Article
Multidisciplinary Sciences
Xiuxiu Lu, Venkata R. Sabbasani, Vasty Osei-Amponsa, Christine N. Evans, Julianna C. King, Sergey G. Tarasov, Marzena Dyba, Sudipto Das, King C. Chan, Charles D. Schwieters, Sulbha Choudhari, Caroline Fromont, Yongmei Zhao, Bao Tran, Xiang Chen, Hiroshi Matsuo, Thorkell Andresson, Raj Chari, Rolf E. Swenson, Nadya I. Tarasova, Kylie J. Walters
Summary: The authors have identified and characterized XL5, a lead compound that binds to the N-terminal Pru domain of human Rpn13 (hRpn13), solved the NMR structure of XL5-ligated hRpn13 Pru, and developed XL5-PROTACs that preferentially target an identified hRpn13 Pru fragment present in multiple myeloma cells.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Patricia G. Santamaria, Pierre Dubus, Jose Bustos-Tauler, Alfredo Floristan, Alberto Vazquez-Naharro, Saleta Morales, Amparo Cano, Francisco Portillo
Summary: This study found that the lack of LOXL3 leads to perinatal lethality and abnormal skeletal development in mice, and LOXL2 and LOXL3 may have overlapping functions during mouse development. The widespread expression of LOXL2 can suppress the lethality associated with LOXL3 knockout mice.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Jijun Yu, Xinying Li, Junxia Cao, Ting Zhu, Shuifeng Liang, Le Du, Meng Cao, Haitao Wang, Yaolin Zhang, Yinxi Zhou, Beifen Shen, Jiannan Feng, Jiyan Zhang, Jing Wang, Jianfeng Jin
Summary: The study found that JNK1/2 and MKK7 levels were significantly upregulated in HCC samples compared to paracarcinoma tissues, whereas MKK4 was downregulated. ROC analysis suggested that JNK2 and MKK7 may serve as suitable diagnostic genes for HCC, and targeting MKK7 may be a promising therapeutic strategy in HCC therapy.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Vasty Osei-Amponsa, Kylie J. Walters
Summary: The ubiquitin-proteasome system (UPS) plays a critical role in protein quality control and regulation of protein lifespans. This article provides an overview of UPS, focusing on its receptors and deubiquitinating enzymes (DUBs). The importance of dynamics and the presence of functional domains in substrate receptors for binding and processing ubiquitin chains are highlighted. The UPS offers therapeutic opportunities, including the use of proteasome inhibitors and the development of PROTACs for degrading disease-associated proteins. The therapeutic potential of proteasome receptors, such as hRpn13, is discussed.
TRENDS IN BIOCHEMICAL SCIENCES
(2022)
Review
Cell Biology
Emily Fisher, Jian Feng
Summary: Alternative RNA splicing increases transcript diversity and is regulated by RNA splicing regulators (RSRs), primarily involved in neurogenesis. Nine families of RSRs play essential roles in neural development, providing novel insights into the role of splicing in brain development and health.
WILEY INTERDISCIPLINARY REVIEWS-RNA
(2022)
Article
Biotechnology & Applied Microbiology
Chang Liu, Xiya Zhu, Jin Zhang, Meng Shen, Kai Chen, Xiangkui Fu, Lian Ma, Xuelin Liu, Chang Zhou, Dao-Xiu Zhou, Gongwei Wang
Summary: The regulation of gene expression is crucial for plant phenotype and adaptation. In this study, transcriptome sequencing was used to identify exonic variants and quantify gene expression in 287 rice accessions. Genome-wide association study identified numerous expression quantitative trait loci (eQTLs), both local and distant hotspots. A transcriptome-wide association study further screened candidate genes for starch content regulation. The key regulator bHLH026 was found to enhance diterpenoid antitoxin synthesis and disease resistance in rice. These findings contribute to a better understanding of gene expression regulation and complex regulatory networks in the rice genome.
PLANT BIOTECHNOLOGY JOURNAL
(2022)
Article
Cell Biology
Deepa Kumari, Edward A. Fisher, Jeffrey L. Brodsky
Summary: This study reveals the roles of Hsp40 molecular chaperones in the synthesis and degradation of ApoB. Among them, class A ER-associated Hsp40 Ydj1 is involved in the degradation of ApoB, while class B Hsp40 DNAJB1 helps stabilize ApoB.
MOLECULAR BIOLOGY OF THE CELL
(2022)
Review
Cell Biology
Nancy B. Schwartz, Miriam S. Domowicz
Summary: The extracellular matrix (ECM) plays a crucial role in cellular processes, regulating cell phenotypes through bidirectional signaling with small molecules and providing biochemical and contextual information. Cells can also reshape the ECM to alter their environments.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Immunology
Yueman Zhang, Yunlu Guo, Ruqi Li, Tingting Huang, Yan Li, Wanqin Xie, Chen Chen, Weijie Chen, Jieqing Wan, Weifeng Yu, Peiying Li
Summary: Using single-cell RNA sequencing, researchers identified two microglia subclusters, CH25H(+) and OASL(+), that play important roles in ischemic stroke. CH25H(+) microglia exhibits increased phagocytosis and neuroprotective properties, while OASL(+) microglia is associated with neuroinflammation.
JOURNAL OF NEUROINFLAMMATION
(2023)
Article
Biochemical Research Methods
Lennart van der Wal, Karel Bezstarosti, Jeroen A. A. Demmers
Summary: This study investigated the specificities and functional roles of proteasome associated DUBs using quantitative ubiquitinomics. The results showed distinct effects on the global ubiquitinome upon removal of USP14 or UCH37, suggesting less functional redundancy than previously anticipated. The study also questioned the alleged specificity of the small molecule inhibitor b-AP15 due to its broad and severe off-target effects.
JOURNAL OF PROTEOMICS
(2022)
Article
Multidisciplinary Sciences
Bo Liang, Lifeng Zhang, Yan Zhang, Craig T. Werner, Nicholas J. Beacher, Alex J. Denman, Yun Li, Rong Chen, Charles R. Gerfen, Giovanni Barbera, Da-Ting Lin
Summary: The dorsal striatum plays a crucial role in movement control and motor skill learning. This study explores how the medium spiny neurons (MSNs) in the direct and indirect pathways of the striatum encode motor skill learning. By combining miniature fluorescence microscopy and an accelerating rotarod procedure, the researchers identified two distinct subpopulations of MSNs involved in accelerating rotarod learning. They found that early-stage neurons in both the D1 and D2 MSNs displayed activity tuned to acceleration during early stages of trials and movement speed during late stages of trials. The evolution of D1 MSNs correlated strongly with performance improvement, and inhibiting early-stage neural activity in D1 MSNs impaired accelerating rotarod learning.
Review
Genetics & Heredity
Brian DeVeale, Jennifer Swindlehurst-Chan, Robert Blelloch
Summary: MiRNAs play crucial regulatory roles in mouse development by negatively regulating multiple mRNA targets. They coordinate cell fate transitions during development and contribute to organismal fitness through homeostatic roles in adults. Recent advances in miRNA-knockout phenotypes and related targets, dosage, and interactions have enhanced our understanding of their roles in mammalian development and adaptive responses.
NATURE REVIEWS GENETICS
(2021)
Article
Biochemistry & Molecular Biology
Andrew C. Marshall, Jerry Cummins, Simon Kobelke, Tianyi Zhu, Jocelyn Widagdo, Victor Anggono, Anthony Hyman, Archa H. Fox, Charles S. Bond, Mihwa Lee
Summary: Demixing of proteins and nucleic acids into condensed liquid phases is a common mechanism in cellular organization. Proteins with low sequence complexity often form liquid-like condensates. RNA-binding proteins with prion-like regions drive condensate formation, but this study finds that the longer prion-like region of SFPQ attenuates condensation, serving a regulatory role in preventing aberrant condensate formation.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Article
Cardiac & Cardiovascular Systems
Michael Warkala, Dongying Chen, AnnJosette Ramirez, Ali Jubran, Michael Schonning, Xia Wang, Huaning Zhao, Sophie Astrof
Summary: The development of the fourth pharyngeal arch arteries involves a multistep process with contributions from SHF-derived ECs, remodeling of endothelial plexus into PAAs, and remodeling of PAAs into the aortic arch artery and its major branches. Cell-ECM interactions regulated by integrin alpha 5 beta 1 and Fn1 are essential at each developmental stage.
CIRCULATION RESEARCH
(2021)
Article
Oncology
Yingying Luo, Danfang Deng, Lamei Lin, Yikun Zhou, Lan Wang, Xinrong Zou, Xiaoqin Wang
Summary: This study found that different isoforms of FGF2 played different roles in EMT in diabetic nephropathy, with LMW FGF2 promoting the process and HMW FGF2 exerting a protective effect.
EXPERIMENTAL CELL RESEARCH
(2022)
Article
Pathology
Heather Tillman, Laura J. Janke, Amy Funk, Peter Vogel, Jerold E. Rehg
VETERINARY PATHOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Fahad Zadjali, Prashant Kumar, Ying Yao, Daniel Johnson, Aristotelis Astrinidis, Peter Vogel, Kenneth W. Gross, John J. Bissler
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Immunology
R. K. Subbarao Malireddi, Prajwal Gurung, Sannula Kesavardhana, Parimal Samir, Amanda Burton, Harisankeerth Mummareddy, Peter Vogel, Stephane Pelletier, Sandeepta Burgula, Thirumala-Devi Kanneganti
JOURNAL OF EXPERIMENTAL MEDICINE
(2020)
Correction
Multidisciplinary Sciences
Benoit Briard, Thierry Fontaine, Parimal Samir, David E. Place, Laetitia Muszkieta, R. K. Subbarao Malireddi, Rajendra Karki, Shelbi Christgen, Perrine Bomme, Peter Vogel, Remi Beau, Emilia Mellado, Oumaima Ibrahim-Granet, Bernard Henrissat, Ravi C. Kalathur, Cam Robinson, Jean-Paul Latge, Thirumala-Devi Kanneganti
Article
Multidisciplinary Sciences
David E. Place, R. K. Subbarao Malireddi, Jieun Kim, Peter Vogel, Masahiro Yamamoto, Thirumala-Devi Kanneganti
Summary: This study reveals that IFN and IFN-induced guanylate-binding proteins play important roles in regulating bone immunology, contributing to limiting inflammatory and age-associated bone loss.
NATURE COMMUNICATIONS
(2021)
Article
Oncology
Sarang Tartey, Geoffrey Neale, Peter Vogel, R. K. Subbarao Malireddi, Thirumala-Devi Kanneganti
Summary: Macrophages play critical roles in tissue homeostasis, cell proliferation, and tumor metastasis. Tumor-associated macrophages (TAM) are known for their immunosuppressive functions in solid tumors, with MYD88 playing a key role in tumor progression. Targeting the MYD88/IL1 receptor axis could potentially enhance anti-tumor effects in a variety of cancers through regulating immune responses.
Article
Hematology
Meghan E. Turnis, Ewa Kaminska, Kaitlyn H. Smith, Brittany J. Kartchner, Peter Vogel, Jonathan D. Laxton, Richard A. Ashmun, Paul A. Ney, Joseph T. Opferman
Summary: Deletion of erythroid-specific Mcl1 results in embryonic lethality due to severe anemia caused by lack of mature red blood cells. MCL-1 is required only during early definitive erythropoiesis, with developing erythrocytes becoming MCL-1 independent and upregulating BCL-xL expression during later stages.
Article
Immunology
Min Zheng, Rajendra Karki, Evan Peter Williams, Dong Yang, Elizabeth Fitzpatrick, Peter Vogel, Colleen Beth Jonsson, Thirumala-Devi Kanneganti
Summary: The study revealed that the envelope protein of SARS-CoV-2 is sensed by TLR2, leading to the production of inflammatory cytokines, and the severity of the disease is associated with the expression of TLR2 and MYD88. The findings demonstrate the critical role of TLR2 signaling in promoting proinflammatory cytokine production during coronavirus infection, providing new insights for therapeutic strategies against the ongoing COVID-19 pandemic.
Article
Pathology
Peter Vogel, Robert W. Read, Gwenn M. Hansen, David R. Powell
Summary: The development of mouse models that replicate the genetic and pathological features of human disease is crucial for preclinical research, as they allow for meaningful pharmacokinetic, safety, and efficacy studies. Histopathology is important in identifying specific phenotypic traits that may not be detected by other physiological or behavioral screening tests. Its inclusion in phenotype screening protocols can help uncover novel genetic myopathies that may be clinically silent or missed by traditional screening methods.
VETERINARY PATHOLOGY
(2021)
Article
Virology
Yi Xue, Dong Yang, Peter Vogel, Jennifer Stabenow, Lillian Zalduondo, Ying Kong, Yazhini Ravi, Chittoor B. Sai-Sudhakar, Jyothi Parvathareddy, Ernestine Hayes, Shannon Taylor, Elizabeth Fitzpatrick, Colleen B. Jonsson
Summary: The Syrian hamster has been proven to be a useful model for evaluating the treatment and vaccines of SARS-CoV-2. The evaluation of lung histopathology scores at 4 dpi and 8 dpi showed that these time points are prime indicators for assessing moderate lung pathology, including bronchial hyperplasia, alveolar involvement, and bronchiolization. Furthermore, early infection in the hamsters led to increased neutrophil levels, red blood cell count, and hematocrit. The examination also revealed severe damage to the pulmonary vasculature, suggesting endothelialitis as a possible determinant of the pathological findings along with the host inflammatory response. In addition, the pathological examination of the heart showed evidence of intracardiac platelet/fibrin aggregates, indicating a hypercoagulative state in the infected hamsters.
Article
Immunology
Brianna L. Bullard, Jennifer DeBeauchamp, Matthew J. Pekarek, Erika Petro-Turnquist, Peter Vogel, Richard J. Webby, Eric A. Weaver
Summary: There is a critical need for an improved H3N2 influenza virus vaccine due to low efficacy rates and increased morbidity and mortality associated with H3N2-dominated influenza seasons. In this study, a computational design strategy was used to create epitope-optimized, broadly cross-reactive H3 hemagglutinins for a universal H3N2 influenza vaccine. The results showed that the Epigraph vaccine induced stronger cross-reactive antibody responses and T-cell immunity compared to the traditional egg-based vaccine, providing higher protection against a wide range of H3N2 strains.
Letter
Oncology
Fabienne R. S. Adriaanse, Jennifer L. Kamens, Peter Vogel, Sadie M. Sakurada, Shondra M. Pruett-Miller, Ronald W. Stam, C. Michel Zwaan, Tanja A. Gruber
Article
Genetics & Heredity
Eric P. Rahrmann, David Shorthouse, Amir Jassim, Linda P. Hu, Mariaestela Ortiz, Betania Mahler-Araujo, Peter Vogel, Marta Paez-Ribes, Atefeh Fatemi, Gregory J. Hannon, Radhika Iyer, Jay A. Blundon, Filipe C. Lourenco, Jonathan Kay, Rosalynn M. Nazarian, Benjamin A. Hall, Stanislav S. Zakharenko, Douglas J. Winton, Liqin Zhu, Richard J. Gilbertson
Summary: The ion channel NALCN has been identified as a key regulator of cancer metastasis and nonmalignant cell dissemination, even in the absence of oncogenic mutations, allowing normal structures to form at secondary sites. This finding uncovers a potential new target for antimetastatic therapies.
Article
Pathology
Jerrold M. Ward, Peter Vogel, John P. Sundberg
Summary: This study describes the histopathological findings of brain and spinal cord in 20-month-old mice from 28 inbred Jackson Laboratory mouse strains. Common lesions include axonal dystrophy in the sensory tract of the dorsal medulla and mineralization in the thalamus. Most strains showed evidence of impairment of the ubiquitin-proteasome system and/or suspected autophagy.
VETERINARY PATHOLOGY
(2022)
Article
Multidisciplinary Sciences
Lalita Mazgaeen, Matthew Yorek, Saurabh Saini, Peter Vogel, David K. Meyerholz, Thirumala-Devi Kanneganti, Prajwal Gurung
Summary: Mice with a specific amino acid substitution in SHP1 protein (Ptpn6(spin) mice) develop an autoinflammatory disease. When Ptpn6(spin) bone marrow cells are transferred into Cd47-deficient mice, marked weight loss and death occur. The study suggests that gut leakage caused by pathogenic neutrophils may contribute to the morbidity and mortality in Cd47(-/-) mice receiving Ptpn6(spin) cells. IL-1 blockade with anakinra can rescue the disease phenotype.