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- Callaway, EM, et al.
(författare)
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A multimodal cell census and atlas of the mammalian primary motor cortex
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 598:7879, s. 86-102
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Tidskriftsartikel (refereegranskat)abstract
- Here we report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties and cellular resolution input–output mapping, integrated through cross-modal computational analysis. Our results advance the collective knowledge and understanding of brain cell-type organization1–5. First, our study reveals a unified molecular genetic landscape of cortical cell types that integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a consensus taxonomy of transcriptomic types and their hierarchical organization that is conserved from mouse to marmoset and human. Third, in situ single-cell transcriptomics provides a spatially resolved cell-type atlas of the motor cortex. Fourth, cross-modal analysis provides compelling evidence for the transcriptomic, epigenomic and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types. We further present an extensive genetic toolset for targeting glutamatergic neuron types towards linking their molecular and developmental identity to their circuit function. Together, our results establish a unifying and mechanistic framework of neuronal cell-type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties.
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- Nystrom, T, et al.
(författare)
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Effects of glucagon-like peptide-1 on endothelial function in type 2 diabetes patients with stable coronary artery disease
- 2004
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Ingår i: American Journal of Physiology: Endocrinology and Metabolism. - : American Physiological Society. - 1522-1555 .- 0193-1849. ; 287:6, s. 1209-1215
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Tidskriftsartikel (refereegranskat)abstract
- GLP-1 stimulates insulin secretion, suppresses glucagon secretion, delays gastric emptying, and inhibits small bowel motility, all actions contributing to the anti-diabetogenic peptide effect. Endothelial dysfunction is strongly associated with insulin resistance and type 2 diabetes mellitus and may cause the angiopathy typifying this debilitating disease. Therefore, interventions affecting both endothelial dysfunction and insulin resistance may prove useful in improving survival in type 2 diabetes patients. We investigated GLP-1's effect on endothelial function and insulin sensitivity (S-I) in two groups: 1) 12 type 2 diabetes patients with stable coronary artery disease and 2) 10 healthy subjects with normal endothelial function and S-I. Subjects underwent infusion of recombinant GLP-1 or saline in a random crossover study. Endothelial function was measured by postischemic FMD of brachial artery, using ultrasonography. S-I [in (10(-4) dl.kg(-1).min(-1))/(muU/ml)] was measured by hyperinsulinemic isoglycemic clamp technique. In type 2 diabetic subjects, GLP-1 infusion significantly increased relative changes in brachial artery diameter from baseline FMD(%) (3.1 +/- 0.6 vs. 6.6 +/- 1.0%, P < 0.05), with no significant effects on S-I (4.5 &PLUSMN; 0.8 vs. 5.2 &PLUSMN; 0.9, P = NS). In healthy subjects, GLP-1 infusion affected neither FMD(%) (11.9 &PLUSMN; 0.9 vs. 10.3 &PLUSMN; 1.0%, P = NS) nor S-I (14.8 &PLUSMN; 1.8 vs. 11.6 &PLUSMN; 2.0, P = NS). We conclude that GLP-1 improves endothelial dysfunction but not insulin resistance in type 2 diabetic patients with coronary heart disease. This beneficial vascular effect of GLP-1 adds yet another salutary property of the peptide useful in diabetes treatment.
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- Zhou, QJ, et al.
(författare)
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Seroprevalence of Cytomegalovirus and Associated Factors Among Preconception Women: A Cross-Sectional Nationwide Study in China
- 2021
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Ingår i: Frontiers in public health. - : Frontiers Media SA. - 2296-2565. ; 9, s. 631411-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cytomegalovirus seroconversion during pregnancy is common and has a substantial risk of congenital infection with longterm sequale. Screening during pregnancy or vaccination have not been shown to be effective for eliminating congenital infections. Preconception screening policy has not been evaluated adequately in a large scale. This nationwide study aimed to investigate epidemiological features of cytomegalovirus seropositivity and its geographic variation among Chinese women planning a pregnancy to gather epidemiological evidence as an essential for developing novel prevention strategies.Method: This cross-sectional sero-epidemiological survey enrolled women intending to become pregnant within 6 months in mainland China during 2010–2012. The primary outcomes in this study were cytomegalovirus Immunoglobulin G and M seropositivity. Secondary outcomes were the associations between Immunoglobulin G and Immunoglobulin M, with socio-demographic characteristics, including age, occupation, education level, place of residence, and ethnicity. The overall seropositivity and regional disparity was analyzed on the individual and regional level, respectively.Results: This study included data from 1,564,649 women from 31 provinces in mainland China. Among participants, 38.6% (n = 603,511) were cytomegalovirus immunoglobulin G+, 0.4% (n = 6,747) were immunoglobulin M+, and 0.2% (n = 2,879) were immunoglobulin M+ and immunoglobulin G+. On individual level, participant's age, ethnicity, and residing region were significantly associated with IgG+, IgM+, and IgM+IgG+ (P < 0.001), while occupation, education level, and place of residence were not statistically significant (P > 0.05). On regional level, cytomegalovirus immunoglobulin G and immunoglobulin M seropositivity was highest in the eastern region (49.5 and 0.5%, respectively), and lowest in the western region (26.9 and 0.4%, respectively). This geographic variation was also noted at the provincial level, characterized by higher provincial immunoglobulin M+ and immunoglobulin G+ rates associated with higher immunoglobulin G seropositivity. In the subgroup analysis of immunoglobulin G seropositivity, areas of higher immunoglobulin G positivity had a higher rate of immunoglobulin M+, indicating an expected increased risk of reinfection and primary infection.Conclusions: A substantial proportion of women (>60%) were susceptible to cytomegalovirus in preconception period in China, and immunoglobulin G seropositivity was seen at a low-medium level with substantial geographic variation. Integration of cytomegalovirus antibody testing in preconception screening program based on regional immunoglobulin G seropositivity, should be considered to promote strategies directed toward preventing sero-conversion during pregnancy to reduce the risk of this congenital infection.
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- Kappe, C, et al.
(författare)
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Evidence for paracrine/autocrine regulation of GLP-1-producing cells
- 2013
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Ingår i: American journal of physiology. Cell physiology. - : American Physiological Society. - 1522-1563 .- 0363-6143. ; 305:10, s. C1041-C1049
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Tidskriftsartikel (refereegranskat)abstract
- Glucagon-like peptide-1 (GLP-1), secreted from gut L cells upon nutrient intake, forms the basis for novel drugs against type 2 diabetes (T2D). Secretion of GLP-1 has been suggested to be impaired in T2D and in conditions associated with hyperlipidemia and insulin resistance. Further, recent studies support lipotoxicity of GLP-1-producing cells in vitro. However, little is known about the regulation of L-cell viability/function, the effects of insulin signaling, or the potential effects of stable GLP-1 analogs and dipeptidyl peptidase-4 (DPP-4) inhibitors. We determined effects of insulin as well as possible autocrine action of GLP-1 on viability/apoptosis of GLP-1-secreting cells in the presence/absence of palmitate, while also assessing direct effects on function. The studies were performed using the GLP-1-secreting cell line GLUTag, and palmitate was used to simulate hyperlipidemia. Our results show that palmitate induced production of reactive oxygen species and caspase-3 activity and reduced cell viability are significantly attenuated by preincubation with insulin/exendin-4. The indicated lipoprotective effect of insulin/exendin-4 was not detectable in the presence of the GLP-1 receptor (GLP-1R) antagonist exendin (9–39) and attenuated in response to pharmacological inhibition of exchange protein activated by cAMP (Epac) signaling, while protein kinase A inhibition had no significant effect. Insulin/exendin-4 also significantly stimulate acute and long-term GLP-1 secretion in the presence of glucose, suggesting novel beneficial effects of insulin signaling and GLP-1R activation on glycemia through enhanced mass of GLP-1-producing cells and enhanced GLP-1 secretion. In addition, the effects of insulin indicate that not only is GLP-1 important for insulin secretion but altered insulin signaling may contribute to an altered GLP-1 secretion.
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- Khatri, C, et al.
(författare)
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Outcomes after perioperative SARS-CoV-2 infection in patients with proximal femoral fractures: an international cohort study
- 2021
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:11, s. e050830-
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Tidskriftsartikel (refereegranskat)abstract
- Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.SettingProspective, international, multicentre, observational cohort study.ParticipantsPatients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.ResultsThis study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p<0.001), age >80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).ConclusionsPatients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration numberNCT04323644
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- Schoch, CL, et al.
(författare)
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Nuclear ribosomal internal transcribed spacer (ITS) region as a universal DNA barcode marker for Fungi
- 2012
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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. - 1091-6490. ; 109:16, s. 6241-6246
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Tidskriftsartikel (refereegranskat)abstract
- Six DNA regions were evaluated as potential DNA barcodes for Fungi, the second largest kingdom of eukaryotic life, by a multinational, multilaboratory consortium. The region of the mitochondrial cytochrome c oxidase subunit 1 used as the animal barcode was excluded as a potential marker, because it is difficult to amplify in fungi, often includes large introns, and can be insufficiently variable. Three subunits from the nuclear ribosomal RNA cistron were compared together with regions of three representative protein-coding genes (largest subunit of RNA polymerase II, second largest subunit of RNA polymerase II, and minichromosome maintenance protein). Although the protein-coding gene regions often had a higher percent of correct identification compared with ribosomal markers, low PCR amplification and sequencing success eliminated them as candidates for a universal fungal barcode. Among the regions of the ribosomal cistron, the internal transcribed spacer (ITS) region has the highest probability of successful identification for the broadest range of fungi, with the most clearly defined barcode gap between inter- and intraspecific variation. The nuclear ribosomal large subunit, a popular phylogenetic marker in certain groups, had superior species resolution in some taxonomic groups, such as the early diverging lineages and the ascomycete yeasts, but was otherwise slightly inferior to the ITS. The nuclear ribosomal small subunit has poor species-level resolution in fungi. ITS will be formally proposed for adoption as the primary fungal barcode marker to the Consortium for the Barcode of Life, with the possibility that supplementary barcodes may be developed for particular narrowly circumscribed taxonomic groups.
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| 29. |
- Bravo, L, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 30. |
- Tabiri, S, et al.
(författare)
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- 2021
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swepub:Mat__t
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