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1. Limits to reproduction and seed size-number trade-offs that shape forest dominance and future recovery

Author

Tong Qiu, Robert Andrus, Marie-Claire Aravena, Davide Ascoli, Yves Bergeron, Roberta Berretti, Daniel Berveiller, Michal Bogdziewicz, Thomas Boivin, Raul Bonal, Don C. Bragg, Thomas Caignard, Rafael Calama, J. Julio Camarero, Chia-Hao Chang-Yang, Natalie L. Cleavitt, Benoit Courbaud, Francois Courbet, Thomas Curt, Adrian J. Das, Evangelia Daskalakou, Hendrik Davi, Nicolas Delpierre, Sylvain Delzon, Michael Dietze, Sergio Donoso Calderon, Laurent Dormont, Josep Espelta, Timothy J. Fahey, William Farfan-Rios, Catherine A. Gehring, Gregory S. Gilbert, Georg Gratzer, Cathryn H. Greenberg, Qinfeng Guo, Andrew Hacket-Pain, Arndt Hampe, Qingmin Han, Janneke Hille Ris Lambers, Kazuhiko Hoshizaki, Ines Ibanez, Jill F. Johnstone, Valentin Journé, Daisuke Kabeya, Christopher L. Kilner, Thomas Kitzberger, Johannes M. H. Knops, Richard K. Kobe, Georges Kunstler, Jonathan G. A. Lageard, Jalene M. LaMontagne, Mateusz Ledwon, Francois Lefevre, Theodor Leininger, Jean-Marc Limousin, James A. Lutz, Diana Macias, Eliot J. B. McIntire, Christopher M. Moore, Emily Moran, Renzo Motta, Jonathan A. Myers, Thomas A. Nagel, Kyotaro Noguchi, Jean-Marc Ourcival, Robert Parmenter, Ian S. Pearse, Ignacio M. Perez-Ramos, Lukasz Piechnik, John Poulsen, Renata Poulton-Kamakura, Miranda D. Redmond, Chantal D. Reid, Kyle C. Rodman, Francisco Rodriguez-Sanchez, Javier D. Sanguinetti, C. Lane Scher, William H. Schlesinger, Harald Schmidt Van Marle, Barbara Seget, Shubhi Sharma, Miles Silman, Michael A. Steele, Nathan L. Stephenson, Jacob N. Straub, I-Fang Sun, Samantha Sutton, Jennifer J. Swenson, Margaret Swift, Peter A. Thomas, Maria Uriarte, Giorgio Vacchiano, Thomas T. Veblen, Amy V. Whipple, Thomas G. Whitham, Andreas P. Wion, Boyd Wright, S. Joseph Wright, Kai Zhu, Jess K. Zimmerman, Roman Zlotin, Magdalena Zywiec, and James S. Clark

Subjects
Science
Abstract

The relationships that control seed production in trees are key to understand evolutionary pressures that have shaped forests. A global synthesis of fecundity data reveals that while seed production is not constrained by a strict size-number trade-off, it is influenced by taxonomy and nutrient allocation.

Published
2022
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2. Continent-wide tree fecundity driven by indirect climate effects

Author

James S. Clark, Robert Andrus, Melaine Aubry-Kientz, Yves Bergeron, Michal Bogdziewicz, Don C. Bragg, Dale Brockway, Natalie L. Cleavitt, Susan Cohen, Benoit Courbaud, Robert Daley, Adrian J. Das, Michael Dietze, Timothy J. Fahey, Istem Fer, Jerry F. Franklin, Catherine A. Gehring, Gregory S. Gilbert, Cathryn H. Greenberg, Qinfeng Guo, Janneke HilleRisLambers, Ines Ibanez, Jill Johnstone, Christopher L. Kilner, Johannes Knops, Walter D. Koenig, Georges Kunstler, Jalene M. LaMontagne, Kristin L. Legg, Jordan Luongo, James A. Lutz, Diana Macias, Eliot J. B. McIntire, Yassine Messaoud, Christopher M. Moore, Emily Moran, Jonathan A. Myers, Orrin B. Myers, Chase Nunez, Robert Parmenter, Sam Pearse, Scott Pearson, Renata Poulton-Kamakura, Ethan Ready, Miranda D. Redmond, Chantal D. Reid, Kyle C. Rodman, C. Lane Scher, William H. Schlesinger, Amanda M. Schwantes, Erin Shanahan, Shubhi Sharma, Michael A. Steele, Nathan L. Stephenson, Samantha Sutton, Jennifer J. Swenson, Margaret Swift, Thomas T. Veblen, Amy V. Whipple, Thomas G. Whitham, Andreas P. Wion, Kai Zhu, and Roman Zlotin

Subjects
Science
Abstract

Disentangling the various pathways by which climate change may drive community shifts in real-world ecosystems is challenging. Here the authors apply a trend attribution approach to a large dataset from the MASTIF database to assess the contribution of direct and indirect effects of climate on tree fecundity in North America, finding that the latter dominate trends by affecting tree growth and size and thereby fecundity.

Published
2021
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3. Framework for quality assessment of whole genome cancer sequences

Author

Justin P. Whalley, Ivo Buchhalter, Esther Rheinbay, Keiran M. Raine, Miranda D. Stobbe, Kortine Kleinheinz, Johannes Werner, Sergi Beltran, Marta Gut, Daniel Hübschmann, Barbara Hutter, Dimitri Livitz, Marc D. Perry, Mara Rosenberg, Gordon Saksena, Jean-Rémi Trotta, Roland Eils, Daniela S. Gerhard, Peter J. Campbell, Matthias Schlesner, and Ivo G. Gut

Subjects
Science
Abstract

Working with cancer genomes from multiple projects can increase investigative power, but quality of sequences can vary. Here, the authors present a framework for comparing whole genome sequencing quality to help researchers guide downstream analyses and exclude poor quality samples.

Published
2020
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4. Rab11b-mediated integrin recycling promotes brain metastatic adaptation and outgrowth

Author

Erin N. Howe, Miranda D. Burnette, Melanie E. Justice, Patricia M. Schnepp, Victoria Hedrick, James W. Clancy, Ian H. Guldner, Alicia T. Lamere, Jun Li, Uma K. Aryal, Crislyn D’Souza-Schorey, Jeremiah J. Zartman, and Siyuan Zhang

Subjects
Science
Abstract

Mechanisms governing adaptation of breast cancer to the brain metastatic microenvironment are unclear. Here, the authors use RNA-sequencing and Drosophila screening to identify Rab11b-mediated endosomal recycling as a unique mechanism for adaptation to a challenging metastatic microenvironment, which can be exploited by repurposing statins.

Published
2020
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5. Author Correction: Continent-wide tree fecundity driven by indirect climate effects

Author

James S. Clark, Robert Andrus, Melaine Aubry-Kientz, Yves Bergeron, Michal Bogdziewicz, Don C. Bragg, Dale Brockway, Natalie L. Cleavitt, Susan Cohen, Benoit Courbaud, Robert Daley, Adrian J. Das, Michael Dietze, Timothy J. Fahey, Istem Fer, Jerry F. Franklin, Catherine A. Gehring, Gregory S. Gilbert, Cathryn H. Greenberg, Qinfeng Guo, Janneke HilleRisLambers, Ines Ibanez, Jill Johnstone, Christopher L. Kilner, Johannes Knops, Walter D. Koenig, Georges Kunstler, Jalene M. LaMontagne, Kristin L. Legg, Jordan Luongo, James A. Lutz, Diana Macias, Eliot J. B. McIntire, Yassine Messaoud, Christopher M. Moore, Emily Moran, Jonathan A. Myers, Orrin B. Myers, Chase Nunez, Robert Parmenter, Sam Pearse, Scott Pearson, Renata Poulton-Kamakura, Ethan Ready, Miranda D. Redmond, Chantal D. Reid, Kyle C. Rodman, C. Lane Scher, William H. Schlesinger, Amanda M. Schwantes, Erin Shanahan, Shubhi Sharma, Michael A. Steele, Nathan L. Stephenson, Samantha Sutton, Jennifer J. Swenson, Margaret Swift, Thomas T. Veblen, Amy V. Whipple, Thomas G. Whitham, Andreas P. Wion, Kai Zhu, and Roman Zlotin

Subjects
Science
Abstract

A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-22025-2

Published
2021
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6. Limits to reproduction and seed size-number trade-offs that shape forest dominance and future recovery

Author

Qiu, Tong, Andrus, Robert, Aravena, Marie-Claire, Ascoli, Davide, Bergeron, Yves, Berretti, Roberta, Berveiller, Daniel, Bogdziewicz, Michal, Boivin, Thomas, Bonal, Raul, Bragg, Don C, Caignard, Thomas, Calama, Rafael, Camarero, J Julio, Chang-Yang, Chia-Hao, Cleavitt, Natalie L, Courbaud, Benoit, Courbet, Francois, Curt, Thomas, Das, Adrian J, Daskalakou, Evangelia, Davi, Hendrik, Delpierre, Nicolas, Delzon, Sylvain, Dietze, Michael, Calderon, Sergio Donoso, Dormont, Laurent, Espelta, Josep, Fahey, Timothy J, Farfan-Rios, William, Gehring, Catherine A, Gilbert, Gregory S, Gratzer, Georg, Greenberg, Cathryn H, Guo, Qinfeng, Hacket-Pain, Andrew, Hampe, Arndt, Han, Qingmin, Hille Ris Lambers, Janneke, Hoshizaki, Kazuhiko, Ibanez, Ines, Johnstone, Jill F, Journé, Valentin, Kabeya, Daisuke, Kilner, Christopher L, Kitzberger, Thomas, Knops, Johannes MH, Kobe, Richard K, Kunstler, Georges, Lageard, Jonathan GA, LaMontagne, Jalene M, Ledwon, Mateusz, Lefevre, Francois, Leininger, Theodor, Limousin, Jean-Marc, Lutz, James A, Macias, Diana, McIntire, Eliot JB, Moore, Christopher M, Moran, Emily, Motta, Renzo, Myers, Jonathan A, Nagel, Thomas A, Noguchi, Kyotaro, Ourcival, Jean-Marc, Parmenter, Robert, Pearse, Ian S, Perez-Ramos, Ignacio M, Piechnik, Lukasz, Poulsen, John, Poulton-Kamakura, Renata, Redmond, Miranda D, Reid, Chantal D, Rodman, Kyle C, Rodriguez-Sanchez, Francisco, Sanguinetti, Javier D, Scher, C Lane, Schlesinger, William H, Schmidt Van Marle, Harald, Seget, Barbara, Sharma, Shubhi, Silman, Miles, Steele, Michael A, Stephenson, Nathan L, Straub, Jacob N, Sun, I-Fang, Sutton, Samantha, Swenson, Jennifer J, Swift, Margaret, Thomas, Peter A, Uriarte, Maria, Vacchiano, Giorgio, Veblen, Thomas T, Whipple, Amy V, Whitham, Thomas G, Wion, Andreas P, Wright, Boyd, Wright, S Joseph, Zhu, Kai, and Zimmerman, Jess K

Subjects
Agricultural, Veterinary and Food Sciences, Biological Sciences, Ecology, Contraception/Reproduction, Fertility, Forests, Reproduction, Seeds, Trees
Abstract

The relationships that control seed production in trees are fundamental to understanding the evolution of forest species and their capacity to recover from increasing losses to drought, fire, and harvest. A synthesis of fecundity data from 714 species worldwide allowed us to examine hypotheses that are central to quantifying reproduction, a foundation for assessing fitness in forest trees. Four major findings emerged. First, seed production is not constrained by a strict trade-off between seed size and numbers. Instead, seed numbers vary over ten orders of magnitude, with species that invest in large seeds producing more seeds than expected from the 1:1 trade-off. Second, gymnosperms have lower seed production than angiosperms, potentially due to their extra investments in protective woody cones. Third, nutrient-demanding species, indicated by high foliar phosphorus concentrations, have low seed production. Finally, sensitivity of individual species to soil fertility varies widely, limiting the response of community seed production to fertility gradients. In combination, these findings can inform models of forest response that need to incorporate reproductive potential.

Published
2022

7. Continent-wide tree fecundity driven by indirect climate effects.

Author

Clark, James S, Andrus, Robert, Aubry-Kientz, Melaine, Bergeron, Yves, Bogdziewicz, Michal, Bragg, Don C, Brockway, Dale, Cleavitt, Natalie L, Cohen, Susan, Courbaud, Benoit, Daley, Robert, Das, Adrian J, Dietze, Michael, Fahey, Timothy J, Fer, Istem, Franklin, Jerry F, Gehring, Catherine A, Gilbert, Gregory S, Greenberg, Cathryn H, Guo, Qinfeng, HilleRisLambers, Janneke, Ibanez, Ines, Johnstone, Jill, Kilner, Christopher L, Knops, Johannes, Koenig, Walter D, Kunstler, Georges, LaMontagne, Jalene M, Legg, Kristin L, Luongo, Jordan, Lutz, James A, Macias, Diana, McIntire, Eliot JB, Messaoud, Yassine, Moore, Christopher M, Moran, Emily, Myers, Jonathan A, Myers, Orrin B, Nunez, Chase, Parmenter, Robert, Pearse, Sam, Pearson, Scott, Poulton-Kamakura, Renata, Ready, Ethan, Redmond, Miranda D, Reid, Chantal D, Rodman, Kyle C, Scher, C Lane, Schlesinger, William H, Schwantes, Amanda M, Shanahan, Erin, Sharma, Shubhi, Steele, Michael A, Stephenson, Nathan L, Sutton, Samantha, Swenson, Jennifer J, Swift, Margaret, Veblen, Thomas T, Whipple, Amy V, Whitham, Thomas G, Wion, Andreas P, Zhu, Kai, and Zlotin, Roman

Subjects
Trees, Seasons, Fertility, Geography, Models, Theoretical, North America, Climate Change, Models, Theoretical
Abstract

Indirect climate effects on tree fecundity that come through variation in size and growth (climate-condition interactions) are not currently part of models used to predict future forests. Trends in species abundances predicted from meta-analyses and species distribution models will be misleading if they depend on the conditions of individuals. Here we find from a synthesis of tree species in North America that climate-condition interactions dominate responses through two pathways, i) effects of growth that depend on climate, and ii) effects of climate that depend on tree size. Because tree fecundity first increases and then declines with size, climate change that stimulates growth promotes a shift of small trees to more fecund sizes, but the opposite can be true for large sizes. Change the depresses growth also affects fecundity. We find a biogeographic divide, with these interactions reducing fecundity in the West and increasing it in the East. Continental-scale responses of these forests are thus driven largely by indirect effects, recommending management for climate change that considers multiple demographic rates.

Published
2021

8. Author Correction: Continent-wide tree fecundity driven by indirect climate effects

Author

Clark, James S., Andrus, Robert, Aubry-Kientz, Melaine, Bergeron, Yves, Bogdziewicz, Michal, Bragg, Don C., Brockway, Dale, Cleavitt, Natalie L., Cohen, Susan, Courbaud, Benoit, Daley, Robert, Das, Adrian J., Dietze, Michael, Fahey, Timothy J., Fer, Istem, Franklin, Jerry F., Gehring, Catherine A., Gilbert, Gregory S., Greenberg, Cathryn H., Guo, Qinfeng, HilleRisLambers, Janneke, Ibanez, Ines, Johnstone, Jill, Kilner, Christopher L., Knops, Johannes, Koenig, Walter D., Kunstler, Georges, LaMontagne, Jalene M., Legg, Kristin L., Luongo, Jordan, Lutz, James A., Macias, Diana, McIntire, Eliot J. B., Messaoud, Yassine, Moore, Christopher M., Moran, Emily, Myers, Jonathan A., Myers, Orrin B., Nunez, Chase, Parmenter, Robert, Pearse, Sam, Pearson, Scott, Poulton-Kamakura, Renata, Ready, Ethan, Redmond, Miranda D., Reid, Chantal D., Rodman, Kyle C., Scher, C. Lane, Schlesinger, William H., Schwantes, Amanda M., Shanahan, Erin, Sharma, Shubhi, Steele, Michael A., Stephenson, Nathan L., Sutton, Samantha, Swenson, Jennifer J., Swift, Margaret, Veblen, Thomas T., Whipple, Amy V., Whitham, Thomas G., Wion, Andreas P., Zhu, Kai, and Zlotin, Roman

Published
2021
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9. Framework for quality assessment of whole genome cancer sequences

Author

Whalley, Justin P., Buchhalter, Ivo, Rheinbay, Esther, Raine, Keiran M., Stobbe, Miranda D., Kleinheinz, Kortine, Werner, Johannes, Beltran, Sergi, Gut, Marta, Hübschmann, Daniel, Hutter, Barbara, Livitz, Dimitri, Perry, Marc D., Rosenberg, Mara, Saksena, Gordon, Trotta, Jean-Rémi, Eils, Roland, Gerhard, Daniela S., Campbell, Peter J., Schlesner, Matthias, and Gut, Ivo G.

Published
2020
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11. Time-series sewage metagenomics distinguishes seasonal, human-derived and environmental microbial communities potentially allowing source-attributed surveillance

Author

Ágnes Becsei, Alessandro Fuschi, Saria Otani, Ravi Kant, Ilja Weinstein, Patricia Alba, József Stéger, Dávid Visontai, Christian Brinch, Miranda de Graaf, Claudia M. E. Schapendonk, Antonio Battisti, Alessandra De Cesare, Chiara Oliveri, Fulvia Troja, Tarja Sironen, Olli Vapalahti, Frédérique Pasquali, Krisztián Bányai, Magdolna Makó, Péter Pollner, Alessandra Merlotti, Marion Koopmans, Istvan Csabai, Daniel Remondini, Frank M. Aarestrup, and Patrick Munk

Subjects
Science
Abstract

Abstract Sewage metagenomics has risen to prominence in urban population surveillance of pathogens and antimicrobial resistance (AMR). Unknown species with similarity to known genomes cause database bias in reference-based metagenomics. To improve surveillance, we seek to recover sewage genomes and develop a quantification and correlation workflow for these genomes and AMR over time. We use longitudinal sewage sampling in seven treatment plants from five major European cities to explore the utility of catch-all sequencing of these population-level samples. Using metagenomic assembly methods, we recover 2332 metagenome-assembled genomes (MAGs) from prokaryotic species, 1334 of which were previously undescribed. These genomes account for ~69% of sequenced DNA and provide insight into sewage microbial dynamics. Rotterdam (Netherlands) and Copenhagen (Denmark) show strong seasonal microbial community shifts, while Bologna, Rome, (Italy) and Budapest (Hungary) have occasional blooms of Pseudomonas-dominated communities, accounting for up to ~95% of sample DNA. Seasonal shifts and blooms present challenges for effective sewage surveillance. We find that bacteria of known shared origin, like human gut microbiota, form communities, suggesting the potential for source-attributing novel species and their ARGs through network community analysis. This could significantly improve AMR tracking in urban environments.

Published
2024
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12. Framework for quality assessment of whole genome cancer sequences

Author

Miranda D. Stobbe, Justin P. Whalley, Barbara Hutter, Johannes Werner, Dimitri Livitz, Sergi Beltran, Ivo Gut, Daniela S. Gerhard, Marta Gut, Matthias Schlesner, Daniel Hübschmann, Kortine Kleinheinz, Ivo Buchhalter, Peter J. Campbell, Keiran Raine, Mara Rosenberg, Gordon Saksena, Roland Eils, Esther Rheinbay, Marc D. Perry, and Jean-Rémi Trotta

Subjects
0301 basic medicine, Male, Quality Control, Computer science, Science, media_common.quotation_subject, DNA Mutational Analysis, General Physics and Astronomy, Computational biology, Genome, General Biochemistry, Genetics and Molecular Biology, Poor quality, Article, 03 medical and health sciences, 0302 clinical medicine, Neoplasms, Cancer genomics, Chromosomes, Human, Humans, Quality (business), Rating system, DNA sequencing, ddc:610, lcsh:Science, media_common, Protocol (science), Multidisciplinary, Whole Genome Sequencing, Quality assessment, Genome, Human, fungi, Chromosome Mapping, High-Throughput Nucleotide Sequencing, food and beverages, General Chemistry, Genomics, 3. Good health, Research data, 030104 developmental biology, Mutation, Female, lcsh:Q, 030217 neurology & neurosurgery, Software
Abstract

Bringing together cancer genomes from different projects increases power and allows the investigation of pan-cancer, molecular mechanisms. However, working with whole genomes sequenced over several years in different sequencing centres requires a framework to compare the quality of these sequences. We used the Pan-Cancer Analysis of Whole Genomes cohort as a test case to construct such a framework. This cohort contains whole cancer genomes of 2832 donors from 18 sequencing centres. We developed a non-redundant set of five quality control (QC) measurements to establish a star rating system. These QC measures reflect known differences in sequencing protocol and provide a guide to downstream analyses and allow for exclusion of samples of poor quality. We have found that this is an effective framework of quality measures. The implementation of the framework is available at: https://dockstore.org/containers/quay.io/jwerner_dkfz/pancanqc:1.2.2., Working with cancer genomes from multiple projects can increase investigative power, but quality of sequences can vary. Here, the authors present a framework for comparing whole genome sequencing quality to help researchers guide downstream analyses and exclude poor quality samples.

Published
2020
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13. Author Correction: Time-series sewage metagenomics distinguishes seasonal, human-derived and environmental microbial communities potentially allowing source-attributed surveillance

Author

Ágnes Becsei, Alessandro Fuschi, Saria Otani, Ravi Kant, Ilja Weinstein, Patricia Alba, József Stéger, Dávid Visontai, Christian Brinch, Miranda de Graaf, Claudia M. E. Schapendonk, Antonio Battisti, Alessandra De Cesare, Chiara Oliveri, Fulvia Troja, Tarja Sironen, Olli Vapalahti, Frédérique Pasquali, Krisztián Bányai, Magdolna Makó, Péter Pollner, Alessandra Merlotti, Marion Koopmans, Istvan Csabai, Daniel Remondini, Frank M. Aarestrup, and Patrick Munk

Subjects
Science
Published
2024
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14. Author Correction: Continent-wide tree fecundity driven by indirect climate effects

Author

Don C. Bragg, Adrian J. Das, Christopher M. Moore, Thomas T. Veblen, Robert Daley, Erin Shanahan, Eliot J. B. McIntire, Cathryn H. Greenberg, Margaret Swift, C. D. Reid, Kristin Legg, Amanda M. Schwantes, Samantha Sutton, Inés Ibáñez, Dale G. Brockway, Michael A. Steele, Diana Macias, Orrin Myers, Natalie L. Cleavitt, Jordan Luongo, Shubhi Sharma, Michał Bogdziewicz, James A. Lutz, Georges Kunstler, Kyle C. Rodman, Qinfeng Guo, Jennifer J. Swenson, Jerry F. Franklin, Emily V. Moran, Yassine Messaoud, Renata Poulton-Kamakura, William H. Schlesinger, Johannes M. H. Knops, Christopher L. Kilner, Andreas P. Wion, Gregory S. Gilbert, Kai Zhu, Jonathan Myers, Susan L. Cohen, Istem Fer, Amy V. Whipple, Walter D. Koenig, Jalene M. LaMontagne, Benoît Courbaud, Sam Pearse, Catherine A. Gehring, C. Lane Scher, Yves Bergeron, Robert A. Andrus, Miranda D. Redmond, Jill F. Johnstone, James S. Clark, Ethan Ready, Mélaine Aubry-Kientz, Janneke HilleRisLambers, Chase L. Nuñez, Roman Zlotin, Thomas G. Whitham, Timothy J. Fahey, Michael Dietze, Scott M. Pearson, Robert R. Parmenter, and Nathan L. Stephenson

Subjects
Tree (data structure), Multidisciplinary, Geography, Ecology, Science, General Physics and Astronomy, General Chemistry, Fecundity, General Biochemistry, Genetics and Molecular Biology, Climate effects
Abstract

A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-22025-2

Published
2021

15. A patient-based iPSC-derived hepatocyte model of alcohol-associated cirrhosis reveals bioenergetic insights into disease pathogenesis.

Author

Mukhopadhyay B, Marietta C, Shen PH, Oiseni A, Mirshahi F, Mazzu M, Hodgkinson C, Winkler E, Yuan Q, Miranda D, Kunos G, Sanyal AJ, and Goldman D

Subjects
Humans, Male, Membrane Proteins metabolism, Membrane Proteins genetics, Female, Middle Aged, Adult, Oxidative Stress, Hepatocytes metabolism, Hepatocytes pathology, Induced Pluripotent Stem Cells metabolism, Energy Metabolism, Lipid Droplets metabolism, Liver Cirrhosis, Alcoholic metabolism, Liver Cirrhosis, Alcoholic pathology, Liver Cirrhosis, Alcoholic genetics, Lipase metabolism, Lipase genetics, Mitochondria metabolism, Acyltransferases, Phospholipases A2, Calcium-Independent
Abstract

Only ~20% of heavy drinkers develop alcohol cirrhosis (AC). While differences in metabolism, inflammation, signaling, microbiome signatures and genetic variations have been tied to the pathogenesis of AC, the key underlying mechanisms for this interindividual variability, remain to be fully elucidated. Induced pluripotent stem cell-derived hepatocytes (iHLCs) from patients with AC and healthy controls differ transcriptomically, bioenergetically and histologically. They include a greater number of lipid droplets (LDs) and LD-associated mitochondria compared to control cells. These pre-pathologic indicators are effectively reversed by Aramchol, an inhibitor of stearoyl-CoA desaturase. Bioenergetically, AC iHLCs have lower spare capacity, slower ATP production and their mitochondrial fuel flexibility towards fatty acids and glutamate is weakened. MARC1 and PNPLA3, genes implicated by GWAS in alcohol cirrhosis, show to correlate with lipid droplet-associated and mitochondria-mediated oxidative damage in AC iHLCs. Knockdown of PNPLA3 expression exacerbates mitochondrial deficits and leads to lipid droplets alterations. These findings suggest that differences in mitochondrial bioenergetics and lipid droplet formation are intrinsic to AC hepatocytes and can play a role in its pathogenesis., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Published
2024
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16. Effects of biological sex mismatch on neural progenitor cell transplantation for spinal cord injury in mice.

Author

Pitonak M, Aceves M, Kumar PA, Dampf G, Green P, Tucker A, Dietz V, Miranda D, Letchuman S, Jonika MM, Bautista D, Blackmon H, and Dulin JN

Subjects
Animals, Female, Humans, Male, Mice, Neuroglia, Neurons, Stem Cell Transplantation, Neural Stem Cells transplantation, Spinal Cord Injuries therapy
Abstract

Despite advancement of neural progenitor cell transplantation to spinal cord injury clinical trials, there remains a lack of understanding of how biological sex of transplanted cells influences outcomes after transplantation. To address this, we transplanted GFP-expressing sex-matched, sex-mismatched, or mixed donor cells into sites of spinal cord injury in adult male and female mice. Biological sex of the donor cells does not influence graft neuron density, glial differentiation, formation of the reactive glial cell border, or graft axon outgrowth. However, male grafts in female hosts feature extensive hypervascularization accompanied by increased vascular diameter and perivascular cell density. We show greater T-cell infiltration within male-to-female grafts than other graft types. Together, these findings indicate a biological sex-specific immune response of female mice to male donor cells. Our work suggests that biological sex should be considered in the design of future clinical trials for cell transplantation in human injury., (© 2022. The Author(s).)

Published
2022
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17. The limits of near field immersion microwave microscopy evaluated by imaging bilayer graphene moiré patterns.

Author

Ohlberg DAA, Tami D, Gadelha AC, Neto EGS, Santana FC, Miranda D, Avelino W, Watanabe K, Taniguchi T, Campos LC, Ramirez JC, do Rego CG, Jorio A, and Medeiros-Ribeiro G

Abstract

Near field scanning Microwave Impedance Microscopy can resolve structures as small as 1 nm using radiation with wavelengths of 0.1 m. Combining liquid immersion microscopy concepts with exquisite force control exerted on nanoscale water menisci, concentration of electromagnetic fields in nanometer-size regions was achieved. As a test material we use twisted bilayer graphene, because it provides a sample where the modulation of the moiré superstructure pattern can be systematically tuned from Ångstroms up to tens of nanometers. Here we demonstrate that a probe-to-pattern resolution of 10 8 can be obtained by analyzing and adjusting the tip-sample distance influence on the dynamics of water meniscus formation and stability.

Published
2021
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