| 1. |
|
|
| 2. |
- Hess, Timo, et al.
(författare)
-
Dissecting the genetic heterogeneity of gastric cancer
- 2023
-
Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 92
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Gastric cancer (GC) is clinically heterogenous according to location (cardia/non-cardia) and histopathology (diffuse/intestinal). We aimed to characterize the genetic risk architecture of GC according to its subtypes. Another aim was to examine whether cardia GC and oesophageal adenocarcinoma (OAC) and its precursor lesion Barrett's oesophagus (BO), which are all located at the gastro-oesophageal junction (GOJ), share polygenic risk architecture.Methods: We did a meta-analysis of ten European genome-wide association studies (GWAS) of GC and its subtypes. All patients had a histopathologically confirmed diagnosis of gastric adenocarcinoma. For the identification of risk genes among GWAS loci we did a transcriptome-wide association study (TWAS) and expression quantitative trait locus (eQTL) study from gastric corpus and antrum mucosa. To test whether cardia GC and OAC/BO share genetic aetiology we also used a European GWAS sample with OAC/BO.Findings: Our GWAS consisting of 5816 patients and 10,999 controls highlights the genetic heterogeneity of GC according to its subtypes. We newly identified two and replicated five GC risk loci, all of them with subtype-specific association. The gastric transcriptome data consisting of 361 corpus and 342 antrum mucosa samples revealed that an upregulated expression of MUC1, ANKRD50, PTGER4, and PSCA are plausible GC-pathomechanisms at four GWAS loci. At another risk locus, we found that the blood-group 0 exerts protective effects for non-cardia and diffuse GC, while blood-group A increases risk for both GC subtypes. Furthermore, our GWAS on cardia GC and OAC/BO (10,279 patients, 16,527 controls) showed that both cancer entities share genetic aetiology at the polygenic level and identified two new risk loci on the single-marker level.Interpretation: Our findings show that the pathophysiology of GC is genetically heterogenous according to location and histopathology. Moreover, our findings point to common molecular mechanisms underlying cardia GC and OAC/BO.
|
|
| 3. |
- Rydén, Lars, et al.
(författare)
-
ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD
- 2013
-
Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 34:39, s. 3035-3087
-
Tidskriftsartikel (refereegranskat)abstract
- This is the second iteration of the European Society of Cardiology (ESC) and European Association for the Study of Diabetes (EASD) joining forces to write guidelines on the management of diabetes mellitus (DM), pre-diabetes, and cardiovascular disease (CVD), designed to assist clinicians and other healthcare workers to make evidence-based management decisions. The growing awareness of the strong biological relationship between DM and CVD rightly prompted these two large organizations to collaborate to generate guidelines relevant to their joint interests, the first of which were published in 2007. Some assert that too many guidelines are being produced but, in this burgeoning field, five years in the development of both basic and clinical science is a long time and major trials have reported in this period, making it necessary to update the previous Guidelines.
|
|
| 4. |
- Schael, S., et al.
(författare)
-
Electroweak measurements in electron positron collisions at W-boson-pair energies at LEP
- 2013
-
Ingår i: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 532:4, s. 119-244
-
Forskningsöversikt (refereegranskat)abstract
- Electroweak measurements performed with data taken at the electron positron collider LEP at CERN from 1995 to 2000 are reported. The combined data set considered in this report corresponds to a total luminosity of about 3 fb(-1) collected by the four LEP experiments ALEPH, DELPHI, 13 and OPAL, at centre-of-mass energies ranging from 130 GeV to 209 GeV. Combining the published results of the four LEP experiments, the measurements include total and differential cross-sections in photon-pair, fermion-pair and four-fermion production, the latter resulting from both double-resonant WW and ZZ production as well as singly resonant production. Total and differential cross-sections are measured precisely, providing a stringent test of the Standard Model at centre-of-mass energies never explored before in electron positron collisions. Final-state interaction effects in four-fermion production, such as those arising from colour reconnection and Bose Einstein correlations between the two W decay systems arising in WW production, are searched for and upper limits on the strength of possible effects are obtained. The data are used to determine fundamental properties of the W boson and the electroweak theory. Among others, the mass and width of the W boson, m(w) and Gamma(w), the branching fraction of W decays to hadrons, B(W -> had), and the trilinear gauge-boson self-couplings g(1)(Z), K-gamma and lambda(gamma), are determined to be: m(w) = 80.376 +/- 0.033 GeV Gamma(w) = 2.195 +/- 0.083 GeV B(W -> had) = 67.41 +/- 0.27% g(1)(Z) = 0.984(-0.020)(+0.018) K-gamma - 0.982 +/- 0.042 lambda(gamma) = 0.022 +/- 0.019. (C) 2013 Elsevier B.V. All rights reserved.
|
|
| 5. |
- Schael, S, et al.
(författare)
-
Precision electroweak measurements on the Z resonance
- 2006
-
Ingår i: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 427:5-6, s. 257-454
-
Forskningsöversikt (refereegranskat)abstract
- We report on the final electroweak measurements performed with data taken at the Z resonance by the experiments operating at the electron-positron colliders SLC and LEP. The data consist of 17 million Z decays accumulated by the ALEPH, DELPHI, L3 and OPAL experiments at LEP, and 600 thousand Z decays by the SLID experiment using a polarised beam at SLC. The measurements include cross-sections, forward-backward asymmetries and polarised asymmetries. The mass and width of the Z boson, m(Z) and Gamma(Z), and its couplings to fermions, for example the p parameter and the effective electroweak mixing angle for leptons, are precisely measured: m(Z) = 91.1875 +/- 0.0021 GeV, Gamma(Z) = 2.4952 +/- 0.0023 GeV, rho(l) = 1.0050 +/- 0.0010, sin(2)theta(eff)(lept) = 0.23153 +/- 0.00016. The number of light neutrino species is determined to be 2.9840 +/- 0.0082, in agreement with the three observed generations of fundamental fermions. The results are compared to the predictions of the Standard Model (SM). At the Z-pole, electroweak radiative corrections beyond the running of the QED and QCD coupling constants are observed with a significance of five standard deviations, and in agreement with the Standard Model. Of the many Z-pole measurements, the forward-backward asymmetry in b-quark production shows the largest difference with respect to its SM expectation, at the level of 2.8 standard deviations. Through radiative corrections evaluated in the framework of the Standard Model, the Z-pole data are also used to predict the mass of the top quark, m(t) = 173(+10)(+13) GeV, and the mass of the W boson, m(W) = 80.363 +/- 0.032 GeV. These indirect constraints are compared to the direct measurements, providing a stringent test of the SM. Using in addition the direct measurements of m(t) and m(W), the mass of the as yet unobserved SM Higgs boson is predicted with a relative uncertainty of about 50% and found to be less than 285 GeV at 95% confidence level. (c) 2006 Elsevier B.V. All rights reserved.
|
|
| 6. |
- Siebzehnrübl, Florian A., et al.
(författare)
-
Early postnatal behavioral, cellular, and molecular changes in models of Huntington disease are reversible by HDAC inhibition
- 2018
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 115:37, s. 8765-8774
-
Tidskriftsartikel (refereegranskat)abstract
- Huntington disease (HD) is an autosomal dominant neurodegenerative disorder caused by expanded CAG repeats in the huntingtin gene (HTT). Although mutant HTT is expressed during embryonic development and throughout life, clinical HD usually manifests later in adulthood. A number of studies document neurodevelopmental changes associated with mutant HTT, but whether these are reversible under therapy remains unclear. Here, we identify very early behavioral, molecular, and cellular changes in preweaning transgenic HD rats and mice. Reduced ultrasonic vocalization, loss of prepulse inhibition, and increased risk taking are accompanied by disturbances of dopaminergic regulation in vivo, reduced neuronal differentiation capacity in subventricular zone stem/progenitor cells, and impaired neuronal and oligodendrocyte differentiation of mouse embryo-derived neural stem cells in vitro. Interventional treatment of this early phenotype with the histone deacetylase inhibitor (HDACi) LBH589 led to significant improvement in behavioral changes and markers of dopaminergic neurotransmission and complete reversal of aberrant neuronal differentiation in vitro and in vivo. Our data support the notion that neurodevelopmental changes contribute to the prodromal phase of HD and that early, presymptomatic intervention using HDACi may represent a promising novel treatment approach for HD.
|
|
| 7. |
|
|
| 8. |
- Datta-Chaudhuri, Timir, et al.
(författare)
-
The Fourth Bioelectronic Medicine Summit "Technology Targeting Molecular Mechanisms" : current progress, challenges, and charting the future
- 2021
-
Ingår i: Bioelectronic medicine. - : BioMed Central. - 2332-8886. ; 7:1
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- There is a broad and growing interest in Bioelectronic Medicine, a dynamic field that continues to generate new approaches in disease treatment. The fourth bioelectronic medicine summit "Technology targeting molecular mechanisms" took place on September 23 and 24, 2020. This virtual meeting was hosted by the Feinstein Institutes for Medical Research, Northwell Health. The summit called international attention to Bioelectronic Medicine as a platform for new developments in science, technology, and healthcare. The meeting was an arena for exchanging new ideas and seeding potential collaborations involving teams in academia and industry. The summit provided a forum for leaders in the field to discuss current progress, challenges, and future developments in Bioelectronic Medicine. The main topics discussed at the summit are outlined here.
|
|
| 9. |
- Delle, Simone, et al.
(författare)
-
Motives for not drinking alcohol : why adults in late middle age abstain
- 2022
-
Ingår i: Addiction Research and Theory. - : Informa UK Limited. - 1606-6359 .- 1476-7392. ; 30:2, s. 126-133
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Older individuals are not only more sensitive to the impact of alcohol but also face significant health risks from alcohol-drug interactions. To alter current drinking patterns, it is crucial to understand the motives for abstention of adults in late middle age.Objectives: We hypothesized that, for adults in late middle age, socio-demographic characteristics and health-related factors predict alcohol abstinence; and that current motives for abstention vary between subgroups of abstainers.Method: Data on adults aged 50-64 years (n = 2,308) came from the German Epidemiological Survey of Substance Abuse (ESA). Logistic regression was used to examine the association between different types of abstinence and socio-demographic and health-related variables.Results: Low income, low education and poor self-rated physical health predicted 12-month abstinence. Men with a chronic disease had a 9.5 % chance to be abstinent, whilst it was 17.7 % for women. Main motives for older lifetime abstainers were 'dislike of taste or smell', 'loss of control' and 'family constraints'. For 12-month abstainers, it was 'loss of control', 'health constraints' and 'dislike of taste or smell'.Conclusion: Poor health in middle-aged drinkers offers an opportunity to recommend reduction or cessation of alcohol use by explaining the negative health effects from alcohol. Future research investigating abstention needs to differentiate between lifetime and 12-month abstainers.
|
|
| 10. |
- Hoffmann, Markus, et al.
(författare)
-
Camostat mesylate inhibits SARS-CoV-2 activation by TMPRSS2-related proteases and its metabolite GBPA exerts antiviral activity
- 2021
-
Ingår i: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 65
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Antivirals are needed to combat the COVID-19 pandemic, which is caused by SARS-CoV-2. The clinically-proven protease inhibitor Camostat mesylate inhibits SARS-CoV-2 infection by blocking the virus-activating host cell protease TMPRSS2. However, antiviral activity of Camostat mesylate metabolites and potential viral resistance have not been analyzed. Moreover, antiviral activity of Camostat mesylate in human lung tissue remains to be demonstrated. Methods: We used recombinant TMPRSS2, reporter particles bearing the spike protein of SARS-CoV-2 or authentic SARS-CoV-2 to assess inhibition of TMPRSS2 and viral entry, respectively, by Camostat mesylate and its metabolite GBPA. Findings: We show that several TMPRSS2-related proteases activate SARS-CoV-2 and that two, TMPRSS11D and TMPRSS13, are robustly expressed in the upper respiratory tract. However, entry mediated by these proteases was blocked by Camostat mesylate. The Camostat metabolite GBPA inhibited recombinant TMPRSS2 with reduced efficiency as compared to Camostat mesylate. In contrast, both inhibitors exhibited similar antiviral activity and this correlated with the rapid conversion of Camostat mesylate into GBPA in the presence of serum. Finally, Camostat mesylate and GBPA blocked SARS-CoV-2 spread in human lung tissue ex vivo and the related protease inhibitor Nafamostat mesylate exerted augmented antiviral activity. Interpretation: Our results suggest that SARS-CoV-2 can use TMPRSS2 and closely related proteases for spread in the upper respiratory tract and that spread in the human lung can be blocked by Camostat mesylate and its metabolite GBPA. Funding: NIH, Damon Runyon Foundation, ACS, NYCT, DFG, EU, Berlin Mathematics center MATH+, BMBF, Lower Saxony, Lundbeck Foundation, Novo Nordisk Foundation.
|
|
| 11. |
- Izsak, Julia, et al.
(författare)
-
Differential acute impact of therapeutically effective and overdose concentrations of lithium on human neuronal single cell and network function
- 2021
-
Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 11
-
Tidskriftsartikel (refereegranskat)abstract
- Lithium salts are used as mood-balancing medication prescribed to patients suffering from neuropsychiatric disorders, such as bipolar disorder and major depressive disorder. Lithium salts cross the blood-brain barrier and reach the brain parenchyma within few hours after oral application, however, how lithium influences directly human neuronal function is unknown. We applied patch–clamp and microelectrode array technology on human induced pluripotent stem cell (iPSC)-derived cortical neurons acutely exposed to therapeutic (<1 mM) and overdose concentrations (>1 mM) of lithium chloride (LiCl) to assess how therapeutically effective and overdose concentrations of LiCl directly influence human neuronal electrophysiological function at the synapse, single-cell, and neuronal network level. We describe that human iPSC-cortical neurons exposed to lithium showed an increased neuronal activity under all tested concentrations. Furthermore, we reveal a lithium-induced, concentration-dependent, transition of regular synchronous neuronal network activity using therapeutically effective concentration (<1 mM LiCl) to epileptiform-like neuronal discharges using overdose concentration (>1 mM LiCl). The overdose concentration lithium-induced epileptiform-like activity was similar to the epileptiform-like activity caused by the GABAA-receptor antagonist. Patch–clamp recordings reveal that lithium reduces action potential threshold at all concentrations, however, only overdose concentration causes increased frequency of spontaneous AMPA-receptor mediated transmission. By applying the AMPA-receptor antagonist and anti-epileptic drug Perampanel, we demonstrate that Perampanel suppresses lithium-induced epileptiform-like activity in human cortical neurons. We provide insights in how therapeutically effective and overdose concentration of lithium directly influences human neuronal function at synapse, a single neuron, and neuronal network levels. Furthermore, we provide evidence that Perampanel suppresses pathological neuronal discharges caused by overdose concentrations of lithium in human neurons.
|
|
| 12. |
- Kehoe, Laura, et al.
(författare)
-
Make EU trade with Brazil sustainable
- 2019
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
|
|
| 13. |
- Klionsky, Daniel J., et al.
(författare)
-
Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
-
Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
-
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.
|
|
| 14. |
|
|
| 15. |
- Kneifel, Stefan, et al.
(författare)
-
Individual voxelwise dosimetry of targeted (90)Y-labelled substance P radiotherapy for malignant gliomas.
- 2007
-
Ingår i: European journal of nuclear medicine and molecular imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 34:9, s. 1388-95
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Substance P is the main ligand of neurokinin type 1 (NK-1) receptors, which are consistently overexpressed in malignant gliomas. The peptidic vector (111)In/(90)Y-DOTAGA-substance P binds to these receptors and can be used for local treatment of brain tumours. Dosimetry for this interstitial brachytherapy has mainly been done using geometrical models; however, they often do not faithfully reproduce the in vivo biodistribution of radiopharmaceuticals, which is indispensable to correlate the deposited energy with clinical response. The aim of this study was to establish a reproducible dosimetry protocol for intratumoural radiopeptide therapy. METHODS: For test and therapeutic injections, 2 MBq of (111)In-substance P and 370-3,330 MBq of (90)Y-substance P, respectively, were applied in 12 patients with malignant gliomas. Over a period of 24 h, serial SPECT scans were performed on a dual-head SPECT camera. The scans were acquired in a double-energy window technique together with (99m)Tc-ECD in order to co-register the dose distributions with a separately acquired, contrast-enhanced CT scan. Quantitative voxelwise dose distribution maps (in Gy/GBq) were computed from these data using a mono-exponential decay approach. Pre- and post-therapeutic values were compared. RESULTS: Agreement between pre- and post-therapeutic dosimetry was very good and delivered absolute dose values in Gy per injected GBq. In all patients, the pretherapeutic test injection together with the CT overlay technique could predict the precise localisation of dose deposition in an anatomical context. CONCLUSION: This protocol allows a precise pretherapeutic computation of the expected three-dimensional dose distribution and is clearly superior to the previously used dosimetry based on planar scintigraphic images. It has become an indispensable tool for planning intratumoural radiopeptide therapy in glioma patients.
|
|
| 16. |
- Leebens-Mack, James H., et al.
(författare)
-
One thousand plant transcriptomes and the phylogenomics of green plants
- 2019
-
Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 574:7780, s. 679-
-
Tidskriftsartikel (refereegranskat)abstract
- Green plants (Viridiplantae) include around 450,000-500,000 species(1,2) of great diversity and have important roles in terrestrial and aquatic ecosystems. Here, as part of the One Thousand Plant Transcriptomes Initiative, we sequenced the vegetative transcriptomes of 1,124 species that span the diversity of plants in a broad sense (Archaeplastida), including green plants (Viridiplantae), glaucophytes (Glaucophyta) and red algae (Rhodophyta). Our analysis provides a robust phylogenomic framework for examining the evolution of green plants. Most inferred species relationships are well supported across multiple species tree and supermatrix analyses, but discordance among plastid and nuclear gene trees at a few important nodes highlights the complexity of plant genome evolution, including polyploidy, periods of rapid speciation, and extinction. Incomplete sorting of ancestral variation, polyploidization and massive expansions of gene families punctuate the evolutionary history of green plants. Notably, we find that large expansions of gene families preceded the origins of green plants, land plants and vascular plants, whereas whole-genome duplications are inferred to have occurred repeatedly throughout the evolution of flowering plants and ferns. The increasing availability of high-quality plant genome sequences and advances in functional genomics are enabling research on genome evolution across the green tree of life.
|
|
| 17. |
|
|
| 18. |
- Ludwig, Sebastian, et al.
(författare)
-
Transcatheter Mitral Valve Replacement versus Medical Therapy for Secondary Mitral Regurgitation: A Propensity Score-Matched Comparison.
- 2023
-
Ingår i: Circulation. Cardiovascular interventions. - 1941-7632. ; 16:6
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Transcatheter mitral valve replacement (TMVR) is an emerging therapeutic alternative for patients with secondary mitral regurgitation (MR). Outcomes of TMVR versus guideline-directed medical therapy (GDMT) have not been investigated for this population. This study aimed to compare clinical outcomes of patients with secondary MR undergoing TMVR versus GDMT alone. Methods: The CHOICE-MI registry included patients with MR undergoing TMVR using dedicated devices. Patients with MR etiologies other than secondary MR were excluded. Patients treated with GDMT alone were derived from the control arm of the COAPT trial. We compared outcomes between the TMVR and GDMT groups, using propensity score (PS)-matching to adjust for baseline differences. Results: After PS-matching, 97 patient pairs undergoing TMVR (72.9±8.7 years, 60.8% male, transapical access 91.8%) versus GDMT (73.1±11.0 years, 59.8% male) were compared. At 1 and 2 years, residual MR was ≤1+ in all patients of the TMVR group compared to 6.9% and 7.7%, respectively, in those receiving GDMT alone (both p<0.001). The 2-year rate of HF hospitalization was significantly lower in the TMVR group (32.8% vs. 54.4%, HR 0.59, 95% CI 0.35-0.99; p=0.04). Among survivors, a higher proportion of patients were in NYHA functional class I or II in the TMVR group at 1 year (78.2% vs. 59.7%, p=0.03) and at 2 years (77.8% vs. 53.2%, p=0.09). Two-year mortality was similar in the two groups (TMVR vs. GDMT, 36.8% vs. 40.8%, HR 1.01, 95% CI 0.62-1.64; p=0.98). Conclusions: In this observational comparison, over 2-year follow-up, TMVR using mostly transapical devices in patients with secondary MR was associated with significant reduction of MR, symptomatic improvement, less frequent hospitalizations for HF and similar mortality compared with GDMT.
|
|
| 19. |
- Marque, Christophe, et al.
(författare)
-
Solar radio emission as a disturbance of aeronautical radionavigation
- 2018
-
Ingår i: Journal of Space Weather and Space Climate. - : EDP Sciences. - 2115-7251. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- On November 4th, 2015 secondary air traffic control radar was strongly disturbed in Sweden and some other European countries. The disturbances occurred when the radar antennas were pointing at the Sun. In this paper, we show that the disturbances coincided with the time of peaks of an exceptionally strong (similar to 10(5) Solar Flux Units) solar radio burst in a relatively narrow frequency range around 1 GHz. This indicates that this radio burst is the most probable space weather candidate for explaining the radar disturbances. The dynamic radio spectrum shows that the high flux densities are not due to synchrotron emission of energetic electrons, but to coherent emission processes, which produce a large variety of rapidly varying short bursts (such as pulsations, fiber bursts, and zebra patterns). The radio burst occurs outside the impulsive phase of the associated flare, about 30 min after the soft X-ray peak, and it is temporarily associated with fast evolving activity occurring in strong solar magnetic fields. While the relationship with strong magnetic fields and the coherent spectral nature of the radio burst provide hints towards the physical processes which generate such disturbances, we have so far no means to forecast them. Well-calibrated monitoring instruments of whole Sun radio fluxes covering the UHF band could at least provide a real-time identification of the origin of such disturbances, which reports in the literature show to also affect GPS signal reception.
|
|
| 20. |
|
|
| 21. |
- Ortiz-García, Paloma, et al.
(författare)
-
The Indole-3-Acetamide-Induced Arabidopsis Transcription Factor MYB74 Decreases Plant Growth and Contributes to the Control of Osmotic Stress Responses
- 2022
-
Ingår i: Frontiers in Plant Science. - : Frontiers Media S.A.. - 1664-462X. ; 13
-
Tidskriftsartikel (refereegranskat)abstract
- The accumulation of the auxin precursor indole-3-acetamide (IAM) in the ami1 mutant has recently been reported to reduce plant growth and to trigger abiotic stress responses in Arabidopsis thaliana. The observed response includes the induction of abscisic acid (ABA) biosynthesis through the promotion of NCED3 expression. The mechanism by which plant growth is limited, however, remained largely unclear. Here, we investigated the transcriptional responses evoked by the exogenous application of IAM using comprehensive RNA-sequencing (RNA-seq) and reverse genetics approaches. The RNA-seq results highlighted the induction of a small number of genes, including the R2R3 MYB transcription factor genes MYB74 and MYB102. The two MYB factors are known to respond to various stress cues and to ABA. Consistent with a role as negative plant growth regulator, conditional MYB74 overexpressor lines showed a considerable growth reduction. RNA-seq analysis of MYB74 mutants indicated an association of MYB74 with responses to osmotic stress, water deprivation, and seed development, which further linked MYB74 with the observed ami1 osmotic stress and seed phenotype. Collectively, our findings point toward a role for MYB74 in plant growth control and in responses to abiotic stress stimuli.
|
|
| 22. |
- Osipov, Evgeny, et al.
(författare)
-
Effect of the L499M mutation of the ascomycetous Botrytis aclada laccase on redox potential and catalytic properties
- 2014
-
Ingår i: Acta Crystallographica Section D. - : International Union of Crystallography. - 0907-4449 .- 1399-0047. ; 70:11, s. 2913-2923
-
Tidskriftsartikel (refereegranskat)abstract
- Laccases are members of a large family of multicopper oxidases that catalyze the oxidn. of a wide range of org. and inorg. substrates accompanied by the redn. of dioxygen to water. These enzymes contain four Cu atoms per mol. organized into three sites: T1, T2 and T3. In all laccases, the T1 copper ion is coordinated by two histidines and one cysteine in the equatorial plane and is covered by the side chains of hydrophobic residues in the axial positions. The redox potential of the T1 copper ion influences the enzymic reaction and is detd. by the nature of the axial ligands and the structure of the second coordination sphere. In this work, the laccase from the ascomycete Botrytis aclada was studied, which contains conserved Ile491 and nonconserved Leu499 residues in the axial positions. The three-dimensional structures of the wild-type enzyme and the L499M mutant were detd. by X-ray crystallog. at 1.7 Å resoln. Crystals suitable for X-ray anal. could only be grown after deglycosylation. Both structures did not contain the T2 copper ion. The catalytic properties of the enzyme were characterized and the redox potentials of both enzyme forms were detd.: E 0 = 720 and 580 mV for the wild-type enzyme and the mutant, resp. Since the structures of the wild-type and mutant forms are very similar, the change in the redox potential can be related to the L499M mutation in the T1 site of the enzyme.
|
|
| 23. |
- Pérez-Alonso, Marta-Marina, et al.
(författare)
-
The calcium sensor CBL7 is required for Serendipita indica-induced growth stimulation in Arabidopsis thaliana, controlling defense against the endophyte and K+ homoeostasis in the symbiosis
- 2022
-
Ingår i: Plant, Cell and Environment. - : John Wiley & Sons. - 0140-7791 .- 1365-3040. ; 45:11, s. 3367-3382
-
Tidskriftsartikel (refereegranskat)abstract
- Calcium is an important second messenger in plants. The activation of Ca2+ signalling cascades is critical in the activation of adaptive processes in response to environmental stimuli. Root colonization by the growth promoting endophyte Serendipita indica involves the increase of cytosolic Ca2+ levels in Arabidopsis thaliana. Here, we investigated transcriptional changes in Arabidopsis roots during symbiosis with S. indica. RNA-seq profiling disclosed the induction of Calcineurin B-like 7 (CBL7) during early and later phases of the interaction. Consistently, reverse genetic evidence highlighted the functional relevance of CBL7 and tested the involvement of a CBL7-CBL-interacting protein kinase 13 signalling pathway. The loss-of-function of CBL7 abolished the growth promoting effect and affected root colonization. The transcriptomics analysis of cbl7 revealed the involvement of this Ca2+ sensor in activating plant defense responses. Furthermore, we report on the contribution of CBL7 to potassium transport in Arabidopsis. We analysed K+ contents in wild-type and cbl7 plants and observed a significant increase of K+ in roots of cbl7 plants, while shoot tissues demonstrated K+ depletion. Taken together, our work associates CBL7 with an important role in the mutual interaction between Arabidopsis and S. indica and links CBL7 to K+ transport.
|
|
| 24. |
- Soltani, Amin, et al.
(författare)
-
Direct nanoscopic observation of plasma waves in the channel of a graphene field-effect transistor
- 2020
-
Ingår i: Light: Science and Applications. - : Springer Science and Business Media LLC. - 2047-7538 .- 2095-5545. ; 9:1
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Plasma waves play an important role in many solid-state phenomena and devices. They also become significant in electronic device structures as the operation frequencies of these devices increase. A prominent example is field-effect transistors (FETs), that witness increased attention for application as rectifying detectors and mixers of electromagnetic waves at gigahertz and terahertz frequencies, where they exhibit very good sensitivity even high above the cut-off frequency defined by the carrier transit time. Transport theory predicts that the coupling of radiation at THz frequencies into the channel of an antenna-coupled FET leads to the development of a gated plasma wave, collectively involving the charge carriers of both the two-dimensional electron gas and the gate electrode. In this paper, we present the first direct visualization of these waves. Employing graphene FETs containing a buried gate electrode, we utilize near-field THz nanoscopy at room temperature to directly probe the envelope function of the electric field amplitude on the exposed graphene sheet and the neighboring antenna regions. Mapping of the field distribution documents that wave injection is unidirectional from the source side since the oscillating electrical potentials on the gate and drain are equalized by capacitive shunting. The plasma waves, excited at 2 THz, are overdamped, and their decay time lies in the range of 25–70 fs. Despite this short decay time, the decay length is rather long, i.e., 0.3-0.5 μm, because of the rather large propagation speed of the plasma waves, which is found to lie in the range of 3.5–7 × 10^6 m/s, in good agreement with theory. The propagation speed depends only weakly on the gate voltage swing and is consistent with the theoretically predicted 1414 power law.
|
|
| 25. |
- Speliotes, Elizabeth K., et al.
(författare)
-
Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
- 2010
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 937-948
-
Tidskriftsartikel (refereegranskat)abstract
- Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ~2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10−8), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.
|
|
| 26. |
- Vogl, Thomas, et al.
(författare)
-
Autoinhibitory regulation of S100A8/S100A9 alarmin activity locally restricts sterile inflammation
- 2018
-
Ingår i: Journal of Clinical Investigation. - 0021-9738. ; 128:5, s. 1852-1866
-
Tidskriftsartikel (refereegranskat)abstract
- Autoimmune diseases, such as psoriasis and arthritis, show a patchy distribution of inflammation despite systemic dysregulation of adaptive immunity. Thus, additional tissue-derived signals, such as danger-associated molecular patterns (DAMPs), are indispensable for manifestation of local inflammation. S100A8/S100A9 complexes are the most abundant DAMPs in many autoimmune diseases. However, regulatory mechanisms locally restricting DAMP activities are barely understood. We now unravel for the first time, to our knowledge, a mechanism of autoinhibition in mice and humans restricting S100-DAMP activity to local sites of inflammation. Combining protease degradation, pull-down assays, mass spectrometry, and targeted mutations, we identified specific peptide sequences within the second calcium-binding EF-hands triggering TLR4/MD2-dependent inflammation. These binding sites are free when S100A8/S100A9 heterodimers are released at sites of inflammation. Subsequently, S100A8/S100A9 activities are locally restricted by calcium-induced (S100A8/ S100A9)2 tetramer formation hiding the TLR4/MD2-binding site within the tetramer interphase, thus preventing undesirable systemic effects. Loss of this autoinhibitory mechanism in vivo results in TNF-α-driven fatal inflammation, as shown by lack of tetramer formation in crossing S100A9-/- mice with 2 independent TNF-α-transgene mouse strains. Since S100A8/S100A9 is the most abundant DAMP in many inflammatory diseases, specifically blocking the TLR4-binding site of active S100 dimers may represent a promising approach for local suppression of inflammatory diseases, avoiding systemic side effects.
|
|
| 27. |
- Wagner, Leona, et al.
(författare)
-
Neuropeptide Y (NPY) in cerebrospinal fluid from patients with Huntington's Disease : increased NPY levels and differential degradation of the NPY1-30 fragment
- 2016
-
Ingår i: Journal of Neurochemistry. - : Wiley. - 1471-4159 .- 0022-3042. ; 137:5, s. 820-837
-
Tidskriftsartikel (refereegranskat)abstract
- Huntington's disease (HD) is an inherited and fatal polyglutamine neurodegenerative disorder caused by an expansion of the CAG triplet repeat coding region within the HD gene. Progressive dysfunction and loss of striatal GABAergic medium spiny neurons (MSNs) may account for some of the characteristic symptoms in HD patients. Interestingly, in HD, MSNs expressing neuropeptide Y (NPY) are spared and their numbers is even up-regulated in HD patients. In line with this, we report here on increased immuno-linked NPY (IL-NPY) levels in human cerebrospinal fluid (hCSF) from HD patients. As this antibody-based detection of NPY may provide false positive differences due to the antibody-based detections of only fragments of NPY, the initial finding was validated by investigating the proteolytic stability of NPY in hCSF using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and selective inhibitors. A comparison between resulting NPY-fragments and detailed epitope analysis verified significant differences of IL-NPY1-36/3-36 and NPY1-30 levels between HD patients and control subjects. Ex vivo degradomics analysis demonstrated that NPY is initially degraded to NPY1-30 by cathepsin D (CTSD) in both HD patients and control subjects. Yet, NPY1-30 is then further differentially hydrolyzed by thimet oligopeptidase (TOP) in HD patients and by neprilysin (NEP) in control subjects. Furthermore, altered hCSF TOP-inhibitor Dynorphin A1-13 (Dyn-A1-13 ) and TOP-substrate Dyn-A1-8 levels indicate an impaired Dyn-A-TOP network in HD patients. Thus, we conclude that elevated IL-NPY-levels in conjunction with TOP- / NEP-activity/protein as well as Dyn-A1-13 -protein levels may serve as a potential biomarker in human CSF of HD. This article is protected by copyright. All rights reserved.
|
|
| 28. |
|
|
| 29. |
- Zimmermann, Stefan, et al.
(författare)
-
Out-of-hospital cardiac arrest and percutaneous coronary intervention for ST-elevation myocardial infarction : Long-term survival and neurological outcome
- 2013
-
Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 166:1, s. 236-241
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Predictors of long-term outcome after ST-elevation myocardial infarction (STEMI) complicated by out-of-hospital cardiac arrest (OHCA) are incompletely understood, including the influence of successful coronary reperfusion.METHODS:We analysed clinical and procedural data as well as 1-year outcome of 72 consecutive patients who underwent primary coronary intervention (PCI) after witnessed OHCA and STEMI and compared the results with 695 patients with STEMI and PCI, but without OHCA. Neurological recovery after OHCA was assessed using the Cerebral Performance Category (CPC) scale.RESULTS:PCI was successful in 83.3% after OHCA vs. 84.3% in the non-OHCA group (p=0.87). One-year mortality was 34.7% vs. 9.5% (p<0.001). 58.3% of the OHCA-patients showed complete neurological recovery (CPC 1) or moderate neurological disability (CPC 2). Another 6.9% showed severe cerebral disability (CPC 3) or permanent vegetative status (CPC 4). Delay from collapse until start of Advanced Cardiopulmonary Life Support (ACLS) was shorter for survivors with CPC status ≤2 (median 1min, range 0-11min) compared to non-survivors or survivors with CPC status >2 (median 8min, range 0-13min), p<0.0001. Age-adjusted multivariate analysis identified 'unsuccessful PCI', 'vasopressors on admission' and 'start of ACLS after >6min' as independent predictors of negative long-term outcome (death or CPC >2).CONCLUSIONS: Mortality is high in patients with STEMI complicated by OHCA - even though PCI was performed with the same success rate as in patients without OHCA. The majority of survivors had favourable neurological outcomes at 1year, especially if advanced life support had been started within ≤6min and PCI was successful.
|
|
