bims-nimamd Biomed News
on Neuroimmunity and neuroinflammation in ageing and metabolic disease
Issue of 2022–01–09
73 papers selected by
Fawaz Alzaïd, Sorbonne Université
  1. The unique challenges of studying the genetics of diet and nutrition.
  2. GP73 links SARS-CoV-2 infection with dysglycaemia.
  3. A broken immune clock in old macrophages.
  4. Molecular biologists: let's reconnect with nature.
  5. Lesson of regulatory anatomy: Using integrated functional genomics to dissect the X-inactivation center.
  6. Is precision public health the future - or a contradiction?
  7. Using correlates to accelerate vaccinology.
  8. SnapShot: Astrocyte interactions.
  9. The tricky 'hotspot' volcanoes that belie the name.
  10. Mitochondrial dysfunction and Parkinson's disease.
  11. The surprising genes behind a fingerprint's unique swirls.
  12. Viral infection as an NAD+ battlefield.
  13. The pandemic whistleblower.
  14. Afghan scholars find a warm welcome in Rwanda.
  15. Ring in the new.
  16. Localizing spikes.
  17. Glucose starvation induces a switch in the histone acetylome for activation of gluconeogenic and fat metabolism genes.
  18. Ornithine supports C. difficile gut carriage.
  19. Broaden your scientific audience with video animation.
  20. Engaging with the science of fetal origins.
  21. BRAIN 2.0: Transforming neuroscience.
  22. Terra takes the pain out of 'omics' computing in the cloud.
  23. Plant diversity is blowing in the wind.
  24. Author Correction: Comprehensive characterization of 536 patient-derived xenograft models prioritizes candidates for targeted treatment.
  25. Down-syndrome-induced senescence disrupts the nuclear architecture of neural progenitors.
  26. CLUSTER guide RNAs enable precise and efficient RNA editing with endogenous ADAR enzymes in vivo.
  27. Nuclear destruction: A suicide mission by AKIRIN2 brings intact proteasomes into the nucleus.
  28. Richard Lerner (1938-2021).
  29. Publisher Correction: C9orf72 arginine-rich dipeptide repeats inhibit UPF1-mediated RNA decay via translational repression.
  30. David Livingston (1941-2021).
  31. The SUMO protease SENP3 regulates mitochondrial autophagy mediated by Fis1.
  32. Satellites document rapid expansion of cropland.
  33. Does CB-1 in hepatic stellate cells contribute to liver fibrosis?
  34. CAR keys to unlock the intracellular immunopeptidome.
  35. Antibody-mediated broad sarbecovirus neutralization through ACE2 molecular mimicry.
  36. Immunity against Omicron from breakthrough infection could be a matter of timing.
  37. A tumor-specific pro-IL-12 activates preexisting cytotoxic T cells to control established tumors.
  38. Author Correction: Increased burden of ultra-rare structural variants localizing to boundaries of topologically associated domains in schizophrenia.
  39. Structural insights into inhibitor regulation of the DNA repair protein DNA-PKcs.
  40. Decoding gene regulation in the fly brain.
  41. Atrogin-1 inhibits Akt-dependent cardiac hypertrophy in mice via ubiquitin-dependent coactivation of Forkhead proteins.
  42. Karoline Faust.
  43. Conventional type 1 dendritic cells protect against age-related adipose tissue dysfunction and obesity.
  44. Deep distributed computing to reconstruct extremely large lineage trees.
  45. Comprehensive structure and functional adaptations of the yeast nuclear pore complex.
  46. News at a glance.
  47. Spin-orbit-driven ferromagnetism at half moiré filling in magic-angle twisted bilayer graphene.
  48. Genetic variation influencing DNA methylation provides insights into molecular mechanisms regulating genomic function.
  49. Publisher Correction: Neutral bots probe political bias on social media.
  50. A diverse fibroblastic stromal cell landscape in the spleen directs tissue homeostasis and immunity.
  51. Origins of consciousness, and sustainable cities: Books in brief.
  52. Crosstalk between R848 and abortive HIV-1 RNA-induced signaling enhances antiviral immunity.
  53. Close-up with a parasite that can blind.
  54. Single-nucleus sequencing finds no adult hippocampal neurogenesis in humans.
  55. Mirror symmetry validated for proton and its antimatter twin.
  56. Daily briefing: Omicron struggles to infect the lungs.
  57. A new perspective is needed for positive selection of germinal center B cells with higher-affinity B cell receptors.
  58. GAPDH S-nitrosation contributes to age-related sarcopenia through mediating apoptosis.
  59. Loss of Neuropilin2a/b or Sema3fa alters olfactory sensory axon dynamics and protoglomerular targeting.
  60. Pocket delipidation induced by membrane tension or modification leads to a structurally analogous mechanosensitive channel state.
  61. B-cell intrinsic and extrinsic signals that regulate central tolerance of mouse and human B cells.
  62. Elizabeth Holmes verdict: researchers share lessons for science.
  63. Mendelian randomization analyses support causal relationships between blood metabolites and the gut microbiome.
  64. Omicron's feeble attack on the lungs could make it less dangerous.
  65. CAR T cells produced in vivo to treat cardiac injury.
  66. The CD6/ALCAM pathway promotes lupus nephritis via T cell-mediated responses.
  67. Setting boundaries for tissue patterning.
  68. Daily briefing: Chemist Charles Lieber convicted of hiding his ties to China.
  69. FGF1 and insulin control lipolysis by convergent pathways.
  70. Behavioural immune landscapes of inflammation.
  71. Author Correction: Atrx inactivation drives disease-defining phenotypes in glioma cells of origin through global epigenomic remodeling.
  72. A mighty antibody is the bane of multiple coronaviruses.
  73. From the archive.
  1. Nat Med. 2022 Jan 03.
    The unique challenges of studying the genetics of diet and nutrition.
    Jordi Merino, Deirdre K Tobias.
      
    DOI:  https://doi.org/10.1038/s41591-021-01626-w
  2. Nat Metab. 2022 Jan 06.
    GP73 links SARS-CoV-2 infection with dysglycaemia.
    Katie C Coate.
      
    DOI:  https://doi.org/10.1038/s42255-021-00511-7
  3. Nat Rev Immunol. 2022 Jan 04.
    A broken immune clock in old macrophages.
    Yvonne Bordon.
      
    DOI:  https://doi.org/10.1038/s41577-021-00674-0
  4. Nature. 2022 01;601(7891): 9
    Molecular biologists: let's reconnect with nature.
    Edith Heard.
      
    Keywords:  Climate sciences; Molecular biology; Research management
    DOI:  https://doi.org/10.1038/d41586-021-03818-3
  5. Mol Cell. 2022 Jan 06. pii: S1097-2765(21)01071-6. [Epub ahead of print]82(1): 10-12
    Lesson of regulatory anatomy: Using integrated functional genomics to dissect the X-inactivation center.
    Elphège P Nora.
      Gjaltema et al. (2021) perform systematic screens to identify the long-sought cis-regulatory elements of Xist. They discover that distal elements give Xist a boost as cells exit pluripotency, while proximal elements restrict Xist expression to cells with two X chromosomes.
    DOI:  https://doi.org/10.1016/j.molcel.2021.12.009
  6. Nature. 2022 Jan;601(7891): 18-20
    Is precision public health the future - or a contradiction?
    Carrie Arnold.
      
    Keywords:  Health care; Infection; Society
    DOI:  https://doi.org/10.1038/d41586-021-03819-2
  7. Science. 2022 Jan 07. 375(6576): 22-23
    Using correlates to accelerate vaccinology.
    Peter J M Openshaw.
      [Figure: see text].
    DOI:  https://doi.org/10.1126/science.abn0007
  8. Cell. 2022 Jan 06. pii: S0092-8674(21)01112-0. [Epub ahead of print]185(1): 220-220.e1
    SnapShot: Astrocyte interactions.
    Xinzhu Yu, Baljit S Khakh.
      
    DOI:  https://doi.org/10.1016/j.cell.2021.09.029
  9. Nature. 2022 Jan 06.
    The tricky 'hotspot' volcanoes that belie the name.
      
    Keywords:  Volcanology
    DOI:  https://doi.org/10.1038/d41586-022-00002-z
  10. Nat Neurosci. 2022 Jan;25(1): 2
    Mitochondrial dysfunction and Parkinson's disease.
    Rebecca Wright.
      
    DOI:  https://doi.org/10.1038/s41593-021-00989-0
  11. Nature. 2022 Jan 06.
    The surprising genes behind a fingerprint's unique swirls.
      
    Keywords:  Developmental biology
    DOI:  https://doi.org/10.1038/d41586-021-03850-3
  12. Nat Metab. 2022 Jan 03.
    Viral infection as an NAD+ battlefield.
    Charles Brenner.
      
    DOI:  https://doi.org/10.1038/s42255-021-00507-3
  13. Science. 2022 Jan 07. 375(6576): 16-19
    The pandemic whistleblower.
    Jon Cohen.
      [Figure: see text].
    DOI:  https://doi.org/10.1126/science.acz9922
  14. Science. 2022 Jan 07. 375(6576): 13
    Afghan scholars find a warm welcome in Rwanda.
    Richard Stone.
      [Figure: see text].
    DOI:  https://doi.org/10.1126/science.acz9931
  15. Nature. 2022 Jan 05.
    Ring in the new.
    Deborah Walker.
      
    DOI:  https://doi.org/10.1038/d41586-021-03745-3
  16. Nat Neurosci. 2022 Jan;25(1): 2
    Localizing spikes.
    Sachin Ranade.
      
    DOI:  https://doi.org/10.1038/s41593-021-00993-4
  17. Mol Cell. 2022 Jan 06. pii: S1097-2765(21)01077-7. [Epub ahead of print]82(1): 60-74.e5
    Glucose starvation induces a switch in the histone acetylome for activation of gluconeogenic and fat metabolism genes.
    Wen-Chuan Hsieh, Benjamin M Sutter, Holly Ruess, Spencer D Barnes, Venkat S Malladi, Benjamin P Tu.
      Acetyl-CoA is a key intermediate situated at the intersection of many metabolic pathways. The reliance of histone acetylation on acetyl-CoA enables the coordination of gene expression with metabolic state. Abundant acetyl-CoA has been linked to the activation of genes involved in cell growth or tumorigenesis through histone acetylation. However, the role of histone acetylation in transcription under low levels of acetyl-CoA remains poorly understood. Here, we use a yeast starvation model to observe the dramatic alteration in the global occupancy of histone acetylation following carbon starvation; the location of histone acetylation marks shifts from growth-promoting genes to gluconeogenic and fat metabolism genes. This reallocation is mediated by both the histone deacetylase Rpd3p and the acetyltransferase Gcn5p, a component of the SAGA transcriptional coactivator. Our findings reveal an unexpected switch in the specificity of histone acetylation to promote pathways that generate acetyl-CoA for oxidation when acetyl-CoA is limiting.
    Keywords:  Gcn5p; Rpd3p; SAGA; acetyl-CoA; environmental stress response; fat metabolism; gluconeogenesis; glucose starvation; histone acetylation; transcription
    DOI:  https://doi.org/10.1016/j.molcel.2021.12.015
  18. Nat Metab. 2022 Jan 06.
    Ornithine supports C. difficile gut carriage.
    Matthew J Munneke, Eric P Skaar.
      
    DOI:  https://doi.org/10.1038/s42255-021-00510-8
  19. Nature. 2022 Jan 07.
    Broaden your scientific audience with video animation.
    Alvina Lai.
      
    Keywords:  Arts; Careers; Communication; Lab life
    DOI:  https://doi.org/10.1038/d41586-022-00045-2
  20. Nature. 2022 Jan;601(7891): 26
    Engaging with the science of fetal origins.
    Sarah S Richardson.
      
    Keywords:  Genetics; History; Society
    DOI:  https://doi.org/10.1038/d41586-021-03839-y
  21. Cell. 2022 Jan 06. pii: S0092-8674(21)01387-8. [Epub ahead of print]185(1): 4-8
    BRAIN 2.0: Transforming neuroscience.
    John Ngai.
      The NIH BRAIN Initiative is entering a new phase. Three large new projects-a comprehensive human brain cell atlas, a whole mammalian brain microconnectivity map, and tools for precision access to brain cell types-promise to transform neuroscience research and the treatment of human brain disorders.
    DOI:  https://doi.org/10.1016/j.cell.2021.11.037
  22. Nature. 2022 Jan;601(7891): 154-155
    Terra takes the pain out of 'omics' computing in the cloud.
    Jeffrey M Perkel.
      
    Keywords:  Computational biology and bioinformatics; Databases; Genomics; Software
    DOI:  https://doi.org/10.1038/d41586-021-03822-7
  23. Science. 2022 Jan 07. 375(6576): 14
    Plant diversity is blowing in the wind.
    Elizabeth Pennisi.
      [Figure: see text].
    DOI:  https://doi.org/10.1126/science.acz9932
  24. Nat Commun. 2022 Jan 07. 13(1): 294
    Author Correction: Comprehensive characterization of 536 patient-derived xenograft models prioritizes candidates for targeted treatment.
    NCI PDXNet Consortium
      
    DOI:  https://doi.org/10.1038/s41467-021-27678-7
  25. Cell Stem Cell. 2022 Jan 06. pii: S1934-5909(21)00486-0. [Epub ahead of print]29(1): 116-130.e7
    Down-syndrome-induced senescence disrupts the nuclear architecture of neural progenitors.
    Hiruy S Meharena, Asaf Marco, Vishnu Dileep, Elana R Lockshin, Grace Y Akatsu, James Mullahoo, L Ashley Watson, Tak Ko, Lindsey N Guerin, Fatema Abdurrob, Shruthi Rengarajan, Malvina Papanastasiou, Jacob D Jaffe, Li-Huei Tsai.
      Down syndrome (DS) is a genetic disorder driven by the triplication of chromosome 21 (T21) and characterized by a wide range of neurodevelopmental and physical disabilities. Transcriptomic analysis of tissue samples from individuals with DS has revealed that T21 induces a genome-wide transcriptional disruption. However, the consequences of T21 on the nuclear architecture and its interplay with the transcriptome remain unknown. In this study, we find that unlike human induced pluripotent stem cells (iPSCs), iPSC-derived neural progenitor cells (NPCs) exhibit genome-wide "chromosomal introversion," disruption of lamina-associated domains, and global chromatin accessibility changes in response to T21, consistent with the transcriptional and nuclear architecture changes characteristic of senescent cells. Treatment of T21-harboring NPCs with senolytic drugs alleviates the transcriptional, molecular, and cellular dysfunctions associated with DS. Our findings provide a mechanistic link between T21 and global transcriptional disruption and indicate that senescence-associated phenotypes may play a key role in the neurodevelopmental pathogenesis of DS.
    Keywords:  3D-genome; ATAC-seq; Down syndrome; Hi-C; RNA-seq; aneuploidy; epigenome; lamina-associated domains (LADs); senescence; senolytic drugs; transcriptome
    DOI:  https://doi.org/10.1016/j.stem.2021.12.002
  26. Nat Biotechnol. 2022 Jan 03.
    CLUSTER guide RNAs enable precise and efficient RNA editing with endogenous ADAR enzymes in vivo.
    Philipp Reautschnig, Nicolai Wahn, Jacqueline Wettengel, Annika E Schulz, Ngadhnjim Latifi, Paul Vogel, Tae-Won Kang, Laura S Pfeiffer, Christine Zarges, Ulrike Naumann, Lars Zender, Jin Billy Li, Thorsten Stafforst.
      RNA base editing represents a promising alternative to genome editing. Recent approaches harness the endogenous RNA-editing enzyme adenosine deaminase acting on RNA (ADAR) to circumvent problems caused by ectopic expression of engineered editing enzymes, but suffer from sequence restriction, lack of efficiency and bystander editing. Here we present in silico-optimized CLUSTER guide RNAs that bind their target messenger RNAs in a multivalent fashion, achieve editing with high precision and efficiency and enable targeting of sequences that were not accessible using previous gRNA designs. CLUSTER gRNAs can be genetically encoded and delivered using viruses, and are active in a wide range of cell lines. In cell culture, CLUSTER gRNAs achieve on-target editing of endogenous transcripts with yields of up to 45% without bystander editing. In vivo, CLUSTER gRNAs delivered to mouse liver by hydrodynamic tail vein injection edited reporter constructs at rates of up to 10%. The CLUSTER approach opens avenues for drug development in the field of RNA base editing.
    DOI:  https://doi.org/10.1038/s41587-021-01105-0
  27. Mol Cell. 2022 Jan 06. pii: S1097-2765(21)01010-8. [Epub ahead of print]82(1): 13-14
    Nuclear destruction: A suicide mission by AKIRIN2 brings intact proteasomes into the nucleus.
    Xiang Chen, Kylie J Walters.
      de Almeida et al. (2021) developed a temporally controlled CRISPR-Cas9 screen to identify mechanisms controlling MYC levels and discovered that intact proteasomes are imported into the nucleus by AKIRIN2 binding to proteasomes at one end and a nuclear import receptor at the other.
    DOI:  https://doi.org/10.1016/j.molcel.2021.11.020
  28. Science. 2022 Jan 07. 375(6576): 30
    Richard Lerner (1938-2021).
    Peter Schultz.
      [Figure: see text].
    DOI:  https://doi.org/10.1126/science.abn6377
  29. Nat Commun. 2022 Jan 06. 13(1): 279
    Publisher Correction: C9orf72 arginine-rich dipeptide repeats inhibit UPF1-mediated RNA decay via translational repression.
    Yu Sun, Aziz Eshov, Jeffrey Zhou, Atagun U Isiktas, Junjie U Guo.
      
    DOI:  https://doi.org/10.1038/s41467-021-27859-4
  30. Mol Cell. 2022 Jan 06. pii: S1097-2765(21)01075-3. [Epub ahead of print]82(1): 4-7
    David Livingston (1941-2021).
    Sharon B Cantor, William R Sellers, Shailja Pathania, Roger A Greenberg.
      
    DOI:  https://doi.org/10.1016/j.molcel.2021.12.013
  31. EMBO Rep. 2022 Jan 07. e48754
    The SUMO protease SENP3 regulates mitochondrial autophagy mediated by Fis1.
    Emily Waters, Kevin A Wilkinson, Amy L Harding, Ruth E Carmichael, Darren Robinson, Helen E Colley, Chun Guo.
      Mitochondria are unavoidably subject to organellar stress resulting from exposure to a range of reactive molecular species. Consequently, cells operate a poorly understood quality control programme of mitophagy to facilitate elimination of dysfunctional mitochondria. Here, we used a model stressor, deferiprone (DFP), to investigate the molecular basis for stress-induced mitophagy. We show that mitochondrial fission 1 protein (Fis1) is required for DFP-induced mitophagy and that Fis1 is SUMOylated at K149, an amino acid residue critical for Fis1 mitochondrial localization. We find that DFP treatment leads to the stabilization of the SUMO protease SENP3, which is mediated by downregulation of the E3 ubiquitin (Ub) ligase CHIP. SENP3 is responsible for Fis1 deSUMOylation and depletion of SENP3 abolishes DFP-induced mitophagy. Furthermore, preventing Fis1 SUMOylation by conservative K149R mutation enhances Fis1 mitochondrial localization. Critically, expressing a Fis1 K149R mutant restores DFP-induced mitophagy in SENP3-depleted cells. Thus, we propose a model in which SENP3-mediated deSUMOylation facilitates Fis1 mitochondrial localization to underpin stress-induced mitophagy.
    Keywords:  Fis1; SENP3; SUMO; mitophagy; organellar stress
    DOI:  https://doi.org/10.15252/embr.201948754
  32. Science. 2022 Jan 07. 375(6576): 12
    Satellites document rapid expansion of cropland.
    Gabriel Popkin.
      [Figure: see text].
    DOI:  https://doi.org/10.1126/science.acz9930
  33. J Clin Invest. 2022 Jan 04. pii: e155413. [Epub ahead of print]132(1):
    Does CB-1 in hepatic stellate cells contribute to liver fibrosis?
    Sophie Lotersztajn, Ariane Mallat.
      
    Keywords:  Fibrosis; Hepatology
    DOI:  https://doi.org/10.1172/JCI155413
  34. Sci Immunol. 2022 Jan 07. 7(67): eabn9189
    CAR keys to unlock the intracellular immunopeptidome.
    Gabriel K Griffin.
      [Figure: see text].
    DOI:  https://doi.org/10.1126/sciimmunol.abn9189
  35. Science. 2022 Jan 06. eabm8143
    Antibody-mediated broad sarbecovirus neutralization through ACE2 molecular mimicry.
    Young-Jun Park, Anna De Marco, Tyler N Starr, Zhuoming Liu, Dora Pinto, Alexandra C Walls, Fabrizia Zatta, Samantha K Zepeda, John E Bowen, Kaitlin R Sprouse, Anshu Joshi, Martina Giurdanella, Barbara Guarino, Julia Noack, Rana Abdelnabi, Shi-Yan Caroline Foo, Laura E Rosen, Florian A Lempp, Fabio Benigni, Gyorgy Snell, Johan Neyts, Sean P J Whelan, Herbert W Virgin, Jesse D Bloom, Davide Corti, Matteo Samuele Pizzuto, David Veesler.
      [Figure: see text].
    DOI:  https://doi.org/10.1126/science.abm8143
  36. Nature. 2022 Jan 07.
    Immunity against Omicron from breakthrough infection could be a matter of timing.
    Saima May Sidik.
      
    Keywords:  Immunology; SARS-CoV-2; Vaccines; Virology
    DOI:  https://doi.org/10.1038/d41586-022-00004-x
  37. Sci Immunol. 2022 Jan 07. 7(67): eabi6899
    A tumor-specific pro-IL-12 activates preexisting cytotoxic T cells to control established tumors.
    Diyuan Xue, Benjamin Moon, Jing Liao, Jingya Guo, Zhuangzhi Zou, Yanfei Han, Shuaishuai Cao, Yang Wang, Yang-Xin Fu, Hua Peng.
      [Figure: see text].
    DOI:  https://doi.org/10.1126/sciimmunol.abi6899
  38. Nat Commun. 2022 Jan 05. 13(1): 191
    Author Correction: Increased burden of ultra-rare structural variants localizing to boundaries of topologically associated domains in schizophrenia.
    Matthew Halvorsen, Ruth Huh, Nikolay Oskolkov, Jia Wen, Sergiu Netotea, Paola Giusti-Rodriguez, Robert Karlsson, Julien Bryois, Björn Nystedt, Adam Ameur, Anna K Kähler, NaEshia Ancalade, Martilias Farrell, James J Crowley, Yun Li, Patrik K E Magnusson, Ulf Gyllensten, Christina M Hultman, Patrick F Sullivan, Jin P Szatkiewicz.
      
    DOI:  https://doi.org/10.1038/s41467-021-27826-z
  39. Nature. 2022 Jan 05.
    Structural insights into inhibitor regulation of the DNA repair protein DNA-PKcs.
    Shikang Liang, Sherine E Thomas, Amanda K Chaplin, Steven W Hardwick, Dimitri Y Chirgadze, Tom L Blundell.
      The DNA-dependent protein kinase catalytic subunit (DNA-PKcs) has a central role in non-homologous end joining, one of the two main pathways that detect and repair DNA double-strand breaks (DSBs) in humans1,2. DNA-PKcs is of great importance in repairing pathological DSBs, making DNA-PKcs inhibitors attractive therapeutic agents for cancer in combination with DSB-inducing radiotherapy and chemotherapy3. Many of the selective inhibitors of DNA-PKcs that have been developed exhibit potential as treatment for various cancers4. Here we report cryo-electron microscopy (cryo-EM) structures of human DNA-PKcs natively purified from HeLa cell nuclear extracts, in complex with adenosine-5'-(γ-thio)-triphosphate (ATPγS) and four inhibitors (wortmannin, NU7441, AZD7648 and M3814), including drug candidates undergoing clinical trials. The structures reveal molecular details of ATP binding at the active site before catalysis and provide insights into the modes of action and specificities of the competitive inhibitors. Of note, binding of the ligands causes movement of the PIKK regulatory domain (PRD), revealing a connection between the p-loop and PRD conformations. Electrophoretic mobility shift assay and cryo-EM studies on the DNA-dependent protein kinase holoenzyme further show that ligand binding does not have a negative allosteric or inhibitory effect on assembly of the holoenzyme complex and that inhibitors function through direct competition with ATP. Overall, the structures described in this study should greatly assist future efforts in rational drug design targeting DNA-PKcs, demonstrating the potential of cryo-EM in structure-guided drug development for large and challenging targets.
    DOI:  https://doi.org/10.1038/s41586-021-04274-9
  40. Nature. 2022 Jan 05.
    Decoding gene regulation in the fly brain.
    Jasper Janssens, Sara Aibar, Ibrahim Ihsan Taskiran, Joy N Ismail, Alicia Estacio Gomez, Gabriel Aughey, Katina I Spanier, Florian V De Rop, Carmen Bravo González-Blas, Marc Dionne, Krista Grimes, Xiao Jiang Quan, Dafni Papasokrati, Gert Hulselmans, Samira Makhzami, Maxime De Waegeneer, Valerie Christiaens, Tony Southall, Stein Aerts.
      The Drosophila brain is a frequently used model in neuroscience. Single-cell transcriptome analysis1-6, three-dimensional morphological classification7 and electron microscopy mapping of the connectome8,9 have revealed an immense diversity of neuronal and glial cell types that underlie an array of functional and behavioural traits in the fly. The identities of these cell types are controlled by gene regulatory networks (GRNs), involving combinations of transcription factors that bind to genomic enhancers to regulate their target genes. Here, to characterize GRNs at the cell-type level in the fly brain, we profiled the chromatin accessibility of 240,919 single cells spanning 9 developmental timepoints and integrated these data with single-cell transcriptomes. We identify more than 95,000 regulatory regions that are used in different neuronal cell types, of which 70,000 are linked to developmental trajectories involving neurogenesis, reprogramming and maturation. For 40 cell types, uniquely accessible regions were associated with their expressed transcription factors and downstream target genes through a combination of motif discovery, network inference and deep learning, creating enhancer GRNs. The enhancer architectures revealed by DeepFlyBrain lead to a better understanding of neuronal regulatory diversity and can be used to design genetic driver lines for cell types at specific timepoints, facilitating their characterization and manipulation.
    DOI:  https://doi.org/10.1038/s41586-021-04262-z
  41. J Clin Invest. 2022 Jan 04. pii: e157373. [Epub ahead of print]132(1):
    Atrogin-1 inhibits Akt-dependent cardiac hypertrophy in mice via ubiquitin-dependent coactivation of Forkhead proteins.
    Hui-Hua Li, Monte S Willis, Pamela Lockyer, Nathaniel Miller, Holly McDonough, David J Glass, Cam Patterson.
      
    DOI:  https://doi.org/10.1172/JCI157373
  42. Nat Methods. 2022 Jan 03.
    Karoline Faust.
    Vivien Marx.
      
    DOI:  https://doi.org/10.1038/s41592-021-01367-1
  43. Cell Mol Immunol. 2022 Jan 04.
    Conventional type 1 dendritic cells protect against age-related adipose tissue dysfunction and obesity.
    Elena Hernández-García, Francisco J Cueto, Emma C L Cook, Ana Redondo-Urzainqui, Sara Charro-Zanca, Iñaki Robles-Vera, Ruth Conde-Garrosa, Ivana Nikolić, Guadalupe Sabio, David Sancho, Salvador Iborra.
      Conventional dendritic cells (cDCs) scan and integrate environmental cues in almost every tissue, including exogenous metabolic signals. While cDCs are critical in maintaining immune balance, their role in preserving energy homeostasis is unclear. Here, we showed that Batf3-deficient mice lacking conventional type 1 DCs (cDC1s) had increased body weight and adiposity during aging. This led to impaired energy expenditure and glucose tolerance, insulin resistance, dyslipidemia, and liver steatosis. cDC1 deficiency caused adipose tissue inflammation that was preceded by a paucity of NK1.1+ invariant NKT (iNKT) cells. Accordingly, among antigen-presenting cells, cDC1s exhibited notable induction of IFN-γ production by iNKT cells, which plays a metabolically protective role in lean adipose tissue. Flt3L treatment, which expands the dendritic cell (DC) compartment, mitigated diet-induced obesity and hyperlipidemia in a Batf3-dependent manner. This effect was partially mediated by NK1.1+ cells. These results reveal a new critical role for the cDC1-iNKT cell axis in the regulation of adipose tissue homeostasis.
    Keywords:  Dendritic Cells; FLT3L; NKT; Obesity; ageing
    DOI:  https://doi.org/10.1038/s41423-021-00812-7
  44. Nat Biotechnol. 2022 Jan 06.
    Deep distributed computing to reconstruct extremely large lineage trees.
    Naoki Konno, Yusuke Kijima, Keito Watano, Soh Ishiguro, Keiichiro Ono, Mamoru Tanaka, Hideto Mori, Nanami Masuyama, Dexter Pratt, Trey Ideker, Wataru Iwasaki, Nozomu Yachie.
      Phylogeny estimation (the reconstruction of evolutionary trees) has recently been applied to CRISPR-based cell lineage tracing, allowing the developmental history of an individual tissue or organism to be inferred from a large number of mutated sequences in somatic cells. However, current computational methods are not able to construct phylogenetic trees from extremely large numbers of input sequences. Here, we present a deep distributed computing framework to comprehensively trace accurate large lineages (FRACTAL) that substantially enhances the scalability of current lineage estimation software tools. FRACTAL first reconstructs only an upstream lineage of the input sequences and recursively iterates the same produce for its downstream lineages using independent computing nodes. We demonstrate the utility of FRACTAL by reconstructing lineages from >235 million simulated sequences and from >16 million cells from a simulated experiment with a CRISPR system that accumulates mutations during cell proliferation. We also successfully applied FRACTAL to evolutionary tree reconstructions and to an experiment using error-prone PCR (EP-PCR) for large-scale sequence diversification.
    DOI:  https://doi.org/10.1038/s41587-021-01111-2
  45. Cell. 2021 Dec 29. pii: S0092-8674(21)01453-7. [Epub ahead of print]
    Comprehensive structure and functional adaptations of the yeast nuclear pore complex.
    Christopher W Akey, Digvijay Singh, Christna Ouch, Ignacia Echeverria, Ilona Nudelman, Joseph M Varberg, Zulin Yu, Fei Fang, Yi Shi, Junjie Wang, Daniel Salzberg, Kangkang Song, Chen Xu, James C Gumbart, Sergey Suslov, Jay Unruh, Sue L Jaspersen, Brian T Chait, Andrej Sali, Javier Fernandez-Martinez, Steven J Ludtke, Elizabeth Villa, Michael P Rout.
      Nuclear pore complexes (NPCs) mediate the nucleocytoplasmic transport of macromolecules. Here we provide a structure of the isolated yeast NPC in which the inner ring is resolved by cryo-EM at sub-nanometer resolution to show how flexible connectors tie together different structural and functional layers. These connectors may be targets for phosphorylation and regulated disassembly in cells with an open mitosis. Moreover, some nucleoporin pairs and transport factors have similar interaction motifs, which suggests an evolutionary and mechanistic link between assembly and transport. We provide evidence for three major NPC variants that may foreshadow functional specializations at the nuclear periphery. Cryo-electron tomography extended these studies, providing a model of the in situ NPC with a radially expanded inner ring. Our comprehensive model reveals features of the nuclear basket and central transporter, suggests a role for the lumenal Pom152 ring in restricting dilation, and highlights structural plasticity that may be required for transport.
    Keywords:  NPC evolution; Nuclear pore complex; cryo-electron microscopy; cryo-electron tomography; inner ring dilation; nuclear basket; nucleocytoplasmic transport; nucleoporins; structural isoforms
    DOI:  https://doi.org/10.1016/j.cell.2021.12.015
  46. Science. 2022 Jan 07. 375(6576): 6-8
    News at a glance.
      [Figure: see text].
    DOI:  https://doi.org/10.1126/science.acz9927
  47. Science. 2022 Jan 06. eabh2889
    Spin-orbit-driven ferromagnetism at half moiré filling in magic-angle twisted bilayer graphene.
    Jiang-Xiazi Lin, Ya-Hui Zhang, Erin Morissette, Zhi Wang, Song Liu, Daniel Rhodes, K Watanabe, T Taniguchi, James Hone, J I A Li.
      [Figure: see text].
    DOI:  https://doi.org/10.1126/science.abh2889
  48. Nat Genet. 2022 Jan 03.
    Genetic variation influencing DNA methylation provides insights into molecular mechanisms regulating genomic function.
    MuTHER Consortium
      We determined the relationships between DNA sequence variation and DNA methylation using blood samples from 3,799 Europeans and 3,195 South Asians. We identify 11,165,559 SNP-CpG associations (methylation quantitative trait loci (meQTL), P < 10-14), including 467,915 meQTL that operate in trans. The meQTL are enriched for functionally relevant characteristics, including shared chromatin state, High-throuhgput chromosome conformation interaction, and association with gene expression, metabolic variation and clinical traits. We use molecular interaction and colocalization analyses to identify multiple nuclear regulatory pathways linking meQTL loci to phenotypic variation, including UBASH3B (body mass index), NFKBIE (rheumatoid arthritis), MGA (blood pressure) and COMMD7 (white cell counts). For rs6511961 , chromatin immunoprecipitation followed by sequencing (ChIP-seq) validates zinc finger protein (ZNF)333 as the likely trans acting effector protein. Finally, we used interaction analyses to identify population- and lineage-specific meQTL, including rs174548 in FADS1, with the strongest effect in CD8+ T cells, thus linking fatty acid metabolism with immune dysregulation and asthma. Our study advances understanding of the potential pathways linking genetic variation to human phenotype.
    DOI:  https://doi.org/10.1038/s41588-021-00969-x
  49. Nat Commun. 2022 Jan 05. 13(1): 264
    Publisher Correction: Neutral bots probe political bias on social media.
    Wen Chen, Diogo Pacheco, Kai-Cheng Yang, Filippo Menczer.
      
    DOI:  https://doi.org/10.1038/s41467-021-27855-8
  50. Sci Immunol. 2022 Jan 07. 7(67): eabj0641
    A diverse fibroblastic stromal cell landscape in the spleen directs tissue homeostasis and immunity.
    Yannick O Alexandre, Dominik Schienstock, Hyun Jae Lee, Luke C Gandolfo, Cameron G Williams, Sapna Devi, Bhupinder Pal, Joanna R Groom, Wang Cao, Susan N Christo, Claire L Gordon, Graham Starkey, Rohit D'Costa, Laura K Mackay, Ashraful Haque, Burkhard Ludewig, Gabrielle T Belz, Scott N Mueller.
      [Figure: see text].
    DOI:  https://doi.org/10.1126/sciimmunol.abj0641
  51. Nature. 2022 Jan 07.
    Origins of consciousness, and sustainable cities: Books in brief.
    Andrew Robinson.
      
    Keywords:  Arts; Culture
    DOI:  https://doi.org/10.1038/d41586-022-00032-7
  52. J Leukoc Biol. 2022 Jan 04.
    Crosstalk between R848 and abortive HIV-1 RNA-induced signaling enhances antiviral immunity.
    Melissa Stunnenberg, John L van Hamme, Esther M Zijlstra-Willems, Sonja I Gringhuis, Teunis B H Geijtenbeek.
      Pathogens trigger multiple pattern recognition receptors (PRRs) that together dictate innate and adaptive immune responses. Understanding the crosstalk between PRRs is important to enhance vaccine efficacy. Abortive HIV-1 RNA transcripts are produced during acute and chronic HIV-1 infection and are known ligands for different PRRs, leading to antiviral and proinflammatory responses. Here, we have investigated the crosstalk between responses induced by these 58 nucleotide-long HIV-1 RNA transcripts and different TLR ligands. Costimulation of dendritic cells (DCs) with abortive HIV-1 RNA and TLR7/8 agonist R848, but not other TLR agonists, resulted in enhanced antiviral type I IFN responses as well as adaptive immune responses via the induction of DC-mediated T helper 1 (TH 1) responses and IFNγ+ CD8+ T cells. Our data underscore the importance of crosstalk between abortive HIV-1 RNA and R848-induced signaling for the induction of effective antiviral immunity.
    Keywords:  TLR8; adaptive immunity; immunomodulation; innate immunity; pathogen-associated molecular pattern; pattern recognition receptor
    DOI:  https://doi.org/10.1002/JLB.4A0721-365R
  53. Nature. 2022 Jan;601(7891): 158
    Close-up with a parasite that can blind.
    Chris Woolston.
      
    Keywords:  Health care; Infection; Parasitology
    DOI:  https://doi.org/10.1038/d41586-021-03823-6
  54. Nat Neurosci. 2022 Jan;25(1): 2
    Single-nucleus sequencing finds no adult hippocampal neurogenesis in humans.
    Shari Wiseman.
      
    DOI:  https://doi.org/10.1038/s41593-021-00991-6
  55. Nature. 2022 Jan;601(7891): 32-33
    Mirror symmetry validated for proton and its antimatter twin.
    Ralf Lehnert.
      
    Keywords:  Particle physics
    DOI:  https://doi.org/10.1038/d41586-021-03798-4
  56. Nature. 2022 Jan 06.
    Daily briefing: Omicron struggles to infect the lungs.
    Flora Graham.
      
    DOI:  https://doi.org/10.1038/d41586-022-00039-0
  57. Cell Mol Immunol. 2022 Jan 07.
    A new perspective is needed for positive selection of germinal center B cells with higher-affinity B cell receptors.
    Timo Gaber, Frank Buttgereit.
      
    DOI:  https://doi.org/10.1038/s41423-021-00823-4
  58. Nitric Oxide. 2021 Dec 29. pii: S1089-8603(21)00134-8. [Epub ahead of print]120 1-8
    GAPDH S-nitrosation contributes to age-related sarcopenia through mediating apoptosis.
    Ting Xie, Xinhua Qiao, Chuanxin Sun, Boyu Chu, Jiao Meng, Chang Chen.
      The age-related loss of muscle mass and muscle function known as sarcopenia is a major public health problem among older people. Recent research suggests that activation of apoptotic signaling is a critical aspect of the pathogenesis of age-related sarcopenia. However, little information exists in the literature about the apoptotic mechanism of sarcopenia in aging. Herein, we report that elevated glyceraldehyde-3-phosphate dehydrogenase (GAPDH) S-nitrosation and apoptosis occur in sarcopenia during natural aging and that translocation of S-nitrosated GAPDH to the nucleus and S-nitrosated GAPDH-mediated apoptosis contributed to sarcopenia. The levels and sites of GAPDH S-nitrosation in muscle tissues of young, adult and old mice were studied with a quantitative S-nitrosation proteomic analysis approach. GAPDH S-nitrosation increased with aging, and the GAPDH modification sites Cys150, Cys154 and Cys245 were identified. The upregulated S-nitrosation of GAPDH relies on inducible nitric oxide synthase (iNOS) rather than enzymes involved in denitrosylation. Treatment with the iNOS inhibitor 1400W or mutation of GAPDH S-nitrosation sites alleviated apoptosis of C2C12 cells, further demonstrating that GAPDH S-nitrosation in aging contributes to sarcopenia. Taken together, these findings reveal a new cellular mechanism underlying age-related sarcopenia, and the demonstration of muscle loss mediated by iNOS-induced GAPDH S-nitrosation suggests a potential therapeutic strategy for sarcopenia.
    Keywords:  Aging; Apoptosis; GAPDH; S-nitrosation/S-nitrosylation; Sarcopenia; iNOS
    DOI:  https://doi.org/10.1016/j.niox.2021.12.006
  59. Neural Dev. 2022 Jan 03. 17(1): 1
    Loss of Neuropilin2a/b or Sema3fa alters olfactory sensory axon dynamics and protoglomerular targeting.
    Ryan P Cheng, Puneet Dang, Alemji A Taku, Yoon Ji Moon, Vi Pham, Xiaohe Sun, Ethan Zhao, Jonathan A Raper.
       BACKGROUND: Olfactory Sensory Neuron (OSN) axons project from the zebrafish olfactory epithelium to reproducible intermediate target locations in the olfactory bulb called protoglomeruli at early stages in development. Two classes of OSNs expressing either OMP or TRPC2 exclusively target distinct, complementary protoglomeruli. Using RNAseq, we identified axon guidance receptors nrp2a and nrp2b, and their ligand sema3fa, as potential guidance factors that are differentially expressed between these two classes of OSNs.
    METHODS: To investigate their role in OSN axon guidance, we assessed the protoglomerular targeting fidelity of OSNs labeled by OMP:RFP and TRPC2:Venus transgenes in nrp2a, nrp2b, or sema3fa mutants. We used double mutant and genetic interaction experiments to interrogate the relationship between the three genes. We used live time-lapse imaging to compare the dynamic behaviors of OSN growth cones during protoglomerular targeting in heterozygous and mutant larvae.
    RESULTS: The fidelity of protoglomerular targeting of TRPC2-class OSNs is degraded in nrp2a, nrp2b, or sema3fa mutants, as axons misproject into OMP-specific protoglomeruli and other ectopic locations in the bulb. These misprojections are further enhanced in nrp2a;nrp2b double mutants suggesting that nrp2s work at least partially in parallel in the same guidance process. Results from genetic interaction experiments are consistent with sema3fa acting in the same biological pathway as both nrp2a and nrp2b. Live time-lapse imaging was used to examine the dynamic behavior of TRPC2-class growth cones in nrp2a mutants compared to heterozygous siblings. Some TRPC2-class growth cones ectopically enter the dorsal-medial region of the bulb in both groups, but in fully mutant embryos, they are less likely to correct the error through retraction. The same result was observed when TRPC2-class growth cone behavior was compared between sema3fa heterozygous and sema3fa mutant larvae.
    CONCLUSIONS: Our results suggest that nrp2a and nrp2b expressed in TRPC2-class OSNs help prevent their mixing with axon projections in OMP-specific protoglomeruli, and further, that sema3fa helps to exclude TRPC2-class axons by repulsion from the dorsal-medial bulb.
    Keywords:  Axon guidance; Live imaging; OSN targeting; Odorant map; Olfaction; Olfactory; Olfactory bulb; Olfactory sensory neuron; Protoglomerulus; Zebrafish
    DOI:  https://doi.org/10.1186/s13064-021-00157-x
  60. Structure. 2021 Dec 22. pii: S0969-2126(21)00456-1. [Epub ahead of print]
    Pocket delipidation induced by membrane tension or modification leads to a structurally analogous mechanosensitive channel state.
    Bolin Wang, Benjamin J Lane, Charalampos Kapsalis, James R Ault, Frank Sobott, Hassane El Mkami, Antonio N Calabrese, Antreas C Kalli, Christos Pliotas.
      The mechanosensitive ion channel of large conductance MscL gates in response to membrane tension changes. Lipid removal from transmembrane pockets leads to a concerted structural and functional MscL response, but it remains unknown whether there is a correlation between the tension-mediated state and the state derived by pocket delipidation in the absence of tension. Here, we combined pulsed electron paramagnetic resonance spectroscopy and hydrogen-deuterium exchange mass spectrometry, coupled with molecular dynamics simulations under membrane tension, to investigate the structural changes associated with the distinctively derived states. Whether it is tension- or modification-mediated pocket delipidation, we find that MscL samples a similar expanded subconducting state. This is the final step of the delipidation pathway, but only an intermediate stop on the tension-mediated path, with additional tension triggering further channel opening. Our findings hint at synergistic modes of regulation by lipid molecules in membrane tension-activated mechanosensitive channels.
    Keywords:  EPR spectroscopy; ESSEM; HDX; MD; MscL; MscS; force-from-lipid; lipids; mass spectrometry; mechanosensitive channels
    DOI:  https://doi.org/10.1016/j.str.2021.12.004
  61. Immunol Rev. 2022 Jan 08.
    B-cell intrinsic and extrinsic signals that regulate central tolerance of mouse and human B cells.
    Roberta Pelanda, Sarah A Greaves, Thiago Alves da Costa, Lena M Cedrone, Margaret L Campbell, Raul M Torres.
      The random recombination of immunoglobulin V(D)J gene segments produces unique IgM antibodies that serve as the antigen receptor for each developing B cell. Hence, the newly formed B cell repertoire is comprised of a variety of specificities that display a range of reactivity with self-antigens. Newly generated IgM+ immature B cells that are non-autoreactive or that bind self-antigen with low avidity are licensed to leave the bone marrow with their intact antigen receptor and to travel via the blood to the peripheral lymphoid tissue for further selection and maturation. In contrast, clones with medium to high avidity for self-antigen remain within the marrow and undergo central tolerance, a process that revises their antigen receptor or eliminates the autoreactive B cell altogether. Thus, central B cell tolerance is critical for reducing the autoreactive capacity and avidity for self-antigen of our circulating B cell repertoire. Bone marrow cultures and mouse models have been instrumental for understanding the mechanisms that regulate the selection of bone marrow B cells. Here, we review recent studies that have shed new light on the contribution of the ERK, PI3K, and CXCR4 signaling pathways in the selection of mouse and human immature B cells that either bind or do not bind self-antigen.
    Keywords:  B cell tolerance; CXCR4; ERK; FOXO1; PI3K; autoimmunity; receptor editing
    DOI:  https://doi.org/10.1111/imr.13062
  62. Nature. 2022 Jan 04.
    Elizabeth Holmes verdict: researchers share lessons for science.
    Emily Waltz.
      
    Keywords:  Biotechnology; Funding; Law; Scientific community
    DOI:  https://doi.org/10.1038/d41586-022-00006-9
  63. Nat Genet. 2022 Jan 03.
    Mendelian randomization analyses support causal relationships between blood metabolites and the gut microbiome.
    Xiaomin Liu, Xin Tong, Yuanqiang Zou, Xiaoqian Lin, Hui Zhao, Liu Tian, Zhuye Jie, Qi Wang, Zhe Zhang, Haorong Lu, Liang Xiao, Xuemei Qiu, Jin Zi, Rong Wang, Xun Xu, Huanming Yang, Jian Wang, Yang Zong, Weibin Liu, Yong Hou, Shida Zhu, Huijue Jia, Tao Zhang.
      The gut microbiome has been implicated in a variety of physiological states, but controversy over causality remains unresolved. Here, we performed bidirectional Mendelian randomization analyses on 3,432 Chinese individuals with whole-genome, whole-metagenome, anthropometric and blood metabolic trait data. We identified 58 causal relationships between the gut microbiome and blood metabolites, and replicated 43 of them. Increased relative abundances of fecal Oscillibacter and Alistipes were causally linked to decreased triglyceride concentration. Conversely, blood metabolites such as glutamic acid appeared to decrease fecal Oxalobacter, and members of Proteobacteria were influenced by metabolites such as 5-methyltetrahydrofolic acid, alanine, glutamate and selenium. Two-sample Mendelian randomization with data from Biobank Japan partly corroborated results with triglyceride and with uric acid, and also provided causal support for published fecal bacterial markers for cancer and cardiovascular diseases. This study illustrates the value of human genetic information to help prioritize gut microbial features for mechanistic and clinical studies.
    DOI:  https://doi.org/10.1038/s41588-021-00968-y
  64. Nature. 2022 Jan 05.
    Omicron's feeble attack on the lungs could make it less dangerous.
    Max Kozlov.
      
    Keywords:  SARS-CoV-2; Virology
    DOI:  https://doi.org/10.1038/d41586-022-00007-8
  65. Science. 2022 Jan 07. 375(6576): 91-96
    CAR T cells produced in vivo to treat cardiac injury.
    Joel G Rurik, István Tombácz, Amir Yadegari, Pedro O Méndez Fernández, Swapnil V Shewale, Li Li, Toru Kimura, Ousamah Younoss Soliman, Tyler E Papp, Ying K Tam, Barbara L Mui, Steven M Albelda, Ellen Puré, Carl H June, Haig Aghajanian, Drew Weissman, Hamideh Parhiz, Jonathan A Epstein.
      [Figure: see text].
    DOI:  https://doi.org/10.1126/science.abm0594
  66. J Clin Invest. 2022 Jan 04. pii: e147334. [Epub ahead of print]132(1):
    The CD6/ALCAM pathway promotes lupus nephritis via T cell-mediated responses.
    Samantha A Chalmers, Rajalakshmy Ayilam Ramachandran, Sayra J Garcia, Evan Der, Leal Herlitz, Jeanette Ampudia, Dalena Chu, Nicole Jordan, Ting Zhang, Ioannis Parodis, Iva Gunnarsson, Huihua Ding, Nan Shen, Michelle Petri, Chi Chiu Mok, Ramesh Saxena, Krishna R Polu, Stephen Connelly, Cherie T Ng, Chandra Mohan, Chaim Putterman.
      T cells are central to the pathogenesis of lupus nephritis (LN), a common complication of systemic lupus erythematosus (SLE). CD6 and its ligand, activated leukocyte cell adhesion molecule (ALCAM), are involved in T cell activation and trafficking. Previously, we showed that soluble ALCAM is increased in urine (uALCAM) of patients with LN, suggesting that this pathway contributes to disease. To investigate, uALCAM was examined in 1038 patients with SLE and LN from 5 ethnically diverse cohorts; CD6 and ALCAM expression was assessed in LN kidney cells; and disease contribution was tested via antibody blockade of CD6 in murine models of SLE and acute glomerulonephritis. Extended cohort analysis offered resounding validation of uALCAM as a biomarker that distinguishes active renal involvement in SLE, irrespective of ethnicity. ALCAM was expressed by renal structural cells whereas CD6 expression was exclusive to T cells, with elevated numbers of CD6+ and ALCAM+ cells in patients with LN. CD6 blockade in models of spontaneous lupus and immune-complex glomerulonephritis revealed significant decreases in immune cells, inflammatory markers, and disease measures. Our data demonstrate the contribution of the CD6/ALCAM pathway to LN and SLE, supporting its use as a disease biomarker and therapeutic target.
    Keywords:  Autoimmunity; Lupus
    DOI:  https://doi.org/10.1172/JCI147334
  67. Science. 2022 Jan 07. 375(6576): 26-27
    Setting boundaries for tissue patterning.
    Tyler R Huycke, Zev J Gartner.
      [Figure: see text].
    DOI:  https://doi.org/10.1126/science.abn3054
  68. Nature. 2022 Jan 04.
    Daily briefing: Chemist Charles Lieber convicted of hiding his ties to China.
    Flora Graham.
      
    DOI:  https://doi.org/10.1038/d41586-022-00014-9
  69. Cell Metab. 2022 Jan 04. pii: S1550-4131(21)00623-9. [Epub ahead of print]34(1): 171-183.e6
    FGF1 and insulin control lipolysis by convergent pathways.
    Gencer Sancar, Sihao Liu, Emanuel Gasser, Jacqueline G Alvarez, Christopher Moutos, Kyeongkyu Kim, Tim van Zutphen, Yuhao Wang, Timothy F Huddy, Brittany Ross, Yang Dai, David Zepeda, Brett Collins, Emma Tilley, Matthew J Kolar, Ruth T Yu, Annette R Atkins, Theo H van Dijk, Alan Saghatelian, Johan W Jonker, Michael Downes, Ronald M Evans.
      Inexorable increases in insulin resistance, lipolysis, and hepatic glucose production (HGP) are hallmarks of type 2 diabetes. Previously, we showed that peripheral delivery of exogenous fibroblast growth factor 1 (FGF1) has robust anti-diabetic effects mediated by the adipose FGF receptor (FGFR) 1. However, its mechanism of action is not known. Here, we report that FGF1 acutely lowers HGP by suppressing adipose lipolysis. On a molecular level, FGF1 inhibits the cAMP-protein kinase A axis by activating phosphodiesterase 4D (PDE4D), which separates it mechanistically from the inhibitory actions of insulin via PDE3B. We identify Ser44 as an FGF1-induced regulatory phosphorylation site in PDE4D that is modulated by the feed-fast cycle. These findings establish the FGF1/PDE4 pathway as an alternate regulator of the adipose-HGP axis and identify FGF1 as an unrecognized regulator of fatty acid homeostasis.
    Keywords:  FGF1; PDE4; cAMP; hepatic glucose production; insulin; lipolysis; type 2 diabetes
    DOI:  https://doi.org/10.1016/j.cmet.2021.12.004
  70. Nature. 2022 Jan 05.
    Behavioural immune landscapes of inflammation.
    Georgiana Crainiciuc, Miguel Palomino-Segura, Miguel Molina-Moreno, Jon Sicilia, David G Aragones, Jackson Liang Yao Li, Rodrigo Madurga, José M Adrover, Alejandra Aroca-Crevillén, Sandra Martin-Salamanca, Alfonso Serrano Del Valle, Sandra D Castillo, Heidi C E Welch, Oliver Soehnlein, Mariona Graupera, Fátima Sánchez-Cabo, Alexander Zarbock, Thomas E Smithgall, Mauro Di Pilato, Thorsten R Mempel, Pierre-Louis Tharaux, Santiago F González, Angel Ayuso-Sacido, Lai Guan Ng, Gabriel F Calvo, Iván González-Díaz, Fernando Díaz-de-María, Andrés Hidalgo.
      Transcriptional and proteomic profiling of individual cells have revolutionized interpretation of biological phenomena by providing cellular landscapes of healthy and diseased tissues1,2. These approaches, however, do not describe dynamic scenarios in which cells continuously change their biochemical properties and downstream 'behavioural' outputs3-5. Here we used 4D live imaging to record tens to hundreds of morpho-kinetic parameters describing the dynamics of individual leukocytes at sites of active inflammation. By analysing more than 100,000 reconstructions of cell shapes and tracks over time, we obtained behavioural descriptors of individual cells and used these high-dimensional datasets to build behavioural landscapes. These landscapes recognized leukocyte identities in the inflamed skin and trachea, and uncovered a continuum of neutrophil states inside blood vessels, including a large, sessile state that was embraced by the underlying endothelium and associated with pathogenic inflammation. Behavioural screening in 24 mouse mutants identified the kinase Fgr as a driver of this pathogenic state, and interference with Fgr protected mice from inflammatory injury. Thus, behavioural landscapes report distinct properties of dynamic environments at high cellular resolution.
    DOI:  https://doi.org/10.1038/s41586-021-04263-y
  71. Nat Commun. 2022 Jan 05. 13(1): 190
    Author Correction: Atrx inactivation drives disease-defining phenotypes in glioma cells of origin through global epigenomic remodeling.
    Carla Danussi, Promita Bose, Prasanna T Parthasarathy, Pedro C Silberman, John S Van Arnam, Mark Vitucci, Oliver Y Tang, Adriana Heguy, Yuxiang Wang, Timothy A Chan, Gregory J Riggins, Erik P Sulman, Frederick F Lang, Chad J Creighton, Benjamin Deneen, C Ryan Miller, David J Picketts, Kasthuri Kannan, Jason T Huse.
      
    DOI:  https://doi.org/10.1038/s41467-021-27820-5
  72. Nature. 2022 Jan 06.
    A mighty antibody is the bane of multiple coronaviruses.
      
    Keywords:  SARS-CoV-2
    DOI:  https://doi.org/10.1038/d41586-022-00001-0
  73. Nature. 2022 Jan;601(7891): 30
    From the archive.
      
    Keywords:  History; Mathematics and computing; Zoology
    DOI:  https://doi.org/10.1038/d41586-021-03740-8
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