bims-nimamd Biomed News
on Neuroimmunity and neuroinflammation in ageing and metabolic disease
Issue of 2025–02–09
35 papers selected by
Fawaz Alzaïd, Sorbonne Université
  1. Tolerance during infection.
  2. Is one lymphocyte's brake another lymphocyte's gas?
  3. Human versus mouse PD-1.
  4. Recruiting lymphocytes.
  5. New neurons are born in the adult human brain.
  6. Exhaustion is planned.
  7. Nutrient metabolism shapes epigenetic landscape of T cells.
  8. Transdisciplinary links between societal inequality and brain structure and dynamics.
  9. Are the Internet and AI affecting our memory? What the science says.
  10. Retrograde mitochondrial signaling governs the identity and maturity of metabolic tissues.
  11. How the brain suppresses fear: mouse study offers path to anxiety treatments.
  12. An atlas of cells in the human brain's control hub.
  13. Aspirin inhibits proteasomal degradation and promotes α-synuclein aggregate clearance through K63 ubiquitination.
  14. Starving tumors with fat.
  15. Orphan G protein-coupled receptor GPRC5B controls macrophage function by facilitating prostaglandin E receptor 2 signaling.
  16. The weight-loss drugs being tested in 2025: will they beat Ozempic?
  17. Omega-3 supplements slow biological ageing.
  18. Mitochondria as you've never seen them - January's best science images.
  19. Human MAIT cell response profiles biased toward IL-17 or IL-10 are distinct effector states directed by the cytokine milieu.
  20. Non-canonical lysosomal lipolysis drives mobilization of adipose tissue energy stores with fasting.
  21. How to make the perfect egg: give it lukewarm baths.
  22. Retrotrans-genomics identifies aberrant THE1B endogenous retrovirus fusion transcripts in the pathogenesis of sarcoidosis.
  23. Metabolic deficiencies underlie reduced plasmacytoid dendritic cell IFN-I production following viral infection.
  24. Time for lipid cell biology.
  25. Inspiring the next generation of engineers and scientists to be champions of equitable change.
  26. Shared pathway of WDFY4-dependent cross-presentation of immune complexes by cDC1 and cDC2.
  27. IL-4 induces CD22 expression to restrain the effector program of virtual memory T cells.
  28. Single-cell atlas of human pancreatic islet and acinar endothelial cells in health and diabetes.
  29. Faulty mitochondria jump between tumours and T cells.
  30. Grand canyons on the Moon.
  31. Lactate homeostasis is maintained through regulation of glycolysis and lipolysis.
  32. Grand Canyons on the Moon.
  33. Even at one month, a baby's brain shows an aptitude for smell.
  34. Subcutaneous depth-selective spectral imaging with mμSORS enables noninvasive glucose monitoring.
  35. Endothelial insulin resistance induced by adrenomedullin mediates obesity-associated diabetes.
  1. Nat Immunol. 2025 Feb;26(2): 149
    Tolerance during infection.
    Stephanie Houston.
      
    DOI:  https://doi.org/10.1038/s41590-025-02083-0
  2. Sci Immunol. 2025 Feb 07. 10(104): eadw3656
    Is one lymphocyte's brake another lymphocyte's gas?
    Thomas T Xu, Shiv Pillai.
      PD-1 contributes to memory B cell development and robust antibody responses through B cell extrinsic and intrinsic mechanisms.
    DOI:  https://doi.org/10.1126/sciimmunol.adw3656
  3. Nat Immunol. 2025 Feb;26(2): 149
    Human versus mouse PD-1.
    Ioana Staicu.
      
    DOI:  https://doi.org/10.1038/s41590-025-02086-x
  4. Nat Immunol. 2025 Feb;26(2): 149
    Recruiting lymphocytes.
    Laurie A Dempsey.
      
    DOI:  https://doi.org/10.1038/s41590-025-02085-y
  5. Nat Med. 2025 Feb 06.
    New neurons are born in the adult human brain.
    Fred H Gage.
      
    DOI:  https://doi.org/10.1038/s41591-025-03497-x
  6. Nat Immunol. 2025 Feb;26(2): 149
    Exhaustion is planned.
    Nicholas J Bernard.
      
    DOI:  https://doi.org/10.1038/s41590-025-02084-z
  7. Nat Immunol. 2025 Jan 31.
    Nutrient metabolism shapes epigenetic landscape of T cells.
    Annika Poch, Daniel T Utzschneider.
      
    DOI:  https://doi.org/10.1038/s41590-025-02080-3
  8. Nat Aging. 2025 Feb 05.
    Transdisciplinary links between societal inequality and brain structure and dynamics.
      
    DOI:  https://doi.org/10.1038/s43587-025-00822-4
  9. Nature. 2025 Feb;638(8049): 26-28
    Are the Internet and AI affecting our memory? What the science says.
    Helen Pearson.
      
    Keywords:  Brain; Neuroscience; Psychology
    DOI:  https://doi.org/10.1038/d41586-025-00292-z
  10. Science. 2025 Feb 06. eadf2034
    Retrograde mitochondrial signaling governs the identity and maturity of metabolic tissues.
    Emily M Walker, Gemma L Pearson, Nathan Lawlor, Ava M Stendahl, Anne Lietzke, Vaibhav Sidarala, Jie Zhu, Tracy Stromer, Emma C Reck, Jin Li, Elena Levi-D'Ancona, Mabelle B Pasmooij, Dre L Hubers, Aaron Renberg, Kawthar Mohamed, Vishal S Parekh, Irina X Zhang, Benjamin Thompson, Deqiang Zhang, Sarah A Ware, Leena Haataja, Nathan Qi, Stephen C J Parker, Peter Arvan, Lei Yin, Brett A Kaufman, Leslie S Satin, Lori Sussel, Michael L Stitzel, Scott A Soleimanpour.
      Mitochondrial damage is a hallmark of metabolic diseases, including diabetes, yet the consequences of compromised mitochondria in metabolic tissues are often unclear. Here, we report that dysfunctional mitochondrial quality control engages a retrograde (mitonuclear) signaling program that impairs cellular identity and maturity in β-cells, hepatocytes, and brown adipocytes. Targeted deficiency throughout the mitochondrial quality control pathway, including genome integrity, dynamics, or turnover, impaired the oxidative phosphorylation machinery, activating the mitochondrial integrated stress response, eliciting chromatin remodeling, and promoting cellular immaturity rather than apoptosis to yield metabolic dysfunction. Indeed, pharmacologic blockade of the integrated stress response in vivo restored β-cell identity following loss of mitochondrial quality control. Targeting mitochondrial retrograde signaling may therefore be promising in the treatment or prevention of metabolic disorders.
    DOI:  https://doi.org/10.1126/science.adf2034
  11. Nature. 2025 Feb 06.
    How the brain suppresses fear: mouse study offers path to anxiety treatments.
    Felicity Nelson.
      
    Keywords:  Brain; Neuroscience; Post-traumatic stress disorder
    DOI:  https://doi.org/10.1038/d41586-025-00363-1
  12. Nature. 2025 Feb 05.
    An atlas of cells in the human brain's control hub.
      
    Keywords:  Brain; Neuroscience; Transcriptomics
    DOI:  https://doi.org/10.1038/d41586-025-00314-w
  13. Nat Commun. 2025 Feb 07. 16(1): 1438
    Aspirin inhibits proteasomal degradation and promotes α-synuclein aggregate clearance through K63 ubiquitination.
    Jing Gao, Yang Liu, Chenfang Si, Rui Guo, Shouqiao Hou, Xiaosong Liu, Houfang Long, Di Liu, Daichao Xu, Zai-Rong Zhang, Cong Liu, Bing Shan, Christoph W Turck, Kaiwen He, Yaoyang Zhang.
      Aspirin is a potent lysine acetylation inducer, but its impact on lysine ubiquitination and ubiquitination-directed protein degradation is unclear. Herein, we develop the reversed-pulsed-SILAC strategy to systematically profile protein degradome in response to aspirin. By integrating degradome, acetylome, and ubiquitinome analyses, we show that aspirin impairs proteasome activity to inhibit proteasomal degradation, rather than directly suppressing lysine ubiquitination. Interestingly, aspirin increases lysosomal degradation-implicated K63-linked ubiquitination. Accordingly, using the major pathological protein of Parkinson's disease (PD), α-synuclein (α-syn), as an example of protein aggregates, we find that aspirin is able to reduce α-syn in cultured cells, neurons, and PD model mice with rescued locomotor ability. We further reveal that the α-syn aggregate clearance induced by aspirin is K63-ubiquitination dependent in both cells and PD mice. These findings suggest two complementary mechanisms by which aspirin regulates the degradation of soluble and insoluble proteins, providing insights into its diverse pharmacological effects that can aid in future drug development efforts.
    DOI:  https://doi.org/10.1038/s41467-025-56737-6
  14. Nat Biotechnol. 2025 Feb 04.
    Starving tumors with fat.
      
    DOI:  https://doi.org/10.1038/s41587-024-02550-3
  15. Nat Commun. 2025 Feb 07. 16(1): 1448
    Orphan G protein-coupled receptor GPRC5B controls macrophage function by facilitating prostaglandin E receptor 2 signaling.
    Jeonghyeon Kwon, Haruya Kawase, Kenny Mattonet, Stefan Guenther, Lisa Hahnefeld, Jamal Shamsara, Jan Heering, Michael Kurz, Sina Kirchhofer, Cornelius Krasel, Michaela Ulrich, Margherita Persechino, Sripriya Murthy, Cesare Orlandi, Christian D Sadik, Gerd Geisslinger, Moritz Bünemann, Peter Kolb, Stefan Offermanns, Nina Wettschureck.
      Macrophages express numerous G protein-coupled receptors (GPCRs) that regulate adhesion, migration, and activation, but the function of orphan receptor GPRC5B in macrophages is unknown. Both resident peritoneal and bone marrow-derived macrophages from myeloid-specific GPRC5B-deficient mice show increased migration and phagocytosis, resulting in improved bacterial clearance in a peritonitis model. In other models such as myocardial infarction, increased myeloid cell recruitment has adverse effects. Mechanistically, we found that GPRC5B physically interacts with GPCRs of the prostanoid receptor family, resulting in enhanced signaling through the prostaglandin E receptor 2 (EP2). In GPRC5B-deficient macrophages, EP2-mediated anti-inflammatory effects are diminished, resulting in hyperactivity. Using in silico modelling and docking, we identify residues potentially mediating GPRC5B/EP2 dimerization and show that their mutation results in loss of GPRC5B-mediated facilitation of EP2 signaling. Finally, we demonstrate that decoy peptides mimicking the interacting sequence are able to reduce GPRC5B-mediated facilitation of EP2-induced cAMP signaling in macrophages.
    DOI:  https://doi.org/10.1038/s41467-025-56713-0
  16. Nature. 2025 Feb 06.
    The weight-loss drugs being tested in 2025: will they beat Ozempic?
    Giorgia Guglielmi.
      
    Keywords:  Drug discovery; Obesity
    DOI:  https://doi.org/10.1038/d41586-025-00376-w
  17. Nature. 2025 Feb 03.
    Omega-3 supplements slow biological ageing.
    Felicity Nelson.
      
    Keywords:  Ageing; Epigenetics; Molecular biology
    DOI:  https://doi.org/10.1038/d41586-025-00355-1
  18. Nature. 2025 Jan 31.
    Mitochondria as you've never seen them - January's best science images.
    Emma Stoye.
      
    Keywords:  Media
    DOI:  https://doi.org/10.1038/d41586-025-00269-y
  19. Proc Natl Acad Sci U S A. 2025 Feb 11. 122(6): e2414230122
    Human MAIT cell response profiles biased toward IL-17 or IL-10 are distinct effector states directed by the cytokine milieu.
    Caroline Boulouis, Elli Mouchtaridi, Thomas R Müller, Jeffrey Y W Mak, David P Fairlie, Peter Bergman, Jakob Michaëlsson, Jonas Halfvarson, Jenny Mjösberg, Marcus Buggert, Johan K Sandberg.
      Mucosal-associated invariant T (MAIT) cells are unconventional T cells that mediate rapid antimicrobial immune responses to antigens derived from microbial riboflavin pathway metabolites presented by the evolutionarily conserved MR1 molecules. MAIT cells represent a large pre-expanded T cell subset in humans and are involved in both protective immunity and inflammatory immunopathology. However, what controls the functional heterogeneity of human MAIT cell responses is still largely unclear. Here, combining functional and transcriptomic analyses, we investigate how MAIT cell response programs are influenced by the cytokine milieu at the time of antigen recognition. Activation by MR1-presented antigen together with IL-12 induces intermediate levels of IFNγ and TNF, as well as a regulatory profile with substantial IL-10 production and elevated expression of TIM-3, LAG-3, and PD-1. Activation by the combination of antigen and IL-12 induces a c-MAF-dependent program required for IL-10 production. The MAIT cell-derived IL-10 mediates both autocrine and paracrine immune regulation. In contrast, coactivation of MAIT cells with IL-18 induces IL-17, GM-CSF, IFNγ, and TNF, without IL-10. Notably, IL-18 dominantly counteracts IL-10 expression. The activation states biased toward IL-10 or IL-17 production are reversible and do not represent stable subsets. Finally, MR1-restricted TCR-mediated activation without cytokine coactivation drives primarily granzyme B cytolytic arming. Altogether, these findings demonstrate that human MAIT cells adapt their functional effector response during antigen recognition to cytokine cues in the microenvironment, and identify programs biased toward either regulatory c-MAF-dependent IL-10 expression, or an inflammatory IL-17 and GM-CSF profile.
    Keywords:  IL-10; MAIT cells; MR1; T cells; human
    DOI:  https://doi.org/10.1073/pnas.2414230122
  20. Nat Commun. 2025 Feb 04. 16(1): 1330
    Non-canonical lysosomal lipolysis drives mobilization of adipose tissue energy stores with fasting.
    G V Naveen Kumar, Rui-Sheng Wang, Ankit X Sharma, Natalie L David, Tânia Amorim, Daniel S Sinden, Nandini K Doshi, Martin Wabitsch, Sebastien Gingras, Asim Ejaz, J Peter Rubin, Bradley A Maron, Pouneh K Fazeli, Matthew L Steinhauser.
      Physiological adaptations to fasting enable humans to survive for prolonged periods without food and involve molecular pathways that may drive life-prolonging effects of dietary restriction in model organisms. Mobilization of fatty acids and glycerol from adipocyte lipid stores by canonical neutral lipases, including the rate limiting adipose triglyceride lipase (Pnpla2/ATGL), is critical to the adaptive fasting response. Here we discovered an alternative mechanism of lipolysis in adipocytes involving a lysosomal program. We functionally tested lysosomal lipolysis with pharmacological and genetic approaches in mice and in murine and human adipocyte and adipose tissue explant culture, establishing dependency on lysosomal acid lipase (LIPA/LAL) and the microphthalmia/transcription factor E (MiT/TFE) family. Our study establishes a model whereby the canonical pathway is critical for rapid lipolytic responses to adrenergic stimuli operative in the acute stage of fasting, while the alternative lysosomal pathway dominates with prolonged fasting.
    DOI:  https://doi.org/10.1038/s41467-025-56613-3
  21. Nature. 2025 Feb;638(8050): 297
    How to make the perfect egg: give it lukewarm baths.
      
    Keywords:  Applied physics
    DOI:  https://doi.org/10.1038/d41586-025-00237-6
  22. Nat Commun. 2025 Feb 07. 16(1): 1318
    Retrotrans-genomics identifies aberrant THE1B endogenous retrovirus fusion transcripts in the pathogenesis of sarcoidosis.
    Shunsuke Funaguma, Aritoshi Iida, Yoshihiko Saito, Jantima Tanboon, Francia Victoria De Los Reyes, Kyuto Sonehara, Yu-Ichi Goto, Yukinori Okada, Shinichiro Hayashi, Ichizo Nishino.
      Transposon-like human element 1B (THE1B) originates from ancient retroviral sequences integrated into the primate genome approximately 50 million years ago, now accounting for at least 27,233 copies in the human genome, suggesting their extensive influence on human genomic architecture. Here we report identification of 19 THE1B fusion transcripts through short- and long-read RNA-seq analysis, 15 of which are previously unmapped, showing elevated expression in 16 individuals with sarcoid myopathy (SM), as compared to 400 controls with various other muscle diseases. Analysis of publicly available RNA-seq data indicated a correlation between the reduced expression of eight THE1B fusion transcripts and clinical improvement in individuals with cutaneous sarcoidosis receiving tofacitinib treatment. Single-cell or single-nucleus RNA-seq analyses of sarcoidosis not only confirmed these transcripts but also revealed a novel read-through transcript, SIRPB1-SIRPD, and TREM2.1, predominantly in granuloma-associated macrophages. The expression profiles of THE1B fusion transcripts in tuberculosis (TB) significantly differed from SM in single-cell RNA-seq data, suggesting that the differences between TB's caseous granulomas and sarcoidosis's non-caseous granulomas might be linked to disparate expression patterns of THE1B fusion transcripts. Our retrotrans-genomics approach has not only identified the genomic landscape of sarcoidosis but also provided new insights into its etiology.
    DOI:  https://doi.org/10.1038/s41467-025-56567-6
  23. Nat Commun. 2025 Feb 07. 16(1): 1460
    Metabolic deficiencies underlie reduced plasmacytoid dendritic cell IFN-I production following viral infection.
    Trever T Greene, Yeara Jo, Carolina Chiale, Monica Macal, Ziyan Fang, Fawziyah S Khatri, Alicia L Codrington, Katelynn R Kazane, Elizabeth Akbulut, Shobha Swaminathan, Yu Fujita, Patricia Fitzgerald-Bocarsly, Thekla Cordes, Christian Metallo, David A Scott, Elina I Zúñiga.
      Type I Interferons (IFN-I) are central to host protection against viral infections, with plasmacytoid dendritic cells (pDC) being the most significant source, yet pDCs lose their IFN-I production capacity following an initial burst of IFN-I, resulting in susceptibility to secondary infections. The underlying mechanisms of these dynamics are not well understood. Here we find that viral infection reduces the capacity of pDCs to engage both oxidative and glycolytic metabolism. Mechanistically, we identify lactate dehydrogenase B (LDHB) as a positive regulator of pDC IFN-I production in mice and humans; meanwhile, LDHB deficiency is associated with suppressed IFN-I production, pDC metabolic capacity, and viral control following infection. In addition, preservation of LDHB expression is sufficient to partially retain the function of otherwise exhausted pDCs, both in vitro and in vivo. Furthermore, restoring LDHB in vivo in pDCs from infected mice increases IFNAR-dependent, infection-associated pathology. Our work thus identifies a mechanism for balancing immunity and pathology during viral infections, while also providing insight into the highly preserved infection-driven pDC inhibition.
    DOI:  https://doi.org/10.1038/s41467-025-56603-5
  24. Nat Cell Biol. 2025 Feb 05.
    Time for lipid cell biology.
    Xiao-Wei Chen, Anthony S Don, Maria Fedorova, Takeshi Harayama, Natalie Krahmer, Shigekazu Nagata, Priyanka Narayan, Dequina Nicholas, Sara M Nowinski, Yasunori Saheki, Clay F Semenkovich, Xiaoai Zhao, Yilong Zou.
      
    DOI:  https://doi.org/10.1038/s41556-025-01609-w
  25. Cell. 2025 Feb 06. pii: S0092-8674(25)00043-1. [Epub ahead of print]188(3): 586-588
    Inspiring the next generation of engineers and scientists to be champions of equitable change.
    Nyasha Milanzi.
      Nyasha Milanzi is a winner of the fifth annual Rising Black Scientists Awards for a scholar in the physical, data, earth, and environmental sciences. We asked emerging Black scientists to tell us about their scientific vision and goals, experiences that sparked their interest in science, how they want to contribute to a more inclusive scientific community, and how these all fit together on their journey. This is her story.
    DOI:  https://doi.org/10.1016/j.cell.2025.01.014
  26. J Exp Med. 2025 Apr 07. pii: e20240955. [Epub ahead of print]222(4):
    Shared pathway of WDFY4-dependent cross-presentation of immune complexes by cDC1 and cDC2.
    Suin Jo, Ray A Ohara, Derek J Theisen, Sunkyung Kim, Tiantian Liu, Christopher B Bullock, Michelle He, Feiya Ou, Jing Chen, Sytse J Piersma, J Luke Postoak, Wayne M Yokoyama, Michael S Diamond, Theresa L Murphy, Kenneth M Murphy.
      Priming CD8+ T cells against tumors or viral pathogens results largely from cross-presentation of exogenous antigens by type 1 conventional dendritic cells (cDC1s). Although monocyte-derived DCs and cDC2s can cross-present in vitro, their physiological relevance remains unclear. Here, we used genetic models to evaluate the role of cDC subsets in presentation of cell-associated and immune complex antigens to CD4+ and CD8+ T cells in vivo. For cell-associated antigens, cDC1s were necessary and sufficient to prime both CD4+ and CD8+ T cells. In contrast, for immune complex antigens, either cDC1 or cDC2, but not monocyte-derived DCs, could carry out cross-presentation to CD8+ T cells. Mice lacking cDC1 and vaccinated with immune complexes could cross-prime CD8+ T cells that were sufficient to mediate tumor rejection. Notably, this cross-presentation mediated by cDC2 was also WDFY4 dependent, similar to cross-presentation of cell-associated antigens by cDC1. These results demonstrate a previously unrecognized activity of WDFY4 in cDC2s and suggest a cross-presentation pathway shared by cDC subsets.
    DOI:  https://doi.org/10.1084/jem.20240955
  27. Sci Immunol. 2025 Feb 07. 10(104): eadk4841
    IL-4 induces CD22 expression to restrain the effector program of virtual memory T cells.
    Bin Yang, Ophélie Piedfort, Guillem Sanchez-Sanchez, Arnaud Lavergne, Meijiao Gong, Garrie Peng, Ariel Madrigal, Georgios Petrellis, Brunette Katsandegwaza, Lucia Rodriguez Rodriguez, Alexis Balthazar, Sarah J Meyer, Gert Van Isterdael, Julie Van Duyse, Fabienne Andris, Qiang Bai, Thomas Marichal, Bénédicte Machiels, Lars Nitschke, Hamed S Najafabadi, Irah L King, David Vermijlen, Benjamin G Dewals.
      Parasitic helminths induce the production of interleukin-4 (IL-4), which causes the expansion of virtual memory CD8+ T cells (TVM cells), a cell subset that contributes to the control of coinfection with intracellular pathogens. However, the mechanisms regulating IL-4-dependent TVM cell activation and expansion remain ill defined. Here, we used single-cell RNA sequencing of CD8+ T cells to identify pathways that control IL-4-dependent TVM cell responses. Gene signature analysis of CD8+ T cells identified a cell cluster marked by CD22, a canonical regulator of B cell activation, as a selective surface marker of IL-4-induced TVM cells. CD22+ TVM cells were enriched for interferon-γ and granzyme A and retained a diverse TCR repertoire while enriched in self-reactive CDR3 sequences. CD22 intrinsically regulated the IL-4-induced CD8+ T cell effector program, resulting in reduced responsiveness of CD22+ TVM cells and regulatory functions to infection and inflammation. Thus, helminth-induced IL-4 drives the expansion and activation of TVM cells that is counterinhibited by CD22.
    DOI:  https://doi.org/10.1126/sciimmunol.adk4841
  28. Nat Commun. 2025 Feb 06. 16(1): 1338
    Single-cell atlas of human pancreatic islet and acinar endothelial cells in health and diabetes.
    Rebecca Craig-Schapiro, Ge Li, Kevin Chen, Jesus M Gomez-Salinero, Ryan Nachman, Aleksandra Kopacz, Ryan Schreiner, Xiaojuan Chen, Qiao Zhou, Shahin Rafii, David Redmond.
      Characterization of the vascular heterogeneity within the pancreas has previously been lacking. Here, we develop strategies to enrich islet-specific endothelial cells (ISECs) and acinar-specific endothelial cells (ASECs) from three human pancreases and corroborate these findings with three published pancreatic datasets. Single-cell RNA sequencing reveals the unique molecular signatures of ISECs, including structural genes COL13A1, ESM1, PLVAP, UNC5B, and LAMA4, angiocrine genes KDR, THBS1, BMPs and CXCR4, and metabolic genes ACE, PASK and F2RL3. ASECs display distinct signatures including GPIHBP1, CCL14, CD74, AQP1, KLF4, and KLF2, which may manage the inflammatory and metabolic needs of the exocrine pancreas. Ligand-receptor analysis suggests ISECs and ASECs interact with LUM+ fibroblasts and RGS5+ pericytes and smooth muscle cells via VEGF-A:VEGFR2, CXCL12:CXCR4, and LIF:LIFR pathways. Comparative expression and immunohistochemistry indicate disruption of endothelial-expressed CD74, ESM1, PLVAP, THBD, VWA1, and VEGF-A cross-talk among vascular and other cell types in diabetes. Thus, our data provide a single-cell vascular atlas of human pancreas, enabling deeper understanding of pancreatic pathophysiology in health and disease.
    DOI:  https://doi.org/10.1038/s41467-024-55415-3
  29. Nat Rev Immunol. 2025 Feb 07.
    Faulty mitochondria jump between tumours and T cells.
    Lucy Bird.
      
    DOI:  https://doi.org/10.1038/s41577-025-01143-8
  30. Nat Commun. 2025 Feb 04. 16(1): 1146
    Grand canyons on the Moon.
    David A Kring, Danielle P Kallenborn, Gareth S Collins.
      High energy streams of rock ejected from the Schrödinger impact basin carved two canyons in the lunar crust that are comparable in size to the Grand Canyon of North America. Here we use photogeologic mapping of those canyons and related impact ejecta deposits to show the trajectory of the impacting asteroid or comet, which produced an asymmetrical pattern of crater excavation and transport of ejected debris. The flow directions of that ejected debris and the speed of its subsequent impact with the lunar surface are calculated, as is the energy that carved the canyons in less than ten minutes. The study implies that most of the excavated debris was ejected away from the lunar south pole, minimizing the amount of debris that covers the > 4 billion year old units that will be explored by Artemis astronauts.
    DOI:  https://doi.org/10.1038/s41467-024-55675-z
  31. Cell Metab. 2025 Jan 29. pii: S1550-4131(24)00491-1. [Epub ahead of print]
    Lactate homeostasis is maintained through regulation of glycolysis and lipolysis.
    Won Dong Lee, Daniel R Weilandt, Lingfan Liang, Michael R MacArthur, Natasha Jaiswal, Olivia Ong, Charlotte G Mann, Qingwei Chu, Craig J Hunter, Rolf-Peter Ryseck, Wenyun Lu, Anna M Oschmann, Alexis J Cowan, Tara A TeSlaa, Caroline R Bartman, Cholsoon Jang, Joseph A Baur, Paul M Titchenell, Joshua D Rabinowitz.
      Lactate is among the highest flux circulating metabolites. It is made by glycolysis and cleared by both tricarboxylic acid (TCA) cycle oxidation and gluconeogenesis. Severe lactate elevations are life-threatening, and modest elevations predict future diabetes. How lactate homeostasis is maintained, however, remains poorly understood. Here, we identify, in mice, homeostatic circuits regulating lactate production and consumption. Insulin induces lactate production by upregulating glycolysis. We find that hyperlactatemia inhibits insulin-induced glycolysis, thereby suppressing excess lactate production. Unexpectedly, insulin also promotes lactate TCA cycle oxidation. The mechanism involves lowering circulating fatty acids, which compete with lactate for mitochondrial oxidation. Similarly, lactate can promote its own consumption by lowering circulating fatty acids via the adipocyte-expressed G-protein-coupled receptor hydroxycarboxylic acid receptor 1 (HCAR1). Quantitative modeling suggests that these mechanisms suffice to produce lactate homeostasis, with robustness to noise and perturbation of individual regulatory mechanisms. Thus, through regulation of glycolysis and lipolysis, lactate homeostasis is maintained.
    Keywords:  HCAR1 signaling; TCA cycle; competitive catabolism; diabetes mellitus; insulin resistance; insulin signaling; lactate metabolism; metabolic flux; metabolic homeostasis; quantitative modeling
    DOI:  https://doi.org/10.1016/j.cmet.2024.12.009
  32. Nature. 2025 Feb 04.
    Grand Canyons on the Moon.
    Dan Fox.
      
    Keywords:  Asteroids, comets and Kuiper belt; Geology; Planetary science; Space physics
    DOI:  https://doi.org/10.1038/d41586-025-00263-4
  33. Nature. 2025 Feb;638(8049): 11
    Even at one month, a baby's brain shows an aptitude for smell.
      
    Keywords:  Neuroscience
    DOI:  https://doi.org/10.1038/d41586-025-00236-7
  34. Nat Metab. 2025 Feb 05.
    Subcutaneous depth-selective spectral imaging with mμSORS enables noninvasive glucose monitoring.
    Yifei Zhang, Lili Zhang, Long Wang, Shuai Shao, Bei Tao, Chunrui Hu, Yufei Chen, Yue Shen, Xianbiao Zhang, Shijia Pan, Hua Cao, Ming Sun, Jia Shi, Chunhong Jiang, Minghui Chen, Lin Zhou, Guang Ning, Chang Chen, Weiqing Wang.
      Noninvasive blood glucose monitoring offers substantial advantages for patients, but current technologies are often not sufficiently accurate for clinical applications or require personalized calibration. Here we report multiple μ-spatially offset Raman spectroscopy, which captures Raman signals at varying skin depths, and show that it accurately detects blood glucose levels in humans. In 35 individuals with or without type 2 diabetes, we first determine the optimal depth for glucose detection to be at or below the capillary-rich dermal-epidermal junction, where we observe a strong correlation between specific Raman bands and venous plasma glucose concentrations. In a second study, comprising 230 participants, we then improve accuracy of our regression model to reach a mean absolute relative difference of 14.6%, without personalized calibration, whereby 99.4% of calculated glucose values fall into clinically acceptable zones of the consensus error grid (zones A and B). These findings highlight the ability and robustness of multiple μ-spatially offset Raman spectroscopy for noninvasive blood glucose measurement in a clinical setting.
    DOI:  https://doi.org/10.1038/s42255-025-01217-w
  35. Science. 2025 Feb 07. 387(6734): 674-682
    Endothelial insulin resistance induced by adrenomedullin mediates obesity-associated diabetes.
    Haaglim Cho, Chien-Cheng Lai, Rémy Bonnavion, Mohamad Wessam Alnouri, ShengPeng Wang, Kenneth Anthony Roquid, Haruya Kawase, Diana Campos, Min Chen, Lee S Weinstein, Alfredo Martínez, Mario Looso, Miloslav Sanda, Stefan Offermanns.
      Insulin resistance is a hallmark of obesity-associated type 2 diabetes. Insulin's actions go beyond metabolic cells and also involve blood vessels, where insulin increases capillary blood flow and delivery of insulin and nutrients. We show that adrenomedullin, whose plasma levels are increased in obese humans and mice, inhibited insulin signaling in human endothelial cells through protein-tyrosine phosphatase 1B-mediated dephosphorylation of the insulin receptor. In obese mice lacking the endothelial adrenomedullin receptor, insulin-induced endothelial nitric oxide-synthase activation and skeletal muscle perfusion were increased. Treating mice with adrenomedullin mimicked the effect of obesity and induced endothelial and systemic insulin resistance. Endothelial loss or blockade of the adrenomedullin receptor improved obesity-induced insulin resistance. These findings identify a mechanism underlying obesity-induced systemic insulin resistance and suggest approaches to treat obesity-associated type 2 diabetes.
    DOI:  https://doi.org/10.1126/science.adr4731
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