurements that cautions for great care when combining density data sets for climate reconstructions; and (iii) insights into the relevance of analytical measurement resolution in signals derived from tree-ring density data. Finally, we provide recommendations expected to facilitate futureinter-comparability and interpretations for global change research.
|
|
| 9. |
- Christensen, T. H., et al.
(författare)
-
Application of LCA modelling in integrated waste management
- 2020
-
Ingår i: Waste Management. - : Elsevier. - 0956-053X .- 1879-2456. ; 118, s. 313-322
-
Tidskriftsartikel (refereegranskat)abstract
- Life cycle assessment (LCA) has been used in waste management for the last two decades and hundreds of journal papers have been published. The use of LCA in waste management has provided a much-improved holistic view of waste management including waste flows and potential environmental impacts. Although much knowledge has been obtained from LCA studies, there is still a need to use LCA models in integrated waste management. This paper describes six areas where LCA is expected to play a role in waste management in the future: 1) understanding an existing waste management system; 2) improving existing waste management systems; 3) comparing alternative technologies/ technology performance; 4) technology development/prospective technologies; 5) policy development/strategic development; and 6) reporting. Illustrative examples are provided for each application area.
|
|
| 10. |
- Dunnett, S. B, et al.
(författare)
-
Mechanisms and use of neural transplants for brain repair
- 2017
-
Ingår i: Functional Neural Transplantation IV Translation to Clinical Application, Part A. - : Elsevier. - 9780128117385 ; 230, s. 1-51
-
Bokkapitel (refereegranskat)abstract
- Under appropriate conditions, neural tissues transplanted into the adult mammalian brain can survive, integrate, and function so as to influence the behavior of the host, opening the prospect of repairing neuronal damage, and alleviating symptoms associated with neuronal injury or neurodegenerative disease. Alternative mechanisms of action have been postulated: nonspecific effects of surgery; neurotrophic and neuroprotective influences on disease progression and host plasticity; diffuse or locally regulated pharmacological delivery of deficient neurochemicals, neurotransmitters, or neurohormones; restitution of the neuronal and glial environment necessary for proper host neuronal support and processing; promoting local and long-distance host and graft axon growth; formation of reciprocal connections and reconstruction of local circuits within the host brain; and up to full integration and reconstruction of fully functional host neuronal networks. Analysis of neural transplants in a broad range of anatomical systems and disease models, on simple and complex classes of behavioral function and information processing, have indicated that all of these alternative mechanisms are likely to contribute in different circumstances. Thus, there is not a single or typical mode of graft function; rather grafts can and do function in multiple ways, specific to each particular context. Consequently, to develop an effective cell-based therapy, multiple dimensions must be considered: the target disease pathogenesis; the neurodegenerative basis of each type of physiological dysfunction or behavioral symptom; the nature of the repair required to alleviate or remediate the functional impairments of particular clinical relevance; and identification of a suitable cell source or delivery system, along with the site and method of implantation, that can achieve the sought for repair and recovery.
|
|
| 11. |
|
|
| 12. |
- Kirkeby, A., et al.
(författare)
-
Strategies for bringing stem cell-derived dopamine neurons to the clinic : A European approach (STEM-PD)
- 2017
-
Ingår i: Functional Neural Transplantation IV Translation to Clinical Application, Part A. - : Elsevier. - 0079-6123. - 9780128117385 ; 230, s. 165-190
-
Bokkapitel (refereegranskat)abstract
- The treatment of Parkinson's disease (PD) has for over 50 years relied on dopaminergic therapies that are highly effective especially in the early years of the condition, but ultimately are limited by the development of side effects that relate to the nonphysiological stimulation of dopamine receptors including in nonstriatal areas. Targeted regenerative therapies designed to restore specifically the lost dopaminergic innervation of the striatum would therefore represent a major advance in treating PD. Transplantation of human fetal ventral midbrain tissue to the striatum of PD patients has provided proof-of-principle that such an approach can provide long-term clinical benefits with a reduced dependency on any oral dopaminergic agents. However, fetal tissue is associated with several ethical and logistical problems and therefore does not represent a realistic route to the clinical treatment of PD in the future. As a result, alternative cell sources have been explored and the methods for producing authentic midbrain dopaminergic neurons from pluripotent cells have now advanced to a stage which makes it possible to efficiently and reproducibly produce DA progenitors at a much higher purity than can be obtained from human fetal tissue. A stem cell-based therapy for PD therefore has the potential to circumvent many of the problems currently associated with fetal tissue grafting. Here, we describe the challenges faced and the strategies that have been pursued in our European effort to bring a human embryonic stem cell (hESC)-derived dopamine cell product to clinical trial for PD.
|
|
| 13. |
- La Rosa, A. D., et al.
(författare)
-
Life cycle assessment of a novel hybrid glass-hemp/thermoset composite
- 2013
-
Ingår i: Journal of Cleaner Production. - : Elsevier. - 0959-6526 .- 1879-1786. ; 44, s. 69-76
-
Tidskriftsartikel (refereegranskat)abstract
- Bio-based materials have come increasingly into focus during the last years, as alternatives to conventional materials such as fossil-based polymers, metals, and glass. The present paper is an application of life cycle assessment (LCA) methodology in order to explore the possibility of improving the eco efficiency of glass fibre composite materials by replacing part of the glass fibres with hemp mats. The main purpose and contribution of this study is the exploration of the eco-efficiency of this new material. To a minor degree, it is also a contribution in the sense that it provides life cycle inventory data on composites, which as yet is scarce in the LCA community. The study is a development of a previous work conducted on a pipe system used to transport cooling sea waters in a Sicilian petrochemical company. A comparative LCA was performed of two different elbow–fittings made of glass fibre/thermoset composite and hybrid (glass fibre-hemp)/thermoset composite, respectively. Primary data were collected mainly for the manufacturing process of the composite, while the Ecoinvent v2.2 database (PRè- Product Ecology Consultants, 2012) was used to model other parts of the system. Significant environmental benefits of using hemp mats were found mainly in the production phase. An LCC was also carried out from cradle to grave to find ways to optimise the costs. Material costs reduction was significant for the hybrid elbow formulation.
|
|
| 14. |
- Lindqvist, Ulla, et al.
(författare)
-
The diurnal variation of serum hyaluronan in health and disease
- 1988
-
Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - 0036-5513 .- 1502-7686. ; 48:8, s. 765-770
-
Tidskriftsartikel (refereegranskat)abstract
- The variation of the serum concentration of hyaluronan during the day and between days has been investigated. In a group of healthy volunteers, the mean hyaluronan level was very stable over time except for a moderate but significant elevation after rising from bed in the morning. Patients with rheumatoid arthritis showed markedly increased hyaluronan concentrations 0.5-2 h after leaving bed. Patients with primary biliary cirrhosis exhibited high and rather constant levels during the day. A reference group of hospitalized patients with other diseases did not show any diurnal variation. The best reproducibility in hyaluronan determinations is obtained if specimens are taken before the subjects rise from bed or a few hours later, i.e. after the morning elevation of serum hyaluronan has subsided. In rheumatoid arthritis valuable information can be obtained by repeated sampling during the morning hours.
|
|
| 15. |
- Nunes, A. K. D., et al.
(författare)
-
Sildenafil (Viagra (R)) prevents and restores LPS-induced inflammation in astrocytes
- 2016
-
Ingår i: Neuroscience Letters. - : Elsevier BV. - 0304-3940. ; 630, s. 59-65
-
Tidskriftsartikel (refereegranskat)abstract
- Astrocytes are effectively involved in the pathophysiological processes in the central nervous system (CNS) and may contribute to or protect against development of inflammatory and degenerative diseases. Sildenafil is a potent and selective phosphodiesterase-5 (PDE-5) inhibitor, which induces cyclic GMP accumulation. However, the mechanisms of actions on glial cells are not clear. The aim of the present work is to evaluate the role of sildenafil in lipopolysaccharide (LPS)-stimulated astrocytes. The cytoskeleton integrity and Ca2+ waves were assessed as indicators of inflammatory state. Two main groups were done: (A) one prevention and (B) one restoration. Each of these groups: A1: control; A2: LPS for 24h; A3: sildenafil 1 or 10 mu M for 4h and then sildenafil 1 or 10 mu M + LPS for 24 h. B1: control; B2: LPS for 24 h; B3: LPS for 24 h and then LPS + sildenafil 1 or 10 mu M for 24 h. Cytoskeleton integrity was analyzed through GFAP immunolabeling and actin labeling with an Alexa 488-conjugated phalloidin probe. Calcium responses were assessed through a Ca2+-sensitive fluorophore Fura-2/AM. The results show that both preventive and restorative treatments with sildenafil (in both concentrations) reduced the Ca2+ responses in intensity and induced a more organized actin fiber pattern, compared to LPS treated cells. This work demonstrated for the first time that astrocytes are a key part of the sildenafil protective effects in the CNS.
|
|
| 16. |
- Alimohammadi, Mohammad, et al.
(författare)
-
Autoimmune Polyendocrine Syndrome Type 1 : NALP5 in Autoimmune Polyendocrine Syndrome Type 1
- 2006
-
Ingår i: The New England Journal of Medicine. ; 358:10, s. 1018-28
-
Tidskriftsartikel (refereegranskat)abstract
- Background Autoimmune polyendocrine syndrome type 1 (APS-1) is a multiorgan autoimmune disorder caused by mutations in AIRE, the autoimmune regulator gene. Though recent studies concerning AIRE deficiency have begun to elucidate the molecular pathogenesis of organ-specific autoimmunity in patients with APS-1, the autoantigen responsible for hypoparathyroidism, a hallmark of APS-1 and its most common autoimmune endocrinopathy, has not yet been identified. Methods We performed immunoscreening of a human parathyroid complementary DNA library, using serum samples from patients with APS-1 and hypoparathyroidism, to identify patients with reactivity to the NACHT leucine-rich-repeat protein 5 (NALP5). Subsequently, serum samples from 87 patients with APS-1 and 293 controls, including patients with other autoimmune disorders, were used to determine the frequency and specificity of autoantibodies against NALP5. In addition, the expression of NALP5 was investigated in various tissues. Results NALP5-specific autoantibodies were detected in 49% of the patients with APS-1 and hypoparathyroidism but were absent in all patients with APS-1 but without hypoparathyroidism, in all patients with other autoimmune endocrine disorders, and in all healthy controls. NALP5 was predominantly expressed in the cytoplasm of parathyroid chief cells. Conclusions NALP5 appears to be a tissue-specific autoantigen involved in hypoparathyroidism in patients with APS-1. Autoantibodies against NALP5 appear to be highly specific and may be diagnostic for this prominent component of APS-1.
|
|
| 17. |
- Alimohammadi, Mohammad, et al.
(författare)
-
Autoimmune polyendocrine syndrome type 1 and NALP5, a parathyroid autoantigen
- 2008
-
Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 358:10, s. 1018-1028
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Autoimmune polyendocrine syndrome type 1 (APS-1) is a multiorgan autoimmune disorder caused by mutations in AIRE, the autoimmune regulator gene. Though recent studies concerning AIRE deficiency have begun to elucidate the molecular pathogenesis of organ-specific autoimmunity in patients with APS-1, the autoantigen responsible for hypoparathyroidism, a hallmark of APS-1 and its most common autoimmune endocrinopathy, has not yet been identified. METHODS: We performed immunoscreening of a human parathyroid complementary DNA library, using serum samples from patients with APS-1 and hypoparathyroidism, to identify patients with reactivity to the NACHT leucine-rich-repeat protein 5 (NALP5). Subsequently, serum samples from 87 patients with APS-1 and 293 controls, including patients with other autoimmune disorders, were used to determine the frequency and specificity of autoantibodies against NALP5. In addition, the expression of NALP5 was investigated in various tissues. RESULTS: NALP5-specific autoantibodies were detected in 49% of the patients with APS-1 and hypoparathyroidism but were absent in all patients with APS-1 but without hypoparathyroidism, in all patients with other autoimmune endocrine disorders, and in all healthy controls. NALP5 was predominantly expressed in the cytoplasm of parathyroid chief cells. CONCLUSIONS: NALP5 appears to be a tissue-specific autoantigen involved in hypoparathyroidism in patients with APS-1. Autoantibodies against NALP5 appear to be highly specific and may be diagnostic for this prominent component of APS-1.
|
|
| 18. |
- Barker, Roger A., et al.
(författare)
-
GDNF and Parkinson's Disease : Where Next? A Summary from a Recent Workshop
- 2020
-
Ingår i: Journal of Parkinson's Disease. - 1877-7171. ; 10:3, s. 875-891
-
Tidskriftsartikel (refereegranskat)abstract
- The concept of repairing the brain with growth factors has been pursued for many years in a variety of neurodegenerative diseases including primarily Parkinson's disease (PD) using glial cell line-derived neurotrophic factor (GDNF). This neurotrophic factor was discovered in 1993 and shown to have selective effects on promoting survival and regeneration of certain populations of neurons including the dopaminergic nigrostriatal pathway. These observations led to a series of clinical trials in PD patients including using infusions or gene delivery of GDNF or the related growth factor, neurturin (NRTN). Initial studies, some of which were open label, suggested that this approach could be of value in PD when the agent was injected into the putamen rather than the cerebral ventricles. In subsequent double-blind, placebo-controlled trials, the most recent reporting in 2019, treatment with GDNF did not achieve its primary end point. As a result, there has been uncertainty as to whether GDNF (and by extrapolation, related GDNF family neurotrophic factors) has merit in the future treatment of PD. To critically appraise the existing work and its future, a special workshop was held to discuss and debate this issue. This paper is a summary of that meeting with recommendations on whether there is a future for this therapeutic approach and also what any future PD trial involving GDNF and other GDNF family neurotrophic factors should consider in its design.
|
|
| 19. |
- Beziat, Vivien, et al.
(författare)
-
NK cell responses to cytomegalovirus infection lead to stable imprints in the human KIR repertoire and involve activating KIRs
- 2013
-
Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 121:14, s. 2678-2688
-
Tidskriftsartikel (refereegranskat)abstract
- Human natural killer (NK) cells are functionally regulated by killer cell immunoglobulin-like receptors (KIRs) and their interactions with HLA class I molecules. As KIR expression in a given NK cell is genetically hard-wired, we hypothesized that KIR repertoire perturbations reflect expansions of unique NK-cell subsets and may be used to trace adaptation of the NK-cell compartment to virus infections. By determining the human KIR-ome at a single-cell level in more than 200 donors, we were able to analyze the magnitude of NK cell adaptation to virus infections in healthy individuals. Strikingly, infection with human cytomegalovirus (CMV), but not with other common herpesviruses, induced expansion and differentiation of KIR-expressing NK cells, visible as stable imprints in the repertoire. Education by inhibitory KIRs promoted the clonal-like expansion of NK cells, causing a bias for self-specific inhibitory KIRs. Furthermore, our data revealed a unique contribution of activating KIRs (KIR2DS4, KIR2DS2, or KIR3DS1), in addition to NKG2C, in the expansion of human NK cells. These results provide new insight into the diversity of KIR repertoire and its adaptation to virus infection, suggesting a role for both activating and inhibitory KIRs in immunity to CMV infection.
|
|
| 20. |
|
|
| 21. |
|
|
| 22. |
- Björklund, Justina A., et al.
(författare)
-
Comparisons of polybrominated diphenyl ether and hexabromocyclododecane concentrations in dust collected with two sampling methods and matched breast milk samples
- 2012
-
Ingår i: Indoor Air. - : Hindawi Limited. - 0905-6947 .- 1600-0668. ; 22:4, s. 279-288
-
Tidskriftsartikel (refereegranskat)abstract
- Household dust from 19 Swedish homes was collected using two different sampling methods: from the occupants own home vacuum cleaner after insertion of a new bag and using a researcher-collected method where settled house dust was collected from surfaces above floor level. The samples were analyzed for 16 polybrominated diphenyl ether (PBDE) congeners and total hexabromocyclododecane (HBCD). Significant correlations (r = 0.600.65, Spearman r = 0.470.54, P < 0.05) were found between matched dust samples collected with the two sampling methods for ?OctaBDE and ?DecaBDE but not for ?PentaBDE or HBCD. Statistically significantly higher concentrations of all PBDE congeners were found in the researcher-collected dust than in the home vacuum cleaner bag dust (VCBD). For HBCD, however, the concentrations were significantly higher in the home VCBD samples. Analysis of the bags themselves indicated no or very low levels of PBDEs and HBCD. This indicates that there may be specific HBCD sources to the floor and/or that it may be present in the vacuum cleaners themselves. The BDE-47 concentrations in matched pairs of VCBD and breast milk samples were significantly correlated (r = 0.514, P = 0.029), indicating that one possible exposure route for this congener may be via dust ingestion. Practical Implications The statistically significant correlations found for several individual polybrominated diphenyl ether (PBDE) congeners, ?OctaBDE and ?DecaBDE between the two dust sampling methods in this study indicate that the same indoor sources contaminate both types of dust or that common processes govern the distribution of these compounds in the indoor environment. Therefore, either method is adequate for screening ?OctaBDE and ?DecaBDE in dust. The high variability seen between dust samples confirms results seen in other studies. For hexabromocyclododecane (HBCD), divergent results in the two dust types indicate differences in contamination sources to the floor than to above-floor surfaces. Thus, it is still unclear which dust sampling method is most relevant for HBCD as well as for ?PentaBDE in dust and, further, which is most relevant for determining human exposure to PBDEs and HBCD.
|
|
| 23. |
- Björklund, RB, et al.
(författare)
-
Partial Reduction of a Vanadia/Silica-Titania Catalyst with NH3 + NO at 473 K Studied by Electrical Conductance and ESR Measurements
- 1992
-
Ingår i: Journal of Physical Chemistry. - : American Chemical Society (ACS). - 0022-3654 .- 1541-5740. ; 96:26, s. 10953-10959
-
Tidskriftsartikel (refereegranskat)abstract
- Partial reduction of vanadia supported on silica-titania by NH3 + NO has been studied by electrical conductance and ESR measurements. The relationship between electrical conductance and degree of reduction was determined by oxidative and reductive titrations of V(IV) and V(V) species leached from catalyst samples which had been reduced to different levels. In situ monitoring of the steady-state V(IV) ion concentration by electrical conductance during reduction with NH3 + NO in the concentration range 0-600 ppm for each reactant in a 2 vol % O2/Ar carrier gas was performed. In a large excess of NH3, the V(IV) ion concentration increased sharply with even small additions of NO. In a large excess of NO, the NH3 + NO mixture exhibited first an oxidizing character, and the V(IV) ion concentration increased when P(NH3) > 1/6P(NO). The reaction order with respect to the NO concentration, determined from both the NO conversion and the initial rate of catalyst reduction in excess NH3, was found to be less than unity. Determination of the stoichiometry of the reaction with respect to O2 indicated that the gas-phase O2 concentration required to balance the reducing character of NH3 + NO mixtures on the surface was significantly higher than predicted by the balanced equation describing the reaction. ESR measurements on the catalyst detected V(IV) ions as vanadyl groups having two different coordination spheres. Reduction of the catalyst with NH3 + NO caused an increase in the V(IV) signal and a decrease of the hyperfine structure.
|
|
| 24. |
- Bohn, Pernille, et al.
(författare)
-
Abiotic degradation of antibiotic ionophores
- 2013
-
Ingår i: Environmental Pollution. - 0269-7491 .- 1873-6424. ; 182, s. 177-183
-
Tidskriftsartikel (refereegranskat)abstract
- Hydrolytic and photolytic degradation were investigated for the ionophore antibiotics lasalocid, monensin, salinomycin, and narasin. The hydrolysis study was carried out by dissolving the ionophores in solutions of pH 4, 7, and 9, followed by incubation at three temperatures of 6, 22, and 28 °C for maximum 34 days. Using LC–MS/MS for chemical analysis, lasalocid was not found to hydrolyse in any of the tested environments. Monensin, salinomycin, and narasin were all stable in neutral or alkaline solution but hydrolysed in the solution with a pH of 4. Half-lives at 25 °C were calculated to be 13, 0.6, and 0.7 days for monensin, salinomycin, and narasin, respectively. Absorbance spectra from each compound indicated that only lasalocid is degraded by photolysis (half-life below 1 h) due to an absorbance maximum around 303 nm, and monensin, salinomycin, and narasin are resistant to direct photolysis because they absorb light of environmentally irrelevant wavelengths.
|
|
| 25. |
- Bohn, Pernille, et al.
(författare)
-
Abiotic degradation of antibiotic ionophores
- 2013
-
Ingår i: Environmental Pollution. - : Elsevier Ltd.. - 0269-7491 .- 1873-6424. ; 182, s. 177-183
-
Tidskriftsartikel (refereegranskat)abstract
- Hydrolytic and photolytic degradation were investigated for the ionophore antibiotics lasalocid, monensin, salinomycin, and narasin. The hydrolysis study was carried out by dissolving the ionophores in solutions of pH 4, 7, and 9, followed by incubation at three temperatures of 6, 22, and 28 °C for maximum 34 days. Using LC–MS/MS for chemical analysis, lasalocid was not found to hydrolyse in any of the tested environments. Monensin, salinomycin, and narasin were all stable in neutral or alkaline solution but hydrolysed in the solution with a pH of 4. Half-lives at 25 °C were calculated to be 13, 0.6, and 0.7 days for monensin, salinomycin, and narasin, respectively. Absorbance spectra from each compound indicated that only lasalocid is degraded by photolysis (half-life below 1 h) due to an absorbance maximum around 303 nm, and monensin, salinomycin, and narasin are resistant to direct photolysis because they absorb light of environmentally irrelevant wavelengths.
|
|
| 26. |
|
|
| 27. |
- Brundin, Patrik, et al.
(författare)
-
Bilateral caudate and putamen grafts of embryonic mesencephalic tissue treated with lazaroids in Parkinson's disease
- 2000
-
Ingår i: Brain. - 1460-2156. ; 123, s. 1380-1390
-
Tidskriftsartikel (refereegranskat)abstract
- Five parkinsonian patients were transplanted bilaterally into the putamen and caudate nucleus with human embryonic mesencephalic tissue from between seven and nine donors. To increase graft survival, the lipid peroxidation inhibitor tirilazad mesylate was administered to the tissue before implantation and intravenously to the patients for 3 days thereafter. During the second postoperative year, the mean daily L-dopa dose was reduced by 54% and the UPDRS (Unified Parkinson's Disease Rating Scale) motor score in 'off' phase was reduced by a mean of 40%. At 10-23 months after grafting, PET showed a mean 61% increase of 6-L-[(18)F]fluorodopa uptake in the putamen, and 24% increase in the caudate nucleus, compared with preoperative values. No obvious differences in the pattern of motor recovery were observed between these and other previously studied cases with putamen grafts alone. The amount of mesencephalic tissue implanted in each putamen and caudate nucleus was 42 and 50% lower, respectively, compared with previously transplanted patients from our centre. Despite this reduction in grafted tissue, the magnitudes of symptomatic relief and graft survival were very similar. These findings suggest that tirilazad mesylate may improve survival of grafted dopamine neurons in patients, which is in agreement with observations in experimental animals.
|
|
| 28. |
|
|
| 29. |
- Cenci, M A, et al.
(författare)
-
Characterization of in vivo noradrenaline release from superior cervical ganglia or fetal locus coeruleus transplanted to the subcortically deafferented hippocampus in the rat
- 1993
-
Ingår i: Experimental Neurology. - : Elsevier BV. - 0014-4886. ; 122:1, s. 73-87
-
Tidskriftsartikel (refereegranskat)abstract
- Solid grafts of autologous superior cervical ganglia (SCG) or fetal locus coeruleus (LC) were implanted unilaterally into a fimbria-fornix lesion cavity adjacent to the hippocampal formation after a 6-hydroxydopamine lesion of the intrinsic noradrenergic system. Twelve to 15 months after transplantation, one microdialysis probe was implanted in the dorsal hippocampus ipsilateral to the graft, and extracellular levels of noradrenaline (NA) were monitored during the application of pharmacological or behavioral stimuli. Age-matched intact and lesion-only animals served as controls. Morphological examination of the grafts was performed on sections processed for dopamine-beta-hydroxylase (DBH) immunohistochemistry. In the lesion-only controls, the hippocampus was totally devoid of DBH-immunoreactive fibers and hippocampal levels of NA were generally undetectable. Although both SCG and LC grafts gave rise to an extensive DBH-immunoreactive fiber ingrowth in the ipsilateral hippocampus, baseline NA release was strikingly different in the two graft groups, being markedly lower than normal in the SCG-grafted rats (3.5 +/- 0.1 fmol/30 microliters) and significantly higher than normal in the LC-grafted rats (44.5 +/- 12.3 fmol/30 microliters). The response to potassium-induced depolarization (100 mM KCl in the perfusion fluid), neuronal uptake blockade (5 microM desipramine), and sodium-channel blockade (1 microM TTX) was similar to normal in both graft groups. Exposure of the animals to mild (handling) or severe (immobilization) stressful stimuli significantly enhanced NA release in the intact controls, whereas no clear-cut effect could be detected in either graft group. Electrical stimulation of the medial septum, applied in an attempt to activate possible afferents to the grafts from the host septum, did not enhance NA release in any of the groups. The results show that grafts of both central and peripheral noradrenergic neurons can provide a source of steady-state NA release in the denervated hippocampus, but that the spontaneous activity of the grafted ganglionic neurons is very low compared to that of the LC neurons, probably due to the absence of a functional preganglionic input to the grafted SCG neurons. Although extracellular NA recovered from both the SCG- and the LC-grafted hippocampi is likely to derive from impulse-dependent neuronal release, it was largely unaffected by physiological stimuli applied to the host.
|
|
| 30. |
- Clifton, Luke A, et al.
(författare)
-
Design and use of model membranes to study biomolecular interactions using complementary surface-sensitive techniques.
- 2020
-
Ingår i: Advances in Colloid and Interface Science. - : Elsevier. - 0001-8686 .- 1873-3727. ; 277
-
Tidskriftsartikel (refereegranskat)abstract
- Cellular membranes are complex structures and simplified analogues in the form of model membranes or biomembranes are used as platforms to understand fundamental properties of the membrane itself as well as interactions with various biomolecules such as drugs, peptides and proteins. Model membranes at the air-liquid and solid-liquid interfaces can be studied using a range of complementary surface-sensitive techniques to give a detailed picture of both the structure and physicochemical properties of the membrane and its resulting interactions. In this review, we will present the main planar model membranes used in the field to date with a focus on monolayers at the air-liquid interface, supported lipid bilayers at the solid-liquid interface and advanced membrane models such as tethered and floating membranes. We will then briefly present the principles as well as the main type of information on molecular interactions at model membranes accessible using a Langmuir trough, quartz crystal microbalance with dissipation monitoring, ellipsometry, atomic force microscopy, Brewster angle microscopy, Infrared spectroscopy, and neutron and X-ray reflectometry. A consistent example for following biomolecular interactions at model membranes is used across many of the techniques in terms of the well-studied antimicrobial peptide Melittin. The overall objective is to establish an understanding of the information accessible from each technique, their respective advantages and limitations, and their complementarity.
|
|
| 31. |
|
|
| 32. |
|
|
| 33. |
|
|
| 34. |
|
|
| 35. |
|
|
| 36. |
- Harrad, Stuart, et al.
(författare)
-
Indoor Contamination with Hexabromocyclododecanes, Polybrominated Diphenyl Ethers, and Perfluoroalkyl Compounds : An Important Exposure Pathway for People?
- 2010
-
Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 44:9, s. 3221-3231
-
Forskningsöversikt (refereegranskat)abstract
- This review underlines the importance of indoor contamination as a pathway of human exposure to hexabromocyclododecanes (HBCDs), polybrominated diphenyl ethers (PBDEs), and perfluoroalkyl compounds (PFCs). There is ample evidence of substantial contamination of indoor dust with these chemicals and that their concentrations in indoor air exceed substantially those outdoors. Studies examining the relationship between body burden and exposure via indoor dust are inconsistent while some indicate a link between body burdens and PBDE and HBCD exposure via dust ingestion, others find no correlation. Likewise, while concentrations in indoor dust and human tissues are both highly skewed, this does not necessarily imply causality. Evidence suggests exposure via dust ingestion is higher for toddlers than adults. Research priorities include identifying means of reducing indoor concentrations and indoor monitoring methods that provide the most ""biologically-relevant"" measures of exposure as well as monitoring a wider range of microenvironment categories. Other gaps include studies to improve understanding of the following: emission rates and mechanisms via which these contaminants migrate from products into indoor air and dust; relationships between indoor exposures and human body burdens; relevant physicochemical properties; the gastrointestinal uptake by humans of these chemicals from indoor dust; and human dust ingestion rates.
|
|
| 37. |
|
|
| 38. |
- Kaiser, A., et al.
(författare)
-
Pharmaceutical consumption patterns in four coastal regions of the South Baltic Sea : Germany, Sweden, Poland and Lithuania
- 2019
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This report of MORPHEUS Project Partners documents the outcome of WP3 – consumption patterns. Herein, the project aims to identify and quantify the emission of selected pharmaceuticals especially discharged via wastewater of WWTP. A comprehensive data research was performed and prioritized pharmaceutical consumption loads have been calculated for the model areas in Lithuania, Poland, Sweden and Germany. The outcome of this report can be summarized in the following key facts:1. Consumption data is based on either sales data of wholesalers/pharmacies or data from health care institutions. The unit of consumption is number of reimbursed packages andDDD, respectively.2. The resolution and data coverage (only partly including OTC, hospital etc.) is country- specific: The best time-resolution was found in Poland (monthly), the best spatial resolution in Lithuania (population group <3000).3. Country-specific consumption was comparable by a developed value intake load per inhabitant per year.4. For Swedish and German data, a comparison of different distributing sites of pharmaceuticals was possible (over the counter sales, application in hospitals, prescriptions/pharmacies).5. For Lithuanian data, the high spatial resolution enabled a potential correlation with the local demographic data in regard of consumption of beta blocking pharmaceuticals.6. For Polish data, a seasonal variation can be clearly shown for antibiotics.7. For German data, an accumulation within the river catchment shows that a complete picture of the whole system is essential to understand the actual burden of pharmaceuticals in the environment.8. Comparing the model areas, all results have been in the same order of magnitude more or less depending on consumption and doses. Metformin and diverse analgesics revealed high intake loads. In general, mostly German intake loads exceed the others which may lies in the fact that the selection of pharmaceuticals is mostly based on German literature and statistics due to availability/accessibility. An adjustment to each country-specific list may lead to other results.9. Some substances remain unclear: Contrast media and hormones are still a matter of burden to the environment but caused some difficulties during data collection andresearch.
|
|
| 39. |
- Kaiser, A., et al.
(författare)
-
Pharmaceutical consumption patterns in four coastal regions of the South Baltic Sea : Germany, Sweden, Poland and Lithuania
- 2019
-
Bok (övrigt vetenskapligt/konstnärligt)abstract
- This report of MORPHEUS Project Partners documents the outcome of WP3 – consumption patterns. Herein, the project aims to identify and quantify the emission of selected pharmaceuticals especially discharged via wastewater of WWTP. A comprehensive data research was performed and prioritized pharmaceutical consumption loads have been calculated for the model areas in Lithuania, Poland, Sweden and Germany. The outcome of this report can be summarized in the following key facts: 1. Consumption data is based on either sales data of wholesalers/pharmacies or data from health care institutions. The unit of consumption is number of reimbursed packages andDDD, respectively. 2. The resolution and data coverage (only partly including OTC, hospital etc.) is country- specific: The best time-resolution was found in Poland (monthly), the best spatial resolution in Lithuania (population group <3000). 3. Country-specific consumption was comparable by a developed value intake load per inhabitant per year. 4. For Swedish and German data, a comparison of different distributing sites of pharmaceuticals was possible (over the counter sales, application in hospitals, prescriptions/pharmacies). 5. For Lithuanian data, the high spatial resolution enabled a potential correlation with the local demographic data in regard of consumption of beta blocking pharmaceuticals. 6. For Polish data, a seasonal variation can be clearly shown for antibiotics. 7. For German data, an accumulation within the river catchment shows that a complete picture of the whole system is essential to understand the actual burden of pharmaceuticals in the environment. 8. Comparing the model areas, all results have been in the same order of magnitude more or less depending on consumption and doses. Metformin and diverse analgesics revealed high intake loads. In general, mostlyGerman intake loads exceed the others which may lies in the fact that the selection of pharmaceuticals is mostly based on German literature and statistics due to availability/accessibility. An adjustment to each country-specific list may lead to other results. 9. Some substances remain unclear: Contrast media and hormones are still a matter of burden to the environment but caused some difficulties during data collection andresearch.
|
|
| 40. |
|
|
| 41. |
|
|
| 42. |
- Kalén, P, et al.
(författare)
-
Intracerebral microdialysis as a tool to monitor transmitter release from grafted cholinergic and monoaminergic neurons
- 1990
-
Ingår i: Journal of Neuroscience Methods. - 0165-0270. ; 34:1-3, s. 15-107
-
Tidskriftsartikel (refereegranskat)abstract
- In the present study the microdialysis technique has been used as a tool for the study of functional regulation of intracerebrally grafted cholinergic and monoaminergic neurons as well as for the analysis of graft-host interactions. Fetal noradrenergic, serotonergic, dopaminergic, and cholinergic neurons were transplanted into the hippocampus or striatum previously denervated of their intrinsic monoaminergic or cholinergic afferents. After a few months survival, when the grafts had reinnervated the surrounding target, dialysis probes were implanted into the graft-reinnervated region. Although the graft-derived fiber and terminal density varied substantially from one animal to another the transmitters in the extracellular space were maintained at near-normal levels, not only under baseline conditions, but also during K(+)-induced depolarization, transmitter-selective uptake blockade, and tetrodotoxin. This suggests that the grafted neurons possess efficient autoregulatory properties despite their ectopic location. The results also show that monoamine release in the graft-reinnervated host target is impulse-dependent, and that the neurons are spontaneously functionally active at the synaptic level. Electrical stimulation of the lateral habenula (which has previously been identified as a powerful activator of the intrinsic hippocampal cholinergic and noradrenergic afferents) produced a similar increase in the release of these transmitters in the intact and grafted hippocampi. A complex environmental stimulus, such as handling, induced a consistent increase in acetylcholine but not noradrenaline release in the hippocampus. These findings suggest that grafted cholinergic and noradrenergic neurons can be functionally activated by host brain inputs.
|
|
| 43. |
- Kristiansen, Trine A., et al.
(författare)
-
Cellular Barcoding Links B-1a B Cell Potential to a Fetal Hematopoietic Stem Cell State at the Single-Cell Level
- 2016
-
Ingår i: Immunity. - : Elsevier BV. - 1074-7613. ; 45:2, s. 346-357
-
Tidskriftsartikel (refereegranskat)abstract
- Hematopoietic stem cells (HSCs) undergo a functional switch in neonatal mice hallmarked by a decrease in self-renewing divisions and entry into quiescence. Here, we investigated whether the developmental attenuation of B-1a cell output is a consequence of a shift in stem cell state during ontogeny. Using cellular barcoding for in vivo single-cell fate analyses, we found that fetal liver definitive HSCs gave rise to both B-1a and B-2 cells. Whereas B-1a potential diminished in all HSCs with time, B-2 output was maintained. B-1a and B-2 plasticity could be reinitiated in a subset of adult HSCs by ectopic expression of the RNA binding protein LIN28B, a key regulator of fetal hematopoiesis, and this coincided with the clonal reversal to fetal-like elevated self-renewal and repopulation potential. These results anchor the attenuation of B-1a cell output to fetal HSC behavior and demonstrate that the developmental decline in regenerative potential represents a reversible HSC state.
|
|
| 44. |
|
|
| 45. |
|
|
| 46. |
|
|
| 47. |
|
|
| 48. |
|
|
| 49. |
|
|
| 50. |
|
|
