Chiba, N. | Search bioRxiv

bioRxiv2025

Rapid water flow navigates long-distance migration of thermophilic bacteria

Bacteria thrive in nearly all environments on Earth, demonstrating remarkable adaptability to physical stimuli, as well as chemicals and light. However, the mechanisms by which bacteria locate and settle in ecological niches optimal for their growth remains poorly understood. Here, we show that Thermus thermophilus, a highly thermophilic non-flagellated species of bacteria, exhibits positive rheotaxis, navigating upstream in unidirectional rapid water flow. Mimicking their natural habitat at 70{degrees}C with a water current under optical microscopy, cells traveled distances up to 1 mm in 30 min, with infrequent directional changes. This long-distance surface migration is driven by type IV pili, facilitating vertical attachment at the cell pole, and shear-induced tilting of the cell body, resulting in alignment of the leading pole toward the direction of water flow. Direct visualization of T4P filaments and their dynamics revealed that rheotaxis is triggered by weakened attachment at the cell pole, regulated by ATPase activity, which was further validated by a mathematical modeling. Flow experiments on 16 bacterial strains and species in the Deinococcus-Thermus phylum revealed that positive rheotaxis is highly conserved among rod-shaped Thermaceae, whereas no rheotactic behavior was observed in spherical-shaped Deinococcus. Our findings suggest that thermophilic bacteria reach their ecological niches by responding to the physical stimulus of rapid water flow, a ubiquitous feature in hot spring environments. This study highlights unforeseen survival strategies, showcasing an evolutionary adaptation to a surface-associated lifestyle where swimming bacteria would otherwise be swept away.

microbiology↗

bioRxiv2024

YORU: social behavior detection based on user-defined animal appearance using deep learning

The creation of tools using deep learning methodologies for animal behavior analysis has revolutionized neuroethology. They allow researchers to analyze animal behaviors and reveal causal relationships between specific neural circuits and behaviors. However, the application of such annotation/manipulation systems to social behaviors, in which multiple individuals interact dynamically, remains challenging. Here, we applied an object detection algorithm to classify animal social behaviors. Our system, packaged as "YORU" (Your Optimal Recognition Utility), classifies animal behaviors, including social behaviors, based on the shape of the animal as a "behavior object". It successfully classified several types of social behaviors ranging from vertebrates to insects. We also integrated a closed-loop control system for operating optogenetic devices into the YORU package. YORU enables real-time delivery of photostimulation feedback to specific individuals during specific behaviors, even when multiple individuals are close together. We hope that the YORU system will accelerate the understanding of the neural basis of social behaviors.

neuroscience↗

bioRxiv2023

CTRP7 as a Molecular Biomarker for Predicting Responsiveness to Pulmonary Vasodilators: Insights from Human and Animal Studies in Pulmonary Arterial Hypertension

BackgroundPulmonary arterial hypertension (PAH) is a life-threatening condition. Although pulmonary vasodilators have shown promise in managing PAH, the overall prognosis improvement is modest, partly because of the absence of a biomarker for guiding their selection. This study aimed to identify the molecular-based predictors of responsiveness to pulmonary vasodilators by combining human and basic studies. Methods and ResultsRNA sequencing was conducted on cultured pulmonary artery smooth muscle cells (PASMCs) from patients with and without PAH, identifying variations in 2,076 genes. The candidates were narrowed down to established clinical biomarkers, and their plasma levels were assessed in PAH (n = 123) and non-PAH patients (n = 25). C1q/TNF-related protein 7 (CTRP7) exhibited elevated expression in PASMCs (5.37 Log2 fold change, p < 0.01), and the plasma of patients with PAH compared to non-PAH (28.2 (9.3- 101.2) vs. 9.32 (4.6-18.6) ng/ml, p < 0.01). A plasma assessment revealed a significant correlation between CTRP7 and interleukin 6 (IL-6) levels (r = 0.544, p < 0.001). Chromatin immunoprecipitation demonstrated that IL-6 upregulated CTRP7 expression in PASMCs. Among pivotal factors, CTRP7 reduced prostacyclin analog receptor (PTGIR) expression through Rab5a-mediated internalization, resulting in diminished responsiveness to selexipag (a prostacyclin analog). Incorporating the human study, hypoxic PH mice demonstrated reduced PTGIR expression in the pulmonary arteries, which correlated with limited responses to selexipag treatment (low cardiac output and persistent pulmonary artery resistance), which was mitigated by silencing CTRP7 expression in the pulmonary arteries using adeno-associated virus 6. ConclusionsAmong the candidates with increased expression in patients with PAH based on RNA sequencing of PASMCs, CTRP7 demonstrated elevated plasma levels compared to non-PAH. CTRP7 regulated PTGIR internalization via inflammation and Rab5a, influencing responsiveness to selexipag. CTRP7 emerged as a compelling biomarker for predicting responsiveness to prostacyclin analogs, potentially advancing the development of innovative PAH treatment strategies. Novel and SignificanceO_ST_ABSWhat Is Known?C_ST_ABSO_LIPulmonary arterial hypertension (PAH) is a life-threatening vascular disease with limited treatment options. C_LIO_LIAlthough pulmonary vasodilators have shown promise in managing PAH, the overall improvement in prognosis is modest. C_LIO_LIFurther research is needed to understand the molecular features of pulmonary vasodilators and identify biomarkers for appropriate selection. C_LI What New Information Does This Article Contribute?O_LIC1q/TNF-related protein 7 (CTRP7) was found to be elevated in the pulmonary artery smooth muscle cells (PASMCs) and plasma of patients with pulmonary arterial hypertension (PAH). C_LIO_LIThis study established a connection between inflammation and pulmonary vascular responsiveness via CTRP7-mediated internalization and degradation of the prostacyclin analog receptor. C_LIO_LIThis study indicated the possibility of using plasma CTRP levels as a clinical biomarker to monitor pulmonary responsiveness, which can contribute to the development of novel treatment strategies for patients with PAH. C_LI Pulmonary arterial hypertension (PAH) is a life-threatening and enigmatic lung vascular disorder characterized by progressive pulmonary vascular remodeling and vasoconstriction. Despite significant advancements in the treatment of PAH using pulmonary vasodilators, some individuals display limited responses, primarily due to a lack of understanding of the molecular features of each pulmonary vasodilator and the absence of a biomarker for appropriate selection. The present study aimed to identify promising biomarkers for predicting a patients responsiveness to pulmonary vasodilators through a two-step approach, involving RNA sequencing of PASMCs and the measurement of plasma levels. CTRP7 emerged as a prominent biomarker, displaying increased expression in both PASMCs and plasma obtained from patients with PAH. Mechanistically, IL-6 transcriptionally modulated CTPR7, leading to the internalization and degradation of PTGIR, resulting in a reduced response to selexipag (prostacyclin analog) in PASMCs. Integrating the human studies, a hypoxic mouse model exhibited lower PTGIR expression in pulmonary arteries, correlating with limited responses to selexipag treatment, which were ameliorated by silencing CTRP7 expression in pulmonary arteries using adeno-associated virus 6 transduction. This study collectively demonstrates that CTRP7 emerges as a compelling biomarker for predicting responsiveness to prostacyclin analogs, with the potential to advance the development of innovative PAH treatment strategies.

molecular biology↗