“A very big challenge”: a qualitative study to explore the early barriers and enablers to implementing a national genomic medicine service in England by Bettina Friedrich, Cecilia Vindrola-Padros, Anneke M. Lucassen, Anneke M. Lucassen, Chris Patch, Angus Clarke, Monica Lakhanpaul, Celine Lewis, Celine Lewis

“…Challenges include: 1) concerns around the lack of trained and available workforce (clinicians and scientists) to seek consent from patients, interpret findings and communicate results; 2) the lack of a digital, coordinated infrastructure in place to support and standardize delivery with knock-on effects including onerous administrative aspects required to consent patients and order WGS tests; 3) that the “mainstreaming agenda”, whilst considered important, encountered reluctance to become engaged from those who did not see it as a priority or viewed it as being politically rather than clinically driven; 4) the timelines and targets set for the GMS were perceived by some as too ambitious. …”
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Genetic background influences the 5XFAD Alzheimer's disease mouse model brain proteome by Cheyenne D. Hurst, Cheyenne D. Hurst, Amy R. Dunn, Eric B. Dammer, Eric B. Dammer, Duc M. Duong, Duc M. Duong, Sarah M. Shapley, Sarah M. Shapley, Nicholas T. Seyfried, Nicholas T. Seyfried, Nicholas T. Seyfried, Catherine C. Kaczorowski, Catherine C. Kaczorowski, Erik C. B. Johnson, Erik C. B. Johnson

“…Our findings suggest that the genetic diversity introduced by crossing B6 and D2 inbred backgrounds influences proteomic changes related to disease in the 5XFAD model, and that proteomic analysis of other genetic backgrounds in transgenic and knock-in AD mouse models is warranted to capture the full range of molecular heterogeneity in genetically diverse models of AD.…”
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Consistency and reproducibility of large panel next-generation sequencing: Multi-laboratory assessment of somatic mutation detection on reference materials with mismatch repair and... by Duo Wang, Yuanfeng Zhang, Rui li, Jinming Li, Rui Zhang

“…Methods: Genes involved in mismatch repair and DNA proofreading were knocked down using the CRISPR-Cas9 technology to accumulate somatic mutations in a defined GM12878 cell line. …”
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Epigenetic inactivation of the 5-methylcytosine RNA methyltransferase NSUN7 is associated with clinical outcome and therapeutic vulnerability in liver cancer by Vanessa Ortiz-Barahona, Marta Soler, Veronica Davalos, Carlos A. García-Prieto, Maxime Janin, Fernando Setien, Irene Fernández-Rebollo, Joan J. Bech-Serra, Carolina De La Torre, Sonia Guil, Alberto Villanueva, Pei-Hong Zhang, Li Yang, Marco Guarnacci, Ulrike Schumann, Thomas Preiss, Ugne Balaseviciute, Robert Montal, Josep M. Llovet, Manel Esteller

“…NSUN7 epigenetic inactivation was common in liver malignant cells and we coupled bisulfite conversion of cellular RNA with next-generation sequencing (bsRNA-seq) to find the RNA targets of this poorly characterized putative RNA methyltransferase. Using knock-out and restoration-of-function models, we observed that the mRNA of the coiled-coil domain containing 9B (CCDC9B) gene required NSUN7-mediated methylation for transcript stability. …”
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Detection of endogenous NPY release determined by novel GRAB sensor in cultured cortical neurons by Emma Kragelund Christensen, Ainoa Konomi-Pilkati, Joscha Rombach, Raquel Comaposada-Baro, Huan Wang, Huan Wang, Yulong Li, Yulong Li, Andreas Toft Sørensen

“…Studies on the role of NPY have primarily been limited to exogenous application, transgene expression, or knock-out in biological systems, which are often combined with pharmacological probes to delineate the involvement of specific NPY receptors. …”
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Inhibition of the SLC35B2–TPST2 Axis of Tyrosine Sulfation Attenuates the Growth and Metastasis of Pancreatic Ductal AdenocarcinomSummary by Xinran Cai, Sihan Li, Xuemei Zeng, Meishu Xu, Zehua Wang, Aatur D. Singhi, Daolin Tang, Song Li, Nathan A. Yates, Da Yang, Wen Xie

“…Results: High expressions of SLC35B2 and TPST2 were correlated with poor PDAC patient survival. Knocking down SLC35B2 or TPST2, or pharmacologicically inhibiting sulfation, resulted in the inhibition of PDAC cell proliferation and migration in vitro. …”
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Inhibition of SAT1 alleviates chondrocyte inflammation and ferroptosis by repressing ALOX15 expression and activating the Nrf2 pathway by Jingting Xu, Zhaoxuan Ruan, Zhou Guo, Liangcai Hou, Genchun Wang, Zehang Zheng, Xiong Zhang, Haigang Liu, Kai Sun, Fengjing Guo

“…We used small interfering RNA (siRNA) to knock down the spermidine/spermine N1-acetyltransferase 1 (Sat1) and arachidonate 15-lipoxygenase (Alox15), and examined damage-associated events including inflammation, ferroptosis, and oxidative stress of chondrocytes. …”
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Acetylation-Mimic Mutation of TRIM28-Lys304 to Gln Attenuates the Interaction with KRAB-Zinc-Finger Proteins and Affects Gene Expression in Leukemic K562 Cells by Yao-Jen Chang, Steven Lin, Zhi-Fu Kang, Bin-Jon Shen, Wen-Hai Tsai, Wen-Ching Chen, Hsin-Pin Lu, Yu-Lun Su, Shu-Jen Chou, Shu-Yu Lin, Sheng-Wei Lin, Yin-Jung Huang, Hsin-Hui Wang, Ching-Jin Chang

“…The <i>TRIM28</i>-K304Q knock-in cells were created in K562 erythroleukemia cells by CRISPR-Cas9 (Clustered regularly interspaced short palindromic repeats/CRISPR-associated protein nuclease 9) gene editing method. …”
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Creating saponin‐free yellow pea seeds by CRISPR/Cas9‐enabled mutagenesis on β‐amyrin synthase by Connor L. Hodgins, Eman M. Salama, Rahul Kumar, Yang Zhao, Susan A. Roth, Irene Z. Cheung, Jieyu Chen, Gene C. Arganosa, Thomas D. Warkentin, Pankaj Bhowmik, Byung‐Kook Ham, Dae‐Kyun Ro

“…Saponins are glycosylated triterpenoids and are a major source of bitter, astringent, and metallic off‐flavors in pea products. β‐amyrin synthase (BAS) is the entry point enzyme for saponin biosynthesis in pea and therefore is an ideal target for knock‐out using CRISPR/Cas9 genome editing to produce saponin deficient pea varieties. …”
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A human mitofusin 2 mutation can cause mitophagic cardiomyopathy by Antonietta Franco, Jiajia Li, Daniel P Kelly, Ray E Hershberger, Ali J Marian, Renate M Lewis, Moshi Song, Xiawei Dang, Alina D Schmidt, Mary E Mathyer, John R Edwards, Cristina de Guzman Strong, Gerald W Dorn

“…CRISPR editing of the R400Q mutation into the mouse Mfn2 gene induced perinatal cardiomyopathy with no other organ involvement; knock-in of Mfn2 T105M or M376V did not affect the heart. …”
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Potential Involvement of <i>ewsr1-w</i> Gene in Ovarian Development of Chinese Tongue Sole, <i>Cynoglossus semilaevis</i> by Peng Cheng, Zhangfan Chen, Wenteng Xu, Na Wang, Qian Yang, Rui Shi, Xihong Li, Zhongkai Cui, Jiayu Cheng, Songlin Chen

“…Our results will provide clues on the gene expression level, transcriptional regulation and knock-down effect of <i>ewsr1</i> gene during ovarian development in teleost.…”
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Chronic CD40L blockade is required for long-term cardiac allograft survival with a clinically relevant CTLA4-Ig dosing regimen by Lukas W. Unger, Lukas W. Unger, Moritz Muckenhuber, Benedikt Mahr, Christoph Schwarz, Christoph Schwarz, Nina Pilat, Nicolas Granofszky, Heinz Regele, Thomas Wekerle

“…The aim of this study was to define the conditions under which the combination of CTLA4-Ig and CD40L blockade leads to rejection-free permanent graft survival in a stringent murine heart transplantation model.MethodsNaïve wild-type or CD40L (CD154) knock-out mice received a fully mismatched BALB/c cardiac allograft. …”
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NAT10 Maintains OGA mRNA Stability Through ac4C Modification in Regulating Oocyte Maturation by Jiayu Lin, Yuting Xiang, Yuting Xiang, Jiana Huang, Haitao Zeng, Yanyan Zeng, Jiawen Liu, Taibao Wu, Qiqi Liang, Xiaoyan Liang, Jingjie Li, Chuanchuan Zhou

“…To find out whether the influence of NAT10-mediated ac4C on oocyte maturation was mediated by OGA, we further explored the role of OGA in IVM. After knocking down OGA of oocytes, oocyte maturation was inhibited. …”
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Urokinase-type plasminogen activator (uPA) regulates invasion and matrix remodelling in colorectal cancer by Auxtine Micalet, Luke J. Tappouni, Katarzyna Peszko, Despoina Karagianni, Ashley Lam, John R. Counsell, Sergio A. Quezada, Emad Moeendarbary, Umber Cheema

“…Results: We showed that uPA is highly expressed in invasive breast and colorectal cancers, and these invasive cancer cells locally degrade their TME. PLAU (uPA) gene knock-out (KO) completely stopped matrix remodelling and significantly reduced cancer invasion. …”
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Transformation to small cell lung cancer is irrespective of EGFR and accelerated by SMAD4-mediated ASCL1 transcription independently of RB1 in non-small cell lung cancer by Xi Ding, Min-xing Shi, Di Liu, Jing-xue Cao, Kai-xuan Zhang, Run-dong Zhang, Li-ping Zhang, Kai-xing Ai, Bo Su, Jie Zhang

“…To validate the putative gene function, we established knocked-out models by CRISPR-Cas 9 in HCC827 and A549-TP53-/- cells and investigated the effects on tumor growth, drug sensitivity and neuroendocrine phenotype in vitro and in vivo. …”
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Development and verification of a combined immune- and cancer-associated fibroblast related prognostic signature for colon adenocarcinoma by Jingsun Wei, Jingsun Wei, Jingsun Wei, Xiaoxu Ge, Xiaoxu Ge, Xiaoxu Ge, Yucheng Qian, Yucheng Qian, Yucheng Qian, Kai Jiang, Kai Jiang, Kai Jiang, Xin Chen, Xin Chen, Xin Chen, Wei Lu, Wei Lu, Wei Lu, Hang Yang, Hang Yang, Hang Yang, Dongliang Fu, Dongliang Fu, Dongliang Fu, Yimin Fang, Yimin Fang, Yimin Fang, Xinyi Zhou, Xinyi Zhou, Xinyi Zhou, Qian Xiao, Qian Xiao, Qian Xiao, Yang Tang, Yang Tang, Yang Tang, Kefeng Ding, Kefeng Ding, Kefeng Ding

“…Integration of these variables led to more precise prediction of treatment efficacy, enabling personalized immunotherapy for COAD patients. Knocking down S1PR5 can enhance the efficacy of PD-1 monoclonal antibody, promoting the cytotoxicity of T cells against HCT116 cells ((p&lt;0.05).DiscussionThese findings indicate that the ICRG signature may be a valuable tool for predicting prognostic risk, evaluating the efficacy of immunotherapy, and tailoring personalized treatment options for patients with COAD.…”
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Rhomboid domain-containing protein 1 promotes breast cancer progression by regulating the p-Akt and CDK2 levels by Xin Zhang, Yuechao Zhao, Changjun Wang, Hongge Ju, Wenjie Liu, Xiaohui Zhang, Shiying Miao, Linfang Wang, Qiang Sun, Wei Song

“…Methods Immunohistochemistry was performed to evaluate RHBDD1 expression in 116 breast cancer tissue and 39 adjacent normal tissue and expression of RHBDD1, phospho-Akt (p-Akt) and cyclin-dependent kinase 2 (CDK2) in the same 84 breast cancer specimens. RHBDD1-knock-out cells were established using breast cancer cell lines. …”
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Ablation of Shank3 alleviates cardiac dysfunction in aging mice by promoting CaMKII activation and Parkin-mediated mitophagy by Ying Wang, Yuerong Xu, Wangang Guo, Yexian Fang, Lang Hu, Runze Wang, Ran Zhao, Dong Guo, Bingchao Qi, Gaotong Ren, Jun Ren, Yan Li, Mingming Zhang

“…In an in vitro study, senescent cardiomyocytes treated with D-gal exhibited reduced mitophagy and significantly elevated Shank3 expression. Shank3 knock-down restored mitophagy, leading to increased mitochondrial membrane potential, decreased mitochondrial oxidative stress, and reduced apoptosis in senescent cardiomyocytes, whereas Shank3 overexpression mimicked D-gal-induced mitophagy inhibition and mitochondrial dysfunction in normally cultured cardiomyocytes. …”
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Circ_0084043-miR-134-5p axis regulates PCDH9 to suppress melanoma by Guiyue Cai, Guiyue Cai, Ruitao Zou, Ruitao Zou, Huizhi yang, Jiahao Xie, Xiaoxuan Chen, Chunchan Zheng, Sujun Luo, Na Wei, Shuang Liu, Rongyi Chen, Rongyi Chen

“…Ectopic expression or knock down (KD) of PCDH9 with a lentivirus vector, we explored its effects on the proliferation, invasion, and apoptosis of melanoma and verified its regulatory effect on ras-related C3 botulinum toxin substrate 1 (RAC1), proline-rich tyrosine kinase 2 (Pyk2), Cyclin D1, matrix metalloproteinase 2 (MMP2), and MMP9. …”
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Overcoming doxorubicin resistance in triple-negative breast cancer using the class I-targeting HDAC inhibitor bocodepsin/OKI-179 to promote apoptosis by Stephen G. Smoots, Anna R. Schreiber, Marilyn M. Jackson, Stacey M. Bagby, Adrian T A. Dominguez, Evan D. Dus, Cameron A. Binns, Morgan MacBeth, Phaedra A. Whitty, Jennifer R. Diamond, Todd M. Pitts

“…In vivo, the combination resulted in increased tumor growth inhibition compared to either single agent. shRNA knock-down of p53 led to increased doxorubicin-induced senescence that was decreased with the addition of OKI-005 in vitro. …”
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