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Item Advances in Optical Contrast Agents for Medical Imaging: Fluorescent Probes and Molecular Imaging(MDPI, 2025-03-18) Tripathi, Divya; Hardaniya, Mayurakshi; Pande, Suchita; Maity, Dipak; Chemistry and Chemical Biology, School of ScienceOptical imaging is an excellent non-invasive method for viewing visceral organs. Most importantly, it is safer as compared to ionizing radiation-based methods like X-rays. By making use of the properties of photons, this technique generates high-resolution images of cells, molecules, organs, and tissues using visible, ultraviolet, and infrared light. Moreover, optical imaging enables real-time evaluation of soft tissue properties, metabolic alterations, and early disease markers in real time by utilizing a variety of techniques, including fluorescence and bioluminescence. Innovative biocompatible fluorescent probes that may provide disease-specific optical signals are being used to improve diagnostic capabilities in a variety of clinical applications. However, despite these promising advancements, several challenges remain unresolved. The primary obstacle includes the difficulty of developing efficient fluorescent probes, and the tissue autofluorescence, which complicates signal detection. Furthermore, the depth penetration restrictions of several imaging modalities limit their use in imaging of deeper tissues. Additionally, enhancing biocompatibility, boosting fluorescent probe signal-to-noise ratios, and utilizing cutting-edge imaging technologies like machine learning for better image processing should be the main goals of future research. Overcoming these challenges and establishing optical imaging as a fundamental component of modern medical diagnoses and therapeutic treatments would require cooperation between scientists, physicians, and regulatory bodies.Item Hydrogel Innovations in Biosensing: A New Frontier for Pancreatitis Diagnostics(MDPI, 2025-03-03) Sutar, Prerna; Pethe, Atharv; Kumar, Piyush; Tripathi, Divya; Maity, Dipak; Chemistry and Chemical Biology, School of SciencePancreatitis is a prominent and severe type of inflammatory disorder that has grabbed a lot of scientific and clinical interest to prevent its onset. It should be detected early to avoid the development of serious complications, which occur due to long-term damage to the pancreas. The accurate measurement of biomarkers that are released from the pancreas during inflammation is essential for the detection and early treatment of patients with severe acute and chronic pancreatitis, but this is sub-optimally performed in clinically relevant practices, mainly due to the complexity of the procedure and the cost of the treatment. Clinically available tests for the early detection of pancreatitis are often time-consuming. The early detection of pancreatitis also relates to disorders of the exocrine pancreas, such as cystic fibrosis in the hereditary form and cystic fibrosis-like syndrome in the acquired form of pancreatitis, which are genetic disorders with symptoms that can be correlated with the overexpression of specific markers such as creatinine in biological fluids like urine. In this review, we studied how to develop a minimally invasive system using hydrogel-based biosensors, which are highly absorbent and biocompatible polymers that can respond to specific stimuli such as enzymes, pH, temperature, or the presence of biomarkers. These biosensors are helpful for real-time health monitoring and medical diagnostics since they translate biological reactions into quantifiable data. This paper also sheds light on the possible use of Ayurvedic formulations along with hydrogels as a treatment strategy. These analytical devices can be used to enhance the early detection of severe pancreatitis in real time.Item Experimental Evidence for Phosphorylation-Driven Allosteric Regulation of Alpha Synuclein Function(bioRxiv, 2025-02-26) Dollar, Ashlyn N.; Webb, Ian K.; Chemistry and Chemical Biology, School of SciencePhosphorylation of serine 129 (pS129) in the intrinsically disordered protein alpha synuclein has long been associated with neurodegenerative disease. In the past several years, the functional relevance of pS219 has been uncovered by electrophysiology, immunoprecipitation, and proteomics as intricately connected with neurotransmitter release and synaptic vesicle (SV) cycling. Unexpectedly, binding to SNARE complex proteins VAMP-2 and synapsin only occurs with phosphorylation-competent alpha synuclein. The VAMP-2 binding domain has been shown to be residues 96-110, which does not include the phosphorylated residue, hinting at allosteric regulation of alpha synuclein protein-protein interactions by pS129. Within this study, cross-linking, covalent labeling, and collision induced unfolding of alpha synuclein and pS129 - as well as an additional encountered form in the brain, oxidized-M1, M5, M116, M127 alpha synuclein - are studied utilizing tandem mass spectrometry. Collision induced unfolding of proteins gives a fingerprint of the structures' relative compactness and stabilities of various conformations. Covalent labeling of proteins identifies solvent accessible residues and reveals the hydrophobicity (or hydrophilicity) of their microenvironment, while cross-linking of proteins maps the proximity of residue pairs. The combination of collision induced unfolding, covalent labeling, and cross-linking show unequivocally that phosphorylated-S129 alpha synuclein results in a more stable, more compact form. Our results provide evidence of an extensively folded amphipathic region that interacts strongly with the VAMP-2 binding domain. The phosphorylation-induced folding of the amphipathic region likely tunes other protein-protein interactions and interactions with SVs and membranes.Item The DDN Catalytic Motif Is Required for Metnase Functions in Non-homologous End Joining (NHEJ) Repair and Replication Restart(Elsevier, 2014) Kim, Hyun-Suk; Chen, Qiujia; Kim, Sung-Kyung; Nickoloff, Jac A.; Hromas, Robert; Georgiadis, Millie M.; Lee, Suk-Hee; Chemistry and Chemical Biology, School of ScienceMetnase (or SETMAR) arose from a chimeric fusion of the Hsmar1 transposase downstream of a protein methylase in anthropoid primates. Although the Metnase transposase domain has been largely conserved, its catalytic motif (DDN) differs from the DDD motif of related transposases, which may be important for its role as a DNA repair factor and its enzymatic activities. Here, we show that substitution of DDN(610) with either DDD(610) or DDE(610) significantly reduced in vivo functions of Metnase in NHEJ repair and accelerated restart of replication forks. We next tested whether the DDD or DDE mutants cleave single-strand extensions and flaps in partial duplex DNA and pseudo-Tyr structures that mimic stalled replication forks. Neither substrate is cleaved by the DDD or DDE mutant, under the conditions where wild-type Metnase effectively cleaves ssDNA overhangs. We then characterized the ssDNA-binding activity of the Metnase transposase domain and found that the catalytic domain binds ssDNA but not dsDNA, whereas dsDNA binding activity resides in the helix-turn-helix DNA binding domain. Substitution of Asn-610 with either Asp or Glu within the transposase domain significantly reduces ssDNA binding activity. Collectively, our results suggest that a single mutation DDN(610) → DDD(610), which restores the ancestral catalytic site, results in loss of function in Metnase.Item Assessment of Course-Based Undergraduate Research Experiences: AMeeting Report(American Society for Cell Biology, 2014) Auchincloss, Lisa Corwin; Laursen, Sandra L.; Branchaw, Janet L.; Eagan, Kevin; Graham, Mark; Hanauer, David I.; Lawrie, Gwendolyn; McLinn, Colleen M.; Pelaez, Nancy; Rowland, Susan; Towns, Marcy; Trautmann, Nancy M.; Varma-Nelson, Pratibha; Weston, Timothy J.; Dolan, Erin L.; Chemistry and Chemical Biology, School of ScienceThe Course-Based Undergraduate Research Experiences Network (CUREnet) was initiated in 2012 with funding from the National Science Foundation program for Research Coordination Networks in Undergraduate Biology Education. CUREnet aims to address topics, problems, and opportunities inherent to integrating research experiences into undergraduate courses. During CUREnet meetings and discussions, it became apparent that there is need for a clear definition of what constitutes a CURE and systematic exploration of what makes CUREs meaningful in terms of student learning. Thus, we assembled a small working group of people with expertise in CURE instruction and assessment to: 1) draft an operational definition of a CURE, with the aim of defining what makes a laboratory course or project a "research experience"; 2) summarize research on CUREs, as well as findings from studies of undergraduate research internships that would be useful for thinking about how students are influenced by participating in CUREs; and 3) identify areas of greatest need with respect to CURE assessment, and directions for future research on and evaluation of CUREs. This report summarizes the outcomes and recommendations of this meeting.Item A 24-year longitudinal study on a STEM gateway general chemistry course and the reduction of achievement disparities(Public Library of Science, 2025-02-26) Basu, Partha; Malik, David J.; Graunke, Steven; Chemistry and Chemical Biology, School of ScienceThe "First Year Experience" is a critical component of retention of STEM majors. Often, general chemistry has been labeled as a "gatekeeper" course for STEM careers due to a high attrition rate and a course that leads to increased time for graduation when students are inadequately prepared. We demonstrate that the active learning strategy Peer-Led Team Learning (PLTL) model increases student retention (%DFW calculated from earned grades A through F plus withdrawals, W) and success (%ABC calculated from earned grades A through F). We have analyzed approximately 24 years of data in general chemistry I (~20,000 students), using Analysis of Covariance (ANCOVA), which showed progressive, significant improvement in both student success and completion metrics. A Hierarchical Linear Modeling (HLM), using a combination of course and student-level variables, demonstrated the impact of PLTL on internal exam metrics and overall course grades. Further, HLM modeling assessed the impact of PLTL controlling for various student demographics. PLTL strongly impacted URM student completion rates to a greater degree than well-represented students, reducing the URM/non-URM achievement gap.Item Artificial Intelligence in Biomedical Engineering and Its Influence on Healthcare Structure: Current and Future Prospects(MDPI, 2025-02-08) Tripathi, Divya; Hajra, Kasturee; Mulukutla, Aditya; Shreshtha, Romi; Maity, Dipak; Chemistry and Chemical Biology, School of ScienceArtificial intelligence (AI) is a growing area of computer science that combines technologies with data science to develop intelligent, highly computation-able systems. Its ability to automatically analyze and query huge sets of data has rendered it essential to many fields such as healthcare. This article introduces you to artificial intelligence, how it works, and what its central role in biomedical engineering is. It brings to light new developments in medical science, why it is being applied in biomedicine, key problems in computer vision and AI, medical applications, diagnostics, and live health monitoring. This paper starts with an introduction to artificial intelligence and its major subfields before moving into how AI is revolutionizing healthcare technology. There is a lot of emphasis on how it will transform biomedical engineering through the use of AI-based devices like biosensors. Not only can these machines detect abnormalities in a patient's physiology, but they also allow for chronic health tracking. Further, this review also provides an overview of the trends of AI-enabled healthcare technologies and concludes that the adoption of artificial intelligence in healthcare will be very high. The most promising are in diagnostics, with highly accurate, non-invasive diagnostics such as advanced imaging and vocal biomarker analyzers leading medicine into the future.Item Plasma drug screening using paper spray mass spectrometry with integrated solid phase extraction(Wiley, 2025) Zimmerman-Federle, Hannah; Ren, Greta; Dowling, Sarah; Warren, Cassandra; Rusyniak, Daniel; Avera, Robert; Manicke, Nicholas E.; Chemistry and Chemical Biology, School of ScienceDrug overdoses have risen dramatically in recent years. We developed a simple nontargeted method using a disposable paper spray cartridge with an integrated solid phase extraction column. This method was used to screen for ~160 fentanyl analogs, synthetic cannabinoids, other synthetic drugs, and traditional drugs of abuse in over 300 authentic overdose samples collected at emergency departments in Indianapolis. A solid phase extraction step was implemented on the paper spray cartridge to enable subnanograms per milliliter synthetic drugs screening in plasma. Analysis was performed on a quadrupole orbitrap mass spectrometer using the sequential window acquisition of all theoretical fragment ion spectra approach in which tandem mass spectrometry was performed using 7 m/z isolation windows in the quadrupole. Calibration curves with isotopically labeled internal standards were constructed for 35 of the most frequently encountered synthetic and traditional illicit drugs by US toxicology labs. Additional qualitative‐only drugs in a suspect screening list were also included. Limits of detection in plasma for synthetic cannabinoids ranged from 0.1 to 0.5 and 0.1 to 0.3 ng/mL for fentanyl and its analogs and between 1 and 5 ng/mL for most other drugs. Relative matrix effects were evaluated by determining the variation of the calibration slope in 10 different lots of biofluid and found to be between 3% and 20%. The method was validated on authentic overdose samples collected from two emergency departments in Indianapolis, Indiana, from suspected or known overdoses. Commonly detected synthetic drugs included fentanyl related substances, designer benzodiazepines such as flubromazolam, and the synthetic cannabinoid 5F‐PB‐22.Item Polyrate 2023: A computer program for the calculation of chemical reaction rates for polyatomics. New version announcement(Elsevier, 2024) Meana-Pañeda, Rubén; Zheng, Jingjing; Bao, Junwei Lucas; Zhang, Shuxia; Lynch, Benjamin J.; Corchado, José C.; Chuang, Yao-Yuan; Fast, Patton L.; Hu, Wei-Ping; Liu, Yi-Ping; Lynch, Gillian C.; Nguyen, Kiet A.; Jackels, Charles F.; Fernández-Ramos, Antonio; Ellingson, Benjamin A.; Melissas, Vasilios S.; Villà, Jordi; Rossi, Ivan; Coitiño, Elena L.; Pu, Jingzhi; Albu, Titus V.; Zhang, Rui Ming; Xu, Xuefei; Ratkiewicz, Artur; Steckler, Rozeanne; Garrett, Bruce C.; Isaacson, Alan D.; Truhlar, Donald G.; Chemistry and Chemical Biology, School of SciencePolyrate is a suite of computer programs for the calculation of chemical reaction rates of polyatomic species (including atoms and diatoms as special cases) by variational transition state theory (VTST); conventional transition state theory is also supported. Polyrate can calculate the rate constants for both bimolecular reactions and unimolecular reactions, and it can be applied to reactions in the gas phase, liquid solution phase, or solid state and to reactions at gas–solid interfaces. Polyrate can perform VTST calculations on gas-phase reactions with both tight and loose transition states. For tight transition states it uses the reaction-path (RP) variational transition state theory developed by Garrett and Truhlar, and for loose transition states it uses variable-reaction-coordinate (VRC) variational transition state theory developed by Georgievskii and Klippenstein. The RP methods used for tight transition states are conventional transition state theory, canonical variational transition state theory (CVT), and microcanonical variational transition state theory (μVT) with multidimensional semiclassical approximations for tunneling and nonclassical reflection. For VRC calculations, rate constants may be calculated for canonical or microcanonical ensembles or energy- and total-angular-momentum resolved microcanonical ensembles. Pressure-dependent rate constants for elementary reactions can be computed using system-specific quantum RRK theory (SS-QRRK) with the information obtained from high-pressure-limit VTST calculation as input by using the SS-QRRK utility code. Alternatively, Polyrate 2023 may be interfaced with TUMME 2023 for a master-equation treatment of pressure dependence or to obtain phenomenological rate constants for complex mechanisms. Potential energy surfaces may be analytic functions evaluated by subroutines, or they may be implicit surfaces defined by electronic structure input files or interface subroutines containing energies, gradients, and force constants (Hessians). For the latter, Polyrate can be used in conjunction with various interfaces to electronic structure programs for direct dynamics, and it has routines designed to make such interfacing straightforward. Polyrate supports six options for direct dynamics, namely (i) straight single-level direct dynamics, (ii) zero-order interpolated variational transition state theory (IVTST-0), (iii) first-order interpolated variational transition state theory (IVTST-1), (iv) interpolated variational transition state theory by mapping (IVTST-M), (v) variational transition state theory with interpolated single-point energies (VTST-ISPE), and (vi) variational transition state theory with interpolated optimized corrections (VTST-IOC). Polyrate can handle multistructural and torsional-potential anharmonicity in conjunction with the MSTor program. Polyrate 2023 contains 112 test runs, and 46 of these are for direct dynamics calculations; 85 of the test runs are single-level runs, and 27 are dual-level calculations.Item Characterization of an odor permeable membrane device for the storage of explosives and use as canine training aids(Wiley, 2023-05) Davis, Kymeri; Reavis, Madison; Goodpaster, John V.; Chemistry and Chemical Biology, School of ScienceThe storage and use of explosives is regulated at the state and federal level, with a particular focus on physical security and rigorous accounting of the explosive inventory. For those working with explosives for the training and testing of explosive-detecting canines, cross-contamination is an important concern. Hence, explosives intended for use with canine teams must be placed into secondary storage containers that are new, clean, and airtight. A variety of containers meet these requirements and include screw-top glass jars (e.g., mason jars). However, an additional need from the explosive-detecting canine community is secondary containers that can also be used as training aids whereby the volatiles emitted by explosives are emitted in a predictable and stable manner. Currently, a generally accepted method for the storage of explosives and controlled emission of explosive vapor for canine detection does not exist. Ideally, such containers should allow odor to escape from the training aid but block external contaminates such as particulates or other volatiles. One method in use places the explosive inside a permeable cotton bag when in use for training and then stores the cotton bag inside an impermeable nylon bag for long-term storage. This paper describes the testing of an odor permeable membrane device (OPMD) as a new way to store and deploy training aids. We measured the evaporation rate and flux of various liquid explosives and volatile compounds that have been identified in the headspace of actual explosives. OPMDs were used in addition to traditional storage containers to monitor the contamination and degradation of 14 explosives used as canine training aids. Explosives were stored individually using traditional storage bags or inside an OPMD at two locations, one of which actively used the training aids. Samples from each storage type at both locations were collected at 0, 3, 6, and 9 months and analyzed using Fourier Transform Infrared (FTIR) Spectroscopy and Gas Chromatography–Mass Spectrometry (GC–MS) with Solid-Phase Microextraction (SPME). FTIR analyses showed no signs of degradation. GC–MS identified cross-contamination from ethylene glycol dinitrate (EGDN) and/or 2,3-dimethyl-2,3-dinitrobutane (DMNB) across almost all samples regardless of storage condition. The contamination was found to be higher among training aids that were stored in traditional ways and that were in active use by canine teams.