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- 2019
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Tidskriftsartikel (refereegranskat)
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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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- Qin, Shuang-Jian, et al.
(författare)
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Neurotoxicity of fine and ultrafine particulate matter : a comprehensive review using a toxicity pathway-oriented adverse outcome pathway framework
- 2024
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Ingår i: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 947
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Forskningsöversikt (refereegranskat)abstract
- Fine particulate matter (PM2.5) can cause brain damage and diseases. Of note, ultrafine particles (UFPs) with an aerodynamic diameter less than or equal to 100 nm are a growing concern. Evidence has suggested toxic effects of PM2.5 and UFPs on the brain and links to neurological diseases. However, the underlying mechanism has not yet been fully illustrated due to the variety of the study models, different endpoints, etc. The adverse outcome pathway (AOP) framework is a pathway-based approach that could systematize mechanistic knowledge to assist health risk assessment of pollutants. Here, we constructed AOPs by collecting molecular mechanisms in PM-induced neurotoxicity assessments. We chose particulate matter (PM) as a stressor in the Comparative Toxicogenomics Database (CTD) and identified the critical toxicity pathways based on Ingenuity Pathway Analysis (IPA). We found 65 studies investigating the potential mechanisms linking PM2.5 and UFPs to neurotoxicity, which contained 2, 675 genes in all. IPA analysis showed that neuroinflammation signaling and glucocorticoid receptor signaling were the common toxicity pathways. The upstream regulator analysis (URA) of PM2.5 and UFPs demonstrated that the neuroinflammation signaling was the most initially triggered upstream event. Therefore, neuroinflammation was recognized as the MIE. Strikingly, there is a clear sequence of activation of downstream signaling pathways with UFPs, but not with PM2.5. Moreover, we found that inflammation response and homeostasis imbalance were key cellular events in PM2.5 and emphasized lipid metabolism and mitochondrial dysfunction, and blood-brain barrier (BBB) impairment in UFPs. Previous AOPs, which only focused on phenotypic changes in neurotoxicity upon PM exposure, we for the first time propose AOP framework in which PM2.5 and UFPs may activate pathway cascade reactions, resulting in adverse outcomes associated with neurotoxicity. Our toxicity pathway-based approach not only advances risk assessment for PM-induced neurotoxicity but shines a spotlight on constructing AOP frameworks for new chemicals.
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- Wu, Runrun, et al.
(författare)
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Efficient capture, rapid killing and ultrasensitive detection of bacteria by a nano-decorated multi-functional electrode sensor
- 2018
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Ingår i: Biosensors & bioelectronics. - : Elsevier. - 0956-5663 .- 1873-4235. ; 101, s. 52-59
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Tidskriftsartikel (refereegranskat)abstract
- In this work, we demonstrated a nano-decorated porous impedance electrode sensor for efficient capture, rapid killing and ultrasensitive detection of bacteria. The multi-functional sensor was prepared by a facile sono-chemical method via in situ deposition of antibacterial prickly Zn-CuO nanoparticles and graphene oxide (GO) nanosheets on a Ni porous electrode. Due to the surface burr-like nanostructures, the nano-decorated impedance sensor exhibited very good bacterial-capture efficiency (70 - 80% in 20 min) even at a low concentration of 50 CFU mL(-1), rapid antibacterial rate (100% killing in 30 min) and high detection sensitivity (as low as 10 CFU mL(-1)). More importantly, the nano-decorated sensor has proven to be highly effective in quantitative detection of bacteria in a biological sample, for example, a rat blood sample spiked with E. coll. Despite the complexity of blood, the sensor still exhibited excellent detection precision within 30 min at bacteria concentrations ranging from 10 - 10(5) CFU mL(-1). The simplicity, rapidity, sensitivity, practicability and multifunctionality of this impedance sensor would greatly facilitate applications in portable medical devices for on-the-spot diagnosis and even the possibility for simultaneous therapy of diseases caused by bacterial infections.
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- Björkander, Sophia, et al.
(författare)
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SARS-CoV-2-specific B- and T-cell immunity in a population-based study of young Swedish adults
- 2022
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 149:1, s. 65-75
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Tidskriftsartikel (refereegranskat)abstract
- Background: Young adults are now considered major spreaders of coronavirus disease 2019 (COVID-19) disease. Although most young individuals experience mild to moderate disease, there are concerns of long-term adverse health effects. The impact of COVID-19 disease and to which extent population-level immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exists in young adults remain unclear.Objective: We conducted a population-based study on humoral and cellular immunity to SARS-CoV-2 and explored COVID-19 disease characteristics in young adults.Methods: We invited participants from the Swedish BAMSE (Barn [Children], Allergy Milieu, Stockholm, Epidemiology) birth cohort (age 24-27 years) to take part in a COVID-19 followup. From 980 participants (October 2020 to June 2021), we here present data on SARS-CoV-2 receptor-binding domain-specific IgM, IgA, and IgG titers measured by ELISA and on symptoms and epidemiologic factors associated with seropositivity. Further, SARS-CoV-2-specific memory B-and T-cell responses were detected for a subpopulation (n 5 108) by ELISpot and FluoroSpot.Results: A total of 28.4% of subjects were seropositive, of whom 18.4% were IgM single positive. One in 7 seropositive subjects was asymptomatic. Seropositivity was associated with use of public transport, but not with sex, asthma, rhinitis, IgE sensitization, smoking, or body mass index. In a subset of representative samples, 20.7% and 35.0% had detectable SARSCoV-2 specific B-and T-cell responses, respectively. B-and T-cell memory responses were clearly associated with seropositivity, but T-cell responses were also detected in 17.2% of seronegative subjects.Conclusions: Assessment of IgM and T-cell responses may improve population-based estimations of SARS-CoV-2 infection. The pronounced surge of both symptomatic and asymptomatic infections among young adults indicates that the large-scale vaccination campaign should be continued. (J Allergy Clin Immunol 2022;149:65-75.)
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| 8. |
- Chemouil, Prosper, et al.
(författare)
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Special Issue on Advances in Artificial Intelligence and Machine Learning for Networking
- 2020
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Ingår i: IEEE Journal on Selected Areas in Communications. - : IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC. - 0733-8716 .- 1558-0008. ; 38:10, s. 2229-2233
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Artificial Intelligence (AI) and Machine Learning (ML) approaches have emerged in the networking domain with great expectation. They can be broadly divided into AI/ML techniques for network engineering and management, network designs for AI/ML applications, and system concepts. AI/ML techniques for networking and management improve the way we address networking. They support efficient, rapid, and trustworthy engineering, operations, and management. As such, they meet the current interest in softwarization and network programmability that fuels the need for improved network automation in agile infrastructures, including edge and fog environments. Network design and optimization for AI/ML applications addresses the complementary topic of supporting AI/ML-based systems through novel networking techniques, including new architectures and algorithms. The third topic area is system implementation and open-source software development.
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| 10. |
- Chen, Hui, et al.
(författare)
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Associations of the Mediterranean-DASH Intervention for Neurodegenerative Delay diet with brain structural markers and their changes
- 2024
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Ingår i: Alzheimer's & Dementia. - 1552-5260 .- 1552-5279. ; 20:2, s. 1190-1200
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: The associations of the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet with brain structural changes are unclear.METHODS: Among 26,466 UK Biobank participants, a 15-point MIND score was calculated from 24-hour diet recalls from 2009 to 2012. We assessed its associations with 17 magnetic-resonance-derived brain volumetric markers and their longitudinal changes and explored whether genetic factors modify the associations.RESULTS: Higher MIND adherence was associated with larger volumes of thalamus, putamen, pallidum, hippocampus, and accumbens (beta per 3-unit increment ranging from 0.024 to 0.033) and lower white matter hyperintensities (P-trends < 0.05), regardless of genetic predispositions of Alzheimer's disease. MIND score was not associated with their longitudinal changes (P > 0.05) over a median of 2.2 years among participants with repeated imaging assessments (N = 2963), but was associated with slower atrophy in putamen (beta: 0.026, P-trend = 0.044) and pallidum (beta: 0.030, P-trend = 0.033) among APOE ε4 non-carriers (N = 654).DISCUSSION: The MIND diet showed beneficial associations with certain brain imaging markers, and its associations with long-term brain structural changes warrants future investigation.
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