Article
Biochemistry & Molecular Biology
Federico Giovannoni, Cecilia A. Vazquez, Pablo Thomas, Ricardo M. Gomez, Cybele C. Garcia
Summary: This study reveals that the interaction between the New World mammarenavirus Junin (JUNV) and the antiviral protein PML is different from that of the Old World mammarenavirus lymphocytic choriomeningitis virus (LCMV). It also demonstrates that the mechanism of JUNV restriction in human cells is distinct from LCMV.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Virology
Liting Shao, Kang Ning, Jianke Wang, Fang Cheng, Shengqi Wang, Jianming Qiu
Summary: In this study, we discovered a direct interaction between the large nonstructural protein NS1 of parvovirus and Ku70, which is critical for HBoV1 replication.
JOURNAL OF VIROLOGY
(2022)
Article
Multidisciplinary Sciences
Sai Li, Michael R. Wasserman, Olga Yurieva, Lu Bai, Michael E. O'Donnell, Shixin Liu
Summary: This study found that the ORC can eject histones from a nucleosome in an ATP-dependent manner. It selectively evicts H2A-H2B dimers but leaves the (H3-H4)2 tetramer on DNA. It also discriminates canonical H2A from the H2A.Z variant, evicting the former while retaining the latter. These findings suggest that the ORC is a bona fide nucleosome remodeler that functions to create a local chromatin environment optimal for origin activity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Virology
Weiran Shen, Zekun Wang, Kang Ning, Fang Cheng, John F. Engelhardt, Ziying Yan, Jianming Qiu
Summary: Our study demonstrates that productive parvovirus DNA replication can occur independently of hairpin transfer. Through experiments with human bocavirus 1 (HBoV1) duplex genomes, we show that viruses can be generated and infect human airway epithelium without the need for hairpin sequences. This discovery may have implications in the development of parvovirus-based viral vectors with alternative properties.
JOURNAL OF VIROLOGY
(2021)
Article
Oncology
Camilla Coulson-Gilmer, Robert D. Morgan, Louisa Nelson, Bethany M. Barnes, Anthony Tighe, Rene Wardenaar, Diana C. J. Spierings, Helene Schlecht, George J. Burghel, Floris Foijer, Sudha Desai, Joanne C. McGrail, Stephen S. Taylor
Summary: A subset of ovarian cancers are intrinsically sensitive to pharmacological PARG blockade, including drug-resistant disease, underpinned by a common mechanism of replication catastrophe. We explore the use of a transcript-based biomarker, and provide insight into the design of future clinical trials of PARGi in patients with ovarian cancer. However, our results highlight the complexity of developing a predictive biomarker for PARGi sensitivity.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2021)
Editorial Material
Biochemistry & Molecular Biology
Jason A. Halliwell, Eva R. Hoffmann
Summary: The study reveals evolutionary conservation between replication timing and meiotic recombination in males through mapping replication origins directly in mammalian tissue for the first time. This provides new insights into understanding germ cell formation.
Article
Multidisciplinary Sciences
Kendall A. Torres, Felipe A. Calil, Ann L. Zhou, Matthew L. DuPrie, Christopher D. Putnam, Richard D. Kolodner
Summary: The conserved motif in the Mlh1 linker plays a crucial role in mismatch repair by promoting the endonuclease activity of Mlh1-Pms1 through interactions with DNA, PCNA, RFC, or other domains of the complex.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Roopesh Anand, Erika Buechelmaier, Ondrej Belan, Matthew Newton, Aleksandra Vancevska, Artur Kaczmarczyk, Tohru Takaki, David S. Rueda, Simon N. Powell, Simon J. Boulton
Summary: HELQ is a superfamily 2 helicase with 3' to 5' polarity, and disruption in mice causes germ cells loss, infertility, and increased predisposition to ovarian and pituitary tumors. Defects in HELQ result in cellular hypersensitivity to cisplatin and mitomycin C, as well as persistence of RAD51 foci after DNA damage. HELQ possesses an intrinsic ability to capture RPA-bound DNA strands and facilitate annealing of complementary sequences.
Article
Virology
Jonathan L. Sanchez, Niloofar Ghadirian, Nancy C. Horton
Summary: This paper presents two new structures of the N-terminal domain of the main replication protein, NS1, from human parvovirus B19 (B19V). The NS1-nuc domain plays a crucial role in the rolling hairpin replication of the B19V DNA genome by recognizing origin of replication sequences in double-stranded DNA and cleaving single-stranded DNA at the terminal resolution site (trs). The high-resolution structures of NS1-nuc provide insights into DNA recognition and cleavage by B19V NS1-nuc and predict the important residues involved in DNA cleavage and sequence-specific recognition at the viral origin of replication.
JOURNAL OF VIROLOGY
(2022)
Editorial Material
Genetics & Heredity
Cristian Polo Rivera, Tom D. Deegan
Summary: Repliconseq is a new genome-wide DNA sequencing technology introduced by Claussin et al. that enables high-resolution monitoring of individual replisomes in vivo.
TRENDS IN GENETICS
(2022)
Article
Multidisciplinary Sciences
Nichole Owen, Irina G. Minko, Samantha A. Moellmer, Sydney K. Cammann, R. Stephen Lloyd, Amanda K. McCullough
Summary: Human clinical trials suggest that inhibition of enzymes in the DNA base excision repair (BER) pathway, such as PARP1 and APE1, can be useful in anticancer strategies when combined with certain DNA-damaging agents. Specifically, in acute myeloid leukemia (AML), AML cell lines deficient in OGG1 have enhanced sensitivity to cytarabine (Ara-C) treatment. This enhanced cytotoxicity is likely due to the insertion of Ara-C opposite unrepaired 8-oxo-dG in OGG1-deficient AML cells.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Cell Biology
Chao Li, Yong-Peng Tan, Xue-Shan Ma, Zhen-Bo Wang, Tie-Gang Meng, Qing-Yuan Sun
Summary: This study investigated the roles of CDT1 and MCM2 in oocyte meiotic maturation and early embryonic development. The results showed that CDT1 is the major regulator of DNA replication, while MCM2 has no effect on oocyte meiotic maturation. The degradation of CDT1 is essential for preventing DNA re-replication in zygotes.
CELL PROLIFERATION
(2023)
Article
Cell Biology
Wei Zhuo, Meng Sun, Kun Wang, Lu Zhang, Kai Li, Danyang Yi, Mengjie Li, Qiang Sun, Xixi Ma, Wei Liu, Lisong Teng, Chengqi Yi, Tianhua Zhou
Summary: This study reveals the significance of PCIF1 and m(6)Am modification in gastric cancer. Increased expression of PCIF1 and m(6)Am modification are associated with gastric cancer progression and poor prognosis. Silencing PCIF1 inhibits the proliferation and invasion of gastric cancer cells, and suppresses tumor growth and metastasis in a mouse model. PCIF1 modifies TM9SF1 mRNA with m(6)Am, leading to decreased TM9SF1 translation. TM9SF1 reverses the effects of PCIF1 on gastric cancer cell aggressiveness.
Article
Microbiology
Qian Du, Xuezhi Zhang, Ning Xu, Mengyu Ma, Bicheng Miao, Yong Huang, Dewen Tong
Summary: This study identified CCT5 as a host interacting protein of PPV NS1 and showed that CCT5 mediates the interaction of PPV NS1 and COPE, regulating viral replication.
VETERINARY MICROBIOLOGY
(2022)
Article
Oncology
Safa Majeed, Mansi K. Aparnathi, Kevin C. J. Nixon, Vidhyasagar Venkatasubramanian, Fariha Rahman, Lifang Song, Jessica Weiss, Ranya Barayan, Vijithan Sugumar, Samir H. Barghout, Joel D. Pearson, Rod Bremner, Aaron D. Schimmer, Ming S. Tsao, Geoffrey Liu, Benjamin H. Lok
Summary: TAK-243 exhibits efficacy in preclinical models of small cell lung cancer (SCLC), with associations to various gene sets. TAK-243 synergizes with cisplatin/etoposide chemotherapy (C/E) and PARP inhibitor olaparib. TAK-243 is a potential therapeutic strategy to improve SCLC patient outcomes.
CLINICAL CANCER RESEARCH
(2022)
Article
Nanoscience & Nanotechnology
Youngee Seo, Lida Ghazanfari, Alyssa Master, Hemant M. Vishwasrao, Xiaomeng Wan, Marina Sokolsky-Papkov, Alexander Kabanov
Summary: This study reports the development of a novel theranostic system called NanoFerrogels, which combines magnetic nanoparticles and polymeric micelles for cancer diagnosis and treatment. NanoFerrogels function as imaging agents for magnetic resonance imaging and as drug loading compartments. The experiments demonstrate the potential of NanoFerrogels as a remotely actuated theranostic platform for cancer therapy.
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
(2022)
Article
Chemistry, Multidisciplinary
Kin Man Au, Roland Tisch, Andrew Z. Wang
Summary: Failure to establish immune tolerance can lead to autoimmune diseases. This study demonstrates a potential new strategy for treating autoimmune diseases by bioengineering programmed death-ligand 1 (PD-L1)- and cluster of differentiation 86 (CD86)-functionalized mouse Schwann cells (SCs) to modify disease progression and ameliorate symptoms without inducing systemic immunosuppression.
ADVANCED MATERIALS
(2022)
Article
Engineering, Biomedical
Xintao Zhang, Zheng Chai, Amanda Lee Dobbins, Michelle S. Itano, Charles Askew, Zhe Miao, Hongqian Niu, R. Jude Samulski, Chengwen Li
Summary: This study identifies a BBB shuttle peptide, PB5-3, that enhances the transduction of AAV9 in mouse brains. The peptide increases AAV9 transcytosis efficiency in a BBB cell model and slows the clearance of AAV9 from blood.
Article
Materials Science, Biomaterials
Matthew J. Haney, Hong Yuan, Steven T. Shipley, Zhanhong Wu, Yuling Zhao, Kelly Pate, Jonathan E. Frank, Nicole Massoud, Paul W. Stewart, Joel S. Perlmutter, Elena Batrakova
Summary: This study investigated the biodistribution and brain retention of PBMCs and EVs in adult rhesus macaques using PET/MRI imaging. The route of administration had a significant impact on brain retention of the carriers, with PBMCs showing higher brain retention when administered intrathecally. EVs demonstrated superior brain accumulation when administered intraperitoneally and intravenously, respectively. No cytotoxic effects were observed for either carrier in blood samples. Overall, living cells and EVs have great potential for drug delivery to the brain, and the route of administration plays a crucial role in CNS drug delivery.
Article
Chemistry, Multidisciplinary
Benjamin T. Ledford, Adam W. Akerman, Kui Sun, David C. Gillis, Jenna M. Weiss, Johnny Vang, Smaranda Willcox, Tristan D. Clemons, Hiroaki Sai, Ruomeng Qiu, Mark R. Karver, Jack D. Griffith, Nick D. Tsihlis, Samuel Stupp, John S. Ikonomidis, Melina R. Kibbe
Summary: This study reports the development of injectable supramolecular nanofibers that target fragmented elastin, matrix metalloproteinase 2, and membrane type 1 matrix metalloproteinase to reduce the risks associated with a ruptured abdominal aortic aneurysm. The results show that one of the nanofibers was able to better localize to the aneurysm tissue and had an optimal dose.
Article
Chemistry, Multidisciplinary
Limei Shen, Jingjing Li, Qi Liu, Manisit Das, Wantong Song, Xueqiong Zhang, Karthik Tiruthani, Oleksandra Dorosheva, Haiyang Hu, Samuel K. Lai, Rihe Liu, Leaf Huang
Summary: Interaction between different cell types in the tumor microenvironment affects tumor growth. Tumor-associated fibroblasts produce CXCL13, which recruits B cells to the tumor microenvironment. B cells in the tumor microenvironment differentiate into regulatory B cells (Bregs). CXCL13 also stimulates epithelial-mesenchymal transition (EMT) of tumor cells. Using plasmid DNA encoding a CXCL13 trap to reduce Bregs differentiation and normalize EMT suppresses tumor growth.
JOURNAL OF CONTROLLED RELEASE
(2022)
Article
Chemistry, Multidisciplinary
Anne M. Talkington, Morgan D. McSweeney, Timothy Wessler, Marielle K. Rath, Zibo Li, Tao Zhang, Hong Yuan, Jonathan E. Frank, M. Gregory Forest, Yanguang Cao, Samuel K. Lai
Summary: PEGylation is commonly used to prolong the circulation time of protein therapeutics and nanomedicines. However, individuals exposed to PEGylated therapeutics may develop antibodies specific to PEG, increasing the risk of hypersensitivity and accelerated drug clearance. In this study, a PBPK model was developed to investigate the impact of anti-PEG antibodies on the pharmacokinetics and biodistribution of PEGylated drugs.
JOURNAL OF CONTROLLED RELEASE
(2022)
Article
Medicine, Research & Experimental
Liu Zhou, Ruiling Long, Mei Hu, Nan Liu, Yue Feng, Lin Qiu, Zibo Li, Yue Chen, Li Wang
Summary: Boron neutron capture therapy (BNCT) is a promising cancer treatment strategy that utilizes boron-containing ligands. In this study, a series of substituted boramino acids were synthesized and evaluated for their potential use in BNCT with integrated positron emission tomography (PET). The compound R-[F-18]-5a demonstrated the best tumor uptake and stability among tested agents, making it a promising candidate for future evaluation in PET and BNCT combination therapy.
MOLECULAR PHARMACEUTICS
(2022)
Article
Biochemistry & Molecular Biology
Li Wang, Yubai Zhou, Xuedan Wu, Xinrui Ma, Bing Li, Ransheng Ding, Michael A. Stashko, Zhanhong Wu, Xiaodong Wang, Zibo Li
Summary: MerTK is abnormally expressed in various cancers, but the sensitivity of tumors to MerTK suppression may vary. In this study, a radiolabeled agent [F-18]-MerTK-6 was developed and showed prominent uptake in tumors in initial evaluation, suggesting it as a promising PET agent for MerTK imaging.
Article
Biotechnology & Applied Microbiology
Pritha Agarwalla, Edikan A. Ogunnaike, Sarah Ahn, Kristen A. Froehlich, Anton Jansson, Frances S. Ligler, Gianpietro Dotti, Yevgeny Brudno
Summary: This study introduces a novel implantable multifunctional scaffold (MASTER) that streamlines in vivo CAR-T cell manufacturing, resulting in the rapid generation and release of functional CAR-T cells in mice. MASTER shows improved therapeutic efficacy and persistence compared to conventional CAR-T cells, promising to transform CAR-T cell therapy.
NATURE BIOTECHNOLOGY
(2022)
Article
Multidisciplinary Sciences
Hongxia Li, Emily B. Harrison, Huizhong Li, Koichi Hirabayashi, Jing Chen, Qi-Xiang Li, Jared Gunn, Jared Weiss, Barbara Savoldo, Joel S. Parker, Chad Pecot, Gianpietro Dotti, Hongwei Du
Summary: Therapeutic options for non-small cell lung cancer patients with brain metastases are limited. CAR-T cells targeting B7-H3 and expressing the chemokine receptor CCR2b show improved accumulation in the brain and enhanced anti-tumor activity. This strategy could improve the efficacy of adoptive T-cell therapies in patients with solid tumors presenting with brain metastases.
NATURE COMMUNICATIONS
(2022)
Article
Materials Science, Biomaterials
Devika M. Varma, Cole J. Batty, Rebeca T. Stiepel, Elizabeth G. Graham-Gurysh, John A. Roque, Erik S. Pena, M. Shamim Hasan Zahid, Kunyu Qiu, Aaron Anselmo, David B. Hill, Ted M. Ross, Eric M. Bachelder, Kristy M. Ainslie
Summary: This study investigates the use of nasal gel formulation for influenza vaccination and demonstrates that nasal gel can generate rapid serum and mucosal humoral immune responses.
ACS BIOMATERIALS SCIENCE & ENGINEERING
(2022)
Article
Multidisciplinary Sciences
Esteban A. Oyarzabal, Li-Ming Hsu, Manasmita Das, Tzu-Hao Harry Chao, Jingheng Zhou, Sheng Song, Weiting Zhang, Kathleen G. Smith, Natale R. Sciolino, Irina Y. Evsyukova, Hong Yuan, Sung-Ho Lee, Guohong Cui, Patricia Jensen, Yen-Yu Ian Shih
Summary: This study reveals the selective neuromodulatory effect of norepinephrine-releasing neurons in the locus coeruleus on the default mode network of the brain. The activation of these neurons alters neuronal activity coupling and cerebral blood volume within the frontal DMN, strengthens functional connectivity within the frontal DMN, and is mediated by reduced modulatory inputs from retrosplenial and hippocampal regions.
Article
Microbiology
Kinsey N. N. Morris, Angela M. M. Mitchell
Summary: This article investigates the synthesis of ECA(PG) in the outer membrane of Enterobacterales and discovers that phosphatidylglycerol (PG) is the lipid donor for its synthesis. Understanding this process can lead to the development of molecules to increase outer membrane permeability, expanding the range of antibiotics available for treating Gram-negative infections.
JOURNAL OF BACTERIOLOGY
(2023)
Article
Cell Biology
Nazira El-Hage, Matthew J. Haney, Yuling Zhao, Myosotys Rodriguez, Zhanhong Wu, Mori Liu, Carson J. Swain, Hong Yuan, Elena V. Batrakova
Summary: We have developed a novel EV-based drug delivery system for the treatment of Batten disease (BD) by transporting the lysosomal enzyme TPP1. The EVs were loaded with TPP1 through transfection of parent cells and showed successful delivery to the brain in a mouse model of BD. The TPP1-loaded EVs exhibited therapeutic effects by eliminating lipofuscin aggregates, reducing inflammation, and improving neuronal survival, possibly through activation of the autophagy pathway. Continued research into effective therapies for BD is crucial for improving patient outcomes.