Article
Biotechnology & Applied Microbiology
Du Yu, Li Xin, Xu Qing, Zhang Hao, Wang Yong, Jiangjiang Zhu, Yaqiu Lin
Summary: In this study, potential circRNAs involved in goat intramuscular adipocyte differentiation were identified and their biological functions were predicted. An interaction network between circRNAs and miRNAs was created. By analyzing the network, 5 key mRNAs related to adipocyte differentiation were identified.
Article
Multidisciplinary Sciences
Greg Holmes, Ana S. Gonzalez-Reiche, Madrikha Saturne, Susan M. Motch Perrine, Xianxiao Zhou, Ana C. Borges, Bhavana Shewale, Joan T. Richtsmeier, Bin Zhang, Harm van Bakel, Ethylin Wang Jabs
Summary: Research found enriched expression of Hhip in the mesenchyme of the murine coronal suture, and sutural dysgenesis in Hhip-/- mutants, indicating the necessity of Hhip for normal development of the coronal suture.
NATURE COMMUNICATIONS
(2021)
Article
Biology
Rodolfo Gomez, Matt J. Barter, Ana Alonso-Perez, Andrew J. Skelton, Carole Proctor, Gabriel Herrero-Beaumont, David A. Young
Summary: In this study, the relationship between DNA-methylation changes during osteoblastogenesis and the transcription factors that interact with these regions were investigated. The DNA-methylation profile of MSCs differentiated into osteoblasts and adipocytes was determined using the Illumina HumanMethylation450 BeadChip array. A bioinformatic tool was developed to analyze the differentially methylated regions and identify the TFs associated with them. ZEB1 TF was identified as a key mediator in adipogenesis, osteoblastogenesis, and obesity-related bone adiposity.
BIOLOGICAL RESEARCH
(2023)
Article
Multidisciplinary Sciences
Laura M. Pikkupeura, Raul B. Bressan, Jordi Guiu, Yun Chen, Martti Maimets, Daniela Mayer, Pawel J. Schweiger, Stine L. Hansen, Grzegorz J. Maciag, Hjalte L. Larsen, Kadi Lohmussaar, Marianne Terndrup Pedersen, Joji M. Yap Teves, Jette Bornholdt, Vladimir Benes, Albin Sandelin, Kim B. Jensen
Summary: During intestinal organogenesis, the maturation of intestinal stem cells is not fully understood. In this study, we used intestinal organoid cultures to analyze the transcriptional, chromatin accessibility, DNA methylation, and three-dimensional chromatin conformation landscapes in fetal and adult epithelial cells. We found differences in gene expression, enhancer activity, 3D organization, DNA accessibility, and methylation between the two states. We identified sustained Yes-Associated Protein (YAP) activity as a major regulator of the immature fetal state, likely coordinated by changes in extracellular matrix composition.
Article
Immunology
Danfeng Lu, Zhuoyue Li, Pei Zhu, Zhenxing Yang, Heng Yang, Zhanhong Li, Huachun Li, Zhuoran Li
Summary: This study provides insights into the comprehensive characterization of BTV-host interactome and BTV infection and pathogenic mechanisms through whole-transcriptome sequencing and bioinformatics analysis.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Orthopedics
Jiamei Liu, Qin Fu, Shengye Liu
Summary: The study identified GABARAPL1, GABARAPL2, and ATG13 as co-expressed autogenes, which were downregulated in OA synovial tissues. A protein-protein interaction network of these genes revealed their association with autophagy-related functions, and key hub genes and control modules were identified within the network.
Article
Biochemistry & Molecular Biology
Edward J. Calabrese
Summary: This paper provides a thorough assessment of hormetic dose responses in embryonic stem cells, suggesting that this response may serve as a fundamental and highly conserved evolutionary strategy.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
Article
Biochemistry & Molecular Biology
Xiang Zhao, Bethany N. Radford, Mark Ungrin, Wendy Dean, Myriam Hemberger
Summary: Normal developmental progression relies on close interactions between the embryonic and extraembryonic lineages in the pre- and peri-gastrulation stage conceptus. Trophoblast cells of the extraembryonic ectoderm play a role in delaying cardiomyocyte differentiation dynamics and prolonging pluripotency in embryonic stem cells (ESCs). These findings provide insights into the intricate crosstalk between different compartments of the early conceptus and have implications for synthetic embryo research.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Larina Pinto, Rajesh P. Shastry, Shivakiran Alva, R. Shyama Prasad Rao, Sudeep D. Ghate
Summary: This study utilized in-silico based functional network analysis to investigate the virulence and resistance mechanisms of multidrug-resistant bacterium Stenotrophomonas maltophilia. The protein-protein interaction network analysis revealed 8 hub proteins, which were further studied for docking with 58 selected phytochemicals. Deoxytubulosine and corosolic acid were identified as potential inhibitors of hub proteins in pathogenic S. maltophilia.
MICROBIAL PATHOGENESIS
(2023)
Article
Oncology
Kai Wang, Man Zhang, Jiao Wang, Pan Sun, Jizhuang Luo, Haizhen Jin, Rong Li, Changqing Pan, Liming Lu
Summary: This study revealed key regulators contributing to cell proliferation in human LUAD and identified four potential therapeutic agents for treatment strategy.
FRONTIERS IN ONCOLOGY
(2021)
Article
Multidisciplinary Sciences
John P. Gleeson, Namit Chaudhary, Katherine C. Fein, Rose Doerfler, Patricia Hredzak-Showalter, Kathryn A. Whitehead
Summary: Breast milk contains cells that are beneficial for infant development, but little is known about these cells. This study characterized the cells in mature breast milk from healthy donors and identified the main cell population as epithelial cells, with several subpopulations including previously unidentified ones. These findings provide insights into the potential applications of breast milk cells in maternal and infant medicine.
Article
Endocrinology & Metabolism
Harish Joshi, Basavaraj Vastrad, Nidhi Joshi, Chanabasayya Vastrad, Anandkumar Tengli, Iranna Kotturshetti
Summary: This study aimed to diagnose differentially expressed genes associated with obesity development, identifying important DEGs that may serve as novel biomarkers or potential therapeutic targets. Through bioinformatics analysis, a set of key hub genes related to obesity were identified, providing reliable molecular biomarkers for screening and diagnosis, prognosis, and potential therapeutic intervention for obesity.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Genetics & Heredity
Laura A. Genovesi, Amanda Millar, Elissa Tolson, Matthew Singleton, Emily Hassall, Marija Kojic, Caterina Brighi, Emily Girard, Clara Andradas, Mani Kuchibhotla, Dharmesh D. Bhuva, Raelene Endersby, Nicholas G. Gottardo, Anne Bernard, Christelle Adolphe, James M. Olson, Michael D. Taylor, Melissa J. Davis, Brandon J. Wainwright
Summary: Medulloblastoma is a common malignant pediatric brain tumor with aggressive treatment protocols leading to significant disabilities. Through a network-based systems-pharmacogenomics approach, candidate drugs targeting CDK4, CDK6, AURKA, and TUBB, CAD, SNRPA, SLC1A5, PTPRS, P4HB, and CHEK2 were identified for potential treatment of MB. The study also demonstrated the efficacy of ixabepilone in inhibiting tumor growth in vivo, presenting a promising therapeutic candidate.
Article
Biochemistry & Molecular Biology
Pakorn Sagulkoo, Apichat Suratanee, Kitiporn Plaimas
Summary: The study constructed an immune-related protein interaction network using a network diffusion technique and identified key proteins and potential drugs associated with severe COVID-19. The network was found to be mainly associated with antiviral, innate immune, apoptosis, cell division, and cell cycle regulation signaling pathways.
Article
Genetics & Heredity
Basdeo Kushwaha, Neha Srivastava, Murali S. Kumar, Ravindra Kumar
Summary: This study aimed to understand the interaction of the brain-gonad system in Clarias magur reproduction by analyzing differentially expressed genes (DEG). Thirteen key genes in female brain & ovary and twelve key genes in male brain & testis were identified based on network analysis. Functional annotation revealed their involvement in important reproduction-related pathways. This study provides insights into the interaction between the brain and gonads in the regulation of Clarias magur reproduction through a protein-protein interaction network.
Article
Immunology
Carmine Fedele, Shuai Li, Kai Wen Teng, Connor J. R. Foster, David Peng, Hao Ran, Paolo Mita, Mitchell J. Geer, Takamitsu Hattori, Akiko Koide, Yubao Wang, Kwan Ho Tang, Joshua Leinwand, Wei Wang, Brian Diskin, Jiehui Deng, Ting Chen, Igor Dolgalev, Ugur Ozerdem, George Miller, Shohei Koide, Kwok-Kin Wong, Benjamin G. Neel
Summary: The combination of SHP2 inhibitor and KRAS (G12C) inhibitor shows significant survival benefits in PDAC and NSCLC, inducing favorable changes in the tumor microenvironment by reducing myeloid suppressor cells, increasing CD8(+) T cells, and enhancing sensitivity to PD-1 blockade.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Masamichi Nagae, Kei Suzuki, Norihisa Yasui, Terukazu Nogi, Takao Kohno, Mitsuharu Hattori, Junichi Takagi
Summary: Reelin is a glycoprotein that regulates embryonic brain development and adult brain functions. Its N-terminal region is crucial for multimer formation and efficient signal transduction.
JOURNAL OF BIOCHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Norihisa Yasui, Kazuaki Nakamura, Atsuko Yamashita
Summary: Synthetic binding proteins generated through phage display using monellin as a non-antibody scaffold showed moderate but significant affinities for target proteins, such as GFPuv and yeast small ubiquitin-related modifier. The diversified loops of scMonellin were found to be involved in target recognition, making it a promising scaffold for designing and generating synthetic binding proteins.
JOURNAL OF BIOCHEMISTRY
(2021)
Article
Biochemical Research Methods
Takamitsu Hattori, Akiko Koide, Tatyana Panchenko, Larizbeth A. Romero, Kai Wen Teng, Alexis D. Corrado, Shohei Koide
Summary: Accurate quantification of protein-ligand interactions is crucial in biology and medicine, and multiplex bead binding assays (MBBAs) provide a powerful method for analyzing multiple interactions simultaneously. This research introduces a cost-effective MBBA method using the irreversible biotin-streptavidin interaction, offering a way to improve throughput and reduce antigen consumption in characterization assays.
JOURNAL OF IMMUNOLOGICAL METHODS
(2021)
Article
Biochemistry & Molecular Biology
Takamitsu Hattori, Akiko Koide, Maria G. Noval, Tatyana Panchenko, Larizbeth A. Romero, Kai Wen Teng, Takuya Tada, Nathaniel R. Landau, Kenneth A. Stapleford, Shohei Koide
Summary: The experimentation revealed that only a small fraction of antibodies targeted the ACE2-interacting surface of the spike protein, while other regions of the virus were more immunogenic. This has significant implications for the treatment and vaccine development for COVID-19.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Maria G. Noval, Maria E. Kaczmarek, Akiko Koide, Bruno A. Rodriguez-Rodriguez, Ping Louie, Takuya Tada, Takamitsu Hattori, Tatyana Panchenko, Larizbeth A. Romero, Kai Wen Teng, Andrew Bazley, Maren de Vries, Marie Samanovic, Jeffrey N. Weiser, Ioannis Aifantis, Joan Cangiarella, Mark J. Mulligan, Ludovic Desvignes, Meike Dittmann, Nathaniel R. Landau, Maria Aguero-Rosenfeld, Shohei Koide, Kenneth A. Stapleford
Summary: Studies have shown that a majority of recovered healthcare workers produce antibodies with low neutralization capacity against SARS-CoV-2, with only a small percentage showing high neutralizing titers. Higher neutralizing sera are correlated with detection of a broader range of antibodies, while individuals with only IgG antibodies exhibit poor neutralization response.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Sarah E. Garnish, Yanxiang Meng, Akiko Koide, Jarrod J. Sandow, Eric Denbaum, Annette V. Jacobsen, Wayland Yeung, Andre L. Samson, Christopher R. Horne, Cheree Fitzgibbon, Samuel N. Young, Phoebe P. C. Smith, Andrew I. Webb, Emma J. Petrie, Joanne M. Hildebrand, Natarajan Kannan, Peter E. Czabotar, Shohei Koide, James M. Murphy
Summary: Phosphorylation of MLKL by RIPK3 kinase leads to MLKL oligomerization, translocation, and membrane permeabilization to induce cell death. Monobodies can bind to the MLKL pseudokinase domain, revealing distinct conformations during activation and disengagement from RIPK3, a key regulatory step in necroptosis. These structural and functional studies shed light on the mechanism of MLKL activation and regulation in necroptosis.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Kai Wen Teng, Steven T. Tsai, Takamitsu Hattori, Carmine Fedele, Akiko Koide, Chao Yang, Xuben Hou, Yingkai Zhang, Benjamin G. Neel, John P. O'Bryan, Shohei Koide
Summary: A monobody named 12VC1 that can selectively recognize and bind to the active state of KRAS mutants has been discovered in this study, showing great potential in inhibiting the proliferation of RAS-driven cancer cell lines. This finding suggests a new strategy for treating oncogenic RAS mutants through inhibition and degradation.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Lauren Wallon, Imran Khan, Kai Wen Teng, Akiko Koide, Mariyam Zuberi, Jianping Li, Gayatri Ketavarapu, Nathaniel J. Traaseth, John P. O'Bryan, Shohei Koide
Summary: A new class of tool biologics called JAM20, which can bind to all RAS isoforms, has been developed and shown to inhibit RAS-mediated signaling and tumorigenesis in vivo.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Oncology
Takamitsu Hattori, Lorenzo Maso, Kiyomi Y. Araki, Akiko Koide, James Hayman, Padma Akkapeddi, Injin Bang, Benjamin G. Neel, Shohei Koide
Summary: The study establishes a platform technology that creates distinct neoantigens using hapten-peptide conjugates generated by covalent inhibitors, effectively marking cancer cells. HapImmune antibodies, developed using FDA-approved covalent inhibitors sotorasib and osimertinib, selectively bind to drug-peptide conjugate/MHC complexes but not to free drugs. A HapImmune-based bispecific T-cell engager is capable of selectively and potently killing sotorasib-resistant lung cancer cells. This strategy creates targetable neoantigens by design, combining targeted and immune therapies.
Article
Multidisciplinary Sciences
Kosaku Okuda, Kengo Nakahara, Akihiro Ito, Yuta Iijima, Ryosuke Nomura, Ashutosh Kumar, Kana Fujikawa, Kazuya Adachi, Yuki Shimada, Satoshi Fujio, Reina Yamamoto, Nobumasa Takasugi, Kunishige Onuma, Mitsuhiko Osaki, Futoshi Okada, Taichi Ukegawa, Yasuo Takeuchi, Norihisa Yasui, Atsuko Yamashita, Hiroyuki Marusawa, Yosuke Matsushita, Toyomasa Katagiri, Takahiro Shibata, Koji Uchida, Sheng-Yong Niu, Nhi B. Lang, Tomohiro Nakamura, Kam Y. J. Zhang, Stuart A. Lipton, Takashi Uehara
Summary: DNA methyltransferases (DNMTs) catalyze methylation at the C5 position of cytosine and regulate gene expression. This study shows that S-nitrosylation of a cysteine residue in DNMT3B reduces its enzymatic activity and leads to aberrant upregulation of gene expression, including Cyclin D2 (Ccnd2) involved in tumor cell proliferation. By screening chemical compounds, a lead compound called DBIC is discovered to specifically inhibit S-nitrosylation of DNMT3B without affecting its enzymatic activity. Treatment with DBIC prevents NO-induced cancerous transformation and attenuates tumor development in a mouse model. These findings suggest that DNMT3B-mediated DNA methylation is regulated by NO and DBIC protects against tumor formation by preventing aberrant S-nitrosylation of DNMT3B.
NATURE COMMUNICATIONS
(2023)
Article
Biology
Nanako Atsumi, Keiko Yasumatsu, Yuriko Takashina, Chiaki Ito, Norihisa Yasui, Robert F. Margolskee, Atsuko Yamashita
Summary: The perception of salt taste is complex, with NaCl at low and high concentrations being preferentially or aversively perceived through different pathways. Cl- is believed to participate in taste sensation through an unknown mechanism. This study found that Cl- ions specifically bind to the ligand-binding domain (LBD) of taste receptor type 1 (T1r), inducing a conformational change in the receptor. The oral application of Cl- to mice increased the activity of taste nerves connected to T1r-expressing taste cells and influenced their behavioral preferences, which could be attenuated by blocking T1r or knocking out T1r3.
Article
Biochemistry & Molecular Biology
Atsuki Yoshida, Ayumi Ito, Norihisa Yasui, Atsuko Yamashita
Summary: This study reveals the possibility of calmodulin-mediated Ca2+-dependent feedback regulation of sweet and umami taste receptors. The interaction between calmodulin and the cytosolic side of taste receptor subunits suggests that calmodulin may regulate receptor functions within the cytosol. The binding affinity of calmodulin to different T1r subtypes varies, with T1r3 and T1r2 showing higher affinity than T1r1.
JOURNAL OF BIOCHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Kyosuke Ohnuma, Atsuko Yamashita, Norihisa Yasui
Summary: Single-chain monellin (SCM) is an engineered protein that can be used as a sugar replacement in food and beverages and has a wide range of applications. This study demonstrates that substituting Cys41 with Ala or Val increases the stability of SCM and provides insights into the structural basis of this improvement.
Article
Chemistry, Analytical
Jessica R. Chapman, Max Paukner, Micheal Leser, Kai Wen Teng, Shohei Koide, Marlene Holder, Karim-Jean Armache, Chris Becker, Beatrix Ueberheide, Michael Brenowitz
Summary: Correlating the structure and dynamics of proteins with biological function is critical for understanding cellular mechanisms. A quantitative method using common equipment for protein oxidative footprinting is described. The method allows dose-dependent oxidation of protein samples to be observed and quantitated by mass spectrometry, with high resolution. The method's efficacy is demonstrated by mapping protein interfaces.
ANALYTICAL CHEMISTRY
(2023)