| 1. |
- Long, John A., et al.
(författare)
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Copulation in antiarch placoderms and the origin of gnathostome internal fertilization
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 517:7533, s. 196-199
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Tidskriftsartikel (refereegranskat)abstract
- Reproduction in jawed vertebrates (gnathostomes) involves either external or internal fertilization. It is commonly argued that internal fertilization can evolve from external, but not the reverse. Male copulatoryclaspers are present in certain placoderms, fossil jawed vertebrates retrieved as a paraphyletic segment of the gnathostome stem group in recent studies. This suggests that internal fertilization could be primitive for gnathostomes, but such a conclusion depends on demonstrating that copulation was not just a specialized feature of certain placoderm subgroups. The reproductive biology of antiarchs, consistently identified as the least crownward placoderms and thus of great interest in this context, has until now remained unknown. Here we show that certain antiarchs possessed dermal claspers in the males, while females bore paired dermal plates inferred to have facilitated copulation. These structures are not associated with pelvic fins. The clasper morphology resembles that of ptyctodonts, a more crownward placoderm group, suggesting that all placoderm claspers are homologous and that internal fertilization characterized all placoderms. This implies that external fertilization and spawning, which characterize most extant aquatic gnathostomes, must be derived from internal fertilization, even though this transformation has been thought implausible. Alternatively, the substantial morphological evidence for placoderm paraphyly must be rejected.
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| 2. |
- Agrawal, Vikas, et al.
(författare)
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The AAAI-13 Conference Workshops
- 2013
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Ingår i: The AI Magazine. - : Association for the Advancement of Artificial Intelligence. - 0738-4602 .- 2371-9621. ; 34:4, s. 108-115
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Tidskriftsartikel (refereegranskat)abstract
- The AAAI-13 Workshop Program, a part of the 27th AAAI Conference on Artificial Intelligence, was held Sunday and Monday, July 14-15, 2013, at the Hyatt Regency Bellevue Hotel in Bellevue, Washington, USA. The program included 12 workshops covering a wide range of topics in artificial intelligence, including Activity Context-Aware System Architectures (WS-13-05); Artificial Intelligence and Robotics Methods in Computational Biology (WS-13-06); Combining Constraint Solving with Mining and Learning (WS-13-07); Computer Poker and Imperfect Information (WS-13-08); Expanding the Boundaries of Health Informatics Using Artificial Intelligence (WS-13-09); Intelligent Robotic Systems (WS-13-10); Intelligent Techniques for Web Personalization and Recommendation (WS-13-11); Learning Rich Representations from Low-Level Sensors (WS-13-12); Plan, Activity,, and Intent Recognition (WS-13-13); Space, Time, and Ambient Intelligence (WS-13-14); Trading Agent Design and Analysis (WS-13-15); and Statistical Relational Artificial Intelligence (WS-13-16)
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| 3. |
- Bjurman, Christian, 1983, et al.
(författare)
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Decreased admissions and hospital costs with a neutral effect on mortality following lowering of the troponin T cutoff point to the 99th percentile
- 2017
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Ingår i: Cardiology journal. - 1897-5593 .- 1898-018X. ; 24:6, s. 612-622
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Tidskriftsartikel (refereegranskat)abstract
- Background: The implementation of high-sensitivity cardiac troponin T (hs-cTnT) assays and a cutoff based on the 99th cTnT percentile in the evaluation of patients with suspected acute coronary syndrome has not been uniform due to uncertain effects on health benefits and utilization of limited resources.Methods:Clinical and laboratory data from patients with chest pain or dyspnea at the emergency department (ED) were evaluated before (n = 20516) and after (n = 18485) the lowering of the hs-cTnT cutoff point from 40 ng/L to the 99th hs-cTnT percentile of 14 ng/L in February 2012. Myocardial infarction (MI) was diagnosed at the discretion of the attending clinicians responsible for the patient.Results:Following lowering of the hs-cTnT cutoff point fewer ED patients with chest pain or dyspnea as the principal complaint were analyzed with an hs-cTnT sample (81% vs. 72%, p < 0.001). Overall 30-day mortality was unaffected but increased among patients not analyzed with an hs-cTnT sample (5.3% vs. 7.6%, p < 0.001). The MI frequency was unchanged (4.0% vs. 3.9%, p = 0.72) whereas admission rates decreased (51% vs. 45%, p < 0.001) as well as hospital costs. Coronary angiographies were used more frequently (2.8% vs. 3.3%, p = 0.004) but with no corresponding change in coronary interventions.Conclusions:At the participating hospital, lowering of the hs-cTnT cutoff point to the 99th percentile decreased admissions and hospital costs but did not result in any apparent prognostic or treatment benefits for the patients.
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| 4. |
- Bjurman, Christian, 1983, et al.
(författare)
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Small changes in Troponin T levels are common in patients with non-ST-elevation myocardial infarction and are linked to higher mortality
- 2013
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 62:14, s. 1231-1238
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE:To examine the extent of change in Troponin T levels in patients with non-ST-elevation myocardial infarction (NSTEMI).BACKGROUND:Changes in cardiac troponin levels are required for the diagnosis of NSTEMI, according to the new universal definition of acute myocardial infarction. A relative change of 20-230 % and an absolute change of 7- 9 ng/L have been suggested as cut-off points.METHOD:In a clinical setting, where a change in cTnT was not mandatory for the diagnosis of NSTEMI, serial samples of cTnT were measured with a high-sensitive cTnT (hs-cTnT) assay, and 37 clinical parameters were evaluated in 1178 patients with a final diagnosis of NSTEMI presenting <24h after symptom onset.RESULTS:After six hours of observation, the relative change in the hs-cTnT level remained <20 % in 26 % and the absolute change <9 ng/L in 12 % of the NSTEMI patients. A relative hs-cTnT change <20% was linked to higher long-term mortality across quartiles (p=0.002) and in multivariate analyses (HR 1.61 (1.17-2.21) p=0.004), whereas 30-day mortality was similar across quartiles of relative hs-cTnT changeCONCLUSION:Because stable hs-TnT levels are common in patients with a clinical diagnosis of NSTEMI in our hospital, a small hs-cTnT change may not be useful to exclude NSTEMI, particularly as these patients show both short-term and long-term mortality at least as high as patients with large changes in hs-cTnT.
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| 5. |
- Docherty, Kieran F., et al.
(författare)
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Effect of Dapagliflozin on Outpatient Worsening of Patients With Heart Failure and Reduced Ejection Fraction : A Prespecified Analysis of DAPA- HF.
- 2020
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Ingår i: Circulation. ; 142:17, s. 1623-1632
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In the DAPA-HF trial (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure), dapagliflozin, added to guideline-recommended therapies, reduced the risk of mortality and heart failure (HF) hospitalization. We examined the frequency and significance of episodes of outpatient HF worsening, requiring the augmentation of oral therapy, and the effects of dapagliflozin on these additional events. METHODS: Patients in New York Heart Association functional class II to IV, with a left ventricular ejection fraction
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| 6. |
- Espeland, Marianne, 1981-
(författare)
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Diversification on an ancient Darwinian island : Evolutionary history of caddisflies (Trichoptera) and other organisms on New Caledonia
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Islands are either of continental or oceanic origin, and the biota of such islands are a result of vicariance and dispersal, respectively. New Caledonia, in the South Pacific, is a part of former Gondwana, but the origin of its biota is heavily debated. Geological studies show that the island was submerged in the Eocene, and that oceanic crust was obducted onto New Caledonia leaving a thick layer of ultramafic rocks on top of the island. We tested the null hypothesis that New Caledonian biota are a result of old Gondwanan vicariance by fitting diversification models on phylogenies from the literature and calculating the gamma statistic. According to the null hypothesis diversification is gradual over time. If on the other hand the biota are a result of recent dispersal or have survived in refugia we would expect slowing of diversification over time. Based on our results we can reject the null hypothesis of old vicariance for the New Caledonian biota. The caddisfly (Trichoptera) fauna on New Caledonia is exceptionally rich with around 600 species, and more than 99.9% are endemic. Molecular phylogenetic hypotheses for three monophyletic caddisfly radiations, Xanthochorema, Caledopsyche et al. and Agmina, are presented. Age estimates agrees with the geological evidence. Three new species of Xanthochorema are described and more than 63% of the Agmina species are new to science. The ultramafic rock substrate, with high heavy metal concentration, has led to high levels of plant adaptation on New Caledonia. We show that caddisflies adapted early to this substrate and subsequently dispersed to non-ultramafic substrate several times, with significantly fewer dispersal events back to the toxic substrate, indicating that adaptation to ultramafic substrate is required and recolonization is difficult when this adaptation has been lost. Ultramafic substrate and other environmental factors have been important in driving the diversification of New Caledonian caddisflies.
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| 7. |
- Florio, Marilina, et al.
(författare)
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Characterization of the Aquaporin-9 Inhibitor RG100204 In Vitro and in db/db Mice
- 2022
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Ingår i: Cells. - : MDPI AG. - 2073-4409. ; 11:19
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Tidskriftsartikel (refereegranskat)abstract
- Aquaporin-9 (AQP9) is a facilitator of glycerol and other small neutral solute transmembrane diffusion. Identification of specific inhibitors for aquaporin family proteins has been difficult, due to high sequence similarity between the 13 human isoforms, and due to the limited channel surface areas that permit inhibitor binding. The few AQP9 inhibitor molecules described to date were not suitable for in vivo experiments. We now describe the characterization of a new small molecule AQP9 inhibitor, RG100204 in cell-based calcein-quenching assays, and by stopped-flow light-scattering recordings of AQP9 permeability in proteoliposomes. Moreover, we investigated the effects of RG100204 on glycerol metabolism in mice. In cell-based assays, RG100204 blocked AQP9 water permeability and glycerol permeability with similar, high potency (~5 × 10 -8 M). AQP9 channel blocking by RG100204 was confirmed in proteoliposomes. After oral gavage of db/db mice with RG100204, a dose-dependent elevation of plasma glycerol was observed. A blood glucose-lowering effect was not statistically significant. These experiments establish RG100204 as a direct blocker of the AQP9 channel, and suggest its use as an experimental tool for in vivo experiments on AQP9 function.
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| 8. |
- Hammarsten, Ola, et al.
(författare)
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Troponin T percentiles from a random population sample, emergency room patients and patients with myocardial infarction
- 2012
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Ingår i: Clinical Chemistry. - : Oxford University Press (OUP). - 1530-8561 .- 0009-9147. ; 58:3, s. 628-637
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: High-sensitivity cardiac troponin T (cTnT) assays detect small clinically important myocardial infarctions (MI) but also yield higher rates of false-positive results owing to increased concentrations sometimes present in patients without MI. Better understanding is needed of factors influencing the 99th percentile of cTnT concentrations across populations and the frequency of changes in cTnT concentrations >20% often used in combination with increased cTnT concentrations for diagnosis of MI. METHODS: cTnT percentiles were determined by use of the Elecsys® hscTnT immunoassay (Modular® Analytics E170) in a random population sample, in emergency room (ER) patients, and in patients with non–ST-elevation MI (NSTEMI). Changes in cTnT concentrations were determined in hospitalized patients without MI. RESULTS: The 99th cTnT percentile in a random population sample (median age, 65 years) was 24 ng/L. In ER patients <65 years old without obvious conditions that increase cTnT, the 99th cTnT percentile was 12 ng/L with little age dependence, whereas in those >65 years old it was 82 ng/L and highly age dependent. In hospitalized patients without MI the 97.5th percentile for change in the cTnT concentration was 51%–67%. cTnT remained below the 99th percentile (12 ng/L) in 1% of patients with NSTEMI until 8.5 h after symptom onset and 6 h after ER arrival. CONCLUSIONS: Age >65 years was the dominant factor associated with increased cTnT in ER patients. This age association was more prominent in ER patients than in a random population sample. Changes in serial cTnT concentrations >20% were common in hospitalized patients without MI.
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| 9. |
- Jelen, Sabina, et al.
(författare)
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Aquaporin-9 Protein Is the Primary Route of Hepatocyte Glycerol Uptake for Glycerol Gluconeogenesis in Mice
- 2011
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 286:52, s. 44319-44325
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Tidskriftsartikel (refereegranskat)abstract
- It has been hypothesized that aquaporin-9 (AQP9) is part of the unknown route of hepatocyte glycerol uptake. In a previous study, leptin receptor-deficient wild-type mice became diabetic and suffered from fasting hyperglycemia whereas isogenic AQP9(-/-) knock-out mice remained normoglycemic. The reason for this improvement in AQP9(-/-) mice was not established before. Here, we show increased glucose output (by 123% +/- 36% S. E.) in primary hepatocyte culture when 0.5 mM extracellular glycerol was added. This increase depended on AQP9 because it was absent in AQP9(-/-) cells. Likewise, the increase was abolished by 25 mu M HTS13286 (IC(50) similar to 2 mu M), a novel AQP9 inhibitor, which we identified in a small molecule library screen. Similarly, AQP9 deletion or chemical inhibition eliminated glycerol-enhanced glucose output in perfused liver preparations. The following control experiments suggested inhibitor specificity to AQP9: (i) HTS13286 affected solute permeability in cell lines expressing AQP9, but not in cell lines expressing AQPs 3, 7, or 8. (ii) HTS13286 did not influence lactate-and pyruvate-dependent hepatocyte glucose output. (iii) HTS13286 did not affect glycerol kinase activity. Our experiments establish AQP9 as the primary route of hepatocyte glycerol uptake for gluconeogenesis and thereby explain the previously observed, alleviated diabetes in leptin receptor-deficient AQP9(-/-) mice.
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| 10. |
- Johanson, Ted, et al.
(författare)
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Strain engineering for stereoselective bioreduction of dicarbonyl compounds by yeast reductases
- 2005
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Ingår i: FEMS Yeast Research. - : Oxford University Press (OUP). - 1567-1364 .- 1567-1356. ; 5:6-7, s. 513-525
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Forskningsöversikt (refereegranskat)abstract
- Pure chiral molecules are needed in the pharmaceutical and chemical industry as intermediates for the production of drugs or fine chemicals. Microorganisms represent an attractive alternative to chemical synthesis since they have the potential to generate single stereoisomers in high enantiomeric excess (ee). The baker's yeast Saccharomyces cerevisiae can notably reduce dicarbonyl compounds (in particular alpha- and beta-diketones and keto esters) to chiral alcohols with high ee. However, products are formed at a low rate. Moreover, large amounts of co-substrate are required for the regeneration of NADPH that is the preferred co-factor in almost all the known dicarbonyl reductions. Traditionally, better ee, reduction rate and product titre have been achieved via process engineering. The advent of recombinant DNA technology provides an alternative strategy to improve productivity and yield by strain engineering. This review discusses two aspects of strain engineering: (i) the generation of strains with higher reductase activity towards dicarbonyl compounds and (ii) the optimisation of co-substrate utilisation for NADPH cofactor regeneration. (c) 2005 Federation of European Microbiological Societies. Published by Elsevier B.V. All rights reserved.
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