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| 2. |
- van Rheenen, W, et al.
(författare)
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Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology
- 2021
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 53:12, s. 1636-
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Tidskriftsartikel (refereegranskat)abstract
- Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons.
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| 3. |
- Gaur, D., et al.
(författare)
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Ydj1 interaction at nucleotide-binding-domain of yeast Ssa1 impacts Hsp90 collaboration and client maturation
- 2022
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 18:11
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Tidskriftsartikel (refereegranskat)abstract
- Hsp90 constitutes one of the major chaperone machinery in the cell. The Hsp70 assists Hsp90 in its client maturation though the underlying basis of the Hsp70 role remains to be explored. In the present study, using S. cerevisiae strain expressing Ssa1 as sole Ssa Hsp70, we identified novel mutations in the nucleotide-binding domain of yeast Ssa1 Hsp70 (Ssa1-T175N and Ssa1-D158N) that adversely affect the maturation of Hsp90 clients v-Src and Ste11. The identified Ssa1 amino acids critical for Hsp90 function were also found to be conserved across species such as in E.coli DnaK and the constitutive Hsp70 isoform (HspA8) in humans. These mutations are distal to the C-terminus of Hsp70, that primarily mediates Hsp90 interaction through the bridge protein Sti1, and proximal to Ydj1 (Hsp40 cochaperone of Hsp70 family) binding region. Intriguingly, we found that the bridge protein Sti1 is critical for cellular viability in cells expressing Ssa1-T175N (A1-T175N) or Ssa1-D158N (A1-D158N) as sole Ssa Hsp70. The growth defect was specific for sti1Δ, as deletion of none of the other Hsp90 co-chaperones showed lethality in A1-T175N or A1-D158N. Mass-spectrometry based whole proteome analysis of A1-T175N cells lacking Sti1 showed an altered abundance of various kinases and transcription factors suggesting compromised Hsp90 activity. Further proteomic analysis showed that pathways involved in signaling, signal transduction, and protein phosphorylation are markedly downregulated in the A1-T175N upon repressing Sti1 expression using doxycycline regulatable promoter. In contrast to Ssa1, the homologous mutations in Ssa4 (Ssa4-T175N/D158N), the stress inducible Hsp70 isoform, supported cell growth even in the absence of Sti1. Overall, our data suggest that Ydj1 competes with Hsp90 for binding to Hsp70, and thus regulates Hsp90 interaction with the nucleotide-binding domain of Hsp70. The study thus provides new insight into the Hsp70-mediated regulation of Hsp90 and broadens our understanding of the intricate complexities of the Hsp70-Hsp90 network.
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| 4. |
- Gaur, V K, et al.
(författare)
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Sustainable strategies for combating hydrocarbon pollution : Special emphasis on mobil oil bioremediation
- 2022
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Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 832
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Tidskriftsartikel (refereegranskat)abstract
- The global rise in industrialization and vehicularization has led to the increasing trend in the use of different crude oil types. Among these mobil oil has major application in automobiles and different machines. The combustion of mobil oil renders a non-usable form that ultimately enters the environment thereby causing problems to environmental health. The aliphatic and aromatic hydrocarbon fraction of mobil oil has serious human and environmental health hazards. These components upon interaction with soil affect its fertility and microbial diversity. The recent advancement in the omics approach viz. metagenomics, metatranscriptomics and metaproteomics has led to increased efficiency for the use of microbial based remediation strategy. Additionally, the use of biosurfactants further aids in increasing the bioavailability and thus biodegradation of crude oil constituents. The combination of more than one approach could serve as an effective tool for efficient reduction of oil contamination from diverse ecosystems. To the best of our knowledge only a few publications on mobil oil have been published in the last decade. This systematic review could be extremely useful in designing a micro-bioremediation strategy for aquatic and terrestrial ecosystems contaminated with mobil oil or petroleum hydrocarbons that is both efficient and feasible. The state-of-art information and future research
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| 5. |
- Mondal, I. C., et al.
(författare)
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Organosulfur/Selenium-Based Highly Fluorogenic Molecular Probes for Live-Cell Nucleolus Imaging
- 2022
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Ingår i: Chemistry - An Asian Journal. - : Wiley. - 1861-4728 .- 1861-471X. ; 17:7
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Tidskriftsartikel (refereegranskat)abstract
- We present fluorogenic cationic organo chalcogens that are highly selective to RNA. We have demonstrated that the conformational dynamics and subsequently the optical properties of these dyes can be controlled to facilitate efficient bioimaging. We report the application of organoselenium and organosulfur-based cell-permeable red-emissive probes bearing a favorable cyclic sidearm for selective and high contrast imaging of cell nucleoli. The probes exhibit high quantum yield upon interacting with RNA in an aqueous solution. An in-depth multiscale simulation study reveals that the prominent rotational freezing of the electron-donating sidearm of the probes in the microenvironment of RNA helps in attaining more planar conformation when compared to DNA. It exerts a greater extent of intramolecular charge transfer and hence leads to enhanced fluorescence emission. A systematic structure-interaction relationship study highlighted the impact of heavy-chalcogens toward the improved emissive properties of the probes.
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| 6. |
- Dhiman, Vinit, et al.
(författare)
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Multiband optical variability of the TeV blazar PG 1553+113 in 2019
- 2022
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 519:2, s. 2796-2811
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Tidskriftsartikel (refereegranskat)abstract
- We report the flux and spectral variability of PG 1553 + 113 on intra-night (IDV) to short-term time-scales using BVRI data collected over 91 nights from 28 February to 8 November 2019 employing 10 optical telescopes: three in Bulgaria, two each in India and Serbia, and one each in Greece, Georgia, and Latvia. We monitored the blazar quasi-simultaneously for 16 nights in the V and R bands and 8 nights in the V, R, I bands and examined the light curves (LCs) for intra-day flux and colour variations using two powerful tests: the power-enhanced F-test and the nested ANOVA test. The source was found to be significantly (>99 per cent) variable in 4 nights out of 27 in R-band, 1 out of 16 in V-band, and 1 out of 6 nights in I-band. No temporal variations in the colours were observed on IDV time-scale. During the course of these observations the total variation in R-band was 0.89 mag observed. We also investigated the spectral energy distribution (SED) using B-, V-, R-, and I-band data. We found optical spectral indices in the range of 0.878 +/- 0.029 to 1.106 +/- 0.065 by fitting a power law (F-nu proportional to nu(-alpha)) to these SEDs of PG 1553 + 113. We found that the source follows a bluer-when-brighter trend on IDV time-scales. We discuss possible physical causes of the observed spectral variability.
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| 7. |
- Gaur, V. K., et al.
(författare)
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Production of biosurfactants from agro-industrial waste and waste cooking oil in a circular bioeconomy : An overview
- 2022
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Ingår i: Bioresource Technology. - : Elsevier Ltd. - 0960-8524 .- 1873-2976. ; 343
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Forskningsöversikt (refereegranskat)abstract
- Waste generation is becoming a global concern owing to its adverse effects on environment and human health. The utilization of waste as a feedstock for production of value-added products has opened new avenues contributing to environmental sustainability. Microorganisms have been employed for production of biosurfactants as secondary metabolites by utilizing waste streams. Utilization of waste as a substrate significantly reduces the cost of overall process. Biosurfactant(s) derived from these processes can be utilized in environmental and different industrial sectors. This review focuses on global market of biosurfactants followed by discussion on production of biosurfactants from waste streams such as agro-industrial waste and waste cooking oil. The need for waste stream derived circular bioeconomy and scale up of biosurfactant production have been narrated with applications of biosurfactants in environment and industrial sectors. Road blocks and future directions for research have also been discussed. © 2021 Elsevier Ltd
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| 8. |
- Machard, Anaïs, et al.
(författare)
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Typical and extreme weather datasets for studying the resilience of buildings to climate change and heatwaves
- 2024
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Ingår i: Scientific Data. - : Springer. - 2052-4463. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- We present unprecedented datasets of current and future projected weather files for building simulations in 15 major cities distributed across 10 climate zones worldwide. The datasets include ambient air temperature, relative humidity, atmospheric pressure, direct and diffuse solar irradiance, and wind speed at hourly resolution, which are essential climate elements needed to undertake building simulations. The datasets contain typical and extreme weather years in the EnergyPlus weather file (EPW) format and multiyear projections in comma-separated value (CSV) format for three periods: historical (2001–2020), future mid-term (2041–2060), and future long-term (2081–2100). The datasets were generated from projections of one regional climate model, which were bias-corrected using multiyear observational data for each city. The methodology used makes the datasets among the first to incorporate complex changes in the future climate for the frequency, duration, and magnitude of extreme temperatures. These datasets, created within the IEA EBC Annex 80 “Resilient Cooling for Buildings”, are ready to be used for different types of building adaptation and resilience studies to climate change and heatwaves.
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