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1. Taurine deficiency as a driver of aging.

Author

Singh, Parminder, Gollapalli, Kishore, Mangiola, Stefano, Schranner, Daniela, Yusuf, Mohd, Chamoli, Manish, Shi, Sting, Lopes Bastos, Bruno, Nair, Tripti, Riermeier, Annett, Vayndorf, Elena, Wu, Judy, Nilakhe, Aishwarya, Nguyen, Christina, Muir, Michael, Kiflezghi, Michael, Foulger, Anna, Junker, Alex, Devine, Jack, Sharan, Kunal, Chinta, Shankar, Rajput, Swati, Rane, Anand, Baumert, Philipp, Schönfelder, Martin, Iavarone, Francescopaolo, di Lorenzo, Giorgia, Kumari, Swati, Gupta, Alka, Sarkar, Rajesh, Khyriem, Costerwell, Chawla, Amanpreet, Sharma, Ankur, Sarper, Nazan, Chattopadhyay, Naibedya, Biswal, Bichitra, Settembre, Carmine, Nagarajan, Perumal, Targoff, Kimara, Picard, Martin, Gupta, Sarika, Velagapudi, Vidya, Papenfuss, Anthony, Kaya, Alaattin, Ferreira, Miguel, Kennedy, Brian, Andersen, Julie, Lithgow, Gordon, Ali, Abdullah, Mukhopadhyay, Arnab, Palotie, Aarno, Kastenmüller, Gabi, Kaeberlein, Matt, Wackerhage, Henning, Pal, Bhupinder, and Yadav, Vijay

Subjects
Animals, Humans, Mice, Aging, Cellular Senescence, Haplorhini, Longevity, Taurine, Dietary Supplements, DNA Damage, Telomerase
Abstract

Aging is associated with changes in circulating levels of various molecules, some of which remain undefined. We find that concentrations of circulating taurine decline with aging in mice, monkeys, and humans. A reversal of this decline through taurine supplementation increased the health span (the period of healthy living) and life span in mice and health span in monkeys. Mechanistically, taurine reduced cellular senescence, protected against telomerase deficiency, suppressed mitochondrial dysfunction, decreased DNA damage, and attenuated inflammaging. In humans, lower taurine concentrations correlated with several age-related diseases and taurine concentrations increased after acute endurance exercise. Thus, taurine deficiency may be a driver of aging because its reversal increases health span in worms, rodents, and primates and life span in worms and rodents. Clinical trials in humans seem warranted to test whether taurine deficiency might drive aging in humans.

Published
2023

2. Femtosecond symmetry breaking and coherent relaxation of methane cations via x-ray spectroscopy

Author

Ridente, Enrico, Hait, Diptarka, Haugen, Eric A, Ross, Andrew D, Neumark, Daniel M, Head-Gordon, Martin, and Leone, Stephen R

Subjects
Physical Sciences, Chemical Sciences, Physical Chemistry, Theoretical and Computational Chemistry, CSD-01-AMOS-A, CSD-46-All CSGB, CSD-04-GPCP-A, General Science & Technology
Abstract

Understanding the relaxation pathways of photoexcited molecules is essential to gain atomistic-level insight into photochemistry. We performed a time-resolved study of ultrafast molecular symmetry breaking through geometric relaxation (Jahn-Teller distortion) on the methane cation. Attosecond transient absorption spectroscopy with soft x-rays at the carbon K-edge revealed that the distortion occurred within 10 ± 2 femtoseconds after few-femtosecond strong-field ionization of methane. The distortion activated coherent oscillations in the asymmetric scissoring vibrational mode of the symmetry-broken cation, which were detected in the x-ray signal. These oscillations were damped within 58 ± 13 femtoseconds because vibrational coherence was lost with the energy redistributing into lower-frequency vibrational modes. This study completely reconstructs the molecular relaxation dynamics of this prototypical example and opens avenues for exploring complex systems.

Published
2023

3. Single-cell RNA-seq reveals cell type–specific molecular and genetic associations to lupus

Author

Perez, Richard K, Gordon, M Grace, Subramaniam, Meena, Kim, Min Cheol, Hartoularos, George C, Targ, Sasha, Sun, Yang, Ogorodnikov, Anton, Bueno, Raymund, Lu, Andrew, Thompson, Mike, Rappoport, Nadav, Dahl, Andrew, Lanata, Cristina M, Matloubian, Mehrdad, Maliskova, Lenka, Kwek, Serena S, Li, Tony, Slyper, Michal, Waldman, Julia, Dionne, Danielle, Rozenblatt-Rosen, Orit, Fong, Lawrence, Dall'Era, Maria, Balliu, Brunilda, Regev, Aviv, Yazdany, Jinoos, Criswell, Lindsey A, Zaitlen, Noah, and Ye, Chun Jimmie

Subjects
Autoimmune Disease, Genetics, Lupus, Human Genome, 2.1 Biological and endogenous factors, Aetiology, Inflammatory and immune system, Good Health and Well Being, CD8-Positive T-Lymphocytes, Case-Control Studies, Humans, Interferon Type I, Leukocytes, Mononuclear, Lupus Erythematosus, Systemic, RNA-Seq, Transcription, Genetic, General Science & Technology
Abstract

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease. Knowledge of circulating immune cell types and states associated with SLE remains incomplete. We profiled more than 1.2 million peripheral blood mononuclear cells (162 cases, 99 controls) with multiplexed single-cell RNA sequencing (mux-seq). Cases exhibited elevated expression of type 1 interferon-stimulated genes (ISGs) in monocytes, reduction of naïve CD4+ T cells that correlated with monocyte ISG expression, and expansion of repertoire-restricted cytotoxic GZMH+ CD8+ T cells. Cell type-specific expression features predicted case-control status and stratified patients into two molecular subtypes. We integrated dense genotyping data to map cell type-specific cis-expression quantitative trait loci and to link SLE-associated variants to cell type-specific expression. These results demonstrate mux-seq as a systematic approach to characterize cellular composition, identify transcriptional signatures, and annotate genetic variants associated with SLE.

Published
2022

4. Temperature-adaptive radiative coating for all-season household thermal regulation

Author

Tang, Kechao, Dong, Kaichen, Li, Jiachen, Gordon, Madeleine P, Reichertz, Finnegan G, Kim, Hyungjin, Rho, Yoonsoo, Wang, Qingjun, Lin, Chang-Yu, Grigoropoulos, Costas P, Javey, Ali, Urban, Jeffrey J, Yao, Jie, Levinson, Ronnen, and Wu, Junqiao

Subjects
Earth Sciences, Atmospheric Sciences, Engineering, Affordable and Clean Energy, MSD-General, MSD-EMAT, General Science & Technology
Abstract

The sky is a natural heat sink that has been extensively used for passive radiative cooling of households. A lot of focus has been on maximizing the radiative cooling power of roof coating in the hot daytime using static, cooling-optimized material properties. However, the resultant overcooling in cold night or winter times exacerbates the heating cost, especially in climates where heating dominates energy consumption. We approached thermal regulation from an all-season perspective by developing a mechanically flexible coating that adapts its thermal emittance to different ambient temperatures. The fabricated temperature-adaptive radiative coating (TARC) optimally absorbs the solar energy and automatically switches thermal emittance from 0.20 for ambient temperatures lower than 15°C to 0.90 for temperatures above 30°C, driven by a photonically amplified metal-insulator transition. Simulations show that this system outperforms existing roof coatings for energy saving in most climates, especially those with substantial seasonal variations.

Published
2021

5. Sequence diversity analyses of an improved rhesus macaque genome enhance its biomedical utility

Author

Warren, Wesley C, Harris, R Alan, Haukness, Marina, Fiddes, Ian T, Murali, Shwetha C, Fernandes, Jason, Dishuck, Philip C, Storer, Jessica M, Raveendran, Muthuswamy, Hillier, LaDeana W, Porubsky, David, Mao, Yafei, Gordon, David, Vollger, Mitchell R, Lewis, Alexandra P, Munson, Katherine M, DeVogelaere, Elizabeth, Armstrong, Joel, Diekhans, Mark, Walker, Jerilyn A, Tomlinson, Chad, Graves-Lindsay, Tina A, Kremitzki, Milinn, Salama, Sofie R, Audano, Peter A, Escalona, Merly, Maurer, Nicholas W, Antonacci, Francesca, Mercuri, Ludovica, Maggiolini, Flavia AM, Catacchio, Claudia Rita, Underwood, Jason G, O'Connor, David H, Sanders, Ashley D, Korbel, Jan O, Ferguson, Betsy, Kubisch, H Michael, Picker, Louis, Kalin, Ned H, Rosene, Douglas, Levine, Jon, Abbott, David H, Gray, Stanton B, Sanchez, Mar M, Kovacs-Balint, Zsofia A, Kemnitz, Joseph W, Thomasy, Sara M, Roberts, Jeffrey A, Kinnally, Erin L, Capitanio, John P, Skene, JH Pate, Platt, Michael, Cole, Shelley A, Green, Richard E, Ventura, Mario, Wiseman, Roger W, Paten, Benedict, Batzer, Mark A, Rogers, Jeffrey, and Eichler, Evan E

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Genetics, Human Genome, HIV/AIDS, Biotechnology, Animals, Genetic Predisposition to Disease, Genetic Variation, Genome, Humans, Macaca mulatta, Molecular Sequence Annotation, Polymorphism, Single Nucleotide, Whole Genome Sequencing, General Science & Technology
Abstract

The rhesus macaque (Macaca mulatta) is the most widely studied nonhuman primate (NHP) in biomedical research. We present an updated reference genome assembly (Mmul_10, contig N50 = 46 Mbp) that increases the sequence contiguity 120-fold and annotate it using 6.5 million full-length transcripts, thus improving our understanding of gene content, isoform diversity, and repeat organization. With the improved assembly of segmental duplications, we discovered new lineage-specific genes and expanded gene families that are potentially informative in studies of evolution and disease susceptibility. Whole-genome sequencing (WGS) data from 853 rhesus macaques identified 85.7 million single-nucleotide variants (SNVs) and 10.5 million indel variants, including potentially damaging variants in genes associated with human autism and developmental delay, providing a framework for developing noninvasive NHP models of human disease.

Published
2020

6. Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms

Author

Gordon, David E, Hiatt, Joseph, Bouhaddou, Mehdi, Rezelj, Veronica V, Ulferts, Svenja, Braberg, Hannes, Jureka, Alexander S, Obernier, Kirsten, Guo, Jeffrey Z, Batra, Jyoti, Kaake, Robyn M, Weckstein, Andrew R, Owens, Tristan W, Gupta, Meghna, Pourmal, Sergei, Titus, Erron W, Cakir, Merve, Soucheray, Margaret, McGregor, Michael, Cakir, Zeynep, Jang, Gwendolyn, O’Meara, Matthew J, Tummino, Tia A, Zhang, Ziyang, Foussard, Helene, Rojc, Ajda, Zhou, Yuan, Kuchenov, Dmitry, Hüttenhain, Ruth, Xu, Jiewei, Eckhardt, Manon, Swaney, Danielle L, Fabius, Jacqueline M, Ummadi, Manisha, Tutuncuoglu, Beril, Rathore, Ujjwal, Modak, Maya, Haas, Paige, Haas, Kelsey M, Naing, Zun Zar Chi, Pulido, Ernst H, Shi, Ying, Barrio-Hernandez, Inigo, Memon, Danish, Petsalaki, Eirini, Dunham, Alistair, Marrero, Miguel Correa, Burke, David, Koh, Cassandra, Vallet, Thomas, Silvas, Jesus A, Azumaya, Caleigh M, Billesbølle, Christian, Brilot, Axel F, Campbell, Melody G, Diallo, Amy, Dickinson, Miles Sasha, Diwanji, Devan, Herrera, Nadia, Hoppe, Nick, Kratochvil, Huong T, Liu, Yanxin, Merz, Gregory E, Moritz, Michelle, Nguyen, Henry C, Nowotny, Carlos, Puchades, Cristina, Rizo, Alexandrea N, Schulze-Gahmen, Ursula, Smith, Amber M, Sun, Ming, Young, Iris D, Zhao, Jianhua, Asarnow, Daniel, Biel, Justin, Bowen, Alisa, Braxton, Julian R, Chen, Jen, Chio, Cynthia M, Chio, Un Seng, Deshpande, Ishan, Doan, Loan, Faust, Bryan, Flores, Sebastian, Jin, Mingliang, Kim, Kate, Lam, Victor L, Li, Fei, Li, Junrui, Li, Yen-Li, Li, Yang, Liu, Xi, Lo, Megan, Lopez, Kyle E, Melo, Arthur A, Moss, Frank R, Nguyen, Phuong, Paulino, Joana, Pawar, Komal Ishwar, and Peters, Jessica K

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Infectious Diseases, Coronaviruses Therapeutics and Interventions, Lung, Coronaviruses, Pneumonia, Emerging Infectious Diseases, Genetics, Biodefense, Pneumonia & Influenza, Generic health relevance, Infection, Good Health and Well Being, COVID-19, Conserved Sequence, Coronavirus Nucleocapsid Proteins, Cryoelectron Microscopy, Host Microbial Interactions, Humans, Mitochondrial Membrane Transport Proteins, Mitochondrial Precursor Protein Import Complex Proteins, Phosphoproteins, Protein Conformation, Protein Interaction Maps, Severe acute respiratory syndrome-related coronavirus, SARS-CoV-2, Severe Acute Respiratory Syndrome, QCRG Structural Biology Consortium, Zoonomia Consortium, General Science & Technology
Abstract

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a grave threat to public health and the global economy. SARS-CoV-2 is closely related to the more lethal but less transmissible coronaviruses SARS-CoV-1 and Middle East respiratory syndrome coronavirus (MERS-CoV). Here, we have carried out comparative viral-human protein-protein interaction and viral protein localization analyses for all three viruses. Subsequent functional genetic screening identified host factors that functionally impinge on coronavirus proliferation, including Tom70, a mitochondrial chaperone protein that interacts with both SARS-CoV-1 and SARS-CoV-2 ORF9b, an interaction we structurally characterized using cryo-electron microscopy. Combining genetically validated host factors with both COVID-19 patient genetic data and medical billing records identified molecular mechanisms and potential drug treatments that merit further molecular and clinical study.

Published
2020

7. Zika virus infection enhances future risk of severe dengue disease

Author

Katzelnick, Leah C, Narvaez, César, Arguello, Sonia, Lopez Mercado, Brenda, Collado, Damaris, Ampie, Oscarlett, Elizondo, Douglas, Miranda, Tatiana, Bustos Carillo, Fausto, Mercado, Juan Carlos, Latta, Krista, Schiller, Amy, Segovia-Chumbez, Bruno, Ojeda, Sergio, Sanchez, Nery, Plazaola, Miguel, Coloma, Josefina, Halloran, M Elizabeth, Premkumar, Lakshmanane, Gordon, Aubree, Narvaez, Federico, de Silva, Aravinda M, Kuan, Guillermina, Balmaseda, Angel, and Harris, Eva

Subjects
Rare Diseases, Vector-Borne Diseases, Vaccine Related, Infectious Diseases, Emerging Infectious Diseases, Prevention, Biodefense, Aetiology, 2.1 Biological and endogenous factors, Infection, Good Health and Well Being, Antibodies, Viral, Dengue Vaccines, Dengue Virus, Humans, Immunogenicity, Vaccine, Nicaragua, Risk, Serogroup, Severe Dengue, Zika Virus, Zika Virus Infection, General Science & Technology
Abstract

The Zika pandemic sparked intense interest in whether immune interactions among dengue virus serotypes 1 to 4 (DENV1 to -4) extend to the closely related Zika virus (ZIKV). We investigated prospective pediatric cohorts in Nicaragua that experienced sequential DENV1 to -3 (2004 to 2015), Zika (2016 to 2017), and DENV2 (2018 to 2020) epidemics. Risk of symptomatic DENV2 infection and severe disease was elevated by one prior ZIKV infection, one prior DENV infection, or one prior DENV infection followed by one ZIKV infection, compared with being flavivirus-naïve. By contrast, multiple prior DENV infections reduced dengue risk. Further, although high preexisting anti-DENV antibody titers protected against DENV1, DENV3, and ZIKV disease, intermediate titers induced by previous ZIKV or DENV infection enhanced future risk of DENV2 disease and severity, as well as DENV3 severity. The observation that prior ZIKV infection can modulate dengue disease severity like a DENV serotype poses challenges to development of dengue and Zika vaccines.

Published
2020

8. High-resolution comparative analysis of great ape genomes

Author

Kronenberg, Zev N, Fiddes, Ian T, Gordon, David, Murali, Shwetha, Cantsilieris, Stuart, Meyerson, Olivia S, Underwood, Jason G, Nelson, Bradley J, Chaisson, Mark JP, Dougherty, Max L, Munson, Katherine M, Hastie, Alex R, Diekhans, Mark, Hormozdiari, Fereydoun, Lorusso, Nicola, Hoekzema, Kendra, Qiu, Ruolan, Clark, Karen, Raja, Archana, Welch, AnneMarie E, Sorensen, Melanie, Baker, Carl, Fulton, Robert S, Armstrong, Joel, Graves-Lindsay, Tina A, Denli, Ahmet M, Hoppe, Emma R, Hsieh, PingHsun, Hill, Christopher M, Pang, Andy Wing Chun, Lee, Joyce, Lam, Ernest T, Dutcher, Susan K, Gage, Fred H, Warren, Wesley C, Shendure, Jay, Haussler, David, Schneider, Valerie A, Cao, Han, Ventura, Mario, Wilson, Richard K, Paten, Benedict, Pollen, Alex, and Eichler, Evan E

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Genetics, Stem Cell Research, Human Genome, Biotechnology, Aetiology, Underpinning research, 1.1 Normal biological development and functioning, 2.1 Biological and endogenous factors, Generic health relevance, Animals, Contig Mapping, Evolution, Molecular, Genetic Variation, Genome, Human, Hominidae, Humans, Molecular Sequence Annotation, Sequence Analysis, DNA, General Science & Technology
Abstract

Genetic studies of human evolution require high-quality contiguous ape genome assemblies that are not guided by the human reference. We coupled long-read sequence assembly and full-length complementary DNA sequencing with a multiplatform scaffolding approach to produce ab initio chimpanzee and orangutan genome assemblies. By comparing these with two long-read de novo human genome assemblies and a gorilla genome assembly, we characterized lineage-specific and shared great ape genetic variation ranging from single- to mega-base pair-sized variants. We identified ~17,000 fixed human-specific structural variants identifying genic and putative regulatory changes that have emerged in humans since divergence from nonhuman apes. Interestingly, these variants are enriched near genes that are down-regulated in human compared to chimpanzee cerebral organoids, particularly in cells analogous to radial glial neural progenitors.

Published
2018

9. Quantitative analysis of population-scale family trees with millions of relatives

Author

Kaplanis, Joanna, Gordon, Assaf, Shor, Tal, Weissbrod, Omer, Geiger, Dan, Wahl, Mary, Gershovits, Michael, Markus, Barak, Sheikh, Mona, Gymrek, Melissa, Bhatia, Gaurav, MacArthur, Daniel G, Price, Alkes L, and Erlich, Yaniv

Subjects
Genetics, Generic health relevance, Datasets as Topic, Family, Genealogy and Heraldry, Humans, Longevity, Models, Genetic, Pedigree, Population, General Science & Technology
Abstract

Family trees have vast applications in fields as diverse as genetics, anthropology, and economics. However, the collection of extended family trees is tedious and usually relies on resources with limited geographical scope and complex data usage restrictions. We collected 86 million profiles from publicly available online data shared by genealogy enthusiasts. After extensive cleaning and validation, we obtained population-scale family trees, including a single pedigree of 13 million individuals. We leveraged the data to partition the genetic architecture of human longevity and to provide insights into the geographical dispersion of families. We also report a simple digital procedure to overlay other data sets with our resource.

Published
2018

10. Coherently aligned nanoparticles within a biogenic single crystal: A biological prestressing strategy

Author

Polishchuk, Iryna, Bracha, Avigail Aronhime, Bloch, Leonid, Levy, Davide, Kozachkevich, Stas, Etinger-Geller, Yael, Kauffmann, Yaron, Burghammer, Manfred, Giacobbe, Carlotta, Villanova, Julie, Hendler, Gordon, Sun, Chang-Yu, Giuffre, Anthony J, Marcus, Matthew A, Kundanati, Lakshminath, Zaslansky, Paul, Pugno, Nicola M, Gilbert, Pupa UPA, Katsman, Alex, and Pokroy, Boaz

Subjects
Engineering, Materials Engineering, Animals, Biological Products, Calcium Carbonate, Crystallization, Echinodermata, Magnesium, Nanoparticles, Stress, Mechanical, General Science & Technology
Abstract

In contrast to synthetic materials, materials produced by organisms are formed in ambient conditions and with a limited selection of elements. Nevertheless, living organisms reveal elegant strategies for achieving specific functions, ranging from skeletal support to mastication, from sensors and defensive tools to optical function. Using state-of-the-art characterization techniques, we present a biostrategy for strengthening and toughening the otherwise brittle calcite optical lenses found in the brittlestar Ophiocoma wendtii This intriguing process uses coherent nanoprecipitates to induce compressive stresses on the host matrix, functionally resembling the Guinier-Preston zones known in classical metallurgy. We believe that these calcitic nanoparticles, being rich in magnesium, segregate during or just after transformation from amorphous to crystalline phase, similarly to segregation behavior from a supersaturated quenched alloy.

Published
2017

11. Catalytic molten metals for the direct conversion of methane to hydrogen and separable carbon

Author

Upham, D Chester, Agarwal, Vishal, Khechfe, Alexander, Snodgrass, Zachary R, Gordon, Michael J, Metiu, Horia, and McFarland, Eric W

Subjects
Affordable and Clean Energy, General Science & Technology
Abstract

Metals that are active catalysts for methane (Ni, Pt, Pd), when dissolved in inactive low-melting temperature metals (In, Ga, Sn, Pb), produce stable molten metal alloy catalysts for pyrolysis of methane into hydrogen and carbon. All solid catalysts previously used for this reaction have been deactivated by carbon deposition. In the molten alloy system, the insoluble carbon floats to the surface where it can be skimmed off. A 27% Ni-73% Bi alloy achieved 95% methane conversion at 1065°C in a 1.1-meter bubble column and produced pure hydrogen without CO2 or other by-products. Calculations show that the active metals in the molten alloys are atomically dispersed and negatively charged. There is a correlation between the amount of charge on the atoms and their catalytic activity.

Published
2017

13. Long-read sequence assembly of the gorilla genome

Author

Gordon, David, Huddleston, John, Chaisson, Mark JP, Hill, Christopher M, Kronenberg, Zev N, Munson, Katherine M, Malig, Maika, Raja, Archana, Fiddes, Ian, Hillier, LaDeana W, Dunn, Christopher, Baker, Carl, Armstrong, Joel, Diekhans, Mark, Paten, Benedict, Shendure, Jay, Wilson, Richard K, Haussler, David, Chin, Chen-Shan, and Eichler, Evan E

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Genetics, Human Genome, Biotechnology, Generic health relevance, Animals, Contig Mapping, Evolution, Molecular, Expressed Sequence Tags, Female, Genetic Variation, Genome, Human, Genomics, Gorilla gorilla, Humans, Sequence Alignment, Sequence Analysis, DNA, General Science & Technology
Abstract

Accurate sequence and assembly of genomes is a critical first step for studies of genetic variation. We generated a high-quality assembly of the gorilla genome using single-molecule, real-time sequence technology and a string graph de novo assembly algorithm. The new assembly improves contiguity by two to three orders of magnitude with respect to previously released assemblies, recovering 87% of missing reference exons and incomplete gene models. Although regions of large, high-identity segmental duplications remain largely unresolved, this comprehensive assembly provides new biological insight into genetic diversity, structural variation, gene loss, and representation of repeat structures within the gorilla genome. The approach provides a path forward for the routine assembly of mammalian genomes at a level approaching that of the current quality of the human genome.

Published
2016

14. Gut bacteria that prevent growth impairments transmitted by microbiota from malnourished children

Author

Blanton, Laura V, Charbonneau, Mark R, Salih, Tarek, Barratt, Michael J, Venkatesh, Siddarth, Ilkaveya, Olga, Subramanian, Sathish, Manary, Mark J, Trehan, Indi, Jorgensen, Josh M, Fan, Yue-Mei, Henrissat, Bernard, Leyn, Semen A, Rodionov, Dmitry A, Osterman, Andrei L, Maleta, Kenneth M, Newgard, Christopher B, Ashorn, Per, Dewey, Kathryn G, and Gordon, Jeffrey I

Subjects
Microbiology, Biological Sciences, Biomedical and Clinical Sciences, Pediatric, Nutrition, Oral and gastrointestinal, Zero Hunger, Animals, Bacteria, Bifidobacterium, Body Weight, Bone Development, Clostridiales, Disease Models, Animal, Feces, Femur, Gastrointestinal Microbiome, Germ-Free Life, Humans, Infant, Infant Nutrition Disorders, Malawi, Male, Mice, Mice, Inbred C57BL, General Science & Technology
Abstract

Undernourished children exhibit impaired development of their gut microbiota. Transplanting microbiota from 6- and 18-month-old healthy or undernourished Malawian donors into young germ-free mice that were fed a Malawian diet revealed that immature microbiota from undernourished infants and children transmit impaired growth phenotypes. The representation of several age-discriminatory taxa in recipient animals correlated with lean body mass gain; liver, muscle, and brain metabolism; and bone morphology. Mice were cohoused shortly after receiving microbiota from healthy or severely stunted and underweight infants; age- and growth-discriminatory taxa from the microbiota of the former were able to invade that of the latter, which prevented growth impairments in recipient animals. Adding two invasive species, Ruminococcus gnavus and Clostridium symbiosum, to the microbiota from undernourished donors also ameliorated growth and metabolic abnormalities in recipient animals. These results provide evidence that microbiota immaturity is causally related to undernutrition and reveal potential therapeutic targets and agents.

Published
2016

15. The Genome of the Natural Genetic Engineer Agrobacterium tumefaciens C58

Author

Wood, Derek W., Setubal, Joao C., Kaul, Rajinder, Monks, Dave E., Kitajima, Joao P., Okura, Vagner K., Zhou, Yang, Chen, Lishan, Wood, Gwendolyn E., Almeida, Nalvo F., Woo, Lisa, Chen, Yuching, Paulsen, Ian T., Eisen, Jonathan A., Karp, Peter D., Bovee, Donald, Chapman, Peter, Clendenning, James, Deatherage, Glenda, Gillet, Will, Grant, Charles, Kutyavin, Tatyana, Levy, Ruth, Li, Meng-Jin, McClelland, Erin, Palmieri, Anthony, Raymond, Christopher, Rouse, Gregory, Saenphimmachak, Channakhone, Wu, Zaining, Romero, Pedro, Gordon, David, Zhang, Shiping, Yoo, Heayun, Tao, Yumin, Biddle, Phyllis, Jung, Mark, Krespan, William, Perry, Michael, Gordon-Kamm, Bill, Liao, Li, Kim, Sun, Hendrick, Carol, Zhao, Zuo-Yu, Dolan, Maureen, Chumley, Forrest, Tingey, Scott V., Tomb, Jean-Francois, Gordon, Milton P., Olson, Maynard V., and Nester, Eugene W.

Published
2001

16. Genome Sequence of the Tsetse Fly (Glossina morsitans): Vector of African Trypanosomiasis

Author

Initiative, International Glossina Genome, Attardo, Geoffrey M, Abila, Patrick P, Auma, Joanna E, Baumann, Aaron A, Benoit, Joshua B, Brelsfoard, Corey L, Ribeiro, José MC, Cotton, James A, Pham, Daphne QD, Darby, Alistair C, Van Den Abbeele, Jan, Denlinger, David L, Field, Linda M, Nyanjom, Steven RG, Gaunt, Michael W, Geiser, Dawn L, Gomulski, Ludvik M, Haines, Lee R, Hansen, Immo A, Jones, Jeffery W, Kibet, Caleb K, Kinyua, Johnson K, Larkin, Denis M, Lehane, Michael J, Rio, Rita VM, Macdonald, Sandy J, Macharia, Rosaline W, Malacrida, Anna R, Marco, Heather G, Marucha, Kevin K, Masiga, Daniel K, Meuti, Megan E, Mireji, Paul O, Obiero, George FO, Koekemoer, Jacobus JO, Okoro, Chinyere K, Omedo, Irene A, Osamor, Victor C, Balyeidhusa, Apollo SP, Peyton, Justin T, Price, David P, Quail, Michael A, Ramphul, Urvashi N, Rawlings, Neil D, Riehle, Michael A, Robertson, Hugh M, Sanders, Mandy J, Scott, Maxwell J, Dashti, Zahra Jalali Sefid, Snyder, Anna K, Srivastava, Tulika P, Stanley, Eleanor J, Swain, Martin T, Hughes, Daniel ST, Tarone, Aaron M, Taylor, Todd D, Telleria, Erich L, Thomas, Gavin H, Walshe, Deirdre P, Wilson, Richard K, Winzerling, Joy J, Acosta-Serrano, Alvaro, Aksoy, Serap, Arensburger, Peter, Aslett, Martin, Bateta, Rosemary, Benkahla, Alia, Berriman, Matthew, Bourtzis, Kostas, Caers, Jelle, Caljon, Guy, Christoffels, Alan, Falchetto, Marco, Friedrich, Markus, Fu, Shuhua, Gäde, Gerd, Githinji, George, Gregory, Richard, Hall, Neil, Harkins, Gordon, Hattori, Masahira, Hertz-Fowler, Christiane, Hide, Winston, Hu, Wanqi, Imanishi, Tadashi, Inoue, Noboru, Jonas, Mario, Kawahara, Yoshihiro, Koffi, Mathurin, Kruger, Adele, Lawson, Daniel, Lehane, Stella, Lehväslaiho, Heikki, Luiz, Thiago, Makgamathe, Mmule, Malele, Imna, Manangwa, Oliver, Manga, Lucien, and Megy, Karyn

Subjects
Vector-Borne Diseases, Genetics, Prevention, Infectious Diseases, Biotechnology, 2.2 Factors relating to the physical environment, Aetiology, Infection, Good Health and Well Being, Animals, Blood, Feeding Behavior, Female, Genes, Insect, Genome, Insect, Insect Proteins, Insect Vectors, Microbiota, Molecular Sequence Annotation, Molecular Sequence Data, Reproduction, Salivary Glands, Sensation, Sequence Analysis, DNA, Symbiosis, Trypanosoma, Trypanosomiasis, African, Tsetse Flies, Wolbachia, International Glossina Genome Initiative, General Science & Technology
Abstract

Tsetse flies are the sole vectors of human African trypanosomiasis throughout sub-Saharan Africa. Both sexes of adult tsetse feed exclusively on blood and contribute to disease transmission. Notable differences between tsetse and other disease vectors include obligate microbial symbioses, viviparous reproduction, and lactation. Here, we describe the sequence and annotation of the 366-megabase Glossina morsitans morsitans genome. Analysis of the genome and the 12,308 predicted protein-encoding genes led to multiple discoveries, including chromosomal integrations of bacterial (Wolbachia) genome sequences, a family of lactation-specific proteins, reduced complement of host pathogen recognition proteins, and reduced olfaction/chemosensory associated genes. These genome data provide a foundation for research into trypanosomiasis prevention and yield important insights with broad implications for multiple aspects of tsetse biology.

Published
2014

17. A luminous fast radio burst that probes the Universe at redshift 1

Author

Ryder, S. D., primary, Bannister, K. W., additional, Bhandari, S., additional, Deller, A. T., additional, Ekers, R. D., additional, Glowacki, M., additional, Gordon, A. C., additional, Gourdji, K., additional, James, C. W., additional, Kilpatrick, C. D., additional, Lu, W., additional, Marnoch, L., additional, Moss, V. A., additional, Prochaska, J. X., additional, Qiu, H., additional, Sadler, E. M., additional, Simha, S., additional, Sammons, M. W., additional, Scott, D. R., additional, Tejos, N., additional, and Shannon, R. M., additional

Published
2023
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18. The chromatin accessibility landscape of primary human cancers

Author

The Cancer Genome Atlas Analysis Network, Corces, M. Ryan, Granja, Jeffrey M., Shams, Shadi, Louie, Bryan H., Seoane, Jose A., Zhou, Wanding, Silva, Tiago C., Groeneveld, Clarice, Wong, Christopher K., Cho, Seung Woo, Satpathy, Ansuman T., Mumbach, Maxwell R., Hoadley, Katherine A., Robertson, A. Gordon, Sheffield, Nathan C., Felau, Ina, Castro, Mauro A. A., Berman, Benjamin P., Staudt, Louis M., Zenklusen, Jean C., Laird, Peter W., Curtis, Christina, Greenleaf, William J., and Chang, Howard Y.

Published
2018

21. Global carbon intensity of crude oil production

Author

Masnadi, Mohammad S., El-Houjeiri, Hassan M., Schunack, Dominik, Li, Yunpo, Englander, Jacob G., Badahdah, Alhassan, Monfort, Jean-Christophe, Anderson, James E., Wallington, Timothy J., Bergerson, Joule A., Gordon, Deborah, Koomey, Jonathan, Przesmitzki, Steven, Azevedo, Inês L., Bi, Xiaotao T., Duffy, James E., Heath, Garvin A., Keoleian, Gregory A., McGlade, Christophe, Meehan, D. Nathan, Yeh, Sonia, You, Fengqi, Wang, Michael, and Brandt, Adam R.

Published
2018

22. SciComm speaks

Author

Forster, Victoria J., Gordon, Beth R., and Wright, Glen

Published
2018

23. The science of fake news

Author

Lazer, David M. J., Baum, Matthew A., Benkler, Yochai, Berinsky, Adam J., Greenhill, Kelly M., Menczer, Filippo, Metzger, Miriam J., Nyhan, Brendan, Pennycook, Gordon, Rothschild, David, Schudson, Michael, Sloman, Steven A., Sunstein, Cass R., Thorson, Emily A., Watts, Duncan J., and Zittrain, Jonathan L.

Published
2018

25. Femtosecond symmetry breaking and coherent relaxation of methane cations via x-ray spectroscopy

Author

Enrico Ridente, Diptarka Hait, Eric A. Haugen, Andrew D. Ross, Daniel M. Neumark, Martin Head-Gordon, and Stephen R. Leone

Subjects
Multidisciplinary
Abstract

Understanding the relaxation pathways of photoexcited molecules is essential to gain atomistic-level insight into photochemistry. We performed a time-resolved study of ultrafast molecular symmetry breaking through geometric relaxation (Jahn-Teller distortion) on the methane cation. Attosecond transient absorption spectroscopy with soft x-rays at the carbon K-edge revealed that the distortion occurred within 10 ± 2 femtoseconds after few-femtosecond strong-field ionization of methane. The distortion activated coherent oscillations in the asymmetric scissoring vibrational mode of the symmetry-broken cation, which were detected in the x-ray signal. These oscillations were damped within 58 ± 13 femtoseconds because vibrational coherence was lost with the energy redistributing into lower-frequency vibrational modes. This study completely reconstructs the molecular relaxation dynamics of this prototypical example and opens avenues for exploring complex systems.

Published
2023

26. Gut Microbiota from Twins Discordant for Obesity Modulate Metabolism in Mice

Author

Ridaura, Vanessa K, Faith, Jeremiah J, Rey, Federico E, Cheng, Jiye, Duncan, Alexis E, Kau, Andrew L, Griffin, Nicholas W, Lombard, Vincent, Henrissat, Bernard, Bain, James R, Muehlbauer, Michael J, Ilkayeva, Olga, Semenkovich, Clay F, Funai, Katsuhiko, Hayashi, David K, Lyle, Barbara J, Martini, Margaret C, Ursell, Luke K, Clemente, Jose C, Van Treuren, William, Walters, William A, Knight, Rob, Newgard, Christopher B, Heath, Andrew C, and Gordon, Jeffrey I

Subjects
Prevention, Obesity, Nutrition, Aetiology, 2.1 Biological and endogenous factors, Cardiovascular, Oral and gastrointestinal, Stroke, Metabolic and endocrine, Adiposity, Adult, Animals, Bacteroidetes, Cecum, Diet, Fat-Restricted, Feces, Female, Gastrointestinal Tract, Germ-Free Life, Humans, Metabolome, Metagenome, Mice, Mice, Inbred C57BL, Mice, Obese, Thinness, Twins, Weight Gain, Young Adult, General Science & Technology
Abstract

The role of specific gut microbes in shaping body composition remains unclear. We transplanted fecal microbiota from adult female twin pairs discordant for obesity into germ-free mice fed low-fat mouse chow, as well as diets representing different levels of saturated fat and fruit and vegetable consumption typical of the U.S. diet. Increased total body and fat mass, as well as obesity-associated metabolic phenotypes, were transmissible with uncultured fecal communities and with their corresponding fecal bacterial culture collections. Cohousing mice harboring an obese twin's microbiota (Ob) with mice containing the lean co-twin's microbiota (Ln) prevented the development of increased body mass and obesity-associated metabolic phenotypes in Ob cage mates. Rescue correlated with invasion of specific members of Bacteroidetes from the Ln microbiota into Ob microbiota and was diet-dependent. These findings reveal transmissible, rapid, and modifiable effects of diet-by-microbiota interactions.

Published
2013

27. Repeated Cortico-Striatal Stimulation Generates Persistent OCD-Like Behavior

Author

Ahmari, Susanne E, Spellman, Timothy, Douglass, Neria L, Kheirbek, Mazen A, Simpson, H Blair, Deisseroth, Karl, Gordon, Joshua A, and Hen, René

Subjects
Behavioral and Social Science, Anxiety Disorders, Brain Disorders, Basic Behavioral and Social Science, Mental Health, Adenoviridae, Animals, Artificial Gene Fusion, Bacterial Proteins, Behavior, Animal, Channelrhodopsins, Corpus Striatum, Electric Stimulation, Fluoxetine, Frontal Lobe, Luminescent Proteins, Male, Mice, Obsessive-Compulsive Disorder, Optogenetics, Serotonin Uptake Inhibitors, Thalamus, Selective Serotonin Reuptake Inhibitors, General Science & Technology
Abstract

Although cortico-striato-thalamo-cortical (CSTC) circuit dysregulation is correlated with obsessive compulsive disorder (OCD), causation cannot be tested in humans. We used optogenetics in mice to simulate CSTC hyperactivation observed in OCD patients. Whereas acute orbitofrontal cortex (OFC)-ventromedial striatum (VMS) stimulation did not produce repetitive behaviors, repeated hyperactivation over multiple days generated a progressive increase in grooming, a mouse behavior related to OCD. Increased grooming persisted for 2 weeks after stimulation cessation. The grooming increase was temporally coupled with a progressive increase in light-evoked firing of postsynaptic VMS cells. Both increased grooming and evoked firing were reversed by chronic fluoxetine, a first-line OCD treatment. Brief but repeated episodes of abnormal circuit activity may thus set the stage for the development of persistent psychopathology.

Published
2013

28. Phytophthora Genome Sequences Uncover Evolutionary Origins and Mechanisms of Pathogenesis

Author

Tyler, Brett M., Tripathy, Sucheta, Zhang, Xuemin, Dehal, Paramvir, Aerts, Andrea, Arredondo, Felipe D., Baxter, Laura, Bensasson, Douda, Beynon, Jim L., Chapman, Jarrod, Dorrance, Anne E., Dou, Daolong, Dickerman, Allan W., Dubchak, Inna L., Garbelotto, Matteo, Gijzen, Mark, Gordon, Stuart G., Govers, Francine, Grunwald, Niklaus J., Huang, Wayne, Ivors, Kelly L., Jones, Richard W., Kamoun, Sophien, Krampis, Konstantinos, Lamour, Kurt H., Lee, Mi-Kyung, McDonald, W. Hayes, Medina, Mónica, Nordberg, Eric K., Maclean, Donald J., Ospina-Giraldo, Manuel D., Morris, Paul F., Phuntumart, Vipaporn, Putnam, Nicholas H., Rash, Sam, Sakihama, Yasuko, Salamov, Asaf A., Savidor, Alon, Scheuring, Chantel F., Smith, Brian M., Terry, Astrid, Torto-Alalibo, Trudy A., Win, Joe, Xu, Zhanyou, Zhang, Hongbin, Grigoriev, Igor V., Rokhsar, Daniel S., and Boore, Jeffrey L.

Published
2006

29. Massive-Star Supernovae as Major Dust Factories

Author

Ercolano, Barbara, Barlow, M. J., Clayton, Geoffrey C., Zijlstra, Albert A., Meixner, Margaret, Speck, Angela, Gledhill, Tim M., Panagia, Nino, Cohen, Martin, Gordon, Karl D., Meyer, Martin, Fabbri, Joanna, Welch, Douglas L., Regan, Michael W., and Kennicutt, Robert C.

Published
2006

34. Global Consequences of Land Use

Author

Foley, Jonathan A., DeFries, Ruth, Asner, Gregory P., Barford, Carol, Bonan, Gordon, Carpenter, Stephen R., Chapin, F. Stuart, Coe, Michael T., Daily, Gretchen C., Gibbs, Holly K., Helkowski, Joseph H., Holloway, Tracey, Howard, Erica A., Kucharik, Christopher J., Monfreda, Chad, Patz, Jonathan A., Prentice, I. Colin, Ramankutty, Navin, and Snyder, Peter K.

Published
2005

39. Southern Ocean Iron Enrichment Experiment: Carbon Cycling in High- and Low-Si Waters

Author

Coale, Kenneth H., Johnson, Kenneth S., Chavez, Francisco P., Buesseler, Ken O., Barber, Richard T., Brzezinski, Mark A., Cochlan, William P., Millero, Frank J., Falkowski, Paul G., Bauer, James E., Wanninkhof, Rik H., Kudela, Raphael M., Altabet, Mark A., Hales, Burke E., Takahashi, Taro, Landry, Michael R., Bidigare, Robert R., Wang, Xiujun, Chase, Zanna, Strutton, Pete G., Friederich, Gernot E., Gorbunov, Maxim Y., Lance, Veronica P., Hilting, Anna K., Hiscock, Michael R., Demarest, Mark, Hiscock, William T., Sullivan, Kevin F., Tanner, Sara J., Gordon, R. Mike, Hunter, Craig N., Elrod, Virginia A., Fitzwater, Steve E., Jones, Janice L., Tozzi, Sasha, Koblizek, Michal, Roberts, Alice E., Herndon, Julian, Brewster, Jodi, Ladizinsky, Nicolas, Smith, Geoffrey, Cooper, David, Timothy, David, Brown, Susan L., Selph, Karen E., Sheridan, Cecelia C., Twining, Benjamin S., and Johnson, Zackary I.

Published
2004

40. The Challenges of an HIV Vaccine Enterprise

Author

Zinkernagel, Rolf M., Wolf, Hans, Klausner, Richard D., Fauci, Anthony S., Corey, Lawrence, Nabel, Gary J., Gayle, Helene, Berkley, Seth, Haynes, Barton F., Baltimore, David, Collins, Chris, Douglas, R. Gordon, Esparza, Jose, Francis, Donald P., Ganguly, N. K., Gerberding, Julie Louise, Johnson, Margaret I., Kazatchkine, Michel D., McMichael, Andrew J., Makgoba, Malegapuru W., Pantaleo, Giuseppe, Piot, Peter, Shao, Yiming, Tramont, Edmund, Varmus, Harold, and Wasserheit, Judith N.

Published
2004

42. Global Mapping of the Yeast Genetic Interaction Network

Author

Lesage, Guillaume, Bader, Gary D., Ding, Huiming, Xu, Hong, Xin, Xiaofeng, Young, James, Berriz, Gabriel F., Brost, Renee L., Chang, Michael, Chen, YiQun, Cheng, Xin, Chua, Gordon, Friesen, Helena, Goldberg, Debra S., Haynes, Jennifer, Humphries, Christine, He, Grace, Hussein, Shamiza, Ke, Lizhu, Krogan, Nevan, Li, Zhijian, Levinson, Joshua N., Lu, Hong, Ménard, Patrice, Munyana, Christella, Parsons, Ainslie B., Ryan, Owen, Tonikian, Raffi, Roberts, Tania, Sdicu, Anne-Marie, Shapiro, Jesse, Sheikh, Bilal, Suter, Bernhard, Wong, Sharyl L., Zhang, Lan V., Zhu, Hongwei, Burd, Christopher G., Munro, Sean, Sander, Chris, Rine, Jasper, Greenblatt, Jack, Peter, Matthias, Bretscher, Anthony, Bell, Graham, Roth, Frederick P., Brown, Grant W., Andrews, Brenda, Bussey, Howard, and Boone, Charles

Published
2004

45. Genomic history of the seventh pandemic of cholera in Africa

Author

Weill, François-Xavier, Domman, Daryl, Njamkepo, Elisabeth, Tarr, Cheryl, Rauzier, Jean, Fawal, Nizar, Keddy, Karen H., Salje, Henrik, Moore, Sandra, Mukhopadhyay, Asish K., Bercion, Raymond, Luquero, Francisco J., Ngandjio, Antoinette, Dosso, Mireille, Monakhova, Elena, Garin, Benoit, Bouchier, Christiane, Pazzani, Carlo, Mutreja, Ankur, Grunow, Roland, Sidikou, Fati, Bonte, Laurence, Breurec, Sébastien, Damian, Maria, Njanpop-Lafourcade, Berthe-Marie, Sapriel, Guillaume, Page, Anne-Laure, Hamze, Monzer, Henkens, Myriam, Chowdhury, Goutam, Mengel, Martin, Koeck, Jean-Louis, Fournier, Jean-Michel, Dougan, Gordon, Grimont, Patrick A. D., Parkhill, Julian, Holt, Kathryn E., Piarroux, Renaud, Ramamurthy, Thandavarayan, Quilici, Marie-Laure, and Thomson, Nicholas R.

Published
2017

46. Integrated view of Vibrio cholerae in the Americas

Author

Domman, Daryl, Quilici, Marie-Laure, Dorman, Matthew J., Njamkepo, Elisabeth, Mutreja, Ankur, Mather, Alison E., Delgado, Gabriella, Morales-Espinosa, Rosario, Grimont, Patrick A. D., Lizárraga-Partida, Marcial Leonardo, Bouchier, Christiane, Aanensen, David M., Kuri-Morales, Pablo, Tarr, Cheryl L., Dougan, Gordon, Parkhill, Julian, Campos, Josefina, Cravioto, Alejandro, Weill, François-Xavier, and Thomson, Nicholas R.

Published
2017

47. Lactobacillus reuteri induces gut intraepithelial CD4⁺CD8αα⁺ T cells

Author

Cervantes-Barragan, Luisa, Chai, Jiani N., Tianero, Ma. Diarey, Di Luccia, Blanda, Ahern, Philip P., Merriman, Joseph, Cortez, Victor S., Caparon, Michael G., Donia, Mohamed S., Gilfillan, Susan, Cella, Marina, Gordon, Jeffrey I., Hsieh, Chyi-Song, and Colonna, Marco

Published
2017

49. Mechanism of transmembrane signaling by sensor histidine kinases

Author

Gushchin, Ivan, Melnikov, Igor, Polovinkin, Vitaly, Ishchenko, Andrii, Yuzhakova, Anastasia, Buslaev, Pavel, Bourenkov, Gleb, Grudinin, Sergei, Round, Ekaterina, Balandin, Taras, Borshchevskiy, Valentin, Willbold, Dieter, Leonard, Gordon, Büldt, Georg, Popov, Alexander, and Gordeliy, Valentin

Published
2017

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