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- Czeszumski, Artur, et al.
(författare)
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#EEGManyLabs: Investigating the Replicability of Influential EEG Experiments
- 2024
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- There is growing awareness across the neuroscience community that the replicability of findings on the relationship between brain activity and cognitive phenomena can be improved by conducting studies with high statistical power that adhere to well-defined and standardized analysis pipelines. Inspired by efforts from the psychological sciences, and with the desire to examine some of the foundational findings using electroencephalography (EEG), we have launched #EEGManyLabs, a large-scale international collaborative replication effort. Since its discovery in the early 20th century, EEG has had a profound influence on our understanding of human cognition, but there is limited evidence on the replicability of some of the most highly cited discoveries. After a systematic search and selection process, we have identified 27 of the most influential and continually cited studies in the field. We plan to directly test the replicability of key findings from 20 of these studies in teams of at least three independent laboratories. The design and protocol of each replication effort will be submitted as a Registered Report and peer-reviewed prior to data collection. Prediction markets, open to all EEG researchers, will be used as a forecasting tool to examine which findings the community expects to replicate. This project will update our confidence in some of the most influential EEG findings and generate a large open access database that can be used to inform future research practices. Finally, through this international effort, we hope to create a cultural shift towards inclusive, high-powered multi-laboratory collaborations.
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| 3. |
- Clifton, Luke A., et al.
(författare)
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Creation of distinctive Bax-lipid complexes at mitochondrial membrane surfaces drives pore formation to initiate apoptosis
- 2023
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Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 9:22
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Tidskriftsartikel (refereegranskat)abstract
- Apotosis is an essential process tightly regulated by the Bcl-2 protein family where proapoptotic Bax triggers cell death by perforating the mitochondrial outer membrane. Although intensively studied, the molecular mechanism by which these proteins create apoptotic pores remains elusive. Here, we show that Bax creates pores by extracting lipids from outer mitochondrial membrane mimics by formation of Bax/lipid clusters that are deposited on the membrane surface. Time-resolved neutron reflectometry and Fourier transform infrared spectroscopy revealed two kinetically distinct phases in the pore formation process, both of whichwere critically dependent on cardiolipin levels. The initially fast adsorption of Bax on the mitochondrial membrane surface is followed by a slower formation of pores and Bax-lipid clusters on the membrane surface. Our findings provide a robust molecular understanding of mitochondrial membrane perforation by cell-killing Bax protein and illuminate the initial phases of programmed cellular death.
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| 4. |
- Clifton, Luke A., et al.
(författare)
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Insight into Bcl-2 proteins' functioning at mitochondrial membrane level
- 2023
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Ingår i: Biophysical Journal. - : Elsevier. - 0006-3495 .- 1542-0086. ; 122:3S1, s. 232a-232a
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Tidskriftsartikel (refereegranskat)abstract
- Programmed cell death (apoptosis) is essential in life. In its intrinsic apoptotic pathway opposing members of the B-cell lymphoma 2 (Bcl-2) protein family control the permeability of the mitochondrial outer membrane (MOM) and the release of apoptotic factors such as cytochrome c. Any misregulation of this process can cause disorders most prominently cancer, where often upregulation of cell protecting (anti-apoptotic) Bcl-2 members such as the Bcl-2 membrane protein itself plays a notorious role by blocking MOM perforation by - often drug induced - apoptotic proteins such as Bax which would cause cancer cell death normally. Here, we apply neutron reflectometry (NR) on supported lipid bilayers which mimic MOM environment and solid state/liquid state NMR spectroscopy to unravel the molecular basis driving opposing proteins to interact with each other at the MOM; a mechanism which is not really understood yet due to lack of high-resolution structural insight. Based on our central hypothesis that Bcl-2 drives its cell-protecting function at a membrane-embedded location as revealed by NR (1), we focus i) to determine the structure of human Bcl-2 protein in its membrane setting by combining solution and solid-state NMR; ii) use NR to study the kinetics and lipid/protein pore assemblied upon binding of Bax to mitochondrial membranes and its membrane destroying activities there; and iii) unravel the nature of direct interaction between Bcl-2 and Bax to neutralize each other. Knowledge generated here, will be indispensable in understanding the regulative function of the Bcl-2 family at mitochondrial membranes.
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| 5. |
- Mushtaq, Afshan, et al.
(författare)
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Catalytic oxidative desulfurization of thio-compounds by employing χ-Anderson-type polyoxometalates-porphyrin covalent organic framework (COF)
- 2023
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Ingår i: Tetrahedron. - : Elsevier. - 0040-4020 .- 1464-5416. ; 144
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Tidskriftsartikel (refereegranskat)abstract
- Severe environmental sulfur contents due to the consumption of fuels in automobiles and industries resulted in serious health hazards and pollution because of it, desulfurization of diesel become inevitable. Targeting the profound desulfurization of diesel, we performed experiments to deeply desulphurized the thio-compounds by catalytic-oxidative desulfurization technique. We synthesized new metalloporphyrin (C52H36N4O8Sn)4MeO-SnPor which after conversion into (C64H64N8O16Sn)4Tris-SnTP leading towards the synthesis of covalent organic framework [(N(C4H9)4]12[HNC(CH2O)3]4[(CO)4C44H24N4Sn] [NiMo6O18]4(SnTP@NiAdCOF). SnTP@NiAd COF showed the outstanding catalytic property for deep desulfurization of thio-compounds above than 96% of thiobenzoic acid (TB) and 99% of 2-aminothiophenol (2-ATP) sulfur contents were oxides after 100 min of reaction using H2O2 as an oxidant at room temperature with constant stirring. During desulfurization percentage desulfurization efficiency was checked for different time intervals by TLC and further confirmed by reverse phase high-performance liquid chromatography (RP-HPLC). Reverse-phase high-performance liquid chromatograms indicated that the peak area and peak height of thio-compounds decrease gradually with the passage of reaction time which confirmed the removal of thio-compounds from the reaction mixture. Sulfur contents removed up to 5 ppmw showed excellent catalytic characteristics of synthesized SnTP@NiAdCOF. The exceptional catalytic efficiency of prepared catalyst SnTP@NiAdCOF was because of the existence of active oxidizing centers of χ-NiAd and metalloporphyrin that are MoO and [(Por)SnII], respectively. The potential mechanism appeared to be the formation of Mo(O2) and [(Por)SnII–OOH] from MoO and [(Por)SnII], respectively that act as active oxidizing centers and efficiently converted the thio-group into oxides and sulfones. Effective removal of sulfur grants the desulfurization of fuels by using SnTP@NiAdCOF catalyst to lessen the energy expenditure and also to enhance the production of environmentally-safe fuels.
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| 10. |
- Verma, Apoorv, et al.
(författare)
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Insights into the evolution of enzymatic specificity and catalysis : from Asgard archaea to human adenylate kinases
- 2022
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Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 8:44
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Tidskriftsartikel (refereegranskat)abstract
- Enzymatic catalysis is critically dependent on selectivity, active site architecture, and dynamics. To contribute insights into the interplay of these properties, we established an approach with NMR, crystallography, and MD simulations focused on the ubiquitous phosphotransferase adenylate kinase (AK) isolated from Odinarchaeota (OdinAK). Odinarchaeota belongs to the Asgard archaeal phylum that is believed to be the closest known ancestor to eukaryotes. We show that OdinAK is a hyperthermophilic trimer that, contrary to other AK family members, can use all NTPs for its phosphorylation reaction. Crystallographic structures of OdinAK-NTP complexes revealed a universal NTP-binding motif, while 19F NMR experiments uncovered a conserved and rate-limiting dynamic signature. As a consequence of trimerization, the active site of OdinAK was found to be lacking a critical catalytic residue and is therefore considered to be "atypical." On the basis of discovered relationships with human monomeric homologs, our findings are discussed in terms of evolution of enzymatic substrate specificity and cold adaptation.
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