28 research outputs found

    Super-resolution microscopy reveals functional organization of dopamine transporters into cholesterol and neuronal activity-dependent nanodomains

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    The dopamine transporter (DAT) has a crucial role in the regulation of neurotransmission. Here, the authors use super-resolution imaging to show that DAT clusters into cholesterol-dependent membrane regions that are reversibly regulated by ionotropic glutamate receptors activation

    Bone Status in Obese, Non-diabetic, Antipsychotic-Treated Patients, and Effects of the Glucagon-Like Peptide-1 Receptor Agonist Exenatide on Bone Turnover Markers and Bone Mineral Density

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    Background: Low bone mineral density (BMD) may constitute an underestimated comorbidity in schizophrenia patients undergoing long-term antipsychotic treatment. Glucagon-like peptide 1 (GLP-1) receptor agonists are antidiabetic drugs, which may also affect bone turnover.Methods: In planned secondary analyses of a 3 months, double-blind, randomized, placebo-controlled trial (n = 45), we explored effects of the GLP-1 receptor agonist exenatide 2 mg once-weekly (n = 23), or placebo (n = 22) on bone turnover markers (BTMs) and BMD in chronic, obese, antipsychotic-treated patients with schizophrenia spectrum disorder. Baseline BTMs were compared to sex- and age-adjusted reference values from a Danish population cohort, and T- and Z-scores were calculated for BMD.Results: In women (n = 24), all baseline BTM measurements of procollagen type I N-terminal propeptide (PINP) and C-terminal cross-linking telopeptide of type I collagen (CTX) were within reference values. In men (n = 21), 5% displayed lower PINP and 14% displayed lower CTX. One patient displayed BMD Z-score Conclusions: Sex- and age-adjusted measures of bone status in chronic, obese, antipsychotic-treated patients appeared comparable to the reference population. Subtle changes in bone markers during 3 months exenatide treatment may suggest beneficial effects of GLP-1 receptor agonists on bone status in antipsychotic-treated patients, and further studies should consider the potential influence of prolactin.</p

    Large Gliadin Peptides Detected in the Pancreas of NOD and Healthy Mice following Oral Administration

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    Gluten promotes type 1 diabetes in nonobese diabetic (NOD) mice and likely also in humans. In NOD mice and in non-diabetes-prone mice, it induces inflammation in the pancreatic lymph nodes, suggesting that gluten can initiate inflammation locally. Further, gliadin fragments stimulate insulin secretion from beta cells directly. We hypothesized that gluten fragments may cross the intestinal barrier to be distributed to organs other than the gut. If present in pancreas, gliadin could interact directly with the immune system and the beta cells to initiate diabetes development. We orally and intravenously administered 33-mer and 19-mer gliadin peptide to NOD, BALB/c, and C57BL/6 mice and found that the peptides readily crossed the intestinal barrier in all strains. Several degradation products were found in the pancreas by mass spectroscopy. Notably, the exocrine pancreas incorporated large amounts of radioactive label shortly after administration of the peptides. The study demonstrates that, even in normal animals, large gliadin fragments can reach the pancreas. If applicable to humans, the increased gut permeability in prediabetes and type 1 diabetes patients could expose beta cells directly to gliadin fragments. Here they could initiate inflammation and induce beta cell stress and thus contribute to the development of type 1 diabetes

    Standards in semen examination:publishing reproducible and reliable data based on high-quality methodology

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    Biomedical science is rapidly developing in terms of more transparency, openness and reproducibility of scientific publications. This is even more important for all studies that are based on results from basic semen examination. Recently two concordant documents have been published: the 6th edition of the WHO Laboratory Manual for the Examination and Processing of Human Semen, and the International Standard ISO 23162:2021. With these tools, we propose that authors should be instructed to follow these laboratory methods in order to publish studies in peer-reviewed journals, preferable by using a checklist as suggested in an Appendix to this article.Peer reviewe

    Quantifying the response of tree hyraxes (Dendrohyrax validus) to human disturbance in the Udzungwa Mountains, Tanzania

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    Quantifying the effects of human disturbance on rare species is crucial for conservation. The eastern tree hyrax (Dendrohyrax validus), restricted to East Africa, is one of the region’s least studied mammals. This study assesses the effect of hunting and logging on density and calling behavior. We evaluate three methods for estimating relative density: circular plot counts of calling individuals, latrine counts, and daytime transect counts. Circular plots show that the density of calling individuals within one forest is positively related to canopy cover. Furthermore we estimate densities of 17.3 calling individuals ha-1 in a little-disturbed forest, 12.1 in a lightly disturbed forest, and zero in an intensely hunted and formerly logged forest. Other methods support this trend, thus confirming that D. validus is dependent on intact forest. Estimation of hyrax density (and relative density) is however highly problematic and the magnitude of the trend varied between methods. Despite methodological problems, the results clearly highlight the discordance between Forest Reserve legislation and management, a conservation concern throughout the tropics

    Relative densities of mammals in response to different levels of bushmeat hunting in the Udzungwa Mountains, Tanzania

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    Bushmeat hunting constitutes the most immediate threat to wildlife populations in the Udzungwa Mountains of the Eastern Afromontane biodiversity hotspot. This study assesses the impact of hunting by comparing densities of mammalian species between the little hunted West Kilombero Scarp Forest Reserve (WKSFR), the medium-hunted Udzungwa Scarp Forest Reserve (USFR) and the intensively hunted New Dabaga Ulangambi Forest Reserve (NDUFR). Of the 22 species recorded, 20 were present in WKSFR, 17 in USFR and 12 in NDUFR. Most large species (>40 kg.) were absent from hunted areas, while medium-sized species were reduced more than smaller species. Few traces of Abbot’s duiker were observed in hunted areas and bush pig was reduced below 85% in hunted areas. Hunting appears to have little effect on primates, blue duiker, Harvey’s duiker, aardvark, eastern tree hyrax, and giant pouched rat in USFR, while hunting in NDUFR only seems of less concern for primates and giant pouched rat. Thus, the effect of hunting appears to be proportional to the size of the species and the intensity of hunting, although effects of life history strategy, forest fragment size, isolation, and previous logging cannot be excluded. Reductions of hunting levels are paramount to the survival of large bodied species in USFR and for the continued presence of most species in NDUFR. This study furthermore constitutes an important baseline for monitoring the effect of current efforts to implement joint forest management in the Udzungwa Mountains
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