Article
Microbiology
Juri Kim, Eun-Ah Park, Mee Young Shin, Soon-Jung Park
Summary: This study investigated the functional roles of Giardia lamblia CDKs (GlCDKs) and their cognate cyclins. Using morpholino-mediated knockdown and coimmunoprecipitation, the functions of GlCDK1 and GlCDK2 were distinguished. GlCDK1 with Glcyclin 3977 plays a crucial role in flagellum formation and cell cycle control of G. lamblia, while GlCDK2 with Glcyclin 22394/6584 is involved in cell cycle control.
MICROBIOLOGY SPECTRUM
(2023)
Review
Biochemistry & Molecular Biology
Pawel Lukasik, Irena Baranowska-Bosiacka, Katarzyna Kulczycka, Izabela Gutowska
Summary: Recent studies have shown that small molecule drugs targeting CDK inhibitors have become attractive options for treating cancer and neurodegenerative disorders. Most CDK inhibitors target the ATP binding pocket, but the similarity in structure among CDK kinases makes achieving selectivity challenging. Therefore, inhibitors binding outside the ATP binding site have attracted great interest for their potential applications in the biomedical field.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Alan Umfress, Sarbjit Singh, Kevin J. Ryan, Ayanabha Chakraborti, Florian Plattner, Yogesh Sonawane, Jayapal Reddy Mallareddy, Edward P. Acosta, Amarnath Natarajan, James A. Bibb
Summary: Cyclin-dependent kinase 5 (Cdk5) is a crucial regulator of neuronal signal transduction and its activity is implicated in various neuropsychiatric and neurodegenerative conditions. In this study, a novel brain-penetrant Cdk5 inhibitor 25-106 was identified, which showed promising effects on behavior and has significant potential as a neurological/neuropsychiatric therapeutic.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Plant Sciences
Zhiqiang Zhang, Wenqi Huo, Xingxing Wang, Zhongying Ren, Junjie Zhao, Yangai Liu, Kunlun He, Fei Zhang, Wei Li, Shuangxia Jin, Daigang Yang
Summary: This study comprehensively analyzed the origin, evolution, and diversification of the wall-associated kinase (WAK) gene family in plants. The results revealed the origin, evolution, and diversification of WAK genes in green plants. The functional diversity of WAK genes in Arabidopsis and rice was demonstrated through phylogenetic and expression pattern analyses. This study provides important insights for future investigations on the functionality of WAK genes.
PLANT CELL REPORTS
(2023)
Review
Chemistry, Medicinal
Sonal M. Manohar
Summary: This article reviews cyclin-dependent kinases as potential targets for colorectal cancer (CRC) and discusses therapeutic candidates to target CDKs.
FUTURE MEDICINAL CHEMISTRY
(2022)
Review
Pharmacology & Pharmacy
Marzena Staniszewska, Kajetan Kielbowski, Klaudia Rusinska, Estera Bakinowska, Ewa Gromowska, Andrzej Pawlik
Summary: In this review, the potential of cyclin-dependent kinases (CDK) as novel therapeutic targets in rheumatoid arthritis (RA) and psoriasis is evaluated. CDK inhibitors show promise due to their potential multidirectional effects on osteoclastogenesis, neutrophil apoptosis, and macrophage apoptosis, all of which play important roles in the development of joint destruction and inflammation in RA and psoriasis. However, further clinical trials are needed to assess the efficacy and safety of CDK-blocking therapy in these conditions.
EXPERT OPINION ON THERAPEUTIC TARGETS
(2023)
Review
Oncology
Alessia Schirripa, Veronika Sexl, Karoline Kollmann
Summary: The cell cycle is controlled by CDKs, and dysregulation of CDK inhibitors is associated with neoplastic transformation, especially in hematological malignancies.
FRONTIERS IN ONCOLOGY
(2022)
Article
Cell Biology
Christin Riess, Dirk Koczan, Bjoern Schneider, Charlotte Linke, Katharina del Moral, Carl Friedrich Classen, Claudia Maletzki
Summary: Therapeutic activity of selective CDK inhibitors in GBM has been confirmed through comprehensive analysis, showing effects on tumor model viability, morphology, senescence induction, mitochondrial dysfunction, and DNA damage. The combination of dinaciclib and abemaciclib may exhibit synergistic effects, while the simultaneous combination with TMZ shows antagonistic effects on therapeutic outcome.
CELL DEATH DISCOVERY
(2021)
Article
Oncology
Emanuel Raschi, Michele Fusaroli, Andrea Ardizzoni, Elisabetta Poluzzi, Fabrizio De Ponti
Summary: This post-marketing research studied the role of cyclin-dependent kinase 4/6 inhibitors in cancer-associated thrombosis, finding a potential class effect for venous thrombosis and distinctive arterial events for ribociclib. The study suggests proactive monitoring by oncologists for thromboembolic events with CDK4/6 inhibitors and supports pharmacovigilance for safe prescribing in oncology.
Review
Chemistry, Medicinal
Mohammed Al-Kassim Hassan, Zeynep Ates-Alagoz
Summary: Breast cancer is the leading cause of cancer-related deaths in women worldwide. FDA has approved three CDK4/6 inhibitors for the targeted treatment of advanced or metastatic breast cancer, and several compounds derived from various synthetic scaffolds are showing promising results in clinical trials. This review highlights the potent anti-CDK4/6 activities of these compounds and emphasizes the potential for discovering novel CDK inhibitor compounds in the future, expanding therapeutic options for cancer treatment.
MINI-REVIEWS IN MEDICINAL CHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Shivani Batra, Shagufta Jahan, Anam Ashraf, Bandar Alharby, Talha Jawaid, Asimul Islam, Imtaiyaz Hassan
Summary: Cyclin-dependent kinase 5 (CDK5) is a serine/threonine-directed kinase primarily found in the brain that plays a crucial role in the development of the central nervous system. Recent research has shown that CDK5 is activated by specific cyclins, which regulate its expression and activity. This review examines the role of CDK5 in neurons, synaptic plasticity, DNA damage repair, and the cell cycle, highlighting its therapeutic potential as a target for neurodegenerative diseases. The structural features of CDK5 and its binding with designed inhibitors are also discussed, providing insights for the development of attractive strategies in therapeutic targeting.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Review
Oncology
Ajay Dhaka, Carla Falkson, Ruth M. O'Regan
Summary: The use of CDK4/6 inhibitors has improved outcomes for patients with metastatic HR-positive breast cancer, but trials evaluating their use in the adjuvant setting have shown mixed results, highlighting the need for further research on patient selection and predictive biomarkers.
Review
Biochemistry & Molecular Biology
Georgia Gomatou, Ioannis Trontzas, Stephanie Ioannou, Maria Drizou, Nikolaos Syrigos, Elias Kotteas
Summary: CDK 4/6 inhibitors have shown promise in treating breast cancer, but patients often develop resistance. Studies indicate that resistance mechanisms involve aberrations of cell cycle molecules and rewiring of the cell to reduce dependence on CDK 4/6.
MOLECULAR BIOLOGY REPORTS
(2021)
Editorial Material
Chemistry, Medicinal
Mark Klein
Summary: Cyclin-dependent kinases (CDKs) have important roles in normal cells and can be targeted for cancer therapy. CDK4 inhibitors have been approved for advanced breast cancer treatment. However, the development of selective inhibitors for individual CDKs is challenging due to the highly conserved ATP-binding site.
Review
Biochemistry & Molecular Biology
Pawel Lukasik, Michal Zaluski, Izabela Gutowska
Summary: Cyclin-dependent kinases are crucial in various cellular processes and their dysregulation can lead to diseases, making them potential drug targets.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Allergy
Yotesawee Srisomboon, Koji Iijima, Mathia Colwell, Peter J. Maniak, Marissa Macchietto, Christopher Faulk, Hirohito Kita, Scott M. O'Grady
Summary: This study reveals a novel, allergen-induced mechanism of rapid DNA release that amplifies type 2 immunity in airways, driven by Alternaria alternata and house dust mite exposure.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2023)
Article
Environmental Sciences
Mathia L. Colwell, Nicole Flack, Amanda Rezabek, Christopher Faulk
Summary: Inorganic arsenic (iAs) is a major toxic exposure that affects human health globally. Exposure to iAs during pregnancy can disrupt the epigenome of F1 offspring and their F2 grand-offspring through fetal primordial germ cells (PGCs). This study aimed to understand the intergenerational effects of in utero iAs exposure on the epigenetic profile and disease phenotypes in adult F1 and F2 offspring. The results showed persistent changes in weight, body composition, and glucose metabolism, as well as dysregulation of genes associated with cancer, T2D, and obesity. The study suggests that prenatal exposure to iAs can have long-lasting effects on the epigenome and metabolism.
ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
(2023)
Article
Plant Sciences
Hamada AbdElgawad, Gaurav Zinta, Johann Hornbacher, Jutta Papenbrock, Marios N. Markakis, Han Asard, Gerrit T. S. Beemster
Summary: The study found that increased CO2 concentration has a significant effect on drought resistance, especially through the promotion of aliphatic glucosinolate (GL) synthesis. By regulating the expression of transcription factors ABI5 and WRKY63, the synergistic effect of MYB28/29, and increasing the accumulation of GL precursors, CO2 can promote GL synthesis. In addition, overexpression of MYB28, 29, and 76 genes can improve drought tolerance by maintaining plant water and stomatal closure, while the loss of cyp79f genes weakens the drought resistance and mitigating effect of CO2.
PLANT CELL AND ENVIRONMENT
(2023)
Article
Plant Sciences
Emad A. Alsherif, Omar Almaghrabi, Ahmed M. Elazzazy, Mohamed Abdel-Mawgoud, Gerrit T. S. Beemster, Hamada AbdElgawad
Summary: Drought is a global threat, and investigating the interactive effect of compost, arbuscular mycorrhizal fungi, and carbon nanoparticles on maize plants can effectively improve soil fertility and promote growth, reducing drought-induced oxidative damages.
PLANT PHYSIOLOGY AND BIOCHEMISTRY
(2023)
Article
Plant Sciences
Narender Kumar, Chloe Caldwell, Anjali S. Iyer-Pascuzzi
Summary: The root cap plays critical roles in root growth, protecting the root meristem and influencing soil penetration, as well as perceiving and transmitting environmental signals for root branching patterns. However, the mechanism by which the root cap integrates endogenous developmental pathways with environmental signals remains unclear. This study demonstrates that the transcription factor NLP7 links nitrate signaling with auxin pathways to regulate root cap development in Arabidopsis. NLP7 is involved in the release of root cap cells under low nitrate conditions and impacts auxin pathways in the last layer of the root cap. Mutations in NLP7 affect the expression of auxin carriers and transcription factors that regulate auxin transport. Overall, NLP7 acts as a key regulator in integrating nitrate signaling and endogenous auxin pathways for root cap development.
JOURNAL OF EXPERIMENTAL BOTANY
(2023)
Article
Plant Sciences
Cindy M. S. Laine, Hamada AbdElgawad, Gerrit T. S. Beemster
Summary: Maize, a cold-sensitive crop, requires cold tolerance for extending the growing season in temperate climates. A meta-analysis was conducted to investigate the effect of cold stress on maize leaf using data from literature. Response curves to temperature and exposure durations were constructed for various parameters, and the importance of these parameters for cold tolerance was evaluated using cold tolerant and cold sensitive lines. The results showed interacting effects of temperature and exposure durations on different response parameters, with electrolyte leakage being a reliable indicator for cold tolerance studies.
PLANT CELL AND ENVIRONMENT
(2023)
Article
Plant Sciences
Jiayi Zhao, Xin Gui, Ziming Ren, Huiqi Fu, Chao Yang, Wenyi Wang, Qingpei Liu, Min Zhang, Chong Wang, Arp Schnittger, Bing Liu
Summary: This study demonstrates the important role of the ATM kinase in maintaining meiotic genome stability under heat stress in Arabidopsis.
Article
Environmental Sciences
Hamada AbdElgawad, Pooja Negi, Gaurav Zinta, Afrah E. Mohammed, Modhi O. Alotaibi, Gerrit Beemster, Ahmed M. Saleh, Ashish Kumar Srivastava
Summary: In this study, the combination of thiourea (TU) and Actinobacteria (Act) was evaluated as a low-cost approach for reducing arsenic (As) toxicity in rice. ThioAC treatment stabilized photosynthetic performance and improved root lignin levels. ThioAC also activated enzymatic and non-enzymatic antioxidant systems, resulting in improved antioxidant defense against As stress.
SCIENCE OF THE TOTAL ENVIRONMENT
(2023)
Article
Plant Sciences
Sorin Tanasa, Neha Shukla, Albert Cairo, Ranjani S. Ganji, Pavlina Mikulkova, Sona Valuchova, Vivek K. Raxwal, Claudio Capitao, Arp Schnittger, Zbynek Zdrahal, Karel Riha
Summary: Meiosis is a specialized cell division that reduces the number of chromosomes, followed by mitotic divisions to form haploid gametophytes in angiosperm plants. In Arabidopsis, the termination of meiosis and transition to gametophytic development are regulated by TDM1 and SMG7, which inhibit translation. Mutants deficient in this mechanism show aberrant nuclear divisions due to the failure to downregulate cyclin dependent kinases during meiotic exit. A mutation in cyclin-dependent kinase D;3 (CDKD;3) was identified as a suppressor that alleviates meiotic defects in smg7 deficient plants by preventing aberrant meiotic divisions or delaying their onset. CDKD;3 acts independently of CDKA;1 and interacts with proteins involved in cytokinesis, suggesting a complex role in cell cycle regulation.
Article
Genetics & Heredity
Nicole Flack, Melissa Drown, Carrie Walls, Jay Pratte, Adam McLain, Christopher Faulk
Summary: Pallas's cat, a small felid found in central Asia, faces various challenges such as climate change and habitat fragmentation. To improve its genomic resources, researchers used nanopore sequencing to assemble the nuclear and mitochondrial genomes of the species. The assembly provided insights into genetic variations and DNA methylation patterns.
NAR GENOMICS AND BIOINFORMATICS
(2023)
Article
Biochemistry & Molecular Biology
Christopher Faulk
Summary: Genome skimming, using low-pass sequencing, is commonly used for mitochondrial genome recovery and species identification. Nanopore sequencers are highly accurate for global DNA methylation and transposon assessment. This method is accessible for epigenetic assessment in various fields due to its low cost and portability.
Article
Plant Sciences
Kieu-Nga Tran, Pramod Pantha, Guannan Wang, Narender Kumar, Chathura Wijesinghege, Dong-Ha Oh, Samadhi Wimalagunasekara, Nick Duppen, Hongfei Li, Hyewon Hong, John C. Johnson, Ross Kelt, Megan G. Matherne, Thu T. Nguyen, Jason R. Garcia, Ashley Clement, David Tran, Colt Crain, Prava Adhikari, Yanxia Zhang, Maryam Foroozani, Guido Sessa, John C. Larkin, Aaron P. Smith, David Longstreth, Patrick Finnegan, Christa Testerink, Simon Barak, Maheshi Dassanayake
Summary: Schrenkiella parvula, a leading extremophyte model in Brassicaceae, is capable of growing and completing its lifecycle in high salinity conditions. This study aimed to identify the key physiological and structural traits that contribute to the plant's stress-resilient and uncompromised growth. The plant's resilient growth was promoted by traits such as primary root growth, expansion of xylem vessels, and the development of thicker succulent leaves to maintain tissue water levels during salt stress. Additionally, salt-induced early flowering was observed, which contributed to successful reproductive transition and viable seed production.
Article
Multidisciplinary Sciences
Gabela Nelson, Alexis Strain, Atsuko Isu, Alireza Rahnama, Ken-ichi Wakabayashi, Adam T. T. Melvin, Naohiro Kato
Summary: The mechanisms governing chemotaxis in Chlamydomonas reinhardtii are still poorly understood. In this study, a modified Petri dish assay revealed a novel mechanism for ammonium chemotaxis in Chlamydomonas. Light exposure enhanced the chemotactic response, but phototaxis-incompetent mutant strains still exhibited normal chemotaxis. Collective migration was observed during chemotaxis but not phototaxis. The AGG1 protein was found to suppress collective migration during chemotaxis.
SCIENTIFIC REPORTS
(2023)
Article
Multidisciplinary Sciences
Yan Gong, Renee Dale, Hannah F. Fung, Gabriel O. Amador, Margot E. Smit, Dominique C. Bergmann
Summary: This study reveals that stem cells of the Arabidopsis stomatal lineage transition from asymmetric self-renewing divisions to commitment and terminal differentiation triggered by crossing a critical cell size threshold. Computational simulation and genetic manipulations demonstrate that this cell size-mediated transition allows flexible control of stem cell proliferation.
Review
Clinical Neurology
Joseph M. M. Palumbo, Brian F. F. Thomas, Dejan Budimirovic, Steven Siegel, Flora Tassone, Randi Hagerman, Christopher Faulk, Stephen O'Quinn, Terri Sebree
Summary: Multiple lines of evidence have shown the importance of the endocannabinoid system (ECS) in neuronal development, cognitive function, and the pathogenesis of fragile X syndrome (FXS). This review discusses the role of the ECS in the central nervous system, its dysregulation in FXS, and the potential use of cannabidiol as a treatment for FXS. FXS is caused by the deficiency of the fragile X messenger ribonucleoprotein 1 (FMR1) protein, FMRP, due to the methylation of the FMR1 gene promoter. The absence of FMRP disrupts ECS signaling, leading to overstimulation, desensitization, and internalization of presynaptic CB1 receptors. Cannabidiol acts as a negative allosteric modulator of CB1, helping to restore synaptic homeostasis and potentially benefiting patients with FXS.
JOURNAL OF NEURODEVELOPMENTAL DISORDERS
(2023)