Review
Cell Biology
Natalie A. Hager, Ceara K. McAtee, Mitchell A. Lesko, Allyson F. O'Donnell
Summary: Potassium (K+) homeostasis is crucial for cell and organismal health, and Kir family member Kir2.1 plays a significant role in maintaining potassium ion balance. Kir2.1 has specific functions in heart, muscle, and bone development, and its mutations are associated with diseases such as cardiomyopathies and neurological disorders.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Neurosciences
Saad B. Hannan, Reka Penzinger, Ginte Mickute, Trevor G. Smart
Summary: GABA receptors, particularly GABABRs, are important therapeutic targets for neurodevelopmental and neuropsychiatric disorders. However, a widely used positive allosteric modulator, CGP7930, was found to have effects on both GABABRs and GABAARs, as well as GIRK channels, making it unsuitable as a specific GABABR PAM.
Article
Cardiac & Cardiovascular Systems
Takuro Nishimura, Gaurav A. Upadhyay, Zaid A. Aziz, Andrew D. Beaser, Dalise Y. Shatz, Hemal M. Nayak, Roderick Tung
Summary: By analyzing high-resolution mapping of human ventricular tachycardias, it was found that outer loop conduction velocity, rather than isthmus size, is the primary determinant of tachycardia rate. There were no significant differences in circuit dimensions between different types of VT, and long, continuous electrograms were predictive of VT termination.
Article
Physics, Fluids & Plasmas
Sergei F. Pravdin, Timur Nezlobinsky, Alexander Panfilov, Hans Dierckx
Summary: Studying the phenomenon of eliminating vortices in excitable media by stimulating them with a smaller period, even in three-dimensional scroll waves, shows promising results. However, in cases with negative filament tension, longer stimulation periods may lead to three-dimensional instabilities, making elimination impossible.
Article
Neurosciences
Mina Peric, Ljiljana Nikolic, Pavle R. Andjus, Danijela Bataveljic
Summary: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the death of motor neurons, with oligodendrocytes playing an important role in disease progression. Studies in the SOD1(G93A) rat model of ALS show reduced expression of Kir4.1 in spinal cord oligodendrocytes, along with morphological abnormalities indicative of degeneration. Additionally, functional impairment of oligodendrocytes, including decreased Kir currents, suggests a potential role of Kir4.1 channel dysfunction in ALS pathophysiology.
EUROPEAN JOURNAL OF NEUROSCIENCE
(2021)
Article
Neurosciences
Karthikeyan Rajagopal, Janarthanan Ramadoss, Shaobo He, Prakash Duraisamy, Anitha Karthikeyan
Summary: This article discusses various dynamical properties of a four-dimensional mammalian cold receptor model, focusing on the effects of noise and temperature on collective behavior. By introducing obstacles in the network, the study shows how they affect wave reentry and proposes a new technique to identify it using individual node periods.
COGNITIVE NEURODYNAMICS
(2023)
Article
Neurosciences
Ezequiel Marron Fernandez de Velasco, Megan E. Tipps, Bushra Haider, Anna Souders, Carolina Aguado, Timothy R. Rose, Baovi N. Vo, Margot C. DeBaker, Rafael Lujan, Kevin Wickman
Summary: This study found that ethanol exposure weakened the somatodendritic inhibitory effect of GABABR activation on principal neurons in the BLA, attributable to suppression of GIRK channel activity and redistribution of GABABR and GIRK channels. Viral suppression of GIRK channel activity replicated some mood-related behaviors observed during ethanol withdrawal.
BIOLOGICAL PSYCHIATRY
(2023)
Review
Cardiac & Cardiovascular Systems
James L. Cox, S. Chris Malaisrie, Andrei Churyla, Chris Mehta, Jane Kruse, Olga N. Kislitsina, Patrick M. McCarthy
Summary: Cryosurgery has been used for treating cardiac arrhythmias for decades, but the mechanisms and techniques for producing optimal cryolesions in atrial fibrillation treatment are still not well understood. The creation of effective cryolesions depends on factors such as cryoprobe temperature, target myocardium temperature, duration of cryothermia application, and the presence of a heat or cooling sink. Cryothermia kills myocardial cells during both freezing and thawing phases, with a critical lethal temperature of -30°C for myocardium.
ANNALS OF THORACIC SURGERY
(2021)
Article
Physiology
Isabelle Bidaud, Alicia D'Souza, Gabriella Forte, Eleonora Torre, Denis Greuet, Steeve Thirard, Cali Anderson, Antony Chung You Chong, Angelo G. Torrente, Julien Roussel, Kevin Wickman, Mark R. Boyett, Matteo E. Mangoni, Pietro Mesirca
Summary: Genetic ablation of cardiac I-KACh in mice prevents exercise-induced sinus bradycardia by suppressing training-induced remodeling of inward currents I-f, I-CaT and I-CaL. This finding may offer an alternative to pacemaker implantation for the bradyarrhythmias seen in some veteran athletes.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Anatomy & Morphology
Martin R. Silic, Sarah Haruka Murata, Sung Jun Park, GuangJun Zhang
Summary: Our study identified and renamed 31 kir genes in zebrafish, and analyzed their evolutionary history through phylogenetic and syntenic analyses. The expression of zebrafish kir genes during early embryogenesis showed distinct gene expression domains, indicating subfunctionalization of ohnologous genes from whole-genome duplication. The varied temporal gene expression domains suggest a potential role of Kir channels in embryonic patterning or regulation.
DEVELOPMENTAL DYNAMICS
(2022)
Article
Cell Biology
Matthijs J. M. Cluitmans, Laura R. Bear, Uyen C. Nguyen, Bianca van Rees, Job Stoks, Rachel M. A. ter Bekke, Casper Mihl, Jordi Heijman, Kevin D. Lau, Edward Vigmond, Jason Bayer, Charly N. W. Belterman, Emma Abell, Louis Labrousse, Julien Rogier, Olivier Bernus, Michel Haissaguerre, Rutger J. Hassink, Remi Dubois, Ruben Coronel, Paul G. A. Volders
Summary: This study shows that vulnerability to ventricular fibrillation is related to the steepness of RT gradient and size of early RT areas, rather than markers on the body-surface electrocardiogram. Patients with idiopathic VF have steeper RT gradients and more balanced early versus late RT regions compared to controls.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Article
Cardiac & Cardiovascular Systems
Maged F. Nageh, Robert Murdock
Summary: This report describes the use of conduction system pacing for the diagnosis of bundle branch reentry ventricular tachycardia (BBRVT) in patients with conduction disease. Two patients with infra-nodal conduction disease were induced with BBRVT, showing left bundle branch block morphology in the first patient (type A) and right bundle branch block morphology in the second patient (type C). Selective and non-selective right bundle (RB) pacing was observed during apical right ventricular pacing, with evidence of manifest entrainment with non-selective RB capture in the first patient, and concealed entrainment by selective RB capture in the second patient. Other criteria for entrainment, such as a short post-pacing interval at the right bundle pacing site, were also noted.
Article
Pharmacology & Pharmacy
Allison Anderson, Baovi N. Vo, Ezequiel Marron Fernandez de Velasco, Corey R. Hopkins, C. David Weaver, Kevin Wickman
Summary: The newly identified GIRK channel inhibitor VU0468554 shows effective inhibition of cardiac GIRK channels, indicating promising therapeutic implications for relevant cardiac arrhythmias. Studies suggest that VU0468554 selectively targets cardiac over neuronal GIRK channels and partially reverses GIRK-mediated bradycardia in isolated mouse heart models.
MOLECULAR PHARMACOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Nour Raad, Philip Bittihn, Marine Cacheux, Dongtak Jeong, Zeki Ilkan, Delaine Ceholski, Erik Kohlbrenner, Lu Zhang, Chen-Leng Cai, Evangelia G. Kranias, Roger J. Hajjar, Francesca Stillitano, Fadi G. Akar
Summary: This study highlights the crucial role of primary electrical remodeling caused by the hPLN(R14del) mutation in early-stage arrhythmogenic phenotype. The preferential right ventricular action potential prolongation and steep repolarization gradient at the left ventricular/right ventricular interface are key mechanisms underlying the increased arrhythmia susceptibility in R14del hearts. The unique spatiotemporal dynamics of high-frequency rotors pinned to the right ventricle contribute to their increased stability in R14del compared with wildtype hearts.
Review
Biochemistry & Molecular Biology
Andrei Alexandru Mircea, Mihaela Rusu, Elisa Anamaria Liehn, Octavian Bucur
Summary: This review focuses on newly developed strategies, such as vernakalant and stereotactic ablative therapy, for the treatment of arrhythmias. These therapies are important for improving the management of atrial fibrillation and ventricular tachycardia, offering higher success rates and lower costs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Immunology
Tejas Deshmukh, Peter Emerson, Patricia Anderson, Eddy Kizana, Philip J. O'Connell, D. Jane Holmes-Walker, James J. H. Chong
Summary: Cardiac autonomic neuropathy (CAN) is a significant issue for individuals with type 1 (T1D) and type 2 (T2D) diabetes. This study compared heart rate variability (HRV) among different groups, finding that CAN was not reversible in T1D patients post-islet cell transplantation at a median of 4 years. Differences in HRV parameters between control groups and T1D, as well as between control groups and T2D, suggest potential impacts of hypoglycemia on HRV.
Article
Microbiology
Chih-Yuan Chiang, Yang Zhong, Michael D. Ward, Douglas J. Lane, Tara Kenny, Raysa Rosario-Acevedo, Brett P. Eaton, Sylvia R. Trevino, Taylor B. Chance, Meghan Hu, Patricia L. Worsham, David M. Waag, Richard T. Moore, Lisa H. Cazares, Christopher K. Cote, Yingyao Zhou, Rekha G. Panchal
Summary: Burkholderia mallei, the causative agent of glanders, poses a serious biological threat due to its infectivity, antibiotic resistance, and lack of approved vaccines. Studying host responses in non-human primates has revealed insights into the pathogenesis of glanders. Integration of proteomics data has led to the construction of a predictive protein-protein interaction network, shedding light on the molecular mechanisms underlying B. mallei infections.
FRONTIERS IN MICROBIOLOGY
(2021)
Correction
Multidisciplinary Sciences
Christopher D. Go, James D. R. Knight, Archita Rajasekharan, Bhavisha Rathod, Geoffrey G. Hesketh, Kento T. Abe, Ji-Young Youn, Payman Samavarchi-Tehrani, Hui Zhang, Lucie Y. Zhu, Evelyn Popiel, Jean-Philippe Lambert, Etienne Coyaud, Sally W. T. Cheung, Dushyandi Rajendran, Cassandra J. Wong, Hana Antonicka, Laurence Pelletier, Alexander F. Palazzo, Eric A. Shoubridge, Brian Raught, Anne-Claude Gingras
Article
Medicine, Research & Experimental
Ryan P. Bennett, Elena N. Postnikova, Brett P. Eaton, Yingyun Cai, Shuiqing Yu, Charles O. Smith, Janie Liang, Huanying Zhou, Gregory A. Kocher, Michael J. Murphy, Harold C. Smith, Jens H. Kuhn
Summary: Sangivamycin is an antiviral drug that shows broad-spectrum activity against different viruses, including SARS-CoV-2. It demonstrates potent inhibitory effects on SARS-CoV-2 replication in various cell types, surpassing the efficacy of remdesivir. Pharmacokinetic and toxicity studies suggest favorable properties for clinical administration. Additionally, Sangivamycin has the potential for combination therapy and may help combat drug-resistant or vaccine-escaping SARS-CoV-2 variants.
Article
Medicine, Research & Experimental
Vanessa Monteil, Brett Eaton, Elena Postnikova, Michael Murphy, Benedict Braunsfeld, Ian Crozier, Franz Kricek, Janine Niederhofer, Alice Schwarzbock, Helene Breid, Stephanie Devignot, Jonas Klingstrom, Charlotte Thalin, Max J. Kellner, Wanda Christ, Sebastian Havervall, Stefan Mereiter, Sylvia Knapp, Anna Sanchez Jimenez, Agnes Bugajska-Schretter, Alexander Dohnal, Christine Ruf, Romana Gugenberger, Astrid Hagelkruys, Nuria Montserrat, Ivona Kozieradzki, Omar Hasan Ali, Johannes Stadlmann, Michael R. Holbrook, Connie Schmaljohn, Chris Oostenbrink, Robert H. Shoemaker, Ali Mirazimi, Gerald Wirnsberger, Josef M. Penninger
Summary: The emergence of multiple SARS-CoV-2 variants has raised concerns due to reduced vaccine efficacy and resistance to neutralizing antibody therapies. However, research shows that soluble ACE2 can inhibit current SARS-CoV-2 variants, providing proof of principle for a pan-SARS-CoV-2 therapeutic.
EMBO MOLECULAR MEDICINE
(2022)
Article
Multidisciplinary Sciences
Cherrelle Dacon, Courtney Tucker, Linghang Peng, Chang-Chun D. Lee, Ting-Hui Lin, Meng Yuan, Yu Cong, Lingshu Wang, Lauren Purser, Jazmean K. Williams, Chul-Woo Pyo, Ivan Kosik, Zhe Hu, Ming Zhao, Divya Mohan, Andrew J. R. Cooper, Mary Peterson, Jeff Skinner, Saurabh Dixit, Erin Kollins, Louis Huzella, Donna Perry, Russell Byrum, Sanae Lembirik, David Drawbaugh, Brett Eaton, Yi Zhang, Eun Sung Yang, Man Chen, Kwanyee Leung, Rona S. Weinberg, Amarendra Pegu, Daniel E. Geraghty, Edgar Davidson, Iyadh Douagi, Susan Moir, Jonathan W. Yewdell, Connie Schmaljohn, Peter D. Crompton, Michael R. Holbrook, David Nemazee, John R. Mascola, Ian A. Wilson, Joshua Tan
Summary: This study identified six monoclonal antibodies that bind to spike proteins from all seven human-infecting coronaviruses. Two of these antibodies, COV44-62 and COV44-79, showed broad neutralizing activity against alpha- and betacoronaviruses, including the Omicron subvariants of SARS-CoV-2. The fusion peptide region in the spike protein was found to be a potential candidate epitope for next-generation coronavirus vaccine development.
Article
Virology
Renuka Rao, Melad Farraha, Grant J. Logan, Sindhu Igoor, Cindy Y. Kok, James J. H. Chong, Ian E. Alexander, Eddy Kizana
Summary: This study compared two production methods for cardiotropic rAAVs, finding that rAAV produced by the traditional HEK293 method outperformed vector produced using the baculovirus/Sf9 system in vitro and in vivo. This underscores the importance of thorough assessment of vector performance when using diverse rAAV production methods.
Article
Multidisciplinary Sciences
Paula P. Coelho, Geoffrey G. Hesketh, Annika Pedersen, Elena Kuzmin, Anne-Marie N. Fortier, Emily S. Bell, Colin D. H. Ratcliffe, Anne-Claude Gingras, Morag Park
Summary: This study uncovers an LC3C-Endocytic-Associated-Pathway (LEAP) that selectively recruits plasma membrane cargo to autophagosomes, providing new understanding of the selective coupling of plasma membrane signaling with autophagic degradation.
NATURE COMMUNICATIONS
(2022)
Article
Biology
Yong Zi Tan, Yazan M. Abbas, Jing Ze Wu, Di Wu, Kristine A. Keon, Geoffrey G. Hesketh, Stephanie A. Bueler, Anne-Claude Gingras, Carol Robinson, Sergio Grinstein, John L. Rubinstein
Summary: CryoEM analysis revealed an interaction between mEAK-7 and V-ATPase, which is disrupted by ATP-induced rotation. Exogenous mEAK-7 does not inhibit V-ATPase activity unlike its yeast homolog.
LIFE SCIENCE ALLIANCE
(2022)
Article
Biochemistry & Molecular Biology
Melad Farraha, Renuka Rao, Sindhu Igoor, Thi Y. L. Le, Michael A. Barry, Christopher Davey, Cindy Kok, James J. H. Chong, Eddy Kizana
Summary: This study aimed to develop a biological alternative to electronic pacemakers by using gene therapy to convert cardiomyocytes into sinoatrial node-like cells. The results showed that the transduction of hTBX18 gene resulted in morphological, molecular, physiological, and functional changes in the cardiomyocytes, recapitulating the pacemaker phenotype. The use of a clinically relevant vector opens new prospects for the development of biological pacemakers.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cardiac & Cardiovascular Systems
Robert D. Hume, Shaan Kanagalingam, Tejas Deshmukh, Siqi Chen, Suzanne M. Mithieux, Fairooj N. Rashid, Iman Roohani, Juntang Lu, Tram Doan, Dinny Graham, Zoe E. Clayton, Eugene Slaughter, Eddy Kizana, April S. Stempien-Otero, Paula Brown, Liza Thomas, Anthony S. Weiss, James J. H. Chong
Summary: This study demonstrated that tropoelastin can improve post-MI healing by enhancing cardiac repair and reducing scar formation. Tropoelastin injection significantly improved left ventricular function, reduced scar size, and increased scar elastin content. Furthermore, it promoted elastic fiber formation and reduced immune response. The findings suggest potential therapeutic strategies for manipulating scar synthesis after MI.
CIRCULATION RESEARCH
(2023)
Review
Cardiac & Cardiovascular Systems
Megha Kadian, Cindy Y. Kok, Dhanya Ravindran, Freda Passam, Leonardo Pasalic, Eddy Kizana
Summary: Cardioembolic stroke is a leading cause of ischemic stroke, and current therapeutic options are limited. Atrial appendage occlusion devices can be used for patients ineligible for oral anticoagulants, but there are still risks and limitations. Gene therapy is a promising strategy to target the underlying cause of cardioembolic stroke and further research is needed.
HEART LUNG AND CIRCULATION
(2023)
Article
Cell Biology
Thayne H. Dickey, Rui Ma, Sachy Orr-Gonzalez, Tarik Ouahes, Palak Patel, Holly McAleese, Brandi Butler, Elizabeth Eudy, Brett Eaton, Michael Murphy, Jennifer L. Kwan, Nichole D. Salinas, Michael R. Holbrook, Lynn E. Lambert, Niraj H. Tolia
Summary: Continued vaccination against SARS-CoV-2 is necessary due to waning immunity and emerging variants. A nanoparticle vaccine displaying the spike receptor-binding domain (RBD) has been developed, with improvements in stability, immune response, and manufacturing ease. The engineered RBD nanoparticles elicit potent neutralizing antibodies that surpass monomeric RBDs, providing protection against emerging variants.
Article
Multidisciplinary Sciences
Dinesh Selvakumar, Emma Wilkie, Tejas Deshmukh, Dhanya Ravindran, Yasuhito Kotake, Juntang Lu, Tony Barry, Vu Tran, Hugh Paterson, Alfred Hing, Timothy Campbell, Saurabh Kumar, Eddy Kizana, James J. H. Chong
Summary: Myocardial infarction is a major cause of death and disability worldwide, and new cardioprotective or regenerative strategies are urgently needed. Physiologically relevant large animal models are crucial for assessing the feasibility and effectiveness of therapeutic delivery strategies. Swine, due to their similarities to humans in cardiovascular physiology and anatomy, are preferred in preclinical evaluation of new therapies for myocardial infarction.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2023)
Article
Biochemistry & Molecular Biology
Cindy Y. Kok, Lauren M. MacLean, Renuka Rao, Shinya Tsurusaki, Eddy Kizana
Summary: The study aimed to identify a gene that can be delivered to the heart to protect against cancer therapy-induced cardiotoxicity. By replacing the CMV promoter with the cardiac-specific NCX1 promoter, a lentiviral vector capable of inducing the expression of cardioprotective gene Bcl-2 was successfully produced.