Biology subjects

Nieto, C.

Publications and source records attributed to Nieto, C..

24 records · Page 2Linked to original sources

bioRxiv2021

Day length-dependent thermal COP1 dynamics integrate conflicting seasonal cues in the control of Arabidopsis elongation

As the summer approaches, plants experience enhanced light inputs and elevated temperatures, two environmental cues with an opposite morphogenic impact. How plants integrate this conflicting information throughout seasons remains unclear. Key components of the plant response to light and temperature include phytochrome B (phyB), PHYTOCROME INTERACTING FACTOR 4 (PIF4), EARLY FLOWERING 3 (ELF3) and CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1). Here, we used hypocotyl lengths of single and double mutant/over-expression lines to fit a mathematical model incorporating known interactions of these genes. The fitted model recapitulates day length-dependent thermoelongation of all lines studied, and correctly predicts temperature responsiveness of new genotypes. Whilst previous works pointed to a lightindependent thermal function of COP1, simulations of our model suggested that COP1 has a role in temperature-signaling only during daytime. Based on by this prediction, we show that COP1 overexpression increases thermal response in continuous white light, while it has little effect in darkness. Defective thermal response of cop1-4 mutants is epistatic to phyB-9 and elf3-8, indicating that COP1 activity is essential to the transduction of phyB and ELF3 thermosensory function. Our model accurately captures phyB, ELF3 and PIF4 dynamics, providing an excellent toolbox for identification of best allelic combinations towards optimized crops resilience to climate change at different geographical latitudes.

plant biology↗

bioRxiv2021

Hysteresis in PIF4 and ELF3 dynamics dominates warm daytime memory in Arabidopsis

Plants may experience large diurnal temperature fluctuations. Our knowledge of the molecular mechanisms of integration of these fluctuations and the resulting growth patterns is limited. Here we show that hypocotyl growth during the night responded not only to the current temperature but also to preceding daytime temperatures, revealing a memory of previous conditions. Daytime temperature affected the nuclear levels of PHYTOCHROME INTERACTING FACTOR 4 (PIF4) and LONG HYPOCOTYL 5 (HY5) during the next night. These jointly accounted for the observed growth kinetics, whereas memory of prior daytime temperature was impaired in the pif4 and hy5 mutants. PIF4 promoter activity largely accounted for the temperature dependent changes in PIF4 protein levels. Noteworthy, the decrease in PIF4 promoter activity triggered by cooling required a stronger temperature shift than the increase caused by warming. This hysteretic pattern required EARLY-FLOWERING 3 (ELF3). Warm temperatures promoted the formation of nuclear condensates of ELF3 in hypocotyl cells during the afternoon but not in the morning. These nuclear speckles showed poor sensitivity to subsequent cooling. We conclude that ELF3 achieves hysteresis and drives the PIF4 promoter into the same behaviour, enabling a memory of daytime temperature conditions.

plant biology↗

bioRxiv2020

PyEcoLib: a python library for simulating E. coli stochastic size dynamics

Recent studies describe bacterial division as a jump process triggered when it reaches a fixed number of stochastic discrete events at a rate depending on the cell-size. This theoretical approach enabled the computation of stochastic cell-size transient dynamics with arbitrary precision, with the possibility of being coupled to other continuous processes as gene expression. Here we synthesize most of this theory in the tool PyEcoLib, a python-based library to estimate bacterial cell size stochastic dynamics including continuous growth and division events. In this library, we include examples predicting statistical properties seen in experiments.

systems biology↗

bioRxiv2020

Continuous Rate Modelling of bacterial stochastic size dynamics

Bacterial division is an inherently stochastic process. However, theoretical tools to simulate and study the stochastic transient dynamics of cell-size are scarce. Here, we present a general theoretical approach based on the Chapman-Kolmogorov formalism to describe these stochastic dynamics including continuous growth and division events as jump processes. Using this approach, we analyze the effect of different sources of noise on the dynamics of the size distribution. Oscillations in the distribution central moments were found as consequence of the discrete translation invariance of the system with period of one doubling time, these oscillations are found in both the central moments of the size distribution and the auto-correlation function and do not disappear including stochasticity on division times or size heterogeneity on the population but only after include noise in either growth rate or septum position.

systems biology↗

bioRxiv2020

Noise signature in added size suggests bacteria target a commitment size to enable division

Recent experiments suggested that sizer-like division strategy, a deviation from the adder paradigm might be produced by additional degradation events of cell division machinery molecules. We revisited single cell size data from a recently microfluidics setup using the above model. We observed that such additional degradation process, although reproduces size observations in the mean sense, it is unable to capture cell size fluctuations. We further extended recently proposed power law models to include commitment size. Our proposal is in agreement of both mean and fluctuation profiles seen in experiments. Our approach suggests further uses of noise profiles on dissecting cell size regulatory mechanisms. SIGNIFICANCEWe contrast cell division models against bacteria cell size data in minimal media. Our results seems to support the idea that division starts once bacteria meet a given commitment size.

systems biology↗

bioRxiv2019

5-HT2B serotonin receptor agonist BW723C86 shapes the macrophage gene profile via AhR and impairs monocyte-to-osteoclast differentiation

Peripheral serotonin (5-HT) exacerbates or limits inflammatory pathologies through interaction with seven types of 5-HT receptors (5-HT1-7). As central regulators of inflammation, macrophages are critical targets of 5-HT, which promotes their anti-inflammatory and pro-fibrotic polarization primarily via the 5-HT7-Protein Kinase A (PKA) axis. However, anti-inflammatory human macrophages are also characterized by the expression of 5-HT2B, an off-target of anesthetics, anti-parkinsonian drugs and Selective Serotonin Reuptake Inhibitors (SSRI) that contributes to 5-HT-mediated pathologies. Since 5-HT2B prevents mononuclear phagocyte degeneration in amyotrophic lateral sclerosis and modulates motility of murine microglial processes, we sought to determine the functional and transcriptional consequences of 5-HT2B activation in human macrophages. Ligation of 5-HT2B by the 5-HT2B-specific agonist BW723C86, which exhibits antidepressant- and anxiolytic-like effects in animal models, significantly modified the cytokine profile and the transcriptional signature in macrophages. Importantly, 5-HT2B agonist-induced transcriptional changes were partly mediated through activation of the Aryl hydrocarbon Receptor (AhR), a ligand-dependent transcription factor that regulates immune responses and the biological responses to xenobiotics. Besides, BW723C86 triggered transcriptional effects that could not be abrogated by 5-HT2B antagonists and impaired monocyte-to-osteoclast differentiation by affecting the expression of negative (IRF8) and positive (PRDM1) regulators of osteoclastogenesis. Therefore, our results demonstrate the existence of a functional 5-HT2B-AhR axis in human macrophages and indicate that the commonly used 5-HT2B agonist BW723C86 exhibits 5-HT2B-independent effects. The 5-HT2B-AhR link extends the range of signaling pathways initiated upon 5-HT receptor engagement and identifies a point of convergence for endogenous and exogenous agents with ability to modulate inflammatory responses.\n\nKEY POINTS- The serotonin receptor 5-HT2B modifies the human macrophage transcriptome through activation of the Aryl Hydrocarbon Receptor.\n- BW723C86, an agonist used for 5-HT2B activation in vivo, exerts 5-HT2B-independent effects and limits monocyte osteoclastogenic potential.

immunology↗