Review
Biochemistry & Molecular Biology
Anugraha Gandhirajan, Sanjoy Roychowdhury, Vidula Vachharajani
Summary: Sepsis and septic shock are the leading causes of death among hospitalized patients in the US. This immune response in sepsis transitions from a pro-inflammatory to an anti-inflammatory phase, with sirtuins playing a crucial role in orchestrating this transition. Epigenetic programming is integral to the shift from hyper- to hypo-inflammation in sepsis, but hypo-inflammation can increase susceptibility to secondary infections in hosts.
Review
Plant Sciences
Elina Welchen, Maria Victoria Canal, Diana E. Gras, Daniel H. Gonzalez
Summary: Plant mitochondria play a crucial role in shaping various cellular processes through signal transduction, including metabolic, redox, ion fluxes, protein relocalization, and physical contacts with other organelles. In addition, changes in mitochondrial physiology also affect the activity of signaling pathways that regulate plant growth and stress responses. As a result, mitochondria have a significant impact on the responses to internal and external factors that modify the activity of these pathways and associated biological processes in plants.
JOURNAL OF EXPERIMENTAL BOTANY
(2021)
Review
Biochemistry & Molecular Biology
Vicente Montejano-Ramirez, Eduardo Valencia-Cantero
Summary: Plants are susceptible to attack by pathogens and also experience iron deficiency. They have developed strategies to address iron deficiency, including rhizosphere acidification and iron reduction, as well as iron chelation. There is a cross-talk between pathogenic defense and iron uptake, as the production and secretion of antimicrobial molecules increase in response to iron deficiency, and phytohormones that induce pathogen-resistant genes also modulate genes related to iron uptake. Iron deficiency also induces the expression of defense-related genes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Alice Yu, Yuanyuan Li, Irene Li, Michael G. Ozawa, Christine Yeh, Aaron E. Chiou, Winston L. Trope, Jonathan Taylor, Joseph Shrager, Sylvia K. Plevritis
Summary: The study introduces a graph-based algorithm REMI that predicts ligand-receptor (LR) interactions and reconstructs interactomes from RNA sequencing data. By leveraging single-cell transcriptomics data for cell type resolution and identifying LR prognostic signatures among tumor-stroma-immune subpopulations, the study confirmed an interaction associated with LUAD progression.
Article
Multidisciplinary Sciences
Tetsuo Toyama, Tatiana V. Kudryashova, Asako Ichihara, Stefania Lenna, Agnieszka Looney, Yuanjun Shen, Lifeng Jiang, Leyla Teos, Theodore Avolio, Derek Lin, Ulas Kaplan, Grace Marden, Vrinda Dambal, Dmitry Goncharov, Horace Delisser, Robert Lafyatis, Francesca Seta, Elena A. Goncharova, Maria Trojanowska
Summary: Deficiency of transcription factor GATA6 plays a crucial role in the development of pulmonary arterial hypertension (PAH), contributing to hyper-proliferative cellular phenotypes, vascular remodeling, and oxidative stress. Targeting GATA6 deficiency may offer a therapeutic approach for PAH patients.
SCIENTIFIC REPORTS
(2023)
Article
Biochemistry & Molecular Biology
Yuanjun Shen, Dmitry A. Goncharov, Andressa Pena, Jeffrey Baust, Andres Chavez Barragan, Arnab Ray, Analise Rode, Timothy N. Bachman, Baojun Chang, Lifeng Jiang, Paul Dieffenbach, Laura E. Fredenburgh, Mauricio Rojas, Horace DeLisser, Ana L. Mora, Tatiana V. Kudryashova, Elena A. Goncharova
Summary: This study found that TSC2 abundance is decreased in pulmonary arterial hypertension (PAH) patients, and the loss of TSC2 leads to increased proliferation and survival of vascular smooth muscle cells. The study also found that extracellular matrix produced by remodeled cells stimulates the proliferation of other cells. Restoring TSC2 abundance can inhibit cell proliferation and induce cell apoptosis, providing a potential therapeutic option for treating PAH.
Article
Neurosciences
Khalid Elsaafien, Matthew K. Kirchner, Mazher Mohammed, Sophia A. Eikenberry, Chloe West, Karen A. Scott, Annette D. de Kloet, Javier E. Stern, Eric G. Krause
Summary: The PVNAgtr1a neurons play a key role in coordinating neuroendocrine axes and sympathetic nervous system responses to stress. These neurons synthesize CRH and activate neighboring neurons expressing CRHR1, ultimately regulating blood pressure in male mice through the hypothalamic-pituitary-adrenal axis and sympathetically mediated vasoconstriction.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Plant Sciences
Sampurna Garai, Citu, Sneh L. Singla-Pareek, Sudhir K. Sopory, Charanpreet Kaur, Gitanjali Yadav
Summary: This study revealed the widespread presence of Prion-like proteins (PrLPs) in plants through a comprehensive meta-analysis of 39 genomes, shedding light on their role in plant stress and memory. The rice prionome was found to be significantly enriched in transposons/retrotransposons and over 60 rice PrLPs were identified to be differentially regulated in stress and developmental responses, suggesting their importance in stress memory. The integrative meta-analysis connected transient and transgenerational memory mechanisms in plants with PrLPs, indicating that plant memory may rely not only on chromatin-based epigenetic signals but also on protein-based signals.
FRONTIERS IN PLANT SCIENCE
(2021)
Review
Cell Biology
Miguel Ramirez Moreno, Natalia A. Bulgakova
Summary: EGFR and E-cadherin are major regulators of proliferation and differentiation in epithelial cells, and defects in either can lead to malignancies. The reciprocal interactions between EGFR and E-cadherin contribute to tumorigenesis and cancer cell invasion through modulation of adhesion and activity regulation. Understanding the crosstalk between EGFR and E-cadherin is important for tissue morphogenesis, homeostasis, and cancer progression.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biophysics
Xi Zhuo Jiang, Michael S. Goligorsky, Kai H. Luo
Summary: This study investigates the interactions between glycocalyces of RBCs and endothelial cells using mathematical modeling and numerical simulation. Results show that circulating RBCs cause contactless deformation of the endothelial glycocalyx (EG), with deformation dependent on various factors such as chain layout, chain length, and RBC velocities. The study also suggests that RBCs drive EG deformation via near-field flow, while marginal propulsion of RBCs by the EG is observed. The findings provide new insights into the roles of glycocalyx in mechanotransduction and microvascular permeability under various conditions.
BIOPHYSICAL JOURNAL
(2021)
Article
Multidisciplinary Sciences
Luming Zhou, Guiping Kong, Ilaria Palmisano, Maria Teresa Cencioni, Matt Danzi, Francesco De Virgiliis, Jessica S. Chadwick, Greg Crawford, Zicheng Yu, Fred De Winter, Vance Lemmon, John Bixby, Radhika Puttagunta, Joost Verhaagen, Constandina Pospori, Cristina Lo Celso, Jessica Strid, Marina Botto, Simone Di Giovanni
Summary: Aging is associated with increased prevalence of axonal injuries, and the underlying mechanisms remain unclear. This study found that T cell signaling is enriched in mice before and after sciatic nerve injury (SNI), and this signaling promotes immune cell recruitment and axonal injury through the activation of specific proteins. Inhibition of T cell recruitment facilitates axonal regeneration.
Review
Biochemistry & Molecular Biology
Mohammad Hassan Emami, Nasrin Sereshki, Zahra Malakoutikhah, Sayed Ali Ehsan Dehkordi, Alireza Fahim, Samane Mohammadzadeh, Fatemeh Maghool
Summary: A large number of people worldwide are affected by chronic metal exposure, which is associated with various types of cancer. Excessive reactive oxygen species (ROS) generated by chronic metal exposure contributes to tumor cell death through regulating angiogenesis and ROS signaling pathways. The Nrf2 signaling pathway, as a regulator of oxidative stress and detoxification enzyme gene expression, plays an important role in cancer chemoprevention, but constitutive Nrf2 activation in cancer cells may promote cancer progression and resistance to chemotherapy.
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Qiyun Xiao, Johannes Werner, Nachiyappan Venkatachalam, Kim E. Boonekamp, Matthias P. Ebert, Tianzuo Zhan
Summary: Targeting cancer hallmarks is crucial for improving anti-cancer treatment, but cross-talk between signaling pathways often leads to resistance. This article provides an overview of the molecular interactions between the p53 and Wnt pathways in cancer, including complex feedback loops and reciprocal transactivation, as well as the mutational landscape of genes associated with these pathways.
Review
Medicine, General & Internal
Ahmed Ahmed Touni, Rohan S. Shivde, Harika Echuri, Rasha T. A. Abdel-Aziz, Hossam Abdel-Wahab, Roopal V. Kundu, I. Caroline Le Poole
Summary: Vitiligo is a common skin disorder characterized by the progressive loss of melanocytes. Keratinocytes, which are closely associated with melanocytes, play a crucial role in maintaining melanocyte function and homeostasis. Dysfunctional keratinocytes contribute to melanocyte loss through apoptosis, impairment of adhesion, presentation of melanocyte antigens, and recruitment of inflammatory T cells. Keratinocytes also fail to produce essential factors for melanocyte survival and interfere with repigmentation. Therefore, keratinocyte dysfunction is implicated in the development of vitiligo.
FRONTIERS IN MEDICINE
(2023)
Article
Plant Sciences
Luis F. D. Martini, Jose A. Noldin, Carlos E. Schaedler, Marcus Fipke, Vivian E. Viana, Carolina T. Borges, Paulo D. Zimmer, Dirceu Agostinetto, Luis A. Avila
Summary: Shifting the rice planting date to early spring improves weed control but exposes rice seedlings to cold stress. This study found that low temperature stimulates lipid peroxidation and total phenol accumulation, and also affects herbicide selectivity.
Article
Multidisciplinary Sciences
Pratyusha Mandal, John D. Lyons, Eileen M. Burd, Michael Koval, Edward S. Mocarski, Craig M. Coopersmith
Summary: The method described allows evaluation of multiple factors in one mouse, reducing overall animal use and minimizing inter-animal variability, providing a new approach to address humane concerns in animal experiments.
Review
Biochemistry & Molecular Biology
Michael Koval, Aleksandra Cwiek, Thomas Carr, Miranda E. Good, Alexander W. Lohman, Brant E. Isakson
Summary: Panx1 is a widely expressed protein forming large channels involved in inflammation and injury responses by releasing ATP and metabolites. It plays a crucial role in mediating signaling in response to pro-inflammatory stimuli, with a focus on vasculature coordination.
PURINERGIC SIGNALLING
(2021)
Article
Multidisciplinary Sciences
Rachel Morgan, Candela Manfredi, Kristen F. Easley, Lionel D. Watkins, William R. Hunt, Steven L. Goudy, Eric J. Sorscher, Michael Koval, Samuel A. Molina
Summary: This study successfully differentiated human basal cells isolated from the nasal and conducting airway into mature epithelial cells at the air-liquid interface (ALI) using a medium with normal resting glucose levels, avoiding the need for high glucose concentrations. The use of normal glucose-containing ALI medium also enabled differentiation of nasal and tracheal cells and allowed for long-term cell responsiveness.
SCIENTIFIC REPORTS
(2022)
Article
Substance Abuse
Shanawaj Khair, Lisa A. Brenner, Michael Koval, Derrick Samuelson, Jessica A. Cucinello-Regland, Paige Anton, Mariann R. Piano, Liz Simon, Kathryn Crotty, Farah Sharieh, Jeffrey B. Travers, Vaibhav Singh, Abigail Cannon, Adam Kim, Rebecca L. McCullough, Samantha M. Yeligar, Todd A. Wyatt, Rachel H. McMahan, Mashkoor A. Choudhry, Elizabeth J. Kovacs
Summary: The 2021 AIRIG meeting focused on the impact of alcohol misuse on the immune system and improving treatment for alcohol-related diseases.
Article
Virology
Lucky Sarkar, Lauren Oko, Soham Gupta, Andrew N. Bubak, Bishnu Das, Parna Gupta, Abass Alao Safiriyu, Chirag Singhal, Ujjwal Neogi, David Bloom, Arup Banerjee, Ravi Mahalingam, Randall J. Cohrs, Michael Koval, Kenneth S. Shindler, Debnath Pal, Maria Nagel, Jayasri Das Sarma
Summary: Emerging mutations in the SARS-CoV-2 genome pose a challenge for vaccine development and antiviral therapy. Azadirachta indica bark extract (NBE) exhibited antiviral efficacy against SARS-CoV-2 and m-CoVRSA59 infections, inhibiting viral replication and spread. In vitro and in vivo studies demonstrated that NBE could ameliorate neuroinflammation and hepatitis, potentially making it a promising antiviral agent against pan-beta-Coronaviruses.
Article
Biochemistry & Molecular Biology
John D. Lyons, Pratyusha Mandal, Shunsuke Otani, Deena B. Chihade, Kristen F. Easley, David A. Swift, Eileen M. Burd, Zhe Liang, Michael Koval, Edward S. Mocarski, Craig M. Coopersmith
Summary: Deletion or mutation of RIPK3 reduces inflammation and mortality in mice with Pseudomonas pneumonia. RIPK3 kinase activity is dispensable for cell killing but is involved in cytokine production. The RIPK3 scaffold domain mediates deleterious inflammation and may be a target for reducing lung inflammation during infection.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2023)
Article
Peripheral Vascular Disease
Luke. S. Dunaway, Marie Billaud, Edgar Macal, Miranda. E. Good, Christopher. B. Medina, Ulrike Lorenz, Kodi Ravichandran, Michael Koval, Brant. E. Isakson
Summary: This study suggests that Panx1 in smooth muscle cells plays a role in regulating sympathetic nerve constriction and blood pressure. The findings also demonstrate the feasibility of using Panx1-mouse models to test potential drugs for hypertension.
Article
Biochemistry & Molecular Biology
Abhishek Bose, Grishma Kasle, Rishika Jana, Mahua Maulik, Deepthi Thomas, Vaishali Mulchandani, Priyanka Mukherjee, Michael Koval, Jayasri Das Sarma
Summary: Gap junctional intercellular communication involving astrocytes is essential for CNS homeostasis. Infection with MHV-A59 disrupts the trafficking of Cx43, the main GJ protein in astrocytes, but the underlying mechanism is not clear. In this study, we found that retention of Cx43 due to MHV-A59 infection is associated with increased ER stress and reduced expression of chaperone protein ERp29. Treatment with a chemical chaperone rescues Cx43 transport, increases GJIC, and reduces ER stress. These findings provide insights into a therapeutically targetable mechanism where ERp29 modulates beta-coronavirus infectivity by alleviating ER stress and restoring Cx43 trafficking.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Critical Care Medicine
Deena B. Chihade, Prestina Smith, David A. Swift, Shunsuke Otani, Wenxiao Zhang, Ching-Wen Chen, Lauren A. Jeffers, Zhe Liang, Takashi Shimazui, Eileen M. Burd, Alton B. Farris, Bashar S. Staitieh, David M. Guidot, Mandy L. Ford, Michael Koval, Craig M. Coopersmith
Summary: Increased permeability in sepsis is mediated by disruptions in tight junctions, and genetic deletion of myosin light chain kinase (MLCK) reverses this effect in intra-abdominal sepsis. However, in this study, MLCK deletion unexpectedly increased mortality in pneumonia-induced sepsis, associated with worsened alveolar epithelial leak and systemic inflammation. These findings caution against targeting MLCK for therapeutic gain in sepsis.
Article
Pharmacology & Pharmacy
Michael Koval, Wyatt J. Schug, Brant E. Isakson
Summary: Pannexin channels have important roles in regulating inflammation and are associated with various diseases. Blocking these channels pharmacologically is crucial for therapeutic approaches. This review discusses the current state of agents that can block pannexin channels, focusing on pharmaceuticals and peptide mimetics targeting pannexin 1. It also provides guidance on interpreting results obtained with pannexin pharmacologics and evaluates the strengths and limitations of different agents in terms of specificity and clinical application.
CURRENT OPINION IN PHARMACOLOGY
(2023)
Review
Pharmacology & Pharmacy
Anastasia Kolousek, Ezra Pak-Harvey, Oliver Liu-Lam, Mia White, Prestina Smith, Fernanda Henning, Michael Koval, Joshua M. Levy
Summary: The endocannabinoid system is a potential therapeutic target for chronic inflammatory disease, including respiratory illnesses. This scoping review explores the impact of endocannabinoid activity on eicosanoid production and its role in airway inflammation. The findings suggest that endocannabinoid activation can increase COX-2 expression and lead to increased levels of prostaglandin E-2.
CANNABIS AND CANNABINOID RESEARCH
(2023)
Article
Substance Abuse
Viranuj Sueblinvong, Xian Fan, Craishun Hart, Samuel Molina, Michael Koval, David M. Guidot
Summary: Chronic alcohol ingestion induces dysregulated TGF beta 1 and GM-CSF in lung fibroblasts, leading to impaired airway epithelial barrier function. Co-culturing ethanol-exposed lung fibroblasts with airway epithelial cells resulted in decreased transepithelial electrical resistance, reduced expression of tight junction protein ZO-1, and increased expression of collagen type 1A1 and α-smooth muscle actin. These effects were mediated through the activation of TGF beta 1 signaling and suppression of GM-CSF, and could be prevented by blocking TGF beta 1 activity.
ALCOHOL-CLINICAL AND EXPERIMENTAL RESEARCH
(2023)
Article
Biology
Samuel A. Molina, Daniela Maier-Begandt, Brant E. Isakson, Michael Koval
Summary: The permeability of blood vessels is regulated by endothelial cells. This permeability is influenced by factors such as the type of blood vessel and the specific disease state. Most studies on endothelial permeability have been conducted using isolated cells in culture, which may not accurately reflect the native cell environment. In this study, the authors describe a method that allows for the measurement of endothelial properties in intact blood vessels, providing a more accurate analysis of the response to various stresses in the context of the intact vessel.
Meeting Abstract
Biochemistry & Molecular Biology
Kristen Easley, Ashish Mehta, Bashar Staitieh, Michael Koval
Meeting Abstract
Biochemistry & Molecular Biology
Lauren Jeffers, Carissa James, Ryan Reed, Michael Koval