| 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. |
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| 3. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 4. |
- Ademuyiwa, Adesoji O., et al.
(författare)
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Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
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Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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| 5. |
- Harper, Graham M., et al.
(författare)
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Sofia-exes observations of betelgeuse during the great dimming of 2019/2020
- 2020
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8205 .- 2041-8213. ; 893:1
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Tidskriftsartikel (refereegranskat)abstract
- In 2019 October Betelgeuse began a decline in V-band brightness that went beyond the minimum expected from its quasi-periodic ∼420 day cycle, becoming the faintest in recorded photometric history. Observations obtained in 2019 December with Very Large Telescope/SPHERE have shown that the southern half of the star has become markedly fainter than in 2019 January, indicating that a major change has occurred in, or near, the photosphere. We present Stratospheric Observatory for Infrared Astronomy (SOFIA) Echelon Cross Echelle Spectrograph (EXES) high spectral-resolution observations of [Fe II] 25.99 μm and [S I] 25.25 μm emission lines from Betelgeuse obtained during the unprecedented 2020 February V-band brightness minimum to investigate potential changes in the circumstellar flow. These spectra are compared to observations obtained in 2015 and 2017 when the V magnitude was typical of brighter phases. We find only very small changes in the gas velocities reflected by either of the line profiles, no significant changes in the flux to continuum ratios, and hence no significant changes in the [Fe ii]/[S i] flux ratios. There is evidence that absorption features have appeared in the 2020 continuum. The Alfvén wave-crossing time from the upper photosphere is sufficiently long that one would not expect a change in the large-scale magnetic field to reach the circumstellar [Fe ii] and [S i] line-forming regions, 3 < R (R ∗) < 20. However, the light-crossing time is of order a few hours and a reduction in luminosity may reduce the dust-gas heating rate and [O i] 63.19 μm emission, which has contributions from R > 20R ∗, where significant circumstellar oxygen-rich dust is observed.
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| 6. |
- Sumaila, U. Rashid, et al.
(författare)
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WTO must ban harmful fisheries subsidies
- 2021
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 374:6567, s. 544-544
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 7. |
- Harper, Graham M., et al.
(författare)
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The Photospheric Temperatures of Betelgeuse during the Great Dimming of 2019/2020 : No New Dust Required
- 2020
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 905:1
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Tidskriftsartikel (refereegranskat)abstract
- The processes that shape the extended atmospheres of red supergiants, heat their chromospheres, create molecular reservoirs, drive mass loss, and create dust remain poorly understood. Betelgeuse's V-band "Great Dimming"event of 2019 September/2020 February and its subsequent rapid brightening provides a rare opportunity to study these phenomena. Two different explanations have emerged to explain the dimming; new dust appeared in our line of sight attenuating the photospheric light, or a large portion of the photosphere had cooled. Here we present five years of Wing three-filter (A, B, and C band) TiO and near-IR photometry obtained at the Wasatonic Observatory. These reveal that parts of the photosphere had a mean effective temperature (T eff) significantly lower than that found by Levesque & Massey. Synthetic photometry from MARCS-model photospheres and spectra reveal that the V band, TiO index, and C-band photometry, and previously reported 4000-6800 Å spectra can be quantitatively reproduced if there are multiple photospheric components, as hinted at by Very Large Telescope (VLT)-SPHERE images in Montargès et al. If the cooler component has ΔT eff ≥ 250 K cooler than 3650 K, then no new dust is required to explain the available empirical constraints. A coincidence of the dominant short-(∼430 days) and long-period (∼5.8 yr) V-band variations occurred near the time of deep minimum (Guinan et al. 2019a). This is in tandem with the strong correlation of V mag and photospheric radial velocities, recently reported by Dupree et al. (2020b). These suggest that the cooling of a large fraction of the visible star has a dynamic origin related to the photospheric motions, perhaps arising from pulsation or large-scale convective motions.
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| 8. |
- Harper, Jon Alexander, et al.
(författare)
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Systematic review reveals multiple sexually antagonistic polymorphisms affecting human disease and complex traits
- 2021
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Ingår i: Evolution. - : John Wiley & Sons. - 0014-3820 .- 1558-5646. ; 75:12, s. 3087-3097
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Tidskriftsartikel (refereegranskat)abstract
- An evolutionary model for sex differences in disease risk posits that alleles conferring higher risk in one sex may be protective in the other. These sexually antagonistic (SA) alleles are predicted to be maintained at frequencies higher than expected under purifying selection against unconditionally deleterious alleles, but there are apparently no examples in humans. Discipline-specific terminology, rather than a genuine lack of such alleles, could explain this disparity. We undertook a two-stage review of evidence for SA polymorphisms in humans using search terms from (i) evolutionary biology and (ii) biomedicine. Although the first stage returned no eligible studies, the second revealed 51 genes with sex-opposite effects; 22 increased disease risk or severity in one sex but protected the other. Those with net positive effects occurred at higher frequencies. None were referred to as SA. Our review reveals significant communication barriers to fields as a result of discipline-specific terminology.
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| 9. |
- Harper, Jon Alexander, et al.
(författare)
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Systematic review reveals sexually antagonistic knockouts in model organisms
- 2022
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Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 12:12
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Forskningsöversikt (refereegranskat)abstract
- Sexual antagonism is thought to be an important selective force in multiple evolutionary processes, but very few examples of the genes involved are known. Such a deficit of loci could partially be explained by the lack of overlap in terminology between scientific disciplines. Following a similar review in humans, we searched systematically for studies that described genes with sexually antagonistic or sex-opposite effects in any taxa, using terms designed to capture alternative descriptions of sexual antagonism. Despite drawing on a potentially very large pool of studies we found only eight articles, which between them described seven candidate variants, five of these were gene knockouts. In every case, the variants had net negative effects on the focal trait. One locus was independently validated between studies, but in comparison to previous data on variants in humans and the fruit-fly, the studies generally suffered from small sample sizes, with concomitant high variance. Our review highlights the radically different effects that gene deletions can have on males and females, where the beneficial effects seen in one sex may facilitate the evolution of gene loss. We searched systematically for genetic variants with sexually antagonistic or sex-opposite effects in any taxa. Of 2116 articles, we found seven candidate variants, five of which were gene knockouts. Our review highlights the radically different effects that gene deletions can have on males and females, where the beneficial effects seen in one sex may facilitate the evolution of gene loss.
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| 10. |
- Mah, Jean K, et al.
(författare)
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A multinational study on motor function in early-onset FSHD.
- 2018
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Ingår i: Neurology. - 1526-632X. ; 90:15, s. e1333-e1338
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Tidskriftsartikel (refereegranskat)abstract
- To investigate motor function associations with age, sex, and D4Z4 repeats among participants with early-onset facioscapulohumeral muscular dystrophy (FSHD) type 1 as defined by weakness onset before 10 years of age.We collected standardized motor assessments, including manual muscle testing (MMT), quantitative muscle testing, functional motor evaluations, and clinical severity scores (CSSs), at 12 Cooperative International Neuromuscular Research Group centers. To measure associations, we used linear regression models adjusted for sex, evaluation age, age at onset of weakness, and D4Z4 repeats.Among 52 participants (60% female, mean age 22.9 ± 14.7 years), weakness was most pronounced in the shoulder and abdominal musculature. Older enrollment age was associated with greater CSSs (p = 0.003). When adjusted for enrollment age, sex, and D4Z4 repeats, younger age at onset of facial weakness was associated with greater CSSs, slower velocities in timed function tests, and lower MMT scores (p < 0.05).Significant clinical variability was observed in early-onset FSHD. Earlier age at onset of facial weakness was associated with greater disease severity. Longitudinal assessments are needed to determine the rate of disease progression in this population.
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