Article
Biology
Maeva Dufies, Annelies Verbiest, Lindsay S. Cooley, Papa Diogop Ndiaye, Xingkang He, Nicolas Nottet, Wilfried Souleyreau, Anais Hagege, Stephanie Torrino, Julien Parola, Sandy Giuliano, Delphine Borchiellini, Renaud Schiappa, Baharia Mograbi, Jessica Zucman-Rossi, Karim Bensalah, Alain Ravaud, Patrick Auberger, Andreas Bikfalvi, Emmanuel Chamorey, Nathalie Rioux-Leclercq, Nathalie M. Mazure, Benoit Beuselinck, Yihai Cao, Jean Christophe Bernhard, Damien Ambrosetti, Gilles Pages
Summary: Dufies et al. found high Plk1 expression levels in aggressive clear cell renal cell carcinoma and discovered that Plk1 is transcriptionally upregulated in a manner dependent on HIF-2. They also found that high Plk1 expression is correlated to a poor prognosis and resistance to tyrosine kinase inhibitor against VEGF receptor, suggesting a critical role for hypoxia/HIF-2-induced Plk1 in disease progression.
COMMUNICATIONS BIOLOGY
(2021)
Article
Oncology
Rouven Hoefflin, Sabine Harlander, Behnaz A. Abhari, Asin Peighambari, Mojca Adlesic, Philipp Seidel, Kyra Zodel, Stefan Haug, Burulca Goecmen, Yong Li, Bernd Lahrmann, Niels Grabe, Danijela Heide, Melanie Boerries, Anna Koettgen, Mathias Heikenwalder, Ian J. Frew
Summary: Clear cell renal cell carcinoma is a common kidney tumor with most tumors harboring an inactivation of the VHL gene, leading to the accumulation of HIF-1 alpha and HIF-2 alpha. Promising clinical results of specific HIF-2 alpha inhibitors provide new treatment options for advanced cancer patients, but resistance remains a challenge. Additionally, studies show that HIF-2 alpha inhibition can suppress the tumor immune microenvironment.
Article
Biochemistry & Molecular Biology
Yangsook Song Green, Maria C. Ferreira dos Santos, Daniel Fuja, Ethan Reichert, Alexandre R. Campos, Sophie J. Cowman, Karen Acuna Pilarte, Jessica Kohan, Sheryl R. Tripp, Elizabeth A. Leibold, Deepika Sirohi, Neeraj Agarwal, Xiaohui Liu, Mei Yee Koh
Summary: This study found that targeting ISCA2 protein can reduce HIF-1/2 alpha protein levels and inhibit the development of clear cell renal cell carcinoma (ccRCC) by inducing ferroptosis. ISCA2 inhibition not only decreases HIF-2 alpha protein levels by blocking IRE-dependent translation, but can also reduce HIF-1 alpha translation at higher concentrations through unknown mechanisms. Additionally, ISCA2 inhibition triggers the iron starvation response, leading to iron/metals overload and cell death.
Article
Oncology
Bo Zhan, Xiao Dong, Yulin Yuan, Zheng Gong, Bohan Li
Summary: The study reveals that HIF-1α is downregulated in ccRCC, inhibiting cell proliferation, migration, and invasion, which has important biological implications.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Fengqi Yan, Qinhao Wang, Mingyuan Xia, Yi Ru, Wei Hu, Guang Yan, Xin Xiong, Mei Zhang, Jiancai Wang, Qi Li, Bo Zhang, He Wang, Wei Lin, Guojun Wu, Xia Li
Summary: MIIP is identified as a novel tumor suppressor in ccRCC, inhibiting cancer cell proliferation and angiogenesis through negative regulation of the HIF-2 alpha-CYR61 axis.
CANCER BIOLOGY & MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Song Chen, Yejinpeng Wang, Yaoyi Xiong, Tianchen Peng, Mengxin Lu, Lian Zhang, Zhongqiang Guo
Summary: The study found that wild-type IDH1 could inhibit the proliferation and migration of RCC cells, as well as promote apoptosis, while the mutant IDH1 lacked this biological function. Additionally, the study verified the correlation between IDH1 and hypoxia signal-related proteins, and the potential role of α-KG in RCC treatment.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2021)
Review
Oncology
Borivoj Golijanin, Kamil Malshy, Sari Khaleel, Galina Lagos, Ali Amin, Liang Cheng, Dragan Golijanin, Anthony Mega
Summary: Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer, and its pathogenesis is mainly caused by biallelic loss of the tumor suppressor gene VHL. Dysfunctional degradation of HIF due to VHL loss leads to overaccumulation of HIF, resulting in the activation of genes responsible for cell survival and proliferation in ccRCC. Previous therapies have targeted downstream effectors of HIF, but there is now a focus on interfering with upstream targets.
CANCER TREATMENT REVIEWS
(2023)
Review
Oncology
Sonia Mazumder, Paul J. Higgins, Rohan Samarakoon
Summary: Mutations in the VHL gene contribute to the development of renal cell carcinoma, particularly the clear cell variant. HIF-2 alpha plays a crucial role in promoting tumor progression and metastasis in these cases. Inhibiting HIF-2 alpha and its associated molecular pathways can be an effective strategy to suppress the aggressiveness of ccRCC.
Article
Medicine, Research & Experimental
Zhuonan Liu, Tianshui Sun, Chiyuan Piao, Zhe Zhang, Chuize Kong
Summary: The study found that METTL13 is downregulated in ccRCC and is associated with poor prognosis; METTL13 can inhibit the growth and metastasis of ccRCC cells through multiple molecular mechanisms.
JOURNAL OF TRANSLATIONAL MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Junhui Hu, Ping Tan, Moe Ishihara, Nicholas A. Bayley, Shiruyeh Schokrpur, Jeremy G. Reynoso, Yangjun Zhang, Raymond J. Lim, Camelia Dumitras, Lu Yang, Steven M. Dubinett, Parmjit S. Jat, Jacques Van Snick, Jiaoti Huang, Arnold I. Chin, Robert M. Prins, Thomas G. Graeber, Hua Xu, Lily Wu
Summary: Loss of function of the VHL tumor suppressor gene is a characteristic of ccRCC. Heterogeneity in the loss of this gene is important but often overlooked. By studying intratumoral VHL heterogeneity, the researchers found that VHL gene-deleted cells exhibited increased motility but decreased proliferation and tumorigenicity compared to VHL-expressing cells. Combined tumors with both VHL+ and VHL-KO cells showed rampant lung metastases, driven by the crosstalk between these heterogeneous cell populations. Targeting the soluble protein POSTN, secreted by VHL- cells, could effectively suppress lung metastases. This work suggests a new strategy to disrupt the metastatic crosstalk within tumors and halt the progression of ccRCC.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2023)
Article
Chemistry, Medicinal
Yancheng Yu, Fulai Yang, Quanwei Yu, Simeng Liu, Chenyang Wu, Kaijun Su, Le Yang, Xiaoqian Bao, Zhihong Li, Xiang Li, Xiaojin Zhang
Summary: A novel HIF-2 alpha agonist, compound 26, was discovered with potent nanomolar activity and the ability to enhance HIF-2 dimerization. It showed good pharmacokinetic and in vivo safety profiles, and when combined with the prolyl hydroxylase inhibitor AKB-6548, it synergistically increased plasma erythropoietin levels in mice and alleviated zebrafish anemia induced by doxorubicin. These findings suggest potential therapeutic implications for HIF-2 alpha agonists in the treatment of renal anemia.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Ming-xiao Zhang, Li-zhen Zhang, Liang-min Fu, Hao-hua Yao, Lei Tan, Zi-hao Feng, Jia-ying Li, Jun Lu, Yi-hui Pan, Guan-nan Shu, Peng-ju Li, Yi-ming Tang, Zhuang-yao Liao, Jin-huan Wei, Wei Chen, Jian-ping Guo, Jun-hang Luo, Zhen-hua Chen
Summary: In this study, the oncogenic lncRNA PVT1 was found to promote the development of ccRCC by stabilizing HIF2 alpha, forming a positive feedback loop. High expression of PVT1 was associated with poor prognosis in ccRCC patients, and PVT1 enhanced cell proliferation, migration, invasion, and tumor angiogenesis. The interaction between PVT1 and HIF2 alpha played a key role in tumorigenesis and progression of ccRCC.
Article
Oncology
Rusha Yin, Shuai Liu
Summary: SHARPIN upregulation in ccRCC patients leads to poor prognosis and is positively associated with HIF-2α; SHARPIN promotes the ubiquitination and degradation of pVHL to sustain HIF-2α activation.
Review
Endocrinology & Metabolism
Haiyan Zhu, Xin Wang, Shihao Lu, Kongbo Ou
Summary: Clear cell renal cell carcinoma (ccRCC) is a malignancy characterized by metabolic reprogramming, which provides potential targets for therapeutic interventions. This review summarizes recent discoveries of metabolic alterations in ccRCC, including changes in glucose, lipid, and amino acid metabolism. It also discusses the development of metabolic drugs targeting these pathways and proposes future trends in drug development. Overall, this review highlights the potential for developing new treatments for ccRCC based on metabolic alterations.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Pharmacology & Pharmacy
Elshad Hasanov, Eric Jonasch
Summary: Von Hippel-Lindau (VHL) disease is a genetic syndrome caused by mutations in the VHL gene, resulting in tumors and cysts in multiple organs. Surgery is the standard treatment for localized tumors, but repeated surgeries lead to significant morbidity. MK-6482, a small-molecule HIF 2 alpha inhibitor, has shown promising efficacy and safety in VHL disease-related tumors.
EXPERT OPINION ON INVESTIGATIONAL DRUGS
(2021)
Article
Public, Environmental & Occupational Health
Leny Sanchez, Louisa A. Messenger, Tapan Bhattacharyya, Robert H. Gilman, Holger Mayta, Rony Colanzi, Ricardo Bozo, Manuela Verastegui, Michael A. Miles, Caryn Bern
Summary: This study in Bolivia identified Trypanosoma cruzi DTUs in maternal and infant specimens, with all infant samples genotyped as TcV. Transmitters had significantly higher maternal parasite loads and absorbance values by the lysate ELISA, but no significant difference in reaction to the lineage-specific peptide ELISA was observed.
TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE
(2022)
Article
Biochemistry & Molecular Biology
Wanwisa Dejnirattisai, Jiandong Huo, Daming Zhou, Jiri Zahradnik, Piyada Supasa, Chang Liu, Helen M. E. Duyvesteyn, Helen M. Ginn, Alexander J. Mentzer, Aekkachai Tuekprakhon, Rungtiwa Nutalai, Beibei Wang, Aiste Dijokaite, Suman Khan, Ori Avinoam, Mohammad Bahar, Donal Skelly, Sandra Adele, Sile Ann Johnson, Ali Amini, Thomas G. Ritter, Chris Mason, Christina Dold, Daniel Pan, Sara Assadi, Adam Bellass, Nicola Omo-Dare, David Koeckerling, Amy Flaxman, Daniel Jenkin, Parvinder K. Aley, Merryn Voysey, Sue Ann Costa Clemens, Felipe Gomes Naveca, Valdinete Nascimento, Fernanda Nascimento, Cristiano Fernandes da Costa, Paola Cristina Resende, Alex Pauvolid-Correa, Marilda M. Siqueira, Vicky Baillie, Natali Serafin, Gaurav Kwatra, Kelly Da Silva, Shabir A. Madhi, Marta C. Nunes, Tariq Malik, Peter J. M. Openshaw, J. Kenneth Baillie, Malcolm G. Semple, Alain R. Townsend, Kuan-Ying A. Huang, Tiong Kit Tan, Miles W. Carroll, Paul Klenerman, Eleanor Barnes, Susanna J. Dunachie, Bede Constantinides, Hermione Webster, Derrick Crook, Andrew J. Pollard, Teresa Lambe, Neil G. Paterson, Mark A. Williams, David R. Hall, Elizabeth E. Fry, Juthathip Mongkolsapaya, Jingshan Ren, Gideon Schreiber, David Stuart, Gavin R. Screaton
Summary: On November 24, 2021, the sequence of a new SARS-CoV-2 variant, Omicron-B.1.1.529, was announced. Compared to previous variants, Omicron has a higher number of mutations in the Spike (S) protein. Serum neutralization of Omicron by individuals vaccinated or previously infected with Alpha, Beta, Gamma, or Delta variants is significantly reduced or ineffective. Third vaccine doses can boost neutralization titers against Omicron, and high titers are observed in both vaccinated individuals and those infected with the Delta variant. Most potent monoclonal antibodies and antibodies under development are unable to effectively neutralize Omicron due to mutations in its Spike protein. Omicron has structural changes compared to earlier viruses and utilizes mutations that enhance its binding to ACE2, allowing for immune escape. This results in a large number of mutations in the ACE2 binding site and a rebalancing of receptor affinity similar to earlier pandemic viruses.
Article
Cardiac & Cardiovascular Systems
Tom Norris, Cameron Razieh, Francesco Zaccardi, Thomas Yates, Nazrul Islam, Clare L. Gillies, Yogini Chudasama, Alex Rowlands, Melanie J. Davies, Gerry P. McCann, Amitava Banerjee, Carolyn S. P. Lam, Annemarie B. Docherty, Peter J. M. Openshaw, J. Kenneth Baillie, Malcolm Gracie Semple, Claire Alexandra Lawson, Kamlesh Khunti
Summary: In hospitalized patients with COVID-19, cardiovascular complications or death impacts nearly half of all patients, with the highest risk in those of South Asian or Black ethnicity and in patients with cardiometabolic multimorbidity.
Article
Multidisciplinary Sciences
Bo Meng, Adam Abdullahi, Isabella A. T. M. Ferreira, Niluka Goonawardane, Akatsuki Saito, Izumi Kimura, Daichi Yamasoba, Pehuen Pereyra Gerber, Saman Fatihi, Surabhi Rathore, Samantha K. Zepeda, Guido Papa, Steven A. Kemp, Terumasa Ikeda, Mako Toyoda, Toong Seng Tan, Jin Kuramochi, Shigeki Mitsunaga, Takamasa Ueno, Kotaro Shirakawa, Akifumi Takaori-Kondo, Teresa Brevini, Donna L. Mallery, Oscar J. Charles, John E. Bowen, Anshu Joshi, Alexandra C. Walls, Laurelle Jackson, Darren Martin, Kenneth G. C. Smith, John Bradley, John A. G. Briggs, Jinwook Choi, Elo Madissoon, Kerstin B. Meyer, Petra Mlcochova, Lourdes Ceron-Gutierrez, Rainer Doffinger, Sarah A. Teichmann, Andrew J. Fisher, Matteo S. Pizzuto, Anna de Marco, Davide Corti, Myra Hosmillo, Joo Hyeon Lee, Leo C. James, Lipi Thukral, David Veesler, Alex Sigal, Fotios Sampaziotis, Ian G. Goodfellow, Nicholas J. Matheson, Kei Sato, Ravindra K. Gupta
Summary: The Omicron variant of SARS-CoV-2 has a higher affinity for ACE2 and can evade neutralizing antibodies more effectively compared to the Delta variant. A third dose of mRNA vaccine can provide enhanced protection. Omicron has lower replication in lung and gut cells and less efficiently cleaves its spike protein compared to Delta.
Article
Biochemistry & Molecular Biology
Sebastien Fromentin, Sofia K. Forslund, Kanta Chechi, Judith Aron-Wisnewsky, Rima Chakaroun, Trine Nielsen, Valentina Tremaroli, Boyang Ji, Edi Prifti, Antonis Myridakis, Julien Chilloux, Petros Andrikopoulos, Yong Fan, Michael T. Olanipekun, Renato Alves, Solia Adiouch, Noam Bar, Yeela Talmor-Barkan, Eugeni Belda, Robert Caesar, Luis Pedro Coelho, Gwen Falony, Soraya Fellahi, Pilar Galan, Nathalie Galleron, Gerard Helft, Lesley Hoyles, Richard Isnard, Emmanuelle Le Chatelier, Hanna Julienne, Lisa Olsson, Helle Krogh Pedersen, Nicolas Pons, Benoit Quinquis, Christine Rouault, Hugo Roume, Joe-Elie Salem, Thomas S. B. Schmidt, Sara Vieira-Silva, Peishun Li, Maria Zimmermann-Kogadeeva, Christian Lewinter, Nadja B. Sondertoft, Tue H. Hansen, Dominique Gauguier, Jens Peter Gotze, Lars Kober, Ran Kornowski, Henrik Vestergaard, Torben Hansen, Jean-Daniel Zucker, Serge Hercberg, Ivica Letunic, Fredrik Backhed, Jean-Michel Oppert, Jens Nielsen, Jeroen Raes, Peer Bork, Michael Stumvoll, Eran Segal, Karine Clement, Marc-Emmanuel Dumas, S. Dusko Ehrlich, Oluf Pedersen
Summary: This study investigates the alterations of the metabolome and microbiome from dysmetabolic conditions to ischemic heart disease (IHD). The findings suggest that major changes in the gut microbiome and metabolome may occur long before the clinical onset of IHD. Specific microbiome and metabolome features associated with IHD could better differentiate individuals with IHD from healthy individuals, indicating their pathophysiological relevance.
Article
Multidisciplinary Sciences
Dinesh Aggarwal, Ben Warne, Aminu S. Jahun, William L. Hamilton, Thomas Fieldman, Louis du Plessis, Verity Hill, Beth Blane, Emmeline Watkins, Elizabeth Wright, Grant Hall, Catherine Ludden, Richard Myers, Myra Hosmillo, Yasmin Chaudhry, Malte L. Pinckert, Iliana Georgana, Rhys Izuagbe, Danielle Leek, Olisaeloka Nsonwu, Gareth J. Hughes, Simon Packer, Andrew J. Page, Marina Metaxaki, Stewart Fuller, Gillian Weale, Jon Holgate, Christopher A. Brown, Rob Howes, Duncan McFarlane, Gordon Dougan, Oliver G. Pybus, Daniela De Angelis, Patrick H. Maxwell, Sharon J. Peacock, Michael P. Weekes, Chris Illingworth, Ewan M. Harrison, Nicholas J. Matheson, Ian G. Goodfellow
Summary: Understanding the transmission of SARS-CoV-2 in higher education settings is crucial in limiting spread among students and at-risk populations. A study conducted at the University of Cambridge analyzed viral isolates and found limited introductions of the virus into the university. Student cases were primarily linked to a single genetic cluster, likely originating from social gatherings outside of the university. Transmission was observed within student accommodations and courses but was effectively contained through local infection control measures and a national lockdown. The study highlights important factors in SARS-CoV-2 transmission and effective interventions in higher education settings.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Ao Chen, Sha Liao, Mengnan Cheng, Kailong Ma, Liang Wu, Yiwei Lai, Xiaojie Qiu, Jin Yang, Jiangshan Xu, Shijie Hao, Xin Wang, Huifang Lu, Xi Chen, Xing Liu, Xin Huang, Zhao Li, Yan Hong, Yujia Jiang, Jian Peng, Shuai Liu, Mengzhe Shen, Chuanyu Liu, Quanshui Li, Yue Yuan, Xiaoyu Wei, Huiwen Zheng, Weimin Feng, Zhifeng Wang, Yang Liu, Zhaohui Wang, Yunzhi Yang, Haitao Xiang, Lei Han, Baoming Qin, Pengcheng Guo, Guangyao Lai, Pura Munoz-Canoves, Patrick H. Maxwell, Jean Paul Thiery, Qing-Feng Wu, Fuxiang Zhao, Bichao Chen, Mei Li, Xi Dai, Shuai Wang, Haoyan Kuang, Junhou Hui, Liqun Wang, Ji-Feng Fei, Ou Wang, Xiaofeng Wei, Haorong Lu, Bo Wang, Shiping Liu, Ying Gu, Ming Ni, Wenwei Zhang, Feng Mu, Ye Yin, Huanming Yang, Michael Lisby, Richard J. Cornall, Jan Mulder, Mathias Uhlen, Miguel A. Esteban, Yuxiang Li, Longqi Liu, Xun Xu, Jian Wang
Summary: Spatially resolved transcriptomic technologies enable us to study complex biological processes such as mammalian embryogenesis. However, current methods have limitations in resolution, gene capture, and field of view, which hinders their systematic application to large and three-dimensional mid- and late-gestation embryos. In this study, we developed Stereo-seq, a spatially enhanced resolution omics-sequencing method, by combining DNA nanoball-patterned arrays and in situ RNA capture. We used Stereo-seq to generate the mouse organogenesis spatiotemporal transcriptomic atlas, MOSTA, which provides single cell resolution and high sensitivity for mapping the kinetics and directionality of transcriptional variation during mouse organogenesis. By utilizing this atlas, we investigated the molecular basis of spatial cell heterogeneity and cell fate specification in developing tissues like the dorsal midbrain. Our panoramic atlas will facilitate in-depth research into long-standing questions about normal and abnormal mammalian development.
Article
Multidisciplinary Sciences
Md. Abdul Mazid, Carl Ward, Zhiwei Luo, Chuanyu Liu, Yunpan Li, Yiwei Lai, Liang Wu, Jinxiu Li, Wenqi Jia, Yu Jiang, Hao Liu, Lixin Fu, Yueli Yang, David P. Ibanez, Junjian Lai, Xiaoyu Wei, Juan An, Pengcheng Guo, Yue Yuan, Qiuting Deng, Yang Wang, Ying Liu, Fei Gao, Junwen Wang, Shahriar Zaman, Baoming Qin, Guangming Wu, Patrick H. Maxwell, Xun Xu, Longqi Liu, Wenjuan Li, Miguel A. Esteban
Summary: This study presents a method for producing eight-cell-like cells (8CLCs) from human pluripotent stem cells, and identifies key molecular events and gene networks associated with this conversion through single-cell analysis. The experiments demonstrate the important roles of DPPA3 and TPRX1 in this process. This research provides a resource to uncover the molecular process of early human embryogenesis.
Article
Multidisciplinary Sciences
Lei Han, Xiaoyu Wei, Chuanyu Liu, Giacomo Volpe, Zhenkun Zhuang, Xuanxuan Zou, Zhifeng Wang, Taotao Pan, Yue Yuan, Xiao Zhang, Peng Fan, Pengcheng Guo, Yiwei Lai, Ying Lei, Xingyuan Liu, Feng Yu, Shuncheng Shangguan, Guangyao Lai, Qiuting Deng, Ya Liu, Liang Wu, Quan Shi, Hao Yu, Yunting Huang, Mengnan Cheng, Jiangshan Xu, Yang Liu, Mingyue Wang, Chunqing Wang, Yuanhang Zhang, Duo Xie, Yunzhi Yang, Yeya Yu, Huiwen Zheng, Yanrong Wei, Fubaoqian Huang, Junjie Lei, Waidong Huang, Zhiyong Zhu, Haorong Lu, Bo Wang, Xiaofeng Wei, Fengzhen Chen, Tao Yang, Wensi Du, Jing Chen, Shibo Xu, Juan An, Carl Ward, Zongren Wang, Zhong Pei, Chi-Wai Wong, Xiaolei Liu, Huafeng Zhang, Mingyuan Liu, Baoming Qin, Axel Schambach, Joan Isern, Liqiang Feng, Yan Liu, Xiangyu Guo, Zhen Liu, Qiang Sun, Patrick H. Maxwell, Nick Barker, Pura Munoz-Canoves, Ying Gu, Jan Mulder, Mathias Uhlen, Tao Tan, Shiping Liu, Huanming Yang, Jian Wang, Yong Hou, Xun Xu, Miguel A. Esteban, Longqi Liu
Summary: Studying tissue composition and function in non-human primates is crucial for understanding the nature of human species. This study presents a large-scale cell transcriptomic atlas of the non-human primate Macaca fascicularis, providing a vast annotated resource for studying a species closely related to humans. The atlas has been used to reconstruct cell-cell interaction networks, map the distribution of receptors for viruses causing human infectious diseases, and establish potential clinical associations with human genetic diseases.
Article
Medicine, General & Internal
Felicity Liew, Shubha Talwar, Andy Cross, Brian J. Willett, Sam Scott, Nicola Logan, Matthew K. Siggins, Dawid Swieboda, Jasmin K. Sidhu, Claudia Efstathiou, Shona C. Moore, Chris Davis, Noura Mohamed, Jose Nunag, Clara King, A. A. Roger Thompson, Sarah L. Rowland-Jones, Annemarie B. Docherty, James D. Chalmers, Ling-Pei Ho, Alexander Horsley, Betty Raman, Krisnah Poinasamy, Michael Marks, Onn Min Kon, Luke Howard, Daniel G. Wootton, Susanna Dunachie, Jennifer K. Quint, Rachael A. Evans, Louise V. Wain, Sara Fontanella, Thushan I. de Silva, Antonia Ho, Ewen Harrison, J. Kenneth Baillie, Malcolm G. Semple, Christopher Brightling, Ryan S. Thwaites, Lance Turtle, Peter J. M. Openshaw
Summary: This study examined the nasal and plasma antibody responses in COVID-19 hospitalized patients one year after discharge and vaccination. The findings showed sustained elevated antibody responses in both nasal and plasma samples for at least 12 months, but the nasal antibody response was minimally influenced by vaccination. These findings highlight the importance of developing vaccines that enhance nasal immunity.
Article
Multidisciplinary Sciences
Erola Pairo-Castineira, Konrad Rawlik, Andrew D. Bretherick, Ting Qi, Yang Wu, Isar Nassiri, Glenn A. McConkey, Marie Zechner, Lucija Klaric, Fiona Griffiths, Wilna Oosthuyzen, Athanasios Kousathanas, Anne Richmond, Jonathan Millar, Clark D. Russell, Tomas Malinauskas, Ryan Thwaites, Kirstie Morrice, Sean Keating, David Maslove, Alistair Nichol, Malcolm G. Semple, Julian Knight, Manu Shankar-Hari, Charlotte Summers, Charles Hinds, Peter Horby, Lowell Ling, Danny McAuley, Hugh Montgomery, Peter J. M. Openshaw, Colin Begg, Timothy Walsh, Albert Tenesa, Carlos Flores, Jose A. Riancho, Augusto Rojas-Martinez, Pablo Lapunzina, Jian Yang, Chris P. Ponting, James F. Wilson, Veronique Vitart, Malak Abedalthagafi, Andre D. Luchessi, Esteban J. Parra, Raquel Cruz, Angel Carracedo, Angie Fawkes, Lee Murphy, Kathy Rowan, Alexandre C. Pereira, Andy Law, Benjamin Fairfax, Sara Clohisey Hendry, J. Kenneth Baillie
Summary: This study analyzed genetic data from 24,202 severe COVID-19 cases and identified potentially druggable targets, including inflammatory signaling, monocyte-macrophage activation and endothelial permeability, immunometabolism, and host factors required for viral entry and replication.
Correction
Multidisciplinary Sciences
Erola Pairo-Castineira, Konrad Rawlik, Andrew D. Bretherick, Ting Qi, Yang Wu, Isar Nassiri, Glenn A. McConkey, Marie Zechner, Lucija Klaric, Fiona Griffiths, Wilna Oosthuyzen, Athanasios Kousathanas, Anne Richmond, Jonathan Millar, Clark D. Russell, Tomas Malinauskas, Ryan Thwaites, Kirstie Morrice, Sean Keating, David Maslove, Alistair Nichol, Malcolm G. Semple, Julian Knight, Manu Shankar-Hari, Charlotte Summers, Charles Hinds, Peter Horby, Lowell Ling, Danny McAuley, Hugh Montgomery, Peter J. M. Openshaw, Colin Begg, Timothy Walsh, Albert Tenesa, Carlos Flores, Jose A. Riancho, Augusto Rojas-Martinez, Pablo Lapunzina, Sara Clohisey, Javier Abellan, Beatrice Alex, Janie F. Shelton, Jian Yang, Chris P. Ponting, James F. Wilson, Veronique Vitart, Malak Abedalthagafi, Andre D. Luchessi, Esteban J. Parra, Raquel Cruz, Angel Carracedo, Angie Fawkes, Lee Murphy, Kathy Rowan, Alexandre C. Pereira, Andy Law, Benjamin Fairfax, Sara Clohisey Hendry, J. Kenneth Baillie
Article
Multidisciplinary Sciences
Petros Andrikopoulos, Judith Aron-Wisnewsky, Rima Chakaroun, Antonis Myridakis, Sofia K. Forslund, Trine Nielsen, Solia Adriouch, Bridget Holmes, Julien Chilloux, Sara Vieira-Silva, Gwen Falony, Joe-Elie Salem, Fabrizio Andreelli, Eugeni Belda, Julius Kieswich, Kanta Chechi, Francesc Puig-Castellvi, Mickael Chevalier, Emmanuelle Le Chatelier, Michael T. Olanipekun, Lesley Hoyles, Renato Alves, Gerard Helft, Richard Isnard, Lars Kober, Luis Pedro Coelho, Christine Rouault, Dominique Gauguier, Jens Peter Gotze, Edi Prifti, Philippe Froguel, Jean-Daniel Zucker, Fredrik Backhed, Henrik Vestergaard, Torben Hansen, Jean-Michel Oppert, Matthias Bluher, Jens Nielsen, Jeroen Raes, Peer Bork, Muhammad M. Yaqoob, Michael Stumvoll, Oluf Pedersen, S. Dusko Ehrlich, Karine Clement, Marc-Emmanuel Dumas
Summary: The study reveals that kidney function is the main determinant of circulating TMAO levels, while microbiota composition and diet play minor but significant roles. Mediation analysis suggests a causal relationship between TMAO and kidney function, which is supported by preclinical models. The study also finds that anti-diabetic drugs with reno-protective properties can lower TMAO levels.
NATURE COMMUNICATIONS
(2023)
Article
Biotechnology & Applied Microbiology
Hannah Goldswain, Xiaofeng Dong, Rebekah Penrice-Randal, Muhannad Alruwaili, Ghada T. Shawli, Tessa Prince, Maia Kavanagh Williamson, Jayna Raghwani, Nadine Randle, Benjamin Jones, I'ah Donovan-Banfield, Francisco J. Salguero, Julia A. Tree, Yper Hall, Catherine Hartley, Maximilian Erdmann, James Bazire, Tuksin Jearanaiwitayakul, Malcolm G. Semple, Peter J. M. Openshaw, J. Kenneth Baillie, Stevan R. Emmett, Paul Digard, David A. Matthews, Lance Turtle, Alistair C. Darby, Andrew D. Davidson, Miles W. Carroll, Julian A. Hiscox
Summary: The mutational landscape of SARS-CoV-2 varies between the dominant viral genome sequence and minor genomic variant population. The emergence of D614G substitution in the spike protein is associated with increased transmissibility. The P323L substitution in the viral polymerase is also observed, but not under strong selective pressure.
Article
Medical Informatics
Fiina Narhi, S. Ramani Moonesinghe, Susan D. Shenkin, Thomas M. Drake, Rachel H. Mulholland, Cara Donegan, Jake Dunning, Cameron J. Fairfield, Michelle Girvan, Hayley E. Hardwick, Antonia Ho, Gary Leeming, Jonathan S. Nguyen-Van-Tam, Riinu Pius, Clark D. Russell, Catherine A. Shaw, Rebecca G. Spencer, Lance Turtle, Peter J. M. Openshaw, J. Kenneth Baillie, Ewen M. Harrison, Malcolm G. Semple, Annemarie B. Docherty
Summary: The study evaluated the clinical implementation of corticosteroids in COVID-19 patients in the UK and found that patients older than 70, those with chronic neurological diseases and dementia, as well as pregnant women, were less likely to receive corticosteroids. This reflects potential inequalities in access to life-saving care among certain patient groups.
LANCET DIGITAL HEALTH
(2022)
