Biology subjects

Rose, T.

Publications and source records attributed to Rose, T..

9 recordsLinked to original sources

bioRxiv2025

Fluke-borne viruses are a risk factor for diseases caused by carcinogenic trematodes

Three trematode parasites, Schistosoma haematobium, Opisthorchis viverrini, and Clonorchis sinensis are recognized group 1 carcinogens for their roles in squamous cell carcinoma of the urinary bladder and bile duct cancer (cholangiocarcinoma). We aimed to assess the presence of fluke viruses and their association with malignancy in fluke infections. We showed that all three carcinogenic trematodes harbored related viruses. Focusing on O. viverrini, we observed virus persistence at discrete life stages and viral tropism for the fluke tegument, and we provided molecular and serological evidence of parasitized hosts exposure to viral RNA and proteins. Serological analyses confirmed seroconversion of residents in endemic sites and revealed that antibody titers and avidity against fluke-borne viruses increase in individuals with hepatobiliary diseases. Random forest models discriminated efficiently between liver-fluke-infected participants without disease and those with periductal fibrosis or cholangiocarcinoma. Thus, we show that fluke-borne viruses are risk factors and diagnostic targets for fluke-associated cancer.

microbiology↗

bioRxiv2024

Uncovering the simple adhesive strategy of the Toxoplasma parasite for high-speed motility

Toxoplasma gondii is a protozoan parasite that has evolved a developmental morphotype called tachyzoite that navigates between cells and moves in and out of them in a wide repertoire of homeothermic hosts. Relying on a uniquely constant apicobasal bipolarity coupled to an actomyosin-driven retrograde surface flow, the tachyzoite has elaborated a molecular machinery to assemble transient anchoring contacts with the environment, which support the traction force required to power a typical helical gliding motility. Combining micropatterning with live, reflection interference contrast and expansion microscopies, we bring first nanoscale evidence that the tachyzoite needs to build only one apical anchoring contact with the substrate, thus spatially defining a minimal force transmission platform over which it can slide. We uncover that the apicobasal driven surface flow is set up in response to extracellular biochemical cues independent of adhesin release and tachyzoite-surface interactions, hence prior to motile activity. Furthermore, to identify the minimal adhesion requirements for helical gliding at the level of individual molecular species, we combine biochemical and biophysical quantitative assays based on tunable surface chemistry and quartz crystal microbalance with dissipation monitoring. These approaches uncover that glycosaminoglycan (GAG)-parasite interactions are sufficient to promote a productive contact for helical gliding and pave the way for the characterization of the structure and density of the molecules functionally engaged at this essential parasite-substrate mechanosensitive interface.

cell biology↗

bioRxiv2023

Sensory experience steers representational drift in mouse visual cortex

Representational drift - the gradual continuous change of neuronal representations - has been observed across many brain areas. It is unclear whether drift is caused by synaptic plasticity elicited by sensory experience, or by the intrinsic volatility of synapses. Here, using chronic two-photon calcium imaging in mouse primary visual cortex, we find that the preferred stimulus orientation of individual neurons slowly drifts over the course of weeks. By using cylinder lens goggles to limit visual experience to a narrow range of orientations, we show that the direction of drift, but not its magnitude, is biased by the statistics of visual input. A network model suggests that drift of preferred orientation largely results from synaptic volatility, which under normal visual conditions is counteracted by experience-driven Hebbian mechanisms, stabilizing preferred orientation. Under deprivation conditions these Hebbian mechanisms enable adaptation. Thus, Hebbian synaptic plasticity steers drift to match the statistics of the environment.

neuroscience↗

bioRxiv2022

OsPSTOL1 is prevalent in upland rice and its expression in wheat enhances root growth and hastens low phosphate signaling

PHOSPHORUS-STARVATION TOLERANCE 1 (OsPSTOL1) benefits crown root growth and phosphorus (P) sufficiency in rice (Oryza sativa L.). To better understand the importance of this variably present gene, we carried out a biogeographic survey of landraces and cultivars, confirming that functional OsPSTOL1 alleles prevail in low nutrient and drought-prone rainfed ecosystems, whereas loss-of-function alleles and absence haplotypes predominate in control-irrigated paddy varieties of east Asia. To address the evolutionary history of OsPSTOL1 and related genes in cereal crops, phylogenetic and transcript meta-analyses were performed. Finally, to evaluate its potential value in another Gramineae, wheat (Triticum aestivum L.) lines overexpressing OsPSTOL1 were evaluated under field and controlled low P conditions. OsPSTOL1 enhances growth, crown root number, and overall root plasticity under low P in wheat. Survey of root and shoot crown transcriptomes at two developmental stages identifies transcription factors that are differentially regulated in OsPSTOL1 wheat that are similarly controlled by the gene in rice. In wheat, OsPSTOL1 alters the timing and amplitude of regulators of root development in dry soils and hastens induction of the core P-starvation response. Based on these findings, OsPSTOL1 and related genes may aid more sustainable cultivation of cereal crops. Summary statementMight a rice gene that controls root plasticity confer a similar benefit in another grain crop. Here, we evaluate the genetic variation and evolutionary history of OsPSTOL1 and demonstrate its impact in wheat.

plant biology↗

bioRxiv2021

Functional and structural features of L2/3 pyramidal cells continuously covary with pial depth in mouse visual cortex

Pyramidal cells of neocortical layer 2/3 (L2/3 PyrCs) integrate signals from numerous brain areas and project throughout the neocortex. Within L2/3, PyrCs show functional and structural specializations depending on their pial depth, indicating participation in different functional microcircuits. However, it is unknown whether these depth-dependent differences result from separable L2/3 PyrC subtypes or whether functional and structural features represent a continuum while correlating with pial depth. Here, we assessed the stimulus selectivity, electrophysiological properties, dendritic morphology, and excitatory and inhibitory synaptic connectivity across the depth of L2/3 in the binocular visual cortex (bV1) of female mice. We find that the structure of the apical but not the basal dendritic tree varies with pial depth, which is accompanied by differences in passive but not active electrophysiological properties. PyrCs in lower L2/3 receive increased excitatory and inhibitory input from L4, while upper L2/3 PyrCs receive a larger proportion of intralaminar input. Complementary in vivo calcium imaging revealed a systematic change in visual responsiveness, with deeper L2/3 PyrCs showing more robust responses than superficial PyrCs. Furthermore, deeper L2/3 PyrCs are more strongly driven by contralateral than ipsilateral eye stimulation. In contrast, orientation- and direction-selectivity of L2/3 PyrCs are not dependent on pial depth. Importantly, the transitions of the various properties are gradual, and cluster analysis does not support the classification of L2/3 PyrCs into discrete subtypes. These results show that L2/3 PyrCs multiple functional and structural properties systematically correlate with their depth within L2/3, forming a continuum rather than representing discrete subtypes. SIGNIFICANCE STATEMENTNeocortical pyramidal cells in layer 2/3 (L2/3 PyrCs) are crucial for cortical computation and display heterogenous properties. We investigated whether and how these properties vary across the depth of L2/3 and whether L2/3 PyrCs can be subdivided into distinct subtypes. This is important for a better understanding of the coding strategy and information integration processes within L2/3. We find that multiple properties such as morphology, physiology, connectivity, and functional in vivo responses of L2/3 PyrCs correlate with cortical depth in mouse visual cortex. These variations are continuous and do not support classification of L2/3 PyrCs into discrete subtypes. In contrast to L5 and L6, PyrCs in L2/3 therefore process information based on a continuous property space.

neuroscience↗

bioRxiv2021

Functional network topography of the medial entorhinal cortex

The medial entorhinal cortex (MEC) creates a map of local space, based on the firing patterns of grid, head direction (HD), border, and object-vector (OV) cells. How these cell types are organized anatomically is debated. In-depth analysis of this question requires collection of precise anatomical and activity data across large populations of neurons during unrestrained behavior, which neither electrophysiological nor previous imaging methods fully afford. Here we examined the topographic arrangement of spatially modulated neurons in MEC and adjacent parasubiculum using miniaturized, portable two-photon microscopes, which allow mice to roam freely in open fields. Grid cells exhibited low levels of co-occurrence with OV cells and clustered anatomically, while border, HD and OV cells tended to intermingle. These data suggest that grid-cell networks might be largely distinct from those of border, HD and OV cells and that grid cells exhibit strong coupling among themselves but weaker links to other cell types. Highlights- Grid and object vector cells show low levels of regional co-occurrence - Grid cells exhibit the strongest tendency to cluster among all spatial cell types - Grid cells stay separate from border, head direction and object vector cells - The territories of grid, head direction and border cells remain stable over weeks

neuroscience↗

bioRxiv2020

Selective connectivity limits functional binocularity in the retinogeniculate pathway of the mouse

Eye-specific segregation of retinal ganglion cell (RGC) axons in the dorsal lateral geniculate nucleus (dLGN) is considered a hallmark of visual system development. However, a recent anatomical study showed that nearly half of the neurons in dLGN of adult mice still receive input from both retinae, but functional data about binocularity in mature dLGN is conflicting. Here, we found that a variable but small fraction of thalamocortical neurons is binocular in vivo. Using dual-channel optogenetics in vitro we correspondingly found that dLGN neurons are dominated by retinogeniculate input from one eye only, although most neurons also received small but detectable input from the non-dominant eye. Anatomical overlap between RGC axons and dLGN neuron dendrites did not explain this strong bias towards monocularity. Our data rather suggest that functional input selection and refinement, leaving the remaining non-dominant eye inputs in a juvenile-like state, underlies the prevalent monocularity of neurons in dLGN.

neuroscience↗

bioRxiv2020

Relationship between input connectivity, morphology and orientation tuning of layer 2/3 pyramidal cells in mouse visual cortex

Neocortical pyramidal cells (PCs) display functional specializations defined by their excitatory and inhibitory circuit connectivity. For layer 2/3 (L2/3) PCs, little is known about the detailed relationship between their neuronal response properties, dendritic structure and their underlying circuit connectivity at the level of single cells. Here, we ask whether L2/3 PCs in mouse primary visual cortex (V1) differ in their functional intra- and interlaminar connectivity patterns, and how this relates to differences in visual response properties. Using a combined approach, we first characterized the orientation and direction tuning of individual L2/3 PCs with in vivo 2-photon calcium imaging. Subsequently, we performed excitatory and inhibitory synaptic input mapping of the same L2/3 PCs in brain slices using laser scanning photostimulation (LSPS). Our data from this structure-connectivity-function analysis show that the sources of excitatory and inhibitory synaptic input are different in their laminar origin and horizontal location with respect to cell position: On average, L2/3 PCs receive more inhibition than excitation from within L2/3, whereas excitation dominates input from L4 and L5. Horizontally, inhibitory input originates from locations closer to the horizontal position of the soma, while excitatory input arises from more distant locations in L4 and L5. In L2/3, the excitatory and inhibitory inputs spatially overlap on average. Importantly, at the level of individual neurons, PCs receive inputs from presynaptic cells located spatially offset, vertically and horizontally, relative to the soma. These input offsets show a systematic correlation with the preferred orientation of the postsynaptic L2/3 PC in vivo. Unexpectedly, this correlation is higher for inhibitory input offsets within L2/3 than for excitatory input offsets. When relating the dendritic complexity of L2/3 PCs to their orientation tuning, we find that sharply tuned cells have a less complex apical tree compared to broadly tuned cells. These results indicate that the spatial input offsets of the functional input connectivity are linked to orientation preference, while the orientation selectivity of L2/3 PCs is more related to the dendritic complexity.

neuroscience↗

bioRxiv2017

Lateral geniculate neurons show robust ocular dominance plasticity

Experience-dependent plasticity in the mature visual system is considered exclusively cortical. Using chronic two-photon Ca2+ imaging, we found evidence against this tenet: dLGN cells showed robust ocular dominance shifts after monocular deprivation. Most, but not all responses of dLGN cell boutons in binocular visual cortex were monocular during baseline. Following deprivation, however, deprived-eye dominated boutons became responsive to the non-deprived eye. Thus, plasticity of dLGN neurons contributes to cortical ocular dominance shifts.

neuroscience↗