Latest Publications
Adenosine signalling to astrocytes coordinates brain metabolism and function
Shefeeq M. Theparambil, Olga Kopach, Alice Braga, Shereen Nizari, Patrick S. Hosford, Virag Sagi-Kiss, Anna Hadjihambi, Christos Konstantinou, Noemi Esteras, Ana Gutierrez Del Arroyo, Gareth L. Ackland, Anja G. Teschemacher, Nicholas Dale, Tobias Eckle, Petros Andrikopoulos, Dmitri A. Rusakov, Sergey Kasparov & Alexander V. Gourine
Brain computation performed by billions of nerve cells relies on a sufficient and uninterrupted nutrient and oxygen supply. Astrocytes, the ubiquitous glial neighbours of neurons, govern brain glucose uptake and metabolism, but the exact mechanisms of metabolic coupling between neurons and astrocytes that ensure on-demand support of neuronal energy needs are not fully understood. Here we show, using experimental in vitro and in vivo animal models, that neuronal activity-dependent metabolic activation of astrocytes is mediated by neuromodulator adenosine acting on astrocytic A2B receptors. The data identifies the adenosine A2B receptor as an astrocytic sensor of neuronal activity and show that cAMP signalling in astrocytes tunes brain energy metabolism to support its fundamental functions such as sleep and memory.
A Multipronged Bioengineering, Spectroscopic and Theoretical Approach in Unravelling the Excited-State Dynamics of the Archetype Mycosporine Amino Acid
Michael Hymas, Sopida Wongwas, Simin Roshan, Abigail L. Whittock, Christophe Corre, Reza Omidyan and Vasilios G. Stavros
Mycosporine glycine (MyG) was produced by the fermentation of a purposely engineered bacterial strain and isolated from this sustainable source. The ultrafast spectroscopy of MyG was then investigated in its native, zwitterionic form (MyGzwitter), via femtosecond transient electronic absorption spectroscopy. Complementary nonadiabatic (NAD) simulations suggest that, upon photoexcitation to the lowest excited singlet state (S1), MyGzwitter undergoes efficient nonradiative decay to repopulate the electronic ground state (S0). We propose an initial ultrafast ring-twisting mechanism toward an S1/S0 conical intersection, followed by internal conversion to S0 and subsequent vibrational cooling. This study illuminates the workings of the archetype mycosporine, providing photoprotection, in the UV–B range, to organisms such as corals, macroalgae, and cyanobacteria. This study also contributes to our growing understanding of the photoprotection mechanisms of life.
Within-Host Viral Growth and Immune Response Rates Predict Foot-and-Mouth Disease Virus Transmission Dynamics for African Buffalo
Joshua C. Macdonald, Hayriye Gulbudak, Brianna Beechler, Erin E. Gorsich, Simon Gubbins, Eva P茅rez-Martin and Anna E. Jolles
We investigated within-host dynamics and among-host transmission of three strains (SAT-1, -2, -3) of foot-and-mouth disease viruses (FMDVs) in their wildlife host, African buffalo. Our data reveals contrasting within-host dynamics among viral strains, with SAT-2 eliciting more rapid and effective immune responses than SAT-1 and SAT-3. Within-host viral fitness was overwhelmingly determined by variation among hosts in immune response activation rates but not by variation among individual hosts in viral growth rate. Our analyses investigating across-scale linkages indicate that viral replication rate in the host correlates with transmission rates among buffalo and that adaptive immune activation rate determines the infectious period. These parameters define the virus鈥檚 relative basic reproductive number (鈩0), suggesting that viral invasion potential may be predictable from within-host dynamics.
Development of inoculation methods for Pythium violae to evaluate resistance of carrot cultivars and efficacy of crop protection products for cavity spot control
Nicole Pereira, Kathryn R. Hales, Andrew Mead, Lauren H. K. Chappell, Guy C. Barker, John P. Clarkson
In Europe, cavity spot disease continues to have a major impact on marketable yield. The lack of reliable inoculation methods for these Pythium pathogens has, for many years, hampered the identification of new effective crop protection products or carrot varieties that are resistant to the disease. In this research, inoculation methods were developed for P. violae using mycelium or oospores, each of which successfully induced typical cavity spot symptoms in both pot- and field-grown carrots as well as consistent root stunting in the former. These methods were also used to successfully identify carrot cultivars with resistance to cavity spot and confirmed the efficacy of the fungicide metalaxylM against the disease. Results therefore demonstrated that the inoculation methods should be reliable for identifying the efficacy of crop protection products, assessing cavity spot resistance and for further studies investigating the biology and epidemiology of the pathogen.
An atlas of the tomato epigenome reveals that KRYPTONITE shapes TAD-like boundaries through the control of H3K9ac distribution
Jing An, Rim Brik Chaouche, Leonardo I Pereyra-Bistra铆n, Hugo Zalzal茅, Qingyi Wang, Ying Huang, Xiaoning He, Chlo茅 Dias Lopes, Javier Antunez-Sanchez, Catherine Bergounioux, Claire Boulogne, Cynthia Dupas, Cynthia Gillet, Jos茅 Manuel P茅rez-P茅rez, Olivier Mathieu, Nicolas Bouch茅, Sotirios Fragkostefanakis, Yijing Zhang, Shaojian Zheng, Martin Crespi, Magdy M Mahfouz, Federico Ariel, Jose Gutierrez-Marcos, C茅cile Raynaud, David Latrasse, Moussa Benhamed
In recent years, the exploration of genome three-dimensional (3D) conformation has yielded profound insights into the regulation of gene expression and cellular functions in both animals and plants. Employing advanced high-throughput sequencing and microscopy techniques, we investigated the landscape of 26 histone modifications and RNA polymerase II distribution in tomato (Solanum lycopersicum). Our study unveiled a rich and nuanced epigenetic landscape, shedding light on distinct chromatin states associated with heterochromatin formation and gene silencing. Moreover, we elucidated the intricate interplay between these chromatin states and the overall topology of the genome. Employing a genetic approach, we delved into the role of the histone modification H3K9ac in genome topology. Notably, our investigation revealed that the ectopic deposition of this chromatin mark triggered a reorganization of the 3D chromatin structure, defining different TAD-like borders. Our work emphasizes the critical role of H3K9ac in shaping the topology of the tomato genome, providing valuable insights into the epigenetic landscape of this agriculturally significant crop species.
Johannes Boltze publications
Perioperative stroke deteriorates white matter integrity by enhancing cytotoxic CD8 + T鈥恈ell activation
Yuxi Zhou, Xin Wang, Wen Yin, Yan Li, Yunlu Guo, Chen Chen, Johannes Boltze, Arthur Liesz, Tim Sparwasser, Daxiang Wen, Weifeng Yu, and Peiying Li
Here we explore the regulatory mechanisms of microglia鈥恗ediated cytotoxic CD8+ T鈥恈ell infiltration in the white matter injury of perioperative stroke (PIS). We found surgery aggravated white matter injury and deteriorated sensorimotor deficits up to 28 days following PIS. The PIS mice exhibited significantly increased activation of peripheral and central CD8+ T cells, while significantly reduced numbers of mature oligodendrocytes compared to IS mice. Neutralizing CD8+ T cells partly reversed the aggravated demyelination following PIS. Pharmacological blockage or genetic deletion of receptor鈥恑nteracting protein kinase 1 (RIPK1) activity could alleviate CD8+ T鈥恈ell infiltration and demyelination in PIS mice. Surgery exacerbates demyelination and worsens neurological function by promoting infiltration of CD8+ T cells and microglia necroptosis, suggesting that modulating interactions of CD8+ T cells and microglia could be a novel therapeutic target of long鈥恡erm neurological deficits of PIS..
The association between air pollutant exposure and cerebral small vessel disease imaging markers with modifying effects of PRS-defined genetic susceptibility
Studies have highlighted a possible link between air pollution and cerebral small vessel disease (CSVD) imaging markers. However, the exact association and effects of polygenic risk score (PRS) defined genetic susceptibility remains unclear. This cross-sectional study used data from the UK Biobank. Participants aged 40–69 years were recruited between the year 2006 and 2010. The annual average concentrations of NOX, NO2, PM2.5, PM2.5–10, PM2.5 absorbance, and PM10, were estimated, and joint exposure to multiple air pollutants was reflected in the air pollution index (APEX). Air pollutant exposure was classified into the low (T1), intermediate (T2), and high (T3) tertiles.. Our study demonstrated that air pollutant exposure may be associated with CSVD imaging markers, with females being more susceptible, and that PRS-defined genetic susceptibility may modify the associations of air pollutants.