Review
Cell Biology
Leon N. K. Quaye, Catherine E. Dalzell, Panos Deloukas, Andrew J. P. Smith
Summary: This review examines the importance of genome-wide association studies (GWAS) in coronary artery disease (CAD) research and highlights the vascular pathways as a new opportunity for CAD treatment. By studying the genetic loci, the potential role of these loci in the pathogenesis of CAD can be understood, leading to the development of novel therapeutic tools for cardiovascular disorders.
Article
Medicine, General & Internal
Martine E. Bol, J. B. Huckriede, K. G. H. van de Pas, T. Delhaas, R. Lorusso, G. A. F. Nicolaes, J. E. M. Sels, M. C. G. van de Poll
Summary: This study aimed to compare different indices of glycocalyx shedding and dysfunction in patients undergoing coronary artery bypass grafting (CABG) surgery. The results showed that glycocalyx thinning was accompanied by impaired glycocalyx function and increased endothelial activation during CABG surgery with cardiopulmonary bypass (CPB).
FRONTIERS IN MEDICINE
(2022)
Article
Cardiac & Cardiovascular Systems
Charles U. Solomon, David G. McVey, Catherine Andreadi, Peng Gong, Lenka Turner, Paulina J. Stanczyk, Sonja Khemiri, Julie C. Chamberlain, Wei Yang, Tom R. Webb, Christopher P. Nelson, Nilesh J. Samani, Shu Ye
Summary: This comprehensive analysis shows that a large percentage of CAD loci can modulate gene expression in VSMCs and influence VSMC behavior. Several candidate causal genes identified are likely to be druggable and thus represent potential therapeutic targets.
Review
Genetics & Heredity
Shuquan Rao, Yao Yao, Daniel E. Bauer
Summary: The review discusses emerging experimental approaches for functional studies of causal variants and translational advances from GWAS findings to disease prevention and treatment. It highlights the use of genome editing technologies in GWAS functional studies with proof-of-principle examples, and discusses challenges in interrogating causal variants and potential therapeutic opportunities.
Article
Plant Sciences
Siva K. Chamarthi, Avjinder S. Kaler, Hussein Abdel-Haleem, Felix B. Fritschi, Jason D. Gillman, Jeffery D. Ray, James R. Smith, Arun P. Dhanapal, Charles A. . King, Larry C. Purcell
Summary: This study identified 188 significant SNPs associated with canopy wilting in soybean, with 183 candidate genes identified near these SNPs. Genomic estimated breeding values (GEBVs) were found to have predictive ability for canopy wilting in different genotypes and environments. The candidate genes may play roles in plant stress responses, potentially affecting transpiration or water conservation.
FRONTIERS IN PLANT SCIENCE
(2021)
Review
Medicine, General & Internal
A. Blum
Summary: Women have a clinical advantage in atherosclerotic cardiovascular disease (CVD) compared to men, but this advantage diminishes with aging. By their seventh decade, women have an equal risk of developing CVD as men of the same age. Various theories have been proposed to explain this gender difference, including hormonal and cardiovascular system differences. This review aims to review and discuss these different mechanisms.
QJM-AN INTERNATIONAL JOURNAL OF MEDICINE
(2023)
Article
Horticulture
Irina Vasylyk, Svetlana Gorislavets, Elena Matveikina, Ekaterina Lushchay, Kirill Lytkin, Elizaveta Grigoreva, Dmitry Karzhaev, Vladimir Volkov, Vitalii Volodin, Gennady Spotar, Valentina Risovannaya, Vladimir Likhovskoi, Vladimir Volynkin, Elena Potokina
Summary: This study evaluated the host tolerance of three grapevine hybrid populations against leaf-feeding grape phylloxera and discovered SNP loci associated with leaf infestation and gall formation. Some of these SNPs overlapped with previously reported QTLs for root phylloxera resistance and apoptosis-related genes.
Article
Multidisciplinary Sciences
Daiane Hemerich, Roelof A. J. Smit, Michael Preuss, Lauren Stalbow, Sander W. van der Laan, Folkert W. Asselbergs, Jessica van Setten, Vinicius Tragante
Summary: Genome-wide association studies have identified numerous loci associated with type 2 diabetes (T2D), but the mechanisms through which these loci contribute to disease progression remain unclear. This study investigated the role of tissue-specific regulatory elements and expression quantitative trait loci (eQTLs) in T2D-associated outcomes. The results suggest that there is no specific disease progression profile based on tissue-specific regulatory and transcriptome information.
SCIENTIFIC REPORTS
(2023)
Article
Genetics & Heredity
Ilakya Selvarajan, Anu Toropainen, Kristina M. Garske, Maykel Lopez Rodriguez, Arthur Ko, Zong Miao, Dorota Kaminska, Kadri Ounap, Tiit Ord, Aarthi Ravindran, Oscar H. Liu, Pierre R. Moreau, Ashik Jawahar Deen, Ville Mannisto, Calvin Pan, Anna-Liisa Levonen, Aldons J. Lusis, Sami Heikkinen, Casey E. Romanoski, Jussi Pihlajamaki, Paivi Pajukanta, Minna U. Kaikkonen
Summary: Genetic factors underlying coronary artery disease (CAD) have been extensively studied using genome-wide association studies (GWAS). This study identified potential target genes related to liver function by analyzing the function of non-coding single-nucleotide polymorphisms in CAD GWAS loci located within liver-specific enhancer elements. Furthermore, the analysis identified a significant number of unique SNPs with allele-specific regulatory activity, particularly enhancers near key genes involved in cholesterol homeostasis.
AMERICAN JOURNAL OF HUMAN GENETICS
(2021)
Article
Immunology
Xiaoxuan Ma, Meiming Su, Qingze He, Zhidan Zhang, Fanshun Zhang, Zhenghong Liu, Lu Sun, Jianping Weng, Suowen Xu
Summary: By analyzing human plaque tissue data and conducting experiments on mice, this study identifies PHACTR1 as being associated with endothelial dysfunction, which it regulates through inflammation response and NO production, and finds that its expression can be reduced by certain drugs.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Plant Sciences
Sahar Bennani, Ahmed Birouk, Mohammed Jlibene, Miguel Sanchez-Garcia, Nasserelhaq Nsarellah, Fatima Gaboun, Wuletaw Tadesse
Summary: The present research aims to identify the efficient combination of drought-tolerance selection criteria and associated quantitative trait loci. The results showed that grain number, biomass, number of fertile spikes per plant and ground cover exhibited significant correlation with grain yield, and can be potential secondary selection criteria for yield under drought conditions. Certain markers were associated with yield increase, biomass increase, and improved drought tolerance performance.
Article
Agriculture, Multidisciplinary
Baoqing Zhang, Yuxin Huang, Lijun Zhang, Zhongfeng Zhou, Shan Zhou, Weixing Duan, Cuifang Yang, Yijing Gao, Sicheng Li, Meiyan Chen, Yangrui Li, Xiping Yang, Gemin Zhang, Dongliang Huang
Summary: This study evaluated yield-related traits and identified markers and candidate genes for improving sugarcane yields using molecular techniques. The findings provide valuable information for marker-assisted breeding to increase sugarcane productivity.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Praveen Hariharan, Josee Dupuis
Summary: Through gene and pathway-based association tests, novel genes and pathways associated with coronary artery disease (CAD) were identified, including statistically significant genes and previously unreported associations. Among the top 1% non-lipid pathways, pathways regulating coagulation, inflammation, neuronal aging, and wound healing were detected.
SCIENTIFIC REPORTS
(2021)
Article
Genetics & Heredity
Krishna G. Aragam, Tao Jiang, Anuj Goel, Stavroula Kanoni, Brooke N. Wolford, Deepak S. Atri, Elle M. Weeks, Minxian Wang, George Hindy, Wei Zhou, Christopher Grace, Carolina Roselli, Nicholas A. Marston, Frederick K. Kamanu, Ida Surakka, Loreto Munoz Venegas, Paul Sherliker, Satoshi Koyama, Kazuyoshi Ishigaki, Bjorn O. Asvold, Michael R. Brown, Ben Brumpton, Paul S. de Vries, Olga Giannakopoulou, Panagiota Giardoglou, Daniel F. Gudbjartsson, Ulrich Gueldener, Syed M. Ijlal Haider, Anna Helgadottir, Maysson Ibrahim, Adnan Kastrati, Thorsten Kessler, Theodosios Kyriakou, Tomasz Konopka, Ling Li, Lijiang Ma, Thomas Meitinger, Soeren Mucha, Matthias Munz, Federico Murgia, Jonas B. Nielsen, Markus M. Noethen, Shichao Pang, Tobias Reinberger, Gavin Schnitzler, Damian Smedley, Gudmar Thorleifsson, Moritz von Scheidt, Jacob C. Ulirsch, David O. Arnar, Noel P. Burtt, Maria C. Costanzo, Jason Flannick, Kaoru Ito, Dong-Keun Jang, Yoichiro Kamatani, Amit V. Khera, Issei Komuro, Iftikhar J. Kullo, Luca A. Lotta, Christopher P. Nelson, Robert Roberts, Gudmundur Thorgeirsson, Unnur Thorsteinsdottir, Thomas R. Webb, Aris Baras, Johan L. M. Bjoerkegren, Eric Boerwinkle, George Dedoussis, Hilma Holm, Kristian Hveem, Olle Melander, Alanna C. Morrison, Marju Orho-Melander, Loukianos S. Rallidis, Arno Ruusalepp, Marc S. Sabatine, Kari Stefansson, Pierre Zalloua, Patrick T. Ellinor, Martin Farrall, John Danesh, Christian T. Ruff, Hilary K. Finucane, Jemma C. Hopewell, Robert Clarke, Rajat M. Gupta, Jeanette Erdmann, Nilesh J. Samani, Heribert Schunkert, Hugh Watkins, Cristen J. Willer, Panos Deloukas, Sekar Kathiresan, Adam S. Butterworth
Summary: This study identified and characterized over 250 risk loci for coronary artery disease (CAD) through a genome-wide association study, shedding light on the potential causal mechanisms for CAD. The research findings revealed the involvement of early developmental processes, cell cycle signaling, and vascular cell migration and proliferation in the pathogenesis of CAD.
Article
Genetics & Heredity
Victor Wakim, Elie Abi Khalil, Angelique K. Salloum, Georges Khazen, Michella Ghassibe-Sabbagh, Pierre A. Zalloua
Summary: This study identifies new genetic factors associated with severe stenosis and different risk factors related to a young age at diagnosis of CAD.
BMC MEDICAL GENOMICS
(2021)
Article
Biotechnology & Applied Microbiology
Kathleen A. Christie, Jimmy A. Guo, Rachel A. Silverstein, Roman M. Doll, Megumu Mabuchi, Hannah E. Stutzman, Jiecong Lin, Linyuan Ma, Russell T. Walton, Luca Pinello, G. Brett Robb, Benjamin P. Kleinstiver
Summary: In this study, the utility of a near-PAMless SpCas9 variant named SpRY as a universal DNA cleavage tool for various cloning applications was explored. It was found that SpRY can cleave DNA in vitro without the need for a PAM, and can cleave DNA at practically any sequence, including sites refractory to cleavage with wild-type SpCas9. The versatility and effectiveness of SpRYgests were illustrated to improve the precision of several cloning workflows, and a rapid and simple one-pot gRNA synthesis protocol was optimized to streamline SpRYgest implementation.
NATURE BIOTECHNOLOGY
(2023)
Article
Clinical Neurology
Siddharth Srivastava, Hagar Mor Shaked, Kenneth Gable, Sita D. Gupta, Xueyang Pan, Niranjanakumari Somashekarappa, Gongshe Han, Payam Mohassel, Marc Gotkine, Elizabeth Doney, Paula Goldenberg, Queenie K. G. Tan, Yi Gong, Benjamin Kleinstiver, Brian Wishart, Heidi Cope, Claudia Brito Pires, Hannah Stutzman, Rebecca C. Spillmann, Reza Sadjadi, Orly Elpeleg, Chia-Hsueh Lee, Hugo J. Bellen, Simon Edvardson, Florian Eichler, Teresa M. Dunn
Summary: Sphingolipids, abundant in myelin membranes, are crucial for the structural and signalling functions in the mammalian nervous system. Serine palmitoyltransferase (SPTSSA) is the enzyme responsible for the rate-limiting reaction in sphingolipid synthesis and its activity is tightly regulated by ORMDL proteins. Excessive sphingolipid synthesis due to impaired homeostatic regulation of serine palmitoyltransferase was found to be responsible for defects in early brain development and function. SRivastava et al. identified SPTSSA variants that disrupt ORMDL-mediated regulation of SPT, leading to hereditary spastic paraplegia.
Article
Biotechnology & Applied Microbiology
Connor J. Tou, Benno Orr, Benjamin P. Kleinstiver
Summary: We engineered new CRISPR-associated transposases (CASTs) called HELIX, which improves the purity and specificity of DNA insertion, overcoming the limitations of off-target integration and undesired recombination products. HELIX enables efficient and specific integration in human cell contexts.
NATURE BIOTECHNOLOGY
(2023)
Article
Immunology
Julie Brault, Taylor Liu, Siyuan Liu, Amanda Lawson, Uimook Choi, Nikita Kozhushko, Vera Bzhilyanskaya, Mara Pavel-Dinu, Ronald J. Meis, Michael A. Eckhaus, Sandra S. Burkett, Marita Bosticardo, Benjamin P. Kleinstiver, Luigi D. Notarangelo, Cicera R. Lazzarotto, Shengdar Q. Tsai, Xiaolin Wu, Gary A. Dahl, Matthew H. Porteus, Harry L. Malech, Suk See De Ravin
Summary: Ex vivo gene therapy has shown significant clinical benefits in treating Inborn errors of Immunity (IEIs) through the use of engineered retroviral vectors. However, concerns regarding potential genotoxicities have arisen due to random vector integrations. The targeted correction through CRISPR-Cas9-based genome editing offers improved precision and safety for functional correction of IEIs.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Microbiology
Borja Alonso-Lerma, Ylenia Jabalera, Sara Samperio, Matias Morin, Almudena Fernandez, Logan T. Hille, Rachel A. Silverstein, Ane Quesada-Ganuza, Antonio Reifs, Sergio Fernandez-Penalver, Yolanda Benitez, Lucia Soletto, Jose A. Gavira, Adrian Diaz, Wim Vranken, Avencia Sanchez-Mejias, Marc Guell, Francisco J. M. Mojica, Benjamin P. Kleinstiver, Miguel A. Moreno-Pelayo, Lluis Montoliu, Raul Perez-Jimenez
Summary: Research reveals that ancient Cas9 protein from extinct bacteria exhibit significant differences in guide RNA and protospacer-adjacent motif requirements compared to modern Cas9 enzymes. Additionally, these ancient Cas9 proteins evolved from nickase to double-strand break activity, have high activity with single-stranded DNA and RNA targets, and are capable of gene editing in human cells.
NATURE MICROBIOLOGY
(2023)
Article
Immunology
Mate G. Kiss, John E. Mindur, Abi G. Yates, Donghoon Lee, John F. Fullard, Atsushi Anzai, Wolfram C. Poller, Kathleen A. Christie, Yoshiko Iwamoto, Vladimir Roudko, Jeffrey Downey, Christopher T. Chan, Pacific Huynh, Henrike Janssen, Achilles Ntranos, Jan D. Hoffmann, Walter Jacob, Sukanya Goswami, Sumnima Singh, David Leppert, Jens Kuhle, Seunghee Kim-Schulze, Matthias Nahrendorf, Benjamin P. Kleinstiver, Fay Probert, Panos Roussos, Filip K. Swirski, Cameron S. McAlpine
Summary: Glial cells and central nervous system-infiltrating leukocytes play a role in multiple sclerosis (MS), and a network involving IL-3:IL-3RA promotes immune cell recruitment to the CNS, exacerbating MS. Astrocytes and infiltrating T cells produce IL-3, while microglia and myeloid cells express IL-3 receptors. IL3RA-expressing myeloid cells with chemotactic programming were found in MS plaques, and the expression of IL3RA and the level of IL-3 correlated with MS severity.
Article
Biotechnology & Applied Microbiology
Cole W. Peters, Killian S. Hanlon, Maryna Ivanchenko, Eric Zinn, Elizabeth F. Linarte, Yaqiao Li, Jonathan M. Levy, David R. Liu, Benjamin P. Kleinstiver, Artur A. Indzhykulian, David P. Corey
Summary: Usher syndrome type 1F (USH1F) is a genetic disorder characterized by congenital hearing and balance loss and progressive vision loss. This study shows that an adenine base editor (ABE) can reverse a specific mutation (R245X) in the PCDH15 gene, restoring its function and improving hearing in a mouse model of USH1F.
Article
Biochemistry & Molecular Biology
Young-hoon Kim, Nahye Kim, Ikenna Okafor, Sungchul Choi, Seonwoo Min, Joonsun Lee, Seung-Min Bae, Keunwoo Choi, Janice Choi, Vinayak Harihar, Youngho Kim, Jin-Soo Kim, Benjamin P. Kleinstiver, Jungjoon K. Lee, Taekjip Ha, Hyongbum Henry Kim
Summary: Researchers have developed an improved version of Sniper-Cas9, called Sniper2L, which combines high specificity with retained high activity for efficient and specific genome editing at a large number of target sequences.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Health Care Sciences & Services
Melissa Beaudoin, Stephane Potvin, Kingsada Phraxayavong, Alexandre Dumais
Summary: Avatar Therapy has a significant impact on symptoms, beliefs, and quality of life of treatment-resistant schizophrenia patients. Through semi-guided interviews and content analysis, it was found that patients experienced a reduction in psychotic symptoms, better self-esteem, increased hobbies and projects, and an overall improved lifestyle and mood after therapy. This research provides a deeper understanding of how Avatar Therapy can lead to meaningful changes and promote recovery for patients with treatment-resistant schizophrenia.
JOURNAL OF PERSONALIZED MEDICINE
(2023)
Article
Health Care Sciences & Services
Alexandre Hudon, Melissa Beaudoin, Kingsada Phraxayavong, Stephane Potvin, Alexandre Dumais
Summary: This study conducted unsupervised machine learning on the verbatims of psychotherapeutic interventions for individuals with treatment-resistant schizophrenia using avatar therapy. The findings showed that the interactions between the patients and avatars can be categorized into three clusters, providing quantitative insights into the inner interactions of this therapy method.
JOURNAL OF PERSONALIZED MEDICINE
(2023)
Article
Health Care Sciences & Services
Sabrina Giguere, Stephane Potvin, Melissa Beaudoin, Laura Dellazizzo, Charles-Edouard Giguere, Alexandra Furtos, Karine Gilbert, Kingsada Phraxayavong, Alexandre Dumais
Summary: Cannabis use disorder (CUD) is a complex issue, especially when co-occurring with a severe mental disorder (SMD). Virtual reality (VR) integration has the potential to increase efficacy in CUD treatment. A pilot clinical trial evaluated the short-term effectiveness of an avatar intervention for CUD. Results showed a significant reduction in cannabis use, indicating promising results for this unique intervention.
JOURNAL OF PERSONALIZED MEDICINE
(2023)
Article
Pharmacology & Pharmacy
Melissa Beaudoin, Laura Dellazizzo, Sabrina Giguere, Jean-Pierre Guay, Charles-Edouard Giguere, Stephane Potvin, Alexandre Dumais
Summary: Recent studies have shown a positive relationship between cannabis use and violence in people with severe mental disorders, but the dose-response relationship has been rarely investigated. This study aims to determine if such a relationship exists in a psychiatric population.
CANNABIS AND CANNABINOID RESEARCH
(2023)