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1. Single-cell multi-ome and immune profiles of the Inspiration4 crew reveal conserved, cell-type, and sex-specific responses to spaceflight

Author

Kim, JangKeun, Tierney, Braden T., Overbey, Eliah G., Dantas, Ezequiel, Fuentealba, Matias, Park, Jiwoon, Narayanan, S. Anand, Wu, Fei, Najjar, Deena, Chin, Christopher R., Meydan, Cem, Loy, Conor, Mathyk, Begum, Klotz, Remi, Ortiz, Veronica, Nguyen, Khiem, Ryon, Krista A., Damle, Namita, Houerbi, Nadia, Patras, Laura I., Schanzer, Nathan, Hutchinson, Gwyneth A., Foox, Jonathan, Bhattacharya, Chandrima, Mackay, Matthew, Afshin, Evan E., Hirschberg, Jeremy Wain, Kleinman, Ashley S., Schmidt, Julian C., Schmidt, Caleb M., Schmidt, Michael A., Beheshti, Afshin, Matei, Irina, Lyden, David, Mullane, Sean, Asadi, Amran, Lenz, Joan S., Mzava, Omary, Yu, Min, Ganesan, Saravanan, De Vlaminck, Iwijn, Melnick, Ari M., Barisic, Darko, Winer, Daniel A., Zwart, Sara R., Crucian, Brian E., Smith, Scott M., Mateus, Jaime, Furman, David, and Mason, Christopher E.

Published
2024
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4. Immune resilience despite inflammatory stress promotes longevity and favorable health outcomes including resistance to infection

Author

Ahuja, Sunil K, Manoharan, Muthu Saravanan, Lee, Grace C, McKinnon, Lyle R, Meunier, Justin A, Steri, Maristella, Harper, Nathan, Fiorillo, Edoardo, Smith, Alisha M, Restrepo, Marcos I, Branum, Anne P, Bottomley, Matthew J, Orrù, Valeria, Jimenez, Fabio, Carrillo, Andrew, Pandranki, Lavanya, Winter, Caitlyn A, Winter, Lauryn A, Gaitan, Alvaro A, Moreira, Alvaro G, Walter, Elizabeth A, Silvestri, Guido, King, Christopher L, Zheng, Yong-Tang, Zheng, Hong-Yi, Kimani, Joshua, Blake Ball, T, Plummer, Francis A, Fowke, Keith R, Harden, Paul N, Wood, Kathryn J, Ferris, Martin T, Lund, Jennifer M, Heise, Mark T, Garrett, Nigel, Canady, Kristen R, Abdool Karim, Salim S, Little, Susan J, Gianella, Sara, Smith, Davey M, Letendre, Scott, Richman, Douglas D, Cucca, Francesco, Trinh, Hanh, Sanchez-Reilly, Sandra, Hecht, Joan M, Cadena Zuluaga, Jose A, Anzueto, Antonio, Pugh, Jacqueline A, Agan, Brian K, Root-Bernstein, Robert, Clark, Robert A, Okulicz, Jason F, and He, Weijing

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Clinical Sciences, Immunology, Biodefense, Infectious Diseases, Aging, Vaccine Related, Prevention, Aetiology, 2.1 Biological and endogenous factors, Inflammatory and immune system, Infection, Good Health and Well Being, Female, Humans, Longevity, COVID-19, Inflammation, Outcome Assessment, Health Care, South Texas Veterans Health Care System COVID-19 team
Abstract

Some people remain healthier throughout life than others but the underlying reasons are poorly understood. Here we hypothesize this advantage is attributable in part to optimal immune resilience (IR), defined as the capacity to preserve and/or rapidly restore immune functions that promote disease resistance (immunocompetence) and control inflammation in infectious diseases as well as other causes of inflammatory stress. We gauge IR levels with two distinct peripheral blood metrics that quantify the balance between (i) CD8+ and CD4+ T-cell levels and (ii) gene expression signatures tracking longevity-associated immunocompetence and mortality-associated inflammation. Profiles of IR metrics in ~48,500 individuals collectively indicate that some persons resist degradation of IR both during aging and when challenged with varied inflammatory stressors. With this resistance, preservation of optimal IR tracked (i) a lower risk of HIV acquisition, AIDS development, symptomatic influenza infection, and recurrent skin cancer; (ii) survival during COVID-19 and sepsis; and (iii) longevity. IR degradation is potentially reversible by decreasing inflammatory stress. Overall, we show that optimal IR is a trait observed across the age spectrum, more common in females, and aligned with a specific immunocompetence-inflammation balance linked to favorable immunity-dependent health outcomes. IR metrics and mechanisms have utility both as biomarkers for measuring immune health and for improving health outcomes.

Published
2023

6. Integrative omics identifies conserved and pathogen-specific responses of sepsis-causing bacteria

Author

Mu, Andre, Klare, William P., Baines, Sarah L., Ignatius Pang, C. N., Guérillot, Romain, Harbison-Price, Nichaela, Keller, Nadia, Wilksch, Jonathan, Nhu, Nguyen Thi Khanh, Phan, Minh-Duy, Keller, Bernhard, Nijagal, Brunda, Tull, Dedreia, Dayalan, Saravanan, Chua, Hwa Huat Charlie, Skoneczny, Dominik, Koval, Jason, Hachani, Abderrahman, Shah, Anup D., Neha, Nitika, Jadhav, Snehal, Partridge, Sally R., Cork, Amanda J., Peters, Kate, Bertolla, Olivia, Brouwer, Stephan, Hancock, Steven J., Álvarez-Fraga, Laura, De Oliveira, David M. P., Forde, Brian, Dale, Ashleigh, Mujchariyakul, Warasinee, Walsh, Calum J., Monk, Ian, Fitzgerald, Anna, Lum, Mabel, Correa-Ospina, Carolina, Roy Chowdhury, Piklu, Parton, Robert G., De Voss, James, Beckett, James, Monty, Francois, McKinnon, Jessica, Song, Xiaomin, Stephen, John R., Everest, Marie, Bellgard, Matt I., Tinning, Matthew, Leeming, Michael, Hocking, Dianna, Jebeli, Leila, Wang, Nancy, Ben Zakour, Nouri, Yasar, Serhat A., Vecchiarelli, Stefano, Russell, Tonia, Zaw, Thiri, Chen, Tyrone, Teng, Don, Kassir, Zena, Lithgow, Trevor, Jenney, Adam, Cole, Jason N., Nizet, Victor, Sorrell, Tania C., Peleg, Anton Y., Paterson, David L., Beatson, Scott A., Wu, Jemma, Molloy, Mark P., Syme, Anna E., Goode, Robert J. A., Hunter, Adam A., Bowland, Grahame, West, Nicholas P., Wilkins, Marc R., Djordjevic, Steven P., Davies, Mark R., Seemann, Torsten, Howden, Benjamin P., Pascovici, Dana, Tyagi, Sonika, Schittenhelm, Ralf B., De Souza, David P., McConville, Malcolm J., Iredell, Jonathan R., Cordwell, Stuart J., Strugnell, Richard A., Stinear, Timothy P., Schembri, Mark A., and Walker, Mark J.

Published
2023
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8. Central American mountains inhibit eastern North Pacific seasonal tropical cyclone activity.

Author

Fu, Dan, Chang, Ping, Patricola, Christina M, Saravanan, R, Liu, Xue, and Beck, Hylke E

Abstract

The eastern North Pacific (ENP) has the highest density of tropical cyclones (TCs) on earth, and yet the controls on TCs, from individual events to seasonal totals, remain poorly understood. One effect that has not been fully considered is the unique geography of the Central American mountains. Although observational studies suggest these mountains can readily fuel individual TCs through dynamical processes, here we show that these mountains indeed play the opposite role on the seasonal timescale, hindering seasonal ENP TC activity by up to 35%. We found that these mountains significantly interrupt the abundant moisture transport from the Caribbean Sea to the ENP, limiting deep convection over the open ocean area where TCs preferentially occur. This study advances our fundamental understanding of ENP TC genesis mechanisms across the weather-to-climate timescales, and also highlights the importance of topography representation in improving the ENP regional climate simulations, as well as TC seasonal predictions and future projections.

Published
2021

9. Ocean fronts and eddies force atmospheric rivers and heavy precipitation in western North America.

Author

Liu, Xue, Ma, Xiaohui, Chang, Ping, Jia, Yinglai, Fu, Dan, Xu, Guangzhi, Wu, Lixin, Saravanan, R, and Patricola, Christina

Abstract

Atmospheric rivers (ARs) are responsible for over 90% of poleward water vapor transport in the mid-latitudes and can produce extreme precipitation when making landfall. However, weather and climate models still have difficulty simulating and predicting landfalling ARs and associated extreme precipitation, highlighting the need to better understand AR dynamics. Here, using high-resolution climate models and observations, we demonstrate that mesoscale sea-surface temperature (SST) anomalies along the Kuroshio Extension can exert a remote influence on landfalling ARs and related heavy precipitation along the west coast of North America. Inclusion of mesoscale SST forcing in the simulations results in approximately a 40% increase in landfalling ARs and up to a 30% increase in heavy precipitation in mountainous regions and this remote impact occurs on two-week time scales. The asymmetrical response of the atmosphere to warm vs. cold mesoscale SSTs over the eddy-rich Kuroshio Extension region is proposed as a forcing mechanism that results in a net increase of moisture flux above the planetary boundary layer, prompting AR genesis via enhancing moisture transport into extratropical cyclones in the presence of mesoscale SST forcing.

Published
2021

10. Inhibition of mitochondrial complex I reverses NOTCH1-driven metabolic reprogramming in T-cell acute lymphoblastic leukemia

Author

Natalia Baran, Alessia Lodi, Yogesh Dhungana, Shelley Herbrich, Meghan Collins, Shannon Sweeney, Renu Pandey, Anna Skwarska, Shraddha Patel, Mathieu Tremblay, Vinitha Mary Kuruvilla, Antonio Cavazos, Mecit Kaplan, Marc O. Warmoes, Diogo Troggian Veiga, Ken Furudate, Shanti Rojas-Sutterin, Andre Haman, Yves Gareau, Anne Marinier, Helen Ma, Karine Harutyunyan, May Daher, Luciana Melo Garcia, Gheath Al-Atrash, Sujan Piya, Vivian Ruvolo, Wentao Yang, Sriram Saravanan Shanmugavelandy, Ningping Feng, Jason Gay, Di Du, Jun J. Yang, Fieke W. Hoff, Marcin Kaminski, Katarzyna Tomczak, R. Eric Davis, Daniel Herranz, Adolfo Ferrando, Elias J. Jabbour, M. Emilia Di Francesco, David T. Teachey, Terzah M. Horton, Steven Kornblau, Katayoun Rezvani, Guy Sauvageau, Mihai Gagea, Michael Andreeff, Koichi Takahashi, Joseph R. Marszalek, Philip L. Lorenzi, Jiyang Yu, Stefano Tiziani, Trang Hoang, and Marina Konopleva

Subjects
Science
Abstract

Notch1 is frequently activated promoting T-cell acute lymphoblastic leukaemia (T-ALL). Here, the authors show that Notch1 induces oxidative phosphorylation dependency in T-ALL and synergism when inhibiting both mitochondrial complex I and glutaminolysis in preclinical murine and human xenograft models.

Published
2022
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11. Inhibition of mitochondrial complex I reverses NOTCH1-driven metabolic reprogramming in T-cell acute lymphoblastic leukemia

Author

Baran, Natalia, Lodi, Alessia, Dhungana, Yogesh, Herbrich, Shelley, Collins, Meghan, Sweeney, Shannon, Pandey, Renu, Skwarska, Anna, Patel, Shraddha, Tremblay, Mathieu, Kuruvilla, Vinitha Mary, Cavazos, Antonio, Kaplan, Mecit, Warmoes, Marc O., Veiga, Diogo Troggian, Furudate, Ken, Rojas-Sutterin, Shanti, Haman, Andre, Gareau, Yves, Marinier, Anne, Ma, Helen, Harutyunyan, Karine, Daher, May, Garcia, Luciana Melo, Al-Atrash, Gheath, Piya, Sujan, Ruvolo, Vivian, Yang, Wentao, Shanmugavelandy, Sriram Saravanan, Feng, Ningping, Gay, Jason, Du, Di, Yang, Jun J., Hoff, Fieke W., Kaminski, Marcin, Tomczak, Katarzyna, Eric Davis, R., Herranz, Daniel, Ferrando, Adolfo, Jabbour, Elias J., Emilia Di Francesco, M., Teachey, David T., Horton, Terzah M., Kornblau, Steven, Rezvani, Katayoun, Sauvageau, Guy, Gagea, Mihai, Andreeff, Michael, Takahashi, Koichi, Marszalek, Joseph R., Lorenzi, Philip L., Yu, Jiyang, Tiziani, Stefano, Hoang, Trang, and Konopleva, Marina

Published
2022
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15. Phase transformation mechanism in lithium manganese nickel oxide revealed by single-crystal hard X-ray microscopy

Author

Kuppan, Saravanan, Xu, Yahong, Liu, Yijin, and Chen, Guoying

Subjects
Engineering, Materials Engineering, Chemical Sciences
Abstract

Understanding the reaction pathway and kinetics of solid-state phase transformation is critical in designing advanced electrode materials with better performance and stability. Despite the first-order phase transition with a large lattice mismatch between the involved phases, spinel LiMn1.5Ni0.5O4 is capable of fast rate even at large particle size, presenting an enigma yet to be understood. The present study uses advanced two-dimensional and three-dimensional nano-tomography on a series of well-formed LixMn1.5Ni0.5O4 (0≤x≤1) crystals to visualize the mesoscale phase distribution, as a function of Li content at the sub-particle level. Inhomogeneity along with the coexistence of Li-rich and Li-poor phases are broadly observed on partially delithiated crystals, providing direct evidence for a concurrent nucleation and growth process instead of a shrinking-core or a particle-by-particle process. Superior kinetics of (100) facets at the vertices of truncated octahedral particles promote preferential delithiation, whereas the observation of strain-induced cracking suggests mechanical degradation in the material.

Published
2017

17. A collection of bacterial isolates from the pig intestine reveals functional and taxonomic diversity

Author

Wylensek, David, Hitch, Thomas C. A., Riedel, Thomas, Afrizal, Afrizal, Kumar, Neeraj, Wortmann, Esther, Liu, Tianzhe, Devendran, Saravanan, Lesker, Till R., Hernández, Sara B., Heine, Viktoria, Buhl, Eva M., M. D’Agostino, Paul, Cumbo, Fabio, Fischöder, Thomas, Wyschkon, Marzena, Looft, Torey, Parreira, Valeria R., Abt, Birte, Doden, Heidi L., Ly, Lindsey, Alves, João M. P., Reichlin, Markus, Flisikowski, Krzysztof, Suarez, Laura Navarro, Neumann, Anthony P., Suen, Garret, de Wouters, Tomas, Rohn, Sascha, Lagkouvardos, Ilias, Allen-Vercoe, Emma, Spröer, Cathrin, Bunk, Boyke, Taverne-Thiele, Anja J., Giesbers, Marcel, Wells, Jerry M., Neuhaus, Klaus, Schnieke, Angelika, Cava, Felipe, Segata, Nicola, Elling, Lothar, Strowig, Till, Ridlon, Jason M., Gulder, Tobias A. M., Overmann, Jörg, and Clavel, Thomas

Published
2020
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21. Single-cell multi-ome and immune profiles of the Inspiration4 crew reveal conserved, cell-type, and sex-specific responses to spaceflight

Author

JangKeun Kim, Braden T. Tierney, Eliah G. Overbey, Ezequiel Dantas, Matias Fuentealba, Jiwoon Park, S. Anand Narayanan, Fei Wu, Deena Najjar, Christopher R. Chin, Cem Meydan, Conor Loy, Begum Mathyk, Remi Klotz, Veronica Ortiz, Khiem Nguyen, Krista A. Ryon, Namita Damle, Nadia Houerbi, Laura I. Patras, Nathan Schanzer, Gwyneth A. Hutchinson, Jonathan Foox, Chandrima Bhattacharya, Matthew Mackay, Evan E. Afshin, Jeremy Wain Hirschberg, Ashley S. Kleinman, Julian C. Schmidt, Caleb M. Schmidt, Michael A. Schmidt, Afshin Beheshti, Irina Matei, David Lyden, Sean Mullane, Amran Asadi, Joan S. Lenz, Omary Mzava, Min Yu, Saravanan Ganesan, Iwijn De Vlaminck, Ari M. Melnick, Darko Barisic, Daniel A. Winer, Sara R. Zwart, Brian E. Crucian, Scott M. Smith, Jaime Mateus, David Furman, and Christopher E. Mason

Subjects
Science
Abstract

Abstract Spaceflight induces an immune response in astronauts. To better characterize this effect, we generated single-cell, multi-ome, cell-free RNA (cfRNA), biochemical, and hematology data for the SpaceX Inspiration4 (I4) mission crew. We found that 18 cytokines/chemokines related to inflammation, aging, and muscle homeostasis changed after spaceflight. In I4 single-cell multi-omics data, we identified a “spaceflight signature” of gene expression characterized by enrichment in oxidative phosphorylation, UV response, immune function, and TCF21 pathways. We confirmed the presence of this signature in independent datasets, including the NASA Twins Study, the I4 skin spatial transcriptomics, and 817 NASA GeneLab mouse transcriptomes. Finally, we observed that (1) T cells showed an up-regulation of FOXP3, (2) MHC class I genes exhibited long-term suppression, and (3) infection-related immune pathways were associated with microbiome shifts. In summary, this study reveals conserved and distinct immune disruptions occurring and details a roadmap for potential countermeasures to preserve astronaut health.

Published
2024
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22. Prodrug-conjugated tumor-seeking commensals for targeted cancer therapy

Author

Haosheng Shen, Changyu Zhang, Shengjie Li, Yuanmei Liang, Li Ting Lee, Nikhil Aggarwal, Kwok Soon Wun, Jing Liu, Saravanan Prabhu Nadarajan, Cheng Weng, Hua Ling, Joshua K. Tay, De Yun Wang, Shao Q. Yao, In Young Hwang, Yung Seng Lee, and Matthew Wook Chang

Subjects
Science
Abstract

Abstract Prodrugs have been explored as an alternative to conventional chemotherapy; however, their target specificity remains limited. The tumor microenvironment harbors a range of microorganisms that potentially serve as tumor-targeting vectors for delivering prodrugs. In this study, we harness bacteria-cancer interactions native to the tumor microbiome to achieve high target specificity for prodrug delivery. We identify an oral commensal strain of Lactobacillus plantarum with an intrinsic cancer-binding mechanism and engineer the strain to enable the surface loading of anticancer prodrugs, with nasopharyngeal carcinoma (NPC) as a model cancer. The engineered commensals show specific binding to NPC via OppA-mediated recognition of surface heparan sulfate, and the loaded prodrugs are activated by tumor-associated biosignals to release SN-38, a chemotherapy compound, near NPC. In vitro experiments demonstrate that the prodrug-loaded microbes significantly increase the potency of SN-38 against NPC cell lines, up to 10-fold. In a mouse xenograft model, intravenous injection of the engineered L. plantarum leads to bacterial colonization in NPC tumors and a 67% inhibition in tumor growth, enhancing the efficacy of SN-38 by 54%.

Published
2024
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23. The low-density lipoprotein receptor promotes infection of multiple encephalitic alphaviruses

Author

Hongming Ma, Lucas J. Adams, Saravanan Raju, Alan Sariol, Natasha M. Kafai, Hana Janova, William B. Klimstra, Daved H. Fremont, and Michael S. Diamond

Subjects
Science
Abstract

Abstract Members of the low-density lipoprotein receptor (LDLR) family, including LDLRAD3, VLDLR, and ApoER2, were recently described as entry factors for different alphaviruses. However, based on studies with gene edited cells and knockout mice, blockade or abrogation of these receptors does not fully inhibit alphavirus infection, indicating the existence of additional uncharacterized entry factors. Here, we perform a CRISPR-Cas9 genome-wide loss-of-function screen in mouse neuronal cells with a chimeric alphavirus expressing the Eastern equine encephalitis virus (EEEV) structural proteins and identify LDLR as a candidate receptor. Expression of LDLR on the surface of neuronal or non-neuronal cells facilitates binding and infection of EEEV, Western equine encephalitis virus, and Semliki Forest virus. Domain mapping and binding studies reveal a low-affinity interaction with LA domain 3 (LA3) that can be enhanced by concatenation of LA3 repeats. Soluble decoy proteins with multiple LA3 repeats inhibit EEEV infection in cell culture and in mice. Our results establish LDLR as a low-affinity receptor for multiple alphaviruses and highlight a possible path for developing inhibitors that could mitigate infection and disease.

Published
2024
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24. Design principles for sodium superionic conductors

Author

Shuo Wang, Jiamin Fu, Yunsheng Liu, Ramanuja Srinivasan Saravanan, Jing Luo, Sixu Deng, Tsun-Kong Sham, Xueliang Sun, and Yifei Mo

Subjects
Science
Abstract

Abstract Motivated by the high-performance solid-state lithium batteries enabled by lithium superionic conductors, sodium superionic conductor materials have great potential to empower sodium batteries with high energy, low cost, and sustainability. A critical challenge lies in designing and discovering sodium superionic conductors with high ionic conductivities to enable the development of solid-state sodium batteries. Here, by studying the structures and diffusion mechanisms of Li-ion versus Na-ion conducting solids, we reveal the structural feature of face-sharing high-coordination sites for fast sodium-ion conductors. By applying this feature as a design principle, we discover a number of Na-ion conductors in oxides, sulfides, and halides. Notably, we discover a chloride-based family of Na-ion conductors NaxMyCl6 (M = La–Sm) with UCl3-type structure and experimentally validate with the highest reported ionic conductivity. Our findings not only pave the way for the future development of sodium-ion conductors for sodium batteries, but also consolidate design principles of fast ion-conducting materials for a variety of energy applications.

Published
2023
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25. Immune resilience despite inflammatory stress promotes longevity and favorable health outcomes including resistance to infection

Author

Sunil K. Ahuja, Muthu Saravanan Manoharan, Grace C. Lee, Lyle R. McKinnon, Justin A. Meunier, Maristella Steri, Nathan Harper, Edoardo Fiorillo, Alisha M. Smith, Marcos I. Restrepo, Anne P. Branum, Matthew J. Bottomley, Valeria Orrù, Fabio Jimenez, Andrew Carrillo, Lavanya Pandranki, Caitlyn A. Winter, Lauryn A. Winter, Alvaro A. Gaitan, Alvaro G. Moreira, Elizabeth A. Walter, Guido Silvestri, Christopher L. King, Yong-Tang Zheng, Hong-Yi Zheng, Joshua Kimani, T. Blake Ball, Francis A. Plummer, Keith R. Fowke, Paul N. Harden, Kathryn J. Wood, Martin T. Ferris, Jennifer M. Lund, Mark T. Heise, Nigel Garrett, Kristen R. Canady, Salim S. Abdool Karim, Susan J. Little, Sara Gianella, Davey M. Smith, Scott Letendre, Douglas D. Richman, Francesco Cucca, Hanh Trinh, Sandra Sanchez-Reilly, Joan M. Hecht, Jose A. Cadena Zuluaga, Antonio Anzueto, Jacqueline A. Pugh, South Texas Veterans Health Care System COVID-19 team, Brian K. Agan, Robert Root-Bernstein, Robert A. Clark, Jason F. Okulicz, and Weijing He

Subjects
Science
Abstract

Abstract Some people remain healthier throughout life than others but the underlying reasons are poorly understood. Here we hypothesize this advantage is attributable in part to optimal immune resilience (IR), defined as the capacity to preserve and/or rapidly restore immune functions that promote disease resistance (immunocompetence) and control inflammation in infectious diseases as well as other causes of inflammatory stress. We gauge IR levels with two distinct peripheral blood metrics that quantify the balance between (i) CD8+ and CD4+ T-cell levels and (ii) gene expression signatures tracking longevity-associated immunocompetence and mortality-associated inflammation. Profiles of IR metrics in ~48,500 individuals collectively indicate that some persons resist degradation of IR both during aging and when challenged with varied inflammatory stressors. With this resistance, preservation of optimal IR tracked (i) a lower risk of HIV acquisition, AIDS development, symptomatic influenza infection, and recurrent skin cancer; (ii) survival during COVID-19 and sepsis; and (iii) longevity. IR degradation is potentially reversible by decreasing inflammatory stress. Overall, we show that optimal IR is a trait observed across the age spectrum, more common in females, and aligned with a specific immunocompetence-inflammation balance linked to favorable immunity-dependent health outcomes. IR metrics and mechanisms have utility both as biomarkers for measuring immune health and for improving health outcomes.

Published
2023
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26. Integrative omics identifies conserved and pathogen-specific responses of sepsis-causing bacteria

Author

Andre Mu, William P. Klare, Sarah L. Baines, C. N. Ignatius Pang, Romain Guérillot, Nichaela Harbison-Price, Nadia Keller, Jonathan Wilksch, Nguyen Thi Khanh Nhu, Minh-Duy Phan, Bernhard Keller, Brunda Nijagal, Dedreia Tull, Saravanan Dayalan, Hwa Huat Charlie Chua, Dominik Skoneczny, Jason Koval, Abderrahman Hachani, Anup D. Shah, Nitika Neha, Snehal Jadhav, Sally R. Partridge, Amanda J. Cork, Kate Peters, Olivia Bertolla, Stephan Brouwer, Steven J. Hancock, Laura Álvarez-Fraga, David M. P. De Oliveira, Brian Forde, Ashleigh Dale, Warasinee Mujchariyakul, Calum J. Walsh, Ian Monk, Anna Fitzgerald, Mabel Lum, Carolina Correa-Ospina, Piklu Roy Chowdhury, Robert G. Parton, James De Voss, James Beckett, Francois Monty, Jessica McKinnon, Xiaomin Song, John R. Stephen, Marie Everest, Matt I. Bellgard, Matthew Tinning, Michael Leeming, Dianna Hocking, Leila Jebeli, Nancy Wang, Nouri Ben Zakour, Serhat A. Yasar, Stefano Vecchiarelli, Tonia Russell, Thiri Zaw, Tyrone Chen, Don Teng, Zena Kassir, Trevor Lithgow, Adam Jenney, Jason N. Cole, Victor Nizet, Tania C. Sorrell, Anton Y. Peleg, David L. Paterson, Scott A. Beatson, Jemma Wu, Mark P. Molloy, Anna E. Syme, Robert J. A. Goode, Adam A. Hunter, Grahame Bowland, Nicholas P. West, Marc R. Wilkins, Steven P. Djordjevic, Mark R. Davies, Torsten Seemann, Benjamin P. Howden, Dana Pascovici, Sonika Tyagi, Ralf B. Schittenhelm, David P. De Souza, Malcolm J. McConville, Jonathan R. Iredell, Stuart J. Cordwell, Richard A. Strugnell, Timothy P. Stinear, Mark A. Schembri, and Mark J. Walker

Subjects
Science
Abstract

Severe sepsis has a high mortality rate. Here, the authors provide genomic, transcriptomic, proteomic and metabolomic data across four sepsis-causing pathogens and identify a signature of global increase in fatty acid and lipid biosynthesis as well as cholesterol acquisition.

Published
2023
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27. Asgard archaea shed light on the evolutionary origins of the eukaryotic ubiquitin-ESCRT machinery

Author

Tomoyuki Hatano, Saravanan Palani, Dimitra Papatziamou, Ralf Salzer, Diorge P. Souza, Daniel Tamarit, Mehul Makwana, Antonia Potter, Alexandra Haig, Wenjue Xu, David Townsend, David Rochester, Dom Bellini, Hamdi M. A. Hussain, Thijs J. G. Ettema, Jan Löwe, Buzz Baum, Nicholas P. Robinson, and Mohan Balasubramanian

Subjects
Science
Abstract

The ESCRT pathway is crucial for membrane remodelling in eukaryotes. Here, Hatano et al. explore the phylogeny, structure, and biochemistry of homologues of the ESCRT machinery and the associated ubiquitylation system in Asgard archaea, the closest living relatives of eukaryotes.

Published
2022
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28. RETRACTED ARTICLE: Pharmacological perturbation of CXCL1 signaling alleviates neuropathogenesis in a model of HEVA71 infection

Author

Saravanan Gunaseelan, Mohammed Zacky Ariffin, Sanjay Khanna, Mong How Ooi, David Perera, Justin Jang Hann Chu, and John Jia En Chua

Subjects
Science
Abstract

Neurological complications are frequently observed in severe Hand, Foot and Mouth Disease but the underlying causes are unknown. Here, the authors report infected astrocytes release CXCL1 which activates neuronal CXCR2 to cause neuropathogenesis.

Published
2022
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29. Central American mountains inhibit eastern North Pacific seasonal tropical cyclone activity

Author

Dan Fu, Ping Chang, Christina M. Patricola, R. Saravanan, Xue Liu, and Hylke E. Beck

Subjects
Science
Abstract

How the Central American mountains influence tropical cyclone (TC) development in the eastern North Pacific is not well understood. Here, the authors use model simulations to show that on a seasonal timescale, these mountains interrupt moisture transport from the Caribbean Sea and as a result, reduce TC activity by up to 35%.

Published
2021
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30. Defining super-enhancer landscape in triple-negative breast cancer by multiomic profiling

Author

Hao Huang, Jianyang Hu, Alishba Maryam, Qinghua Huang, Yuchen Zhang, Saravanan Ramakrishnan, Jingyu Li, Haiying Ma, Victor W. S. Ma, Wah Cheuk, Grace Y. K. So, Wei Wang, William C. S. Cho, Liang Zhang, Kui Ming Chan, Xin Wang, and Y. Rebecca Chin

Subjects
Science
Abstract

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype with poor prognostic outcomes. Here the authors characterize super-enhancer heterogeneity and they identify genes that are specifically regulated by TNBC-specific super-enhancers, including FOXC1, MET and ANLN.

Published
2021
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31. Ocean fronts and eddies force atmospheric rivers and heavy precipitation in western North America

Author

Xue Liu, Xiaohui Ma, Ping Chang, Yinglai Jia, Dan Fu, Guangzhi Xu, Lixin Wu, R. Saravanan, and Christina M. Patricola

Subjects
Science
Abstract

Atmospheric rivers are responsible for much of the poleward water vapour transport in the mid-latitudes and can cause extreme precipitation after landfall. Here, the authors show that ocean fronts and eddies can influence atmospheric rivers and increase the associated precipitation along the North American west coast.

Published
2021
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33. A collection of bacterial isolates from the pig intestine reveals functional and taxonomic diversity

Author

David Wylensek, Thomas C. A. Hitch, Thomas Riedel, Afrizal Afrizal, Neeraj Kumar, Esther Wortmann, Tianzhe Liu, Saravanan Devendran, Till R. Lesker, Sara B. Hernández, Viktoria Heine, Eva M. Buhl, Paul M. D’Agostino, Fabio Cumbo, Thomas Fischöder, Marzena Wyschkon, Torey Looft, Valeria R. Parreira, Birte Abt, Heidi L. Doden, Lindsey Ly, João M. P. Alves, Markus Reichlin, Krzysztof Flisikowski, Laura Navarro Suarez, Anthony P. Neumann, Garret Suen, Tomas de Wouters, Sascha Rohn, Ilias Lagkouvardos, Emma Allen-Vercoe, Cathrin Spröer, Boyke Bunk, Anja J. Taverne-Thiele, Marcel Giesbers, Jerry M. Wells, Klaus Neuhaus, Angelika Schnieke, Felipe Cava, Nicola Segata, Lothar Elling, Till Strowig, Jason M. Ridlon, Tobias A. M. Gulder, Jörg Overmann, and Thomas Clavel

Subjects
Science
Abstract

The authors present a public collection of 117 bacterial isolates from the pig gut, including the description of 38 novel taxa. Interesting functions discovered in these organisms include a new fucosyltransferease and sactipeptide-like molecules encoded by biosynthetic gene clusters.

Published
2020
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34. A rare variant of African ancestry activates 8q24 lncRNA hub by modulating cancer associated enhancer

Author

Kaivalya Walavalkar, Bharath Saravanan, Anurag Kumar Singh, Ranveer Singh Jayani, Ashwin Nair, Umer Farooq, Zubairul Islam, Deepanshu Soota, Rajat Mann, Padubidri V. Shivaprasad, Matthew L. Freedman, Radhakrishnan Sabarinathan, Christopher A. Haiman, and Dimple Notani

Subjects
Science
Abstract

Genetic variants on chromosome 8q24 are associated with prostate cancer risk in men of African ancestry. Here the authors show that one of these variants, rs72725854 alters the enhancer activity in its region, which upon androgen stimulation, activates multiple oncogenic lncRNAs and c-myc.

Published
2020
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35. Global Fe–O isotope correlation reveals magmatic origin of Kiruna-type apatite-iron-oxide ores

Author

Valentin R. Troll, Franz A. Weis, Erik Jonsson, Ulf B. Andersson, Seyed Afshin Majidi, Karin Högdahl, Chris Harris, Marc-Alban Millet, Sakthi Saravanan Chinnasamy, Ellen Kooijman, and Katarina P. Nilsson

Subjects
Science
Abstract

The origin of giant Kiruna-type iron ores has been debated for nearly 100 years. This study employs extensive stable isotope data from Kiruna-type ores worldwide and magmatic and hydrothermal reference materials to show that iconic Kiruna-type ores originate primarily from ortho-magmatic processes.

Published
2019
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37. Structural basis for endotoxin neutralisation and anti-inflammatory activity of thrombin-derived C-terminal peptides

Author

Rathi Saravanan, Daniel A Holdbrook, Jitka Petrlova, Shalini Singh, Nils A Berglund, Yeu Khai Choong, Sven Kjellström, Peter J Bond, Martin Malmsten, and Artur Schmidtchen

Subjects
Science
Abstract

Thrombin-derived C-terminal peptides (TCPs) have anti-endotoxic functions in wounds by binding to bacterial lipopolysaccharide (LPS) and Gram-negative bacteria. Here authors use a spectrum of biophysical techniques to determine the conformation of a TCP in complex with LPS and define the interaction between TCPs and CD14.

Published
2018
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38. Phase transformation mechanism in lithium manganese nickel oxide revealed by single-crystal hard X-ray microscopy

Author

Saravanan Kuppan, Yahong Xu, Yijin Liu, and Guoying Chen

Subjects
Science
Abstract

As an intercalation electrode material for lithium ion batteries, spinel LixMn1.5Ni0.5O4possesses a metastable nature during the electrochemical operation. Here the authors reveal the phase transformation mechanism by using single-crystal hard X-ray microscopy to detect the local phase distribution.

Published
2017
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39. Counteracting H3K4 methylation modulators Set1 and Jhd2 co-regulate chromatin dynamics and gene transcription

Author

Saravanan Ramakrishnan, Srijana Pokhrel, Sowmiya Palani, Christian Pflueger, Timothy J. Parnell, Bradley R. Cairns, Srividya Bhaskara, and Mahesh B. Chandrasekharan

Subjects
Science
Abstract

Histone H3K4 methylation affects gene transcription from yeast to humans. Here, the authors show that Set1 and Jhd2, the only H3K4 methyltransferase and H3K4 demethylase, respectively, in budding yeast, co-regulate both positive and negative transcription mediated by nucleosomal turnover and occupancy.

Published
2016
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