bims-nimamd Biomed News
on Neuroimmunity and neuroinflammation in ageing and metabolic disease
Issue of 2024–06–16
fifty-two papers selected by
Fawaz Alzaïd, Sorbonne Université
  1. A diamond layer in Mercury's deep interior.
  2. Unease as US drug agency weighs its use of independent scientists.
  3. Clonal associations between lymphocyte subsets and functional states in rheumatoid arthritis synovium.
  4. Daily briefing: Autism triples risk of Parkinson's-like symptoms.
  5. CRISPR improves a crop that feeds billions.
  6. A family's sacrifice.
  7. Alzheimer's drug with modest benefits wins backing of FDA advisers.
  8. Reactive oxygen species regulation by NCF1 governs ferroptosis susceptibility of Kupffer cells to MASH.
  9. Smooth muscle NF90 deficiency ameliorates diabetic atherosclerotic calcification in male mice via FBXW7-AGER1-AGEs axis.
  10. How personalized cancer vaccines could keep tumours from coming back.
  11. How the 'mind's eye' calls up visual memories from the brain.
  12. Release of CD36-associated cell-free mitochondrial DNA and RNA as a hallmark of space environment response.
  13. Ancient DNA from Maya ruins tells story of ritual human sacrifices.
  14. IL-12 induces a B cell-intrinsic IL-12/IFNγ feed-forward loop promoting extrafollicular B cell responses.
  15. Three-dimensional chromatin reorganization regulates B cell development during ageing.
  16. CAR T cells take to the airways.
  17. CellRank 2: unified fate mapping in multiview single-cell data.
  18. ASS1 metabolically contributes to the nuclear and cytosolic p53-mediated DNA damage response.
  19. MYG1 drives glycolysis and colorectal cancer development through nuclear-mitochondrial collaboration.
  20. Waking the sleeping giant: Single-stranded DNA binds Schlafen 11 to initiate innate immune responses.
  21. Counting the cost of fashion's carbon footprint.
  22. Metabolic inflexibility promotes mitochondrial health during liver regeneration.
  23. Single-cell analysis identifies conserved features of immune dysfunction in simulated microgravity and spaceflight.
  24. Retrotransposons in Werner syndrome-derived macrophages trigger type I interferon-dependent inflammation in an atherosclerosis model.
  25. Sacrificed Maya boys tied to myth of 'Hero Twins'.
  26. Super-resolution imaging of T lymphocyte activation reveals chromatin decondensation and disrupted nuclear envelope.
  27. Hope, despair and CRISPR - the race to save one woman's life.
  28. Securing your science: the researcher's guide to financial management.
  29. Twelve scientist-endorsed tips to get over writer's block.
  30. Ribosomal DNA copy number is associated with body mass in humans and other mammals.
  31. SGLT2 regulates immune-mediated senolysis.
  32. Advanced methods for gene network identification and noise decomposition from single-cell data.
  33. Dynamics of collagen oxidation and cross linking in regenerating and irreversibly infarcted myocardium.
  34. Mapping fibrosis pathways with MRI and genetic association analyses.
  35. DOT: a flexible multi-objective optimization framework for transferring features across single-cell and spatial omics.
  36. The TAS1R2 G-protein-coupled receptor is an ambient glucose sensor in skeletal muscle that regulates NAD homeostasis and mitochondrial capacity.
  37. Gel-assisted mass spectrometry imaging enables sub-micrometer spatial lipidomics.
  38. Germline-like TCR-α chains shared between autoreactive T cells in blood and pancreas.
  39. Characterization of genetic variants of GIPR reveals a contribution of β-arrestin to metabolic phenotypes.
  40. Daily briefing: 'I had no choice but to commit misconduct'.
  41. Elite researchers in China say they had 'no choice' but to commit misconduct.
  42. Obesity induces PD-1 on macrophages to suppress anti-tumour immunity.
  43. Proximal termination generates a transcriptional state that determines the rate of establishment of Polycomb silencing.
  44. LDL receptor in alphavirus entry: structural analysis and implications for antiviral therapy.
  45. Heart failure affects innate immune memory.
  46. Metagenomics of the human gut mycobiome.
  47. Charting spatially resolved cell states with CytoSPACE.
  48. Secretome profiling reveals acute changes in oxidative stress, brain homeostasis, and coagulation following short-duration spaceflight.
  49. Do elephants have names for each other?
  50. Far-right gains in European elections: what they mean for climate goals.
  51. Library size normalization affects spatial domain identification.
  52. Mycobacterial D-serine impairs TB control.
  1. Nat Commun. 2024 Jun 14. 15(1): 5062
    A diamond layer in Mercury's deep interior.
    Megan D Mouser.
      
    DOI:  https://doi.org/10.1038/s41467-024-49497-2
  2. Nature. 2024 Jun 14.
    Unease as US drug agency weighs its use of independent scientists.
    Max Kozlov.
      
    Keywords:  Drug discovery; Government; Policy; Scientific community
    DOI:  https://doi.org/10.1038/d41586-024-02020-5
  3. Nat Commun. 2024 Jun 11. 15(1): 4991
    Clonal associations between lymphocyte subsets and functional states in rheumatoid arthritis synovium.
    Accelerating Medicines Partnership Program: Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP RA/SLE) Network
      Rheumatoid arthritis (RA) is an autoimmune disease involving antigen-specific T and B cells. Here, we perform single-cell RNA and repertoire sequencing on paired synovial tissue and blood samples from 12 seropositive RA patients. We identify clonally expanded CD4 + T cells, including CCL5+ cells and T peripheral helper (Tph) cells, which show a prominent transcriptomic signature of recent activation and effector function. CD8 + T cells show higher oligoclonality than CD4 + T cells, with the largest synovial clones enriched in GZMK+ cells. CD8 + T cells with possibly virus-reactive TCRs are distributed across transcriptomic clusters. In the B cell compartment, NR4A1+ activated B cells, and plasma cells are enriched in the synovium and demonstrate substantial clonal expansion. We identify synovial plasma cells that share BCRs with synovial ABC, memory, and activated B cells. Receptor-ligand analysis predicted IFNG and TNFRSF members as mediators of synovial Tph-B cell interactions. Together, these results reveal clonal relationships between functionally distinct lymphocyte populations that infiltrate the synovium of patients with RA.
    DOI:  https://doi.org/10.1038/s41467-024-49186-0
  4. Nature. 2024 May 29.
    Daily briefing: Autism triples risk of Parkinson's-like symptoms.
    Katrina Krämer.
      
    DOI:  https://doi.org/10.1038/d41586-024-01615-2
  5. Nature. 2024 Jun 11.
    CRISPR improves a crop that feeds billions.
      
    Keywords:  CRISPR-Cas9 genome editing
    DOI:  https://doi.org/10.1038/d41586-024-01701-5
  6. Science. 2024 Jun 14. 384(6701): 1270
    A family's sacrifice.
    Abdullah M Abudayyeh.
      
    DOI:  https://doi.org/10.1126/science.adq9622
  7. Nature. 2024 Jun 10.
    Alzheimer's drug with modest benefits wins backing of FDA advisers.
    Sara Reardon.
      
    Keywords:  Alzheimer's disease; Brain; Medical research; Neurodegeneration
    DOI:  https://doi.org/10.1038/d41586-024-01726-w
  8. Cell Metab. 2024 Jun 04. pii: S1550-4131(24)00184-0. [Epub ahead of print]
    Reactive oxygen species regulation by NCF1 governs ferroptosis susceptibility of Kupffer cells to MASH.
    Jing Zhang, Yu Wang, Meiyang Fan, Yanglong Guan, Wentao Zhang, Fumeng Huang, Zhengqiang Zhang, Xiaomeng Li, Bingyu Yuan, Wenbin Liu, Manman Geng, Xiaowei Li, Jing Xu, Congshan Jiang, Wenjuan Zhao, Feng Ye, Wenhua Zhu, Liesu Meng, Shemin Lu, Rikard Holmdahl.
      Impaired self-renewal of Kupffer cells (KCs) leads to inflammation in metabolic dysfunction-associated steatohepatitis (MASH). Here, we identify neutrophil cytosolic factor 1 (NCF1) as a critical regulator of iron homeostasis in KCs. NCF1 is upregulated in liver macrophages and dendritic cells in humans with metabolic dysfunction-associated steatotic liver disease and in MASH mice. Macrophage NCF1, but not dendritic cell NCF1, triggers KC iron overload, ferroptosis, and monocyte-derived macrophage infiltration, thus aggravating MASH progression. Mechanistically, elevated oxidized phospholipids induced by macrophage NCF1 promote Toll-like receptor (TLR4)-dependent hepatocyte hepcidin production, leading to increased KC iron deposition and subsequent KC ferroptosis. Importantly, the human low-functional polymorphic variant NCF190H alleviates KC ferroptosis and MASH in mice. In conclusion, macrophage NCF1 impairs iron homeostasis in KCs by oxidizing phospholipids, triggering hepatocyte hepcidin release and KC ferroptosis in MASH, highlighting NCF1 as a therapeutic target for improving KC fate and limiting MASH progression.
    Keywords:  Kupffer cells; NCF1; ferroptosis; hepatocytes; iron deposition; lipid peroxidation; macrophages; metabolic dysfunction-associated steatohepatitis; oxidized phospholipids; reactive oxygen species
    DOI:  https://doi.org/10.1016/j.cmet.2024.05.008
  9. Nat Commun. 2024 Jun 11. 15(1): 4985
    Smooth muscle NF90 deficiency ameliorates diabetic atherosclerotic calcification in male mice via FBXW7-AGER1-AGEs axis.
    Fei Xie, Bin Liu, Wen Qiao, Jing-Zhen He, Jie Cheng, Zhao-Yang Wang, Ya-Min Hou, Xu Zhang, Bo-Han Xu, Yun Zhang, Yu-Guo Chen, Ming-Xiang Zhang.
      Hyperglycemia accelerates calcification of atherosclerotic plaques in diabetic patients, and the accumulation of advanced glycation end products (AGEs) is closely related to the atherosclerotic calcification. Here, we show that hyperglycemia-mediated AGEs markedly increase vascular smooth muscle cells (VSMCs) NF90/110 activation in male diabetic patients with atherosclerotic calcified samples. VSMC-specific NF90/110 knockout in male mice decreases obviously AGEs-induced atherosclerotic calcification, along with the inhibitions of VSMC phenotypic changes to osteoblast-like cells, apoptosis, and matrix vesicle release. Mechanistically, AGEs increase the activity of NF90, which then enhances ubiquitination and degradation of AGE receptor 1 (AGER1) by stabilizing the mRNA of E3 ubiquitin ligase FBXW7, thus causing the accumulation of more AGEs and atherosclerotic calcification. Collectively, our study demonstrates the effects of VSMC NF90 in mediating the metabolic imbalance of AGEs to accelerate diabetic atherosclerotic calcification. Therefore, inhibition of VSMC NF90 may be a potential therapeutic target for diabetic atherosclerotic calcification.
    DOI:  https://doi.org/10.1038/s41467-024-49315-9
  10. Nature. 2024 Jun;630(8016): 290-292
    How personalized cancer vaccines could keep tumours from coming back.
    Elie Dolgin.
      
    Keywords:  Cancer; Immunology; Medical research
    DOI:  https://doi.org/10.1038/d41586-024-01717-x
  11. Nature. 2024 Jun 14.
    How the 'mind's eye' calls up visual memories from the brain.
    Julian Nowogrodzki.
      
    Keywords:  Brain; Neuroscience
    DOI:  https://doi.org/10.1038/d41586-024-01757-3
  12. Nat Commun. 2024 Jun 11. 15(1): 4814
    Release of CD36-associated cell-free mitochondrial DNA and RNA as a hallmark of space environment response.
    Nailil Husna, Tatsuya Aiba, Shin-Ichiro Fujita, Yoshika Saito, Dai Shiba, Takashi Kudo, Satoru Takahashi, Satoshi Furukawa, Masafumi Muratani.
      A detailed understanding of how spaceflight affects human health is essential for long-term space exploration. Liquid biopsies allow for minimally-invasive multi-omics assessments that can resolve the molecular heterogeneity of internal tissues. Here, we report initial results from the JAXA Cell-Free Epigenome Study, a liquid biopsy study with six astronauts who resided on the International Space Station (ISS) for more than 120 days. Analysis of plasma cell-free RNA (cfRNA) collected before, during, and after spaceflight confirms previously reported mitochondrial dysregulation in space. Screening with 361 cell surface marker antibodies identifies a mitochondrial DNA-enriched fraction associated with the scavenger receptor CD36. RNA-sequencing of the CD36 fraction reveals tissue-enriched RNA species, suggesting the plasma mitochondrial components originated from various tissues. We compare our plasma cfRNA data to mouse plasma cfRNA data from a previous JAXA mission, which had used on-board artificial gravity, and discover a link between microgravity and the observed mitochondrial responses.
    DOI:  https://doi.org/10.1038/s41467-023-41995-z
  13. Nature. 2024 Jun 12.
    Ancient DNA from Maya ruins tells story of ritual human sacrifices.
    Ewen Callaway.
      
    Keywords:  Genomics; History
    DOI:  https://doi.org/10.1038/d41586-024-01759-1
  14. Nat Immunol. 2024 Jun 11.
    IL-12 induces a B cell-intrinsic IL-12/IFNγ feed-forward loop promoting extrafollicular B cell responses.
    Rebecca A Elsner, Shuchi Smita, Mark J Shlomchik.
      While some infections elicit germinal centers, others produce only extrafollicular responses. The mechanisms controlling these dichotomous fates are poorly understood. We identify IL-12 as a cytokine switch, acting directly on B cells to promote extrafollicular and suppress germinal center responses. IL-12 initiates a B cell-intrinsic feed-forward loop between IL-12 and IFNγ, amplifying IFNγ production, which promotes proliferation and plasmablast differentiation from mouse and human B cells, in synergy with IL-12. IL-12 sustains the expression of a portion of IFNγ-inducible genes. Together, they also induce unique gene changes, reflecting both IFNγ amplification and cooperative effects between both cytokines. In vivo, cells lacking both IL-12 and IFNγ receptors are more impaired in plasmablast production than those lacking either receptor alone. Further, B cell-derived IL-12 enhances both plasmablast responses and T helper 1 cell commitment. Thus, B cell-derived IL-12, acting on T and B cells, determines the immune response mode, with implications for vaccines, pathogen protection and autoimmunity.
    DOI:  https://doi.org/10.1038/s41590-024-01858-1
  15. Nat Cell Biol. 2024 Jun;26(6): 991-1002
    Three-dimensional chromatin reorganization regulates B cell development during ageing.
    Fei Ma, Yaqiang Cao, Hansen Du, Fatima Zohra Braikia, Le Zong, Noah Ollikainen, Marc Bayer, Xiang Qiu, Bongsoo Park, Roshni Roy, Satabdi Nandi, Dimitra Sarantopoulou, Andrew Ziman, Aisha Haley Bianchi, Isabel Beerman, Keji Zhao, Rudolf Grosschedl, Ranjan Sen.
      The contribution of three-dimensional genome organization to physiological ageing is not well known. Here we show that large-scale chromatin reorganization distinguishes young and old bone marrow progenitor (pro-) B cells. These changes result in increased interactions at the compartment level and reduced interactions within topologically associated domains (TADs). The gene encoding Ebf1, a key B cell regulator, switches from compartment A to B with age. Genetically reducing Ebf1 recapitulates some features of old pro-B cells. TADs that are most reduced with age contain genes important for B cell development, including the immunoglobulin heavy chain (Igh) locus. Weaker intra-TAD interactions at Igh correlate with altered variable (V), diversity (D) and joining (J) gene recombination. Our observations implicate three-dimensional chromatin reorganization as a major driver of pro-B cell phenotypes that impair B lymphopoiesis with age.
    DOI:  https://doi.org/10.1038/s41556-024-01424-9
  16. Nat Rev Immunol. 2024 Jun 10.
    CAR T cells take to the airways.
    Yvonne Bordon.
      
    DOI:  https://doi.org/10.1038/s41577-024-01055-z
  17. Nat Methods. 2024 Jun 13.
    CellRank 2: unified fate mapping in multiview single-cell data.
    Philipp Weiler, Marius Lange, Michal Klein, Dana Pe'er, Fabian Theis.
      Single-cell RNA sequencing allows us to model cellular state dynamics and fate decisions using expression similarity or RNA velocity to reconstruct state-change trajectories; however, trajectory inference does not incorporate valuable time point information or utilize additional modalities, whereas methods that address these different data views cannot be combined or do not scale. Here we present CellRank 2, a versatile and scalable framework to study cellular fate using multiview single-cell data of up to millions of cells in a unified fashion. CellRank 2 consistently recovers terminal states and fate probabilities across data modalities in human hematopoiesis and endodermal development. Our framework also allows combining transitions within and across experimental time points, a feature we use to recover genes promoting medullary thymic epithelial cell formation during pharyngeal endoderm development. Moreover, we enable estimating cell-specific transcription and degradation rates from metabolic-labeling data, which we apply to an intestinal organoid system to delineate differentiation trajectories and pinpoint regulatory strategies.
    DOI:  https://doi.org/10.1038/s41592-024-02303-9
  18. Nat Metab. 2024 Jun 10.
    ASS1 metabolically contributes to the nuclear and cytosolic p53-mediated DNA damage response.
    Lisha Qiu Jin Lim, Lital Adler, Emma Hajaj, Leandro R Soria, Rotem Ben-Tov Perry, Naama Darzi, Ruchama Brody, Noa Furth, Michal Lichtenstein, Elizabeta Bab-Dinitz, Ziv Porat, Tevie Melman, Alexander Brandis, Yael Aylon, Shifra Ben-Dor, Irit Orr, Amir Pri-Or, Rony Seger, Yoav Shaul, Eytan Ruppin, Moshe Oren, Minervo Perez, Jordan Meier, Nicola Brunetti-Pierri, Efrat Shema, Igor Ulitsky, Ayelet Erez, Sergey Malitsky, Maxim Itkin.
      Downregulation of the urea cycle enzyme argininosuccinate synthase (ASS1) in multiple tumors is associated with a poor prognosis partly because of the metabolic diversion of cytosolic aspartate for pyrimidine synthesis, supporting proliferation and mutagenesis owing to nucleotide imbalance. Here, we find that prolonged loss of ASS1 promotes DNA damage in colon cancer cells and fibroblasts from subjects with citrullinemia type I. Following acute induction of DNA damage with doxorubicin, ASS1 expression is elevated in the cytosol and the nucleus with at least a partial dependency on p53; ASS1 metabolically restrains cell cycle progression in the cytosol by restricting nucleotide synthesis. In the nucleus, ASS1 and ASL generate fumarate for the succination of SMARCC1, destabilizing the chromatin-remodeling complex SMARCC1-SNF5 to decrease gene transcription, specifically in a subset of the p53-regulated cell cycle genes. Thus, following DNA damage, ASS1 is part of the p53 network that pauses cell cycle progression, enabling genome maintenance and survival. Loss of ASS1 contributes to DNA damage and promotes cell cycle progression, likely contributing to cancer mutagenesis and, hence, adaptability potential.
    DOI:  https://doi.org/10.1038/s42255-024-01060-5
  19. Nat Commun. 2024 Jun 11. 15(1): 4969
    MYG1 drives glycolysis and colorectal cancer development through nuclear-mitochondrial collaboration.
    Jianxiong Chen, Shiyu Duan, Yulu Wang, Yuping Ling, Xiaotao Hou, Sijing Zhang, Xunhua Liu, Xiaoli Long, Jiawen Lan, Miao Zhou, Huimeng Xu, Haoxuan Zheng, Jun Zhou.
      Metabolic remodeling is a strategy for tumor survival under stress. However, the molecular mechanisms during the metabolic remodeling of colorectal cancer (CRC) remain unclear. Melanocyte proliferating gene 1 (MYG1) is a 3'-5' RNA exonuclease and plays a key role in mitochondrial functions. Here, we uncover that MYG1 expression is upregulated in CRC progression and highly expressed MYG1 promotes glycolysis and CRC progression independent of its exonuclease activity. Mechanistically, nuclear MYG1 recruits HSP90/GSK3β complex to promote PKM2 phosphorylation, increasing its stability. PKM2 transcriptionally activates MYC and promotes MYC-medicated glycolysis. Conversely, c-Myc also transcriptionally upregulates MYG1, driving the progression of CRC. Meanwhile, mitochondrial MYG1 on the one hand inhibits oxidative phosphorylation (OXPHOS), and on the other hand blocks the release of Cyt c from mitochondria and inhibits cell apoptosis. Clinically, patients with KRAS mutation show high expression of MYG1, indicating a high level of glycolysis and a poor prognosis. Targeting MYG1 may disturb metabolic balance of CRC and serve as a potential target for the diagnosis and treatment of CRC.
    DOI:  https://doi.org/10.1038/s41467-024-49221-0
  20. Sci Immunol. 2024 Jun 14. 9(96): eadp4474
    Waking the sleeping giant: Single-stranded DNA binds Schlafen 11 to initiate innate immune responses.
    Stephanie A Ragland, Jonathan C Kagan.
      Single-stranded DNA containing CGT/A motifs binds to the helicase domain of Schlafen 11 (SLFN11) to initiate cell death and cytokine production via SLFN11 ribonuclease activity (see related Research Article by Zhang et al.).
    DOI:  https://doi.org/10.1126/sciimmunol.adp4474
  21. Nature. 2024 Jun 10.
    Counting the cost of fashion's carbon footprint.
    Dom Byrne.
      
    Keywords:  Careers; Materials science; Policy
    DOI:  https://doi.org/10.1038/d41586-024-01743-9
  22. Science. 2024 Jun 14. 384(6701): eadj4301
    Metabolic inflexibility promotes mitochondrial health during liver regeneration.
    Xun Wang, Cameron J Menezes, Yuemeng Jia, Yi Xiao, Siva Sai Krishna Venigalla, Feng Cai, Meng-Hsiung Hsieh, Wen Gu, Liming Du, Jessica Sudderth, Dohun Kim, Spencer D Shelton, Claire B Llamas, Yu-Hsuan Lin, Min Zhu, Salma Merchant, Divya Bezwada, Sherwin Kelekar, Lauren G Zacharias, Thomas P Mathews, Gerta Hoxhaj, R Max Wynn, Uttam K Tambar, Ralph J DeBerardinis, Hao Zhu, Prashant Mishra.
      Mitochondria are critical for proper organ function and mechanisms to promote mitochondrial health during regeneration would benefit tissue homeostasis. We report that during liver regeneration, proliferation is suppressed in electron transport chain (ETC)-dysfunctional hepatocytes due to an inability to generate acetyl-CoA from peripheral fatty acids through mitochondrial β-oxidation. Alternative modes for acetyl-CoA production from pyruvate or acetate are suppressed in the setting of ETC dysfunction. This metabolic inflexibility forces a dependence on ETC-functional mitochondria and restoring acetyl-CoA production from pyruvate is sufficient to allow ETC-dysfunctional hepatocytes to proliferate. We propose that metabolic inflexibility within hepatocytes can be advantageous by limiting the expansion of ETC-dysfunctional cells.
    DOI:  https://doi.org/10.1126/science.adj4301
  23. Nat Commun. 2024 Jun 11. 15(1): 4795
    Single-cell analysis identifies conserved features of immune dysfunction in simulated microgravity and spaceflight.
    Fei Wu, Huixun Du, Eliah Overbey, JangKeun Kim, Priya Makhijani, Nicolas Martin, Chad A Lerner, Khiem Nguyen, Jordan Baechle, Taylor R Valentino, Matias Fuentealba, Juliet M Bartleson, Heather Halaweh, Shawn Winer, Cem Meydan, Francine Garrett-Bakelman, Nazish Sayed, Simon Melov, Masafumi Muratani, Akos A Gerencser, Herbert G Kasler, Afshin Beheshti, Christopher E Mason, David Furman, Daniel A Winer.
      Microgravity is associated with immunological dysfunction, though the mechanisms are poorly understood. Here, using single-cell analysis of human peripheral blood mononuclear cells (PBMCs) exposed to short term (25 hours) simulated microgravity, we characterize altered genes and pathways at basal and stimulated states with a Toll-like Receptor-7/8 agonist. We validate single-cell analysis by RNA sequencing and super-resolution microscopy, and against data from the Inspiration-4 (I4) mission, JAXA (Cell-Free Epigenome) mission, Twins study, and spleens from mice on the International Space Station. Overall, microgravity alters specific pathways for optimal immunity, including the cytoskeleton, interferon signaling, pyroptosis, temperature-shock, innate inflammation (e.g., Coronavirus pathogenesis pathway and IL-6 signaling), nuclear receptors, and sirtuin signaling. Microgravity directs monocyte inflammatory parameters, and impairs T cell and NK cell functionality. Using machine learning, we identify numerous compounds linking microgravity to immune cell transcription, and demonstrate that the flavonol, quercetin, can reverse most abnormal pathways. These results define immune cell alterations in microgravity, and provide opportunities for countermeasures to maintain normal immunity in space.
    DOI:  https://doi.org/10.1038/s41467-023-42013-y
  24. Nat Commun. 2024 Jun 10. 15(1): 4772
    Retrotransposons in Werner syndrome-derived macrophages trigger type I interferon-dependent inflammation in an atherosclerosis model.
    Sudip Kumar Paul, Motohiko Oshima, Ashwini Patil, Masamitsu Sone, Hisaya Kato, Yoshiro Maezawa, Hiyori Kaneko, Masaki Fukuyo, Bahityar Rahmutulla, Yasuo Ouchi, Kyoko Tsujimura, Mahito Nakanishi, Atsushi Kaneda, Atsushi Iwama, Koutaro Yokote, Koji Eto, Naoya Takayama.
      The underlying mechanisms of atherosclerosis, the second leading cause of death among Werner syndrome (WS) patients, are not fully understood. Here, we establish an in vitro co-culture system using macrophages (iMφs), vascular endothelial cells (iVECs), and vascular smooth muscle cells (iVSMCs) derived from induced pluripotent stem cells. In co-culture, WS-iMφs induces endothelial dysfunction in WS-iVECs and characteristics of the synthetic phenotype in WS-iVSMCs. Transcriptomics and open chromatin analysis reveal accelerated activation of type I interferon signaling and reduced chromatin accessibility of several transcriptional binding sites required for cellular homeostasis in WS-iMφs. Furthermore, the H3K9me3 levels show an inverse correlation with retrotransposable elements, and retrotransposable element-derived double-stranded RNA activates the DExH-box helicase 58 (DHX58)-dependent cytoplasmic RNA sensing pathway in WS-iMφs. Conversely, silencing type I interferon signaling in WS-iMφs rescues cell proliferation and suppresses cellular senescence and inflammation. These findings suggest that Mφ-specific inhibition of type I interferon signaling could be targeted to treat atherosclerosis in WS patients.
    DOI:  https://doi.org/10.1038/s41467-024-48663-w
  25. Science. 2024 Jun 14. 384(6701): 1160-1161
    Sacrificed Maya boys tied to myth of 'Hero Twins'.
    Andrew Curry.
      Ancient DNA shows continuity between living and ancient Maya communities.
    DOI:  https://doi.org/10.1126/science.adr0288
  26. Commun Biol. 2024 Jun 10. 7(1): 717
    Super-resolution imaging of T lymphocyte activation reveals chromatin decondensation and disrupted nuclear envelope.
    Jianquan Xu, Xuejiao Sun, Zhangguo Chen, Hongqiang Ma, Yang Liu.
      T lymphocyte activation plays a pivotal role in adaptive immune response and alters the spatial organization of nuclear architecture that subsequently impacts transcription activities. Here, using stochastic optical reconstruction microscopy (STORM), we observe dramatic de-condensation of chromatin and the disruption of nuclear envelope at a nanoscale resolution upon T lymphocyte activation. Super-resolution imaging reveals that such alterations in nuclear architecture are accompanied by the release of nuclear DNA into the cytoplasm, correlating with the degree of chromatin decompaction within the nucleus. The authors show that under the influence of metabolism, T lymphocyte activation de-condenses chromatin, disrupts the nuclear envelope, and releases DNA into the cytoplasm. Taken together, this result provides a direct, molecular-scale insight into the alteration in nuclear architecture. It suggests the release of nuclear DNA into the cytoplasm as a general consequence of chromatin decompaction after lymphocyte activation.
    DOI:  https://doi.org/10.1038/s42003-024-06393-1
  27. Nature. 2024 Jun;630(8016): 284-288
    Hope, despair and CRISPR - the race to save one woman's life.
    Heidi Ledford.
      
    Keywords:  Biotechnology; CRISPR-Cas9 genome editing; Gene therapy; Medical research
    DOI:  https://doi.org/10.1038/d41586-024-01716-y
  28. Nature. 2024 Jun 14.
    Securing your science: the researcher's guide to financial management.
    Andy Tay.
      
    Keywords:  Careers; Communication; Economics; Education; Funding
    DOI:  https://doi.org/10.1038/d41586-024-02039-8
  29. Nature. 2024 Jun 13.
    Twelve scientist-endorsed tips to get over writer's block.
    Emily Sohn.
      
    Keywords:  Careers; Lab life; Publishing
    DOI:  https://doi.org/10.1038/d41586-024-02013-4
  30. Nat Commun. 2024 Jun 12. 15(1): 5006
    Ribosomal DNA copy number is associated with body mass in humans and other mammals.
    Pui Pik Law, Liudmila A Mikheeva, Francisco Rodriguez-Algarra, Fredrika Asenius, Maria Gregori, Robert A E Seaborne, Selin Yildizoglu, James R C Miller, Hemanth Tummala, Robin Mesnage, Michael N Antoniou, Weilong Li, Qihua Tan, Sara L Hillman, Vardhman K Rakyan, David J Williams, Michelle L Holland.
      Body mass results from a complex interplay between genetics and environment. Previous studies of the genetic contribution to body mass have excluded repetitive regions due to the technical limitations of platforms used for population scale studies. Here we apply genome-wide approaches, identifying an association between adult body mass and the copy number (CN) of 47S-ribosomal DNA (rDNA). rDNA codes for the 18 S, 5.8 S and 28 S ribosomal RNA (rRNA) components of the ribosome. In mammals, there are hundreds of copies of these genes. Inter-individual variation in the rDNA CN has not previously been associated with a mammalian phenotype. Here, we show that rDNA CN variation associates with post-pubertal growth rate in rats and body mass index in adult humans. rDNA CN is not associated with rRNA transcription rates in adult tissues, suggesting the mechanistic link occurs earlier in development. This aligns with the observation that the association emerges by early adulthood.
    DOI:  https://doi.org/10.1038/s41467-024-49397-5
  31. Nat Aging. 2024 Jun 10.
    SGLT2 regulates immune-mediated senolysis.
    Guangran Guo, Corina Amor.
      
    DOI:  https://doi.org/10.1038/s43587-024-00651-x
  32. Nat Commun. 2024 Jun 08. 15(1): 4911
    Advanced methods for gene network identification and noise decomposition from single-cell data.
    Zhou Fang, Ankit Gupta, Sant Kumar, Mustafa Khammash.
      Central to analyzing noisy gene expression systems is solving the Chemical Master Equation (CME), which characterizes the probability evolution of the reacting species' copy numbers. Solving CMEs for high-dimensional systems suffers from the curse of dimensionality. Here, we propose a computational method for improved scalability through a divide-and-conquer strategy that optimally decomposes the whole system into a leader system and several conditionally independent follower subsystems. The CME is solved by combining Monte Carlo estimation for the leader system with stochastic filtering procedures for the follower subsystems. We demonstrate this method with high-dimensional numerical examples and apply it to identify a yeast transcription system at the single-cell resolution, leveraging mRNA time-course experimental data. The identification results enable an accurate examination of the heterogeneity in rate parameters among isogenic cells. To validate this result, we develop a noise decomposition technique exploiting time-course data but requiring no supplementary components, e.g., dual-reporters.
    DOI:  https://doi.org/10.1038/s41467-024-49177-1
  33. Nat Commun. 2024 Jun 10. 15(1): 4648
    Dynamics of collagen oxidation and cross linking in regenerating and irreversibly infarcted myocardium.
    Eman A Akam-Baxter, David Bergemann, Sterling J Ridley, Samantha To, Brittany Andrea, Brianna Moon, Hua Ma, Yirong Zhou, Aaron Aguirre, Peter Caravan, Juan Manuel Gonzalez-Rosa, David E Sosnovik.
      In mammalian hearts myocardial infarction produces a permanent collagen-rich scar. Conversely, in zebrafish a collagen-rich scar forms but is completely resorbed as the myocardium regenerates. The formation of cross-links in collagen hinders its degradation but cross-linking has not been well characterized in zebrafish hearts. Here, a library of fluorescent probes to quantify collagen oxidation, the first step in collagen cross-link (CCL) formation, was developed. Myocardial injury in mice or zebrafish resulted in similar dynamics of collagen oxidation in the myocardium in the first month after injury. However, during this time, mature CCLs such as pyridinoline and deoxypyridinoline developed in the murine infarcts but not in the zebrafish hearts. High levels of newly oxidized collagen were still seen in murine scars with mature CCLs. These data suggest that fibrogenesis remains dynamic, even in mature scars, and that the absence of mature CCLs in zebrafish hearts may facilitate their ability to regenerate.
    DOI:  https://doi.org/10.1038/s41467-024-48604-7
  34. Nat Med. 2024 Jun 10.
    Mapping fibrosis pathways with MRI and genetic association analyses.
      
    DOI:  https://doi.org/10.1038/s41591-024-03059-7
  35. Nat Commun. 2024 Jun 11. 15(1): 4994
    DOT: a flexible multi-objective optimization framework for transferring features across single-cell and spatial omics.
    Arezou Rahimi, Luis A Vale-Silva, Maria Fälth Savitski, Jovan Tanevski, Julio Saez-Rodriguez.
      Single-cell transcriptomics and spatially-resolved imaging/sequencing technologies have revolutionized biomedical research. However, they suffer from lack of spatial information and a trade-off of resolution and gene coverage, respectively. We propose DOT, a multi-objective optimization framework for transferring cellular features across these data modalities, thus integrating their complementary information. DOT uses genes beyond those common to the data modalities, exploits the local spatial context, transfers spatial features beyond cell-type information, and infers absolute/relative abundance of cell populations at tissue locations. Thus, DOT bridges single-cell transcriptomics data with both high- and low-resolution spatially-resolved data. Moreover, DOT combines practical aspects related to cell composition, heterogeneity, technical effects, and integration of prior knowledge. Our fast implementation based on the Frank-Wolfe algorithm achieves state-of-the-art or improved performance in localizing cell features in high- and low-resolution spatial data and estimating the expression of unmeasured genes in low-coverage spatial data.
    DOI:  https://doi.org/10.1038/s41467-024-48868-z
  36. Nat Commun. 2024 Jun 08. 15(1): 4915
    The TAS1R2 G-protein-coupled receptor is an ambient glucose sensor in skeletal muscle that regulates NAD homeostasis and mitochondrial capacity.
    Joan Serrano, Jordan Boyd, Ian S Brown, Carter Mason, Kathleen R Smith, Katalin Karolyi, Santosh K Maurya, Nishita N Meshram, Vanida Serna, Grace M Link, Stephen J Gardell, George A Kyriazis.
      The bioavailability of nicotinamide adenine dinucleotide (NAD) is vital for skeletal muscle health, yet the mechanisms or signals regulating NAD homeostasis remain unclear. Here, we uncover a pathway connecting peripheral glucose sensing to the modulation of muscle NAD through TAS1R2, the sugar-sensing G protein-coupled receptor (GPCR) initially identified in taste perception. Muscle TAS1R2 receptor stimulation by glucose and other agonists induces ERK1/2-dependent phosphorylation and activation of poly(ADP-ribose) polymerase1 (PARP1), a major NAD consumer in skeletal muscle. Consequently, muscle-specific deletion of TAS1R2 (mKO) in male mice suppresses PARP1 activity, elevating NAD levels and enhancing mitochondrial capacity and running endurance. Plasma glucose levels negatively correlate with muscle NAD, and TAS1R2 receptor deficiency enhances NAD responses across the glycemic range, implicating TAS1R2 as a peripheral energy surveyor. These findings underscore the role of GPCR signaling in NAD regulation and propose TAS1R2 as a potential therapeutic target for maintaining muscle health.
    DOI:  https://doi.org/10.1038/s41467-024-49100-8
  37. Nat Commun. 2024 Jun 12. 15(1): 5036
    Gel-assisted mass spectrometry imaging enables sub-micrometer spatial lipidomics.
    Yat Ho Chan, Koralege C Pathmasiri, Dominick Pierre-Jacques, Maddison C Hibbard, Nannan Tao, Joshua L Fischer, Ethan Yang, Stephanie M Cologna, Ruixuan Gao.
      A technique capable of label-free detection, mass spectrometry imaging (MSI) is a powerful tool for spatial investigation of native biomolecules in intact specimens. However, MSI has often been precluded from single-cell applications due to the spatial resolution limit set forth by the physical and instrumental constraints of the method. By taking advantage of the reversible interaction between the analytes and a superabsorbent hydrogel, we have developed a sample preparation and imaging workflow named Gel-Assisted Mass Spectrometry Imaging (GAMSI) to overcome the spatial resolution limits of modern mass spectrometers. With GAMSI, we show that the spatial resolution of MALDI-MSI can be enhanced ~3-6-fold to the sub-micrometer level without changing the existing mass spectrometry hardware or analysis pipeline. This approach will vastly enhance the accessibility of MSI-based spatial analysis at the cellular scale.
    DOI:  https://doi.org/10.1038/s41467-024-49384-w
  38. Nat Commun. 2024 Jun 13. 15(1): 4971
    Germline-like TCR-α chains shared between autoreactive T cells in blood and pancreas.
    Peter S Linsley, Maki Nakayama, Elisa Balmas, Janice Chen, Fariba Barahmand-Pour-Whitman, Shubham Bansal, Ty Bottorff, Elisavet Serti, Cate Speake, Alberto Pugliese, Karen Cerosaletti.
      Human type 1 diabetes (T1D) is caused by autoimmune attack on the insulin-producing pancreatic beta cells by islet antigen-reactive T cells. How human islet antigen-reactive (IAR) CD4+ memory T cells from peripheral blood affect T1D progression in the pancreas is poorly understood. Here, we aim to determine if IAR T cells in blood could be detected in pancreas. We identify paired αβ (TRA/TRB) T cell receptors (TCRs) in IAR T cells from the blood of healthy, at-risk, new-onset, and established T1D donors, and measured sequence overlap with TCRs in pancreata from healthy, at risk and T1D organ donors. We report extensive TRA junction sharing between IAR T cells and pancreas-infiltrating T cells (PIT), with perfect-match or single-mismatch TRA junction amino acid sequences comprising ~29% total unique IAR TRA junctions (942/3,264). PIT-matched TRA junctions were largely public and enriched for TRAV41 usage, showing significant nucleotide sequence convergence, increased use of germline-encoded versus non-templated residues in epitope engagement, and a potential for cross-reactivity. Our findings thus link T cells with distinctive germline-like TRA chains in the peripheral blood with T cells in the pancreas.
    DOI:  https://doi.org/10.1038/s41467-024-48833-w
  39. Nat Metab. 2024 Jun 13.
    Characterization of genetic variants of GIPR reveals a contribution of β-arrestin to metabolic phenotypes.
    Hüsün S Kizilkaya, Kimmie V Sørensen, Jakob S Madsen, Peter Lindquist, Jonathan D Douros, Jette Bork-Jensen, Alessandro Berghella, Peter A Gerlach, Lærke S Gasbjerg, Jacek Mokrosiński, Stephanie A Mowery, Patrick J Knerr, Brian Finan, Jonathan E Campbell, David A D'Alessio, Diego Perez-Tilve, Felix Faas, Signe Mathiasen, Jørgen Rungby, Henrik T Sørensen, Allan Vaag, Jens S Nielsen, Jens-Christian Holm, Jeannet Lauenborg, Peter Damm, Oluf Pedersen, Allan Linneberg, Bolette Hartmann, Jens J Holst, Torben Hansen, Shane C Wright, Volker M Lauschke, Niels Grarup, Alexander S Hauser, Mette M Rosenkilde.
      Incretin-based therapies are highly successful in combatting obesity and type 2 diabetes1. Yet both activation and inhibition of the glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) in combination with glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) activation have resulted in similar clinical outcomes, as demonstrated by the GIPR-GLP-1R co-agonist tirzepatide2 and AMG-133 (ref. 3) combining GIPR antagonism with GLP-1R agonism. This underlines the importance of a better understanding of the GIP system. Here we show the necessity of β-arrestin recruitment for GIPR function, by combining in vitro pharmacological characterization of 47 GIPR variants with burden testing of clinical phenotypes and in vivo studies. Burden testing of variants with distinct ligand-binding capacity, Gs activation (cyclic adenosine monophosphate production) and β-arrestin 2 recruitment and internalization shows that unlike variants solely impaired in Gs signalling, variants impaired in both Gs and β-arrestin 2 recruitment contribute to lower adiposity-related traits. Endosomal Gs-mediated signalling of the variants shows a β-arrestin dependency and genetic ablation of β-arrestin 2 impairs cyclic adenosine monophosphate production and decreases GIP efficacy on glucose control in male mice. This study highlights a crucial impact of β-arrestins in regulating GIPR signalling and overall preservation of biological activity that may facilitate new developments in therapeutic targeting of the GIPR system.
    DOI:  https://doi.org/10.1038/s42255-024-01061-4
  40. Nature. 2024 Jun 11.
    Daily briefing: 'I had no choice but to commit misconduct'.
    Flora Graham.
      
    DOI:  https://doi.org/10.1038/d41586-024-01755-5
  41. Nature. 2024 Jun 11.
    Elite researchers in China say they had 'no choice' but to commit misconduct.
    Smriti Mallapaty.
      
    Keywords:  Authorship; Ethics; Publishing
    DOI:  https://doi.org/10.1038/d41586-024-01697-y
  42. Nature. 2024 Jun 12.
    Obesity induces PD-1 on macrophages to suppress anti-tumour immunity.
    Jackie E Bader, Melissa M Wolf, Gian Luca Lupica-Tondo, Matthew Z Madden, Bradley I Reinfeld, Emily N Arner, Emma S Hathaway, KayLee K Steiner, Gabriel A Needle, Zaid Hatem, Madelyn D Landis, Eden E Faneuff, Amondrea Blackman, Elysa M Wolf, Matthew A Cottam, Xiang Ye, Madison E Bates, Kyra Smart, Wenjun Wang, Laura V Pinheiro, Anthos Christofides, DuPreez Smith, Vassiliki A Boussiotis, Scott M Haake, Kathryn E Beckermann, Kathryn E Wellen, Cynthia A Reinhart-King, C Henrique Serezani, Cheng-Han Lee, Christa Aubrey, Heidi Chen, W Kimryn Rathmell, Alyssa H Hasty, Jeffrey C Rathmell.
      Obesity is a leading risk factor for progression and metastasis of many cancers1,2, yet can in some cases enhance survival3-5 and responses to immune checkpoint blockade therapies, including anti-PD-1, which targets PD-1 (encoded by PDCD1), an inhibitory receptor expressed on immune cells6-8. Although obesity promotes chronic inflammation, the role of the immune system in the obesity-cancer connection and immunotherapy remains unclear. It has been shown that in addition to T cells, macrophages can express PD-19-12. Here we found that obesity selectively induced PD-1 expression on tumour-associated macrophages (TAMs). Type I inflammatory cytokines and molecules linked to obesity, including interferon-γ, tumour necrosis factor, leptin, insulin and palmitate, induced macrophage PD-1 expression in an mTORC1- and glycolysis-dependent manner. PD-1 then provided negative feedback to TAMs that suppressed glycolysis, phagocytosis and T cell stimulatory potential. Conversely, PD-1 blockade increased the level of macrophage glycolysis, which was essential for PD-1 inhibition to augment TAM expression of CD86 and major histocompatibility complex I and II molecules and ability to activate T cells. Myeloid-specific PD-1 deficiency slowed tumour growth, enhanced TAM glycolysis and antigen-presentation capability, and led to increased CD8+ T cell activity with a reduced level of markers of exhaustion. These findings show that obesity-associated metabolic signalling and inflammatory cues cause TAMs to induce PD-1 expression, which then drives a TAM-specific feedback mechanism that impairs tumour immune surveillance. This may contribute to increased cancer risk yet improved response to PD-1 immunotherapy in obesity.
    DOI:  https://doi.org/10.1038/s41586-024-07529-3
  43. Mol Cell. 2024 Jun 05. pii: S1097-2765(24)00437-4. [Epub ahead of print]
    Proximal termination generates a transcriptional state that determines the rate of establishment of Polycomb silencing.
    Govind Menon, Eduardo Mateo-Bonmati, Svenja Reeck, Robert Maple, Zhe Wu, Robert Ietswaart, Caroline Dean, Martin Howard.
      The mechanisms and timescales controlling de novo establishment of chromatin-mediated transcriptional silencing by Polycomb repressive complex 2 (PRC2) are unclear. Here, we investigate PRC2 silencing at ArabidopsisFLOWERINGLOCUS C (FLC), known to involve co-transcriptional RNA processing, histone demethylation activity, and PRC2 function, but so far not mechanistically connected. We develop and test a computational model describing proximal polyadenylation/termination mediated by the RNA-binding protein FCA that induces H3K4me1 removal by the histone demethylase FLD. H3K4me1 removal feeds back to reduce RNA polymerase II (RNA Pol II) processivity and thus enhance early termination, thereby repressing productive transcription. The model predicts that this transcription-coupled repression controls the level of transcriptional antagonism to PRC2 action. Thus, the effectiveness of this repression dictates the timescale for establishment of PRC2/H3K27me3 silencing. We experimentally validate these mechanistic model predictions, revealing that co-transcriptional processing sets the level of productive transcription at the locus, which then determines the rate of the ON-to-OFF switch to PRC2 silencing.
    Keywords:  H3K27me3; H3K4me1; Polycomb silencing; alternative polyadenylation; analog and digital gene regulation; co-transcriptional processing; feedback interactions; mechanistic mathematical modeling; proximal termination; transcriptional antagonism
    DOI:  https://doi.org/10.1016/j.molcel.2024.05.014
  44. Nat Commun. 2024 Jun 08. 15(1): 4906
    LDL receptor in alphavirus entry: structural analysis and implications for antiviral therapy.
    Ningning Wang, Andres Merits, Michael Veit, Laura Sandra Lello, Shuhan Kong, Houqi Jiao, Jie Chen, Yu Wang, Georgi Dobrikov, Félix A Rey, Shuo Su.
      Various low-density lipoprotein receptors (LPRs) have been identified as entry factors for alphaviruses, and structures of the corresponding virion-receptor complexes have been determined. Here, we analyze the similarities and differences in the receptor binding modes of multiple alphaviruses to understand their ability to infect a wide range of hosts. We further discuss the challenges associated with the development of broad-spectrum treatment strategies against a diverse range of alphaviruses.
    DOI:  https://doi.org/10.1038/s41467-024-49301-1
  45. Nat Rev Immunol. 2024 Jun 11.
    Heart failure affects innate immune memory.
    Alexandra Flemming.
      
    DOI:  https://doi.org/10.1038/s41577-024-01054-0
  46. Nat Genet. 2024 Jun;56(6): 1038
    Metagenomics of the human gut mycobiome.
    Tiago Faial.
      
    DOI:  https://doi.org/10.1038/s41588-024-01817-4
  47. Nat Rev Cancer. 2024 Jun 10.
    Charting spatially resolved cell states with CytoSPACE.
    Erin L Brown.
      
    DOI:  https://doi.org/10.1038/s41568-024-00713-7
  48. Nat Commun. 2024 Jun 11. 15(1): 4862
    Secretome profiling reveals acute changes in oxidative stress, brain homeostasis, and coagulation following short-duration spaceflight.
    Nadia Houerbi, JangKeun Kim, Eliah G Overbey, Richa Batra, Annalise Schweickart, Laura Patras, Serena Lucotti, Krista A Ryon, Deena Najjar, Cem Meydan, Namita Damle, Christopher Chin, S Anand Narayanan, Joseph W Guarnieri, Gabrielle Widjaja, Afshin Beheshti, Gabriel Tobias, Fanny Vatter, Jeremy Wain Hirschberg, Ashley Kleinman, Evan E Afshin, Matthew MacKay, Qiuying Chen, Dawson Miller, Aaron S Gajadhar, Lucy Williamson, Purvi Tandel, Qiu Yang, Jessica Chu, Ryan Benz, Asim Siddiqui, Daniel Hornburg, Steven Gross, Bader Shirah, Jan Krumsiek, Jaime Mateus, Xiao Mao, Irina Matei, Christopher E Mason.
      As spaceflight becomes more common with commercial crews, blood-based measures of crew health can guide both astronaut biomedicine and countermeasures. By profiling plasma proteins, metabolites, and extracellular vesicles/particles (EVPs) from the SpaceX Inspiration4 crew, we generated "spaceflight secretome profiles," which showed significant differences in coagulation, oxidative stress, and brain-enriched proteins. While >93% of differentially abundant proteins (DAPs) in vesicles and metabolites recovered within six months, the majority (73%) of plasma DAPs were still perturbed post-flight. Moreover, these proteomic alterations correlated better with peripheral blood mononuclear cells than whole blood, suggesting that immune cells contribute more DAPs than erythrocytes. Finally, to discern possible mechanisms leading to brain-enriched protein detection and blood-brain barrier (BBB) disruption, we examined protein changes in dissected brains of spaceflight mice, which showed increases in PECAM-1, a marker of BBB integrity. These data highlight how even short-duration spaceflight can disrupt human and murine physiology and identify spaceflight biomarkers that can guide countermeasure development.
    DOI:  https://doi.org/10.1038/s41467-024-48841-w
  49. Nature. 2024 Jun 10.
    Do elephants have names for each other?
    Gemma Conroy.
      
    Keywords:  Animal behaviour; Language; Zoology
    DOI:  https://doi.org/10.1038/d41586-024-00797-z
  50. Nature. 2024 Jun 10.
    Far-right gains in European elections: what they mean for climate goals.
    Carissa Wong.
      
    Keywords:  Policy; Politics
    DOI:  https://doi.org/10.1038/d41586-024-01742-w
  51. Nat Genet. 2024 Jun;56(6): 1038
    Library size normalization affects spatial domain identification.
    Michael Fletcher.
      
    DOI:  https://doi.org/10.1038/s41588-024-01815-6
  52. Nat Immunol. 2024 Jun 13.
    Mycobacterial D-serine impairs TB control.
    Maxime Caouaille, Denis Hudrisier, Olivier Neyrolles.
      
    DOI:  https://doi.org/10.1038/s41590-024-01873-2
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