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| 4. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 5. |
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| 6. |
- Abolhassani, H, et al.
(författare)
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Care of patients with inborn errors of immunity in thirty J Project countries between 2004 and 2021
- 2022
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Ingår i: Frontiers in immunology. - : Frontiers Media SA. - 1664-3224. ; 13, s. 1032358-
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Tidskriftsartikel (refereegranskat)abstract
- The J Project (JP) physician education and clinical research collaboration program was started in 2004 and includes by now 32 countries mostly in Eastern and Central Europe (ECE). Until the end of 2021, 344 inborn errors of immunity (IEI)-focused meetings were organized by the JP to raise awareness and facilitate the diagnosis and treatment of patients with IEI.ResultsIn this study, meeting profiles and major diagnostic and treatment parameters were studied. JP center leaders reported patients’ data from 30 countries representing a total population of 506 567 565. Two countries reported patients from JP centers (Konya, Turkey and Cairo University, Egypt). Diagnostic criteria were based on the 2020 update of classification by the IUIS Expert Committee on IEI. The number of JP meetings increased from 6 per year in 2004 and 2005 to 44 and 63 in 2020 and 2021, respectively. The cumulative number of meetings per country varied from 1 to 59 in various countries reflecting partly but not entirely the population of the respective countries. Altogether, 24,879 patients were reported giving an average prevalence of 4.9. Most of the patients had predominantly antibody deficiency (46,32%) followed by patients with combined immunodeficiencies (14.3%). The percentages of patients with bone marrow failure and phenocopies of IEI were less than 1 each. The number of patients was remarkably higher that those reported to the ESID Registry in 13 countries. Immunoglobulin (IgG) substitution was provided to 7,572 patients (5,693 intravenously) and 1,480 patients received hematopoietic stem cell therapy (HSCT). Searching for basic diagnostic parameters revealed the availability of immunochemistry and flow cytometry in 27 and 28 countries, respectively, and targeted gene sequencing and new generation sequencing was available in 21 and 18 countries. The number of IEI centers and experts in the field were 260 and 690, respectively. We found high correlation between the number of IEI centers and patients treated with intravenous IgG (IVIG) (correlation coefficient, cc, 0,916) and with those who were treated with HSCT (cc, 0,905). Similar correlation was found when the number of experts was compared with those treated with HSCT. However, the number of patients treated with subcutaneous Ig (SCIG) only slightly correlated with the number of experts (cc, 0,489) and no correlation was found between the number of centers and patients on SCIG (cc, 0,174).Conclusions1) this is the first study describing major diagnostic and treatment parameters of IEI care in countries of the JP; 2) the data suggest that the JP had tremendous impact on the development of IEI care in ECE; 3) our data help to define major future targets of JP activity in various countries; 4) we suggest that the number of IEI centers and IEI experts closely correlate to the most important treatment parameters; 5) we propose that specialist education among medical professionals plays pivotal role in increasing levels of diagnostics and adequate care of this vulnerable and still highly neglected patient population; 6) this study also provides the basis for further analysis of more specific aspects of IEI care including genetic diagnostics, disease specific prevalence, newborn screening and professional collaboration in JP countries.
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| 9. |
- Farkas, I., et al.
(författare)
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Rates and mechanisms of water exchange of UO22+(aq) and UO2(oxalate)F(H2O)(2)(-) : A variable-temperature O-17 and F-19 NMR study
- 2000
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Ingår i: Inorganic Chemistry. - : American Chemical Society (ACS). - 0020-1669 .- 1520-510X. ; 39:4, s. 799-805
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Tidskriftsartikel (refereegranskat)abstract
- This study consists of two parts: The first part comprised an experimental determination of the kinetic parameters for the exchange of water between UO2(H2O)(5)(2+) and bulk water, including an ab initio study at the SCF and MP2 levels of the geometry of UO2(H2O)(5)(2+), UO2(H2O)(4)(2+), and UO2(H2O)(6)(2+) and the thermodynamics of their reactions with water. In the second part we made an experimental study of the rate of water exchange in uranyl complexes and investigated how this might depend on inter- and intramolecular hydrogen bond interactions. The experimental studies, made by using O-17 NMR, with Tb3+ as a chemical shift reagent, gave the following kinetic parameters at 25 degrees C: k(ex) = (1.30 +/- 0.05) x 10(6) s(-1); Delta H double dagger = 26.(1) +/- 1.(4) kJ/mol; Delta S double dagger = -40 +/- 5 J/(K mol). Additional mechanistic indicators were obtained from the known coordination geometry of U(VI) complexes with unidentate ligands and from the theoretical calculations. A survey of the literature shows that there are no known isolated complexes of UO22+ with unidentate ligands which have a coordination number larger than 5. This was corroborated by quantum chemical calculations which showed that the energy gains by binding an additional water to UO2(H2O)(4)(2+) and UO2(H2O)(5)(2+) are 29.8 and -2.4 kcal/mol, respectively. A comparison of the change in Delta U for the reactions UO2(H2O)(5)(2+) --> UO2(H2O)(4)(2+) + H2O and UO2(H2O)(5)(2+) + H2O --> UO2(H2O)(6)(2+) indicates that the thermodynamics favors the second (associative) reaction in gas phase at 0 K, while the thermodynamics of water transfer between the first and second coordination spheres, UO2(H2O)(5)(2+) --> UO2(H2O)(4)(H2O)(2+) and UO2(H2O)(5)(H2O)(2+) --> UO2(H2O)(6)(2+), favors the first (dissociative) reaction. The energy difference between the associative and dissociative reactions is small, and solvation has to be included in ab initio models in order to allow quantitative comparisons between experimental data and theory. Theoretical calculations of the activation energy were not possible because of the excessive computing time required. On the basis of theoretical and experimental studies, we suggest that the water exchange in UO2(H2O)(5)(2+) follows a dissociative interchange mechanism. The rates of exchange of water in UO2(oxalate)F(H2O)(2-) (and UO2(oxalate)F-2(H2O)(2-) studied previously) are much slower than in the aquation, k(ex) = 1.6 x 10(4) s(-1), an effect which we assign to hydrogen bonding involving coordinated water and fluoride. The kinetic parameters for the exchange of water in UO2(H2O)(5)(2+) and quenching of photo excited *UO2(H2O)(5)(2+) are very near the same, indicating similar mechanisms.
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| 10. |
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| 11. |
- Farkas, I., et al.
(författare)
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Crystal structure of the sodium salt of the uranyl-oxyacetate-fluoride dimer, Na4(UO2)2(OCH2COO)2F 4 · 6H2O
- 1999
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Ingår i: Acta Chemica Scandinavica. - : Danish Chemical Society. - 0904-213X .- 1902-3103. ; 53:11, s. 1009-1012
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Tidskriftsartikel (refereegranskat)abstract
- The structure of the ternary uranyl-oxyacetate-fluoride dimer, (UO2)2(OCH2COO)2F4 4-, was studied by single crystal X-ray diffraction. The space group is P1̄, and the structure contains discrete dimers with a double pentagonal bipyramid geometry, linked by octahedrally coordinated sodium ions. The uranyl ion has a coordination number of five with two fluorides and three oxygens coordinated in a plane perpendicular to the linear UO2 axis. The dimer is formed via bridging oxygen atoms from the deprotonated hydroxyl groups of the glycolate ligands.
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| 12. |
- Gerotziafas, GT, et al.
(författare)
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Guidance for the Management of Patients with Vascular Disease or Cardiovascular Risk Factors and COVID-19: Position Paper from VAS-European Independent Foundation in Angiology/Vascular Medicine
- 2020
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Ingår i: Thrombosis and haemostasis. - : Georg Thieme Verlag KG. - 2567-689X .- 0340-6245. ; 120:12, s. 1597-1628
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Tidskriftsartikel (refereegranskat)abstract
- COVID-19 is also manifested with hypercoagulability, pulmonary intravascular coagulation, microangiopathy, and venous thromboembolism (VTE) or arterial thrombosis. Predisposing risk factors to severe COVID-19 are male sex, underlying cardiovascular disease, or cardiovascular risk factors including noncontrolled diabetes mellitus or arterial hypertension, obesity, and advanced age. The VAS-European Independent Foundation in Angiology/Vascular Medicine draws attention to patients with vascular disease (VD) and presents an integral strategy for the management of patients with VD or cardiovascular risk factors (VD-CVR) and COVID-19. VAS recommends (1) a COVID-19-oriented primary health care network for patients with VD-CVR for identification of patients with VD-CVR in the community and patients' education for disease symptoms, use of eHealth technology, adherence to the antithrombotic and vascular regulating treatments, and (2) close medical follow-up for efficacious control of VD progression and prompt application of physical and social distancing measures in case of new epidemic waves. For patients with VD-CVR who receive home treatment for COVID-19, VAS recommends assessment for (1) disease worsening risk and prioritized hospitalization of those at high risk and (2) VTE risk assessment and thromboprophylaxis with rivaroxaban, betrixaban, or low-molecular-weight heparin (LMWH) for those at high risk. For hospitalized patients with VD-CVR and COVID-19, VAS recommends (1) routine thromboprophylaxis with weight-adjusted intermediate doses of LMWH (unless contraindication); (2) LMWH as the drug of choice over unfractionated heparin or direct oral anticoagulants for the treatment of VTE or hypercoagulability; (3) careful evaluation of the risk for disease worsening and prompt application of targeted antiviral or convalescence treatments; (4) monitoring of D-dimer for optimization of the antithrombotic treatment; and (5) evaluation of the risk of VTE before hospital discharge using the IMPROVE-D-dimer score and prolonged post-discharge thromboprophylaxis with rivaroxaban, betrixaban, or LMWH.
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| 13. |
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| 14. |
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| 15. |
- Toraishi, T., et al.
(författare)
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Complexation of Th(IV) and various lanthanides(III) by glycolic acid; potentiometric, C-13-NMR and EXAFS studies
- 2002
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Ingår i: Journal of the Chemical Society. Dalton Transactions. - : Royal Society of Chemistry (RSC). - 1472-7773 .- 1364-5447. ; :20, s. 3805-3812
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Tidskriftsartikel (refereegranskat)abstract
- The complex formation of tetravalent thorium and various trivalent lanthanides by glycolate HOCH2CO2- = A(-), has been investigated by potentiometry, C-13-NMR spectroscopy and EXAFS. The potentiometric data were used to deduce the stoichiometry and equilibrium constants for the reactions pM(n+) (aq) + rA(-) reversible arrow M(p)H(-q)A(r)(np - q - r) + qH(+) at 25 degreesC, in an ionic medium with a constant concentration of Na+ equal to 3.00 M. Mononuclear complexes Th(HOCH2CO2-)(n); n = 1-4, were identified in the -log[H+] range 2.5-4.5. The equilibrium constants of these complexes obtained using a least-squares analysis of the experimental data agree well with previously published information; these test solutions also contain dinuclear ternary complexes Th(2)H(-2)A(r), r = 2, 4 and 6. The complex formation in the pH range 5-10 was studied at high and constant concentrations of glycolate, 0.50, 0.75 and 1.0 M, respectively. Under these conditions, in addition to the dinuclear species, also tetranuclear complexes M(4)H(-q)A(8) are formed, where q varies from 6 to 13 and 6 to 8 for the Th(IV) and Ln(III) systems, respectively. C-13 NMR spectra show that coordinated and free glycolate are in fast exchange at pH 4.5, while at higher pH there are two separate narrow peaks both in the CH2 and CO2- regions for the coordinated ligand, indicating slow exchange between two equally populated sites. The peak integrals correspond to two bonded ligands per metal for both Th(IV) and Ln(III). EXAFS data were used to deduce bond distances within the tetranuclear Th complexes. These data together with the NMR-data indicate that the tetranuclear complexes have a cubane-like core M-4 (OCH2CO2)(4) to which additional glycolate, oxyacetate and hydroxide ligands are coordinated. The identification of new structure and bonding characteristics of alpha-hydroxycarboxylates, in particular at higher pH, may be used to explore new separation schemes between actinides in different oxidation states, but also for group separations between lanthanide(III) and actinide(III) ions.
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| 16. |
- Veer, IM, et al.
(författare)
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Psycho-social factors associated with mental resilience in the Corona lockdown
- 2021
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Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 11:1, s. 67-
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Tidskriftsartikel (refereegranskat)abstract
- The SARS-CoV-2 pandemic is not only a threat to physical health but is also having severe impacts on mental health. Although increases in stress-related symptomatology and other adverse psycho-social outcomes, as well as their most important risk factors have been described, hardly anything is known about potential protective factors. Resilience refers to the maintenance of mental health despite adversity. To gain mechanistic insights about the relationship between described psycho-social resilience factors and resilience specifically in the current crisis, we assessed resilience factors, exposure to Corona crisis-specific and general stressors, as well as internalizing symptoms in a cross-sectional online survey conducted in 24 languages during the most intense phase of the lockdown in Europe (22 March to 19 April) in a convenience sample of N = 15,970 adults. Resilience, as an outcome, was conceptualized as good mental health despite stressor exposure and measured as the inverse residual between actual and predicted symptom total score. Preregistered hypotheses (osf.io/r6btn) were tested with multiple regression models and mediation analyses. Results confirmed our primary hypothesis that positive appraisal style (PAS) is positively associated with resilience (p < 0.0001). The resilience factor PAS also partly mediated the positive association between perceived social support and resilience, and its association with resilience was in turn partly mediated by the ability to easily recover from stress (both p < 0.0001). In comparison with other resilience factors, good stress response recovery and positive appraisal specifically of the consequences of the Corona crisis were the strongest factors. Preregistered exploratory subgroup analyses (osf.io/thka9) showed that all tested resilience factors generalize across major socio-demographic categories. This research identifies modifiable protective factors that can be targeted by public mental health efforts in this and in future pandemics.
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| 17. |
- Alvarez-Crespo, Mayte, 1980, et al.
(författare)
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The Amygdala as a Neurobiological Target for Ghrelin in Rats: Neuroanatomical, Electrophysiological and Behavioral Evidence
- 2012
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 7:10
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Tidskriftsartikel (refereegranskat)abstract
- Here, we sought to demonstrate that the orexigenic circulating hormone, ghrelin, is able to exert neurobiological effects (including those linked to feeding control) at the level of the amygdala, involving neuroanatomical, electrophysiological and behavioural studies. We found that ghrelin receptors (GHS-R) are densely expressed in several subnuclei of the amygdala, notably in ventrolateral (LaVL) and ventromedial (LaVM) parts of the lateral amygdaloid nucleus. Using whole-cell patch clamp electrophysiology to record from cells in the lateral amygdaloid nucleus, we found that ghrelin reduced the frequency of mEPSCs recorded from large pyramidal-like neurons, an effect that could be blocked by co-application of a ghrelin receptor antagonist. In ad libitum fed rats, intra-amygdala administration of ghrelin produced a large orexigenic response that lasted throughout the 4 hr of testing. Conversely, in hungry, fasted rats ghrelin receptor blockade in the amygdala significantly reduced food intake. Finally, we investigated a possible interaction between ghrelin's effects on feeding control and emotional reactivity exerted at the level of the amygdala. In rats allowed to feed during a 1-hour period between ghrelin injection and anxiety testing (elevated plus maze and open field), intra-amygdala ghrelin had no effect on anxiety-like behavior. By contrast, if the rats were not given access to food during this 1-hour period, a decrease in anxiety-like behavior was observed in both tests. Collectively, these data indicate that the amygdala is a valid target brain area for ghrelin where its neurobiological effects are important for food intake and for the suppression of emotional (anxiety-like) behaviors if food is not available.
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| 18. |
- Bake, Tina, et al.
(författare)
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Ghrelin Receptor Stimulation of the Lateral Parabrachial Nucleus in Rats Increases Food Intake but not Food Motivation
- 2020
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Ingår i: Obesity. - : Wiley. - 1930-7381 .- 1930-739X. ; 28:8, s. 1503-1511
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Tidskriftsartikel (refereegranskat)abstract
- Objective The lateral parabrachial nucleus (lPBN) in the brainstem has emerged as a key area involved in feeding control that is targeted by several circulating anorexigenic hormones. Here, the objective was to determine whether the lPBN is also a relevant site for the orexigenic hormone ghrelin, inspired by studies in mice and rats showing that there is an abundance of ghrelin receptors in this area. Methods This study first explored whether iPBN cells respond to ghrelin involving Fos mapping and electrophysiological studies in rats. Next, rats were injected acutely with ghrelin, a ghrelin receptor antagonist, or vehicle into the lPBN to investigate feeding-linked behaviors. Results Curiously, ghrelin injection (intracerebroventricular or intravenous) increased Fos protein expression in the lPBN yet the predominant electrophysiological response was inhibitory. Intra-lPBN ghrelin injection increased chow or high-fat diet intake, whereas the antagonist decreased chow intake only. In a choice paradigm, intra-lPBN ghrelin increased intake of chow but not lard or sucrose. Intra-lPBN ghrelin did not alter progressive ratio lever pressing for sucrose or conditioned place preference for chocolate. Conclusions The lPBN is a novel locus from which ghrelin can alter consummatory behaviors (food intake and choice) but not appetitive behaviors (food reward and motivation).
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| 19. |
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| 20. |
- Charitakis, Emmanouil, et al.
(författare)
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Risk and protective factors for atrial fibrillation after cardiac surgery and valvular interventions : an umbrella review of meta-analyses
- 2022
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Ingår i: Open heart. - : BMJ Publishing Group. - 2053-3624. ; 9:2
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Forskningsöversikt (refereegranskat)abstract
- Objective Postoperative atrial fibrillation (POAF) is a common complication affecting approximately one-third of patients after cardiac surgery and valvular interventions. This umbrella review systematically appraises the epidemiological credibility of published meta-analyses of both observational and randomised controlled trials (RCT) to assess the risk and protective factors of POAF. Methods Three databases were searched up to June 2021. According to established criteria, evidence of association was rated as convincing, highly suggestive, suggestive, weak or not significant concerning observational studies and as high, moderate, low or very low regarding RCTs. Results We identified 47 studies (reporting 61 associations), 13 referring to observational studies and 34 to RCTs. Only the transfemoral transcatheter aortic valve replacement (TAVR) approach was associated with the prevention of POAF and was supported by convincing evidence from meta-analyses of observational data. Two other associations provided highly suggestive evidence, including preoperative hypertension and neutrophil/lymphocyte ratio. Three associations between protective factors and POAF presented a high level of evidence in meta-analyses, including RCTs. These associations included atrial and biatrial pacing and performing a posterior pericardiotomy. Nineteen associations were supported by moderate evidence, including use of drugs such as amiodarone, b-blockers, glucocorticoids and statins and the performance of TAVR compared with surgical aortic valve replacement. Conclusions Our study provides evidence confirming the protective role of amiodarone, b-blockers, atrial pacing and posterior pericardiotomy against POAF as well as highlights the risk of untreated hypertension. Further research is needed to assess the potential role of statins, glucocorticoids and colchicine in the prevention of POAF.
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| 21. |
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| 22. |
- Cicardi, M., et al.
(författare)
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Icatibant, a New Bradykinin-Receptor Antagonist, in Hereditary Angioedema
- 2010
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Ingår i: New England Journal of Medicine. - 0028-4793. ; 363:6, s. 532-541
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Hereditary angioedema is characterized by recurrent attacks of angioedema of the skin, larynx, and gastrointestinal tract. Bradykinin is the key mediator of symptoms. Icatibant is a selective bradykinin B2 receptor antagonist. METHODS In two double-blind, randomized, multicenter trials, we evaluated the effect of icatibant in patients with hereditary angioedema presenting with cutaneous or abdominal attacks. In the For Angioedema Subcutaneous Treatment (FAST) 1 trial, patients received either icatibant or placebo; in FAST-2, patients received either icatibant or oral tranexamic acid, at a dose of 3 g daily for 2 days. Icatibant was given once, subcutaneously, at a dose of 30 mg. The primary end point was the median time to clinically significant relief of symptoms. RESULTS A total of 56 and 74 patients underwent randomization in the FAST-1 and FAST-2 trials, respectively. The primary end point was reached in 2.5 hours with icatibant versus 4.6 hours with placebo in the FAST-1 trial (P=0.14) and in 2.0 hours with icatibant versus 12.0 hours with tranexamic acid in the FAST-2 trial (P<0.001). In the FAST-1 study, 3 recipients of icatibant and 13 recipients of placebo needed treatment with rescue medication. The median time to first improvement of symptoms, as assessed by patients and by investigators, was significantly shorter with icatibant in both trials. No icatibant-related serious adverse events were reported. CONCLUSIONS In patients with hereditary angioedema having acute attacks, we found a significant benefit of icatibant as compared with tranexamic acid in one trial and a nonsignificant benefit of icatibant as compared with placebo in the other trial with regard to the primary end point. The early use of rescue medication may have obscured the benefit of icatibant in the placebo trial. (Funded by Jerini; ClinicalTrials.gov numbers, NCT00097695 and NCT00500656.)
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| 23. |
- Dagnegård, H.H., et al.
(författare)
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Survival after aortic root replacement with a stentless xenograft is determined by patient characteristics
- 2022
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Ingår i: Journal of Thoracic and Cardiovascular Surgery. - : Mosby Inc.; Elsevier Inc.. - 0022-5223 .- 1097-685X. ; 164:6, s. 1712-1724
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Our objective was to examine intermediate-term survival and reinterventions in unselected patients, stratified according to indication, who received a Freestyle (Medtronic Inc, Minneapolis, Minn) bioprosthesis as a full aortic root replacement. Methods: Data from medical records were retrospectively collected for patients who had aortic root replacement using Freestyle bioprostheses between 1999 and 2018 at 6 North-Atlantic centers. Survival status was extracted from national registries and results stratified according to indication for surgery. Results: We included 1030 implantations in 1008 patients with elective indications for surgery: aneurysm (39.8%), small root (8.3%), and other (13.8%), and urgent/emergent indications: endocarditis (26.7%) and Stanford type A aortic dissection (11.4%). Across indications, 46.3% were nonelective cases and 34.0% were reoperations. Median age was 66.0 (interquartile range, 58.0-71.8) years and median follow-up was 5.0 (interquartile range, 2.6-7.9) years. Thirty-day mortality varied from 2.9% to 27.4% depending on indication. Intermediate survival for 90-day survivors with elective indications were not different from the general population standardized for age and sex (P = .95, 83, and .16 for aneurysms, small roots, and other, respectively). In contrast, patients with endocarditis and type A dissection had excess mortality (P < .001). Freedom from valve reinterventions was 95.0% and 94.4% at 5 and 8 years, respectively. In all, 52 patients (5.2%) underwent reinterventions, most because of endocarditis. Conclusions: At intermediate term follow-up this retrospective study provides further support for the use of the Freestyle bioprosthesis in the real-world setting of diverse, complex, and often high-risk aortic root replacement and suggests that outcome is determined by patient and disease, rather than by prosthesis, characteristics. © 2021 The Authors
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| 24. |
- Dellino, Gaetano I, et al.
(författare)
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Polycomb silencing blocks transcription initiation.
- 2004
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Ingår i: Molecular Cell. - 1097-2765 .- 1097-4164. ; 13:6, s. 887-93
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Tidskriftsartikel (refereegranskat)abstract
- Polycomb (PcG) complexes maintain the silent state of target genes. The mechanism of silencing is not known but has been inferred to involve chromatin packaging to block the access of transcription factors. We have studied the effect of PcG silencing on the hsp26 heat shock promoter. While silencing does decrease the accessibility of some restriction enzyme sites to some extent, it does not prevent the binding of TBP, RNA polymerase, or the heat shock factor to the hsp26 promoter, as shown by chromatin immunoprecipitation. However, we find that in the repressed state, the RNA polymerase cannot initiate transcription. We conclude that, rather than altering chromatin structure to block accessibility, PcG silencing in this construct targets directly the activity of the transcriptional machinery at the promoter.
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| 25. |
- Díaz-Ramos, L. Aranzazú, et al.
(författare)
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Difference in the action spectra for UVR8 monomerisation and HY5 transcript accumulation in Arabidopsis
- 2018
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Ingår i: Photochemical and Photobiological Sciences. - : Royal Society of Chemistry. - 1474-905X .- 1474-9092. ; 17:8, s. 1108-1117
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Tidskriftsartikel (refereegranskat)abstract
- The photoreceptor UV RESISTANCE LOCUS 8 (UVR8) activates photomorphogenic responses when plants are exposed to ultraviolet-B (UVB) light. However, whereas the absorption spectrum of UVR8 peaks at 280 nm, action spectra for several photomorphogenic UV-B responses show maximal photon effectiveness at 290-300 nm. To investigate this apparent discrepancy we measured the effectiveness of UV wavelengths in initiating two responses in Arabidopsis: photoconversion of homodimeric UVR8 into the monomeric form, which is active in signaling, and accumulation of transcripts of the ELONGATED HYPOCOTYL 5 (HY5) transcription factor, which has a key role in UVR8-mediated responses. When purified UVR8 or Arabidopsis leaf extracts were exposed to UV light monomerisation was maximal at approximately 280 nm, which correlates with the UVR8 absorption spectrum. When intact plants were exposed to UV, monomerisation was most strongly initiated at approximately 290 nm, and this shift in maximal effectiveness could be explained by strong absorption or reflectance at 280 nm by leaf tissue. Notably, the action spectrum for accumulation of HY5 transcripts in the same leaf tissue samples used to assay UVR8 dimer/monomer status peaked at approximately 300 nm. Possible reasons for the difference in maximal photon effectiveness of UVR8 monomerisation and HY5 transcript accumulation in leaf tissue are discussed.
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| 26. |
- Estrada-Peña, A., et al.
(författare)
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Association of environmental traits with the geographic ranges of ticks (Acari Ixodidae) of medical and veterinary importance in the western Palearctic : a digital data set
- 2013
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Ingår i: Experimental & applied acarology. - : Springer Science and Business Media LLC. - 0168-8162 .- 1572-9702. ; 59:3, s. 351-366
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Tidskriftsartikel (refereegranskat)abstract
- We compiled information on the distribution of ticks in the western Palearctic (11°W, 45°E; 29°N, 71°N), published during 1970-2010. The literature search was filtered by the tick's species name and an unambiguous reference to the point of capture. Records from some curated collections were included. We focused on tick species of importance to human and animal health, in particular: Ixodes ricinus, Dermacentor marginatus, D. reticulatus, Haemaphysalis punctata, H. sulcata, Hyalomma marginatum, Hy. lusitanicum, Rhipicephalus annulatus, R. bursa, and the R. sanguineus group. A few records of other species (I. canisuga, I. hexagonus, Hy. impeltatum, Hy. anatolicum, Hy. excavatum, Hy. scupense) were also included. A total of 10,280 records was included in the data set. Almost 42 % of published references are not adequately referenced (and not included in the data set), host is reported for only 61 % of records and a reference to time of collection is missed for 84 % of published records. Ixodes ricinus accounted for 44.3 % of total records, with H. marginatum and D. marginatus accounting for 7.1 and 8.1 % of records, respectively. The lack of homogeneity of the references and potential pitfalls in the compilation were addressed to create a digital data set of the records of the ticks. We attached to every record a coherent set of quantitative descriptors for the site of reporting, namely gridded interpolated monthly climate and remotely sensed data on vegetation (NDVI). We also attached categorical descriptors of the habitat: a standard classification of land biomes and an ad hoc classification of the target territory from remotely sensed temperature and NDVI data. A descriptive analysis of the data revealed that a principal components reduction of the environmental (temperature and NDVI) variables described the distribution of the species in the target territory. However, categorical descriptors of the habitat were less effective. We stressed the importance of building reliable collections of ticks with specific references as to collection point, host and date of capture. The data set is freely downloadable.
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| 29. |
- Rai, Neha, et al.
(författare)
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The photoreceptor UVR8 mediates the perception of both UV-B and UV-A wavelengths up to 350 nm of sunlight with responsivity moderated by cryptochromes
- 2020
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Ingår i: Plant, Cell and Environment. - : John Wiley & Sons. - 0140-7791 .- 1365-3040. ; 43:6, s. 1513-1527
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Tidskriftsartikel (refereegranskat)abstract
- The photoreceptors UV RESISTANCE LOCUS 8 (UVR8) and CRYPTOCHROMES 1 and 2 (CRYs) play major roles in the perception of UV-B (280–315 nm) and UV-A/blue radiation (315–500 nm), respectively. However, it is poorly understood how they function in sunlight. The roles of UVR8 and CRYs were assessed in a factorial experiment with Arabidopsis thaliana wild-type and photoreceptor mutants exposed to sunlight for 6 h or 12 h under five types of filters with cut-offs in UV and blue-light regions. Transcriptome-wide responses triggered by UV-B and UV-A wavelengths shorter than 350 nm (UV-Asw) required UVR8 whereas those induced by blue and UV-A wavelengths longer than 350 nm (UV-Alw) required CRYs. UVR8 modulated gene expression in response to blue light while lack of CRYs drastically enhanced gene expression in response to UV-B and UV-Asw. These results agree with our estimates of photons absorbed by these photoreceptors in sunlight and with in vitro monomerization of UVR8 by wavelengths up to 335 nm. Motif enrichment analysis predicted complex signaling downstream of UVR8 and CRYs. Our results highlight that it is important to use UV waveband definitions specific to plants’ photomorphogenesis as is routinely done in the visible region.
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| 30. |
- Richard, Jennifer E., et al.
(författare)
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GLP-1 Receptor Stimulation of the Lateral Parabrachial Nucleus Reduces Food Intake: Neuroanatomical, Electrophysiological, and Behavioral Evidence
- 2014
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Ingår i: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 155:11, s. 4356-4367
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Tidskriftsartikel (refereegranskat)abstract
- The parabrachial nucleus (PBN) is a key nucleus for the regulation of feeding behavior. Inhibitory inputs from the hypothalamus to the PBN play a crucial role in the normal maintenance of feeding behavior, because their loss leads to starvation. Viscerosensory stimuli result in neuronal activation of the PBN. However, the origin and neurochemical identity of the excitatory neuronal input to the PBN remain largely unexplored. Here, we hypothesize that hindbrain glucagon-like peptide 1 (GLP-1) neurons provide excitatory inputs to the PBN, activation of which may lead to a reduction in feeding behavior. Our data, obtained from mice expressing the yellow fluorescent protein in GLP-1-producing neurons, revealed that hindbrain GLP-1-producing neurons project to the lateral PBN (lPBN). Stimulation of lPBN GLP-1 receptors (GLP-1Rs) reduced the intake of chow and palatable food and decreased body weight in rats. It also activated lPBN neurons, reflected by an increase in the number of c-Fos-positive cells in this region. Further support for an excitatory role of GLP-1 in the PBN is provided by electrophysiological studies showing a remarkable increase in firing of lPBN neurons after Exendin-4 application. We show that within the PBN, GLP-1R activation increased gene expression of 2 energy balance regulating peptides, calcitonin gene-related peptide (CGRP) and IL-6. Moreover, nearly 70% of the lPBN GLP-1 fibers innervated lPBN CGRP neurons. Direct intra-lPBN CGRP application resulted in anorexia. Collectively, our molecular, anatomical, electrophysiological, pharmacological, and behavioral data provide evidence for a functional role of the GLP-1R for feeding control in the PBN.
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| 33. |
- Ul-Hassan, Jawad, et al.
(författare)
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Fast growth rate epitaxy on 4((degrees)under-bar) off-cut 4-inch diameter 4H-SiC wafers
- 2014
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Ingår i: SILICON CARBIDE AND RELATED MATERIALS 2013, PTS 1 AND 2. - : Trans Tech Publications. ; , s. 179-182
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Konferensbidrag (refereegranskat)abstract
- We report the development of over 100 mu m/h growth rate process on 4-inch diameter wafers using chlorinated growth. The optimized growth process has shown extremely smooth epilayers completely free of surface step-bunching with very low surface defect density, high uniformity in thickness and doping and high run to run reproducibility in growth rate, controlled doping and defect density.
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| 35. |
- Wagenaar-Bos, Ineke G. A., et al.
(författare)
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Functional C1-inhibitor diagnostics in hereditary angioedema: Assay evaluation and recommendations
- 2008
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Ingår i: Journal of Immunological Methods. - : Elsevier BV. - 1872-7905 .- 0022-1759. ; 338:1-2, s. 14-20
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Tidskriftsartikel (refereegranskat)abstract
- Hereditary angioedema (HAE) is an autosomal dominant disease characterized by recurrent episodes of potentially life-threatening angioedema. The most widespread underlying genetic deficiency is a heterozygous deficiency of the serine protease inhibitor Cl esterase inhibitor (C1-Inh). In addition to low C4 levels, the most important laboratory parameter for correct diagnosis of HAE or angioedema due to acquired C1-Inh deficiency is reduced C1-Inh function (fC1-Inh). No direct recommendations about the assays for fC1-Inh or sample handling conditions are available, although this would prove especially useful when a laboratory first starts to offer assays on fC1-Inh for HAE diagnosis. In the present study we evaluated the performance of fC1-Inh assays in the 15 different laboratories that are specialised in HAE diagnostics and assessed inter-laboratory variation with each laboratory using their own assays and standards. A double-blind survey was conducted using plasma/serum samples from healthy donors and HAE patients and the uniformity of HAE diagnosis was evaluated. It can be concluded that the diagnosis of fC1-Inh deficiency was made correctly inmost cases in this survey. We can recommend the chromogenic assay for the determination of fC1-Inh, while the complex ELISA needs further investigation. (C) 2008 Elsevier B.V. All rights reserved.
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