Latest Publications
Imaging Glucose Metabolism and Dopaminergic Dysfunction in Sheep (Ovis aries) Brain using PET Imaging Reveals Abnormalities in OVT73 Huntington’s Disease Sheep
Williams G.K., Akkermans J., Lawson M., Syta P., Staelens S., Adhikari M.H., Morton A.J., Nitzsche B., Boltze J., Christou C., Bertoglio D., Ahamed M.
The major goal of our preliminary cross-sectional study is to demonstrate the feasibility and utility of the unique transgenic sheep model of HD (OVT73) in positron emission tomography (PET) imaging. In this first-of-its-kind study, we showed the usefulness and validity of HD sheep model in imaging cerebral glucose metabolism and dopamine uptake using PET imaging. The identification of discrete patterns of metabolic abnormality using [18F]FDG and decline of [18F]FDOPA uptake may provide a useful means of quantifying early HD-related changes in these models, particularly in the transition from presymptomatic to early symptomatic phases of HD.
A regulatory module mediating temperature control of cell-cell communication facilitates tree bud dormancy release
Shashank K Pandey, Jay Prakash Maurya, Bibek Aryal, Kamil Drynda, Aswin Nair, Pal Miskolczi, Rajesh Kumar Singh, Xiaobin Wang, Yujiao Ma, Tatiana de Souza Moraes, Emmanuelle M Bayer, Etienne Farcot, George W Bassel, Leah R Band, Rishikesh P Bhalerao
The control of cell–cell communication via plasmodesmata (PD) plays a key role in plant development. In tree buds, low-temperature conditions (LT) induce a switch in plasmodesmata from a closed to an open state, which restores cell-to-cell communication in the shoot apex and releases dormancy. Using genetic and cell-biological approaches, we have identified a previously uncharacterized transcription factor, Low-temperature-Induced MADS-box 1 (LIM1), as an LT-induced, direct upstream activator of the gibberellic acid (GA) pathway. Mathematical modeling and experimental validation suggest that negative feedback regulation of LIM1 by gibberellin could play a crucial role in maintaining the robust temporal regulation of bud responses to low temperature. These results reveal genetic factors linking temperature control of cell–cell communication with regulation of seasonally-aligned growth crucial for adaptation of trees.
Ammonia leakage can underpin nitrogen-sharing among soil microorganisms.
Luke Richards, Kelsey Cremin, Mary Coates, Finley Vigor, Patrick Schäfer, and Orkun S Soyer
Soil microbial communities host a large number of microbial species that support important ecological functions such as biogeochemical cycling and plant nutrition. The extent and stability of these functions are affected by inter-species interactions among soil microorganisms, yet the different mechanisms underpinning microbial interactions in the soil are not fully understood. Here, we study the extent of nutrient-based interactions among two model, plant-supporting soil microorganisms, the fungi Serendipita indica, and the bacteria Bacillus subtilis. Our findings highlight that ammonia based N-sharing can be a previously under-appreciated mechanism underpinning interaction among soil microorganisms and could be influenced by microbial or abiotic alteration of pH in microenvironments.
MSK1 is required for the experience- and ampakine-dependent enhancement of spatial reference memory and reversal learning and for the induction of Arc and BDNF
Lorenzo Morè, Lucia Privitera, Marcia Lopes, J. Simon C. Arthur, Julie C. Lauterborn, Sonia A.L. Corrêa, Bruno G. Frenguelli
One class of cognitive enhancers, the ampakines, has attracted particular attention by virtue of improving cognition associated with animal models of neurodevelopmental, neurodegenerative, and psychiatric conditions, as well as in age-related cognitive impairment. Ampakines elevate CNS levels of BDNF, and it is through this elevation that their beneficial actions are believed to occur. To establish whether MSK1 converts ampakine-induced elevations of BDNF into cognitive enhancement we tested an ampakine (CX929) in male WT mice and in male mice in which the kinase activity of MSK1 was inactivated. We found that MSK1 is required for the ampakine-dependent improvement in spatial reference memory and cognitive flexibility, and for the elevations of BDNF and the plasticity-related protein Arc associated with ampakines and experience. These observations implicate MSK1 as a key enabler of the beneficial effects of ampakines on cognitive function, and furthermore identify MSK1 as a hub for BDNF-elevating nootropic strategies.
A retrospective assessment of forecasting the peak of the SARS-CoV-2 Omicron BA.1 wave in England
Keeling, Matthew James and Dyson, Louise
We discuss the invasion of the Omicron BA.1 variant into England as a paradigm for real-time model fitting and projection. Here we use a mixture of simple SIR-type models, analysis of the early data and a more complex age-structure model fit to the outbreak to understand the dynamics. In particular, we highlight that early data shows that the invading Omicron variant had a substantial growth advantage over the resident Delta variant. However, early data does not allow us to reliably infer other key epidemiological parameters - such as generation time and severity - which influence the expected peak hospital numbers. With more complete epidemic data from January 2022 are we able to capture the true scale of the epidemic in terms of both infections and hospital admissions, driven by different infection characteristics of Omicron compared to Delta and a substantial shift in estimated precautionary behaviour during December. This work highlights the challenges of real time forecasting, in a rapidly changing environment with limited information on the variant’s epidemiological characteristics.
Genetic-epigenetic interplay in the determination of plant 3D genome organization
Xiaoning He, Chloé Dias Lopes, Leonardo I Pereyra-Bistrain, Ying Huang, Jing An, Rim Brik Chaouche, Hugo Zalzalé, Qingyi Wang, Xing Ma, Javier Antunez-Sanchez, Catherine Bergounioux, Sophie Piquerez, Sotirios Fragkostefanakis, Yijing Zhang, Shaojian Zheng, Martin Cresp, Magdy M Mahfouz, Olivier Mathieu, Federico Ariel, Jose Gutierrez-Marcos, Xingwang Li, Nicolas Bouché, Cécile Raynaud, David Latrasse, Moussa Benhamed
The 3D chromatin organization plays a major role in the control of gene expression. In this study, employing a combination of genetics and advanced 3D genomics approaches, we demonstrated that a redistribution of facultative heterochromatin marks in regions usually occupied by constitutive heterochromatin marks disrupts the 3D genome compartmentalisation. This disturbance, in turn, triggers novel chromatin interactions between genic and transposable element (TE) regions. Interestingly, our results imply that epigenetic features, constrained by genetic factors, intricately mold the landscape of 3D genome organisation. This study sheds light on the profound genetic-epigenetic interplay that underlies the regulation of gene expression within the intricate framework of the 3D genome. Our findings highlight the complexity of the relationships between genetic determinants and epigenetic features in shaping the dynamic configuration of the 3D genome.