| 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. |
- Aglago, Elom K., et al.
(författare)
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A Genetic Locus within the FMN1/GREM1 Gene Region Interacts with Body Mass Index in Colorectal Cancer Risk
- 2023
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Ingår i: Cancer Research. - : American Association For Cancer Research (AACR). - 0008-5472 .- 1538-7445. ; 83:15, s. 2572-2583
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Tidskriftsartikel (refereegranskat)abstract
- Colorectal cancer risk can be impacted by genetic, environmental, and lifestyle factors, including diet and obesity. Gene-environment interactions (G × E) can provide biological insights into the effects of obesity on colorectal cancer risk. Here, we assessed potential genome-wide G × E interactions between body mass index (BMI) and common SNPs for colorectal cancer risk using data from 36,415 colorectal cancer cases and 48,451 controls from three international colorectal cancer consortia (CCFR, CORECT, and GECCO). The G × E tests included the conventional logistic regression using multiplicative terms (one degree of freedom, 1DF test), the two-step EDGE method, and the joint 3DF test, each of which is powerful for detecting G × E interactions under specific conditions. BMI was associated with higher colorectal cancer risk. The two-step approach revealed a statistically significant G×BMI interaction located within the Formin 1/Gremlin 1 (FMN1/GREM1) gene region (rs58349661). This SNP was also identified by the 3DF test, with a suggestive statistical significance in the 1DF test. Among participants with the CC genotype of rs58349661, overweight and obesity categories were associated with higher colorectal cancer risk, whereas null associations were observed across BMI categories in those with the TT genotype. Using data from three large international consortia, this study discovered a locus in the FMN1/GREM1 gene region that interacts with BMI on the association with colorectal cancer risk. Further studies should examine the potential mechanisms through which this locus modifies the etiologic link between obesity and colorectal cancer.SIGNIFICANCE: This gene-environment interaction analysis revealed a genetic locus in FMN1/GREM1 that interacts with body mass index in colorectal cancer risk, suggesting potential implications for precision prevention strategies.
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| 3. |
- Andrén, Daniela, 1968, et al.
(författare)
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The Effect of Past Sickness on Current Earnings in Sweden
- 2004
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This paper examines whether sickness history affects annual earnings and/or hourly wages in Sweden, using a unique longitudinal database. If poor health makes people less productive, previous sickness is expected to have a negative effect on hourly wages. If poor health reduces peoplés working capacity, but not their productivity, it is expected to decrease the hours worked, which implies lower annual earnings and no change in their hourly wage. The results indicate that people who are healthy in the current year but have a longer spell of sickness in previous years have lower earnings than persons who have no record of long-term sickness, and that the effect goes through hours of work rather than the wage rate. In addition, in the current year, sickness has a convex relationship with earnings, going through wages. Persons with lower (higher) wages have more (fewer) days of compensated absenteeism.
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| 4. |
- Andrén, Daniela, 1968, et al.
(författare)
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The effect of sickness history on earnings in Sweden
- 2008
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Ingår i: Economic Issues. - : Nottingham Trent University. - 1363-7029. ; 13:1, s. 1-25
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Tidskriftsartikel (refereegranskat)abstract
- This study examines whether sickness history affects annual earnings and/or hourly wages in Sweden. If poor health makes people less productive, previous sickness is expected to have a negative effect on hourly wages. If poor health reduces people's working capacity, but not their productivity, it is expected to decrease the hours worked, which implies lower annual earnings and no change in their hourly wage. The results indicate that people who are healthy in the current year but have a longer spell of sickness in previous years have lower earnings than persons who have no record of long-term sickness, and that the effect goes through hours of work rather than the wage rate.
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| 5. |
- Andrén, Daniela, 1968, et al.
(författare)
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The effect of sickness on earnings
- 2001
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The question addressed in this paper is whether sickness history affects annual earnings and hourly wages in Sweden. If poor health makes people less productive, we expect to find a negative effect of previous health history on hourly wages. If, instead, poor health reduces peoples working capacity, but not their productivity, this implies only a decrease in hours worked. Using a longitudinal database for individual sickness, we estimate both (annual) earnings and (hourly) wage equations, and find that people who are healthy in the current year, but have long-term sickness in the previous five years have lower earnings than persons without long-term sickness.
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| 6. |
- Anna, Klerby, 1977-, et al.
(författare)
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Bridging Partner Lifecycle Earnings and Pension Gaps by Sharing NDC Accounts
- 2019
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Sweden’s gender pension gap is about 33 percent at retirement, reflecting thegender earnings gap – itself a reflection of a structural gender difference in low-pay jobs forwomen and men and career advancement opportunities. The individual nonfinancialdefined contribution (NDC) account data examined show that the allocation of time toinformal care work in the home versus formal market work is the main determinant of thegaps. A case is presented for sharing accounts as the default, making the cost of women’stime in home care explicit and negotiable, reducing the minimum guarantee pension’s roleas an implicit tax-financed spousal subsidy. The paper also analyzes the likelihood ofneeding a guarantee and the effect of sharing under various circumstances.
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| 7. |
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| 8. |
- Bengtsson, Tommy, et al.
(författare)
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Introduction
- 2019
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Ingår i: Demographic Research Monographs. - Cham : Springer International Publishing. - 2197-9286 .- 1613-5520. - 9783030050740 - 9783030050757 ; , s. 1-19
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Bokkapitel (refereegranskat)abstract
- Globally, the twenty-first century will witness rapid population ageing. Already in 2050, one out of five persons in the world, and one out of three in Europe, is expected to be 60 or over (UN 2015). Moreover, we have entered into a new stage of population ageing in terms of its causes, which have altered its consequences. In the first stage, lasting until the middle of the twentieth century in developed countries, population ageing was entirely due to the decline in fertility, with Sweden being commonly used as an example (Coale 1957; Bengtsson and Scott 2010; Lee and Zhou 2017). During this stage, the increase in life expectancy was primarily driven by declines in infant and child mortality. It worked in the opposite direction to the fertility decline, making the population younger since it added more years before, than after retirement (Coale 1957; Lee 1994). In the second stage of population ageing, which is the current situation, population ageing is primarily driven by the increase in life expectancy, which is now due to declining old-age mortality. As a result, more years are added after retirement than in working ages (Lee 1994). Could immigration or an upswing in fertility stop population ageing? The short answer is most likely not. The effect of migration on population aging is generally regarded as minor (Murphy 2017), and since population ageing is a global phenomenon, it will be of no general help anyway. A rapid increase in fertility is improbable and, in any case, an increase would take some 25 years before adding to the labor force. Instead, attention has been focused on how to adapt our social systems to the increasing number of elderly per worker – more so since the increase in the elderly-per-worker ratio came in parallel with a rise in per capita costs for the institutional care, home care, and general health care for the elderly.
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| 9. |
- Bouras, Emmanouil, et al.
(författare)
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Genome-wide interaction analysis of folate for colorectal cancer risk
- 2023
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Ingår i: American Journal of Clinical Nutrition. - : Elsevier. - 0002-9165 .- 1938-3207. ; 118:5, s. 881-891
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Tidskriftsartikel (refereegranskat)abstract
- Background: Epidemiological and experimental evidence suggests that higher folate intake is associated with decreased colorectal cancer (CRC) risk; however, the mechanisms underlying this relationship are not fully understood. Genetic variation that may have a direct or indirect impact on folate metabolism can provide insights into folate's role in CRC.Objectives: Our aim was to perform a genome-wide interaction analysis to identify genetic variants that may modify the association of folate on CRC risk.Methods: We applied traditional case-control logistic regression, joint 3-degree of freedom, and a 2-step weighted hypothesis approach to test the interactions of common variants (allele frequency >1%) across the genome and dietary folate, folic acid supplement use, and total folate in relation to risk of CRC in 30,550 cases and 42,336 controls from 51 studies from 3 genetic consortia (CCFR, CORECT, GECCO).Results: Inverse associations of dietary, total folate, and folic acid supplement with CRC were found (odds ratio [OR]: 0.93; 95% confidence interval [CI]: 0.90, 0.96; and 0.91; 95% CI: 0.89, 0.94 per quartile higher intake, and 0.82 (95% CI: 0.78, 0.88) for users compared with nonusers, respectively). Interactions (P-interaction < 5×10-8) of folic acid supplement and variants in the 3p25.2 locus (in the region of Synapsin II [SYN2]/tissue inhibitor of metalloproteinase 4 [TIMP4]) were found using traditional interaction analysis, with variant rs150924902 (located upstream to SYN2) showing the strongest interaction. In stratified analyses by rs150924902 genotypes, folate supplementation was associated with decreased CRC risk among those carrying the TT genotype (OR: 0.82; 95% CI: 0.79, 0.86) but increased CRC risk among those carrying the TA genotype (OR: 1.63; 95% CI: 1.29, 2.05), suggesting a qualitative interaction (P-interaction = 1.4×10-8). No interactions were observed for dietary and total folate.Conclusions: Variation in 3p25.2 locus may modify the association of folate supplement with CRC risk. Experimental studies and studies incorporating other relevant omics data are warranted to validate this finding.
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| 10. |
- Büntgen, Ulf, et al.
(författare)
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Global wood anatomical perspective on the onset of the Late Antique Little Ice Age (LALIA) in the mid-6th century CE
- 2022
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Ingår i: Science Bulletin. - : Elsevier BV. - 2095-9273. ; 67:22, s. 2336-2344
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Tidskriftsartikel (refereegranskat)abstract
- Linked to major volcanic eruptions around 536 and 540 CE, the onset of the Late Antique Little Ice Age has been described as the coldest period of the past two millennia. The exact timing and spatial extent of this exceptional cold phase are, however, still under debate because of the limited resolution and geographical distribution of the available proxy archives. Here, we use 106 wood anatomical thin sections from 23 forest sites and 20 tree species in both hemispheres to search for cell-level fingerprints of ephemeral summer cooling between 530 and 550 CE. After cross-dating and double-staining, we identified 89 Blue Rings (lack of cell wall lignification), nine Frost Rings (cell deformation and collapse), and 93 Light Rings (reduced cell wall thickening) in the Northern Hemisphere. Our network reveals evidence for the strongest temperature depression between mid-July and early-August 536 CE across North America and Eurasia, whereas more localised cold spells occurred in the summers of 532, 540–43, and 548 CE. The lack of anatomical signatures in the austral trees suggests limited incursion of stratospheric volcanic aerosol into the Southern Hemisphere extra-tropics, that any forcing was mitigated by atmosphere-ocean dynamical responses and/or concentrated outside the growing season, or a combination of factors. Our findings demonstrate the advantage of wood anatomical investigations over traditional dendrochronological measurements, provide a benchmark for Earth system models, support cross-disciplinary studies into the entanglements of climate and history, and question the relevance of global climate averages.
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