| 1. |
- Locke, Adam E, et al.
(författare)
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Genetic studies of body mass index yield new insights for obesity biology.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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| 2. |
- Ried, Janina S., et al.
(författare)
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A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways.
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| 3. |
- Shungin, Dmitry, et al.
(författare)
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New genetic loci link adipose and insulin biology to body fat distribution.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-378
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Tidskriftsartikel (refereegranskat)abstract
- Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
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| 4. |
- Andersson, Rolf G, et al.
(författare)
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Studies of the mechanism of desensitization of anti-IgE-mediated histamine release from human basophils
- 1989
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Ingår i: Agents and actions. - 0065-4299. ; 27:1-2, s. 25-28
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Tidskriftsartikel (refereegranskat)abstract
- Human basophils became hyporesponsive to anti-IgE when exposed to this agent in the absence of Ca2+ for more than 10 min. The desensitization process proceeded in parallel to the releasing-process. The mechanism of desensitization seems to involve a very early step in the release-reaction, since the response to phospholipase A2 and diolein, agents involved in the release-reaction, was not affected by the desensitization.
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| 5. |
- Johansson, Fredrik, et al.
(författare)
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Direct and amplifying effects of the ß-adrenoceptor antagonist propranolol on guinea pig airway contractility in vitro
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- In the present study we establish that the ß-AA antagonist propranolol can, besides its ß-AR blocking effect, either amplify or direct induce a contraction in guinea pig airway preparations, in vitro.Propranolol significantly enhanced the contractile response to ovalbumin (OA). The enhancement was reduced by capsaicin but insensitive to indomethacin pretreatment. These results suggest that propranolol produce airway hyperreactivity to OA by activating a pathway involving tachykinins and that COX-products are of minor significance.We also confirm that propranolol can induce a tracheal smooth muscle contraction directly, although pre-treatment with carbachol/formoterol is a prerequisite. Direct contractile responses were completely diminished by indomethacin and reduced by capsaicin and L-659,877 (a NK2-receptor antagonist) pre-treatment. The present study shows that propranolol also enhances NANC (excitatory non-adrenergic noncholinergic) contractions but this enhancement requires pre-treatment with a 13-agonist. When the pre-treatment was excluded propranolol failed to exert either a direct or an amplifying effect on EFS (electrical field stimulation). These results contrast to the recorded enhancement of the OA-induced response, which did not request any pre-treatment.In addition, propranolol induced an elevation of [Ca2+], in ASMC (airway smooth muscle cells), this effect was not dependent on any pre-treatment and inhibited by indomethacin treatment.The mechanism behind these adverse effects of propranolol is not known, but our results demonstrate that contractile mediators do not originate from the airway epithelium. Since, epithelium removal did not reduce the contractile response. Furthermore, pertussis toxin (PTX) treatment did not effect the propranolol-induced contraction, indicating that a PTX sensitive G-protein coupling pathway not is involved.In conclusion our results show that both indomethacin and capsaicin sensitive pathways are involved in the contractile response to propranolol. The relative significance of these systems differs; the direct contractile effect is strongly dependent on an indomethacin sensitive pathway, while the amplifying effect is sensitive to capsaicin and insensitive to indomethacin pre-treatment.Further studies are required to elucidate the clinical relevance of these results.
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| 6. |
- Onuţ-Brännström, Ioana, et al.
(författare)
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Sharing of photobionts in sympatric populations of Thamnolia and Cetraria lichens : evidence from high-throughput sequencing
- 2018
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- In this study, we explored the diversity of green algal symbionts (photobionts) in sympatric populations of the cosmopolitan lichen-forming fungi Thamnolia and Cetraria. We sequenced with both Sanger and Ion Torrent High-Throughput Sequencing technologies the photobiont ITS-region of 30 lichen thalli from two islands: Iceland and Öland. While Sanger recovered just one photobiont genotype from each thallus, the Ion Torrent data recovered 10–18 OTUs for each pool of 5 lichen thalli, suggesting that individual lichens can contain heterogeneous photobiont populations. Both methods showed evidence for photobiont sharing between Thamnolia and Cetraria on Iceland. In contrast, our data suggest that on Öland the two mycobionts associate with distinct photobiont communities, with few shared OTUs revealed by Ion Torrent sequencing. Furthermore, by comparing our sequences with public data, we identified closely related photobionts from geographically distant localities. Taken together, we suggest that the photobiont composition in Thamnolia and Cetraria results from both photobiont-mycobiont codispersal and local acquisition during mycobiont establishment and/or lichen growth. We hypothesize that this is a successful strategy for lichens to be flexible in the use of the most adapted photobiont for the environment.
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| 7. |
- Andersson, Martin G. I., et al.
(författare)
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Effects of sterilization on dissolved organic carbon (DOC) composition and bacterial utilization of DOC from lakes
- 2018
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Ingår i: Aquatic Microbial Ecology. - : Inter-Research Science Center. - 0948-3055 .- 1616-1564. ; 82:2, s. 199-208
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Tidskriftsartikel (refereegranskat)abstract
- Sterilization of dissolved organic carbon (DOC) is an essential step in research on interactions between DOC and organisms, for example where the effect of different microbial communities on DOC is studied or vice versa. However, few studies have gone beyond acknowledging that sterilization of DOC influences its characteristics. Here, we aimed to provide further knowledge that enables scientists to better tailor their sterilization methods to their research question. To meet this aim, we conducted a sterilization experiment with DOC from 4 boreal lakes treated with 4 sterilization methods, i.e. 2 filtrations (0.2 µm, 0.1 µm) and 2 autoclaving approaches (single and double autoclaving with a single pH adjustment). Quantity and spectroscopic properties of DOC, before and after sterilization, were studied, and DOC was further tested as a substrate for bacterial growth. We found that the filtration methods better preserved the different DOC measures. In contrast, autoclaving caused major inconsistent shifts in both qualitative and quantitative measures of DOC, as well as an increase of the maximum abundance of bacteria in growth experiments. Nonetheless, there remains a trade-off between retaining the quality of DOC and achieving sterile conditions. Therefore, the sterilization method of choice should be guided by the scientific question at hand.
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| 8. |
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| 9. |
- Grenegård, Magnus, et al.
(författare)
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The ATP-gated P2X1 receptor plays a pivotal role in activation of aspirin-treated platelets by thrombin and epinephrine
- 2008
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 283:27, s. 18493-18504
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Tidskriftsartikel (refereegranskat)abstract
- Human platelets express protease-activated receptor 1 (PAR1) and PAR4 but limited data indicate for differences in signal transduction. We studied the involvement of PAR1 and PAR4 in the cross-talk between thrombin and epinephrine. The results show that epinephrine acted via alpha(2A)-adrenergic receptors to provoke aggregation, secretion, and Ca(2+) mobilization in aspirin-treated platelets pre-stimulated with subthreshold concentrations of thrombin. Incubating platelets with antibodies against PAR4 or the PAR4-specific inhibitor pepducin P4pal-i1 abolished the aggregation. Furthermore, platelets pre-exposed to the PAR4-activating peptide AYPGKF, but not to the PAR1-activating peptide SFLLRN, were aggregated by epinephrine, whereas both AYPGKF and SFLLRN synergized with epinephrine in the absence of aspirin. The roles of released ATP and ADP were elucidated by using antagonists of the purinergic receptors P2X(1), P2Y(1), and P2Y(12) (i.e. NF449, MRS2159, MRS2179, and cangrelor). Intriguingly, ATP, but not ADP, was required for the epinephrine/thrombin-induced aggregation. In Western blot analysis, a low concentration of AYPGKF, but not SFLLRN, stimulated phosphorylation of Akt on serine 473. Moreover, the phosphatidyl inositide 3-kinase inhibitor LY294002 antagonized the effect of epinephrine combined with thrombin or AYPGKF. Thus, in aspirin-treated platelets, PAR4, but not PAR1, interacts synergistically with alpha(2A)-adrenergic receptors, and the PI3-kinase/Akt pathway is involved in this cross-talk. Furthermore, in PAR4-pretreated platelets, epinephrine caused dense granule secretion, and subsequent signaling from the ATP-gated P2X(1)-receptor and the alpha(2A)-adrenergic receptor induced aggregation. These results suggest a new mechanism that has ATP as a key element and circumvents the action of aspirin on epinephrine-facilitated PAR4-mediated platelet activation.
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| 10. |
- Howner, K., et al.
(författare)
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Mapping Systematic Reviews on Forensic Psychiatric Care: A Systematic Review Identifying Knowledge Gaps
- 2018
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Ingår i: Frontiers in Psychiatry. - : Frontiers Media SA. - 1664-0640. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Forensic psychiatric care treats mentally disordered offenders who suffer mainly from psychotic disorders, although comorbidities such as personality disorders, neurodevelopmental disorders, and substance abuse are common. A large proportion of these patients have committed violent crimes. Their care is involuntary, and their caregivers' mission is complex: not only to rehabilitate the patient, but also to consider their risk for reoffending and their risk to society. The objective of this overview of systematic reviews is to identify, appraise, and summarize the existing knowledge in forensic psychiatric care and identify knowledge gaps that require further research. Methods: We undertook a systematic literature search for systematic reviews in five defined domains considered important in daily clinical practice within the forensic psychiatric care: (1) diagnostic assessment and risk assessments; (2) pharmacological treatment; (3) psychological interventions; (4) psychosocial interventions, rehabilitation, and habilitation; and (5) restraint interventions. The target population was mentally disordered offenders (forensic psychiatric patients aged >15 years). Each abstract and full text review was assessed by two of the authors. Relevant reviews then were assessed for bias, and those with moderate or low risk of bias were included. Results: Of 38 systematic reviews meeting the inclusion criteria, only four had a moderate risk of bias. Two aimed to incorporate as many aspects of forensic psychiatric care as possible, one investigated non-pharmacological interventions to reduce aggression in forensic psychiatric care, and one focused on women with intellectual disabilities in forensic care. However, most of the primary studies included in these reviews had high risks of bias, and therefore, no conclusions could be drawn. All of our identified domains must be considered knowledge gaps. Conclusion: We could not answer any of our research questions within the five domains because of the high risk of bias in the primary studies in the included systematic reviews. There is an urgent need for more research on forensic psychiatric care since all of our studied domains were considered knowledge gaps.
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