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- Sainsbury, A, et al.
(författare)
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Important role of hypothalamic Y2 receptors in body weight regulation revealed in conditional knockout mice
- 2002
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 99:13, s. 8938-8943
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Tidskriftsartikel (refereegranskat)abstract
- Neuropeptide Y is implicated in energy homeostasis, and contributes to obesity when hypothalamic levels remain chronically elevated. To investigate the specific role of hypothalamic Y2 receptors in this process, we used a conditional Y2 knockout model, using the Cre-lox system and adenoviral delivery of Cre-recombinase. Hypothalamus-specific Y2-deleted mice showed a significant decrease in body weight and a significant increase in food intake that was associated with increased mRNA levels for the orexigenic NPY and AgRP, as well as the anorexic proopiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) in the arcuate nucleus. These hypothalamic changes persisted until at least 34 days after Y2 deletion, yet the effect on body weight and food intake subsided within this time. Plasma concentrations of pancreatic polypeptide and corticosterone were 3- to 5-fold increased in hypothalamus-specific Y2 knockout mice. Germ-line Y2 receptor knockout also produced a significant increase in plasma levels of pancreatic polypeptide. However, these mice differed from conditional knockout mice in that they showed a sustained reduction in body weight and adiposity associated with increased NPY and AgRP but decreased POMC and CART mRNA levels in the arcuate nucleus. The transience of the observed effects on food intake and body weight in the hypothalamus-specific Y2 knockout mice, and the difference of this model from germ-line Y2 knockout mice, underline the importance of conditional models of gene deletion, because developmental, secondary, or extrahypothalamic mechanisms may mask such effects in germ-line knockouts.
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- Aps, R., et al.
(författare)
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Central Baltic Sea herring : effect of environmental trends and fishery management
- 2011
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Ingår i: Ecosystems and Sustainable Development VIII. - Southampton : BioMed Central Ltd.. - 9781845645106 - 9781845645113 ; , s. 69-80
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Konferensbidrag (refereegranskat)abstract
- Uncertainty is an endemic condition of the Baltic Sea herring (Clupea harengus membras, L) fishery management. It is a condition exacerbated by the fishing fleet overcapacity and consequent exploitation of the herring stock at a level believed to be unsustainable. Some sources of uncertainty are mainly related to biology and fishing technique: the unsolved problem of herring assessment and management units, the recruitment–environment relationship and the reduction in mean weights-at-age, uncertain ageing of fish, the problem of unaccounted fishing mortality caused by the fish selection through the trawl net. Fishing fleet overcapacity is believed to be behind of the regulatory overfishing when setting the Total Allowable Catches (TACs) higher than the scientific advice (decision overfishing) and tolerating the extensive underreporting of catches (implementation overfishing). Two scenarios for the Central Baltic Sea herring fishery management options are constructed and the Bayesian networks are used to represent and update uncertainties encountered in the process of the management related situation assessment. First scenario represents the current status of the fishery management resulting in fishing mortality (F) higher than FMSY – the fishing mortality that corresponds to the Maximum Sustainable Yield (MSY). The second scenario demonstrates the assumed potential impact of economic incentives (e.g.zoning, individual transferable quotas (ITQs), territorial use rights etc.) on the reduction of excessive fishing capacity and bringing actual fishing mortality closer to FMSY.
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- Aps, R., et al.
(författare)
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Fisheries management : from linear to collaborative science-policy interface
- 2011
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Ingår i: Management of Natural Resources, Sustainable Development and Ecological Hazards III. - : WIT Press. - 9781845645328 - 1845645324 ; , s. 3-14
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Konferensbidrag (refereegranskat)abstract
- The context of fisheries management, according to recent studies, tends to be complex, uncertain and controversial and it cannot be adequately addressed based on work done within the “linear” science-policy interface (SPI). It is believed that moving towards a more participatory and “collaborative” SPI model would favour implementation of more efficient economic incentives to reduce the fishing fleet capacity and bring the actual fishing mortality closer to the levels considered to be sustainable. Focusing the participatory research basically on fish biology and fish stock assessment seems to be too narrow while, on the other hand, it does not embrace many other important issues of contemporary fisheries management. It is suggested that further involvement of stakeholders into the full-scale bio-economic modelling based participatory research would contribute to better understanding of the dynamics of human natural interface concerned and, consequently, would improve the consensus between different interests.
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- Bensing, Sophie, et al.
(författare)
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Pituitary autoantibodies in autoimmune polyendocrine syndrome type 1
- 2007
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 104:3, s. 949-954
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Tidskriftsartikel (refereegranskat)abstract
- Autoimmune polyendocrine syndrome type 1 (APS1) is a rare autosomal recessive disorder caused by mutations in the autoimmune regulator (AIRE) gene. High titer autoantibodies (Aabs) toward intracellular enzymes are a hallmark for APS1 and serve as diagnostic markers and predictors for disease manifestations. In this study, we aimed to identify pituitary autoantigens in patients with APS1. A pituitary cDNA expression library was screened with APS1 sera and a tudor domain containing protein 6 (TDRD6) cDNA clone was isolated. Positive immunoreactivity against in vitro translated TDRD6 fragments was shown in 42/86 (49%) APS1 patients but not in patients with other autoimmune diseases or in healthy controls. By using immunohistochemistry, sera from 3/6 APS1 patients with growth hormone (GH) deficiency showed immunostaining of a small number of guinea pig anterior pituitary cells, and 40-50% of these cells were GH-positive. No such immunostaining was seen with sera from healthy controls. The APS1 Aab-positive, GH-negative cells may represent a novel subpopulation of anterior pituitary cells. In addition, 4/6 patient sera showed staining of a fiber-plexus in the pituitary intermediate lobe recognizing enzymes of monoamine and GABA synthesis. Thus, we have identified TDRD6 as a major autoantigen in APS1 patients and shown that several sera from GH-deficient patients stain specific cell populations and nerves in the pituitary gland.
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- Fetissov, Sergueï O, et al.
(författare)
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Autoantibodies in autoimmune polyglandular syndrome type I patients react with major brain neurotransmitter systems.
- 2009
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Ingår i: The Journal of comparative neurology. - : Wiley. - 1096-9861 .- 0021-9967. ; 513:1, s. 1-20
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Tidskriftsartikel (refereegranskat)abstract
- Patients with autoimmune polyglandular syndrome type I (APS1) often display high titers of autoantibodies (autoAbs) directed against aromatic L-amino acid decarboxylase (AADC), tyrosine hydroxylase (TH), tryptophan hydroxylase (TPH), and glutamic acid decarboxylase (GAD). Neurological symptoms, including stiff-man syndrome and cerebellar ataxia, can occur in subjects with high levels of GAD autoAbs, particularly when patient sera can immunohistochemically stain gamma-aminobutyric acid (GABA) neurons. However, it was not known if APS1 sera can also stain major monoamine systems in the brain. Therefore, in this work we applied sera from 17 APS1 patients known to contain autoAbs against AADC, TH, TPH, and/or GAD to rat brain sections and processed the sections according to the sensitive immunohistochemical tyramide signal amplification method. We found that autoAbs in sera from 11 patients were able to stain AADC-containing dopaminergic, serotonergic, and noradrenergic as well as AADC only (D-group) neurons and fibers in the rat brain, in several cases with a remarkably high quality and sensitivity (dilution up to 1:1,000,000); and, since they are human antibodies, they offer a good opportunity for performing multiple-labeling experiments using antibodies from other species. Six APS1 sera also stained GABAergic neuronal circuitries. Similar results were obtained in the mouse and primate brain. Our data demonstrate that many APS1 sera can immunostain the major monoamine and GABA systems in the brain. Only in a few cases, however, there was evidence that these autoAbs can be associated with neurological manifestations in APS1 patients, as, e.g., shown in previous studies in stiff-man syndrome.
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