Article
Multidisciplinary Sciences
Jason A. Estep, Lu O. Sun, Martin M. Riccomagno
Summary: Integrin Adhesion Complexes (IACs) act as links between the cytoskeleton and extracellular environment, participating in cellular motility, tissue morphogenesis, anchorage-dependent growth, and cell survival. Focal Adhesion Kinase (FAK) is a critical organizer of IAC signaling events and a genetic and therapeutic target. This study presents the design and characterization of reversible Bimolecular Complementation sensors to monitor FAK phosphorylation in living cells, providing novel means to quantify IAC signaling.
Review
Developmental Biology
Naoya Yamaguchi, Holger Knaut
Summary: Cell-extracellular matrix interactions are essential for cell anchoring and migration, with focal adhesions (FAs) playing a key role. However, the role of FAs in vivo is still not well understood.
Review
Cell Biology
Johanne Le Coq, Ivan Acebron, Barbara Rodrigo Martin, Pilar Lopez Navajas, Daniel Lietha
Summary: In this review, the authors discuss the role of focal adhesion kinase (FAK) in cell-matrix adhesion and migration. They highlight the known structural features of FAK and the challenges in understanding its integration in the focal adhesion complex and the structural changes during focal adhesion maturation.
JOURNAL OF CELL SCIENCE
(2022)
Review
Cell Biology
Yasaswi Gayatri Mishra, Bramanandam Manavathi
Summary: Cell-ECM adhesions, with integrins at their core, serve as a crucial link between the cell cytoskeleton and the extracellular matrix, playing a major role in cell signalling for mechanotransduction, migration, proliferation, and other cellular processes. The diverse integrin adhesion complexes, such as focal adhesions and invadosomes, are not only essential for normal cell survival and development, but also play significant roles in various pathological processes.
CELLULAR SIGNALLING
(2021)
Article
Biology
Yun Qi, Han Liu, Kang Zhang, Yihui Wu, Chenghao Shen, Xinhua Lin
Summary: This study reveals that Ihog proteins play crucial roles in integrin-mediated adhesions and regulate adhesion by interacting with integrins.
SCIENCE CHINA-LIFE SCIENCES
(2023)
Article
Oncology
Pulin Che, Lei Yu, Gregory K. Friedman, Meimei Wang, Xiaoxue Ke, Huafeng Wang, Wenbin Zhang, Burt Nabors, Qiang Ding, Xiaosi Han
Summary: The study investigates the role of integrin alpha v beta 3 engagement with its ligand in metabolic reprogramming in glioblastoma cells. It was found that integrin alpha v beta 3 increases glucose uptake and aerobic glycolysis, while decreasing mitochondrial oxidative phosphorylation. The interaction of integrin alpha v beta 3 with osteopontin plays a crucial role in promoting metabolic shift towards glycolysis and inhibiting mitochondrial oxidative phosphorylation, leading to changes in cell behavior such as migration and invasion.
Article
Food Science & Technology
Yajing Zhang, Yilei Guo, Qin Zhang, Yanrong Zhu, Yufeng Xia, Zhifeng Wei, Yue Dai
Summary: This study found that diallyl trisulfide (DATS) in garlic oil has a beneficial effect of promoting colonic mucosal healing. DATS can promote the migration of colonic epithelial cells and accelerate wound healing by promoting the binding of Rab21 to integrin beta 1 and the endocytosis of integrin beta 1.
MOLECULAR NUTRITION & FOOD RESEARCH
(2023)
Article
Hematology
Bal Krishan Sharma, Duaa Mureb, Sumit Murab, Leah Rosenfeldt, Brenton Francisco, Rachel Cantrell, Rebekah Karns, Lindsey Romick-Rosendale, Miki Watanabe-Chailland, Jacob Mast, Matthew J. Flick, Patrick W. Whitlock, Joseph S. Palumbo
Summary: The absence of fibrinogen in the tumor microenvironment leads to decreased proliferation and increased senescence in CRC tumors, along with differential expression of genes. Studies suggest that fibrinogen may promote colon cancer growth by regulating cellular proliferation and senescence pathways.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2021)
Review
Biochemistry & Molecular Biology
Xiao-Jing Pang, Xiu-Juan Liu, Yuan Liu, Wen-Bo Liu, Yin-Ru Li, Guang-Xi Yu, Xin-Yi Tian, Yan-Bing Zhang, Jian Song, Cheng-Yun Jin, Sai-Yang Zhang
Summary: FAK, a nonreceptor intracellular tyrosine kinase, is overexpressed in many human cancer cell lines, promoting tumor growth by controlling various cellular functions. Targeting FAK with small molecule inhibitors is considered a promising cancer therapy, with several FAK inhibitors undergoing clinical trials in different phases. Additionally, the development of novel FAK inhibitors, including FAK degraders through PROTAC technology, provides potential for new anticancer agents.
Article
Oncology
Di Ye, Huanji Xu, Hongwei Xia, Chenliang Zhang, Qiulin Tang, Feng Bi
Summary: This study elucidated a novel mechanism in colon cancer involving targeting the serotonin transporter to promote the uptake and catabolism of extracellular tryptophan, leading to serotonin biosynthesis and production of oncogenic metabolites. Inhibition of serotonin transporter induced a compensatory effect by promoting tryptophan uptake and catabolism, ultimately enhancing the anti-tumor effects of selective serotonin reuptake inhibitors.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2021)
Article
Cell Biology
Caihua Dong, Xinying Li, Jiao Yang, Detian Yuan, Yuanshuai Zhou, Yina Zhang, Guohua Shi, Ruobing Zhang, Jianping Liu, Peng Fu, Minxuan Sun
Summary: High expression of PPFIBP1 is associated with enhanced invasion and poor prognosis in GBM patients, promoting cell invasion and migration by regulating differential gene clusters involved in Wnt and adhesion-related signaling pathways. PPFIBP1 activates FAK, Src, JNK, and c-Jun to enhance MMP-2 expression, and inhibiting phosphorylation of Src and FAK reverses PPFIBP1-induced invasion and migration in GBM cells.
CELL DEATH & DISEASE
(2021)
Article
Food Science & Technology
Hui-jian Chen, Xi-yue Yan, Ao Sun, Li Zhang, Jing Zhang, You-E Yan
Summary: This study discovers that high-fat-diet-induced extracellular matrix (ECM) deposition promotes adipogenesis by transmitting signals to adipocytes. Glucose and lipid metabolic disorders and upregulation of ECM-related signaling pathways are observed in obese mice and humans. Furthermore, the study finds that these signaling pathways are stronger in subcutaneous adipose tissue than in visceral adipose tissue in mice, but the opposite is observed in humans.
MOLECULAR NUTRITION & FOOD RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Lin Cao, Yurong Wu, Xiuxiu Wang, Xiang Li, Zengqi Tan, Feng Guan
Summary: The deletion of N-glycosylation sites on the I-like domain of integrin beta 1 affects cell migration, adhesion, and signaling, while the Delta 4-6 beta 1 mutant can regulate integrin-mediated functions in recipient cells via small extracellular vesicles (sEVs).
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Clinical Neurology
Hae Nim Lee, Seung Jae Hyeon, Heejung Kim, Kyoung Mi Sim, Yunha Kim, Jeongmin Ju, Junghee Lee, Yingxiao Wang, Hoon Ryu, Jihye Seong
Summary: In Huntington's disease, reduced FAK and FA dynamics impair the formation of neurites, leading to synaptic dysfunctions. Mutant HTT associates with phosphatidylinositol 4,5-biphosphate, altering its distribution at the plasma membrane and inhibiting FAK activation.
ACTA NEUROPATHOLOGICA
(2022)
Review
Pharmacology & Pharmacy
Sheng Chen, Tailin He, Yiming Zhong, Mingjue Chen, Qing Yao, Di Chen, Zengwu Shao, Guozhi Xiao
Summary: The skeletal system plays crucial roles in body shaping, support and movement, protection of internal organs, production of blood cells, and regulation of calcium and phosphate metabolism. Skeletal diseases and disorders such as osteoporosis, arthritis, and intervertebral disc degeneration are becoming increasingly common and have significant social and economic impacts. This review focuses on the molecular mechanisms and therapeutic targets of focal adhesion proteins in skeletal diseases.
ACTA PHARMACEUTICA SINICA B
(2023)
Article
Biochemical Research Methods
Rebecca Irlmeier, Jacob J. Hughey, Lisa Bastarache, Joshua C. Denny, Qingxia Chen
Summary: This study compared the performance of Cox regression and various logistic regression models under delayed event time. The results showed that logistic regression models were more sensitive to delayed event time, while Cox regression models had similar or modest improvement in controlling type I error.
Editorial Material
Medicine, General & Internal
Lisa Bastarache, Joshua C. Denny, Dan M. Roden
Summary: This article discusses the concept and methodology of phenome-wide association studies, which aim to identify associations between genetic variations and phenotypic traits using a dataset.
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
(2022)
Article
Biotechnology & Applied Microbiology
Yen-Chen A. Feng, Ian B. Stanaway, John J. Connolly, Joshua C. Denny, Yuan Luo, Chunhua Weng, Wei-Qi Wei, Scott T. Weiss, Elizabeth W. Karlson, Jordan W. Smoller
Summary: This study evaluated the burden of rare variations in ACMG-56 genes and two psychiatric-associated genes in individuals of European descent and found that there is no association between incidental findings in medically actionable gene mutations and psychiatric disorders.
Article
Public, Environmental & Occupational Health
Shuai Yuan, Lijuan Wang, Jing Sun, Lili Yu, Xuan Zhou, Jie Yang, Yimin Zhu, Dipender Gill, Stephen Burgess, Joshua C. Denny, Susanna C. Larsson, Evropi Theodoratou, Xue Li
Summary: This study used Mendelian randomization to investigate the associations between sex hormone binding globulin (SHBG), testosterone, and estradiol levels and disease outcomes. The results suggest a causal relationship between sex hormones and several health outcomes.
INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
(2022)
Article
Clinical Neurology
E. Singer, M. Niarchou, A. Maxwell-Horn, D. Hucks, R. Johnston, J. S. Sutcliffe, L. K. Davis, B. A. Malow
Summary: This study reviewed a detailed approach to querying sleep problems using electronic health records in a large healthcare center, and found that sleep issues are common in individuals on the autism spectrum. The use of specific keywords in the query structure may be beneficial for future research.
Article
Cardiac & Cardiovascular Systems
Tinuola B. Ajayi, Adrienne L. Mueller, Ike S. Okwuosa, Asha Barshilia, Joseph C. Wu, Emelia J. Benjamin, Joey Barnett, Kendra H. Oliver
Summary: This article describes the initial formation of the American Heart Association's Supporting Undergraduate Research Experiences program and the adjustments made in response to COVID-19 safety precautions. The study found that both in-person and virtual programs resulted in significant improvements in students' scientific proficiency, with the virtual training providing extensive benefits. The authors also summarize the pros and cons of in-person and virtual programming and offer recommendations for future training programs in a postpandemic world with hybrid work and learning systems.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2022)
Article
Oncology
Chenjie Zeng, Lisa A. Bastarache, Ran Tao, Eric Venner, Scott Hebbring, Justin D. Andujar, Sarah T. Bland, David R. Crosslin, Siddharth Pratap, Ayorinde Cooley, Jennifer A. Pacheco, Kurt D. Christensen, Emma Perez, Carrie L. Blout Zawatsky, Leora Witkowski, Hana Zouk, Chunhua Weng, Kathleen A. Leppig, Patrick M. A. Sleiman, Hakon Hakonarson, Marc. S. Williams, Yuan Luo, Gail P. Jarvik, Robert C. Green, Wendy K. Chung, Ali G. Gharavi, Niall J. Lennon, Heidi L. Rehm, Richard A. Gibbs, Josh F. Peterson, Dan M. Roden, Georgia L. Wiesner, Joshua C. Denny
Summary: This study utilized large datasets from three cohorts to identify associations between hereditary cancer genes and various phenotypes, highlighting the potential benefits of early detection and better management of cancer.
Article
Genetics & Heredity
Maria Niarchou, Julia M. Sealock, Peter Straub, Sandra Sanchez-Roige, James S. Sutcliffe, Lea K. Davis
Summary: Testing the association between genetic scores for Attention Deficit Hyperactivity Disorder (ADHD) and health conditions can provide insights into the complex etiology of ADHD. This study found that genetic scores for ADHD were associated with ADHD diagnoses early in life and with a range of health conditions throughout the lifespan. The results highlight the importance of considering genetic factors when studying clinical conditions.
AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS
(2022)
Article
Clinical Neurology
Olivia J. Veatch, Diego R. Mazzotti, Robert T. Schultz, Ted Abel, Jacob J. Michaelson, Edward S. Brodkin, Birkan Tunc, Susan G. Assouline, Thomas Nickl-Jockschat, Beth A. Malow, James S. Sutcliffe, Allan Pack
Summary: By analyzing genetic variations associated with autism spectrum disorder (ASD) and sleep disturbances, this study found that individuals with ASD who accumulate potentially damaging genetic variants are more likely to experience sleep duration problems. Specifically, dysfunction in the development of the cerebral cortex may disrupt sleep homeostasis, which is regulated by this brain region.
JOURNAL OF NEURODEVELOPMENTAL DISORDERS
(2022)
Article
Multidisciplinary Sciences
Xinyuan Zhang, Anastasia M. Lucas, Yogasudha Veturi, Theodore G. Drivas, William P. Bone, Anurag Verma, Wendy K. Chung, David Crosslin, Joshua C. Denny, Scott Hebbring, Gail P. Jarvik, Iftikhar Kullo, Eric B. Larson, Laura J. Rasmussen-Torvik, Daniel J. Schaid, Jordan W. Smoller, Ian B. Stanaway, Wei-Qi Wei, Chunhua Weng, Marylyn D. Ritchie
Summary: Clinical and epidemiological studies have shown that circulatory system diseases and nervous system disorders often co-occur in patients. In this study, the authors used data from eMERGE and UK BioBank to identify genomic regions associated with both phenotypes, providing insight into the relationship between these conditions.
NATURE COMMUNICATIONS
(2022)
Article
Genetics & Heredity
Jack M. Fu, F. Kyle Satterstrom, Minshi Peng, Harrison Brand, Ryan L. Collins, Shan Dong, Brie Wamsley, Lambertus Klei, Lily Wang, Stephanie P. Hao, Christine R. Stevens, Caroline Cusick, Mehrtash Babadi, Eric Banks, Brett Collins, Sheila Dodge, Stacey B. Gabriel, Laura Gauthier, Samuel K. Lee, Lindsay Liang, Alicia Ljungdahl, Behrang Mahjani, Laura Sloofman, Andrey N. Smirnov, Mafalda Barbosa, Catalina Betancur, Alfredo Brusco, Brian H. Y. Chung, Edwin H. Cook, Michael L. Cuccaro, Enrico Domenici, Giovanni Battista Ferrero, J. Jay Gargus, Gail E. Herman, Irva Hertz-Picciotto, Patricia Maciel, Dara S. Manoach, Maria Rita Passos-Bueno, Antonio M. Persico, Alessandra Renieri, James S. Sutcliffe, Flora Tassone, Elisabetta Trabetti, Gabriele Campos, Simona Cardaropoli, Diana Carli, Marcus C. Y. Chan, Chiara Fallerini, Elisa Giorgio, Ana Cristina Girardi, Emily Hansen-Kiss, So Lun Lee, Carla Lintas, Yunin Ludena, Rachel Nguyen, Lisa Pavinato, Margaret Pericak-Vance, Isaac N. Pessah, Rebecca J. Schmidt, Moyra Smith, Claudia I. S. Costa, Slavica Trajkova, Jaqueline Y. T. Wang, Mullin H. C. Yu, David J. Cutler, Silvia De Rubeis, Joseph D. Buxbaum, Mark J. Daly, Bernie Devlin, Kathryn Roeder, Stephan J. Sanders, Michael E. Talkowski
Summary: This study investigated genes associated with functional mutations in individuals with autism spectrum disorder (ASD) and found that some of these genes are also associated with developmental delay (DD). The findings suggest that ASD and DD may share common pathological pathways.
Article
Genetics & Heredity
Kazuyoshi Ishigaki, Saori Sakaue, Chikashi Terao, Yang Luo, Kyuto Sonehara, Kensuke Yamaguchi, Tiffany Amariuta, Chun Lai Too, Vincent A. Laufer, Ian C. Scott, Sebastien Viatte, Meiko Takahashi, Koichiro Ohmura, Akira Murasawa, Motomu Hashimoto, Hiromu Ito, Mohammed Hammoudeh, Samar Al Emadi, Basel K. Masri, Hussein Halabi, Humeira Badsha, Imad W. Uthman, Xin Wu, Li Lin, Ting Li, Darren Plant, Anne Barton, Gisela Orozco, Suzanne M. M. Verstappen, John Bowes, Alexander J. MacGregor, Suguru Honda, Masaru Koido, Kohei Tomizuka, Yoichiro Kamatani, Hiroaki Tanaka, Eiichi Tanaka, Akari Suzuki, Yuichi Maeda, Kenichi Yamamoto, Satoru Miyawaki, Gang Xie, Jinyi Zhang, Christopher Amos, Edward Keystone, Gertjan Wolbink, Irene Van der Horst-Bruinsma, Jing Cui, Katherine P. Liao, Robert J. Carroll, Hye-Soon Lee, So-Young Bang, Katherine A. Siminovitch, Niek de Vries, Lars Alfredsson, Solbritt Rantapaa-Dahlqvist, Elizabeth W. Karlson, Sang-Cheol Bae, Robert P. Kimberly, Jeffrey C. Edberg, Xavier Mariette, Tom Huizinga, Philippe Dieude, Matthias Schneider, Martin Kerick, Joshua C. Denny, Koichi Matsuda, Keitaro Matsuo, Tsuneyo Mimori, Fumihiko Matsuda, Keishi Fujio, Yoshiya Tanaka, Atsushi Kumanogoh, Matthew Traylor, Cathryn M. Lewis, Stephen Eyre, Huji Xu, Richa Saxena, Thurayya Arayssi, Yuta Kochi, Katsunori Ikari, Masayoshi Harigai, Peter K. Gregersen, Kazuhiko Yamamoto, S. Louis Bridges, Leonid Padyukov, Javier Martin, Lars Klareskog, Yukinori Okada, Soumya Raychaudhuri
Summary: This study conducted multi-ancestry genome-wide association analyses and identified 124 risk loci for rheumatoid arthritis, of which 34 are novel. The fine-mapping analysis revealed potential causal variants and improved the genetic predictability of rheumatoid arthritis.
Article
Endocrinology & Metabolism
Jamie R. Robinson, Robert J. Carroll, Lisa Bastarache, Qingxia Chen, James Pirruccello, Zongyang Mou, Wei-Qi Wei, John Connolly, Frank Mentch, Paul K. Crane, Scott J. Hebbring, David R. Crosslin, Adam S. Gordon, Elisabeth A. Rosenthal, Ian B. Stanaway, M. Geoffrey Hayes, Wei Wei, Lynn Petukhova, Bahram Namjou-Khales, Ge Zhang, Mayya S. Safarova, Nephi A. Walton, Christopher Still, Erwin P. Bottinger, Ruth J. F. Loos, Shawn N. Murphy, Gretchen P. Jackson, Naji Abumrad, Iftikhar J. Kullo, Gail P. Jarvik, Eric B. Larson, Chunhua Weng, Dan Roden, Amit V. Khera, Joshua C. Denny
Summary: This study used a genome- and phenome-wide approach to elucidate the overall clinical risk of obesity, and found strong associations between obesity and multiple diseases.
Correction
Multidisciplinary Sciences
Lili Liu, Atlas Khan, Elena Sanchez-Rodriguez, Francesca Zanoni, Yifu Li, Nicholas Steers, Olivia Balderes, Junying Zhang, Priya Krithivasan, Robert A. LeDesma, Clara Fischman, Scott J. Hebbring, John B. Harley, Halima Moncrieffe, Leah C. Kottyan, Bahram Namjou-Khales, Theresa L. Walunas, Rachel Knevel, Soumya Raychaudhuri, Elizabeth W. Karlson, Joshua C. Denny, Ian B. Stanaway, David Crosslin, Thomas Rauen, Juergen Floege, Frank Eitner, Zina Moldoveanu, Colin Reily, Barbora Knoppova, Stacy Hall, Justin T. Sheff, Bruce A. Julian, Robert J. Wyatt, Hitoshi Suzuki, Jingyuan Xie, Nan Chen, Xujie Zhou, Hong Zhang, Lennart Hammarstroem, Alexander Viktorin, Patrik K. E. Magnusson, Ning Shang, George Hripcsak, Chunhua Weng, Tatjana Rundek, Mitchell S. V. Elkind, Elizabeth C. Oelsner, R. Graham Barr, Iuliana Ionita-Laza, Jan Novak, Ali G. Gharavi, Krzysztof Kiryluk
NATURE COMMUNICATIONS
(2023)
Article
Pharmacology & Pharmacy
Shaopeng Gu, Govarthanan Rajendiran, Kennedy Forest, Tam C. C. Tran, Joshua C. C. Denny, Eric A. A. Larson, Russell A. A. Wilke
Summary: This study used retrospective analysis of clinical data from the All of Us database to identify cases of drug-induced liver injury (DILI) related to the use of common antibiotics. The results showed that amoxicillin-clavulanate was the most common cause of DILI among the study participants. The findings highlight the efficiency of mining data from electronic health record-linked research cohorts to identify DILI cases associated with the use of common antibiotics.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)