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| 2. |
- 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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| 3. |
- Alessie, Rob J. M., et al.
(författare)
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Economic conditions at birth and cardiovascular disease risk in adulthood : Evidence from post-1950 cohorts
- 2019
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Ingår i: Social Science and Medicine. - : Elsevier BV. - 0277-9536 .- 1873-5347. ; 224, s. 77-84
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Tidskriftsartikel (refereegranskat)abstract
- Much of the literature that studies long-run effects of early-life economic conditions on health outcomes is based on pre-1940 birth cohorts. Early in these individuals' lives, public social safety nets were at best rudimentary, and female labor force participation was relatively low. We complement the evidence by studying the effects of regional business cycle variations in the post-1950 Netherlands on cardiovascular disease risk in adulthood. We use data from Lifelines, a large cohort study that covers socio-economic, biological and health information from over 75,000 individuals aged between 20 and 63. Cardiovascular risk index is constructed from an extensive set of biomarkers. The results show that for women a 1 percentage point increase in the provincial unemployment level leads to a 0.02 percentage point increase in the risk of a fatal cardiovascular event in the coming 10 years while the effect in men is not significant. We conclude that women born in adverse economic conditions experience higher cardiovascular risk.
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| 4. |
- Beecham, Ashley H, et al.
(författare)
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Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis.
- 2013
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:11, s. 1353-60
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Tidskriftsartikel (refereegranskat)abstract
- Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 1.0 × 10(-4)). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 5.0 × 10(-8)), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals.
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| 5. |
- Fontana, Robert J., et al.
(författare)
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Daclatasvir combined with sofosbuvir or simeprevir in liver transplant recipients with severe recurrent hepatitis C infection
- 2016
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Ingår i: Liver transplantation. - : Ovid Technologies (Wolters Kluwer Health). - 1527-6465 .- 1527-6473. ; 22:4, s. 446-458
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Tidskriftsartikel (refereegranskat)abstract
- Daclatasvir (DCV) is a potent, pangenotypic nonstructural protein 5A inhibitor with demonstrated antiviral efficacy when combined with sofosbuvir (SOF) or simeprevir (SMV) with or without ribavirin (RBV) in patients with chronic hepatitis C virus (HCV) infection. Herein, we report efficacy and safety data for DCV-based all-oral antiviral therapy in liver transplantation (LT) recipients with severe recurrent HCV. DCV at 60mg/day was administered for up to 24 weeks as part of a compassionate use protocol. The study included 97 LT recipients with a mean age of 59.3 +/- 8.2 years; 93% had genotype 1 HCV and 31% had biopsy-proven cirrhosis between the time of LT and the initiation of DCV. The mean Model for End-Stage Liver Disease (MELD) score was 13.0 +/- 6.0, and the proportion with Child-Turcotte-Pugh (CTP) A/B/C was 51%/31%/12%, respectively. Mean HCV RNA at DCV initiation was 14.3x6 log(10) IU/mL, and 37% had severe cholestatic HCV infection. Antiviral regimens were selected by the local investigator and included DCV+SOF (n=77), DCV+SMV (n=18), and DCV+SMV+SOF (n=2); 35% overall received RBV. At the end of treatment (EOT) and 12 weeks after EOT, 88 (91%) and 84 (87%) patients, respectively, were HCV RNA negative or had levels <43 IU/mL. CTP and MELD scores significantly improved between DCV-based treatment initiation and last contact. Three virological breakthroughs and 2 relapses occurred in patients treated with DCV+SMV with or without RBV. None of the 8 patient deaths (6 during and 2 after therapy) were attributed to therapy. In conclusion, DCV-based all-oral antiviral therapy was well tolerated and resulted in a high sustained virological response in LT recipients with severe recurrent HCV infection. Most treated patients experienced stabilization or improvement in their clinical status.
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| 6. |
- Huttenhain, Ruth, et al.
(författare)
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A targeted mass spectrometry strategy for developing proteomic biomarkers : a case study of epithelial ovarian cancer
- 2019
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Ingår i: Molecular and Cellular Proteomics. - 1535-9484. ; 18:9, s. 1836-1850
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Tidskriftsartikel (refereegranskat)abstract
- Protein biomarkers for epithelial ovarian cancer are critical for the early detection of the cancer to improve patient prognosis and for the clinical management of the disease to monitor treatment response and to detect recurrences. Unfortunately, the discovery of protein biomarkers is hampered by the limited availability of reliable and sensitive assays needed for the reproducible quantification of proteins in complex biological matrices such as blood plasma. In recent years, targeted mass spectrometry, exemplified by Selected Reaction Monitoring (SRM) has emerged as a method, capable of overcoming this limitation. Here, we present a comprehensive SRM-based strategy for developing plasma-based protein biomarkers for epithelial ovarian cancer and illustrate how the SRM platform, when combined with rigorous experimental design and statistical analysis, can result in detection of predictive analytes.Our biomarker development strategy first involved a discovery-driven proteomic effort to derive potential N-glycoprotein biomarker candidates for plasma-based detection of human ovarian cancer from a genetically engineered mouse model of endometrioid ovarian cancer, which accurately recapitulates the human disease. Next, 65 candidate markers selected from proteins of different abundance in the discovery dataset were reproducibly quantified with SRM assays across a large cohort of over 200 plasma samples from ovarian cancer patients and healthy controls. Finally, these measurements were used to derive a 5-protein signature for distinguishing individuals with epithelial ovarian cancer from healthy controls. The sensitivity of the candidate biomarker signature in combination with CA125 ELISA-based measurements currently used in clinic, exceeded that of CA125 ELISA-based measurements alone. The SRM-based strategy in this study is broadly applicable. It can be used in any study that requires accurate and reproducible quantification of selected proteins in a high-throughput and multiplexed fashion.
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| 7. |
- Kehoe, Laura, et al.
(författare)
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Inclusion, Transparency, and Enforcement: How the EU-Mercosur Trade Agreement Fails the Sustainability Test Comment
- 2020
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Ingår i: One Earth. - : Elsevier BV. - 2590-3322 .- 2590-3330. ; 3:3, s. 268-272
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Tidskriftsartikel (refereegranskat)abstract
- Trade agreements could help to protect human rights, critical ecosystems, and the climate-but only if sustainability becomes a cornerstone of international trade. The EU-Mercosur trade agreement fails to meet our three tenets of sustainable trade agreements: (1) inclusion of local communities, (2) transparency mechanisms to trace commodities and provide open-access information, and (3) enforcement to legally uphold sustainability commitments.
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| 8. |
- Rescorla, Leslie, et al.
(författare)
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International Epidemiology of Child and Adolescent Psychopathology II: Integration and Applications of Dimensional Findings From 44 Societies
- 2012
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Ingår i: Journal of the American Academy of Child and Adolescent Psychiatry. - : Elsevier BV. - 0890-8567. ; 51:12, s. 1273-1283
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Forskningsöversikt (refereegranskat)abstract
- Objective: To build on Achenbach, Rescorla, and Ivanova (2012) by (a) reporting new international findings for parent, teacher, and self-ratings on the Child Behavior Checklist, Youth Self-Report, and Teacher's Report Form; (b) testing the fit of syndrome models to new data from 17 societies, including previously underrepresented regions; (c) testing effects of society gender, and age in 44 societies by integrating new and previous data; (d) testing cross-society correlations between mean item ratings; (e) describing the construction of multisociety norms; (f) illustrating clinical applications. Method: Confirmatory factor analyses (CFAs) of parent, teacher, and self-ratings, performed separately for each society; tests of societal, gender, and age effects on dimensional syndrome scales, DSM-oriented scales, Internalizing, Externalizing, and Total Problems scales; tests of agreement between low, medium, and high ratings of problem items across societies. Results: CFAs supported the tested syndrome models in all societies according to the primary fit index (Root Mean Square Error of Approximation [RMSEA]), but less consistently according to other indices; effect sizes were small-to-medium for societal differences in scale scores, but very small for gender, age, and interactions with society; items received similarly low, medium, or high ratings in different societies; problem scores from 44 societies fit three sets of multisociety norms. Conclusions: Statistically derived syndrome models fit parent, teacher, and self-ratings when tested individually in all 44 societies according to RMSEAs (but less consistently according to other indices). Small to medium differences in scale scores among societies supported the use of low-, medium-, and high-scoring norms in clinical assessment of individual children. J. Am. Acad. Child Aclolesc. Psychiatry; 2012; 51(12):1273-1283.
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| 9. |
- Valli, Katja, et al.
(författare)
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Can observers link dream content to behaviours in rapid eye movement sleep behaviour disorder? : A cross-sectional experimental pilot study
- 2012
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Ingår i: Journal of Sleep Research. - : Wiley-Blackwell. - 0962-1105 .- 1365-2869. ; 21:1, s. 21-29
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Tidskriftsartikel (refereegranskat)abstract
- Motor activity in rapid eye movement (REM) sleep behaviour disorder (RBD) has been linked to dream content. Systematic and controlled sleep laboratory studies directly assessing the relation between RBD behaviours and experienced dream content are, however, largely lacking. We aimed to investigate whether a link can be established between RBD behaviours and dream content when both are systematically sampled in a controlled setting. We investigated six patients with Parkinson syndrome and RBD who underwent 23 nights of videopolysomnographic recording during which they were awakened from REM sleep (10 min after the onset of the second and successive REM periods). Spontaneous free-worded dream reports and a structured dream questionnaire were obtained. Video recordings of motor manifestations were each combined with four dream reports, and seven judges had to match the video clip with the correctly reported dream content from a choice of four possibilities. Of the 35 REM sleep awakenings performed, a total of 17 (48.6%) motor-behavioural episodes with recalled dream content were obtained. The mean of correctly identified video-dream pairs was 39.5% (range 0100%). Our data showed that reported dream content can be linked to motor behaviours above chance level. Matching accuracy was affected mainly by the clarity of dream reports and the specific nature of movements manifest in video recordings.
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