Article
Biochemistry & Molecular Biology
Liang Ma, Zeyue Gao, Jiegen Wu, Bijunyao Zhong, Yuchen Xie, Wen Huang, Yihan Lin
Summary: The coactivator p300 can dynamically coordinate its functions by forming clusters with transcription factors, enabling spatially defined activation of its catalytic activity. This co-condensation mechanism modulates the transcriptional initiation rate and burst duration of target genes, contributing to nonlinear gene regulation. The results suggest a mechanism where TF and p300 co-condensation contributes to transcriptional bursting regulation and cooperative gene control.
Article
Chemistry, Medicinal
Ilaria Salutari, Amedeo Caflisch
Summary: The control of transcriptional coactivators is critical for gene expression. Molecular dynamics simulations reveal that the autoinhibitory loop of CBP is not stable and cannot bind to the bromodomain. This finding indicates the weak binding of AIL compared to a natural ligand.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Review
Oncology
Jiacheng Lai, Ziqiang Liu, Yulei Zhao, Chengyuan Ma, Haiyan Huang
Summary: I-BET151, an inhibitor of BET proteins, demonstrates potential in cancer treatment by affecting cell cycle, signaling pathways, tumor microenvironment, and telomere elongation. Combination with other drugs can alleviate drug resistance, and even induce cell reprogramming without passing through pluripotent state. Research on I-BET151's anticancer mechanism may lead to new clinical strategies.
FRONTIERS IN ONCOLOGY
(2021)
Article
Medicine, Research & Experimental
Zude Chen, Riwei Yang, Yulong Xu, Leqi Liang, Shan Ao, Zuomin Wang, Ping Bai, Di Gu, Xiaolu Duan, Yongda Liu, Wen Zhong, Peng Xu, Tuo Deng, Guohua Zeng, Changning Wang
Summary: Alcoholic liver disease (ALD) is a major cause of liver disease mortality and has a significant impact on human health. Early and accurate diagnosis of ALD is crucial as the early stage of the disease can be reversible. Currently, there is no imaging technique that is sufficient for the diagnosis of early-stage ALD. Epigenetic modulation plays a significant role in the development and progression of ALD. This study evaluated the role of BET proteins in early-stage ALD using a new PET imaging probe called [C-11]CW22. The results showed that [C-11]CW22 PET/CT imaging can detect early-phase alcohol-induced damage in the liver and brain.
MOLECULAR PHARMACEUTICS
(2022)
Article
Biochemistry & Molecular Biology
Pooja Badhwar, Sabab Hasan Khan, Bhupesh Taneja
Summary: Oligoribonucleases (Orns) play a critical role in the degradation of cyclic-di-GMP (c-di-GMP) in bacteria. This study presents the crystal structure of a unique Orn, MSMEG_4724, from Mycobacterium smegmatis. The extended C-terminal tail of MSMEG_4724 is found to enhance dimerization and increase stability of the enzyme, while also modulating the response to stress agents in vivo. These findings contribute to a better understanding of the signaling and regulation by c-di-GMP in mycobacteria.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Jack A. Brown, Joanne Bal, Monica Simeoni, Peter Williams, Palwinder K. Mander, Peter E. Soden, Shruti Daga, William A. Fahy, Gabriel K. Wong, Jackie C. Bloomer, Lars Erwig, Yi Cui, Disala Fernando, Helen Carnaghan, Edward J. Banham-Hall, Sarah Hopkins, Bill G. Davis, Joao J. D. Oliveira, Rabinder K. Prinjha
Summary: Single doses of GSK3358699 are generally well tolerated in healthy male participants with significant metabolite concentrations detected in target cells. However, a complete assessment of pharmacodynamics was limited by assay variability. A causal relationship could not be excluded for cardiac-related adverse events, resulting in an inability to identify a suitable repeat-dose regimen and study termination.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Xiawei Huang, Hongmiao Hu, Alexandre Webster, Fan Zou, Jiamu Du, Katalin Fejes Toth, Alexei A. Aravin, Sisi Li, Dinshaw J. Patek, Ravi Sachidanandam
Summary: PIWI proteins use piRNAs to repress transposons and protect genomic integrity of gametes, ensuring fertility. Post-translational modification of Aub with sDMA is essential for piRNA biogenesis and transposon silencing. Krimper facilitates piRNA generation through its Tudor domains that bind Aub and Ago3 in different modification and piRNA-loading states.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Multidisciplinary
Jonas Watzel, Elke Duchardt-Ferner, Sepas Sarawi, Helge B. Bode, Jens Wohnert
Summary: Non-ribosomal peptide synthetases (NRPS) assemble natural products from amino acid building blocks through specific N- and C-terminal docking domains. PaxA's small (C)DD cooperates with its preceding thiolation (T-1) domain to bind PaxB's (DD)-D-N with very high affinity, indicating a similar docking interaction is present in other NRPS systems.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Immunology
Maryse Cloutier, Jean-Simon Fortin, Jacques Thibodeau
Summary: Our study indicates that the TRIM domain is not essential for trimerization of Ii or its intracellular trafficking with MHCII molecules. In the absence of TM, TRIM allows the formation of multi-subunit complexes with HLA-DR, while in the absence of TRIM, Ii can assemble into high-order structures with MHCII molecules.
Article
Fisheries
Ping Zhong, Zhongneng Xu, Wei Chen, Kai Peng, Yuping Sun, Xiaopeng Wu, Huiming Sun, Xiaoying Chen, Peng Luo, Chaozheng Li, Huo Li, Wen Huang
Summary: 9C-Jun NH2-terminal kinase (JNK)-interacting protein 4 (JIP4) is identified and characterized in Litopenaeus vannamei, serving as an essential component in organizing and linking the MAPK pathway. Lv-JIP4 is widely expressed in various tissues, with high levels in muscle, and plays a potential role in activating and phosphorylating Lv-p38(MAPK) in response to low-temperature stress.
AQUACULTURE REPORTS
(2021)
Article
Cell Biology
Christian de Groot, Jack Houston, Bethany Davis, Adina Gerson-Gurwitz, Joost Monen, Pablo Lara-Gonzalez, Karen Oegema, Andrew K. Shiau, Arshad Desai
Summary: The extended N-terminal tail of CENP-A in Caenorhabditis elegans plays a crucial role in kinetochore assembly and chromosome condensation by interacting directly with KNL-2 protein. Results demonstrate that the N-terminal tail of CENP-A contains a structured region predicted to be essential for centromeric chromatin assembly, highlighting an evolutionary variation in centromere structure and function in the absence of a specific CENP-A chaperone/targeting factor.
MOLECULAR BIOLOGY OF THE CELL
(2021)
Article
Cell Biology
Thomas Torng, William Wickner
Summary: Intracellular membrane fusion requires a combination of specific lipids such as phosphatidylinositol and phosphatidylinositol-3-phosphate for HOPS activation and other lipids like phosphatidylethanolamine, phosphatidic acid, phosphatidylserine, and diacylglycerol for the terminal bilayer rearrangement step of fusion. Different lipid requirements are crucial for activating HOPS for trans-SNARE assembly and for the final fusion process.
MOLECULAR BIOLOGY OF THE CELL
(2021)
Article
Virology
Morgan Mann, David S. Roberts, Yanlong Zhu, Yi Li, Jia Zhou, Ying Ge, Allan R. Brasier
Summary: The study reveals that RSV infection alters the interaction proteins of BRD4, with 101 proteins significantly enriched in the BRD4 complex responsive to both RSV infection and BRD4 inhibition. These proteins are mainly transcription factors and transcriptional coactivators, including members of the AP1 transcription factor complex.
Article
Virology
Xiaofang Xu, Morgan Mann, Dianhua Qiao, Allan R. Brasier
Summary: The research utilized SMRT sequencing and short-read mRNA sequencing to characterize changes in mRNA processing in epithelial cells in response to RSV infection, revealing differential splicing and polyadenylation, particularly involving cell cycle control and the innate immune response pathway.
Article
Physiology
Dianhua Qiao, Melissa Skibba, Xiaofang Xu, Roberto P. Garofalo, Yingxin Zhao, Allan R. Brasier
Summary: Paramyxoviridae, respiratory syncytial virus (RSV), and murine respirovirus are enveloped, negative-sense RNA viruses that cause vertebrate lower respiratory tract infections (LRTIs). RSV infection induces the activation of the hexosamine biosynthetic pathway (HBP), as well as mesenchymal transition (EMT) and ECM remodeling through the IRE1 alpha-XBP1 arm of the unfolded protein response (UPR). Murine respirovirus induces similar effects in a host-dependent manner, suggesting a role for the IRE1 alpha-XBP1s arm in paramyxovirus-induced metabolic adaptation and mucosal remodeling.
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
(2021)
Article
Genetics & Heredity
Kishor K. Bhakat, Sutapa Ray
Summary: Genomic DNA in the nucleus is wrapped around nucleosomes, consisting of core histones. The histone chaperone complex FACT is involved in nucleosome remodeling during processes like transcription and DNA repair, playing a crucial role in various repair pathways. Overexpression of FACT in cancer is associated with drug resistance and poor prognosis, while inhibitors like curaxins show promise in sensitizing cancer to chemotherapy and radiation.
Review
Medicine, General & Internal
Sutapa Ray, Nagendra K. Chaturvedi, Kishor K. Bhakat, Angie Rizzino, Sidharth Mahapatra
Summary: Medulloblastoma is the most common malignant central nervous system tumor in pediatric patients. Tumors can be divided into average and high-risk status based on age, metastasis at diagnosis, and extent of surgical resection. High-throughput screening has allowed for the identification of four primary subgroups, each with further subdivisions based on cytogenetic and epigenetic events. Exploiting these genetic aberrations may lead to novel targeted therapeutics.
Article
Biochemistry & Molecular Biology
Suravi Pramanik, Yingling Chen, Heyu Song, Irine Khutsishvili, Luis A. Marky, Sutapa Ray, Amarnath Natarajan, Pankaj K. Singh, Kishor K. Bhakat
Summary: This study identifies a novel role for the protein APE1 in regulating stable G4 formation and KRAS expression in PDAC, suggesting that G4 structures could be potential prognostic markers and therapeutic targets for PDAC.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemical Research Methods
Yanlong Zhu, Stephane Esnault, Ying Ge, Nizar N. Jarjour, Allan R. Brasier
Summary: Airway remodeling in patients with asthma is associated with leukocyte numbers and remodeling markers. Patients with lower FEV1 have distinct dynamic responses to allergens.
CLINICAL PROTEOMICS
(2022)
Article
Biochemistry & Molecular Biology
Yanlong Zhu, Stephane Esnault, Ying Ge, Nizar N. Jarjour, Allan R. Brasier
Summary: This study analyzed metabolites in bronchoalveolar fluid (BALF) during a bronchial antigen challenge and identified distinct metabolic responses, providing insight into pathogenic and protective subtypes in allergic asthma.
Editorial Material
Virology
Allan R. Brasier
Article
Biochemistry & Molecular Biology
Dianhua Qiao, Melissa Skibba, Xiaofang Xu, Allan R. Brasier
Summary: Epithelial mesenchymal plasticity (EMP) is a complex cellular reprogramming event that plays a major role in tissue homeostasis. Recently, the unfolded protein response (UPR) was found to trigger EMP through the IRE1 alpha-XBP1s axis, enhancing glucose shunting to protein N glycosylation. By identifying the genomic targets of XBP1s using CUT&RUN, it was discovered that XBP1s peaks were located near various promoters of genes controlling Rho-GTPase signaling, N-linked glycosylation, and ER-Golgi transport. Moreover, the IRE1 alpha-XBP1s pathway was shown to regulate mesenchymal transcription factors and hexosamine biosynthesis in EMP by recruiting activated RNA Pol II to GC-rich promoters.
NUCLEIC ACIDS RESEARCH
(2023)
Editorial Material
Medicine, Research & Experimental
Allan R. Brasier
MOLECULAR THERAPY-NUCLEIC ACIDS
(2023)
Article
Oncology
Kyle A. Rohrer, Heyu Song, Anum Akbar, Yingling Chen, Suravi Pramanik, Phillip J. Wilder, Erin M. McIntyre, Nagendra K. Chaturvedi, Kishor K. Bhakat, Angie Rizzino, Don W. Coulter, Sutapa Ray
Summary: Medulloblastoma (MB) is a common childhood malignant brain tumor that accounts for a significant percentage of pediatric central nervous system tumors. This study reveals the functional role of activated STAT3 in promoting MB tumorigenesis and chemoresistance by inducing the oncogene MYC. Inhibiting STAT3 can reduce the growth and survival of MB cells and improve treatment efficacy, especially in high-risk MYC-amplified tumors.
Review
Medicine, Research & Experimental
Allan. R. R. Brasier, Shannon. L. L. Casey, Peggy Hatfield, Patrick. W. W. Kelly, Whitney. A. A. Sweeney, Marin Schweizer, Bo Liu, Elizabeth. S. S. Burnside
Summary: This study proposes a model for developing leadership in translational teams (TTs) from team formation to dissemination and implementation. It identifies the stable impact of leadership behaviors on team development and emphasizes the importance of ongoing reflection, evaluation, and practice to enhance leadership skills. The study also provides a comprehensive multi-level evaluation framework to track the growth of TT leadership skills.
JOURNAL OF CLINICAL AND TRANSLATIONAL SCIENCE
(2023)
Review
Medicine, Research & Experimental
Allan R. Brasier, Shannon L. Casey, Felice Resnik, Betsy Rolland, Elizabeth S. Burnside
Summary: Successful translation involves the application of research and product development to advance healthcare interventions. Training in team skills and attitudes can enhance translational team performance. Interdisciplinary teams undergo developmental phases, with each phase promoting knowledge generation and translation. Antecedents of stage-dependent competencies and assessment rubrics can guide training interventions for improving performance in the clinical context.
JOURNAL OF CLINICAL AND TRANSLATIONAL SCIENCE
(2023)
Review
Medicine, Research & Experimental
Allan R. Brasier, Elizabeth S. Burnside, Betsy Rolland
Summary: A translational team is a type of interdisciplinary team that aims to improve human health. Understanding how to promote team performance in the areas of affect, communication, management, collaborative problem-solving, and leadership is essential. This study conducted a literature review to identify key competencies that enhance team performance and develop strategies for training interventions.
JOURNAL OF CLINICAL AND TRANSLATIONAL SCIENCE
(2023)