| 1. |
- Kar, Rohan, et al.
(författare)
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The FBXW7-NOTCH interactome : A ubiquitin proteasomal system-induced crosstalk modulating oncogenic transformation in human tissues
- 2021
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Ingår i: Cancer Reports. - : John Wiley & Sons. - 2573-8348. ; 4:4
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Forskningsöversikt (refereegranskat)abstract
- Background Ubiquitin ligases or E3 ligases are well programmed to regulate molecular interactions that operate at a post-translational level. Skp, Cullin, F-box containing complex (or SCF complex) is a multidomain E3 ligase known to mediate the degradation of a wide range of proteins through the proteasomal pathway. The three-dimensional domain architecture of SCF family proteins suggests that it operates through a novel and adaptable "super-enzymatic" process that might respond to targeted therapeutic modalities in cancer. Recent findings Several F-box containing proteins have been characterized either as tumor suppressors (FBXW8, FBXL3, FBXW8, FBXL3, FBXO1, FBXO4, and FBXO18) or as oncogenes (FBXO5, FBXO9, and SKP2). Besides, F-box members like beta TrcP1 and beta TrcP2, the ones with context-dependent functionality, have also been studied and reported. FBXW7 is a well-studied F-box protein and is a tumor suppressor. FBXW7 regulates the activity of a range of substrates, such as c-Myc, cyclin E, mTOR, c-Jun, NOTCH, myeloid cell leukemia sequence-1 (MCL1), AURKA, NOTCH through the well-known ubiquitin-proteasome system (UPS)-mediated degradation pathway. NOTCH signaling is a primitive pathway that plays a crucial role in maintaining normal tissue homeostasis. FBXW7 regulates NOTCH protein activity by controlling its half-life, thereby maintaining optimum protein levels in tissue. However, aberrations in the FBXW7 or NOTCH expression levels can lead to poor prognosis and detrimental outcomes in patients. Therefore, the FBXW7-NOTCH axis has been a subject of intense study and research over the years, especially around the interactome's role in driving cancer development and progression. Several studies have reported the effect of FBXW7 and NOTCH mutations on normal tissue behavior. The current review attempts to critically analyze these mutations prognostic value in a wide range of tumors. Furthermore, the review summarizes the recent findings pertaining to the FBXW7 and NOTCH interactome and its involvement in phosphorylation-related events, cell cycle, proliferation, apoptosis, and metastasis. Conclusion The review concludes by positioning FBXW7 as an effective diagnostic marker in tumors and by listing out recent advancements made in cancer therapeutics in identifying protocols targeting the FBXW7-NOTCH aberrations in tumors.
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| 2. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 3. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 4. |
- Rabiee, Navid, et al.
(författare)
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Green Biomaterials : fundamental principles
- 2023
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Ingår i: Green Biomaterials. - : Taylor & Francis. - 2993-4168. ; 1:1, s. 1-4
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 5. |
- Gawdiya, Sandeep, et al.
(författare)
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Field Screening of Wheat Cultivars for Enhanced Growth, Yield, Yield Attributes, and Nitrogen Use Efficiencies
- 2023
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Ingår i: Agronomy. - : MDPI. - 2073-4395. ; 13:8
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Tidskriftsartikel (refereegranskat)abstract
- Optimizing nitrogen (N) inputs is crucial for maximizing wheat yield and ensuring environmental sustainability. Wheat’s economic significance in India calls for a comprehensive evaluation of its ecological implications to develop a resilient production system. This study aimed to identify and evaluate ten wheat cultivars for their yield and N-use efficiency under varying nitrogen inputs (control (N0), half of the recommended nitrogen (N75), and the recommended nitrogen (N150)) using the surface application of neem-oil-coated urea. All N inputs were applied in three splits, basal, crown root initiation, and tillering stages, and an experiment was conducted in a split-plot design. The application of N150 gave the highest dry matter accumulation (DMA) at harvesting stage (AHS) (871 g m−2), seed/spike (60), grain yield (GY = 7.4 t ha−1), straw yield (SY = 8.9 t ha−1), harvest index (HI = 45.2%), protein (12.5%), and total uptake of N (TUN) (223 kg ha−1) by the cultivar ‘HD 3249’, being closely followed by the cultivar ‘HD3117’. Six cultivars (‘HD 3298’, ‘HD 3117’, ‘HD 3249’, ‘PBW 550’, ‘HD 3086’, ‘HD 2967’) out of the ten cultivars evaluated responded well to different input treatments with respect to the grain yield efficiency index (GYEI ≥ 1). Regarding N input, N75 and N150 recorded the highest increases in plant height, AHS (16.5%; 21.2%), dry matter accumulation (DMA) at 30 days after sowing (DAS) (37.5%; 64%), DMA-60 DAS (42%; 53%), DMA-90 DAS (39.5%; 52.5%), TILL-30 DAS (19.8%; 26.4%), TILL-60 DAS (33.3%; 44%), TILL-90 DAS (37.2%; 47.2%), seed/spike (8%; 10%), 1000-grain weight (7.8%; 12.2%), and protein content (23.3%; and 33%) when compared with N0. Furthermore, the application of N75 and N150 improved GY (72.1%; 142.6%), SY (61.1%; 110.6%), BY (65.5%; 123%), and HI by 4.4% and 9%, respectively, over N0. Nitrogen addition (N75 and N150) also significantly increased total nitrogen uptake (104.7%; 205.6%), respectively, compared to N0. The correlation analysis revealed a positive association among most of the crop parameters. Overall, our research results suggest that the cultivars ‘HD 3249’ and ‘HD 3117’ have the potential to be effective options for improving N utilization efficiency, grain yield, and GYEI in North-West India.
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| 6. |
- Jain, Achint K., et al.
(författare)
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Targeting of diacerein loaded lipid nanoparticles to intra-articular cartilage using chondroitin sulfate as homing carrier for treatment of osteoarthritis in rats
- 2014
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Ingår i: Nanomedicine. - : Elsevier BV. - 1549-9634 .- 1549-9642. ; 10:5, s. 1031-1040
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Tidskriftsartikel (refereegranskat)abstract
- Targeted delivery of antiosteoarthritic drug diacerein to articular tissue could be a major achievement and soluble polysaccharide chondroitin sulfate (ChS) may be a suitable agent for this. Therefore, diacerein loaded solid lipid nanoparticles modified with ChS (ChS-DC-SLN) were prepared for synergistic effect of these agents to combat multidimensional pathology of osteoarthritis (OA). Prepared formulation were of size range 396. ±. 2.7. nm, showed extended release up to 16. h and increased bioavailability of diacerein by 2.8 times. ChS-DC-SLN were evaluated for their effect on histopathology of femoro-tibial joint of rat knee and amount of ChS and rhein (an active metabolite of diacerein) at targeted site. Concentration of rhein was significantly higher in case of ChS-DC-SLN (7.8. ±. 1.23. μg/ml) than that of drug dispersion (2.9. ±. 0.45. μg/ml). It can be stated that ChS served as homing to articular cartilage for targeting of drug. Thus, ChS-DC-SLN have great potential to enhance the overall efficacy of treatment for OA. From the Clinical Editor: This study demonstrates the feasibility of targeted delivery of diacerein to articular tissue using soluble polysaccharide chondroitin sulfate as the targeting vector. This approach has the potential to significantly increase anti-arthritic drug concentration in joints without leading to systemic toxicity
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| 7. |
- Karthic, Anandakrishnan, et al.
(författare)
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Computational Analysis Reveals Monomethylated Triazolopyrimidine as a Novel Inhibitor of SARS-CoV-2 RNA-Dependent RNA Polymerase (RdRp)
- 2022
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Ingår i: Molecules. - : MDPI AG. - 1420-3049. ; 27:3
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Tidskriftsartikel (refereegranskat)abstract
- The human population is still facing appalling conditions due to several outbreaks of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) virus. The absence of specific drugs, appropriate vaccines for mutants, and knowledge of potential therapeutic agents makes this situation more difficult. Several 1, 2, 4-triazolo [1, 5-a] pyrimidine (TP)-derivative compounds were comprehensively studied for antiviral activities against RNA polymerase of HIV, HCV, and influenza viruses, and showed immense pharmacological interest. Therefore, TP-derivative compounds can be repurposed against the RNA-dependent RNA polymerase (RdRp) protein of SARS-CoV-2. In this study, a meta-analysis was performed to ensure the genomic variability and stability of the SARS-CoV-2 RdRp protein. The molecular docking of natural and synthetic TP compounds to RdRp and molecular dynamic (MD) simulations were performed to analyse the dynamic behaviour of TP compounds at the active site of the RdRp protein. TP compounds were also docked against other non-structural proteins (NSP1, NSP2, NSP3, NSP5, NSP8, NSP13, and NSP15) of SARS-CoV-2. Furthermore, the inhibition potential of TP compounds was compared with Remdesivir and Favipi-ravir drugs as a positive control. Additionally, TP compounds were analysed for inhibitory activity against SARS-CoV RdRp protein. This study demonstrates that TP analogues (monomethylated triazolopyrimidine and essramycin) represent potential lead molecules for designing an effective inhibitor to control viral replication. Furthermore, in vitro and in vivo studies will strengthen the use of these inhibitors as suitable drug candidates against SARS-CoV-2.
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| 8. |
- Kumar, Dhananjay, et al.
(författare)
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Affordable phenotyping of winter wheat under field and controlled conditions for drought tolerance
- 2020
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Ingår i: Agronomy. - : MDPI AG. - 2073-4395. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Drought stress is one of the key plant stresses reducing grain yield in cereal crops worldwide. Although it is not a breeding target in Northern Europe, the changing climate and the drought of 2018 have increased its significance in the region. A key challenge, therefore, is to identify novel germplasm with higher drought tolerance, a task that will require continuous characterization of a large number of genotypes. The aim of this work was to assess if phenotyping systems with low-cost consumer-grade digital cameras can be used to characterize germplasm for drought tolerance. To achieve this goal, we built a proximal phenotyping cart mounted with digital cameras and evaluated it by characterizing 142 winter wheat genotypes for drought tolerance under field conditions. The same genotypes were additionally characterized for seedling stage traits by imaging under controlled growth conditions. The analysis revealed that under field conditions, plant biomass, relative growth rates, and Normalized Difference Vegetation Index (NDVI) from different growth stages estimated by imaging were significantly correlated to drought tolerance. Under controlled growth conditions, root count at the seedling stage evaluated by imaging was significantly correlated to adult plant drought tolerance observed in the field. Random forest models were trained by integrating measurements from field and controlled conditions and revealed that plant biomass and relative growth rates at key plant growth stages are important predictors of drought tolerance. Thus, based on the results, it can be concluded that the consumer-grade cameras can be key components of affordable automated phenotyping systems to accelerate pre-breeding for drought tolerance.
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| 9. |
- Mishra, Abhay, et al.
(författare)
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Spectroscopic insight into breast cancer: profiling small extracellular vesicles lipids via infrared spectroscopy for diagnostic precision
- 2024
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Breast cancer, a leading cause of female mortality due to delayed detection owing to asymptomatic nature and limited early diagnostic tools, was investigated using a multi-modal approach. Plasma-derived small EVs from breast cancer patients (BrCa, n = 74) and healthy controls (HC, n = 30) were analyzed. Small EVs (n = 104), isolated through chemical precipitation, underwent characterization via transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). Validation involved antibody-based tests (TSG101, CD9, CD81, CD63). Infrared spectra of small EVs were obtained, revealing significant differences in lipid acyl chains, particularly in the C–H stretching of CH3. The study focused on the lipid region (3050–2900 cm−1), identifying peaks (3015 cm−1, 2960 cm−1, 2929 cm−1) as distinctive lipid characteristics. Spectroscopic lipid-to-lipid ratios [(I3015/I2929), (I2960/I2929)] emerged as prominent breast cancer markers. Exploration of protein, nucleic acid, and carbohydrate ratios indicated variations in alpha helices, asymmetric C–H stretching vibrations, and C–O stretching at 1033 cm−1. Principal component analysis (PCA) successfully differentiated BrCa and HC small EVs, and heatmap analysis and receiver operating characteristic (ROC) curve evaluations underscored the discriminatory power of lipid ratios. Notably, (I2960/I2929) exhibited 100% sensitivity and specificity, highlighting its potential as a robust BrCa sEV marker for breast cancer detection.
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| 10. |
- Rathi, Bhawna, et al.
(författare)
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Anti-biofilm activity of caffeine against uropathogenic E. coli is mediated by curli biogenesis
- 2022
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Biofilms are assemblages of sessile microorganisms that form an extracellular matrix around themselves and mediate attachment to surfaces. The major component of the extracellular matrix of Uropathogenic E. coli and other Enterobacteriaceae are curli fibers, making biofilms robust and resistant to antimicrobials. It is therefore imperative to screen antibiofilm compounds that can impair biofilm formation. In the present study, we investigated the curli-dependent antibiofilm activity of caffeine against UPEC strain CFT073 and commensal strain E. coli K-12MG1655.Caffeine significantly reduced the biofilm formation of both UPEC and E. coli K-12 by 86.58% and 91.80% respectively at 48 mM caffeine as determined by Crystal Violet assay. These results were further confirmed by fluorescence microscopy and Scanning Electron Microscope (SEM). Caffeine significantly reduced the cytotoxicity and survivability of UPEC. Molecular docking analysis revealed a strong interaction between caffeine and curli regulator protein (Csg D) of E. coli. The qRT-PCR data also showed significant downregulation in the expression of CsgBA and the CsgDEFG operon at both 24 mM and 48 mM caffeine. The findings revealed that caffeine could inhibit E. coli biofilm formation by regulating curli assembly and thus may be used as an alternative therapeutic strategy for the treatment of chronic E. coli biofilm-related infections.
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