Biology subjects

Luo, Y.

Publications and source records attributed to Luo, Y..

At least 163 records · Page 9Linked to original sources

bioRxiv2024

The role of PilU in the surface behaviors of Pseudomonas aeruginosa

In Pseudomonas aeruginosa, the dynamic activity of type IV pilus (TFP) is essential for various bacterial behaviors. While PilU is considered a homolog of the TFP disassembling motor PilT, its specific roles remain unclear. Using pilus visualization and single-cell tracking techniques, we characterized TFP dynamics and surface behaviors in wild-type and {Delta}pilU mutants. We found that {Delta}pilU cells displayed increased TFP numbers but reduced cell movement and delayed microcolony formation. Interestingly, beyond affecting the twitching motility, {Delta}pilU cells formed a thick multilayered colony edge on semi-solid surfaces, slowing colony expansion. Cell-cell collision responses changed from touch-turn dominance in wild-type to touch-upright dominance in {Delta}pilU, affecting colony morphology and expansion. These findings expand our understanding of PilUs physiological roles and provide potential targets for developing strategies to control P. aeruginosa biofilm formation and virulence. IMPORTANCEThe dynamic function of TFP can help cells to search appropriate spatial positions and perceive external environments, and is crucial for a variety of cell behaviors including cell movement, pathogenesis, natural transformation and biofilm formation. Beyond the current picture of PilU in generating high retraction forces through a PilT-dependent manner, this study revealed more roles of PilU in cell surface behaviors including single cell behavior like twitching and multicellular behaviors such as microcolony formation and colony expansion. These findings expand our understanding on the physiological roles of PilU in the surface behaviors of P. aeruginosa, and provide us insight in developing TFP-based methods to control the pathogenicity and biofilm formation of P. aeruginosa.

microbiology↗

bioRxiv2024

High-coverage, massively parallel sequencing of single-cell genomes with CAP-seq

Microbial communities are extraordinarily diverse and play crucial roles in health and disease, yet current methods lack the resolution and scalability needed to dissect their genomic and ecological complexity at the single-cell level. Here, we present CAP-seq, a high-throughput single-microbe genomics platform that combines hydrogel-based semi-permeable encapsulation with minimal microfluidics to recover thousands of single-amplified genomes (SAGs) with long reads and high completeness at low sequencing depth. We benchmarked CAP-seq using defined microbial communities, demonstrating strain-level resolution, accurate detection of rare taxa, and genome recovery exceeding 50% at [~]10x coverage. Applying CAP-seq to pediatric Clostridioides difficile infection microbiomes, we generated a high-resolution single-cell atlas comprising tens of thousands of SAGs across hundreds of species. Host-resolved profiling of the cryptic plasmid pBI143 revealed previously hidden low-abundance host associations, six new plasmid versions, and their coexistence within individuals, indicating complex plasmid evolution in situ. Longitudinal analysis during fecal microbiota transplantation and vancomycin treatment uncovered dynamic remodeling of microbial hosts, antimicrobial resistance genes, and plasmids at single-cell resolution. CAP-seq enables scalable, high-performance single-cell genomics and provides a practical, widely accessible platform for microbiome analysis, paving the way for large-scale exploration of microbial dark matter and host-microbe interactions across diverse ecosystems.

genomics↗

bioRxiv2024

Impact of Acetate and Optimized Nitrate Levels on Mixotrophic Growth and Protein Dynamics in Chlorella Sorokiniana

Microalgae are well-known for their role as sustainable bio-factories, offering a promising solution to the global food and nutrition crisis. To clarify the potential of Chlorella sorokiniana UTEX 1230 for food applications, particularly as an alternative protein source, the study employed a mixotrophic cultivation mode with sodium acetate (NaAc) as a cost-effective organic carbon (NaAc-C) source. Varying levels of NaAc-C and nitrate-sourced nitrogen were investigated, optimizing the effect of metabolic characteristics of the microalgal growth. The designed heterotrophic cultivation confirmed the ability of C. sorokiniana UTEX 1230 to grow on NaAc-C, and then the mixotrophic cultures, when supported by both NaAc-C and CO2, exhibited superior growth performance, achieving double the biomass concentration compared to the autotrophic control. The addition of nitrogen (750 mg/L NaNO) facilitated the thorough metabolism of NaAc-C and enhanced photosynthetic activity indicated by a 196% increase in pigment levels, which resulted in a maximum biomass concentration of 2.82 g/L in the 150 mM NaAc-C group. A detailed analysis of nitrogen and protein concentrations over time revealed that higher nitrogen availability led to greater protein accumulation which was then degraded to support essential life activities under nitrogen starvation. Therefore, it is suggested that supplementing nitrate on the 3rd day and harvesting on the 4th day could be strategically implemented to increase protein yield from 0.17 g/L/d to 0.34 g/L/d. These findings offer theoretical guidance for further refining this microalgal strain for use as an alternative protein.

bioengineering↗

bioRxiv2024

HBIcloud: An Integrative Multi-Omics Analysis Platform

As biological datasets have grown exponentially in size and complexity, there has been an increasing need for integrative tools that can handle diverse data types and facilitate comprehensive analyses. Traditional methods often require significant computational expertise, creating barriers for many researchers. HBIcloud is a comprehensive online platform designed to facilitate multi-omics data analysis by integrating a wide array of tools across genomics, transcriptomics, proteomics, metabolomics, phenomics, and multi-omics integration. Developed to address the growing complexity and volume of biological data, HBIcloud provides researchers with a powerful and user-friendly resource for conducting sophisticated analyses without the need for extensive programming skills. With a total of 94 tools, the platform offers standardized workflows, extensive parameter options, and rich documentation, catering to the diverse needs of the scientific community. The research behind HBIcloud aimed to create a centralized, user-friendly platform that simplifies the analytical process, enabling researchers to focus on scientific discovery rather than technical challenges. By integrating a wide array of tools and offering extensive support and documentation, HBIcloud addresses the critical need for standardized, reproducible workflows in multi-omics research. This paper presents a detailed overview of HBIcloud, highlighting its development background, key features, and its significant contribution to advancing multi-omics research. Furthermore, we discuss the future prospects of HBIcloud, including planned enhancements and its potential for high citation impact within the scientific community. By providing a robust and versatile platform, HBIcloud aims to accelerate discovery and innovation in the field of multi-omics, fostering collaborative research and expanding the boundaries of biological understanding. The official website of HBIcloud is https://bioinformatics.hainanu.edu.cn/HBIcloud/.

bioinformatics↗

bioRxiv2024

OsWHY1/OsTRXz/OsMORFs complex is essential for RNA modification and early chloroplast development in rice

WHIRLY (WHY) proteins are single-stranded DNA/RNA-binding proteins that play multifaceted roles in various plant species. The regulatory mechanisms of WHY proteins in rice remains blank. Here we demonstrate that OsWHY1 in rice is required for early chloroplast development. CRISPR/Cas9-generated oswhy1 knockout lines displayed albino seedling phenotypes, abnormal chloroplast structure and comprised redox balance in leaves. OsWHY1 interacts with multiple plastid proteins, including the thioredoxin OsTRXz and two multiple organellar RNA editing factors (OsMORF8 and OsMORF9) in chloroplasts. Accordingly, several plastid genes dependent on plastid-encoded RNA polymerase (PEP) in the oswhy1 mutants were significantly depressed at both transcript and protein levels. The editing of rps14 transcripts and splicing of rpl2, along with their protein expression, were defective in the oswhy1 mutants. OsWHY1 exhibited RNA-binding activity, specifically binding to rps14 and rpl2 precursor RNAs, which underscores its role as a post-transcriptional regulator essential for normal protein synthesis in chloroplasts. Loss-of- function mutants of either OsWHY1 or OsMORF9 and OsTRXz displayed albino phenotypes, disrupted H2O2 homeostasis, and defective RNA processing in rps14 and rpl2, suggesting the OsWHY1-OsTRXz-OsMORFs regulatory module is vital for maintaining chloroplast stability and integrity through its RNA-binding activity and its role in recruiting OsTRXz and OsMORFs to ensure proper RNA modification. One sentence summaryOsWHY1 is integral to chloroplast development in rice through its RNA-binding activity and its role in recruiting OsTRXz and OsMORFs to ensure proper RNA modification.

plant biology↗

bioRxiv2024

Mammalian PIEZO channels rectify anionic currents

Under physiological conditions, mammalian PIEZO channels (PIEZO1 and PIEZO2) elicit transient currents mostly carried by monovalent and divalent cations. PIEZO1 is also known to permeate chloride ions, with a Cl- / Na+ permeability ratio of about 0.2. Yet, little is known about how anions permeate PIEZO channels. Here, by separately measuring sodium and chloride currents using non-permanent counter-ions, we show that both PIEZO1 and PIEZO2 rectify chloride currents outwardly, favoring entry of chloride ions at voltages above their reversal potential, whereas little to no rectification was observed for sodium currents. Interestingly, chloride currents elicited by 9K, an anion-selective PIEZO1 mutant harboring multiple positive residues along intracellular pore fenestrations, also rectify but in the inward direction. Molecular dynamics simulation indicate that the inward rectification of chloride currents in 9K correlates with the largely positive electrostatic potential at the intracellular pore entrance, suggesting that rectification can be tuned by pore polarity. These results demonstrate that the pore of mammalian PIEZO channels inherently rectifies chloride currents. Statement of significanceMechanosensitive PIEZO ion channels play many important roles across cells and tissues. Their open pore facilitates the flow of cations down their electrochemical gradients, eliciting sodium-driven membrane depolarization and calcium-dependent signaling under physiological conditions. Yet, these channels also permeate chloride ions. In this study, we show that the two mammalian PIEZO channel homologs preferentially permeate chloride ions into the cells at voltages more positive than the chloride reversal potential. Although PIEZOs permeate cations more effectively than chloride ions, the influx of chloride ions mediated by PIEZOs could participate in certain physiological processes.

biophysics↗

bioRxiv2024

Temporally resolved single-cell RNA sequencing reveals protective and pathological responses during herpes simplex virus 1 CNS infection

Herpes Simplex Virus 1 (HSV-1) is a common human neurotropic virus with the majority of adults harboring latent-recurrent infections. In rare cases, HSV-1 infection can access the central nervous system through the neuronal route and develop into life-threatening encephalitis. Here, we used a mouse model for HSV-1 infection to describe the transcriptomic profile of the infected brain stem at the single-cell level and with temporal resolution. Among resident brain cells, microglia increased in proportion during the course of infection, while astrocytes, pericytes, and endothelial cell levels decrease. At the levels of peripheral immune cells, we found notably monocytes to strongly influx the infected brain. Large dynamic changes were found in the abundance of subpopulations of the different cell types following virus infection. For instance, we identify one subpopulation of microglia exhibiting very high type I interferon and chemokine expression early during infection. This population was also enriched for viral transcripts, suggesting localization at foci of infection, and orchestrating recruitment of other immune cells. In contrast, for the infiltrating monocytes, we identified a larger panel of unique subpopulations with antiviral and inflammatory phenotypes, and found not all of these being highly positive for viral transcripts, thus indicating monocyte activities beyond the infected brain areas. Finally, investigation of endothelial cell cross-talk with other cell types revealed that cytokines derived from microglia and monocyte, but also T cells, contribute to disturbance of the blood brain barrier. Our work thus reveals for the first time the complex nature of the cellular response in the virus-infected brain, which seeks to eliminate infection but can also prime for pathological changes.

immunology↗

bioRxiv2024

Bibacillin 1: A two-component lantibiotic from Bacillus thuringiensis

Here we describe bibacillin 1 - a two-component lantibiotic from Bacillus thuringiensis. The peptides that comprise bibacillin 1 are modified by a class II lanthipeptide synthetase Bib1M producing two peptides with non-overlapping ring patterns that are reminiscent of cerecidin and the short component of the enterococcal cytolysin (CylLS"), a virulence factor associated with human disease. Stereochemical analysis demonstrated that each component contains LL-methyllanthionine and DL-lanthionine. The mature bibacillin 1 peptides showed cooperative bactericidal activity against Gram-positive bacteria, including members of ESKAPE pathogens, and weak hemolytic activity. Optimal ratio studies suggest that bibacillin 1 works best when the components are present in a 1:1 ratio, but near optimal activity was observed at ratios strongly favouring one component over the other, suggesting that the two peptides may have different but complementary targets. Mechanism of action studies suggest a lipid II-independent killing action distinguishing bibacillin 1 from two other two-component lantibiotics haloduracin and lacticin 3147. One of the two components of bibacillin 1 showed cross reactivity with the cytolysin regulatory system. These result support the involvement of bibacillin 1 in quorum sensing and raise questions about the impact of CylLS"-like natural products on lanthipeptide expression in diverse bacterial communities.

biochemistry↗

bioRxiv2024

Complete sequencing of ape genomes

We present haplotype-resolved reference genomes and comparative analyses of six ape species, namely: chimpanzee, bonobo, gorilla, Bornean orangutan, Sumatran orangutan, and siamang. We achieve chromosome-level contiguity with unparalleled sequence accuracy (<1 error in 500,000 base pairs), completely sequencing 215 gapless chromosomes telomere-to-telomere. We resolve challenging regions, such as the major histocompatibility complex and immunoglobulin loci, providing more in-depth evolutionary insights. Comparative analyses, including human, allow us to investigate the evolution and diversity of regions previously uncharacterized or incompletely studied without bias from mapping to the human reference. This includes newly minted gene families within lineage-specific segmental duplications, centromeric DNA, acrocentric chromosomes, and subterminal heterochromatin. This resource should serve as a definitive baseline for all future evolutionary studies of humans and our closest living ape relatives.

genomics↗

bioRxiv2024

CIB2 as a Ca2+ Sensor for Auditory Mechano-Electrical Transduction and Linked to Genetic-Heterogeneity of TMC1 in Hearing Loss

Non-syndromic sensorineural hearing loss is characterized by genetic heterogeneity, leading to potential clinical misdiagnosis. TMC1, a unique causative gene associated with deafness, exhibits variants with autosomal dominant and recessive inheritance patterns. TMC1 codes for the transmembrane channel-like 1 (TMC1), a key component of the mechano-electrical transduction (MET) machinery for hearing. However, the molecular mechanism of Ca2+ regulation in MET, which is essential for sound perception, remains unclear. CIB2, another MET component associated with deafness, can bind with calcium and may play a role in MET gating. Our study reveals that the TMC1-CIB2 complex undergoes a Ca2+-induced conformational change, highlighting the crucial role of Ca2+ in MET. We identified a vertebrate-specific binding site on TMC1, named CR3, that interacts with apo CIB2, with the binding interface linked to hearing loss. Using an in-vivo animal model, we demonstrated that disruption of the calcium-sensing site of CIB2 perturbs the MET channel conductivity, confirming its role as a Ca2+ sensor for MET. Additionally, after systematically analyzing the hearing-loss variants, we observed that dominant mutations of TMC1 are often located near the ion pore or at the binding interfaces with the Ca2+ sensor CIB2. This provides a detailed mechanism of the genetic heterogeneity of TMC1 in hearing loss at an atomic level.

molecular biology↗

bioRxiv2024

Empowering Integrative and Collaborative Exploration of Single-Cell and Spatial Multimodal Data with SGS

Recent advancements in single-cell and spatial omics technologies have revolutionized our ability to capture multiple modalities data at a genome-wide scale within individual cells. However, visualizing these large-scale, high-dimensional, and complex datasets poses significant challenges. Here, we present SGS, a user-friendly, collaborative and versatile browser for visualizing single-cell and spatial multiomics data. SGS incorporates a novel genome browser framework, flexible visualization modules and a multi-panel adaptive communication mechanism to enable the synchronous visualization of diverse datasets. Notably, SGS empowers users with advanced capabilities for comparative visualization, through features like scCompare, scMultiView, and dual-chromosome module. Additionally, by adopting the "workstation concept", SGS enables data fast visualization and collaborative exploration. We showcase the potential of SGS in the comparative visualization and coordinated exploration of mutlimodal data with two examples. SGS is publicly available at https://sgs.bioinfotoolkits.net/home.

bioinformatics↗

bioRxiv2024

Trait anxiety impairs reciprocity behavior: A multi-modal and computational modeling study

Anxiety significantly impacts reciprocal behavior, crucial for positive social interactions. The neurocomputational mechanisms of anxietys effects on the core (individual propensity) and peripheral (decision context) factors shaping reciprocity remain unclear. Here, we investigated reciprocity in individuals with low and high trait anxiety using a binary trust game with gain/loss framing, combining computational modeling, eye-tracking, and event-related potentials (ERPs). Our computational model, validated by eye-tracking data, identified four psychological components driving reciprocal behavior: reward, guilt aversion, superiority aversion, and superiority attraction. Regarding the core of reciprocity, trait anxiety diminished both overall reciprocity and specific psychological components like guilt aversion and superiority attraction, irrespective of context. The reduction in guilt aversion was supported by ERP findings showing decreased P2 (selective attention) and increased LPP (emotion regulation) amplitudes in anxious individuals. Regarding the periphery of reciprocity, trait anxiety altered the contextual perception of both superiority aversion and reward. Further, trait anxiety reversed the perception of superiority aversion from gain to loss contexts, a pattern that was linked to the N2 amplitudes (cognitive control). Our findings revealed distinct effects of trait anxiety on core and peripheral factors in reciprocity, offering potential targets for interventions aimed at improving reciprocity in individuals with anxiety disorders.

neuroscience↗

bioRxiv2024

Droplet-AI-empowered high-throughput screening of cell-free gene expression

Cell-free gene expression (CFE) systems enable transcription and translation using crude cellular extracts, offering a versatile platform for synthetic biology by eliminating the need to maintain living cells. This allows direct manipulation of molecular components and the focused synthesis of specific products. However, the optimization of CFE systems is constrained by cumbersome composition, high costs, and limited yields due to numerous additional components required to maintain biocatalytic efficiency. While optimizing such complicated systems is daunting for existing high-throughput screening means, we introduce DropAI, a droplet-based, AI-driven screening strategy designed to optimize CFE systems with high throughput and economic efficiency. DropAI employs microfluidics to generate picoliter reactors and utilizes a fluorescent color-based coding-decoding system to address and screen a vast array of additive combinations. The in-droplet screening is complemented by in silico optimization, where experimental results train a machine-learning model to estimate the contribution of the components and predict high-yield combinations, which are then validated in vitro. Applying DropAI to an Escherichia coli-based CFE system, we simplified a set of 12 additives to only 3 essential components. Through further optimization, we achieved a 2.1-fold cost reduction and a 1.9-fold increase in yield for the expression of superfolder green fluorescent protein (sfGFP). This optimized formulation was further validated across 12 different proteins. Notably, the established E. coli model is successfully adapted to a Bacillus subtilis-based system through transfer learning, leading to doubled yield through prediction. DropAI thus offers a generalizable and scalable method for optimizing CFE systems, enhancing their potential for biochemical engineering and biomanufacturing applications.

bioengineering↗

bioRxiv2024

Mealtime alters daily rhythm in nuclear O-GlcNAcome to regulate hepatic gene expression

The liver circadian clock and hepatic transcriptome are highly responsive to metabolic signals generated from feeding-fasting rhythm. Previous studies have identified a number of nutrient-sensitive signaling pathways that could interpret metabolic input to regulate rhythmic hepatic biology. Here, we investigated the role of O-GlcNAcylation, a nutrient-sensitive post-translational modification (PTM) in mediating metabolic regulation of rhythmic biology in the liver. We observe daily oscillation of global nuclear protein O-GlcNAcylation in the liver of mice subjected to night-restricted feeding (NRF) using label-free global O-GlcNAc proteomics. Additional site-specific O-GlcNAc analysis by tandem mass tag mass spectrometry further supports temporal differences in O-GlcNAcylation by revealing day-night differences. Proteins involved in gene expression are enriched among rhythmically O-GlcNAcylated proteins, suggesting rhythmic O-GlcNAcylation may directly regulate the daily rhythmicity of the hepatic transcriptome. We show that rhythmic O-GlcNAcylation can also indirectly modulate the hepatic transcriptome by interacting with phosphorylation. Several proteins harboring O-GlcNAcylation-phosphorylation interplay motif exhibit rhythmic O-GlcNAcylation and phosphorylation. Specifically, we show that O-GlcNAcylation occurs at a phospho-degron of a key circadian transcriptional activator, circadian locomotor output cycles kaput (CLOCK), thus regulating its stability and transcriptional output. Finally, we report that day-restricted feeding (DRF) in the nocturnal mouse significantly alters O-GlcNAcylation rhythm. Whereas global O-GlcNAcylation analysis indicates dampening of global O-GlcNAcylation rhythm in mice fed under DRF, site-specific analysis reveals differential responses of O-GlcNAc sites when timing of food intake is altered. Notably, a substantial number of O-GlcNAcylation sites exhibit inverted day-night profiles when mice are subjected to DRF. This suggests the dysregulation of daily nuclear protein O-GlcNAcylation rhythm may contribute to the disruption in liver transcriptomic rhythm previously observed in DRF condition. In summary, our results provide new mechanistic insights into metabolic regulation of daily hepatic transcriptomic rhythm via interplay between O-GlcNAcylation and phosphorylation and shed light on the deleterious effects of improper mealtimes.

physiology↗

bioRxiv2024

Direcred Micro-Ecology Application System: On-site One-step Fermentation Facilitating Microbial Application through Theoretical and Equipment Innovation

Functional microbial agents play a crucial role in various fields such as agriculture, feed fermentation, aquaculture, and environmental protection. However, traditional microbial agents were confronted with critical challenges such as limited shelf-life, reduced activity, and inconsistent efficacy. In this case, we innovatively proposed the concept of Directed Micro-Ecology (DME) and developed its application system, including a core module named DME intelligent fermentor (DME25). Over 40 functional strains, including bacterial strains and fungus strains, were successfully cultured to 10[~]50 x108 CFU/mL within 20[~]48 h and maintained a relatively low contamination rate (<2.5%). Finally, the stability and effectiveness of these DME-fermented strains were validated in different application areas, all of which exhibited perfect functional characteristics. Firstly, the bacillus strains inhibited the progression of wilt disease and significantly improved the growth of tomatoes. Secondly, all tested lactobacillus strains improved the nutrition and quality of fermented feed, complying with feed industry standards. Lastly, the ammonia nitrogen concentration, nitrite concentration of aquaculture water and phosphate concentration, COD of aquaculture tail water were significantly reduced within 1[~]4 d. The successful application of the DME intelligent fermentor in different fields marks a pivotal breakthrough in technological innovation of microbial agents on-site one-step fermentation. This technological advancement opens new avenues for enhancing the stability and effectiveness of microbial agents, infusing powerful impetus to the development of microbial application.

microbiology↗

bioRxiv2024

Escalation of genome defense capacity enables control of an expanding meiotic driver

SummaryFrom RNA interference to chromatin silencing, diverse genome defense pathways silence selfish genetic elements to safeguard genome integrity1,2. Despite their diversity, different defense pathways share a modular organization, where numerous specificity factors identify diverse targets and common effectors silence them. In the PIWI-interacting RNA (piRNA) pathway, which controls selfish elements in the metazoan germline, diverse target RNAs are first identified by complementary base pairing with piRNAs and then silenced by PIWI-clade nucleases via enzymatic cleavage1,3. Such a binary architecture allows the defense systems to be readily adaptable, where new targets can be captured via the innovation of new specificity factors4,5. Thus, our current understanding of genome defense against lineage-specific selfish genes has been largely limited to the evolution of specificity factors, while it remains poorly understood whether other types of innovations are required. Here, we describe a new type of innovation, which escalates the defense capacity of the piRNA pathway to control a recently expanded selfish gene in Drosophila melanogaster. Through an in vivo RNAi screen for repressors of Stellate--a recently evolved and expanded selfish meiotic driver6-8--we discovered a novel defense factor, Trailblazer. Trailblazer is a transcription factor that promotes the expression of two PIWI-clade nucleases, Aub and AGO3, to match Stellate in abundance. Recent innovation in the DNA-binding domain of Trailblazer enabled it to drastically elevate Aub and AGO3 expression in the D. melanogaster lineage, thereby escalating the silencing capacity of the piRNA pathway to control expanded Stellate and safeguard fertility. As copy-number expansion is a recurrent feature of diverse selfish genes across the tree of life9-12, we envision that augmenting the defense capacity to quantitatively match selfish genes is likely a repeatedly employed defense strategy in evolution.

genetics↗

bioRxiv2024

MCP5, a methyl-accepting chemotaxis protein regulated by both the Hk1-Rrp1 and Rrp2-RpoN-RpoS pathways, is required for the immune evasion of Borrelia burgdorferi

Borrelia (or Borreliella) burgdorferi, the causative agent of Lyme disease, is a motile and invasive zoonotic pathogen, adept at navigating between its arthropod vector and mammalian host. While motility and chemotaxis are well established as essential for its enzootic cycle, the function of methyl-accepting chemotaxis proteins (MCPs) in the infectious cycle of B. burgdorferi remains unclear. In this study, we demonstrate that MCP5, one of the most abundant MCPs in B. burgdorferi, is differentially expressed in response to environmental signals as well as at different stages of the pathogens enzootic cycle. Specifically, the expression of mcp5 is regulated by the Hk1-Rrp1 and Rrp2-RpoN-RpoS pathways, which are critical for the spirochetes colonization of the tick vector and mammalian host, respectively. Infection experiments with an mcp5 mutant revealed that spirochetes lacking MCP5 could not establish infections in either C3H/HeN mice or Severe Combined Immunodeficiency (SCID) mice, which are defective in adaptive immunity, indicating the essential role of MCP5 in mammalian infection. However, the mcp5 mutant could establish infection and disseminate in NOD SCID Gamma (NSG) mice, which are deficient in both adaptive and most innate immune responses, suggesting a crucial role of MCP5 in evading host innate immunity. In the tick vector, the mcp5 mutants survived feeding but failed to transmit to mice, highlighting the importance of MCP5 in transmission. Our findings reveal that MCP5, regulated by the Rrp1 and Rrp2 pathways, is critical for the establishment of infection in mammalian hosts by evading host innate immunity and is important for the transmission of spirochetes from ticks to mammalian hosts, underscoring its potential as a target for intervention strategies. SUMMARYLyme disease is the most commonly reported arthropod-borne illness in the US, Europe, and Asia. The causative agent of Lyme disease, Borrelia burgdorferi, is maintained in an enzootic cycle involving arthropod vectors (Ixodes ticks) and rodent mammalian hosts. Understanding how B. burgdorferi moves within this natural cycle is crucial for developing new strategies to combat Lyme disease. The complex nature of the enzootic cycle necessitates sensory-guided movement in response to environmental stimuli. B. burgdorferi possesses a unique and intricate chemotaxis signaling system, with methyl-accepting chemotaxis proteins (MCPs) at its core. These proteins are responsible for sensing environmental signals and guiding bacterial movement toward or away from stimuli. This study found that one of the MCPs, MCP5, is highly expressed and differentially regulated during the enzootic cycle by the Hk1-Rrp1 and Rrp2-RpoN-RpoS pathways. MCP5 is crucial for mammalian infection, aiding in immune evasion and transmission from ticks to mammals, providing a foundation for further research into B. burgdorferis navigation within its hosts.

microbiology↗

bioRxiv2024

Deep Learning Detection of Subtle Torsional Eye Movements: Preliminary Results

The control of torsional eye position is a key component of ocular motor function. Ocular torsion can be affected by pathologies that involve ocular motor pathways, spanning from the vestibular labyrinth of the inner ears to various regions of the brainstem and cerebellum. Timely and accurate diagnosis enables efficient interventions and management of each case which are crucial for patients with dizziness, vertical double vision, or imbalance. Such detailed evaluation of eye movements may not be possible in all frontline clinical settings, particularly for detecting torsional abnormalities. These abnormalities are often more challenging to identify at the bedside compared to horizontal or vertical eye movements. To address these challenges, we used a dataset of torsional eye movements recorded with video-oculography (VOG) to develop deep learning models for detecting ocular torsion. Our models achieve 0.9308 AUROC and 86.79 % accuracy, leveraging ocular features particularly pertinent to tracking torsional eye position.

neuroscience↗