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Biology subjects

Sassi, M.

Publications and source records attributed to Sassi, M..

7 recordsLinked to original sources

Auxin and cytokinin antagonistically regulate Arabidopsis root distal stem cell fate through opposing pairs of HD-Zip II transcription factors

The antagonistic action of auxin (IAA) and cytokinin (CK) regulates several aspects of plant development including stem cell specification and maintenance. In the Arabidopsis thaliana root, the fate of distal stem cells (DSCs) is mainly regulated by IAA, while the function of CK is still ill-defined. Here, by investigating the role of the HD-Zip II transcription factor family in distal tissues, we uncover CK as a proliferative input for DSCs, acting in opposition to IAA. We show that opposing pairs of HD-Zip II proteins regulate DSCs fate by integrating IAA and CK signals. The {delta} module, composed of HAT3 and ATHB4, is activated by CK and promotes DSCs division. Conversely, the {gamma} module, constituted by HAT1 and ATHB2, acts downstream of IAA to repress CK biosynthesis and DSCs division. The mutual inhibition between {delta} and {gamma} modules downstream of opposite hormone inputs sustains the precise regulation of DSCs homeostasis.

plant biology↗

Aberrant CD4+ T cell refeeding response impairs neuro-immune crosstalk in Parkinson's disease

T cells modulate disease associated neuroinflammation in Parkinsons disease (PD). We report that circulating CD4+ T cells from people with PD have a dysregulated transcriptional and cytokine response to fasting and refeeding and an altered metabolic profile. The CD4+ T cell secretome mediates a metabolic program in neurons that is impaired in PD, revealing dysfunctional neuro-immune signalling that may contribute to disease pathology.

neuroscience↗

Structural characterization of hibernating ribosomes in four Gram-negative pathogenic bacteria

Ribosomes are universal molecular machines that translate messenger RNA into proteins. Depending on what the cells needs for protein synthesis, ribosomes exist in various functional states, and when cells face stressful conditions, their ribosomes may enter into an inactive hibernation state. In bacteria, this ability to become dormant through ribosomal hibernation plays a crucial role in their survival, especially when the cells are targeted by ribosome-targeting antibiotics. The phenomenon occurs when ribosomes bind with hibernation factors. In this work, we examine how these special proteins interact with ribosomes from four different Gram-negative pathogens, and how this leads to translation inhibition, reporting the single-particle cryo-electron microscopy structures of hibernating ribosomes from P. aeruginosa, E. hormaechei, K. quasipneumoniae, and A. baumannii. We show that these ribosomal complexes contain either short HPF or YfiA tightly bound to the 30S A-site, P-site, and even occasionally to the E-site. Our results provide valuable insights into the ribosomal hibernation mechanism, paving the way to both a better understanding of bacterial dormancy and the possibility of developing antibiotics which will target hibernating ribosomes rather than just active ones.

biochemistry↗

CD40 Expression by B cells is Required for Optimal Immunity to Murine Pneumocystis Infection

CD40-CD40L interactions are critical for controlling Pneumocystis infection. However, which CD40-expressing cell populations are important for this interaction have not been well-defined. We used a cohousing mouse model of Pneumocystis infection, combined with flow cytometry and qPCR, to examine the ability of different populations of cells from C57BL/6 mice to reconstitute immunity in CD40 knockout (KO) mice. Unfractionated splenocytes, as well as purified B cells, were able to control Pneumocystis infection, while B cell depleted splenocytes and unstimulated bone-marrow derived dendritic cells (BMDCs) were unable to control infection in CD40 KO mice. Pneumocystis antigen-pulsed BMDCs showed early, but limited, control of infection. Consistent with recent studies that have suggested a role for antigen presentation by B cells, using cells from immunized animals, B cells were able to present Pneumocystis antigens to induce proliferation of T cells. Thus, CD40 expression by B cells appears necessary for robust immunity to Pneumocystis.

microbiology↗

HD-Zip II transcription factors control distal stem cell fate in Arabidopsis roots by linking auxin signaling to the FEZ/SOMBRERO pathway

In multicellular organisms, specialized tissues are generated by specific populations of stem cells through cycles of asymmetric cell divisions, where one daughter undergoes differentiation and the other maintains proliferative properties. In Arabidopsis thaliana roots, the columella - a gravity-sensing tissue which protects and defines the position of the stem cell niche - represents a typical example of a tissue whose organization is exclusively determined by the balance between proliferation and differentiation. The columella derives from a single layer of stem cells through a binary cell fate switch that is precisely controlled by multiple, independent regulatory inputs. Here, we show that the HD-Zip II transcription factors HAT3, ATHB4, and AHTB2, redundantly regulate columella stem cell fate and patterning in the Arabidopsis root. The HD-Zip II transcription factors promote columella stem cell proliferation by acting as effectors of the FEZ/SMB circuit and, at the same time, by interfering with auxin signaling to counteract hormone-induced differentiation. Overall, our work shows that HD-Zip II connect two opposing parallel inputs to fine tune the balance between proliferation and differentiation in columella stem cells. Summary statementHD-Zip II transcription factors redundantly regulate columella stem cells activity by counteracting auxin-mediated differentiation downstream of the FEZ/SMB proliferative input

plant biology↗

Hunger signalling in the olfactory bulb primes exploration, food-seeking and peripheral metabolism.

Growing evidence highlights a complex interaction between olfaction and metabolism with impaired olfactory function observed in obesity and increased olfactory sensitivity during hunger. The mechanisms linking metabolic state and olfaction remain unknown, but increased accessibility of hormones, such as ghrelin, and the diverse expression of hormone receptors such as those for ghrelin (GHSRs) in the olfactory system suggests an underappreciated neuroendocrine role. Here, we examined the hypothesis that GHSRs in the olfactory bulb (OB) link hunger with olfactory sensitivity to influence foraging behaviours and metabolism. Selective deletion of OBGHSRs in adult male mice was achieved with adeno-associated viral expression of cre-recombinase in the OB of floxed-Ghsr mice. OBGHSR deletion significantly affected olfactory discrimination and habituation to both food and pheromone odours, with greatest effect under fasted conditions. Anxiety-like and depression-like behaviour was significantly greater after OBGHSR deletion using 3 independent anxiety behavioural tasks and testing for anhedonia, whereas exploratory behaviour was reduced. No effect on spatial navigation and memory was observed. Although OBGHSR deletion did not affect cumulative food intake, it significantly impacted feeding behaviour as evidenced by altered bout number and duration. Moreover, food-finding after fasting or ip ghrelin was attenuated. Intriguingly, OBGHSR deletion caused an increase in body weight and fat mass, spared fat utilisation on a chow diet and impaired glucose metabolism indicating metabolic dysfunction. We conclude that OBGHSRs maintain olfactory sensitivity, particularly during hunger, and facilitate behavioural adaptations that optimise food-seeking in anxiogenic environments, priming metabolic pathways in preparation for food consumption.

neuroscience↗

The 5:2 diet does not increase adult hippocampal neurogenesis or enhance spatial memory in mice

New neurones are generated throughout life in the mammalian brain in a process known as adult hippocampal neurogenesis (AHN). Since this phenomenon grants a high degree of neuroplasticity influencing learning and memory and mood related behaviour, identifying factors that regulate AHN may be important for ameliorating age-related cognitive decline and neurodegeneration. Calorie restriction (CR), in the absence of malnutrition, has been shown to enhance AHN and improve hippocampal-dependent memory, mediated by the stomach hormone, ghrelin. Intermittent fasting (IF), a dietary strategy offering more flexibility than conventional CR, also promotes aspects of AHN. The 5:2 diet is a popular form of IF linked to a range of health benefits, however its effects on AHN and spatial memory are not well characterised. We hypothesised that the 5:2 diet would enhance AHN in a ghrelin-dependent manner. To assess this, we used immunohistochemistry to quantify new adult-born neurones and new neural stem cells (NSCs) in the hippocampal DG of adolescent and adult wild-type and mice lacking the ghrelin receptor following six weeks on a 5:2 diet. We report an age-related decline in neurogenic processes and identify a novel role for ghrelin-receptor in regulating the formation of new adult born NSCs in an age-dependent manner. However, the 5:2 diet did not affect new neurone or NSC formation in the DG. Consistent with this finding the 5:2 diet did not alter performance on a spatial learning and memory task. These data suggest that the 5:2 diet used in this study does not increase AHN or improve associated spatial memory function. HighlightsO_LI5:2 diet does not increase adult hippocampal neurogenesis C_LIO_LI5:2 diet does not enhance spatial memory performance C_LIO_LIThere is an age-related decline in adult hippocampal neurogenesis C_LIO_LIGhrelin-receptor regulates new neural stem cell and new neurone number in an age-related manner C_LIO_LIGhrelin-receptor is required for intact spatial memory C_LI

neuroscience↗