| 1. |
- 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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| 2. |
- Maguire, K., et al.
(författare)
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A statistical analysis of circumstellar material in Type Ia supernovae
- 2013
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 436:1, s. 222-240
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Tidskriftsartikel (refereegranskat)abstract
- A key tracer of the elusive progenitor systems of Type Ia supernovae (SNe Ia) is the detection of narrow blueshifted time-varying Na I D absorption lines, interpreted as evidence of circumstellar material surrounding the progenitor system. The origin of this material is controversial, but the simplest explanation is that it results from previous mass-loss in a system containing a white dwarf and a non-degenerate companion star. We present new single-epoch intermediate-resolution spectra of 17 low-redshift SNe Ia taken with XShooter on the European Southern Observatory Very Large Telescope. Combining this sample with events from the literature, we confirm an excess (similar to 20 per cent) of SNe Ia displaying blueshifted narrow Na I D absorption features compared to redshifted Na I D features. The host galaxies of SNe Ia displaying blueshifted absorption profiles are skewed towards later-type galaxies, compared to SNe Ia that show no Na I D absorption and SNe Ia displaying blueshifted narrow Na I D absorption features have broader light curves. The strength of the Na I D absorption is stronger in SNe Ia displaying blueshifted Na I D absorption features than those without blueshifted features, and the strength of the blueshifted Na I D is correlated with the B - V colour of the SN at maximum light. This strongly suggests the absorbing material is local to the SN. In the context of the progenitor systems of SNe Ia, we discuss the significance of these findings and other recent observational evidence on the nature of SN Ia progenitors. We present a summary that suggests that there are at least two distinct populations of normal, cosmologically useful SNe Ia.
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| 3. |
- Valenti, S., et al.
(författare)
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PESSTO spectroscopic classification of La Silla-Quest Transients
- 2012
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- PESSTO is the "Public ESO Spectroscopic Survey of Transient Objects" (http://www.pessto.org) using the ESO New Technology Telescope (NTT) at La Silla and the EFOSC2 (optical) and SOFI (near-IR) spectrographs. It is one of two currently running public spectroscopic surveys at ESO. The survey details are as follows: - PESSTO has 90 nights per year on the NTT: 9 lunations (August to April), 10 nights per lunation (we are not observing May-July).
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| 4. |
- Amzaleg, Y., et al.
(författare)
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Estrogens and selective estrogen receptor modulators differentially antagonize Runx2 in ST2 mesenchymal progenitor cells
- 2018
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Ingår i: Journal of Steroid Biochemistry and Molecular Biology. - : Elsevier BV. - 0960-0760 .- 1879-1220. ; 183, s. 10-17
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Tidskriftsartikel (refereegranskat)abstract
- Estrogens attenuate bone turnover by inhibiting both osteoclasts and osteoblasts, in part through antagonizing Runx2. Apparently conflicting, stimulatory effects in osteoblast lineage cells, however, sway the balance between bone resorption and bone formation in favor of the latter. Consistent with this dualism, 17 beta-estradiol (E2) both stimulates and inhibits Runx2 in a locus-specific manner, and here we provide evidence for such locus specific regulation of Runx2 by E2 in vivo. We also demonstrate dual, negative and positive, regulation of Runx2-driven alkaline phosphatase (ALP) activity by increasing E2 concentrations in ST2 osteoblast progenitor cells. We further compared the effects of E2 to those of the Selective Estrogen Receptor Modulators (SERMs) raloxifene (ral) and lasofoxifene (las) and the phytoestrogen puerarin. We found that E2 at the physiological concentrations of 0.1-1 nM, as well as ral and las, but not puerarin, antagonize Runx2-driven ALP activity. At >= 10 nM, E2 and puerarin, but not ral or las, stimulate ALP relative to the activity measured at 0.1-1 nM. Contrasting the difference between E2 and SERMs in ST2 cells, they all shared a similar dose-response profile when inhibiting preosteoclast proliferation. That ral and las poorly mimic the locus-and concentration-dependent effects of E2 in mesenchymal progenitor cells may help explain their limited clinical efficacy.
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| 5. |
- Chambers, John C., et al.
(författare)
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Genetic loci influencing kidney function and chronic kidney disease
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:5, s. 373-375
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Tidskriftsartikel (refereegranskat)abstract
- Using genome-wide association, we identify common variants at 2p12-p13, 6q26, 17q23 and 19q13 associated with serum creatinine, a marker of kidney function (P = 10(-10) to 10(-15)). Of these, rs10206899 (near NAT8, 2p12-p13) and rs4805834 (near SLC7A9, 19q13) were also associated with chronic kidney disease (P = 5.0 x 10(-5) and P = 3.6 x 10(-4), respectively). Our findings provide insight into metabolic, solute and drug-transport pathways underlying susceptibility to chronic kidney disease.
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| 6. |
- Lutz, D., et al.
(författare)
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Molecular outflows in local galaxies: Method comparison and a role of intermittent AGN driving
- 2020
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 633
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Tidskriftsartikel (refereegranskat)abstract
- We report new detections and limits from a NOEMA and ALMA CO(1-0) search for molecular outflows in 13 local galaxies with high far-infrared surface brightness, and combine these with local universe CO outflow results from the literature. The CO line ratios and spatial outflow structure of our targets provide some constraints on the conversion steps from observables to physical quantities such as molecular mass outflow rates. Where available, ratios between outflow emission in higher J CO transitions and in CO(1-0) are typically consistent with excitation R-i1 less than or similar to 1. However, for IRAS 13120 5453, R-31 = 2.10 +/- 0.29 indicates optically thin CO in the outflow. Like much of the outflow literature, we use ff CO(1 0) = 0.8, and we present arguments for using C = 1 in deriving molecular mass outflow rates. (M)over dot(out) = CM(out)v(out)/R-out. We compare the two main methods for molecular outflow detection: CO millimeter interferometry and Herschel OH-based spectroscopic outflow searches. For 26 sources studied with both methods, we find an 80% agreement in detecting vout & 150 km s 1 outflows, and non-matches can be plausibly ascribed to outflow geometry and signal-to-noise ratio. For a published sample of 12 bright ultraluminous infrared galaxies with detailed OH-based outflow modeling, CO outflows are detected in all but one. Outflow masses, velocities, and sizes for these 11 sources agree well between the two methods, and modest remaining di fferences may relate to the di fferent but overlapping regions sampled by CO emission and OH absorption. Outflow properties correlate better with active galactic nucleus (AGN) luminosity and with bolometric luminosity than with far-infrared surface brightness. The most massive outflows are found for systems with current AGN activity, but significant outflows in nonAGN systems must relate to star formation or to AGN activity in the recent past. We report scaling relations for the increase of outflow mass, rate, momentum rate, and kinetic power with bolometric luminosity. Short flow times of similar to 10(6) yr and some sources with resolved multiple outflow episodes support a role of intermittent driving, likely by AGNs.
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| 8. |
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| 9. |
- Powles, T, et al.
(författare)
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Plain language summary of results from the JAVELIN Bladder 100 study: avelumab maintenance treatment for advanced urothelial cancer
- 2022
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Ingår i: Future oncology (London, England). - : Future Medicine Ltd. - 1744-8301 .- 1479-6694. ; 18:19, s. 2361-2371
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Tidskriftsartikel (refereegranskat)abstract
- This is a plain language summary of an article originally published in The New England Journal of Medicine. It is about initial results (collected in October 2019) from the JAVELIN Bladder 100 study (a clinical trial), which looked at avelumab maintenance treatment in people with advanced urothelial cancer. Urothelial cancer is the most common type of bladder cancer. People with advanced urothelial cancer often receive chemotherapy. If this is the first treatment people with advanced disease are given, it is called first-line treatment. If the cancer stops growing or shrinks with first-line chemotherapy, people can be given different treatment to try to prevent the cancer from growing again. This is called maintenance treatment. It may help people live longer. What happened in the JAVELIN Bladder 100 study? In the JAVELIN Bladder 100 study, researchers wanted to find out if maintenance treatment with avelumab would help people with advanced urothelial cancer live longer. Avelumab is a type of medicine called immunotherapy. Immunotherapy helps the body's immune system fight cancer. 700 people took part in the study. To take part, they must have already been treated with first-line chemotherapy. Also, their cancer must have shrunk or not grown with this treatment. They were then treated with either avelumab maintenance treatment plus best supportive care or best supportive care alone. Best supportive care means treatments that help improve symptoms and quality of life. These treatments do not affect the cancer directly and can include medicines to relieve pain. What were the results? Researchers found that people treated with avelumab maintenance treatment plus best supportive care lived, on average, 7 months longer than people who received best supportive care alone. People treated with avelumab had more side effects than those not treated with avelumab, but most were not severe. Common side effects with avelumab included persistent tiredness, itchy skin, urinary tract infection, and diarrhea. What do the results of the study mean? Results from the JAVELIN Bladder 100 study support the use of avelumab as maintenance treatment for people with advanced urothelial cancer whose cancer has shrunk or not grown with first-line chemotherapy. ClinicalTrials.gov NCT number: NCT02603432
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| 10. |
- Röllig, M., et al.
(författare)
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A photon dominated region code comparison study
- 2007
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 467:No. 1 (May III 2007), s. 187-206
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Tidskriftsartikel (refereegranskat)abstract
- Aims.We present a comparison between independent computer codes, modeling the physics and chemistry of interstellar photon dominated regions (PDRs). Our goal was to understand the mutual differences in the PDR codes and their effects on the physical and chemical structure of the model clouds, and to converge the output of different codes to a common solution.Methods. A number of benchmark models have been created, covering low and high gas densities n = 103,105.5 cm-3 and far ultraviolet intensities $\chi$ = 10, 105 in units of the Draine field (FUV: 6
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