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Full-Text Articles in Physical Sciences and Mathematics
Structural Mapping Of The Base Stacks Containing Post-Transcriptionally Modified Bases In Rna, Zakir Ali, Sarabjeet Kaur, Teagan Kukhta, Abd Al-Aziz A Abu-Saleh, Ayush Jhunjhunwala, Abhijit Mitra, John F. Trant, Purshotam Sharma
Structural Mapping Of The Base Stacks Containing Post-Transcriptionally Modified Bases In Rna, Zakir Ali, Sarabjeet Kaur, Teagan Kukhta, Abd Al-Aziz A Abu-Saleh, Ayush Jhunjhunwala, Abhijit Mitra, John F. Trant, Purshotam Sharma
Chemistry and Biochemistry Publications
Post-transcriptionally modified bases play vital roles in many biochemical processes involving RNA. Analysis of the non-covalent interactions associated with these bases in RNA is crucial for providing a more complete understanding of the RNA structure and function; however, the characterization of these interactions remains understudied. To address this limitation, we present a comprehensive analysis of base stacks involving all crystallographic occurrences of the most biologically relevant modified bases in a large dataset of high-resolution RNA crystal structures. This is accompanied by a geometrical classification of the stacking contacts using our established tools. Coupled with quantum chemical calculations and an analysis …
Structural Mapping Of The Base Stacks Containing Post-Transcriptionally Modified Bases In Rna, Zakir Ali, Sarabjeet Kaur, Teagan Kukhta, Abd Al-Aziz A Abu-Saleh, Ayush Jhunjhunwala, Abhijit Mitra, John F. Trant, Purshotam Sharma
Structural Mapping Of The Base Stacks Containing Post-Transcriptionally Modified Bases In Rna, Zakir Ali, Sarabjeet Kaur, Teagan Kukhta, Abd Al-Aziz A Abu-Saleh, Ayush Jhunjhunwala, Abhijit Mitra, John F. Trant, Purshotam Sharma
Chemistry and Biochemistry Publications
Post-transcriptionally modified bases play vital roles in many biochemical processes involving RNA. Analysis of the non-covalent interactions associated with these bases in RNA is crucial for providing a more complete understanding of the RNA structure and function; however, the characterization of these interactions remains understudied. To address this limitation, we present a comprehensive analysis of base stacks involving all crystallographic occurrences of the most biologically relevant modified bases in a large dataset of high-resolution RNA crystal structures. This is accompanied by a geometrical classification of the stacking contacts using our established tools. Coupled with quantum chemical calculations and an analysis …
Mitocans Induce Lipid Flip-Flop And Permeabilize The Membrane To Signal Apoptosis, Stuart R. Castillo, Michael H.L. Nguyen, Mitchell Dipasquale, Elizabeth G. Kelley, Drew Marquardt
Mitocans Induce Lipid Flip-Flop And Permeabilize The Membrane To Signal Apoptosis, Stuart R. Castillo, Michael H.L. Nguyen, Mitchell Dipasquale, Elizabeth G. Kelley, Drew Marquardt
Chemistry and Biochemistry Publications
Pancratistatin (PST) and narciclasine (NRC) are natural therapeutic agents that exhibit specificity toward the mitochondria of cancerous cells and initiate apoptosis. Unlike traditional cancer therapeutic agents, PST and NRC are effective, targeted, and have limited adverse effects on neighboring healthy, noncancerous cells. Currently, the mechanistic pathway of action for PST and NRC remains elusive, which in part inhibits PST and NRC from becoming efficacious therapeutic alternatives. Herein, we use neutron and x-ray scattering in combination with calcein leakage assays to characterize the effects of PST, NRC, and tamoxifen (TAM) on a biomimetic model membrane. We report an increase in lipid …
Boron Neutron Capture Therapy In The New Age Of Accelerator-Based Neutron Production And Preliminary Progress In Canada, Dominik Dziura, Sana Tabbassum, Amanda Macneil, Dalini D. Maharaj, Robert Laxdal, Oliver Kester, Ming Pan, Hiroaki Kumada, Drew Marquardt
Boron Neutron Capture Therapy In The New Age Of Accelerator-Based Neutron Production And Preliminary Progress In Canada, Dominik Dziura, Sana Tabbassum, Amanda Macneil, Dalini D. Maharaj, Robert Laxdal, Oliver Kester, Ming Pan, Hiroaki Kumada, Drew Marquardt
Chemistry and Biochemistry Publications
Each year more than 3000 Canadians are diagnosed with brain cancers like glioblastoma multiforme or recurrent head and neck cancers, which are difficult to treat with conventional radiotherapy techniques. One of the most clinically promising treatments for these cancers is boron neutron capture therapy (BNCT). This procedure involves selectively introducing a boron delivery agent into tumor cells and irradiating them with a neutron beam, which kills the cancer cells due to the high-linear energy transfer radiation produced by the 10B(n,α)7Li capture reaction. The theory of BNCT has been around for a long time since 1936, but has historically been limited …
Investigating The Effect Of Medium Chain Triglycerides On The Elasticity Of Pulmonary Surfactant, Maksymilian Dziura, Stuart R. Castillo, Mitchell Dipasquale, Omotayo Gbadamosi, Piotr Zolnierczuk, Michihiro Nagao, Elizabeth G. Kelley, Drew Marquardt
Investigating The Effect Of Medium Chain Triglycerides On The Elasticity Of Pulmonary Surfactant, Maksymilian Dziura, Stuart R. Castillo, Mitchell Dipasquale, Omotayo Gbadamosi, Piotr Zolnierczuk, Michihiro Nagao, Elizabeth G. Kelley, Drew Marquardt
Chemistry and Biochemistry Publications
In recent years, vaping has increased in both popularity and ease of access. This has led to an outbreak of a relatively new condition known as e-cigarette/vaping-associated lung injury (EVALI). This injury can be caused by physical interactions between the pulmonary surfactant (PS) in the lungs and toxins typically found in vaping solutions, such as medium chain triglycerides (MCT). MCT has been largely used as a carrier agent within many cannabis products commercially available on the market. Pulmonary surfactant ensures proper respiration by maintaining low surface tensions and interface stability throughout each respiratory cycle. Therefore, any impediments to this system …
“Breaking Bud”: The Effect Of Direct Chemical Modifications Of Phytocannabinoids On Their Bioavailability, Physiological Effects, And Therapeutic Potential, Abhinandan Banerjee, John J. Hayward, John F. Trant
“Breaking Bud”: The Effect Of Direct Chemical Modifications Of Phytocannabinoids On Their Bioavailability, Physiological Effects, And Therapeutic Potential, Abhinandan Banerjee, John J. Hayward, John F. Trant
Chemistry and Biochemistry Publications
Tetrahydrocannabinol (THC) and cannabidiol (CBD) are the two “major cannabinoids”. However, their incorporation into clinical and nutraceutical preparations is challenging, owing to their limited bioavailability, low water solubility, and variable pharmacokinetic profiles. Understanding the organic chemistry of the major cannabinoids provides us with potential avenues to overcome these issues through derivatization. The resulting labile pro-drugs offer ready cannabinoid release in vivo, have augmented bioavailability, or demonstrate interesting pharmacological properties in their own right. This review identifies and discusses a subset of these advanced derivatization strategies for the major cannabinoids, where the starting material is the pure phytocannabinoid itself, and …
The “Nitrogen Effect”: Complexation With Macrocycles Potentiates Fused Heterocycles To Form Halogen Bonds In Competitive Solvents, Dr. Kwaku Twum, Sanaz Nadimi, Frank Boateng Osei, Dr. Rakesh Puttreddy, Dr. Yvonne Bessem Ojong, Dr. John J. Hayward, Prof. Kari Rissanen, Prof. John F. Trant, Prof. Ngong Kodiah Beyeh Kodiah Beyeh
The “Nitrogen Effect”: Complexation With Macrocycles Potentiates Fused Heterocycles To Form Halogen Bonds In Competitive Solvents, Dr. Kwaku Twum, Sanaz Nadimi, Frank Boateng Osei, Dr. Rakesh Puttreddy, Dr. Yvonne Bessem Ojong, Dr. John J. Hayward, Prof. Kari Rissanen, Prof. John F. Trant, Prof. Ngong Kodiah Beyeh Kodiah Beyeh
Chemistry and Biochemistry Publications
Weak intermolecular forces are typically very difficult to observe in highly competitive polar protic solvents as they are overwhelmed by the quantity of competing solvent. This is even more challenging for three-component ternary assemblies of pure organic compounds. In this work, we overcome these complications by leveraging the binding of fused aromatic N-heterocycles in an open resorcinarene cavity to template the formation of a three-component halogen-bonded ternary assembly in a protic polar solvent system.
Structural And Energetic Features Of Base–Base Stacking Contacts In Rna, Zakir Ali, Ambika Goyal, Ayush Jhunjhunwala, Abhijit Mitra, John F. Trant, Purshotam Sharma
Structural And Energetic Features Of Base–Base Stacking Contacts In Rna, Zakir Ali, Ambika Goyal, Ayush Jhunjhunwala, Abhijit Mitra, John F. Trant, Purshotam Sharma
Chemistry and Biochemistry Publications
Nucleobase π–π stacking is one of the crucial organizing interactions within three-dimensional (3D) RNA architectures. Characterizing the structural variability of these contacts in RNA crystal structures will help delineate their subtleties and their role in determining function. This analysis of different stacking geometries found in RNA X-ray crystal structures is the largest such survey to date; coupled with quantum-mechanical calculations on typical representatives of each possible stacking arrangement, we determined the distribution of stacking interaction energies. A total of 1,735,481 stacking contacts, spanning 359 of the 384 theoretically possible distinct stacking geometries, were identified. Our analysis reveals preferential occurrences of …
Investigating The Cut-Off Effect Of N-Alcohols On Lipid Movement: A Biophysical Study, Michael H.K. Nguyen, Dominik Dziura, Mitchell Dipasquale, Stuart R. Castillo, Elizabeth G. Kelley, Drew Marquardt
Investigating The Cut-Off Effect Of N-Alcohols On Lipid Movement: A Biophysical Study, Michael H.K. Nguyen, Dominik Dziura, Mitchell Dipasquale, Stuart R. Castillo, Elizabeth G. Kelley, Drew Marquardt
Chemistry and Biochemistry Publications
Cellular membranes are responsible for absorbing the effects of external perturbants for the cell’s survival. Such perturbants include small ubiquitous molecules like n-alcohols which were observed to exhibit anesthetic capabilities, with this effect tapering off at a cut-off alcohol chain length. To explain this cut-off effect and complement prior biochemical studies, we investigated a series of nalcohols (with carbon lengths 2-18) and their impact on several bilayer properties, including lipid flip-flop, intervesicular exchange, diffusion, membrane bending rigidity and more. To this end, we employed an array of biophysical techniques such as time-resolved small angle neutron scattering (TRSANS), small angle X-ray …
Biallelic Mutations In P4htm Cause Syndromic Obesity, Sadia Saeed, Lijiao Ning, Alaa Badreddine, Muhammad Usman Mirza, Mathilde Boissel, Roohia Khanam, Jaida Manzoor, Qasim M. Janjua, Waqas I. Khan, Bénédicte Toussaint, Emmanuel Vaillant, Souhila Amanzougarene, Mehdi Derhourhi, John F. Trant, Anna-Maria Siegert, Brian Y.H. Lam, Giles S.H. Yeo, Layachi Chabraoui, Asmae Touzani, Abhishek Kulkarni, I. Sadaf Farooqi, Amélie Bonnefond, Muhammad Arslan, Philippe Froguel
Biallelic Mutations In P4htm Cause Syndromic Obesity, Sadia Saeed, Lijiao Ning, Alaa Badreddine, Muhammad Usman Mirza, Mathilde Boissel, Roohia Khanam, Jaida Manzoor, Qasim M. Janjua, Waqas I. Khan, Bénédicte Toussaint, Emmanuel Vaillant, Souhila Amanzougarene, Mehdi Derhourhi, John F. Trant, Anna-Maria Siegert, Brian Y.H. Lam, Giles S.H. Yeo, Layachi Chabraoui, Asmae Touzani, Abhishek Kulkarni, I. Sadaf Farooqi, Amélie Bonnefond, Muhammad Arslan, Philippe Froguel
Chemistry and Biochemistry Publications
We previously demonstrated that 50% of children with obesity from consanguineous families from Pakistan carry pathogenic variants in known monogenic obesity genes. Here, we have discovered a novel monogenetic recessive form of severe childhood obesity using an in-house computational staged approach. The analysis included whole-exome sequencing data of 366 children with severe obesity, 1,000 individuals of the Pakistan Risk of Myocardial Infarction Study (PROMIS) study, and 200,000 participants of the UK Biobank to prioritize genes harboring rare homozygous variants with putative effect on human obesity. We identified five rare or novel homozygous missense mutations predicted deleterious in five consanguineous families …