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- López-Ferreras, Lorena, et al.
(författare)
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Lateral hypothalamic GLP-1 receptors are critical for the control of food reinforcement, ingestive behavior and body weight
- 2018
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 23:5, s. 1157-1168
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Tidskriftsartikel (refereegranskat)abstract
- Increased motivation for highly rewarding food is a major contributing factor to obesity. Most of the literature focuses on the mesolimbic nuclei as the core of reward behavior regulation. However, the lateral hypothalamus (LH) is also a key reward-control locus in the brain. Here we hypothesize that manipulating glucagon-like peptide-1 receptor (GLP-1R) activity selectively in the LH can profoundly affect food reward behavior, ultimately leading to obesity. Progressive ratio operant responding for sucrose was examined in male and female rats, following GLP-1R activation and pharmacological or genetic GLP-1R blockade in the LH. Ingestive behavior and metabolic parameters, as well as molecular and efferent targets, of the LH GLP-1R activation were also evaluated. Food motivation was reduced by activation of LH GLP-1R. Conversely, acute pharmacological blockade of LH GLP-1R increased food motivation but only in male rats. GLP-1R activation also induced a robust reduction in food intake and body weight. Chronic knockdown of LH GLP-1R induced by intraparenchymal delivery of an adeno-associated virus-short hairpin RNA construct was sufficient to markedly and persistently elevate ingestive behavior and body weight and ultimately resulted in a doubling of fat mass in males and females. Interestingly, increased food reinforcement was again found only in males. Our data identify the LH GLP-1R as an indispensable element of normal food reinforcement, food intake and body weight regulation. These findings also show, for we believe the first time, that brain GLP-1R manipulation can result in a robust and chronic body weight gain. The broader implications of these findings are that the LH differs between females and males in its ability to control motivated and ingestive behaviors.
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- Armstrong, Kate E., et al.
(författare)
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Patterns of diversification amongst tropical regions compared: a case study in Sapotaceae.
- 2014
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Ingår i: Frontiers in Genetics. - : Frontiers Media SA. - 1664-8021. ; 5:362
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Tidskriftsartikel (refereegranskat)abstract
- Species diversity is unequally distributed across the globe,with the greatest concentration occurring in the tropics. Even within the tropics, there are significant differences in the numbers of taxa found in each continental region. Manilkara is a pantropical genus of trees in the Sapotaceae comprising c.78 species. Its distribution allows for biogeographic investigation and testing of whether rates of diversification differ amongst tropical regions. The age and geographical origin of Manilkara are inferred to determine whether Gondwanan break-up, boreotropical migration or long distance dispersal have shaped its current disjunct distribution. Diversification rates through time are also analyzed to determine whether the timing and tempo of speciation on each continent coincides with geoclimatic events. Bayesian analyses of nuclear (ITS) and plastid (rpl32-trnL,rps16-trnK,and trnS-trnFM) sequences were used to reconstruct a species level phylogeny of Manilkara and related genera in the tribe Mimusopeae. Analyses of the nuclear data using a fossil-calibrated relaxed molecular clock indicate that Manilkara evolved 32–29 million years ago (Mya) in Africa. Lineages within the genus dispersed to the Neotropics 26–18 Mya and to Asia 28–15 Mya. Higher speciation rates are found in the Neotropical Manilkara clade than in either African or Asian clades. Dating of regional diversification correlates with known palaeoclimatic events. In South America, the divergence between Atlantic coastal forest and Amazonian clades coincides with the formation of drier Cerrado and Caatinga habitats between them. In Africa diversification coincides with Tertiary cycles of aridification an duplif tof the east African plateaux. In South east Asia dispersal may have been limited by the relatively recent emergence of land in New Guinea and islands further east c.10 Mya.
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- Freire, Susana E., et al.
(författare)
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The Lucilia group (Asteraceae, Gnaphalieae): phylogenetic and taxonomic considerations based on molecular and morphological evidence.
- 2015
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Ingår i: Plant Systematics and Evolution. - : Springer Science and Business Media LLC. - 0378-2697 .- 1615-6110 .- 2199-6881. ; 301, s. 1227-1248
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Tidskriftsartikel (refereegranskat)abstract
- The Lucilia group sensu Anderberg and Freire comprises nine South American genera: Belloa, Berroa, Chevreulia, Cuatrecasasiella, Facelis, Gamochaetopsis, Jalcophila, Lucilia and Luciliocline. The aims of this contribution were, using DNA sequences from plastid (rpl32-trnL, trnL-F) and nuclear (ITS and ETS) markers, together with morphological characters, to test the monophyly of the Lucilia group and provide new insight into generic circumscriptions. Our studies, including a broad taxon sampling of Gnaphalieae species, suggest that the Lucilia group is paraphyletic, since Antennaria, Chionolaena, Gamochaeta, Loricaria, Micropsis, Mniodes and Stuckertiella are all nested within the Lucilia group. Morphology and molecular analyses combined showed that the traditional generic circumscription of most of the genera (e.g., Berroa, Chevreulia, Chionolaena, Cuatrecasasiella, Facelis, Jalcophila and Micropsis) correlates with the inferred phylogenetic relationships. Conversely, Lucilia and Luciliocline are non-monophyletic. Lucilia is nested in a clade with Berroa, Facelis and Micropsis. Luciliocline is strongly embedded within the clade Belloa pp + Mniodes. Our results are consistent with Dillon’s study that considered Belloa as a montotypic genus (B. chilensis). Luciliocline and the remaining species of Belloa are accommodated in the genus Mniodes, and the necessary combinations are proposed for the expanded Mniodes. All the analyses showed that the monotypic genera Stuckertiella and Gamochaetopsis are in a well-supported clade nested within Gamochaeta, which implies that taxonomic changes are required also for these genera. Internal relationships in the group and the key morphological characters used in the taxonomy of the group, as well as incongruences found between morphological and molecular analyses, are discussed.
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- Gautier, Laurent, et al.
(författare)
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A new species, genus and tribe of Sapotaceae, endemic to Madagascar
- 2013
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Ingår i: Taxon. - 0040-0262 .- 1996-8175. ; 62, s. 972-983
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Tidskriftsartikel (refereegranskat)abstract
- Phylogenetic relationships of the two Malagasy Sapotaceae endemic genera Capurodendron and Tsebona have been unclear until now. Recent collections from Madagascar, as well as a better representation of the tribe Isonandreae, altogether 95 terminals, were used to estimate a phylogeny of subfamily Sapotoideae. We analysed sequences of nrDNA (ITS) and cpDNA (trnH-psbA) with Bayesian inference and parsimony jackknifing. As in previous analyses, Sapoteae and Sideroxyleae are recovered monophyletic. In addition, Isonandreae, distributed in the Indo-Pacific, is for the first time resolved as monophy- letic and sister to Sapoteae. All Malagasy accessions of Capurodendron, Tsebona, and a new species are grouped in another well-supported clade. This clade is accommodated in a new tribe Tseboneae characterized by caducous stipules, 5-merous flowers with quincuncial sepals, contorted aestivation of corolla lobes, absence of corolla appendages, one or three stamens opposite each corolla lobe, villous staminodes, seeds with an adaxial scar and plano-convex cotyledons, lacking endosperm. The new species is described in the new genus Bemangidia (B. lowryi) because it has a unique leaf venation for the tribe and combines different morphological features from Capurodendron and Tsebona. All three genera are well-supported monophy- letic groups. Bemangidia lowryi is threatened with extinction due to extensive ongoing forest destruction and is assigned a preliminary conservation status of Critically Endangered.
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- López-Ferreras, Lorena, et al.
(författare)
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Ghrelin's control of food reward and body weight in the lateral hypothalamic area is sexually dimorphic
- 2017
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Ingår i: Physiology & Behavior. - : Elsevier BV. - 0031-9384. ; 176, s. 40-49
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Tidskriftsartikel (refereegranskat)abstract
- Ghrelin is a stomach-produced hormone that stimulates ingestive behavior and increases motivated behavior to obtain palatable foods. Ghrelin receptors (growth hormone secretagogue receptors; Ghsr) are expressed in the lateral hypothalamic area (LHA), and LHA-targeted ghrelin application increases ingestive behavior in male rodents. However, the effects of LHA ghrelin signaling in females are unexplored. Here we investigated whether LHA ghrelin signaling is necessary and sufficient for control of ingestive and motivated behavior for food in male and female rats. Ghrelin delivered to the LHA increased food intake and motivated behavior for sucrose in both male and female rats, whereas increased food-seeking behavior and body weight were only observed in females. Females had slightly higher Ghsr levels in the LHA compared to males, and importantly, acute blockade of the Ghsr in the LHA significantly reduced food intake, body weight, and motivated behavior for sucrose in female but not male rats. Chronic LHA Ghsr reduction in female rats achieved by RNA inference-mediated Ghsr knockdown, resulting in a 25% reduction in LHA Ghsr mRNA, abolished the reward-driven behavioral effects of LHA-targeted ghrelin, but was not sufficient to affect baseline food intake or food reward responding. Collectively we show that ghrelin acts in the LHA to alter ingestive and motivated behaviors in a sex-specific manner. (C) 2017 The Authors. Published by Elsevier Inc.
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- Veldkamp, R., et al.
(författare)
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Laparoscopic resection of colon Cancer: consensus of the European Association of Endoscopic Surgery (EAES)
- 2004
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Ingår i: Surgical endoscopy. - : Springer Science and Business Media LLC. - 1432-2218 .- 0930-2794. ; 18:8, s. 1163-85
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The European Association of Endoscopic Surgery (EAES) initiated a consensus development conference on the laparoscopic resection of colon cancer during the annual congress in Lisbon, Portugal, in June 2002. METHODS: A systematic review of the current literature was combined with the opinions, of experts in the field of colon cancer surgery to formulate evidence-based statements and recommendations on the laparoscopic resection of colon cancer. RESULTS: Advanced age, obesity, and previous abdominal operations are not considered absolute contraindications for laparoscopic colon cancer surgery. The most common cause for conversion is the presence of bulky or invasive tumors. Laparoscopic operation takes longer to perform than the open counterpart, but the outcome is similar in terms of specimen size and pathological examination. Immediate postoperative morbidity and mortality are comparable for laparoscopic and open colonic cancer surgery. The laparoscopically operated patients had less postoperative pain, better-preserved pulmonary function, earlier restoration of gastrointestinal function, and an earlier discharge from the hospital. The postoperative stress response is lower after laparoscopic colectomy. The incidence of port site metastases is <1%. Survival after laparoscopic resection of colon cancer appears to be at least equal to survival after open resection. The costs of laparoscopic surgery for colon cancer are higher than those for open surgery. CONCLUSION: Laparoscopic resection of colon cancer is a safe and feasible procedure that improves short-term outcome. Results regarding the long-term survival of patients enrolled in large multicenter trials will determine its role in general surgery.
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- Anderberg, C., et al.
(författare)
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Deficiency for endoglin in tumor vasculature weakens the endothelial barrier to metastatic dissemination
- 2013
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Ingår i: Journal of Experimental Medicine. - : Rockefeller University Press. - 0022-1007 .- 1540-9538. ; 210:3, s. 563-579
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Tidskriftsartikel (refereegranskat)abstract
- Therapy-induced resistance remains a significant hurdle to achieve long-lasting responses and cures in cancer patients. We investigated the long-term consequences of genetically impaired angiogenesis by engineering multiple tumor models deprived of endoglin, a co-receptor for TGF-β in endothelial cells actively engaged in angiogenesis. Tumors from endoglin-deficient mice adapted to the weakened angiogenic response, and refractoriness to diminished endoglin signaling was accompanied by increased metastatic capability. Mechanistic studies in multiple mouse models of cancer revealed that deficiency for endoglin resulted in a tumor vasculature that displayed hallmarks of endothelial-to-mesenchymal transition, a process of previously unknown significance in cancer biology, but shown by us to be associated with a reduced capacity of the vasculature to avert tumor cell intra- and extravasation. Nevertheless, tumors deprived of endoglin exhibited a delayed onset of resistance to anti-VEGF (vascular endothelial growth factor) agents, illustrating the therapeutic utility of combinatorial targeting of multiple angiogenic pathways for the treatment of cancer.
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