| 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. |
- Rando, Halie M., et al.
(författare)
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Identification and development of therapeutics for COVID-19
- 2021
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Ingår i: mSystems. - 2379-5077. ; 6:6
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Forskningsöversikt (refereegranskat)abstract
- After emerging in China in late 2019, the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread worldwide, and as of mid- 2021, it remains a significant threat globally. Only a few coronaviruses are known to infect humans, and only two cause infections similar in severity to SARS-CoV-2: Severe acute respiratory syndrome-related coronavirus, a species closely related to SARS-CoV-2 that emerged in 2002, and Middle East respiratory syndrome-related coronavirus, which emerged in 2012. Unlike the current pandemic, previous epidemics were controlled rapidly through public health measures, but the body of research investigating severe acute respiratory syndrome and Middle East respiratory syndrome has proven valuable for identifying approaches to treating and preventing novel coronavirus disease 2019 (COVID-19). Building on this research, the medical and scientific communities have responded rapidly to the COVID-19 crisis and identified many candidate therapeutics. The approaches used to identify candidates fall into four main categories: adaptation of clinical approaches to diseases with related pathologies, adaptation based on virological properties, adaptation based on host response, and data-driven identification (ID) of candidates based on physical properties or on pharmacological compendia. To date, a small number of therapeutics have already been authorized by regulatory agencies such as the Food and Drug Administration (FDA), while most remain under investigation. The scale of the COVID-19 crisis offers a rare opportunity to collect data on the effects of candidate therapeutics. This information provides insight not only into the management of coronavirus diseases but also into the relative success of different approaches to identifying candidate therapeutics against an emerging disease. IMPORTANCE The COVID-19 pandemic is a rapidly evolving crisis. With the worldwide scientific community shifting focus onto the SARS-CoV-2 virus and COVID-19, a large number of possible pharmaceutical approaches for treatment and prevention have been proposed. What was known about each of these potential interventions evolved rapidly throughout 2020 and 2021. This fast-paced area of research provides important insight into how the ongoing pandemic can be managed and also demonstrates the power of interdisciplinary collaboration to rapidly understand a virus and match its characteristics with existing or novel pharmaceuticals. As illustrated by the continued threat of viral epidemics during the current millennium, a rapid and strategic response to emerging viral threats can save lives. In this review, we explore how different modes of identifying candidate therapeutics have borne out during COVID-19.
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| 3. |
- Arun, K. G., et al.
(författare)
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New horizons for fundamental physics with LISA
- 2022
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Ingår i: Living Reviews in Relativity. - : Springer Science and Business Media LLC. - 1433-8351 .- 2367-3613. ; 25:1
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Forskningsöversikt (refereegranskat)abstract
- The Laser Interferometer Space Antenna (LISA) has the potential to reveal wonders about the fundamental theory of nature at play in the extreme gravity regime, where the gravitational interaction is both strong and dynamical. In this white paper, the Fundamental Physics Working Group of the LISA Consortium summarizes the current topics in fundamental physics where LISA observations of gravitational waves can be expected to provide key input. We provide the briefest of reviews to then delineate avenues for future research directions and to discuss connections between this working group, other working groups and the consortium work package teams. These connections must be developed for LISA to live up to its science potential in these areas.
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| 4. |
- Luo, Yifei, et al.
(författare)
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Technology Roadmap for Flexible Sensors
- 2023
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Ingår i: ACS Nano. - : American Chemical Society. - 1936-0851 .- 1936-086X. ; 17:6, s. 5211-5295
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Forskningsöversikt (refereegranskat)abstract
- Humans rely increasingly on sensors to address grand challenges and to improve quality of life in the era of digitalization and big data. For ubiquitous sensing, flexible sensors are developed to overcome the limitations of conventional rigid counterparts. Despite rapid advancement in bench-side research over the last decade, the market adoption of flexible sensors remains limited. To ease and to expedite their deployment, here, we identify bottlenecks hindering the maturation of flexible sensors and propose promising solutions. We first analyze challenges in achieving satisfactory sensing performance for real-world applications and then summarize issues in compatible sensor-biology interfaces, followed by brief discussions on powering and connecting sensor networks. Issues en route to commercialization and for sustainable growth of the sector are also analyzed, highlighting environmental concerns and emphasizing nontechnical issues such as business, regulatory, and ethical considerations. Additionally, we look at future intelligent flexible sensors. In proposing a comprehensive roadmap, we hope to steer research efforts towards common goals and to guide coordinated development strategies from disparate communities. Through such collaborative efforts, scientific breakthroughs can be made sooner and capitalized for the betterment of humanity.
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| 5. |
- Rando, Halie M, et al.
(författare)
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Pathogenesis, Symptomatology, and Transmission of SARS-CoV-2 through Analysis of Viral Genomics and Structure
- 2021
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Ingår i: mSystems. - 2379-5077. ; 6:5
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Forskningsöversikt (refereegranskat)abstract
- The novel coronavirus SARS-CoV-2, which emerged in late 2019, has since spread around the world and infected hundreds of millions of people with coronavirus disease 2019 (COVID-19). While this viral species was unknown prior to January 2020, its similarity to other coronaviruses that infect humans has allowed for rapid insight into the mechanisms that it uses to infect human hosts, as well as the ways in which the human immune system can respond. Here, we contextualize SARS-CoV-2 among other coronaviruses and identify what is known and what can be inferred about its behavior once inside a human host. Because the genomic content of coronaviruses, which specifies the virus's structure, is highly conserved, early genomic analysis provided a significant head start in predicting viral pathogenesis and in understanding potential differences among variants. The pathogenesis of the virus offers insights into symptomatology, transmission, and individual susceptibility. Additionally, prior research into interactions between the human immune system and coronaviruses has identified how these viruses can evade the immune system's protective mechanisms. We also explore systems-level research into the regulatory and proteomic effects of SARS-CoV-2 infection and the immune response. Understanding the structure and behavior of the virus serves to contextualize the many facets of the COVID-19 pandemic and can influence efforts to control the virus and treat the disease. IMPORTANCE COVID-19 involves a number of organ systems and can present with a wide range of symptoms. From how the virus infects cells to how it spreads between people, the available research suggests that these patterns are very similar to those seen in the closely related viruses SARS-CoV-1 and possibly Middle East respiratory syndrome-related CoV (MERS-CoV). Understanding the pathogenesis of the SARS-CoV-2 virus also contextualizes how the different biological systems affected by COVID-19 connect. Exploring the structure, phylogeny, and pathogenesis of the virus therefore helps to guide interpretation of the broader impacts of the virus on the human body and on human populations. For this reason, an in-depth exploration of viral mechanisms is critical to a robust understanding of SARS-CoV-2 and, potentially, future emergent human CoVs (HCoVs).
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| 6. |
- Huang, Ke, et al.
(författare)
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Tailoring magnetic order via atomically stacking 3d/5d electrons to achieve high-performance spintronic devices
- 2020
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Ingår i: Applied Physics Reviews. - : AMER INST PHYSICS. - 1931-9401. ; 7:1
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Forskningsöversikt (refereegranskat)abstract
- The ability to tune magnetic orders, such as magnetic anisotropy and topological spin texture, is desired to achieve high-performance spintronic devices. A recent strategy has been to employ interfacial engineering techniques, such as the introduction of spin-correlated interfacial coupling, to tailor magnetic orders and achieve novel magnetic properties. We chose a unique polar-nonpolar LaMnO3/SrIrO3 superlattice because Mn (3d)/Ir (5d) oxides exhibit rich magnetic behaviors and strong spin-orbit coupling through the entanglement of their 3d and 5d electrons. Through magnetization and magnetotransport measurements, we found that the magnetic order is interface-dominated as the superlattice period is decreased. We were able to then effectively modify the magnetization, tilt of the ferromagnetic easy axis, and symmetry transition of the anisotropic magnetoresistance of the LaMnO3/SrIrO3 superlattice by introducing additional Mn (3d) and Ir (5d) interfaces. Further investigations using in-depth first-principles calculations and numerical simulations revealed that these magnetic behaviors could be understood by the 3d/5d electron correlation and Rashba spin-orbit coupling. The results reported here demonstrate a new route to synchronously engineer magnetic properties through the atomic stacking of different electrons, which would contribute to future applications in high-capacity storage devices and advanced computing.
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| 7. |
- Li, Lin, 1989-, et al.
(författare)
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Maternal pre-pregnancy overweight/obesity and the risk of attention-deficit/hyperactivity disorder in offspring : a systematic review, meta-analysis and quasi-experimental family-based study
- 2020
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Ingår i: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 49:3, s. 857-875
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND: Previous studies are inconclusive concerning the association between maternal pre-pregnancy overweight/obesity and risk of attention-deficit/hyperactivity disorder (ADHD) in offspring. We therefore conducted a systematic review and meta-analysis to clarify this association. To address the variation in confounding adjustment between studies, especially inadequate adjustment of unmeasured familial confounding in most studies, we further performed cousin and sibling comparisons in a nationwide population-based cohort in Sweden.METHODS: We searched PubMed, Embase and PsycINFO during 1975-2018. We used random-effects models to calculate pooled risk ratios (RRs) with 95% confidence interval. In the population-based study, Cox proportional hazard models were used to calculate the unadjusted hazard ratios (HRs) and HRs adjusted for all confounders identified in previous studies. Stratified Cox models were applied to data on full cousins and full siblings to further control for unmeasured familial confounding.RESULTS: Eight cohorts with a total of 784 804 mother-child pairs were included in the meta-analysis. Maternal overweight [RRoverweight = 1.31 (1.25-1.38), I2 = 6.80%] and obesity [RRobesity = 1.92 (1.84-2.00), I2 = 0.00%] were both associated with an increased risk of ADHD in offspring. In the population-based cohort of 971 501 individuals born between 1992 and 2004, unadjusted Cox models revealed similar associations [HRoverweight = 1.30 (1.28-1.34), HRobesity = 1.92 (1.87-1.98)]. These associations gradually attenuated towards the null when adjusted for measured confounders [HRoverweight = 1.21 (1.19-1.25), HRobesity = 1.60 (1.55-1.65)], unmeasured factors shared by cousins [HRoverweight = 1.10 (0.98-1.23), HRobesity = 1.44 (1.22-1.70)] and unmeasured factors shared by siblings [HRoverweight = 1.01 (0.92-1.11), HRobesity = 1.10 (0.94-1.27)].CONCLUSION: Pre-pregnancy overweight/obesity is associated with an increased risk of ADHD in offspring. The observed association is largely due to unmeasured familial confounding.
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| 8. |
- Martin, Scot T., et al.
(författare)
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Sources and properties of Amazonian aerosol particles
- 2010
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Ingår i: Reviews of Geophysics. - 8755-1209. ; 48, s. 2002-2002
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Forskningsöversikt (refereegranskat)abstract
- This review provides a comprehensive account of what is known presently about Amazonian aerosol particles and concludes by formulating outlook and priorities for further research. The review is organized to follow the life cycle of Amazonian aerosol particles. It begins with a discussion of the primary and secondary sources relevant to the Amazonian particle burden, followed by a presentation of the particle properties that characterize the mixed populations present over the Amazon Basin at different times and places. These properties include number and mass concentrations and distributions, chemical composition, hygroscopicity, and cloud nucleation ability. The review presents Amazonian aerosol particles in the context of natural compared to anthropogenic sources as well as variability with season and meteorology. This review is intended to facilitate an understanding of the current state of knowledge on Amazonian aerosol particles specifically and tropical continental aerosol particles in general and thereby to enhance future research in this area.
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| 9. |
- Wang, Qi, et al.
(författare)
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Tracing per- and polyfluoroalkyl substances (PFASs) in the aquatic environment : Target analysis and beyond
- 2023
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Ingår i: TrAC. Trends in analytical chemistry. - : Elsevier. - 0165-9936 .- 1879-3142. ; 169
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Forskningsöversikt (refereegranskat)abstract
- Per-and polyfluoroalkyl substances (PFASs) have been manufactured and used for decades. The aquatic envi-ronment is a critical transportation and transformation compartment for PFASs. Target analysis is the most used method of tracing PFASs in the aquatic environment but is powerless for the large amounts of unknown PFASs. This review summarizes the advantages of three target analysis supplementary approaches, including extractable organofluorine (EOF) analysis, high-resolution mass spectrometry (HRMS) screening, and PFAS precursor oxidative conversion. For known PFASs, more targets, including emerging PFASs, PFAS isomers, ultrashort-chain PFASs, and cationic/zwitterionic PFASs, should be considered. For unknown PFASs and organofluorines, developing comprehensive and low-contaminated sample treatment strategies is essential yet challenging. We propose including PFASs screened via HRMS at confidence level (CL) 3 and above in EOF mass balance analysis and CL 4 for samples collected from a "known source". Appropriate approaches should be applied to investigate unknown PFASs beyond target analysis comprehensively.
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