24 results on '"Ayyagari A"'
Search Results
2. Designing of high entropy alloys with high hardness: a metaheuristic approach
- Author
-
Ansh Poonia, Modalavalasa Kishor, and Kameswari Prasada Rao Ayyagari
- Subjects
Composition optimization ,Phase prediction ,High entropy alloys ,Differential evolution ,Hardness prediction ,Medicine ,Science - Abstract
Abstract The near-infinite compositional space of high-entropy-alloys (HEAs) is a huge resource-intensive task for developing exceptional materials. In the present study, an algorithmic framework has been developed to optimize the composition of an alloy with chosen set of elements, aiming to maximize the hardness of the former. The influence of phase on hardness prediction of HEAs was thoroughly examined. This study aims to establish generalized prediction models that aren’t confined by any specific set of elements. We trained the HEA identification model to classify HEAs from non-HEAs, the multi-labeled phase classification model to predict phases of HEAs also considering the processing route involved in the synthesis of the alloy, and the hardness prediction model for predicting hardness and optimizing the composition of the given alloy. The purposed algorithmic framework uses twenty-nine alloy descriptors to compute the composition that demonstrates maximum hardness for the given set of elements along with its phase(s) and a label stating whether it is classified as HEA or not.
- Published
- 2024
- Full Text
- View/download PDF
3. Design of high bulk moduli high entropy alloys using machine learning
- Author
-
Manjunadh Kandavalli, Abhishek Agarwal, Ansh Poonia, Modalavalasa Kishor, and Kameswari Prasada Rao Ayyagari
- Subjects
Medicine ,Science - Abstract
Abstract In this work, the authors have demonstrated the use of machine learning (ML) models in the prediction of bulk modulus for High Entropy Alloys (HEA). For the first time, ML has been used for optimizing the composition of HEA to achieve enhanced bulk modulus values. A total of 12 ML algorithms were trained to classify the elemental composition as HEA or non-HEA. Among these models, Gradient Boosting Classifier (GBC) was found to be the most accurate, with a test accuracy of 78%. Further, six regression models were trained to predict the bulk modulus of HEAs, and the best results were obtained by LASSO Regression model with an R-square value of 0.98 and an adjusted R-Square value of 0.97 for the test data set. This work effectively bridges the gap in the discovery and property analysis of HEAs. By accelerating material discovery via providing alternate means for designing virtual alloy compositions having favourable bulk modulus for respective applications, this work opens new avenues of applications of HEAs.
- Published
- 2023
- Full Text
- View/download PDF
4. Single cell RNA sequencing confirms retinal microglia activation associated with early onset retinal degeneration
- Author
-
Kumari, Asha, Ayala-Ramirez, Raul, Zenteno, Juan Carlos, Huffman, Kristyn, Sasik, Roman, Ayyagari, Radha, and Borooah, Shyamanga
- Subjects
Genetics ,Eye Disease and Disorders of Vision ,Neurodegenerative ,Neurosciences ,Aetiology ,2.1 Biological and endogenous factors ,Eye ,Animals ,Apolipoproteins E ,Fovea Centralis ,Humans ,Membrane Proteins ,Mice ,Microglia ,Retinal Degeneration ,Sequence Analysis ,RNA - Abstract
Mutations in the Membrane-type frizzled related protein (Mfrp) gene results in an early-onset retinal degeneration associated with retinitis pigmentosa, microphthalmia, optic disc drusen and foveal schisis. In the current study, a previously characterized mouse model of human retinal degeneration carrying homozygous c.498_499insC mutations in Mfrp (MfrpKI/KI) was used. Patients carrying this mutation have retinal degeneration at an early age. The model demonstrates subretinal deposits and develops early-onset photoreceptor degeneration. We observed large subretinal deposits in MfrpKI/KI mice which were strongly CD68 positive and co-localized with autofluorescent spots. Single cell RNA sequencing of MfrpKI/KI mice retinal microglia showed a significantly higher number of pan-macrophage marker Iba-1 and F4/80 positive cells with increased expression of activation marker (CD68) and lowered microglial homeostatic markers (TMEM119, P2ry13, P2ry13, Siglech) compared with wild type mice confirming microglial activation as observed in retinal immunostaining showing microglia activation in subretinal region. Trajectory analysis identified a small cluster of microglial cells with activation transcriptomic signatures that could represent a subretinal microglia population in MfrpKI/KI mice expressing higher levels of APOE. We validated these findings using immunofluorescence staining of retinal cryosections and found a significantly higher number of subretinal Iba-1/ApoE positive microglia in MfrpKI/KI mice with some subretinal microglia also expressing lowered levels of microglial homeostatic marker TMEM119, confirming microglial origin. In summary, we confirm that MfrpKI/KI mice carrying the c.498_499insC mutation had a significantly higher population of activated microglia in their retina with distinct subsets of subretinal microglia. Further, studies are required to confirm whether the association of increased subretinal microglia in MfrpKI/KI mice are causal in degeneration.
- Published
- 2022
5. MXene/graphene oxide nanocomposites for friction and wear reduction of rough steel surfaces
- Author
-
Ali Zayaan Macknojia, Aditya Ayyagari, Elena Shevchenko, and Diana Berman
- Subjects
Medicine ,Science - Abstract
Abstract Development of solid lubricant materials that render reliable performance in ambient conditions, are amenable to industrial size and design complexities, and work on engineered surfaces is reported. These coatings are composed of Ti3C2T x -Graphene Oxide blends, spray-coated onto bearing steel surfaces. The tribological assessment was carried out in ambient environmental conditions and high contact pressures in a ball-on-disc experimental set-up. The evaluation yielded that the use of Ti3C2T x -Graphene-Oxide coatings led to substantial reduction in friction down to 0.065 (at 1 GPa contact pressure and 100 mm/s) in comparison to the uncoated of single-component-coated surfaces, surpassing the state-of-the-art. The coatings also provided excellent protection against wear loss of the substrate and counter-face. The results were explained based on the observations from Raman spectroscopy, scanning electron microscopy, transmission electron microscopy, and nanoindentation measurements. In operando formation of a dense, hard and stiff, dangling-bond-saturated tribolayer was observed to be the reason for the sustained lubricity even at high test loads and sliding speeds. This report presents the holistic exploration and correlation of structure-property-processing pertaining to the advancement of solid lubrication science.
- Published
- 2023
- Full Text
- View/download PDF
6. Design of high bulk moduli high entropy alloys using machine learning
- Author
-
Kandavalli, Manjunadh, Agarwal, Abhishek, Poonia, Ansh, Kishor, Modalavalasa, and Ayyagari, Kameswari Prasada Rao
- Published
- 2023
- Full Text
- View/download PDF
7. MXene/graphene oxide nanocomposites for friction and wear reduction of rough steel surfaces
- Author
-
Macknojia, Ali Zayaan, Ayyagari, Aditya, Shevchenko, Elena, and Berman, Diana
- Published
- 2023
- Full Text
- View/download PDF
8. Author Correction: MXene/graphene oxide nanocomposites for friction and wear reduction of rough steel surfaces
- Author
-
Macknojia, Ali Zayaan, Ayyagari, Aditya, Shevchenko, Elena, and Berman, Diana
- Published
- 2023
- Full Text
- View/download PDF
9. Author Correction: MXene/graphene oxide nanocomposites for friction and wear reduction of rough steel surfaces
- Author
-
Ali Zayaan Macknojia, Aditya Ayyagari, Elena Shevchenko, and Diana Berman
- Subjects
Medicine ,Science - Published
- 2023
- Full Text
- View/download PDF
10. Investigation of associations between Piezo1 mechanoreceptor gain-of-function variants and glaucoma-related phenotypes in humans and mice.
- Author
-
Baxter, Sally L, Keenan, William T, Athanas, Argus J, Proudfoot, James A, Zangwill, Linda M, Ayyagari, Radha, Liebmann, Jeffrey M, Girkin, Christopher A, Patapoutian, Ardem, and Weinreb, Robert N
- Subjects
Retinal Ganglion Cells ,Animals ,Humans ,Mice ,Glaucoma ,Ion Channels ,Cohort Studies ,Mechanotransduction ,Cellular ,Intraocular Pressure ,Genotype ,Phenotype ,Adult ,African Continental Ancestry Group ,European Continental Ancestry Group ,Gain of Function Mutation ,Mechanotransduction ,Cellular - Abstract
Glaucoma disproportionately affects individuals of African descent. Prior studies of the PIEZO1 mechanoreceptor have suggested a possible role in glaucoma pathophysiology. Here, we investigated associations between a Piezo1 gain-of-function variant common in individuals of African descent with glaucoma-related phenotypes. We analyzed whole genome sequences to identify Piezo1 variants and their frequencies among 1565 human participants. For the most common variant (e756del), we compared phenotypes between heterozygotes, homozygotes, and wildtypes. Longitudinal mixed effects models of visual field mean deviation (MD) and retinal nerve fiber layer (RNFL) thickness were used to evaluate progression. Based on trends in the models, further investigation was conducted using Piezo1 gain-of-function mice. About 30% of African descent individuals had at least one e756del allele. There were trends suggesting e756del was associated with higher IOPs, thinner RNFLs, lower optic nerve head capillary densities, and greater decreases in MD and RNFL thickness over time, but these did not reach statistical significance. Among mice, increased Piezo1 activity was not significantly associated with IOP or retinal ganglion cell density. Our study confirms that the Piezo1 e756del gain-of-function variant is a frequent polymorphism present in African descent individuals but is unrelated to examined differences in glaucoma phenotypes. Ongoing work is needed to elucidate the role of Piezo1-mediated mechanotransduction in glaucoma.
- Published
- 2020
11. Machine learning predicts live-birth occurrence before in-vitro fertilization treatment
- Author
-
Goyal, Ashish, Kuchana, Maheshwar, and Ayyagari, Kameswari Prasada Rao
- Published
- 2020
- Full Text
- View/download PDF
12. Towards developing robust solid lubricant operable in multifarious environments
- Author
-
Ayyagari, Aditya V., Mutyala, Kalyan C., and Sumant, Anirudha V.
- Published
- 2020
- Full Text
- View/download PDF
13. Tailored for Real-World: A Whole Slide Image Classification System Validated on Uncurated Multi-Site Data Emulating the Prospective Pathology Workload
- Author
-
Ianni, Julianna D., Soans, Rajath E., Sankarapandian, Sivaramakrishnan, Chamarthi, Ramachandra Vikas, Ayyagari, Devi, Olsen, Thomas G., Bonham, Michael J., Stavish, Coleman C., Motaparthi, Kiran, Cockerell, Clay J., Feeser, Theresa A., and Lee, Jason B.
- Published
- 2020
- Full Text
- View/download PDF
14. High Tensile Ductility and Strength in Dual-phase Bimodal Steel through Stationary Friction Stir Processing
- Author
-
Arora, H. S., Ayyagari, A., Saini, J., Selvam, K., Riyadh, S., Pole, M., Grewal, H. S., and Mukherjee, S.
- Published
- 2019
- Full Text
- View/download PDF
15. Towards developing robust solid lubricant operable in multifarious environments
- Author
-
Anirudha V. Sumant, Aditya Ayyagari, and Kalyan C. Mutyala
- Subjects
Materials science ,lcsh:Medicine ,02 engineering and technology ,engineering.material ,Article ,symbols.namesake ,0203 mechanical engineering ,Coating ,Nanoscience and technology ,Graphite ,Composite material ,Lubricant ,lcsh:Science ,Dry lubricant ,Multidisciplinary ,Moisture ,lcsh:R ,Tribology ,021001 nanoscience & nanotechnology ,020303 mechanical engineering & transports ,Carbon film ,engineering ,symbols ,lcsh:Q ,0210 nano-technology ,Raman spectroscopy - Abstract
Conventional solid lubricants such as MoS2, graphite, or diamond-like carbon films demonstrate excellent tribological performance but only in specific environments due to their inherent materials properties. This limitation prohibits using these solid lubricants in environments that change dynamically. This study presents the results of a novel solid lubricant that was developed using a combination of solution-processed 2D-molybdenum disulfide and graphene-oxide (GO) that can be deposited on to stainless steel substrates using a simple spray-coating technique and show exceptional performance in multifarious environments namely, ambient (humid) atmosphere, dry nitrogen, and vacuum. The tribological performance of the coatings was evaluated using a ball-on-disc sliding test and demonstrated an excellent wear/friction performance in all environments and coating survived even after 44 km of linear sliding. Transmission electron microscopy and Raman spectroscopy analysis of the tribolayers suggested in-operando friction-induced re-orientation of MoS2 layers that were protected by GO layers and, an absence of MoOx peaks indicate a strong resistance to intercalation with moisture and oxygen. The simplicity and robustness of the hybrid MoS2–GO solid lubricant in mitigating wear-friction behavior of steel-on-steel tribopair in a multifarious environment is a game-changing and is promising for various applications.
- Published
- 2020
- Full Text
- View/download PDF
16. Single cell RNA sequencing confirms retinal microglia activation associated with early onset retinal degeneration
- Author
-
Asha Kumari, Raul Ayala-Ramirez, Juan Carlos Zenteno, Kristyn Huffman, Roman Sasik, Radha Ayyagari, and Shyamanga Borooah
- Subjects
Fovea Centralis ,Multidisciplinary ,Sequence Analysis, RNA ,Retinal Degeneration ,Neurosciences ,Membrane Proteins ,Neurodegenerative ,Eye ,Mice ,Apolipoproteins E ,Genetics ,RNA ,2.1 Biological and endogenous factors ,Animals ,Humans ,Microglia ,Aetiology ,Sequence Analysis ,Eye Disease and Disorders of Vision - Abstract
Mutations in the Membrane-type frizzled related protein (Mfrp) gene results in an early-onset retinal degeneration associated with retinitis pigmentosa, microphthalmia, optic disc drusen and foveal schisis. In the current study, a previously characterized mouse model of human retinal degeneration carrying homozygous c.498_499insC mutations in Mfrp (MfrpKI/KI) was used. Patients carrying this mutation have retinal degeneration at an early age. The model demonstrates subretinal deposits and develops early-onset photoreceptor degeneration. We observed large subretinal deposits in MfrpKI/KI mice which were strongly CD68 positive and co-localized with autofluorescent spots. Single cell RNA sequencing of MfrpKI/KI mice retinal microglia showed a significantly higher number of pan-macrophage marker Iba-1 and F4/80 positive cells with increased expression of activation marker (CD68) and lowered microglial homeostatic markers (TMEM119, P2ry13, P2ry13, Siglech) compared with wild type mice confirming microglial activation as observed in retinal immunostaining showing microglia activation in subretinal region. Trajectory analysis identified a small cluster of microglial cells with activation transcriptomic signatures that could represent a subretinal microglia population in MfrpKI/KI mice expressing higher levels of APOE. We validated these findings using immunofluorescence staining of retinal cryosections and found a significantly higher number of subretinal Iba-1/ApoE positive microglia in MfrpKI/KI mice with some subretinal microglia also expressing lowered levels of microglial homeostatic marker TMEM119, confirming microglial origin. In summary, we confirm that MfrpKI/KI mice carrying the c.498_499insC mutation had a significantly higher population of activated microglia in their retina with distinct subsets of subretinal microglia. Further, studies are required to confirm whether the association of increased subretinal microglia in MfrpKI/KI mice are causal in degeneration.
- Published
- 2021
17. Machine learning predicts live-birth occurrence before in-vitro fertilization treatment
- Author
-
Ashish Goyal, Maheshwar Kuchana, and Kameswari Prasada Rao Ayyagari
- Subjects
0301 basic medicine ,Infertility ,Adult ,Male ,Adolescent ,Computer science ,media_common.quotation_subject ,medicine.medical_treatment ,Fertility ,Fertilization in Vitro ,Machine learning ,computer.software_genre ,Article ,Machine Learning ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Human fertilization ,Origin of life ,medicine ,Humans ,Ovulation ,Sperm counts ,Fertilisation ,media_common ,Pregnancy ,030219 obstetrics & reproductive medicine ,Multidisciplinary ,In vitro fertilisation ,business.industry ,Deep learning ,Embryo ,Middle Aged ,medicine.disease ,Sperm ,Computational biology and bioinformatics ,030104 developmental biology ,ROC Curve ,Embryology ,Linear Models ,Female ,Artificial intelligence ,business ,Live birth ,computer ,Live Birth ,Algorithms - Abstract
In-vitro fertilization (IVF) is a popular method of resolving complications such as endometriosis, poor egg quality, a genetic disease of mother or father, problems with ovulation, antibody problems that harm sperm or eggs, the inability of sperm to penetrate or survive in the cervical mucus and low sperm counts, resulting human infertility. Nevertheless, IVF does not guarantee success in the fertilization. Choosing IVF is burdensome for the reason of high cost and uncertainty in the result. As the complications and fertilization factors are numerous in the IVF process, it is a cumbersome task for fertility doctors to give an accurate prediction of a successful birth. Artificial Intelligence (AI) has been employed in this study for predicting the live-birth occurrence. This work mainly focuses on making predictions of live-birth occurrence when an embryo forms from a couple and not a donor. Here, we compare various AI algorithms, including both classical Machine Learning, deep learning architecture, and an ensemble of algorithms on the publicly available dataset provided by Human Fertilisation and Embryology Authority (HFEA). Insights on data and metrics such as confusion matrices, F1-score, precision, recall, receiver operating characteristic (ROC) curves are demonstrated in the subsequent sections. The training process has two settings Without feature selection and With feature selection to train classifier models. Machine Learning, Deep learning, ensemble models classification paradigms have been trained in both settings. The Random Forest model achieves the highest F1-score of 76.49% in without feature selection setting. For the same model, the precision, recall, and area under the ROC Curve (ROC AUC) scores are 77%, 76%, and 84.60%, respectively. The success of the pregnancy depends on both male and female traits and living conditions. This study predicts a successful pregnancy through the clinically relevant parameters in In-vitro fertilization. Thus artificial intelligence plays a promising role in decision making process to support the diagnosis, prognosis, treatment etc.
- Published
- 2020
18. Tailored for Real-World: A Whole Slide Image Classification System Validated on Uncurated Multi-Site Data Emulating the Prospective Pathology Workload
- Author
-
Sivaramakrishnan Sankarapandian, Kiran Motaparthi, Michael J. Bonham, Thomas G. Olsen, Coleman C. Stavish, Julianna D. Ianni, Ramachandra Vikas Chamarthi, Theresa A. Feeser, Rajath E. Soans, Jason B. Lee, Clay J. Cockerell, and Devi Ayyagari
- Subjects
0301 basic medicine ,Pathology ,medicine.medical_specialty ,Skin Neoplasms ,Standard of care ,Classification and taxonomy ,Computer science ,lcsh:Medicine ,Workload ,Article ,Pattern Recognition, Automated ,03 medical and health sciences ,Deep Learning ,0302 clinical medicine ,Suspected skin cancer ,Image Interpretation, Computer-Assisted ,Machine learning ,Image Processing, Computer-Assisted ,medicine ,Humans ,Computational models ,Computer Simulation ,Prospective Studies ,lcsh:Science ,Cell Proliferation ,Multidisciplinary ,business.industry ,Deep learning ,lcsh:R ,Multi site ,Reproducibility of Results ,Identification (information) ,030104 developmental biology ,ROC Curve ,030220 oncology & carcinogenesis ,Calibration ,Whole slide image ,Melanocytes ,lcsh:Q ,Neural Networks, Computer ,Dermatopathology ,Artificial intelligence ,business ,Algorithms - Abstract
Standard of care diagnostic procedure for suspected skin cancer is microscopic examination of hematoxylin & eosin stained tissue by a pathologist. Areas of high inter-pathologist discordance and rising biopsy rates necessitate higher efficiency and diagnostic reproducibility. We present and validate a deep learning system which classifies digitized dermatopathology slides into 4 categories. The system is developed using 5,070 images from a single lab, and tested on an uncurated set of 13,537 images from 3 test labs, using whole slide scanners manufactured by 3 different vendors. The system’s use of deep-learning-based confidence scoring as a criterion to consider the result as accurate yields an accuracy of up to 98%, and makes it adoptable in a real-world setting. Without confidence scoring, the system achieved an accuracy of 78%. We anticipate that our deep learning system will serve as a foundation enabling faster diagnosis of skin cancer, identification of cases for specialist review, and targeted diagnostic classifications.
- Published
- 2020
- Full Text
- View/download PDF
19. High Tensile Ductility and Strength in Dual-phase Bimodal Steel through Stationary Friction Stir Processing
- Author
-
Aditya Ayyagari, Harpreet Singh Grewal, Karthikeyan Selvam, Jaskaran Singh Saini, Sundeep Mukherjee, Mayur Pole, S. Riyadh, and Harpreet Singh Arora
- Subjects
0301 basic medicine ,Austenite ,Multidisciplinary ,Friction stir processing ,Materials science ,lcsh:R ,lcsh:Medicine ,engineering.material ,Instability ,Article ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Phase (matter) ,Martensite ,engineering ,lcsh:Q ,Austenitic stainless steel ,Composite material ,Elongation ,lcsh:Science ,Ductility ,030217 neurology & neurosurgery - Abstract
The combination of high strength and good ductility are very desirable for advanced structural and functional applications. However, measures to enhance strength typically lead to ductility reduction due to their inverse correlation, nano-grained structures for an instance. Bi-modal grain structure is promising in this regard, but its realization is limited by multiple complex processing steps. Here, we demonstrate a facile single-step processing route for the development of bimodal grain structure in austenitic stainless steel, SS316L. The bimodal structure comprised of fine martensite grains (
- Published
- 2019
- Full Text
- View/download PDF
20. Electrochemical and Friction Characteristics of Metallic Glass Composites at the Microstructural Length-scales
- Author
-
Sundeep Mukherjee, Harpreet Singh Arora, Vahid Hasannaeimi, and Aditya Ayyagari
- Subjects
010302 applied physics ,Kelvin probe force microscope ,Multidisciplinary ,Materials science ,Amorphous metal ,lcsh:R ,Alloy ,Composite number ,Delamination ,lcsh:Medicine ,02 engineering and technology ,engineering.material ,021001 nanoscience & nanotechnology ,01 natural sciences ,Article ,Corrosion ,Phase (matter) ,0103 physical sciences ,engineering ,lcsh:Q ,Work function ,Composite material ,lcsh:Science ,0210 nano-technology - Abstract
Metallic glass composites represent a unique alloy design strategy comprising of in situ crystalline dendrites in an amorphous matrix to achieve damage tolerance unseen in conventional structural materials. They are promising for a range of advanced applications including spacecraft gears, high-performance sporting goods and bio-implants, all of which demand high surface degradation resistance. Here, we evaluated the phase-specific electrochemical and friction characteristics of a Zr-based metallic glass composite, Zr56.2Ti13.8Nb5.0Cu6.9Ni5.6Be12.5, which comprised roughly of 40% by volume crystalline dendrites in an amorphous matrix. The amorphous matrix showed higher hardness and friction coefficient compared to the crystalline dendrites. But sliding reciprocating tests for the composite revealed inter-phase delamination rather than preferred wearing of one phase. Pitting during potentiodynamic polarization in NaCl solution was prevalent at the inter-phase boundary, confirming that galvanic coupling was the predominant corrosion mechanism. Scanning vibration electrode technique demonstrated that the amorphous matrix corroded much faster than the crystalline dendrites due to its unfavorable chemistry. Relative work function values measured using scanning kelvin probe showed the amorphous matrix to be more electropositive, which explain its preferred corrosion over the crystalline dendrites as well as its characteristic friction behavior. This study paves the way for careful partitioning of elements between the two phases in a metallic glass composite to tune its surface degradation behavior for a range of advanced applications.
- Published
- 2018
- Full Text
- View/download PDF
21. Electrochemical and Friction Characteristics of Metallic Glass Composites at the Microstructural Length-scales
- Author
-
Ayyagari, Aditya, primary, Hasannaeimi, Vahid, additional, Arora, Harpreet, additional, and Mukherjee, Sundeep, additional
- Published
- 2018
- Full Text
- View/download PDF
22. Effect of curcumin analogs onα-synuclein aggregation and cytotoxicity
- Author
-
A. Anoop, Reeba S. Jacob, Dhiman Ghosh, Subhadeep Das, Irishi N. N. Namboothiri, Narendra Nath Jha, Samir K. Maji, Pradeep K. Singh, and Narasimham Ayyagari
- Subjects
0301 basic medicine ,Curcumin ,Cell Survival ,Rat Plasma ,Plasma protein binding ,Protein aggregation ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,Protein Aggregates ,0302 clinical medicine ,food ,Microscopy, Electron, Transmission ,Cell Line, Tumor ,Spectroscopy, Fourier Transform Infrared ,Humans ,Amyloid Fibril Formation ,Cytotoxicity ,Alpha-synuclein ,Multidisciplinary ,Fibrillization ,Toxicity ,Inhibitors ,Circular Dichroism ,Parkinsons-Disease ,food.cuisine ,Chemopreventive Agent Curcumin ,Vivo ,Kinetics ,030104 developmental biology ,chemistry ,Biochemistry ,Drug development ,nervous system ,Spectrophotometry ,In-Vitro ,Thioflavin T-Fluorescence ,Synuclein ,alpha-Synuclein ,Asian food ,030217 neurology & neurosurgery ,Protein Binding - Abstract
Alpha-synuclein (α-Syn) aggregation into oligomers and fibrils is associated with dopaminergic neuron loss occurring in Parkinson’s disease (PD) pathogenesis. Compounds that modulate α-Syn aggregation and interact with preformed fibrils/oligomers and convert them to less toxic species could have promising applications in the drug development efforts against PD. Curcumin is one of the Asian food ingredient which showed promising role as therapeutic agent against many neurological disorders including PD. However, the instability and low solubility makes it less attractive for the drug development. In this work, we selected various curcumin analogs and studied their toxicity, stability and efficacy to interact with different α-Syn species and modulation of their toxicity. We found a subset of curcumin analogs with higher stability and showed that curcumin and its various analogs interact with preformed fibrils and oligomers and accelerate α-Syn aggregation to produce morphologically different amyloid fibrils in vitro. Furthermore, these curcumin analogs showed differential binding with the preformed α-Syn aggregates. The present data suggest the potential role of curcumin analogs in modulating α-Syn aggregation.
- Published
- 2016
- Full Text
- View/download PDF
23. Effect of curcumin analogs onα-synuclein aggregation and cytotoxicity
- Author
-
Jha, Narendra Nath, primary, Ghosh, Dhiman, additional, Das, Subhadeep, additional, Anoop, Arunagiri, additional, Jacob, Reeba S., additional, Singh, Pradeep K., additional, Ayyagari, Narasimham, additional, Namboothiri, Irishi N. N., additional, and Maji, Samir K., additional
- Published
- 2016
- Full Text
- View/download PDF
24. Single cell RNA sequencing confirms retinal microglia activation associated with early onset retinal degeneration
- Author
-
Asha Kumari, Raul Ayala-Ramirez, Juan Carlos Zenteno, Kristyn Huffman, Roman Sasik, Radha Ayyagari, and Shyamanga Borooah
- Subjects
Medicine ,Science - Abstract
Abstract Mutations in the Membrane-type frizzled related protein (Mfrp) gene results in an early-onset retinal degeneration associated with retinitis pigmentosa, microphthalmia, optic disc drusen and foveal schisis. In the current study, a previously characterized mouse model of human retinal degeneration carrying homozygous c.498_499insC mutations in Mfrp (Mfrp KI/KI) was used. Patients carrying this mutation have retinal degeneration at an early age. The model demonstrates subretinal deposits and develops early-onset photoreceptor degeneration. We observed large subretinal deposits in Mfrp KI/KI mice which were strongly CD68 positive and co-localized with autofluorescent spots. Single cell RNA sequencing of Mfrp KI/KI mice retinal microglia showed a significantly higher number of pan-macrophage marker Iba-1 and F4/80 positive cells with increased expression of activation marker (CD68) and lowered microglial homeostatic markers (TMEM119, P2ry13, P2ry13, Siglech) compared with wild type mice confirming microglial activation as observed in retinal immunostaining showing microglia activation in subretinal region. Trajectory analysis identified a small cluster of microglial cells with activation transcriptomic signatures that could represent a subretinal microglia population in Mfrp KI/KI mice expressing higher levels of APOE. We validated these findings using immunofluorescence staining of retinal cryosections and found a significantly higher number of subretinal Iba-1/ApoE positive microglia in Mfrp KI/KI mice with some subretinal microglia also expressing lowered levels of microglial homeostatic marker TMEM119, confirming microglial origin. In summary, we confirm that Mfrp KI/KI mice carrying the c.498_499insC mutation had a significantly higher population of activated microglia in their retina with distinct subsets of subretinal microglia. Further, studies are required to confirm whether the association of increased subretinal microglia in MfrpKI/KI mice are causal in degeneration.
- Published
- 2022
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.