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Article ; Online: Bacterial surface interactions with organic colloidal particles: Nanoscale hotspots of organic matter in the ocean.

Patel, Nirav / Guillemette, Ryan / Lal, Ratnesh / Azam, Farooq

2022 Volume 17, Issue 8, Page(s) e0272329

Abstract: Colloidal particles constitute a substantial fraction of organic matter in the global ocean and an abundant component of the organic matter interacting with bacterial surfaces. Using E. coli ribosomes as model colloidal particles, we applied high- ... ...

Abstract	Colloidal particles constitute a substantial fraction of organic matter in the global ocean and an abundant component of the organic matter interacting with bacterial surfaces. Using E. coli ribosomes as model colloidal particles, we applied high-resolution atomic force microscopy to probe bacterial surface interactions with organic colloids to investigate particle attachment and relevant surface features. We observed the formation of ribosome films associating with marine bacteria isolates and natural seawater assemblages, and that bacteria readily utilized the added ribosomes as growth substrate. In exposure experiments ribosomes directly attached onto bacterial surfaces as 40-200 nm clusters and patches of individual particles. We found that certain bacterial cells expressed surface corrugations that range from 50-100 nm in size, and 20 nm deep. Furthermore, our AFM studies revealed surface pits in select bacteria that range between 50-300 nm in width, and 10-50 nm in depth. Our findings suggest novel adaptive strategies of pelagic marine bacteria for colloid capture and utilization as nutrients, as well as storage as nanoscale hotspots of DOM.
MeSH term(s)	Bacteria ; Colloids ; Escherichia coli ; Oceans and Seas ; Seawater
Chemical Substances	Colloids
Language	English
Publishing date	2022-08-25
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0272329
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Article ; Online: The structure of tyrosine-10 favors ionic conductance of Alzheimer's disease-associated full-length amyloid-β channels.

Karkisaval, Abhijith G / Hassan, Rowan / Nguyen, Andrew / Balster, Benjamin / Abedin, Faisal / Lal, Ratnesh / Tatulian, Suren A

Nature communications

2024 Volume 15, Issue 1, Page(s) 1296

Abstract: Amyloid β (Aβ) ion channels destabilize cellular ionic homeostasis, which contributes to neurotoxicity in Alzheimer's disease. The relative roles of various Aβ isoforms are poorly understood. We use bilayer electrophysiology, AFM imaging, circular ... ...

Abstract	Amyloid β (Aβ) ion channels destabilize cellular ionic homeostasis, which contributes to neurotoxicity in Alzheimer's disease. The relative roles of various Aβ isoforms are poorly understood. We use bilayer electrophysiology, AFM imaging, circular dichroism, FTIR and fluorescence spectroscopy to characterize channel activities of four most prevalent Aβ peptides, Aβ
MeSH term(s)	Humans ; Amyloid beta-Peptides/metabolism ; Alzheimer Disease ; Tyrosine ; Ion Channels/chemistry ; Solvents ; Peptide Fragments/metabolism
Chemical Substances	Amyloid beta-Peptides ; Tyrosine (42HK56048U) ; Ion Channels ; Solvents ; Peptide Fragments
Language	English
Publishing date	2024-02-13
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-43821-y
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Article ; Online: Bacterial surface interactions with organic colloidal particles

Nirav Patel / Ryan Guillemette / Ratnesh Lal / Farooq Azam

PLoS ONE, Vol 17, Iss 8, p e

Nanoscale hotspots of organic matter in the ocean.

2022 Volume 0272329

Abstract	Colloidal particles constitute a substantial fraction of organic matter in the global ocean and an abundant component of the organic matter interacting with bacterial surfaces. Using E. coli ribosomes as model colloidal particles, we applied high-resolution atomic force microscopy to probe bacterial surface interactions with organic colloids to investigate particle attachment and relevant surface features. We observed the formation of ribosome films associating with marine bacteria isolates and natural seawater assemblages, and that bacteria readily utilized the added ribosomes as growth substrate. In exposure experiments ribosomes directly attached onto bacterial surfaces as 40-200 nm clusters and patches of individual particles. We found that certain bacterial cells expressed surface corrugations that range from 50-100 nm in size, and 20 nm deep. Furthermore, our AFM studies revealed surface pits in select bacteria that range between 50-300 nm in width, and 10-50 nm in depth. Our findings suggest novel adaptive strategies of pelagic marine bacteria for colloid capture and utilization as nutrients, as well as storage as nanoscale hotspots of DOM.
Keywords	Medicine ; R ; Science ; Q
Subject code	551
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
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Article ; Online: Fusarium wilt pandemic: current understanding and molecular perspectives.

Lal, Dalpat / Dev, Devanshu / Kumari, Sarita / Pandey, Saurabh / Aparna / Sharma, Nilesh / Nandni, Sudha / Jha, Ratnesh Kumar / Singh, Ashutosh

Functional & integrative genomics

2024 Volume 24, Issue 2, Page(s) 41

Abstract: Plant diseases pose a severe threat to the food security of the global human population. One such disease is Fusarium wilt, which affects many plant species and causes up to 100% yield losses. Fusarium pathogen has high variability in its genetic ... ...

Abstract	Plant diseases pose a severe threat to the food security of the global human population. One such disease is Fusarium wilt, which affects many plant species and causes up to 100% yield losses. Fusarium pathogen has high variability in its genetic constitution; therefore, it has evolved into different physiological races to infect different plant species spread across the different geographical regions of the world. The pathogen mainly affects plant roots, leading to colonizing and blocking vascular bundle cells, specifically xylem vessels. This blocking results in chlorosis, vascular discoloration, leaf wilting, shortening of plant, and, in severe cases, premature plant death. Due to the soil-borne nature of the wilt pathogen, neither agronomic nor plant protection measures effectively reduce the incidence of the disease. Therefore, the most cost-effective management strategy for Fusarium wilt is developing varieties resistant to a particular race of the fungus wilt prevalent in a given region. This strategy requires understanding the pathogen, its disease cycle, and epidemiology with climate-changing scenarios. Hence, in the review, we will discuss the pathogenic aspect and genetics of the Fusarium wilt, including molecular interventions for developing climate-smart wilt tolerant/resistant varieties of crops. Overall, this review will add to our knowledge for advancing the breeding of resistance against the wilt pandemic.
MeSH term(s)	Humans ; Pandemics ; Fusarium ; Plant Breeding ; Agriculture ; Climate Change
Language	English
Publishing date	2024-02-22
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	2014670-X
ISSN	1438-7948 ; 1438-793X
ISSN (online)	1438-7948
ISSN	1438-793X
DOI	10.1007/s10142-024-01319-w
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Zs.A 5230: Show issues

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Article ; Online: A Machine Learning Approach to COVID-19 Detection via Graphene Field-Effect-Transistor (GFET).

Tsui, Darin / Downey, Francisco / Navaneethan, Shreenithi / Paul, Akshay / Bodily, Tyler / Lee, Min / Xu, Yuchen / Lal, Ratnesh / Cauwenberghs, Gert

Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference

2023 Volume 2023, Page(s) 1–4

Abstract: In the wake of the COVID-19 pandemic, there has been a need for reliable diagnostic testing. However, state-of-the-art detection methods rely on laboratory tests and also vary in accuracy. We evaluate that the usage of a graphene field-effect-transistor ( ...

Abstract	In the wake of the COVID-19 pandemic, there has been a need for reliable diagnostic testing. However, state-of-the-art detection methods rely on laboratory tests and also vary in accuracy. We evaluate that the usage of a graphene field-effect-transistor (GFET) coupled with machine learning can be a promising alternate diagnostic testing method. We processed the current-voltage data gathered from the GFET sensors to assess information about the presence of COVID-19 in biosamples. We perform binary classification using the following machine learning algorithms: Linear Discriminant Analysis (LDA), Support Vector Machines (SVM) with the Radial Basis Function (RBF) kernel, and K-Nearest Neighbors (KNN) in conjunction with Principal Component Analysis (PCA). We find that LDA and SVM with RBF proved to be the most accurate in identifying positive and negative samples, with accuracies of 99% and 98.5%, respectively. Based on these results, there is promise to develop a bioelectronic diagnostic method for COVID-19 detection by combining GFET technology with machine learning.
MeSH term(s)	Humans ; Graphite ; Pandemics ; COVID-19/diagnosis ; Algorithms ; Machine Learning
Chemical Substances	Graphite (7782-42-5)
Language	English
Publishing date	2023-12-08
Publishing country	United States
Document type	Journal Article
ISSN	2694-0604
ISSN (online)	2694-0604
DOI	10.1109/EMBC40787.2023.10339994
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Article ; Online: Lipid-Encapsulated Silica Nanobowls as an Efficient and Versatile DNA Delivery System.

Som, Madhura / Lal, Ratnesh / Ruiz-Velasco, Victor

Bioconjugate chemistry

2020 Volume 31, Issue 12, Page(s) 2697–2711

Abstract: Nonmesoporous Janus silica nanobowls (NBs) are unique in that they possess two different nonporous surfaces per particle for loading biological molecules and can thus be designed with multifunctional properties. Although silica NBs have been successfully ...

Abstract	Nonmesoporous Janus silica nanobowls (NBs) are unique in that they possess two different nonporous surfaces per particle for loading biological molecules and can thus be designed with multifunctional properties. Although silica NBs have been successfully employed for both targeted therapeutic and diagnostic applications, their ability to deliver DNA has not yet been fully explored. The purpose of this study was to design and develop an in vitro transfection agent that would exploit the distinct characteristics of the silica NB. First, we determined that the NB surface can be linked to either supercoiled cDNA plasmids or vectorless, linear cDNA constructs. Additionally, the linearized cDNA can be functionalized and chemisorbed on NBs to obtain a controlled release. Second, the successful transfection of cells studied was dependent on lipid coating of the NB (LNBs). Although both NBs and LNBs were capable of undergoing endocytosis, NBs appeared to remain within vesicles as shown by transmission electron microscopy (TEM). Third, fluorescence microscopy and Western blotting assays revealed that transfection of four different cell lines and acutely isolated rat sensory neurons with LNBs loaded with either linear or supercoiled cDNA constructs coding for the fluorescent protein, clover and tdTomato, resulted in protein expression. Fourth, two separate opioid receptor-ion channel signaling pathways were functionally reconstituted in HEK cells transfected with LNBs loaded with three separate cDNA constructs. Overall, these results lay the foundation for the use and further development of LNBs as in vitro transfection agents.
MeSH term(s)	Capsules ; DNA, Complementary/chemistry ; DNA, Complementary/genetics ; Drug Carriers/chemistry ; Drug Carriers/metabolism ; Drug Liberation ; Endocytosis ; HEK293 Cells ; Humans ; Lipids/chemistry ; Nanostructures/chemistry ; Plasmids/genetics ; Porosity ; Silicon Dioxide/chemistry ; Silicon Dioxide/metabolism ; Transfection
Chemical Substances	Capsules ; DNA, Complementary ; Drug Carriers ; Lipids ; Silicon Dioxide (7631-86-9)
Language	English
Publishing date	2020-11-24
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1024041-x
ISSN	1520-4812 ; 1043-1802
ISSN (online)	1520-4812
ISSN	1043-1802
DOI	10.1021/acs.bioconjchem.0c00493
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Article ; Online: Scavenging amyloid oligomers from neurons with silica nanobowls: Implications for amyloid diseases.

Sant, Vrinda / Som, Madhura / Karkisaval, Abhijith G / Carnahan, Parker / Lal, Ratnesh

Biophysical journal

2021 Volume 120, Issue 16, Page(s) 3329–3340

Abstract: Amyloid-β (Aβ) oligomers are toxic species implicated in Alzheimer's disease (AD). The prevailing hypothesis implicates a major role of membrane-associated amyloid oligomers in AD pathology. Our silica nanobowls (NB) coated with lipid-polymer have ... ...

Abstract	Amyloid-β (Aβ) oligomers are toxic species implicated in Alzheimer's disease (AD). The prevailing hypothesis implicates a major role of membrane-associated amyloid oligomers in AD pathology. Our silica nanobowls (NB) coated with lipid-polymer have submicromolar affinity for Aβ binding. We demonstrate that NB scavenges distinct fractions of Aβs in a time-resolved manner from amyloid precursor protein-null neuronal cells after incubation with Aβ. At short incubation times in cell culture, NB-Aβ seeds have aggregation kinetics resembling that of extracellular fraction of Aβ, whereas at longer incubation times, NB-Aβ seeds scavenge membrane-associated Aβ. Aβ aggregates can be eluted from NB surfaces by mechanical agitation and appear to retain their aggregation driving domains as seen in seeding aggregation experiments. These results demonstrate that the NB system can be used for time-resolved separation of toxic Aβ species from biological samples for characterization and in diagnostics. Scavenging membrane-associated amyloids using lipid-functionalized NB without chemical manipulation has wide applications in the diagnosis and therapy of AD and other neurodegenerative diseases, cancer, and cardiovascular conditions.
MeSH term(s)	Alzheimer Disease ; Amyloid ; Amyloid beta-Peptides ; Humans ; Neurons ; Silicon Dioxide
Chemical Substances	Amyloid ; Amyloid beta-Peptides ; Silicon Dioxide (7631-86-9)
Language	English
Publishing date	2021-07-07
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	218078-9
ISSN	1542-0086 ; 0006-3495
ISSN (online)	1542-0086
ISSN	0006-3495
DOI	10.1016/j.bpj.2021.07.002
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Zs.A 235: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: In pursuit of degenerative brain disease diagnosis: Dementia biomarkers detected by DNA aptamer-attached portable graphene biosensor.

Bodily, Tyler Andrew / Ramanathan, Anirudh / Wei, Shanhong / Karkisaval, Abhijith / Bhatt, Nemil / Jerez, Cynthia / Haque, Md Anzarul / Ramil, Armando / Heda, Prachi / Wang, Yi / Kumar, Sanjeev / Leite, Mikayla / Li, Tie / Zhao, Jianlong / Lal, Ratnesh

Proceedings of the National Academy of Sciences of the United States of America

2023 Volume 120, Issue 47, Page(s) e2311565120

Abstract: Dementia is a brain disease which results in irreversible and progressive loss of cognition and motor activity. Despite global efforts, there is no simple and reliable diagnosis or treatment option. Current diagnosis involves indirect testing of commonly ...

Abstract	Dementia is a brain disease which results in irreversible and progressive loss of cognition and motor activity. Despite global efforts, there is no simple and reliable diagnosis or treatment option. Current diagnosis involves indirect testing of commonly inaccessible biofluids and low-resolution brain imaging. We have developed a portable, wireless readout-based Graphene field-effect transistor (GFET) biosensor platform that can detect viruses, proteins, and small molecules with single-molecule sensitivity and specificity. We report the detection of three important amyloids, namely, Amyloid beta (Aβ), Tau (τ), and α-Synuclein (αS) using DNA aptamer nanoprobes. These amyloids were isolated, purified, and characterized from the autopsied brain tissues of Alzheimer's Disease (AD) and Parkinson's Disease (PD) patients. The limit of detection (LoD) of the sensor is 10 fM, 1-10 pM, 10-100 fM for Aβ, τ, and αS, respectively. Synthetic as well as autopsied brain-derived amyloids showed a statistically significant sensor response with respect to derived thresholds, confirming the ability to define diseased vs. nondiseased states. The detection of each amyloid was specific to their aptamers; Aβ, τ, and αS peptides when tested, respectively, with aptamers nonspecific to them showed statistically insignificant cross-reactivity. Thus, the aptamer-based GFET biosensor has high sensitivity and precision across a range of epidemiologically significant AD and PD variants. This portable diagnostic system would allow at-home and POC testing for neurodegenerative diseases globally.
MeSH term(s)	Humans ; Amyloid beta-Peptides/metabolism ; Aptamers, Nucleotide ; Graphite ; Alzheimer Disease/diagnosis ; Alzheimer Disease/metabolism ; Parkinson Disease/diagnosis ; Biomarkers ; tau Proteins
Chemical Substances	Amyloid beta-Peptides ; Aptamers, Nucleotide ; Graphite (7782-42-5) ; Biomarkers ; tau Proteins
Language	English
Publishing date	2023-11-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2311565120
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Article ; Online: Generating Cyan Fluorescence with De Novo Tripeptides: An In Vitro Mutation Study on the Role of Single Amino Acid Residues and Their Sequence.

Guo, Jun / Ramachandran, Srinivasan / Zhong, Ruibo / Lal, Ratnesh / Zhang, Feng

Chembiochem : a European journal of chemical biology

2019 Volume 20, Issue 18, Page(s) 2324–2330

Abstract: Amino acids are natural choices as building blocks when developing biofunctional entities owing to their superior diversity and versatile physicochemical properties compared to nucleotide bases. A simple permutation of the amino acids creates a broad ... ...

Abstract	Amino acids are natural choices as building blocks when developing biofunctional entities owing to their superior diversity and versatile physicochemical properties compared to nucleotide bases. A simple permutation of the amino acids creates a broad palette of proteins and these have been successfully engineered into useful biofunctional agents. For example, the intrinsic ultraviolet fluorescence of phenylalanine and tryptophan has been engineered to emit in the visible spectrum, which has broad applications for imaging/sensing probes, photothermal therapy agents, optogenetic switches, etc. Nature produces more colorful coats/furs, feathers/hairs, and eyes through various biochemical modifications of tyrosine-based pigmentation. However, it is challenging to modulate the fluorescence wavelength from the UV to the visible region through oligopeptides. Herein, we report an innovative approach to obtain cyan fluorescence by using de novo tripeptides containing glycine, tyrosine, and lysine, which form robust dimer structures under moderate oxidizing conditions. Through an in vitro mutation approach, we deduce that both the amino acids and their sequence play significant roles in modulating the fluorescence. We believe this work holds great promise for developing novel cell imaging and resonance energy-transfer-based fluorescent probes.
MeSH term(s)	Amino Acid Substitution ; Cell Line, Tumor ; Color ; Fluorescence ; Fluorescent Dyes/chemistry ; Fluorescent Dyes/toxicity ; HEK293 Cells ; Humans ; Microscopy, Fluorescence ; Molecular Structure ; Mutation ; Oligopeptides/chemistry ; Oligopeptides/genetics ; Oligopeptides/toxicity ; Protein Multimerization
Chemical Substances	Fluorescent Dyes ; Oligopeptides
Language	English
Publishing date	2019-07-29
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2020469-3
ISSN	1439-7633 ; 1439-4227
ISSN (online)	1439-7633
ISSN	1439-4227
DOI	10.1002/cbic.201900166
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Article: Heme Oxygenase-1 at the Nexus of Endothelial Cell Fate Decision Under Oxidative Stress.

Raghunandan, Sindhushree / Ramachandran, Srinivasan / Ke, Eugene / Miao, Yifei / Lal, Ratnesh / Chen, Zhen Bouman / Subramaniam, Shankar

Frontiers in cell and developmental biology

2021 Volume 9, Page(s) 702974

Abstract: Endothelial cells (ECs) form the inner lining of blood vessels and are central to sensing chemical perturbations that can lead to oxidative stress. The degree of stress is correlated with divergent phenotypes such as quiescence, cell death, or senescence. ...

Abstract	Endothelial cells (ECs) form the inner lining of blood vessels and are central to sensing chemical perturbations that can lead to oxidative stress. The degree of stress is correlated with divergent phenotypes such as quiescence, cell death, or senescence. Each possible cell fate is relevant for a different aspect of endothelial function, and hence, the regulation of cell fate decisions is critically important in maintaining vascular health. This study examined the oxidative stress response (OSR) in human ECs at the boundary of cell survival and death through longitudinal measurements, including cellular, gene expression, and perturbation measurements. 0.5 mM hydrogen peroxide (HP) produced significant oxidative stress, placed the cell at this junction, and provided a model to study the effectors of cell fate. The use of systematic perturbations and high-throughput measurements provide insights into multiple regimes of the stress response. Using a systems approach, we decipher molecular mechanisms across these regimes. Significantly, our study shows that heme oxygenase-1 (HMOX1) acts as a gatekeeper of cell fate decisions. Specifically, HP treatment of HMOX1 knockdown cells reversed the gene expression of about 51% of 2,892 differentially expressed genes when treated with HP alone, affecting a variety of cellular processes, including anti-oxidant response, inflammation, DNA injury and repair, cell cycle and growth, mitochondrial stress, metabolic stress, and autophagy. Further analysis revealed that these switched genes were highly enriched in three spatial locations viz., cell surface, mitochondria, and nucleus. In particular, it revealed the novel roles of HMOX1 on cell surface receptors EGFR and IGFR, mitochondrial ETCs (MTND3, MTATP6), and epigenetic regulation through chromatin modifiers (KDM6A, RBBP5, and PPM1D) and long non-coding RNA (lncRNAs) in orchestrating the cell fate at the boundary of cell survival and death. These novel aspects suggest that HMOX1 can influence transcriptional and epigenetic modulations to orchestrate OSR affecting cell fate decisions.
Language	English
Publishing date	2021-09-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2737824-X
ISSN	2296-634X
ISSN	2296-634X
DOI	10.3389/fcell.2021.702974
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