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Biology subjects

Zago, M.

Publications and source records attributed to Zago, M..

5 recordsLinked to original sources

Mechanistic gene-regulation-based trajectory inference with bowside

While single-cell RNA sequencing enables the in-depth study of differentiation processes, simultaneous trajectory inference and gene regulatory network reconstruction remain challenging. We propose bowside, a shallow neural stochastic differentiation model that mechanistically models gene regulation. Our method successfully recovers gene expression trends and the underlying regulatory interactions. We demonstrate bowside on hematopoiesis and induced pluripotent stem cell reprogramming data, retrieving known fate-determining network motifs.

bioinformatics↗

G-LATO: Inference of Spatial Latent Ordering via Deep Gaussian Processes

Spatial transcriptomics enables the study of cells within their native tissue context, yet identifying gradients of cellular development remains challenging. We introduce a deep Gaussian process model to address this gap. Our method recovers spatially smooth gradients explaining observed gene expression. We illustrate our method on healthy liver and glioblastoma data in reconstructing known spatial organisation and uncovering new pathological gradients, thus providing robust inference for spatial biology.

bioinformatics↗

Visual and vestibular processing of vertical motion: a psychophysical study

The motion of objects and ourselves along the vertical is affected by gravitational acceleration. However, the visual system is poorly sensitive to accelerations, and the vestibular otoliths do not disassociate gravitational and inertial accelerations of ego-motion. Here, we tested the hypothesis that the brain resolves visual and vestibular ambiguities about vertical motion with internal models of gravity, which predict that downward motions are accelerated and upward motions are decelerated by gravity. In visual sessions, a target moved up or down while participants remained stationary. In vestibular sessions, participants were moved up or down, while they fixated an imaginary target moving along. In visual-vestibular sessions, participants were moved up or down while the visual target remained fixed. We found that downward motions of either the visual target or the participant were systematically perceived as lasting less than upward motions of the same duration, and vice-versa for the opposite direction of motion, consistent with the prior assumption that downward motion is accelerated and upward motion is decelerated by gravity. In visual-vestibular sessions, there was no significant difference in the average estimates of duration of downward and upward motion of the participant. However, there was large inter-subject variability of these estimates.

neuroscience↗

Enhancement of vestibular motion discrimination by small stochastic whole-body perturbations in young healthy humans

Noisy galvanic vestibular stimulation has been shown to improve vestibular perception in healthy subjects. Here, we sought to obtain similar results using more natural stimuli consisting of small-amplitude motion perturbations of the whole body. Thirty participants were asked to report the perceived direction of antero-posterior sinusoidal motion on a MOOG platform. We compared the baseline perceptual thresholds with those obtained by applying small, stochastic perturbations at different power levels along the antero-posterior axis, symmetrically distributed around a zero-mean. At the population level, we found that the thresholds for all but the highest level of noise were significantly lower than the baseline threshold. At the individual level, the threshold was lower with at least one noise level than the threshold without noise in 87% of participants. Thus, small, stochastic oscillations of the whole body can increase the probability of detecting subthreshold vestibular signals, possibly due to stochastic resonance mechanisms. We suggest that, just as the external noise of the present experiments, also the spontaneous random oscillations of the body associated with standing posture are beneficial by enhancing vestibular thresholds with a mechanism similar to stochastic resonance. The results are also relevant from a clinical perspective, since they raise the possibility of improving motion perception in people with elevated thresholds due to aging or vestibulopathy by means of small-amplitude motion perturbations. HIGHLIGHTSO_LISmall-amplitude motion perturbations of the whole body improve vestibular perceptual thresholds of motion discrimination in young healthy people C_LIO_LIImprovements occur at optimal levels of noise amplitude, idiosyncratic to each subject C_LIO_LIThe findings are consistent with the phenomenon of stochastic resonance C_LIO_LIThe new method can applied to people with elevated thresholds due to aging or vestibulopathy C_LI

neuroscience↗

Endocrine aryl hydrocarbon receptor signaling is induced by moderate cutaneous exposure to ultraviolet light

Links between solar UV exposure and immunity date back to the ancient Greeks with the development of heliotherapy. Skin contains several UV-sensitive chromophores and exposure to sunlight can produce molecules, such as vitamin D3, that act in an endocrine manner. We investigated whether the aryl hydrocarbon receptor (AHR), an environmental sensor and ligand-regulated transcription factor activated by numerous planar compounds of dietary or environmental origin, could be the target of endocrine photoproducts produced by cutaneous UV exposure. 15-to 30-minute exposure of cells to a minimal erythemal dose of UVB irradiation in vitro induced translocation of the AHR to the nucleus, rapidly inducing site-specific DNA binding and target gene regulation. Importantly, ex vivo studies with Ahr wild-type or null fibroblasts showed that serum from mice whose skin was exposed to a 15 min UVB dose, but not control serum, contained agonist activity within 30 min of UV irradiation, inducing AHR-dependent gene expression. Moreover, a 15-min cutaneous UVB exposure induced AHR site-specific DNA binding and target gene regulation in vivo within 3-6 hr post-irradiation in blood and in peripheral tissues, including intestine. These results show that cutaneous exposure of mice to a single minimal erythemic dose of UVB induces rapid AHR signaling in multiple peripheral organs, providing compelling evidence that moderate sun exposure can exert endocrine control of immunity through the AHR.

molecular biology↗