Biology subjects

LIU, H.

Publications and source records attributed to LIU, H..

3 recordsLinked to original sources

bioRxiv2024

Dimorphic Neural Network Architecture Prioritizes Sexual-related Behaviors in Male C.elegans

Neural network architecture determines its functional output. However, the detailed mechanisms are not well characterized. In this study, we focused on the neural network architectures of male and hermaphrodite C. elegans and the association with sexually dimorphic behaviors. We applied graph theory and computational neuroscience methods to systematically discern the features of these two neural networks. Our findings revealed that a small percentage of sexual-specific neurons exerted dominance throughout the entire male neural net-work, suggesting males prioritized sexual-related behavior outputs. Based on the structural and dynamical characteristics of two complete neural networks, sub-networks containing sex-specific neurons and their immediate neighbors, or sub-networks exclusively comprising sex-shared neurons, we predicted dimorphic behavioral outcomes for males and hermaphrodites. To verify the prediction, we performed behavioral and calcium imaging experiments and dissected a circuit that is specific for the increased spontaneous local search in males for mate-searching. Our research sheds light on the neural circuits that underlie sexually dimorphic behaviors in C. elegans, and provides significant insights into the inter-connected relationship between network architecture and functional outcomes at the whole-brain level.

neuroscience↗

bioRxiv2024

The fully activated open state of KCNQ1 controls the cardiac 'fight-or-flight' response

The cardiac KCNQ1+KCNE1 (IKs) channel regulates heart rhythm in both normal and stress conditions. Under stress, the {beta}-adrenergic stimulation elevates the intracellular cAMP level, leading to KCNQ1 phosphorylation by protein kinase A and increased IKs, which shortens action potentials to adapt to accelerated heart rate. An impaired response to the {beta}-adrenergic stimulation due to KCNQ1 mutations is associated with the occurrence of a lethal congenital long QT syndrome (type 1, also known as LQT1). However, the underlying mechanism of {beta}-adrenergic stimulation of IKs remains unclear, impeding the development of new therapeutics. Here we find that the unique properties of KCNQ1 channel gating with two distinct open states are key to this mechanism. KCNQ1s fully activated open (AO) state is more sensitive to cAMP than its intermediate open (IO) state. By enhancing the AO state occupancy, the small molecules ML277 and C28 are found to effectively enhance the cAMP sensitivity of the KCNQ1 channel, independent of KCNE1 association. This finding of enhancing AO state occupancy leads to a potential novel strategy to rescue the response of IKs to {beta}-adrenergic stimulation in LQT1 mutants. The success of this approach is demonstrated in cardiac myocytes and also in a high-risk LQT1 mutation. In conclusion the present study not only uncovers the key role of the AO state in IKs channel phosphorylation, but also provides a new target for anti-arrhythmic strategy. Significance statementThe increase of IKs potassium currents with adrenalin stimulation is important for "fight-or-flight" responses. Mutations of the IKs channel reducing adrenalin responses are associated with more lethal form of the type-1 long-QT syndrome (LQT). The alpha subunit of the IKs channel, KCNQ1 opens in two distinct open states, the intermediate-open (IO) and activated-open (AO) states, following a two-step voltage sensing domain (VSD) activation process. We found that the AO state, but not the IO state, is responsible for the adrenalin response. Modulators that specifically enhance the AO state occupancy can enhance adrenalin responses of the WT and LQT-associated mutant channels. These results reveal a mechanism of state dependent modulation of ion channels and provide an anti-arrhythmic strategy.

biophysics↗

bioRxiv2023

Crop microbiome responses to pathogen colonisation regulate the host plant defence

AimsSoil-borne pathogens severely damage the yield and quality of crops worldwide. Plant and soil microbiomes (e.g. in the rhizosphere) intimately interact with the plant, the pathogen and influence outcomes of disease infection. Investigation of how these microbiomes respond to disease infection is critical to develop solutions to control diseases. MethodsHere, we conducted a field experiment and collected healthy and crown rot disease infected (caused by Fusarium pseudograminearum, Fp) wheat plants. We investigated their microbiomes in different compartments, plant immune responses and interactions with the pathogen (Fp) aiming at advancing our knowledge on microbiome-mediated regulation of plant responses to pathogens. ResultsWe found that Fp colonised wheat plants in significant loads, accounting for 11.3% and 60.7% of the fungal communities in the rhizosphere and root endosphere, respectively. However, Fp presented with a small fraction of the leaf microbiome, up to 1.2%. Furthermore, Fp-infection led to significant changes in the composition of the microbial communities in the rhizosphere and root endosphere while had little impact on leaves. We further found that wheat defence signalling pathways, wheat microbiomes and the pathogen intimately correlated with each other in structural equation modelling. As such, we also identified ecological clusters explained changes in the wheat defence signalling pathways. Lastly, microbial co-occurrence network complexity was higher in Fp-infected plants relative to healthy plants, suggesting that Fp-infection has potentially induced more microbial interactions in plants. ConclusionsWe provide novel evidence that soil-borne diseases significantly disrupt belowground plant microbiomes influencing the responses of plant immunity to pathogens.

plant biology↗