Latest Publications
Astrocyte ryanodine receptors facilitate gliotransmission and astroglial modulation of synaptic plasticity
Ulyana Lalo, Yuriy Pankratov
Intracellular Ca2+-signaling in astrocytes is instrumental for their brain “housekeeping” role and astroglial control of synaptic plasticity. An important source for elevating the cytosolic Ca2+ level in astrocytes is a release from endoplasmic reticulum which can be triggered via two fundamental pathways: IP3 receptors and calcium-induced calcium release (CICR) mediated by Ca2+-sensitive ryanodine receptors (RyRs). We explored the role for ryanodine receptors in the modulation of cytosolic Ca2+-signaling in the cortical and hippocampal astrocytes, astrocyte-neuron communication and astroglia modulation of synaptic plasticity. Our data demonstrate that ryanodine receptors are essential for astrocytic Ca2+-signaling and efficient astrocyte-neuron communications. The RyR-mediated CICR contributes to astrocytic control of synaptic plasticity and can underlie, at least partially, neuroprotective and cognitive effects of caffein.
A distinct, high affinity, alkaline phosphatase facilitates occupation of P-depleted environments by marine picocyanobacteria
Alberto Torcello-Requena, Andrew Murphy, Ian D. E. A. Lidbury, Frances D. Pitt, Richard Stark, Andrew D. Millard, Richard J. Puxty, Yin Chen, David J. Scanlan
Marine picocyanobacteria of the genera Prochlorococcus and Synechococcus, the two most abundant phototrophs on Earth, thrive in oligotrophic oceanic regions. While it is well known that specific lineages are exquisitely adapted to prevailing in situ light and temperature regimes, much less is known of the molecular machinery required to facilitate occupancy of these low-nutrient environments. Here, we describe a hitherto unknown alkaline phosphatase, Psip1, that has a substantially higher affinity for phosphomonoesters than other well-known phosphatases like PhoA, PhoX, or PhoD and is restricted to clade III Synechococcus and a subset of high light I-adapted Prochlorococcus strains, suggesting niche specificity.
N-terminal tagging of RNA Polymerase II shapes transcriptomes more than C-terminal alterations
Adam Callan-Sidat, Emmanuel Zewdu, Massimo Cavallaro, Juntai Liu, Daniel Hebenstreit
RNA polymerase II (Pol2) has a C-terminal domain (CTD) that is unstructured, consists of a large number of heptad repeats, and whose precise function remains unclear. Here, we investigate how altering the CTD’s length and fusing it with protein tags affects transcriptional output on genome-wide scale in mammalian cells, at single cell resolution. While transcription generally appears to occur in burst-like fashion, where RNA is predominantly made during short bursts of activity that are interspersed with periods of transcriptional silence, the CTD’s role in shaping these dynamics seems gene-dependent; global patterns of bursting appear mostly robust to CTD alterations
RecGraph: recombination-aware alignment of sequences to variation graphs
Jorge Avila Cartes, Paola Bonizzoni, Simone Ciccolella, Gianluca Della Vedova, Luca Denti, Xavier Didelot, Davide Monti, Yuri Pirola
In this paper, we present the extension of the notion of sequence-to-graph alignment to a variation graph that incorporates a recombination, so that the latter are explicitly represented and evaluated in an alignment. Moreover, we present a dynamic programming approach for the special case where there is at most a recombination—we implement this case as RecGraph. From a modelling point of view, a recombination corresponds to identifying a new path of the variation graph, where the new arc is composed of two halves, each extracted from an original path, possibly joined by a new arc. Our experiments show that RecGraph accurately aligns simulated recombinant bacterial sequences that have at most a recombination, providing evidence for the presence of recombination events.
Multiple toxins and a protease contribute to the aphid-killing ability of Pseudomonas fluorescens PpR24
Deepa Paliwal, Mojgan Rabiey, Tim H. Mauchline
Aphids are globally important pests causing damage to a broad range of crops. Due to insecticide resistance, there is an urgent need to develop alternative control strategies. In our previous work, we found Pseudomonas fluorescens PpR24 can orally infect and kill the insecticide-resistant green-peach aphid (Myzus persicae). However, the genetic basis of the insecticidal capability of PpR24 remains unclear. This comprehensive host–pathogen transcriptomic analysis provides novel insight into the molecular basis of bacteria-mediated aphid mortality and the potential of PpR24 as an effective biocontrol agent.
Imaging Single-Cell Ca2+ Dynamics of Brainstem Neurons and Glia in Freely Behaving Mice
Amol M. Bhandare, Nicholas Dale, Robert T. R. Huckstepp
In vivo brain imaging, using a combination of genetically encoded Ca2+ indicators and gradient refractive index (GRIN) lens, is a transformative technology that has become an increasingly potent research tool over the last decade. We have refined the intravital imaging technique to image deep brain nuclei in the ventral medulla oblongata, one of the most difficult brain structures to image due to the movement of brainstem structures outside the cranial cavity during free behaviour (head and neck movement), whose targeting requires GRIN lens insertion through the cerebellum—a key structure for balance and movement. Our protocol refines the implantation method of GRIN lenses, giving the best possible approach to image deep extracranial brainstem structures in awake rodents with improved cell rejection/acceptance criteria during analysis. This revised method paves the way to image challenging brainstem structures to investigate their role in complex behaviours such as breathing, circulation, sleep, digestion, and swallowing, and could be extended to image and study the role of cerebellum in balance, movement, motor learning, and beyond.