SwePub - sökning: WFRF:(Vogl Thomas)

Numrering	Referens	Omslagsbild	Hitta
1.	Klionsky, Daniel J, et al. (författare) Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). 2016 Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 12:1, s. 1-222 Tidskriftsartikel (refereegranskat)
2.	Amare, Azmeraw, et al. (författare) Association of Polygenic Score and the involvement of Cholinergic and Glutamatergic Pathways with Lithium Treatment Response in Patients with Bipolar Disorder. 2023 Ingår i: Research square. - : Research Square Platform LLC. Tidskriftsartikel (refereegranskat)abstract Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental disorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N=2,367) and replicated in the combined PsyCourse (N=89) and BipoLife (N=102) studies. The associations of Li+PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P<��.
3.	Amare, Azmeraw T, et al. (författare) Association of polygenic score and the involvement of cholinergic and glutamatergic pathways with lithium treatment response in patients with bipolar disorder. 2023 Ingår i: Molecular psychiatry. - 1476-5578. ; 28, s. 5251-5261 Tidskriftsartikel (refereegranskat)abstract Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental healthdisorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N=2367) and replicated in the combined PsyCourse (N=89) and BipoLife (N=102) studies. The associations of Li+PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P<0.05. Li+PGS was positively associated with lithium treatment response in the ConLi+Gen cohort, in both the categorical (P=9.8×10-12, R2=1.9%) and continuous (P=6.4×10-9, R2=2.6%) outcomes. Compared to bipolar patients in the 1st decile of the risk distribution, individuals in the 10th decile had 3.47-fold (95%CI: 2.22-5.47) higher odds of responding favorably to lithium. The results were replicated in the independent cohorts for the categorical treatment outcome (P=3.9×10-4, R2=0.9%), but not for the continuous outcome (P=0.13). Gene-based analyses revealed 36 candidate genes that are enriched in biological pathways controlled by glutamate and acetylcholine. Li+PGS may be useful in the development of pharmacogenomic testing strategies by enabling a classification of bipolar patients according to their response to treatment.
4.	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.
5.	Achouiti, Ahmed, et al. (författare) Myeloid-related protein-14 contributes to protective immunity in gram-negative pneumonia derived sepsis 2012 Ingår i: PLoS Pathogens. - San Fransisco : Public Library of Science. - 1553-7374. ; 8:10, s. e1002987- Tidskriftsartikel (refereegranskat)abstract Klebsiella (K.) pneumoniae is a common cause of pneumonia-derived sepsis. Myeloid related protein 8 (MRP8, S100A8) and MRP14 (S100A9) are the most abundant cytoplasmic proteins in neutrophils. They can form MRP8/14 heterodimers that are released upon cell stress stimuli. MRP8/14 reportedly exerts antimicrobial activity, but in acute fulminant sepsis models MRP8/14 has been found to contribute to organ damage and death. We here determined the role of MRP8/14 in K. pneumoniae sepsis originating from the lungs, using an established model characterized by gradual growth of bacteria with subsequent dissemination. Infection resulted in gradually increasing MRP8/14 levels in lungs and plasma. Mrp14 deficient (mrp14(-/-)) mice, unable to form MRP8/14 heterodimers, showed enhanced bacterial dissemination accompanied by increased organ damage and a reduced survival. Mrp14(-/-) macrophages were reduced in their capacity to phagocytose Klebsiella. In addition, recombinant MRP8/14 heterodimers, but not MRP8 or MRP14 alone, prevented growth of Klebsiella in vitro through chelation of divalent cations. Neutrophil extracellular traps (NETs) prepared from wildtype but not from mrp14(-/-) neutrophils inhibited Klebsiella growth; in accordance, the capacity of human NETs to kill Klebsiella was strongly impaired by an anti-MRP14 antibody or the addition of zinc. These results identify MRP8/14 as key player in protective innate immunity during Klebsiella pneumonia.
6.	Björk, Per, et al. (författare) Identification of human S100A9 as a novel target for treatment of autoimmune disease via binding to quinoline-3-carboxamides. 2009 Ingår i: PLoS Biology. - : Public Library of Science (PLoS). - 1545-7885. ; 7:4, s. 800-812 Tidskriftsartikel (refereegranskat)abstract Despite more than 25 years of research, the molecular targets of quinoline-3-carboxamides have been elusive although these compounds are currently in Phase II and III development for treatment of autoimmune/inflammatory diseases in humans. Using photoaffinity cross-linking of a radioactively labelled quinoline-3-carboxamide compound, we could determine a direct association between human S100A9 and quinoline-3-carboxamides. This interaction was strictly dependent on both Zn++ and Ca++. We also show that S100A9 in the presence of Zn++ and Ca++ is an efficient ligand of receptor for advanced glycation end products (RAGE) and also an endogenous Toll ligand in that it shows a highly specific interaction with TLR4/MD2. Both these interactions are inhibited by quinoline-3-carboxamides. A clear structure-activity relationship (SAR) emerged with regard to the binding of quinoline-3-carboxamides to S100A9, as well as these compounds potency to inhibit interactions with RAGE or TLR4/MD2. The same SAR was observed when the compound's ability to inhibit acute experimental autoimmune encephalomyelitis in mice in vivo was analysed. Quinoline-3-carboxamides would also inhibit TNFalpha release in a S100A9-dependent model in vivo, as would antibodies raised against the quinoline-3-carboxamide-binding domain of S100A9. Thus, S100A9 appears to be a focal molecule in the control of autoimmune disease via its interactions with proinflammatory mediators. The specific binding of quinoline-3-carboxamides to S100A9 explains the immunomodulatory activity of this class of compounds and defines S100A9 as a novel target for treatment of human autoimmune diseases.
7.	Blennow, Mattias, et al. (författare) Halo-independent tests of dark matter direct detection signals : Local DM density, LHC, and thermal freeze-out 2015 Ingår i: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; 2015:8 Tidskriftsartikel (refereegranskat)abstract From an assumed signal in a Dark Matter (DM) direct detection experiment a lower bound on the product of the DM-nucleon scattering cross section and the local DM density is derived, which is independent of the local DM velocity distribution. This can be combined with astrophysical determinations of the local DM density. Within a given particle physics model the bound also allows a robust comparison of a direct detection signal with limits from the LHC. Furthermore, the bound can be used to formulate a condition which has to be fulfilled if the particle responsible for the direct detection signal is a thermal relic, regardless of whether it constitutes all DM or only part of it. We illustrate the arguments by adopting a simplified DM model with a Z' mediator and assuming a signal in a future xenon direct detection experiment.
8.	Felkel, Sabine, et al. (författare) The horse Y chromosome as an informative marker for tracing sire lines 2019 Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9 Tidskriftsartikel (refereegranskat)abstract Analysis of the Y chromosome is the best-established way to reconstruct paternal family history in humans. Here, we applied fine-scaled Y-chromosomal haplotyping in horses with biallelic markers and demonstrate the potential of our approach to address the ancestry of sire lines. We de novo assembled a draft reference of the male-specific region of the Y chromosome from Illumina short reads and then screened 5.8 million basepairs for variants in 130 specimens from intensively selected and rural breeds and nine Przewalski's horses. Among domestic horses we confirmed the predominance of a young'crown haplogroup' in Central European and North American breeds. Within the crown, we distinguished 58 haplotypes based on 211 variants, forming three major haplogroups. In addition to two previously characterised haplogroups, one observed in Arabian/Coldblooded and the other in Turkoman/Thoroughbred horses, we uncovered a third haplogroup containing Iberian lines and a North African Barb Horse. In a genealogical showcase, we distinguished the patrilines of the three English Thoroughbred founder stallions and resolved a historic controversy over the parentage of the horse 'Galopin', born in 1872. We observed two nearly instantaneous radiations in the history of Central and Northern European Y-chromosomal lineages that both occurred after domestication 5,500 years ago.
9.	Fiore, A., et al. (författare) Close, bright, and boxy : the superluminous SN 2018hti 2022 Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 512:3, s. 4484-4502 Tidskriftsartikel (refereegranskat)abstract SN 2018hti was a very nearby (z = 0.0614) superluminous supernova with an exceedingly bright absolute magnitude of −21.7 mag in r band at maximum. The densely sampled pre-maximum light curves of SN 2018hti show a slow luminosity evolution and constrain the rise time to ∼50 rest-frame d. We fitted synthetic light curves to the photometry to infer the physical parameters of the explosion of SN 2018hti for both the magnetar and the CSM-interaction scenarios. We conclude that one of two mechanisms could be powering the luminosity of SN 2018hti; interaction with ∼10 M⊙ of circumstellar material or a magnetar with a magnetic field of Bp∼ 1.3 × 1013 G, and initial period of Pspin∼ 1.8 ms. From the nebular spectrum modelling we infer that SN 2018hti likely results from the explosion of a ∼40M⊙∼40M⊙ progenitor star.
10.	Flint, Anne, et al. (författare) Randomised clinical trial: Semaglutide versus placebo reduced liver steatosis but not liver stiffness in subjects with non-alcoholic fatty liver disease assessed by magnetic resonance imaging 2021 Ingår i: Alimentary Pharmacology and Therapeutics. - : Wiley. - 1365-2036 .- 0269-2813. ; 54:9, s. 1150-1161 Tidskriftsartikel (refereegranskat)abstract Background: Glucagon-like peptide-1 receptor agonists may be a treatment option in patients with non-alcoholic fatty liver disease (NAFLD). Aims: To investigate the effects of semaglutide on liver stiffness and liver fat in subjects with NAFLD using non-invasive magnetic resonance imaging (MRI) methods. Methods: This randomised, double-blind, placebo-controlled trial enrolled subjects with liver stiffness 2.50-4.63 kPa by magnetic resonance elastography (MRE) and liver steatosis ≥10% by MRI proton density fat fraction (MRI-PDFF). The primary endpoint was change from baseline to week 48 in liver stiffness assessed by MRE. Results: Sixty-seven subjects were randomised to once-daily subcutaneous semaglutide 0.4 mg (n = 34) or placebo (n = 33). Change from baseline in liver stiffness was not significantly different between semaglutide and placebo at week 48 (estimated treatment ratio 0.96 (95% CI 0.89, 1.03; P = 0.2798); significant differences in liver stiffness were not observed at weeks 24 or 72. Reductions in liver steatosis were significantly greater with semaglutide (estimated treatment ratios: 0.70 [0.59, 0.84], P = 0.0002; 0.47 [0.36, 0.60], P < 0.0001; and 0.50 [0.39, 0.66], P < 0.0001) and more subjects achieved a ≥ 30% reduction in liver fat content with semaglutide at weeks 24, 48 and 72, (all P < 0.001). Decreases in liver enzymes, body weight and HbA1c were also observed with semaglutide. Conclusions: The change in liver stiffness in subjects with NAFLD was not significantly different between semaglutide and placebo. However, semaglutide significantly reduced liver steatosis compared with placebo which, together with improvements in liver enzymes and metabolic parameters, suggests a positive impact on disease activity and metabolic profile.
11.	Kahlhoefer, Felix, et al. (författare) Implications of unitarity and gauge invariance for simplified dark matter models 2016 Ingår i: Journal of High Energy Physics (JHEP). - 1126-6708 .- 1029-8479. ; :2 Tidskriftsartikel (refereegranskat)abstract We show that simplified models used to describe the interactions of dark matter with Standard Model particles do not in general respect gauge invariance and that perturbative unitarity may be violated in large regions of the parameter space. The modifications necessary to cure these inconsistencies may imply a much richer phenomenology and lead to stringent constraints on the model. We illustrate these observations by considering the simplified model of a fermionic dark matter particle and a vector mediator. Imposing gauge invariance then leads to strong constraints from dilepton resonance searches and electroweak precision tests. Furthermore, the new states required to restore perturbative unitarity can mix with Standard Model states and mediate interactions between the dark and the visible sector, leading to new experimental signatures such as invisible Higgs decays. The resulting constraints are typically stronger than the 'classic' constraints on DM simplified models such as monojet searches and make it difficult to avoid thermal overproduction of dark matter.
12.	Källberg, Eva, et al. (författare) S100A9 Interaction with TLR4 Promotes Tumor Growth 2012 Ingår i: PLOS ONE. - San Francisco : Public Library of Science. - 1932-6203. ; 7:3, s. e34207- Tidskriftsartikel (refereegranskat)abstract By breeding TRAMP mice with S100A9 knock-out (S100A9(-/-)) animals and scoring the appearance of palpable tumors we observed a delayed tumor growth in animals devoid of S100A9 expression. CD11b(+) S100A9 expressing cells were not observed in normal prostate tissue from control C57BL/6 mice but were readily detected in TRAMP prostate tumors. Also, S100A9 expression was observed in association with CD68(+) macrophages in biopsies from human prostate tumors. Delayed growth of TRAMP tumors was also observed in mice lacking the S100A9 ligand TLR4. In the EL-4 lymphoma model tumor growth inhibition was observed in S100A9(-/-) and TLR4(-/-), but not in RAGE(-/-) animals lacking an alternative S100A9 receptor. When expression of immune-regulating genes was analyzed using RT-PCR the only common change observed in mice lacking S100A9 and TLR4 was a down-regulation of TGF beta expression in splenic CD11b(+) cells. Lastly, treatment of mice with a small molecule (ABR-215050) that inhibits S100A9 binding to TLR4 inhibited EL4 tumor growth. Thus, S100A9 and TLR4 appear to be involved in promoting tumor growth in two different tumor models and pharmacological inhibition of S100A9-TLR4 interactions is a novel and promising target for anti-tumor therapies.
13.	Moberg, Christina, et al. (författare) De unga gör helt rätt när de stämmer staten 2022 Ingår i: Aftonbladet. - 1103-9000. Tidskriftsartikel (populärvet., debatt m.m.)abstract 1 620 forskare och lärare i forskarvärlden: Vi ställer oss bakom Auroras klimatkrav
14.	Pruenster, Monika, et al. (författare) Extracellular MRP8/14 is a regulator of β2 integrin-dependent neutrophil slow rolling and adhesion. 2015 Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6 Tidskriftsartikel (refereegranskat)abstract Myeloid-related proteins (MRPs) 8 and 14 are cytosolic proteins secreted from myeloid cells as proinflammatory mediators. Currently, the functional role of circulating extracellular MRP8/14 is unclear. Our present study identifies extracellular MRP8/14 as an autocrine player in the leukocyte adhesion cascade. We show that E-selectin-PSGL-1 interaction during neutrophil rolling triggers Mrp8/14 secretion. Released MRP8/14 in turn activates a TLR4-mediated, Rap1-GTPase-dependent pathway of rapid β2 integrin activation in neutrophils. This extracellular activation loop reduces leukocyte rolling velocity and stimulates adhesion. Thus, we identify Mrp8/14 and TLR4 as important modulators of the leukocyte recruitment cascade during inflammation in vivo.
15.	Riva, Matteo, et al. (författare) Induction of NFκB responses by the S100A9 protein is TLR4-dependent. 2012 Ingår i: Immunology. - : Wiley. - 0019-2805. ; 137:2, s. 172-182 Tidskriftsartikel (refereegranskat)abstract Interactions between danger and pathogen-associated molecular patterns (DAMP and PAMP) and pattern recognition receptors such as Toll-like receptors (TLRs) are critical for the regulation of the inflammatory process via activation of NFκB and cytokine secretion. In this report, we investigated the capacity of LPS-free S100A9 (DAMP) protein to activate human and mouse cells compared to lipoprotein-free LPS (PAMP). Firstly, we showed that LPS and S100A9 were able to increase NFκB activity followed by increased cytokine and nitric oxide (NO) secretion both in human THP-1 cells and mouse bone marrow-derived dendritic cells (BM-DC). Surprisingly, although S100A9 triggered a weaker cytokine response compared to LPS, we found that S100A9 more potently induced IκBα degradation and hence NFkB activation. Both the S100A9- and LPS-induced response was completely absent in TLR4 knock-out mice, while it was only slightly affected in RAGE knock-out mice. Also, we showed that LPS and S100A9 NFkB induction were strongly reduced in the presence of specific inhibitors of TLR-signaling. Chloroquine reduced S100A9 but not LPS signaling, indicating that S100A9 may need to be internalized in order to be fully active as a TLR4 inducer. This was confirmed using A488-labeled S100A9 that was internalized in THP-1 cells, showing a raise in fluorescence after 30 minutes at 37°C. Chloroquine treatment significantly reduced the fluorescence. In summary, our data indicate that both human and mouse S100A9 are TLR4 agonists. Importantly, S100A9 induced stronger NFκB activation albeit weaker cytokine secretion than LPS, suggesting that S100A9 and LPS activated NFκB in a qualitative distinct manner. © 2012 The Authors. Immunology © 2012 Blackwell Publishing Ltd, Immunology.
16.	Shankar, Madhu, et al. (författare) Immune Resolution Dilemma: Host Antimicrobial Factor S100A8/A9 Modulates Inflammatory Collateral Tissue Damage During Disseminated Fungal Peritonitis 2021 Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 12 Tidskriftsartikel (refereegranskat)abstract Intra-abdominal infection (peritonitis) is a leading cause of severe disease in surgical intensive care units, as over 70% of patients diagnosed with peritonitis develop septic shock. A critical role of the immune system is to return to homeostasis after combating infection. S100A8/A9 (calprotectin) is an antimicrobial and pro-inflammatory protein complex used as a biomarker for diagnosis of numerous inflammatory disorders. Here we describe the role of S100A8/A9 in inflammatory collateral tissue damage (ICTD). Using a mouse model of disseminated intra-abdominal candidiasis (IAC) in wild-type and S100A8/A9-deficient mice in the presence or absence of S100A9 inhibitor paquinimod, the role of S100A8/A9 during ICTD and fungal clearance were investigated. S100A8/A9-deficient mice developed less ICTD than wild-type mice. Restoration of S100A8/A9 in knockout mice by injection of recombinant protein resulted in increased ICTD and fungal clearance comparable to wild-type levels. Treatment with paquinimod abolished ICTD and S100A9-deficient mice showed increased survival compared to wild-type littermates. The data indicates that S100A8/A9 controls ICTD levels and antimicrobial activity during IAC and that targeting of S100A8/A9 could serve as promising adjunct therapy against this challenging disease.
17.	Sharma, Manish, et al. (författare) Older Patients with Myeloma Derive Similar Benefit from Autologous Transplantation 2014 Ingår i: Biology of blood and marrow transplantation. - : Elsevier BV. - 1083-8791 .- 1523-6536. ; 20:11, s. 1796-1803 Tidskriftsartikel (refereegranskat)abstract Autologous hematopoietic cell transplantation (AHCT) for plasma cell myeloma is performed less often in people >70 years old than in people <= 70 years old. We analyzed 11,430 AHCT recipients for plasma cell myeloma prospectively reported to the Center for International Blood and Marrow Transplant Research between 2008 and 2011, representing the majority of US AHCT activity during this period. Survival (OS) was compared in 3 cohorts: ages 18 to 59 years (n = 5818), 60 to 69 years (n = 4666), and >70 years (n = 946). Median OS was not reached for any cohort. In multivariate analysis, increasing age was associated with mortality (P = .0006). Myeloma-specific mortality was similar among cohorts at 12%, indicating an age-related effect on nonmyeloma mortality. Analyses were performed in a representative subgroup comparing relapse rate, progression-free survival (PFS), and nonrelapse mortality (NRM). One-year NRM was 0% for age >70 years and 2% for other ages (P = not significant). The three-year relapse rate was 56% in age 18 to 59 years, 61% in age 60 to 69 years, and 63% age >70 (P = not significant). Three-year PFS was similar at 42% in age 18 to 59 years, 38% in age 60 to 69 years, and 33% in age >70 years (P = not significant). Postrelapse survival was significantly worse for the older cohort (P = .03). Older subjects selected for AHCT derived similar antimyeloma benefit without worse NRM, relapse rate, or PFS.
18.	Taubenberger, S., et al. (författare) SN2012dn from early to late times : 09dc-like supernovae reassessed 2019 Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 488:4, s. 5473-5488 Tidskriftsartikel (refereegranskat)abstract As a candidate super-Chandrasekhar' or 09dc-like TypeIa supernova (SNIa), SN 2012dn shares many characteristics with other members of this remarkable class of objects but lacks their extraordinary luminosity. Here, we present and discuss the most comprehensive optical data set of this SN to date, comprised of a densely sampled series of early-time spectra obtained within the Nearby Supernova Factory project, plus photometry and spectroscopy obtained at the Very Large Telescope about 1yr after the explosion. The light curves, colour curves, spectral time series, and ejecta velocities of SN 2012dn are compared with those of other 09dc-like and normal SNeIa, the overall variety within the class of 09dc-like SNeIa is discussed, and new criteria for 09dc-likeness are proposed. Particular attention is directed to additional insight that the late-phase data provide. The nebular spectra show forbidden lines of oxygen and calcium, elements that are usually not seen in late-time spectra of SNeIa, while the ionization state of the emitting iron plasma is low, pointing to low ejecta temperatures and high densities. The optical light curves are characterized by an enhanced fading starting similar to 60d after maximum and very low luminosities in the nebular phase, which is most readily explained by unusually early formation of clumpy dust in the ejecta. Taken together, these effects suggest a strongly perturbed ejecta density profile, which might lend support to the idea that 09dc-like characteristics arise from a brief episode of interaction with a hydrogen-deficient envelope during the first hours or days after the explosion.
19.	Vogl, Thomas, et al. (författare) Pro-Inflammatory S100A8 and S100A9 Proteins : Self-Assembly into Multifunctional Native and Amyloid Complexes 2012 Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 13:3, s. 2893-2917 Tidskriftsartikel (refereegranskat)abstract S100A8 and S100A9 are EF-hand Ca2+ binding proteins belonging to the S100 family. They are abundant in cytosol of phagocytes and play critical roles in numerous cellular processes such as motility and danger signaling by interacting and modulating the activity of target proteins. S100A8 and S100A9 expression levels increased in many types of cancer, neurodegenerative disorders, inflammatory and autoimmune diseases and they are implicated in the numerous disease pathologies. The Ca2+ and Zn2+-binding properties of S100A8/A9 have a pivotal influence on their conformation and oligomerization state, including self-assembly into homo- and heterodimers, tetramers and larger oligomers. Here we review how the unique chemical and conformational properties of individual proteins and their structural plasticity at the quaternary level account for S100A8/A9 functional diversity. Additional functional diversification occurs via non-covalent assembly into oligomeric and fibrillar amyloid complexes discovered in the aging prostate and reproduced in vitro. This process is also regulated by Ca2+ and Zn2+-binding and effectively competes with the formation of the native complexes. High intrinsic amyloid-forming capacity of S100A8/A9 proteins may lead to their amyloid depositions in numerous ailments characterized by their elevated expression patterns and have additional pathological significance requiring further thorough investigation.
20.	Wache, Christina, et al. (författare) Myeloid-related protein 14 promote inflammation and injury in meningitis. 2015 Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 212:2, s. 247-257 Tidskriftsartikel (refereegranskat)abstract Neutrophilic inflammation often persists over days despite efficient antibiotic treatment and contributes to brain damage in bacterial meningitis. We proposed here that MRP14, an abundant cytosolic protein in myeloid cells, acts as an endogenous danger signal, driving inflammation and aggravating tissue injury.
21.	Wallner, Barbara, et al. (författare) Y Chromosome Uncovers the Recent Oriental Origin of Modern Stallions 2017 Ingår i: Current Biology. - : CELL PRESS. - 0960-9822 .- 1879-0445. ; 27:13, s. 2029-2035 Tidskriftsartikel (refereegranskat)abstract The Y chromosome directly reflects male genealogies, but the extremely low Y chromosome sequence diversity in horses has prevented the reconstruction of stallion genealogies [1, 2]. Here, weresolve the first Y chromosomegenealogy of modern horses by screening 1.46 Mb of the male-specific region of the Y chromosome (MSY) in 52 horses from 21 breeds. Based on highly accurate pedigree data, we estimated the de novo mutation rate of the horse MSY and showed that various modern horse Y chromosome lineages split much later than the domestication of the species. Apart from few private northern European haplotypes, all modern horse breeds clustered together in a roughly 700-year-old haplogroup that was transmitted to Europe by the import of Oriental stallions. The Oriental horse group consisted of two major subclades: the Original Arabian lineage and the Turkoman horse lineage. We show that the English Thoroughbred MSY was derived from the Turkoman lineage and that English Thoroughbred sires are largely responsible for the predominance of this haplotype in modern horses.
22.	Yanamandra, Kiran, 1977-, et al. (författare) Amyloid formation by the pro-inflammatory S100A8/A9 proteins in the ageing prostate. 2009 Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 4:5, s. e5562- Tidskriftsartikel (refereegranskat)abstract BACKGROUND: The conversion of soluble peptides and proteins into polymeric amyloid structures is a hallmark of many age-related degenerative disorders, including Alzheimer's disease, type II diabetes and a variety of systemic amyloidoses. We report here that amyloid formation is linked to another major age-related phenomenon--prostate tissue remodelling in middle-aged and elderly men. METHODOLOGY/PRINCIPAL FINDINGS: By using multidisciplinary analysis of corpora amylacea inclusions in prostate glands of patients diagnosed with prostate cancer we have revealed that their major components are the amyloid forms of S100A8 and S100A9 proteins associated with numerous inflammatory conditions and types of cancer. In prostate protease rich environment the amyloids are stabilized by dystrophic calcification and lateral thickening. We have demonstrated that material closely resembling CA can be produced from S100A8/A9 in vitro under native and acidic conditions and shows the characters of amyloids. This process is facilitated by calcium or zinc, both of which are abundant in ex vivo inclusions. These observations were supported by computational analysis of the S100A8/A9 calcium-dependent aggregation propensity profiles. We found DNA and proteins from Escherichia coli in CA bodies, suggesting that their formation is likely to be associated with bacterial infection. CA inclusions were also accompanied by the activation of macrophages and by an increase in the concentration of S100A8/A9 in the surrounding tissues, indicating inflammatory reactions. CONCLUSIONS/SIGNIFICANCE: These findings, taken together, suggest a link between bacterial infection, inflammation and amyloid deposition of pro-inflammatory proteins S100A8/A9 in the prostate gland, such that a self-perpetuating cycle can be triggered and may increase the risk of malignancy in the ageing prostate. The results provide strong support for the prediction that the generic ability of polypeptide chains to convert into amyloids could lead to their involvement in an increasing number of otherwise apparently unrelated diseases, particularly those associated with ageing.

Skapa referenser, mejla, bekava och länka

Länka till träfflistan

Träfflista för sökning "WFRF:(Vogl Thomas) "

Avgränsa träffmängd

År