Search

Abstract The valence of stimuli is shaped by various factors, including environmental cues, internal states, genetic variability, and past experience. However, the mechanisms behind this flexibility remain elusive. In the nematode C. elegans, we found that ethanol, an olfactory stimulus, can elicit opposite chemotaxis responses – attraction vs. aversion – depending on NaCl concentration, demonstrating the role of environmental factors in altering valence. Remarkably, a single chemosensory neuron, ASER, orchestrate this bidirectional ethanol chemotaxis by integrating information from both stimuli – ethanol and NaCl – into its neuronal activity dynamics. Specifically, different calcium dynamics in the ASER neuron differentially activate the signaling molecule CMK-1, thereby engaging different downstream interneurons and leading to opposite chemotaxis directions. Consistently, optogenetic manipulations of the ASER neuron reverse the chemotaxis directions, by altering its calcium dynamics. Our findings reveal a mechanism by which a single neuron integrates multisensory inputs to determine context-dependent behavioral valence, contributing to our current understanding of valence encoding.

Abstract Parkinson’s disease (PD) and Dementia with Lewy Bodies (DLB) are neurodegenerative disorders characterized by the accumulation of α-synuclein aggregates. α-synuclein forms droplets via liquid-liquid phase separation (LLPS), followed by liquid-solid phase separation (LSPS) to form amyloids, how this process is physiologically-regulated remains unclear. β-synuclein colocalizes with α-synuclein in presynaptic terminals. Here, we report that β-synuclein partitions into α-synuclein condensates promotes the LLPS, and slows down LSPS of α-synuclein, while disease-associated β-synuclein mutations lose these capacities. Exogenous β-synuclein improves the movement defects and prolongs the lifespan of an α-synuclein-expressing NL5901 Caenorhabditis elegans strain, while disease-associated β-synuclein mutants aggravate the symptoms. Decapeptides targeted at the α-/β-synuclein interaction sites are rationally designed, which suppress the LSPS of α-synuclein, rescue the movement defects, and prolong the lifespan of C. elegans NL5901. Together, we unveil a Yin-Yang balance between α- and β-synuclein underlying the normal and disease states of PD and DLB with therapeutical potentials.

Neurodegenerative diseases such as Alzheimer's disease and polyglutamine diseases are characterized by abnormal accumulation of misfolded proteins, leading to neuronal dysfunction and subsequent neuron death. However, there is a lack of studies that integrate molecular, morphological, and functional analyses in neurodegenerative models to fully characterize these time-dependent processes. In this study, we used C. elegans models expressing Aβ1-42 and polyglutamine to investigate early neuronal pathogenic features in olfactory neurons. Both models demonstrated significant reductions in odor sensitivity in AWB and AWC chemosensory neurons as early as day 1 of adulthood, while AWA chemosensory neurons showed no such decline, suggesting cell-type-specific early neuronal dysfunction. At the molecular level, Aβ1-42 or Q40 expression caused age-dependent protein aggregation and morphological changes in neurons. By day 6, both models displayed prominent protein aggregates in neuronal cell bodies and neurites. Notably, AWB neurons in both models showed significantly shortened cilia and increased instances of enlarged cilia as early as day 1 of adulthood. Furthermore, AWC neurons expressing Aβ1-42 displayed calcium signaling defects, with significantly reduced responses to odor stimuli on day 1, further supporting early behavioral dysfunction. In contrast, AWA neuron did not exhibit reduced calcium responses, consistent with the absence of detectable decreases in olfactory sensitivity in these neurons. These findings suggest that decreased calcium signaling and dysfunction in specific sensory neuron subtypes are early indicators of neurodegeneration in C. elegans, occurring prior to the formation of visible protein aggregates. We found that the ER unfolded protein response (UPR) is significantly activated in worms expressing Aβ1-42. Activation of the AMPK pathway alleviates olfactory defects and reduces fibrillar Aβ in these worms. This study underscores the use of C. elegans olfactory neurons as a model to elucidate mechanisms of proteostasis in neurodegenerative diseases and highlights the importance of integrated approaches.

Video Super-Resolution (VSR) is the task of reconstructing high-resolution (HR) video sequences from low-resolution (LR) video sequences. Apart from spatial information of reference frames, temporal information of neighboring frames is also important for reconstruction. Current VSR methods usually take advantage of the temporal information through optical flow estimation and compensation. However, optical flow estimation is often inaccurate and difficult, which may result in artifacts or blurring in the reconstructed frames. In this paper, we propose a Novel Flow-guided Deformable Alignment Module (NFDAM) for frame alignment. In this module, a lightweight optical network FNet is designed to estimate optical flow as a coarse offset, which then guides the deformable convolution at the feature and image level. On this basis, we propose a Flow-guided Gated Bidirectional Recurrent Separated Network (FGBRSN) for VSR, in which a gated recurrent structure is designed to leverage long-term information and a multilevel residual fusion approach is used in upsampling module. Our experiments on public datasets have shown that the proposed method improves both quantitative evaluation and visual effects compared with the existing methods.

Koumiss, a traditional fermented dairy product made from fresh mare milk, is a sour beverage that contains an abundance of microbial communities, including lactic acid bacteria, yeast and others. Firstly, probiotics such as Lacticaseibacillus in koumiss can induce the secretion of immunoglobulin G in serum and interleukin-2 in the spleen while beneficial Saccharomyces can secrete antibacterial compounds such as citric acid and ascorbic acid for specific immunopotentiation. Additionally, more isoflavone in koumiss can regulate estrogen levels by binding to its receptors to prevent breast cancer directly. Bile salts can be converted into bile acids such as taurine or glycine by lactic acid bacteria to lower cholesterol levels in vivo. Butyric acid secretion would be increased to improve chronic gastrotis by regulating intestinal flora with lactic acid bacteria. Finally, SCFA and lCFA produced by Lacticaseibacillus inhibit the reproduction of pathogenic microorganisms for diarrhea prevention. Therefore, exploring the mechanisms underlying multiple physiological functions through utilizing microbial resources in koumiss represents promising avenues for ameliorating chronic diseases.

Multisensory integration refers to sensory inputs from different sensory modalities being processed simultaneously to produce a unitary output. Surrounded by stimuli from multiple modalities, animals utilize multisensory integration to form a coherent and robust representation of the complex environment. Even though multisensory integration is fundamentally essential for animal life, our understanding of the underlying mechanisms, especially at the molecular, synaptic and circuit levels, remains poorly understood. The study of sensory perception in Caenorhabditis elegans has begun to fill this gap. We have gained a considerable amount of insight into the general principles of sensory neurobiology owing to C. elegans’ highly sensitive perceptions, relatively simple nervous system, ample genetic tools and completely mapped neural connectome. Many interesting paradigms of multisensory integration have been characterized in C. elegans, for which input convergence occurs at the sensory neuron or the interneuron level. In this narrative review, we describe some representative cases of multisensory integration in C. elegans, summarize the underlying mechanisms and compare them with those in mammalian systems. Despite the differences, we believe C. elegans is able to provide unique insights into how processing and integrating multisensory inputs can generate flexible and adaptive behaviors. With the emergence of whole brain imaging, the ability of C. elegans to monitor nearly the entire nervous system may be crucial for understanding the function of the brain as a whole.