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- 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. |
- Bodda, C., et al.
(författare)
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HSV1 VP1-2 deubiquitinates STING to block type I interferon expression and promote brain infection
- 2020
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Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 217:7
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Tidskriftsartikel (refereegranskat)abstract
- Herpes simplex virus (HSV) is the main cause of viral encephalitis in the Western world, and the type I interferon (IFN) system is important for antiviral control in the brain. Here, we have compared Ifnb induction in mixed murine brain cell cultures by a panel of HSV1 mutants, each devoid of one mechanism to counteract the IFN-stimulating cGAS-STING pathway. We found that a mutant lacking the deubiquitinase (DUB) activity of the VP1-2 protein induced particularly strong expression of Ifnb and IFN-stimulated genes. HSV1 ΔDUB also induced elevated IFN expression in murine and human microglia and exhibited reduced viral replication in the brain. This was associated with increased ubiquitination of STING and elevated phosphorylation of STING, TBK1, and IRF3. VP1-2 associated directly with STING, leading to its deubiquitination. Recruitment of VP1-2 to STING was dependent on K150 of STING, which was ubiquitinated by TRIM32. Thus, the DUB activity of HSV1 VP1-2 is a major viral immune-evasion mechanism in the brain. © 2020 Bodda et al.
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| 3. |
- Agholme, M. B., et al.
(författare)
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Incidence, severity, and temporal development of oral complications in pediatric allogeneic hematopoietic stem cell transplant patients - a multicenter study
- 2023
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Ingår i: Supportive Care in Cancer. - 0941-4355. ; 31:12, s. 702-
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Forskningsöversikt (refereegranskat)abstract
- PurposeOral mucositis is a common complication for patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) and causes pain and difficulties in functions like eating and swallowing, resulting in lower quality of life and greater need of treatment with opioids and parenteral nutrition. This prospective multicenter study focused on pediatric recipients of HSCT in the neutropenic phase concerning oral complications, timing, severity, and patient experience.MethodsThe cohort comprised 68 patients, median age 11.1 years (IQR 6.3) receiving allogeneic HSCT at three clinical sites. Medical records were retrieved for therapy regimens, concomitant medications, oral and dental history, and subjective oral complaints. Calibrated dentists conducted an oral and dental investigation before HSCT. After HSCT graft infusion, study personnel made bedside assessments and patients filled out a questionnaire once or twice a week until neutrophil engraftment.ResultsWe followed 63 patients through the neutropenic phase until engraftment. 50% developed oral mucositis of grades 2-4. Peak severity occurred at 8-11 days after stem cell infusion. Altogether, 87% had subjective oral complaints. The temporal distribution of adverse events is similar to the development of oral mucositis. The most bothersome symptoms were blisters and oral ulcerations, including mucositis; 40% reported severe pain and major impact on activities of daily living despite continuous use of opioids.ConclusionThis study highlights the burden of oral complications and their negative effect on the health and quality of life of HSCT recipients.
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| 5. |
- Mogren, A., et al.
(författare)
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Children and adolescents with speech sound disorders are more likely to have orofacial dysfunction and malocclusion
- 2022
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Ingår i: Clinical and Experimental Dental Research. - : Wiley. - 2057-4347. ; 8:5, s. 1130-1141
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Tidskriftsartikel (refereegranskat)abstract
- Background: Children with speech sound disorders (SSD) form a heterogeneous group that differs in terms of underlying cause and severity of speech difficulties. Orofacial dysfunction and malocclusions have been reported in children with SSD. However, the association is not fully explored. Objectives: Our aims were to describe differences in orofacial function and malocclusion between a group of children and adolescents with compared to without SSD and to explore associations between those parameters among the group with SSD. Methods: A total of 105 participants were included, 61 children with SSD (6.0-16.7 years, mean age 8.5 +/- 2.8, 14 girls and 47 boys) and 44 children with typical speech development (TSD) (6.0-12.2 years, mean age 8.8 +/- 1.6, 19 girls and 25 boys). Assessments of orofacial function included an orofacial screening test and assessment of bite force, jaw stability, chewing efficiency, and intraoral sensory-motor function. Possible malocclusions were also assessed. Result: Children with SSD had both poorer orofacial function and a greater prevalence of malocclusion than children with TSD. Furthermore, children with SSD and poorer orofacial function had a greater risk of malocclusion. Conclusion: Our result suggests that children with SSD are more prone to having poorer orofacial function and malocclusion than children with TSD. This illustrates the importance of assessing coexisting orofacial characteristics in children with SSD, especially since orofacial dysfunction may be linked to an increased risk of malocclusion. This result highlights the need for a multiprofessional approach.
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| 6. |
- Mogren, A., et al.
(författare)
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Malocclusion in children with speech sound disorders and motor speech involvement: a cross-sectional clinical study in Swedish children
- 2022
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Ingår i: European Archives of Paediatric Dentistry. - : Springer Science and Business Media LLC. - 1818-6300 .- 1996-9805. ; 23:4, s. 619-628
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Tidskriftsartikel (refereegranskat)abstract
- Objectives The objectives of this study were to investigate the occurrence, types and severity of malocclusions in children with speech sound disorder (SSD) persisting after 6 years of age, and to compare these findings to a control group of children with typical speech development (TSD). Methods In total, 105 children were included: 61 with SSD and motor speech involvement (mean age 8:5 +/- 2:8 years; range 6:0-16:7 years, 14 girls and 47 boys) and 44 children with TSD (mean age 8:8 +/- 1:6; range 6:0-12:2 years, 19 girls and 25 boys). Extra-oral and intra-oral examinations were performed by an orthodontist. The severity of malocclusion was scored using the IOTN-DHC Index. Results There were differences between the SSD and TSD groups with regard to the prevalence, type, and severity of malocclusions; 61% of the children in the SSD group had a malocclusion, as compared to 29% in the TSD group. In addition, the malocclusions in the SSD group were rated as more severe. Functional posterior crossbite and habitual lateral and/or anterior shift appeared more frequently in the SSD group. Class III malocclusion, anterior open bite and scissors bite were found only in the SSD group. Conclusion Children with SSD and motor speech involvement are more likely to have a higher prevalence of and more severe malocclusions than children with TSD.
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