| 1. |
- Macfarlane, M. D., et al.
(författare)
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Shape abnormalities of the caudate nucleus correlate with poorer gait and balance: Results from a subset of the ladis study
- 2015
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Ingår i: The American journal of geriatric psychiatry. - : Elsevier BV. - 1064-7481. ; 23:1, s. 59-
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Tidskriftsartikel (refereegranskat)abstract
- Objective Functional deficits seen in several neurodegenerative disorders have been linked with dysfunction in frontostriatal circuits and with associated shape alterations in striatal structures. The severity of visible white matter hyperintensities (WMHs) on magnetic resonance imaging has been found to correlate with poorer performance on measures of gait and balance. This study aimed to determine whether striatal volume and shape changes were correlated with gait dysfunction. Methods Magnetic resonance imaging scans and clinical gait/balance data (scores from the Short Physical Performance Battery [SPPB]) were sourced from 66 subjects in the previously published LADIS trial, performed in nondisabled individuals older than age 65 years with WMHs at study entry. Data were obtained at study entry and at 3-year follow-up. Caudate nuclei and putamina were manually traced using a previously published method and volumes calculated. The relationships between volume and physical performance on the SPPB were investigated with shape analysis using the spherical harmonic shape description toolkit. Results There was no correlation between the severity of WMHs and striatal volumes. Caudate nuclei volume correlated with performance on the SPPB at baseline but not at follow-up, with subsequent shape analysis showing left caudate changes occurred in areas corresponding to inputs of the dorsolateral prefrontal, premotor, and motor cortex. There was no correlation between putamen volumes and performance on the SPPB. Conclusion Disruption in frontostriatal circuits may play a role in mediating poorer physical performance in individuals with WMHs. Striatal volume and shape changes may be suitable biomarkers for functional changes in this population. © 2015 American Association for Geriatric Psychiatry.
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| 2. |
- Farman, H. H., et al.
(författare)
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Female mice lacking estrogen receptor-α in hypothalamic proopiomelanocortin (POMC) neurons display enhanced estrogenic response on cortical bone mass
- 2016
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Ingår i: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 157:8, s. 3242-3252
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Tidskriftsartikel (refereegranskat)abstract
- Estrogens are important regulators of bone mass and their effects are mainly mediated via estrogen receptor(ER)α.CentralERα exertsaninhibitoryroleonbonemass.ERα ishighlyexpressedinthearcuate (ARC) and the ventromedial (VMN) nuclei in the hypothalamus. To test whether ERα in proopiomelanocortin (POMC) neurons, located in ARC, is involved in the regulation of bone mass, we used mice lacking ERα expression specifically in POMC neurons (POMC-ERα -/- ). Female POMC-ERα -/- and control mice were ovariectomized (OVX) and treated with vehicle or estradiol (0.5 μg/d) for 6 weeks. As expected, estradiol treatment increased the cortical bone thickness in femur, the cortical bone mechanical strength in tibia and the trabecular bone volume fraction in both femur and vertebrae in OVX control mice. Importantly, the estrogenic responses were substantially increased in OVX POMC-ERα -/- mice compared with the estrogenic responses in OVX control mice for cortical bone thickness (+126 ± 34%, P < .01) and mechanical strength (+193 ± 38%, P < .01). To test whether ERα in VMN is involved in the regulation of bone mass, ERα was silenced using an adeno-associated viral vector. Silencing of ERα in hypothalamic VMN resulted in unchanged bone mass. In conclusion, mice lacking ERα in POMC neurons display enhanced estrogenic response on cortical bone mass and mechanical strength. We propose that the balance between inhibitory effects of central ERα activity in hypothalamic POMC neurons in ARC and stimulatory peripheral ERaα-mediated effects in bone determines cortical bone mass in female mice.
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| 3. |
- Nilsson, R. Henrik, 1976, et al.
(författare)
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A comprehensive, automatically updated fungal ITS sequence dataset for reference-based chimera control in environmental sequencing efforts
- 2015
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Ingår i: Microbes and Environments. - 1342-6311 .- 1347-4405. ; 30:2, s. 145-150
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Tidskriftsartikel (refereegranskat)abstract
- The nuclear ribosomal internal transcribed spacer (ITS) region is the most commonly chosen genetic marker for the molecular identification of fungi in environmental sequencing and molecular ecology studies. Several analytical issues complicate such efforts, one of which is the formation of chimeric—artificially joined—DNA sequences during PCR amplification or sequence assembly. Several software tools are currently available for chimera detection, but rely to various degrees on the presence of a chimera-free reference dataset for optimal performance. However, no such dataset is available for use with the fungal ITS region. This study introduces a comprehensive, automatically updated reference dataset for fungal ITS sequences based on the UNITE database for the molecular identification of fungi. This dataset supports chimera detection throughout the fungal kingdom and for full-length ITS sequences as well as partial (ITS1 or ITS2 only) datasets. The performance of the dataset on a large set of artificial chimeras was above 99.5%, and we subsequently used the dataset to remove nearly 1,000 compromised fungal ITS sequences from public circulation. The dataset is available at http://unite.ut.ee/repository.php and is subject to web-based third-party curation.
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| 4. |
- Nilsson, R. Henrik, 1976, et al.
(författare)
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A comprehensive, automatically updated fungal ITS sequence dataset for reference-based chimera control in environmental sequencing efforts
- 2015
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Ingår i: Microbes and Environments. - 1342-6311 .- 1347-4405. ; 30:2, s. 145-150
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Tidskriftsartikel (refereegranskat)abstract
- The nuclear ribosomal internal transcribed spacer (ITS) region is the most commonly chosen genetic marker for the molecular identification of fungi in environmental sequencing and molecular ecology studies. Several analytical issues complicate such efforts, one of which is the formation of chimeric—artificially joined—DNA sequences during PCR amplification or sequence assembly. Several software tools are currently available for chimera detection, but rely to various degrees on the presence of a chimera-free reference dataset for optimal performance. However, no such dataset is available for use with the fungal ITS region. This study introduces a comprehensive, automatically updated reference dataset for fungal ITS sequences based on the UNITE database for the molecular identification of fungi. This dataset supports chimera detection throughout the fungal kingdom and for full-length ITS sequences as well as partial (ITS1 or ITS2 only) datasets. The performance of the dataset on a large set of artificial chimeras was above 99.5%, and we subsequently used the dataset to remove nearly 1,000 compromised fungal ITS sequences from public circulation. The dataset is available at http://unite.ut.ee/repository.php and is subject to web-based third-party curation.
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| 5. |
- Otten, Julia, et al.
(författare)
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Weight loss by two different diets increases the postprandial response of GLP-1 but only the Paleolithic diet increases the postprandial response of GIP
- 2017
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Ingår i: Diabetologia. - : Springer. - 0012-186X .- 1432-0428. ; 60, s. S233-S233
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background and aims: Weight loss by diet intervention has shown conflicting results on postprandial levels of glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). We therefore investigated a Paleolithic diet (PD) and a prudent control diet according to the Nordic nutrition recommendations (CD) and aimed to compare the effect of the two diets on postprandial levels of GLP-1 and GIP.Materials and methods: Seventy healthy, obese, postmenopausal women were randomized to either the PD or the CD. In the PD group participants were advised to eat vegetables, fruit, lean meat, fish, nuts and eggs. Cereals, dairy products, added sugar and salt were excluded. With the CD participants were advised to increase their intake of whole grain, fruit, vegetables and fish. Dairy products and meat were supposed to be low fat. Both diets were without calorie restriction. Plasma levels of GLP-1 and GIP were measured after ingestion of 75 g glucose at baseline and after 6 and 24 months of diet intervention. The incremental area under the curve (iAUC) of GLP-1 and GIP was calculated during 120 min after glucose intake.Results: The PD group showed a more pronounced weight reduction after 6 months (9.2 ± 4.2 kg (mean±SD)) and 24 months (8.1 ± 5.6 kg) compared to the CD group (4.7 ± 4.2 kg at 6 months and 4.9 ± 4.8 kg at 24 months; P<0.001 and P<0.05 for the difference between groups at 6 months and 24 months). For the PD group the iAUC of GLP-1 increased by 34 % after 6 months and by 45 % after 24 months compared to baseline. For the CD group the iAUC of GLP-1 increased by 11 % after 6 months and by 59 % after 24 months. For the PD group the iAUC of GIP increased by 23 % after 6 months compared to baseline but decreased by 3 % in the CD group (P<0.05 for the difference between groups).Conclusion: Postprandial levels of GLP-1 increased through dietinduced weight loss by the Paleolithic diet and the control diet. The postprandial GIP response increased through weight loss by the Paleolithic diet but not by the control diet.
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| 6. |
- Phukhamsakda, C, et al.
(författare)
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The evolution of Massarineae with Longipedicellataceae fam. nov.
- 2016
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Ingår i: Mycosphere. - : Mushroom Research Foundation. - 2077-7000 .- 2077-7019. ; 7:11, s. 1713-1731
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Tidskriftsartikel (refereegranskat)abstract
- Massarineae is a suborder of Pleosporales, the latter being the largest order in Dothideomycetes. Massarineae comprises 14 families and six taxa of uncertain placement. In this study, we introduce an additional new family, Longipedicellataceae in Massarineae, which accommodates the genera Longipedicellata and Pseudoxylomyces. The family inhabits submerged culms of plants in freshwater habitats. The family can be distinguished by its very long pedicellate asci and chlamydospore-like structures, which are produced in culture. A LSU, SSU, and RPB2 dataset from representative strains used in our phylogenetic analyses shows the separation of Longipedicellataceae from the other families of Massarineae. In addition, divergence times of families in Massarineae were estimated using a molecular clock methodology. We used an Eocene fossil of Margaretbarromyces dictyosporus to estimate dates in Pleosporales with emphasis on Massarineae. In this study, the crown of Pleosporales is dated to the late Triassic (211 Mya), while the suborder Massarineae is dated to the Cretaceous (130 Mya) and family Longipedicellataceae is dated to Eocene (56 Mya).
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| 7. |
- Skrtic, Stanko, 1970, et al.
(författare)
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Exploring the insulin secretory properties of the PGD(2)-GPR44/DP2 axis in vitro and in a randomized phase-1 trial of type 2 diabetes patients
- 2018
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 13:12
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Tidskriftsartikel (refereegranskat)abstract
- Aims/Hypothesis GPR44 (DP2, PTGDR2, CRTh2) is the receptor for the pro-inflammatory mediator prosta-glandin D-2 (PGD(2)) and it is enriched in human islets. In rodent islets, PGD(2) is produced in response to glucose, suggesting that the PGD(2)-GPR44/DP2 axis may play a role in human islet function during hyperglycemia. Consequently, the aim of this work was to elucidate the insulinotropic role of GPR44 antagonism in vitro in human beta-cells and in type 2 diabetes (T2DM) patients. We determined the drive on PGD(2) secretion by glucose and IL-1 beta, as well as, the impact on insulin secretion by pharmacological GPR44/DP2 antagonism (AZD1981) in human islets and beta-cells in vitro. To test if metabolic control would be improved by antagonizing a hyperglycemia-driven increased PGD(2) tone, we performed a proof-of-mechanism study in 20 T2DM patients (average 54 years, HbA1c 9.4%, BMI 31.6 kg/m(2)). The randomized, double-blind, placebo-controlled cross-over study consisted of two three-day treatment periods (AZD1981 or placebo) separated by a three-day wash-out period. Mixed meal tolerance test (MMTT) and intravenous graded glucose infusion (GGI) was performed at start and end of each treatment period. Assessment of AZD1981 pharmacokinetics, glucose, insulin, C-peptide, glucagon, GLP-1, and PGD(2) pathway biomarkers were performed. We found (1) that PGD(2) is produced in human islet in response to high glucose or IL-1 beta, but likely by stellate cells rather than endocrine cells; (2) that PGD(2) suppresses both glucose and GLP-1 induced insulin secretion in vitro; and (3) that the GPR44/DP2 antagonist (AZD1981) in human beta-cells normalizes insulin secretion. However, AZD1981 had no impact on neither glucose nor incretin dependent insulin secretion in humans (GGI AUC (C-peptide 1-2h) and MMTT AUC (Glucose 0-4h) LS mean ratios vs placebo of 0.94 (80% CI of 0.90-0.98, p = 0.12) and 0.99 (90% CI of 0.94-1.05, p = 0.45), despite reaching the expected antagonist exposure. Pharmacological inhibition of the PGD(2)-GPR44/DP2 axis has no major impact on the modulation of acute insulin secretion in T2DM patients.
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