Journals Cellular and Molecular Life Sc...

Cellular and Molecular Life Sciences : CMLS
Quintin Lee, Renhua Song, Dang Anh Vu Phan, Natalia Pinello, Jessica Tieng, Anni Su, James M Halstead, Alex C H Wong, Michelle van Geldermalsen, Bob S-L Lee, Bowen Rong, Kristina M Cook, Mark Larance, Renjing Liu, Fei Lan, Jessamy C Tiffen, Justin J-L Wong
Virilizer-like m6 A methyltransferase-associated protein (VIRMA) maintains the stability of the m6 A writer complex. Although VIRMA is critical for RNA m6 A deposition, the impact of aberrant VIRMA expression in human diseases remains unclear. We show that VIRMA is amplified and overexpressed in 15-20% of breast cancers. Of the two known VIRMA isoforms, the nuclear-enriched full-length but not the cytoplasmic-localised N-terminal VIRMA promotes m6 A-dependent breast tumourigenesis in vitro and in vivo. Mechanistically, we reveal that VIRMA overexpression upregulates the m6 A-modified long non-coding RNA, NEAT1, which contributes to breast cancer cell growth...
May 19, 2023: Cellular and Molecular Life Sciences: CMLS
Wenlong Zhang, Liuyan Ding, Mengran Zhang, Shaohui Zheng, Runfang Ma, Junwei Gong, Hengxu Mao, Huaxi Xu, Pingyi Xu, Yunlong Zhang
Parkinson's disease (PD) is a progressive movement disorder characterized by dopaminergic (DA) neuron degeneration and the existence of Lewy bodies formed by misfolded α-synuclein. Emerging evidence supports the benefits of dietary interventions in PD due to their safety and practicality. Previously, dietary intake of α-ketoglutarate (AKG) was proved to extend the lifespan of various species and protect mice from frailty. However, the mechanism of dietary AKG's effects in PD remains undetermined...
May 19, 2023: Cellular and Molecular Life Sciences: CMLS
Jiang Min, Shenglan Yang, Yang Cai, David R Vanderwall, Zhiping Wu, Shuping Li, Songlan Liu, Beibei Liu, Jie Wang, Yingjun Ding, Junxiong Chen, Chao Jiang, Jonathan D Wren, Anna Csiszar, Zoltan Ungvari, Céline Greco, Tomoharu Kanie, Junmin Peng, Xin A Zhang
Inflammation can impair intestinal barrier, while increased epithelial permeability can lead to inflammation. In this study, we found that the expression of Tspan8, a tetraspanin expressed specifically in epithelial cells, is downregulated in mouse model of ulcerative disease (UC) but correlated with those of cell-cell junction components, such as claudins and E-cadherin, suggesting that Tspan8 supports intestinal epithelial barrier. Tspan8 removal increases intestinal epithelial permeability and upregulates IFN-γ-Stat1 signaling...
May 19, 2023: Cellular and Molecular Life Sciences: CMLS
Lia-Raluca Olari, Richard Bauer, Marta Gil Miró, Verena Vogel, Laura Cortez Rayas, Rüdiger Groß, Andrea Gilg, Raphael Klevesath, Armando A Rodríguez Alfonso, Kübra Kaygisiz, Ulrich Rupp, Pradeep Pant, Joel Mieres-Pérez, Lena Steppe, Ramona Schäffer, Lena Rauch-Wirth, Carina Conzelmann, Janis A Müller, Fabian Zech, Fabian Gerbl, Jana Bleher, Nico Preising, Ludger Ständker, Sebastian Wiese, Dietmar R Thal, Christian Haupt, Hendrik R A Jonker, Manfred Wagner, Elsa Sanchez-Garcia, Tanja Weil, Steffen Stenger, Marcus Fändrich, Jens von Einem, Clarissa Read, Paul Walther, Frank Kirchhoff, Barbara Spellerberg, Jan Münch
Antimicrobial peptides (AMPs) are major components of the innate immune defense. Accumulating evidence suggests that the antibacterial activity of many AMPs is dependent on the formation of amyloid-like fibrils. To identify novel fibril forming AMPs, we generated a spleen-derived peptide library and screened it for the presence of amyloidogenic peptides. This approach led to the identification of a C-terminal 32-mer fragment of alpha-hemoglobin, termed HBA(111-142). The non-fibrillar peptide has membranolytic activity against various bacterial species, while the HBA(111-142) fibrils aggregated bacteria to promote their phagocytotic clearance...
May 17, 2023: Cellular and Molecular Life Sciences: CMLS
Kai Zheng, Zhe Ren, Yifei Wang
Accumulating evidence has consolidated the interaction between viral infection and host alternative splicing. Serine-arginine (SR) proteins are a class of highly conserved splicing factors critical for the spliceosome maturation, alternative splicing and RNA metabolism. Serine-arginine protein kinases (SRPKs) are important kinases that specifically phosphorylate SR proteins to regulate their distribution and activities in the central pre-mRNA splicing and other cellular processes. In addition to the predominant SR proteins, other cytoplasmic proteins containing a serine-arginine repeat domain, including viral proteins, have been identified as substrates of SRPKs...
May 17, 2023: Cellular and Molecular Life Sciences: CMLS
Huiwen Cao, Haomang Xu, Yiqing Zhou, Wei Xu, Qinglin Lu, Lingying Jiang, Yan Rong, Qianting Zhang, Chao Yu
The sperm flagellum is a specialized type of motile cilium composed of a typical "9 + 2" axonemal structure with peri-axonemal structures, such as outer dense fibers (ODFs). This flagellar arrangement is crucial for sperm movement and fertilization. However, the association of axonemal integrity with ODFs remains poorly understood. Here, we demonstrate that mouse BBOF1 could interact with both MNS1, an axonemal component, and ODF2, an ODF protein, and is required for sperm flagellar axoneme maintenance and male fertility...
May 17, 2023: Cellular and Molecular Life Sciences: CMLS
Cynthia Lefebvre-Omar, Elise Liu, Carine Dalle, Boris Lamotte d'Incamps, Stéphanie Bigou, Clément Daube, Léa Karpf, Marc Davenne, Noémie Robil, Coline Jost Mousseau, Stéphane Blanchard, Guillaume Tournaire, Charles Nicaise, François Salachas, Lucette Lacomblez, Danielle Seilhean, Christian S Lobsiger, Stéphanie Millecamps, Séverine Boillée, Delphine Bohl
Amyotrophic lateral sclerosis (ALS) is the most common motor neuron (MN) disease in adults with no curative treatment. Neurofilament (NF) level in patient' fluids have recently emerged as the prime biomarker of ALS disease progression, while NF accumulation in MNs of patients is the oldest and one of the best pathological hallmarks. However, the way NF accumulations could lead to MN degeneration remains unknown. To assess NF accumulations and study the impact on MNs, we compared MNs derived from induced pluripotent stem cells (iPSC) of patients carrying mutations in C9orf72, SOD1 and TARDBP genes, the three main ALS genetic causes...
May 15, 2023: Cellular and Molecular Life Sciences: CMLS
Zhichuan Zhu, Rebecca L Johnson, Zhigang Zhang, Laura E Herring, Guochun Jiang, Blossom Damania, Lindsey I James, Pengda Liu
STING acts as a cytosolic nucleotide sensor to trigger host defense upon viral or bacterial infection. While STING hyperactivation can exert anti-tumor effects by increasing T cell filtrates, in other contexts hyperactivation of STING can contribute to autoimmune and neuroinflammatory diseases. Several STING targeting agonists and a smaller subset of antagonists have been developed, yet STING targeted degraders, or PROTACs, remain largely underexplored. Here, we report a series of STING-agonist derived PROTACs that promote STING degradation in renal cell carcinoma (RCC) cells...
May 14, 2023: Cellular and Molecular Life Sciences: CMLS
Qing Li, Chong Cui, Rongyu Liao, Xidi Yin, Daqi Wang, Yanbo Cheng, Bowei Huang, Liqin Wang, Meng Yan, Jinan Zhou, Jingjing Zhao, Wei Tang, Yingyi Wang, Xiaohan Wang, Jun Lv, Jinsong Li, Huawei Li, Yilai Shu
Mutations in GJB2 (Gap junction protein beta 2) are the most common genetic cause of non-syndromic hereditary deafness in humans, especially the 35delG and 235delC mutations. Owing to the homozygous lethality of Gjb2 mutations in mice, there are currently no perfect mouse models carrying Gjb2 mutations derived from patients for mimicking human hereditary deafness and for unveiling the pathogenesis of the disease. Here, we successfully constructed heterozygous Gjb2+/35delG and Gjb2+/235delC mutant mice through advanced androgenic haploid embryonic stem cell (AG-haESC)-mediated semi-cloning technology, and these mice showed normal hearing at postnatal day (P) 28...
May 13, 2023: Cellular and Molecular Life Sciences: CMLS
Dena Panovska, Pouya Nazari, Basiel Cole, Pieter-Jan Creemers, Marleen Derweduwe, Lien Solie, Sofie Van Gassen, Annelies Claeys, Tatjana Verbeke, Elizabeth F Cohen, Michael Y Tolstorukov, Yvan Saeys, David Van der Planken, Francesca M Bosisio, Eric Put, Sven Bamps, Paul M Clement, Michiel Verfaillie, Raf Sciot, Keith L Ligon, Steven De Vleeschouwer, Asier Antoranz, Frederik De Smet
BACKGROUND: Functional profiling of freshly isolated glioblastoma (GBM) cells is being evaluated as a next-generation method for precision oncology. While promising, its success largely depends on the method to evaluate treatment activity which requires sufficient resolution and specificity. METHODS: Here, we describe the 'precision oncology by single-cell profiling using ex vivo readouts of functionality' (PROSPERO) assay to evaluate the intrinsic susceptibility of high-grade brain tumor cells to respond to therapy...
May 12, 2023: Cellular and Molecular Life Sciences: CMLS
Fuping Qian, Guanyun Wei, Yajing Gao, Xin Wang, Jie Gong, Chao Guo, Xiaoning Wang, Xu Zhang, Jinxiang Zhao, Cheng Wang, Mengting Xu, Yuebo Hu, Guoli Yin, Jiahui Kang, Renjie Chai, Gangcai Xie, Dong Liu
No abstract text is available yet for this article.
May 12, 2023: Cellular and Molecular Life Sciences: CMLS
Lei Chong, Negah Ahmadvand, Afshin Noori, Yuqing Lv, Chengshui Chen, Saverio Bellusci, Jin-San Zhang
Alveolar epithelial type II cells (AT2s) together with AT1s constitute the epithelial lining of lung alveoli. In contrast to the large flat AT1s, AT2s are cuboidal and smaller. In addition to surfactant production, AT2s also serve as prime alveolar progenitors in homeostasis and play an important role during regeneration/repair. Based on different lineage tracing strategies in mice and single-cell transcriptomic analysis, recent reports highlight the heterogeneous nature of AT2s. These studies present compelling evidence for the presence of stable or transitory AT2 subpopulations with distinct marker expression, signaling pathway activation and functional properties...
May 11, 2023: Cellular and Molecular Life Sciences: CMLS
Gang Wang, Yulin Luo, Xiaojun Gao, Yu Liang, Feifei Yang, Jianbo Wu, Dan Fang, Mao Luo
Alterations in the vascular smooth muscle cells (VSMC) phenotype play a critical role in the pathogenesis of several cardiovascular diseases, including hypertension, atherosclerosis, and restenosis after angioplasty. MicroRNAs (miRNAs) are a class of endogenous noncoding RNAs (approximately 19-25 nucleotides in length) that function as regulators in various physiological and pathophysiological events. Recent studies have suggested that aberrant miRNAs' expression might underlie VSMC phenotypic transformation, appearing to regulate the phenotypic transformations of VSMCs by targeting specific genes that either participate in the maintenance of the contractile phenotype or contribute to the transformation to alternate phenotypes, and affecting atherosclerosis, hypertension, and coronary artery disease by altering VSMC proliferation, migration, differentiation, inflammation, calcification, oxidative stress, and apoptosis, suggesting an important regulatory role in vascular remodeling for maintaining vascular homeostasis...
May 10, 2023: Cellular and Molecular Life Sciences: CMLS
Caroline Kampmeyer, Martin Grønbæk-Thygesen, Nicole Oelerich, Michael H Tatham, Matteo Cagiada, Kresten Lindorff-Larsen, Wouter Boomsma, Kay Hofmann, Rasmus Hartmann-Petersen
In terms of its relative frequency, lysine is a common amino acid in the human proteome. However, by bioinformatics we find hundreds of proteins that contain long and evolutionarily conserved stretches completely devoid of lysine residues. These so-called lysine deserts show a high prevalence in intrinsically disordered proteins with known or predicted functions within the ubiquitin-proteasome system (UPS), including many E3 ubiquitin-protein ligases and UBL domain proteasome substrate shuttles, such as BAG6, RAD23A, UBQLN1 and UBQLN2...
May 9, 2023: Cellular and Molecular Life Sciences: CMLS
Michael Levin
A critical aspect of evolution is the layer of developmental physiology that operates between the genotype and the anatomical phenotype. While much work has addressed the evolution of developmental mechanisms and the evolvability of specific genetic architectures with emergent complexity, one aspect has not been sufficiently explored: the implications of morphogenetic problem-solving competencies for the evolutionary process itself. The cells that evolution works with are not passive components: rather, they have numerous capabilities for behavior because they derive from ancestral unicellular organisms with rich repertoires...
May 8, 2023: Cellular and Molecular Life Sciences: CMLS
Tahir Ali, Antonia N Klein, Alex Vu, Maria I Arifin, Samia Hannaoui, Sabine Gilch
Currently, no effective therapeutics exist for the treatment of incurable neurodegenerative diseases such as Alzheimer's disease (AD). The cellular prion protein (PrPC ) acts as a high-affinity receptor for amyloid beta oligomers (AβO), a main neurotoxic species mediating AD pathology. The interaction of AβO with PrPC subsequently activates Fyn tyrosine kinase and neuroinflammation. Herein, we used our previously developed peptide aptamer 8 (PA8) binding to PrPC as a therapeutic to target the AβO-PrP-Fyn axis and prevent its associated pathologies...
May 7, 2023: Cellular and Molecular Life Sciences: CMLS
José Manuel Hernandez-Lopez, Cristina Hernandez-Medina, Cristina Medina-Corvalan, Mónica Rodenas, Almagro Francisca, Claudia Perez-Garcia, Diego Echevarria, Francisco Carratala, Emilio Geijo-Barrientos, Salvador Martinez
The COVID-19 pandemic spread around the world is due to the enormous capacity of the SARS-CoV-2 coronavirus to be transmitted between humans, causing a threat to global public health. It has been shown that the entry of this virus into cells is highly facilitated by the presence of angiotensin-converting enzyme 2 (ACE2) in the cell membrane. Currently, we have no precise knowledge of how this receptor expresses in the brain of human fetus and, as a consequence, we do not know how susceptible the neural cells in the developing brain are to being infected through the vertical transmission of this virus, from mother to fetus...
May 7, 2023: Cellular and Molecular Life Sciences: CMLS
Ana Montero-Calle, Raquel Coronel, María Garranzo-Asensio, Guillermo Solís-Fernández, Alberto Rábano, Vivian de Los Ríos, María Jesús Fernández-Aceñero, Marta L Mendes, Javier Martínez-Useros, Diego Megías, María Teresa Moreno-Casbas, Alberto Peláez-García, Isabel Liste, Rodrigo Barderas
BACKGROUND: Alzheimer's disease (AD) is a progressive, chronic, and neurodegenerative disease, and the most common cause of dementia worldwide. Currently, the mechanisms underlying the disease are far from being elucidated. Thus, the study of proteins involved in its pathogenesis would allow getting further insights into the disease and identifying new markers for AD diagnosis. METHODS: We aimed here to analyze protein dysregulation in AD brain by quantitative proteomics to identify novel proteins associated with the disease...
May 7, 2023: Cellular and Molecular Life Sciences: CMLS
Jennifer Hua, Elvira Garcia de Paco, Nathalie Linck, Tangui Maurice, Catherine Desrumaux, Bénédicte Manoury, François Rassendren, Lauriane Ulmann
Numerous evidences support that microglia contributes to the progression of Alzheimer's disease. P2X4 receptors are ATP-gated channels with high calcium permeability, which are de novo expressed in a subset of reactive microglia associated with various pathological contexts, contributing to microglial functions. P2X4 receptors are mainly localized in lysosomes and trafficking to the plasma membrane is tightly regulated. Here, we investigated the role of P2X4 in the context of Alzheimer's disease (AD). Using proteomics, we identified Apolipoprotein E (ApoE) as a specific P2X4 interacting protein...
May 5, 2023: Cellular and Molecular Life Sciences: CMLS
Xiaoqing Guo, Bowei Li, Cheng Wen, Feng Zhang, Xuying Xiang, Lei Nie, Jiaojiao Chen, Ling Mao
Disordered lipid accumulation in the arterial wall is a hallmark of atherosclerosis. Previous studies found that the expression of triggering receptor expressed on myeloid cells 2 (TREM2), a transmembrane receptor of the immunoglobulin family, is increased in mouse atherosclerotic aortic plaques. However, it remains unknown whether TREM2 plays a role in atherosclerosis. Here we investigated the role of TREM2 in atherosclerosis using ApoE knockout (ApoE-/- ) mouse models, primary vascular smooth muscle cells (SMCs), and bone marrow-derived macrophages (BMDMs)...
May 3, 2023: Cellular and Molecular Life Sciences: CMLS
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