| 1. |
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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. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 4. |
- Wang, J., et al.
(författare)
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Final report of the CCQM-K145 : Toxic and essential elements in bovine liver
- 2020
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Ingår i: Metrologia. - : IOP Publishing Ltd. - 0026-1394 .- 1681-7575. ; 57:1 A
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Tidskriftsartikel (refereegranskat)abstract
- Liver plays a major role in metabolism and acts as a source of energy for the body by storing glycogen. With the growing interest and investigation in the biological effects in recent years, it is important and necessary to develop accurate and comparable analytical methods for elements in bio-samples. It has, however, been 10 years since the tissue sample (bovine liver) of CCQM-K49 key comparison. The purpose of CCQM-K145 is to ensure the comparable and traceable measurement results for essential and toxic elements such as P, S, Zn, Mn, Ni, Mo, Sr, Cr, Co, Pb, As and Hg in bovine liver among NMIs and other designated measurement bodies worldwide. The comparison was agreed by IAWG as 6th IAWG Benchmarking Exercise with Zn and Ni as exemplary elements at the meeting in Korea in the early October 2016. The results of CCQM-K145 are expected to cover the measurement capability and support CMCs claiming for inorganic elements in the similar biological tissue materials and food samples. 30 NMIs and DIs registered in CCQM-K145. With respect to the methodology, a variety of techniques such as IDMS, ICP-OES, ICP-MS(non-ID), AAS and NAA were adopted by the participants. For Zn, Ni, Sr, Pb and Hg measurements, most participants chose ID-ICP-MS method, which showed the better performance in terms of consistency and reliability of the measurement results. In aspect of the traceability for the measurement results in CCQM-K145, most participants used their own (in house) CRMs or other NMI's CRMs to guarantee trace to SI unit. Most participants used similar matrix CRMs for quality control or method validation. Base on different statistic way to calculate the reference mass fraction values and associated uncertainties for each measurand, removal of the suspected extreme values, and discussion at the IAWG meetings, the median values are proposed as the KCRV for Zn, Ni, Mn, Mo, Cr, Pb and Hg; the arithmetic mean values are proposed as the KCRV for P, S, Sr, Co and As. In general, the performances of the majority of CCQM-K145 participants are very good, illustrating their measurement capabilities for Zn, Ni, P, S, Mn, Mo, Sr, Cr, As, Co, Pb and Hg in a complex biological tissue matrix. Bovine liver contains many kinds of nutrients and microelements, it can be regarded as a typical representative material of biological tissue and food. In CCQM-K145, the analytes involved alkali metals and transition elements, metalloids/semi-metals and non metals with a range of mass fraction from mg/g to μg/kg. CCQM-K145 also tested the ability of NMIs/DIs to determine elements that were easy to be lost and polluted, and interfered significantly. The chemical pretreatment methods of samples used in the comparison is suitable for general food and biological matrix samples. A variety of measurement methods used in the comparison represent the main instrumental technology for elemental analysis. Therefore, for supporting CMC claim, CCQM-K145 is readily applicable to measurement of more elements in a wide range of biological materials (including liquids and solids) and meat products. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCQM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).
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| 5. |
- Menkveld, Albert J., et al.
(författare)
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Nonstandard Errors
- 2024
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Ingår i: JOURNAL OF FINANCE. - : Wiley-Blackwell. - 0022-1082 .- 1540-6261. ; 79:3, s. 2339-2390
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Tidskriftsartikel (refereegranskat)abstract
- In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty-nonstandard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for more reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants.
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| 6. |
- Li, Josephine H., et al.
(författare)
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Identification of Genetic Variation Influencing Metformin Response in a Multiancestry Genome-Wide Association Study in the Diabetes Prevention Program (DPP)
- 2023
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 72:8, s. 1161-1172
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide significant loci for metformin response in type 2 diabetes reported elsewhere have not been repli-cated in the Diabetes Prevention Program (DPP). To as-sess pharmacogenetic interactions in prediabetes, we conducted a genome-wide association study (GWAS) in the DPP. Cox proportional hazards models tested associations with diabetes incidence in the metformin (MET; n = 876) and placebo (PBO; n = 887) arms. Multiple linear regression assessed association with 1-year change in metformin-related quantitative traits, adjusted for baseline trait, age, sex, and 10 ancestry principal compo-nents. We tested for gene-by-treatment interaction. No significant associations emerged for diabetes inci-dence. We identified four genome-wide significant variants after correcting for correlated traits (P < 9 × 1029). In the MET arm, rs144322333 near ENOSF1 (minor al-lele frequency [MAF]AFR = 0.07; MAFEUR = 0.002) was associated with an increase in percentage of glycated hemoglobin (per minor allele, b = 0.39 [95% CI 0.28, 0.50]; P = 2.8 × 10212). rs145591055 near OMSR (MAF = 0.10 in American Indians) was associated with weight loss (kilograms) (per G allele, b = 27.55 [95% CI 29.88, 25.22]; P = 3.2 × 10210) in the MET arm. Neither variant was significant in PBO; gene-by-treatment interaction was significant for both variants [P(G×T) < 1.0 × 1024 ]. Replication in individuals with diabetes did not yield significant findings. A GWAS for metformin response in prediabetes revealed novel ethnic-specific associations that require further investigation but may have implications for tailored therapy.
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| 7. |
- Bijkerk, Roel, et al.
(författare)
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In Vivo Silencing of MicroRNA-132 Reduces Blood Glucose and Improves Insulin Secretion
- 2019
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Ingår i: Nucleic acid therapeutics. - : Mary Ann Liebert Inc. - 2159-3337 .- 2159-3345. ; 29:2, s. 67-72
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Tidskriftsartikel (refereegranskat)abstract
- Dysfunctional insulin secretion is a hallmark of type 2 diabetes (T2D). Interestingly, several islet microRNAs (miRNAs) are upregulated in T2D, including miR-132. We aimed to investigate whether in vivo treatment with antagomir-132 lowers expression of miR-132 in islets thereby improving insulin secretion and lowering blood glucose. Mice injected with antagomir-132 for 24 h, had reduced expression of miR-132 expression in islets, decreased blood glucose, and increased insulin secretion. In isolated human islets treated with antagomir-132, insulin secretion from four of six donors increased. Target prediction coupled with analysis of miRNA-messenger RNA expression in human islets revealed DESI2, ARIH1, SLC25A28, DIAPH1, and FOXA1 to be targets of miR-132 that are conserved in both species. Increased expression of these targets was validated in mouse islets after antagomir-132 treatment. In conclusion, we identified a post-transcriptional role for miR-132 in insulin secretion, and demonstrated that systemic antagomir-132 treatment in mice can be used to improve insulin secretion and reduce blood glucose in vivo. Our study is a first step towards utilizing antagomirs as therapeutic agents to modulate islet miRNA levels to improve beta cell function.
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| 8. |
- Burke, Michael J., et al.
(författare)
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Transplant Outcomes for Children with T Cell Acute Lymphoblastic Leukemia in Second Remission : A Report from the Center for International Blood and Marrow Transplant Research
- 2015
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Ingår i: Biology of blood and marrow transplantation. - : Elsevier BV. - 1083-8791 .- 1523-6536. ; 21:12, s. 2154-2159
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Tidskriftsartikel (refereegranskat)abstract
- Survival for children with relapsed T cell acute lymphoblastic leukemia (T-ALL) is poor when treated with chemotherapy alone, and outcomes after allogeneic hematopoietic cell transplantation (HCT) is not well described. Two hundred twenty-nine children with T-ALL in second complete remission (CR2) received an HCT after myeloablative conditioning between 2000 and 2011 and were reported to the Center for International Blood and Marrow Transplant Research. Median age was 10 years (range, 2 to 18). Donor source was umbilical cord blood (26%), matched sibling bone marrow (38%), or unrelated bone marrow/peripheral blood (36%). Acute (grades II to IV) and chronic graft-versus-host disease occurred in, respectively, 35% (95% confidence interval [CI], 27% to 45%) and 26% (95% CI, 20% to 33%) of patients. Transplant-related mortality at day 100 and 3-year relapse rates were 13% (95% CI, 9% to 18%) and 30% (95% CI, 24% to 37%), respectively. Three-year overall survival and disease-free survival rates were 48% (95% CI, 41% to 55%) and 46% (95% CI, 39% to 52%), respectively. In multivariate analysis, patients with bone marrow relapse, with or without concurrent extramedullary relapse before HCT, were most likely to relapse (hazard ratio, 3.94; P =.005) as compared with isolated extramedullary disease. In conclusion, HCT for pediatric T-ALL in CR2 demonstrates reasonable and durable outcomes, and consideration for HCT is warranted. (c) 2015 American Society for Blood and Marrow Transplantation.
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| 9. |
- Freud, Lindsay R., et al.
(författare)
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Prenatal vs postnatal diagnosis of 22q11.2 deletion syndrome: cardiac and noncardiac outcomes through 1 year of age
- 2024
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Ingår i: American Journal of Obstetrics and Gynecology. - 0002-9378 .- 1097-6868. ; 230:3
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Tidskriftsartikel (refereegranskat)abstract
- Background: The 22q11.2 deletion syndrome is the most common microdeletion syndrome and is frequently associated with congenital heart disease. Prenatal diagnosis of 22q11.2 deletion syndrome is increasingly offered. It is unknown whether there is a clinical benefit to prenatal detection as compared with postnatal diagnosis. Objective: This study aimed to determine differences in perinatal and infant outcomes between patients with prenatal and postnatal diagnosis of 22q11.2 deletion syndrome. Study Design: This was a retrospective cohort study across multiple international centers (30 sites, 4 continents) from 2006 to 2019. Participants were fetuses, neonates, or infants with a genetic diagnosis of 22q11.2 deletion syndrome by 1 year of age with or without congenital heart disease; those with prenatal diagnosis or suspicion (suggestive ultrasound findings and/or high-risk cell-free fetal DNA screen for 22q11.2 deletion syndrome with postnatal confirmation) were compared with those with postnatal diagnosis. Perinatal management, cardiac and noncardiac morbidity, and mortality by 1 year were assessed. Outcomes were adjusted for presence of critical congenital heart disease, gestational age at birth, and site. Results: A total of 625 fetuses, neonates, or infants with 22q11.2 deletion syndrome (53.4% male) were included: 259 fetuses were prenatally diagnosed (156 [60.2%] were live-born) and 122 neonates were prenatally suspected with postnatal confirmation, whereas 244 infants were postnatally diagnosed. In the live-born cohort (n=522), 1-year mortality was 5.9%, which did not differ between groups but differed by the presence of critical congenital heart disease (hazard ratio, 4.18; 95% confidence interval, 1.56–11.18; P<.001) and gestational age at birth (hazard ratio, 0.78 per week; 95% confidence interval, 0.69–0.89; P<.001). Adjusting for critical congenital heart disease and gestational age at birth, the prenatal cohort was less likely to deliver at a local community hospital (5.1% vs 38.2%; odds ratio, 0.11; 95% confidence interval, 0.06–0.23; P<.001), experience neonatal cardiac decompensation (1.3% vs 5.0%; odds ratio, 0.11; 95% confidence interval, 0.03–0.49; P=.004), or have failure to thrive by 1 year (43.4% vs 50.3%; odds ratio, 0.58; 95% confidence interval, 0.36–0.91; P=.019). Conclusion: Prenatal detection of 22q11.2 deletion syndrome was associated with improved delivery management and less cardiac and noncardiac morbidity, but not mortality, compared with postnatal detection.
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| 10. |
- Insulander Björk, Klara L, 1982, et al.
(författare)
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Irradiation testing of enhanced uranium oxide fuels
- 2019
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Ingår i: Annals of Nuclear Energy. - : Elsevier BV. - 0306-4549 .- 1873-2100. ; 125, s. 99-106
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Tidskriftsartikel (refereegranskat)abstract
- Enhanced uranium oxide fuel types are being tested in the Halden Research Reactor in Norway with the aim is to assess the effect that these enhancements have on fuel performance. Fuel temperatures, rod pressures and dimensional changes are being monitored online and an extensive post-irradiation examination programme is planned. Preliminary data show that fuel centerline temperatures can be lowered by addition of ThO2 to the fuel matrix, or by incorporating Cr or SiO2-TiO2 as a network structure within the fuel. In parallel, two types of cladding coatings are tested in order to investigate their in-core properties. No abnormal behaviour has been noted during the first 100 days of irradiation.
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