Biological physics is the branch of science that applies the principles of physics, chemistry, and mathematics to the biological system to understand the fundamental biological processes such as how biomolecules, cells, tissues, and organs perform vital life functions. Scientists from diverse backgrounds use an experimental, computational, and theoretical approach to explore the mysteries of life. Medical physics applies knowledge of physics in medicine to diagnose and treat human disease using methods like magnetic resonance imaging and radiation treatments. Soft matter physics is an interdisciplinary field where scientists from different areas of science come together to understand the behavior and properties of soft materials like liquid crystals, colloids, polymers, gels, membranes, and cytoskeletons. The Biological/Medical/Soft matter physics session of the ANPA conference taking place on July 19-21, 2024, aims to bring the scientist together to present their findings, discuss their research and foster new collaborations. We invite you and your colleagues to submit abstracts for presentations and look forward to seeing you at the conference.
AI and computational neuroimaging for brain health and disorders
Imaging modalities, such as magnetic resonance imaging (MRI) and positron emission tomography (PET), are among the most significant advancements in physics and engineering design. These non-invasive imaging techniques have transformed numerous sectors, including brain health and disorders. However, MRI and PET neuroimaging data are extremely complex and difficult to interpret. This makes it difficult to reach research and clinical outcomes that are important for clinical diagnosis, prognosis, and future precision medicine. To overcome these obstacles, modern machine learning and artificial intelligence (AI) technologies have shown considerable promise in describing brain systems using non-invasive neuroimaging data. In this talk, we will discuss various AI and computational neuroimaging approaches, as well as their promising applications in identifying novel brain mechanisms in health and disease, with a focus on schizophrenia, first-episode psychosis, autism, and Alzheimer’s disease. These findings indicate that physics-based imaging methods integrated with advanced AI methodologies provide a multidisciplinary perspective for uncovering novel mechanisms about brain health, which may contribute to the development of future computer-aided therapy efforts for brain disorders.
Please look below for detailed schedule.
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Abstract Number: ANPA2024-N00012 Presenting Author: Hari Shankar Mallik Presenter's Affiliation: Central Department of Physics, TU, Kirtipur, Kathmandu, Nepal Title: Level crossing resonance studies of derivatives of hemoglobin using muon Location: In-Person Presentation, CDP Show/Hide Abstract To be added
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Abstract Number: ANPA2024-N00013 Presenting Author: Narayan Gautam Presenter's Affiliation: Central Department of Physics, Tribhuvan University, Kathmandu, Nepal Title: Characterizing HDAC7-MEF2A complex formation Location: In-Person Presentation, CDP Show/Hide Abstract Histone deacetylases (HDACs) regulate gene expression and play an important role in regulation of neuronal cell death through interactions with other binding partners such as MEF2A. Myogenesis, neuronal survivals, and axon branching are associated with HDAC-MEF2 transcription complexes. To the best of our knowledge, structural investigations of this functional complex are limited, and no crystal of HDAC7-MEF2A complex is available. Prior experimental studies were determined the range of amino acids responsible for interactions. In this study, we first modeled the HDAC7-MEF2A complex and then performed molecular dynamics (MD) simulations of the complex to explore the crucial residues that are establish molecular interact between these two proteins. Our results predict that SER82 and LYS96 in HDAC establish Hydrogen bonds with ASP63 in MEF2A, respectively. In addition, LYS96 in HDAC7 and ASP63 in MEF2A also predicted to form a salt bridge. Our analysis of the HDAC7-MEF2A binding shows that hydrophobic interactions play the main role in complex formation and stabilization of the complex.
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Abstract Number: ANPA2024-N00090 Presenting Author: Trailokya Bhattarai Presenter's Affiliation: UNC Charlotte Title: Advancing Disinfection Technology: Solar-Powered UV LED Systems for Microbial Reduction Location: In-Person Presentation, Fayetteville Show/Hide Abstract UV-C radiation is effective in deactivating a wide range of microorganisms. The increasing need for effective microbial deactivation methods has led to the exploration of ultraviolet (UV) light-emitting diodes (LEDs) as a possible solution. This study presents the design, construction, and testing of solar-powered UV LED systems that can deactivate different bacteriophages like MS2 and Phi6. The experimental approach involved designing and building the prototype of UV LEDs disinfection system, testing their effectiveness in deactivating microbes using cell culture method and integrating them with solar power. We developed four distinct UV LED systems with wavelengths of 255 nm, 265 nm, 275 nm, and 285 nm, each demonstrating irradiance levels of 393, 404, 44.7, and 582 µW/cm², respectively at the distance where the microbial samples are placed. This research focuses on precise control of UV exposure parameters, including precise adjustments to UV dose, irradiance, and exposure time resulting in substantial microbial reduction. The result for the 275 nm UV LED system shows a 1.16 log reduction of MS2 with a UV dose of 26.82 mJ/cm² and a 1.26 log reduction of Phi6 with a dose of 32.81 mJ/cm². These correspond to 93% and 94.5% reduction of MS2 and Phi6 respectively. These outcomes show the considerable potential of the designed UV-LED system as a targeted and versatile disinfection technology, showing substantial implications for real-world applications. Moreover, the prospect of integrating solar cell technology in future research endeavors holds promise for the development of self-sustained and renewable disinfection systems. Another possible application of this research in computing is the development of smart disinfection systems. By integrating UV LED systems with sensors, Internet of Things (IoT) devices, and artificial intelligence algorithms, disinfection could become more targeted and efficient.
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Abstract Number: ANPA2024-N000111 Presenting Author: Ganesh Chand (Invited) Presenter's Affiliation: Washington University in St. Louis Title: AI and computational neuroimaging for brain health and disorders Location: Virtual Presentation Show/Hide Abstract Imaging modalities, such as magnetic resonance imaging (MRI) and positron emission tomography (PET), are among the most significant advancements in physics and engineering design. These non-invasive imaging techniques have transformed numerous sectors, including brain health and disorders. However, MRI and PET neuroimaging data are extremely complex and difficult to interpret. This makes it difficult to reach research and clinical outcomes that are important for clinical diagnosis, prognosis, and future precision medicine. To overcome these obstacles, modern machine learning and artificial intelligence (AI) technologies have shown considerable promise in describing brain systems using non-invasive neuroimaging data. In this talk, we will discuss various AI and computational neuroimaging approaches, as well as their promising applications in identifying novel brain mechanisms in health and disease, with a focus on schizophrenia, first-episode psychosis, autism, and Alzheimer's disease. These findings indicate that physics-based imaging methods integrated with advanced AI methodologies provide a multidisciplinary perspective for uncovering novel mechanisms about brain health, which may contribute to the development of future computer-aided therapy efforts for brain disorders.
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Abstract Number: ANPA2024-N000112 Presenting Author: Supriya Dhakal Presenter's Affiliation: Department of Physics and Astronomy, Georgia State University Title: ATR-FTIR Spectroscopy for Carbohydrate Concentration Calibrations Location: Virtual Presentation Show/Hide Abstract Accurate detection and monitoring of biomolecules such as proteins and carbohydrates in body fluids are important for disease diagnosis. Attenuated Total Reflectance-Fourier Transform Infrared (ATR-FTIR) Spectroscopy is a non-invasive, rapid, and reliable analytical method to study the changes in vibrational modes of molecules of biological samples like saliva, blood serum, and tissues. This study leverages prior works where distinct spectral patterns were identified in conditions such as cancer and colitis, providing a foundation for correlating spectral data of glucose, mannose, and other sugars with diseases. Experimental procedures involved acquiring the ATR-FTIR spectral data for known concentrations of these carbohydrates in their pure form. The repeatability of the measurements was ensured through careful consideration of the environmental conditions and instrument parameters. The resulting calibration curve of the absorbance values plotted against the concentration for a characteristic wavenumber shows a linear relationship, confirming the efficacy of these curves in quantifying carbohydrate concentrations. Comparative study of blood serum samples from control and diseased groups helps identify variations in carbohydrate levels and the findings from this analysis will be discussed. Future work will integrate these spectral signature concentrations to enhance the specificity and sensitivity of FTIR-based disease diagnostic protocols.
Keywords: ATR-FTIR Spectroscopy, Calibration Curve, Bio Spectral Signatures, Carbohydrate Concentration, Disease Diagnosis
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Abstract Number: ANPA2024-N000113 Presenting Author: Chandrama Mukherjee Presenter's Affiliation: Georgia State University Title: Differences in Brain Volume Changes between Mild Cognitive Impairment and Alzheimer’s Disease: A Gender-Specific Investigation Incorporating Behavioral Measures Location: Virtual Presentation Show/Hide Abstract Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory impairment, and behavioral changes. Mild cognitive impairment (MCI) represents an intermediate stage between normal aging and dementia, often preceding the development of AD. Diagnosis relies on comprehensive clinical evaluation, neuropsychological testing, and imaging studies to rule out other causes of cognitive decline. Structural MRI is commonly used to visualize and analyze the brain's anatomy and can detect abnormalities, lesions, or structural changes associated with various neurological conditions, including Alzheimer's disease.
In our study, we have used 332 subjects with high-resolution structural MRI (T1-weighted) data from ADNI (Alzheimer's Disease Neuroimaging Initiative) to show volumetric differences of certain brain regions across subject types (Control, MCI, AD). A pairwise correlation between Subject type (Control, MCI, CN) and volumes of pre-hypothesized regions of interest of the brain showed significant contribution from several regions including right entorhinal, left entorhinal, right fusiform, left fusiform, right inferiorparietal, left inferiorparietal, right inferiortemporal, left inferior temporal, both left and right amygdala, hippocampus and accumbensarea. A significant interaction exists between these brain regions and neuropsychological scores like Mini-Mental State Examination (MMSE), and Neuropsychiatric Inventory (NPI); indicating the fact that MMSE and NPI scores can be used as a marker of the gradual progression of Alzheimer’s disease. The ANOVA indicated a stronger association between MMSE scores and brain regions in females compared to males in the AD cohort. Moreover, our multivariate analysis indicates that there is an overall significant interaction between Subject type and Sex, as evidenced by the difference in the Gray Matter Volume (GMV) between males and females, as the disease progresses
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Abstract Number: ANPA2024-N000114 Presenting Author: Navdeep Kalkat Presenter's Affiliation: Boise State University Title: Temperature and Cholesterol Content Modulates the Interaction of Alpha-Crystallin with Model of Lens-Lipid Membrane Location: Virtual Presentation Show/Hide Abstract The binding of α-crystallin with the lens membrane increases with age and cataract; however, how the temperature and cholesterol influence α-crystallin membrane binding is unclear. We have used electron paramagnetic resonance (EPR) spin-labeling methods and investigated the binding of α-crystallin with the cholesterol (Chol)/model of bovine lens-lipid (MBLL) membranes with Chol/MBLL mixing ratio of 0, 0.3, and 1.5. The Chol/MBLL membranes with 1 mol% of Chol analog spin label CSL were prepared with rapid solvent exchange method followed by probe-tip sonication and incubated with α-crystallin at 30, 37, and 45 ℃ for 16 hours followed by the EPR measurements taken at 37 ℃. Our results show that Chol and cholesterol bilayer domain (CBDs) inhibit the binding of α-crystallin to Chol/MBLL membranes independently of temperature. For Chol/MBLL mixing ratios of 0 and 0.3, α-crystallin binds with Chol/MBLL membranes in a saturable manner for all the incubation temperatures, and for Chol/MBLL mixing ratio of 1.5, no binding of α-crystallin to the membrane was observed in all the incubation temperature. For the Chol/MBLL mixing ratio of 0 and 0.3, the maximum percentage of membrane surface occupied (MMSO) by α-crystallin followed the trends: MMSO (37 ℃)> MMSO (45 ℃) > MMSO (30 ℃). For all the temperatures investigated, the mobility near the headgroup of membranes decreases with an increase in α-crystallin concentration at Chol/MBLL mixing ratio of 0 and 0.3. The hydrophobicity near the headgroup regions increases with α-crystallin binding for all the temperatures investigated at Chol/MBLL mixing ratio of 0 and 0.3, suggesting that α-crystallin binding forms the hydrophobic barrier near the membrane surface; however, at Chol/MBLL mixing ratio of 1.5, no significant change in hydrophobicity near the membrane surface was observed suggesting that high Chol and CBDs inhibit α-crystallin binding and prevents the formation of hydrophobic barrier near the membrane surface.
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Abstract Number: ANPA2024-N000124 Presenting Author: Anup Shrestha Presenter's Affiliation: Central Department of Physics, Tribhuvan University, Kathmandu, Nepal Title: Muon dose estimation in brain tumor Location: Virtual Presentation Show/Hide Abstract The first step towards cancer treatment is identifying hypoxia, a low oxygen concentration within the tissue [1]. To estimate the spatial distribution of molecular oxygen in the tissue (especially in tumor), a non-invasive muon method is proposed and tested the sensitivity of the proposed method to detect the low oxygen concentration in dilute protein solutions [2,3]. To understand the muon stopping range and depth distribution in tumors, we perform Monte Carlo simulation using PHITS code to estimate the muon dose in tumors [4].
In this study, depth-dose profile was evaluated for muon beam of energies ranging from 5 – 45 MeV simulated in head phantom containing spherical tumor of 1 cm radius. Detail dose study in the phantoms of soft tissue, brain tissue, skin and compact bone embedded with same dimension of tumor were simulated varying the oxygen concentrations. The study found that, energy of muon to form the Bragg Peak at the end of the tumor is much less for muon beam [4] than that required for proton beam [5]. Simulation for variable oxygen concentration suggested that as the oxygen concentration in tumor decreases energy required to attain Bragg Peak at the same range increases.
References
[1] P. Vaupel and L. Harrison, The Oncologist, 9 (2004) 4–9.
[2] A. D. Pant et. al., Nuclear Instruments and Methods in Physics Research A, 1011 (2021) 165561.
[3] A. D. Pant et. al., Journal of Physics: Conference Series, 551(1) (2014) 012043
[4] A. Shrestha et al, in preparation.
[5] Z. Hashemi et. al., Reports of Practical Oncology & Radiotherapy, 25(6) (2020) 927–933.
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Abstract Number: ANPA2024-N000125 Presenting Author: Roshan Pudasaini Presenter's Affiliation: Kathmandu University Title: Muonium behavior in derivatives of hemoglobin: a first-principles study Location: Virtual Presentation Show/Hide Abstract
There are various methods to detect low oxygen levels or hypoxia in tumor/cancer such as positron emission tomography, magnetic resonance imaging, electron paramagnetic resonance, and pulse oximetry with their limitations as mentioned by Tatum et al [1] and Conner et al [2]. A noninvasive technique is necessary to detect hypoxia and assess its existence, extent, and spatial distribution within a tumor [2]. In order to develop a noninvasive tool for the diagnosis and treatment of cancer, we propose a muon method and detected the molecular oxygen in water and dilute protein solutions (Hb, TBS, albumin, serum) [3,4]. To interpret the muon experiment, theoretical study is necessary to understand the stopping sites and charge states of injected muon into biomolecules. Here, we present density functional theory calculations to estimate the stopping sites, charge states and interaction of muon with nearby molecules in derivatives of hemoglobin (DeoxyHb, OxyHb, COHb and MetHb) [5].
Muon is a like a light proton with mass around 1/9 pf that of proton. Since the muon’s gyromagnetic ratio is around three times greater than that of the proton, it has higher sensitivity with respect to proton to magnetic field. Muonium(Mu) on the other hand, is a bound state of a positive muon and an electron with similar chemical properties of H [6].
Based on minimum potential energy, we found the stopping site of the muonium in the heme group of DeoxyHb, OxyHb, COHb and MetHb around the nitrogen atom of the imidazole ring of histidine [5]. The estimated hyperfine coupling terms will be helpful to support the muon experiment in these derivatives. In the program, the stopping sites and hyperfine coupling interaction of Mu in the derivatives of hemoglobin will be presented.
Reference:
[1] J. L. Tatum, Int. J. Radiat. Biol., 82 (2006) 699–757.
[2] J. P. O’Connor et al., Cancer Res., 76 (2016) 787–795.
[3] A. D. Pant et al., Nucl. Instrum. Methods Phys. Res. A, 1011 (2021) 165561.
[4] A. D. Pant et. al., Journal of Physics: Conference Series, 551 (2014) 012043.
[5] R. Pudasaini et al., Interactions, 245 (2024) 34.
[6] K. Nagamine, Introductory muon science. Cambridge University Press, 2003.
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Abstract Number: ANPA2024-N000126 Presenting Author: Kalpana Gyawali Presenter's Affiliation: Tribhuvan University Title: In silico determination of selected plant-based compounds against SARS-CoV-2 Location: Virtual Presentation Show/Hide Abstract The outbreak of SARS-CoV-2 in late 2019 led to a global pandemic due to its rapid human-to-human transmission. COVID-19 Mpro is a crucial enzyme for the replication and transcription of the virus and an attractive target for the drug discovery. In response to the need for effective antiviral drugs, this study focused on the in silico investigation of plant-based compounds against the SARS-CoV-2 Omicron Mpro. Compounds n-Caffeoyltyramine, quercetin, and 1,3-dicaffeoylquinate underwent molecular docking with SARS-CoV-2 Omicron Mpro and demonstrated strong interactions, resulting in binding energies of -6.89. -6.79, and -6.02 kcal/mol respectively. The binding mechanisms, including H-bonding, electrostatic, van der Waals and hydrophobic interactions, were also analyzed. Various parameters (RMSD, RMSF, Rg, SASA, and the number of hydrogen bonds) observed during 100 ns MD simulations showed that the compound quercetin remained stable. The MM/GBSA free energy calculation for quercetin with Mpro was -16.83 kcal/mol. This compound exhibited favorable scores for drug likeness, bioavailability and pharmacokinetic properties. Based on ADMET parameters, favorable binding affinity and stability observed during MD simulations, quercetin could be considered a potential drug candidate against the SARS-CoV-2 Omicron variant. More research is needed to confirm the effectiveness and safety of this compound in human trials.
Keywords: SARS-CoV-2 Omicron main protease, ADMET parameters, Molecular docking, MD
simulations, MM/GBSA free energy calculations
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Abstract Number: ANPA2024-N000127 Presenting Author: RAJESH MAHARJAN Presenter's Affiliation: Tribhuvan University Title: In Silico Determination of Flavonoids as Antitubercular Agents Location: Virtual Presentation Show/Hide Abstract Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, has been considered a threat to the world health system. It is a contagious malady which assault the lungs and can also devastate other parts of the body. The long-term medication as well as Mtb resistance to existing drugs has become a worldwide issue. This work intends to identify the potential drug candidates against Mtb pathogen by computational approach. Molecular docking was performed on the active site of the M. tuberculosis H37Rv (3R)-hydroxyacyl-ACP (HadAB) dehydratase heterodimer (4RLU.pdb). The possible therapeutic flavonoids naringenin, taxifolin, 3,6-dihydroxyflavone, and apigenin are primarily selected. From ADMET analysis, molecular docking, MD simulations, these compounds are analyzed with H-bonding, electrostatic, van der Waals, hydrophobic interactions and free energy calculations. The compounds in the active site of Mtb protein target. The compounds exhibited strong binding interaction energy ranging from -6.83 to -7.32 kcal/mol with target protein with inhibition constant 9.89 to 4.33 μM. The analysis of RMSD, RMSF, Rg, SASA, H-bond and end point free energy values from 100 ns showed that the three compounds form stable complex with target protein. The selected compounds are non-toxic and have good bioavailability scores and drug-likeness. Mtb in complex with apigenin had the lowest end point free energy of -20.85 kcal/mol which effectively binds to the protein target.
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Abstract Number: ANPA2024-N000128 Presenting Author: Anjan Dahal Presenter's Affiliation: Central Department of Physics, Tribhuvan University, Nepal Title: Anisotropic muonium observed in PBS buffer Location: Virtual Presentation Show/Hide Abstract Abstract
To establish the fundamentals of muon in biology and application to cancer research, we study the muon (positive muon) and muonium behavior in water, buffer, constituents of biomolecules, hemoglobin [1,2] and various biomacromolecules. We conducted a muon experiment in several bio-samples and DFT calculations [3-5]. Here we present experimental study in buffer (phosphate buffer saline, PBS) using pulse muon beam available in MLF, J-PARC center, Japan.
Muon a spin half particle is like a light proton (mm ~ 1/9 mp). It has three times larger magnetic moment than that of the proton which makes it highly sensitive to magnetic field in materials. Muonium is the bound state of a muon and an electron which shows similar chemical but different magnetic properties with atomic hydrogen. In muon spin rotation and relaxation (μSR) method, the positive muon is injected into the sample which picks an electron and forms muonium at the end of radiation track. The mSR is used to know the local electronic and spin states of materials [6].
PBS is used to dissolve proteins and peptides for experimenting, used in transporting cells and tissue and also administered to patients because of solute and ion concentration matching that to the human body. Temperature dependent μSR experiment in PBS were performed at different magnetic fields to observe the muonium precession signal. In liquid phase of PBS, we found an isotropic muonium and a diamagnetic muon species. However, in solid (frozen) PBS, there are two diamagnetic muon species in addition to axially symmetric anisotropic muonium like in the solid water [7]. In the program, temperature dependent behavior of anisotropic muonium in the buffer will be discussed.
References
[1] A. D. Pant et.al, Nuclear Instruments and Methods in Physics Research Section 1011, 165561(2021).
[2] A. D. Pant et. Al, Journal of Physics: Conference Series 551, 012043 (2014)
[3] R. Pudasaini et al. Hyperfine Interact 245, 34 (2024)
[4] A . D. Pant et al, JPS Conf.Proc. 21, 011038 (2018).
[5] A. D. Pant et al, JPS Conf. Proc. 25, 011013 (2019)
[6] A.D. Pant, Journal of Nepal Physical Society, 49–53 (2021)
[7] A. D. Pant et al, submitted.
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Abstract Number: ANPA2024-N000136 Presenting Author: Mehmood Pirzada Presenter's Affiliation: Department of Physics and Astronomy, Georgia State University Title: ATR-FTIR spectroscopic analysis of biomarkers in mice blood serum for disease monitoring Location: Virtual Presentation Show/Hide Abstract The gold standard for diagnosing Inflammatory Bowel Diseases (IBDs), Colonoscopy, offers high sensitivity and specificity. However, in practice, patient compliance in adhering to testing is often low due to multiple factors including extensive preparation time, uncomfortable procedures, and high associated costs. This is particularly concerning as IBDs are increasingly affecting younger age groups worldwide. To address this compliance issue, this study employs Attenuated Total Reflectance- Fourier Transform Infrared (ATR-FTIR) spectroscopy to monitor biochemical changes in mice blood serum, aiming to identify biomarkers for the ulcerative colitis, one of the two prominent IBDs characterized by inflammation of the colon. Mice used in this study were administered drinking water containing 3% Dextran Sodium Sulphate (DSS) which is known to induce colitis in mice. DSS is the most popular and widely used mouse model in IBD research. Colitis-induced mice blood serum (only 1 µl) samples at different time intervals of DSS treatment were subjected to ATR-FTIR spectral analysis. The alterations in biomolecules due to colitis were further analyzed through various statistical analysis techniques in the fingerprint region (900 cm-1 – 1800 cm-1) of the absorbance spectrum. Through p- value calculations, regions of significant differences were identified for samples at different time intervals in the trial. These regions were further analyzed using secondary structure analysis, to obtain component biochemicals, performed through the curve fitting technique. The absorbance difference spectra and the biochemical changes in the specific significant regions further showed the noticeable changes that occurred due to disease progression. Our findings suggest the potential of using ATR-FTIR spectroscopy as a low cost, comfortable, and user-friendly technique to discover new biomarkers for colitis, facilitating disease monitoring over the course of the disease.
Keywords: ATR-FTIR spectroscopy, biomarkers, ulcerative colitis, DSS mice serum
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Abstract Number: ANPA2024-N000137 Presenting Author: Preston Hazen Presenter's Affiliation: Boise State University Title: Alpha-Crystallin Becomes Increasingly Membrane Bound to Human Cortical and Nuclear Lens Lipid Membranes with the Progression of Cortical and Nuclear Cataracts Location: Virtual Presentation Show/Hide Abstract Eye lens α-crystallin becomes increasingly membrane-bound with age and cataract formation; however, the membrane interactions of α-crystallin throughout the development of cortical (CC) and nuclear cataracts (NC) in single human lenses has yet to be studied. In this study, the electron paramagnetic resonance spin-labeling method was used to investigate the interactions of α-crystallin with the nuclear membrane (NM) and cortical membrane (CM) throughout the progression of CC and NC in five pairs of human lenses (3 male and 2 female) ranging in age from 64 to 73 years old. The use of separated individual human lenses allows for incorporating donor health history, sex, and race in the data analysis to account for multiple factors affecting α-crystallin membrane binding and cataract development. This study found the binding of α-crystallin to the male and female eye lens CM and NM increases with increasing CC and NC grade and alters membrane physical properties, leading to decreased mobility, increased order, and increased hydrophobicity at the membrane surface. Additionally, in both males and females, the CM mobility decreased with increasing CC grade, whereas mobility in the NM with increasing NC grade increased in females and showed no significant change in males. The changes in the CM and NM lipid composition, cholesterol content, and cholesterol bilayer domains (CBD) size and number, found with age and cataract formation, are therefore likely altering the membrane surface mobility, hydrophobicity, and consequentially, the membrane interactions of α-crystallin. Furthermore, this study shows how the loss of cholesterol and the reduction in the size and number of CBDs in the cataractous CM and NM directly correlates with the increased binding of α-crystallin found with increasing CC and NC grade, suggesting that cholesterol and CBDs might be a key component in maintaining lens transparency and preventing cataract formation.
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Abstract Number: ANPA2024-N000138 Presenting Author: Krishna Sigdel Presenter's Affiliation: California State Polytechnic University-Pomona Title: Atomic force Microscopy of Peptide-Membrane Interactions Location: Virtual Presentation Show/Hide Abstract Peptides are essential structural components of a cell. The interactions of peptides with the complex phospholipid bilayer environment determine the three-dimensional structure of membrane proteins. Understanding these interactions is important because they dictate the partitioning, folding, stability, and function of this large class of proteins, which are targets for more than half of all current drugs. Moreover, the interaction process is of fundamental importance for understanding the mechanism of action of antimicrobial peptides (AMPs). Antimicrobial peptides (AMPs) form a vital part of the innate immune system and can be universally found in all domains of life (prokaryotes to eukaryotes). These peptides can kill bacteria, fungi, and even cancer cells by permeabilizing the cellular membranes. Due to their activity against bacteria, AMPs have been actively tested as potential candidates for the development of antimicrobial agents. We investigated the effect of a synthetic hybrid peptide, CM15, on the membrane surface. Direct imaging of supported lipid bilayers exposed to various concentrations of the peptide revealed significant membrane remodeling. We found that CM15 interacts with supported lipid bilayers and forms membrane-spanning defects very quickly. The effect of the peptide was found to be lipid species dependent.
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Abstract Number: ANPA2024-N000139 Presenting Author: Beyza Bektasoglu Presenter's Affiliation: Campbellsville University Title: Studying Long QT Syndrome Mutations of KCNE3 using Site-Directed Spin Labeling EPR Spectroscopy Location: Virtual Presentation Show/Hide Abstract KCNE3, a member of the KCNE protein family, is a single-pass transmembrane protein that regulates the function and trafficking of various voltage-gated potassium channels such as KCNQ1. KCNE3 can be expressed in the small intestine, colon, and in the human heart. Certain KCNE3 mutations such as T4A, P39R, and R99H are associated with long QT syndrome (LQTS), while V17M and R53H are linked to atrial fibrillation. A mutation in KCNE3 may alter its structural dynamics, leading to abnormal electrical activity. Understanding how these disease-causing mutations affect the structural dynamic properties of KCNE3 is crucial. Electron paramagnetic resonance (EPR) spectroscopy in combination with site-directed spin labeling (SDSL) technique is very useful structural biology tool to study membrane proteins/peptides. In this study, we performed continuous wave (CW)-EPR spectroscopic measurements on spin-labeled amino acid residue sites nearby diseases-causing mutations to investigate the effect of these mutations on the structural dynamics of KCNE3 in POPC/POPG lipid bilayers. We compared the spin-label mobility (determined as inverse central linewidth) and rotational correlation times between wild-type KCNE3 and KCNE3 with disease-causing mutations. This study will provide important insights into the structure-function relationships of KCNE3 affected by disease-causing mutations.
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Abstract Number: ANPA2024-N000140 Presenting Author: Ganga Sharma Presenter's Affiliation: Fairmont State University Title: Electric Force Model for pH-Dependent Membrane Proteins/Peptides Folding and Insertion Processes Location: Virtual Presentation Show/Hide Abstract Electric forces play a multifaceted role in the folding and insertion of pH-dependent membrane proteins/peptides, contributing to the specificity, efficiency, and stability of the process. The process of membrane protein insertion involves the protein folding into its correct three-dimensional structure and then being transported across the hydrophobic core of the lipid bilayer. Electric forces between charged amino acid residues can influence the folding process, helping to stabilize certain structural motifs and interactions. These proteins have specific signal sequences or domains that direct them to their correct location within the cell membrane. These sequences contain charged amino acids that interact with complimentary charged regions within the membraneor with membrane-associated proteins. These electric interactions help guide the proteins to their correct destination. Electric force facilitates their translocation across lipid bilayer. Therefore, quantitative knowledge about electric force in pH-dependent membrane protein is essential for advancing our understanding of their structure, function as well as designing novel therapeutics, and developing biotechnological applications. This talk will discuss about a new model associated with electric force using concepts of electrostatic self-energy.
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Abstract Number: ANPA2024-N000141 Presenting Author: Amba Datt Pant Presenter's Affiliation: KEK/J-PARC center, Japan Title: Application of muon for life sciences Location: Virtual Presentation Show/Hide Abstract Even though there are some preliminary/pilot studies of application of quantum beam of muons to
understand electron transfer in cytochrome c protein [1-3] and DNA [4], contents in ferritin
proteins isolated from the brain of an Alzheimer's disease patient [5], detection of low oxygenation
for cancer research [6], the information about the muon charge states, stopping sites and separate
behavior of muon and muonium in those macro-biomolecules is not clearly understood yet. We
perform muon experiments starting from water [7], buffer and small biomolecules to macro-
biomolecules to establish the fundamentals of muon in life sciences. To support the experimental
data, we also perform theoretical work through the first-principles approach to estimate the
stopping sites and interaction of muon with local environment. In the program, ongoing study and
further steps will be discussed.
References:
[1] K Nagamine et al., Physica B 289-290 (2000) 631-635
[2] Y Sugawara, et al., JPS Conf. Proc. 2 (2014) 010310
[3] A.D. Pant et al., JPS Conf. Proc. 8 (2015) 033007
[4] E. Torikai, et al., Hyperfine Interactions 138 (2001) 509-513
[5] L. Bossoni, et al., J Phys Condens Matter 29 (2017) 415801
[6] A. D. Pant et al., J. Phys.: Conf. Ser. 551 (2014) 012043; NIMA 1011 (2021) 165561
[7] A. D. Pant et al., submitted.
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Abstract Number: ANPA2024-N000142 Presenting Author: Nawal K. Khadka Presenter's Affiliation: Boise State University Title: Atomic Force Microscopy Approach to Study the Elasticity of Eye Lens Lipid Membranes and the Whole Lens Location: Virtual Presentation Show/Hide Abstract Several discoveries suggest that age-related loss in lens elasticity is a crucial factor for presbyopia. However, the basic molecular processes involved in lens hardening are unclear. Eye lens membranes contain extremely high cholesterol (Chol) content that leads to the formation of cholesterol bilayer domains (CBDs) within the lens membrane; however, the role of CBDs in lens elasticity is unclear. This study investigates the mechanical properties of the bovine lens cortical membrane (CM), nuclear membrane (NM) containing CBDs, and the whole bovine and mouse lenses. The topographical images and the force curves for the CM and NM were obtained in the fluid cell using atomic force microscopy (AFM). The whole bovine and mouse lenses were affixed using 5% agarose gel and submerged in DMEM media, and then the force curves were obtained using the AFM. Force curves were analyzed to estimate the breakthrough force, membrane area compressibility modulus (KA), and Young's modulus (E). Although no significant difference was observed between CM and NM's membrane thickness, the NM containing CBDs exhibited significantly lower breakthrough force, KA, and E than the CM without CBDs. Similarly, the E for CM and NM are significantly higher than E for the whole lens. The E of the bovine lenses between 24 hours and 48 hours postmortem time and E of the mouse lenses between 20 hours and 68 hours postmortem time were not significantly different. The significantly higher stiffness of CM and NM compared to the stiffness of the whole lens suggests that slight modulation in CM and NM stiffness might play a crucial role in altering the overall lens stiffness. Furthermore, the NM-containing CBDs have higher membrane elasticity than CM without CBDs, suggesting a potential protective effect of CBDs against lens hardening and presbyopia.
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