What is quantitative plant biology?

Quantitative plant biology is an interdisciplinary field that builds on a long history of biomathematics and biophysics. Today, thanks to high spatiotemporal resolution tools and computational modelling, it sets a new standard in plant science. Acquired data, whether molecular, geometric or mechanical, are quantified, statistically assessed and integrated at multiple scales and across fields. They feed testable predictions that, in turn, guide further experimental tests. Quantitative features such as variability, noise, robustness, delays or feedback loops are included to account for the inner dynamics of plants and their interactions with the environment. Here, we present the main features of this ongoing revolution, through new questions around signalling networks, tissue topology, shape plasticity, biomechanics, bioenergetics, ecology and engineering. In the end, quantitative plant biology allows us to question and better understand our interactions with plants. In turn, this field opens the door to transdisciplinary projects with the society, notably through citizen science.Peer reviewe

ChemR23 Dampens Lung Inflammation and Enhances Anti-viral Immunity in a Mouse Model of Acute Viral Pneumonia

Viral diseases of the respiratory tract, which include influenza pandemic, children acute bronchiolitis, and viral pneumonia of the elderly, represent major health problems. Plasmacytoid dendritic cells play an important role in anti-viral immunity, and these cells were recently shown to express ChemR23, the receptor for the chemoattractant protein chemerin, which is expressed by epithelial cells in the lung. Our aim was to determine the role played by the chemerin/ChemR23 system in the physiopathology of viral pneumonia, using the pneumonia virus of mice (PVM) as a model. Wild-type and ChemR23 knock-out mice were infected by PVM and followed for functional and inflammatory parameters. ChemR23−/− mice displayed higher mortality/morbidity, alteration of lung function, delayed viral clearance and increased neutrophilic infiltration. We demonstrated in these mice a lower recruitment of plasmacytoid dendritic cells and a reduction in type I interferon production. The role of plasmacytoid dendritic cells was further addressed by performing depletion and adoptive transfer experiments as well as by the generation of chimeric mice, demonstrating two opposite effects of the chemerin/ChemR23 system. First, the ChemR23-dependent recruitment of plasmacytoid dendritic cells contributes to adaptive immune responses and viral clearance, but also enhances the inflammatory response. Second, increased morbidity/mortality in ChemR23−/− mice is not due to defective plasmacytoid dendritic cells recruitment, but rather to the loss of an anti-inflammatory pathway involving ChemR23 expressed by non-leukocytic cells. The chemerin/ChemR23 system plays important roles in the physiopathology of viral pneumonia, and might therefore be considered as a therapeutic target for anti-viral and anti-inflammatory therapies

What is quantitative plant biology?

Quantitative plant biology is an interdisciplinary field that builds on a long history of biomathematics and biophysics. Today, thanks to high spatiotemporal resolution tools and computational modelling, it sets a new standard in plant science. Acquired data, whether molecular, geometric or mechanical, are quantified, statistically assessed and integrated at multiple scales and across fields. They feed testable predictions that, in turn, guide further experimental tests. Quantitative features such as variability, noise, robustness, delays or feedback loops are included to account for the inner dynamics of plants and their interactions with the environment. Here, we present the main features of this ongoing revolution, through new questions around signalling networks, tissue topology, shape plasticity, biomechanics, bioenergetics, ecology and engineering. In the end, quantitative plant biology allows us to question and better understand our interactions with plants. In turn, this field opens the door to transdisciplinary projects with the society, notably through citizen science

Pharmacological blockade of CCR1 ameliorates murine arthritis and alters cytokine networks in vivo

The chemokine receptor CCR1 is a potential target for the treatment of rheumatoid arthritis. To explore the impact of CCR1 blockade in experimental arthritis and the underlying mechanisms, we used J-113863, a non-peptide antagonist of the mouse receptor. Experimental approach: Compound J-113863 was tested in collagen-induced arthritis (CIA) and three models of acute inflammation; Staphylococcus enterotoxin B (SEB)-induced interleukin-2 (IL-2), delayed-type hypersensitivity (DTH) response, and lipopolysaccharide (LPS)-induced tumour necrosis factorΑ (TNFΑ) production. In the LPS model, CCR1 knockout, adrenalectomised, or IL-10-depleted mice were also used. Production of TNFΑ by mouse macrophages and human synovial membrane samples in vitro were also studied. Key results: Treatment of arthritic mice with J-113863 improved paw inflammation and joint damage, and dramatically decreased cell infiltration into joints. The compound did not inhibit IL-2 or DTH, but reduced plasma TNFΑ levels in LPS-treated mice. Surprisingly, CCR1 knockout mice produced more TNFΑ than controls in response to LPS, and J-113863 decreased TNFΑ also in CCR1 null mice, indicating that its effect was unrelated to CCR1. Adrenalectomy or neutralisation of IL-10 did not prevent inhibition of TNFΑ production by J-113863. The compound did not inhibit mouse TNFΑ in vitro, but did induce a trend towards increased TNFΑ release in cells from synovial membranes of rheumatoid arthritis patients. Conclusions and implications: CCR1 blockade improves the development of CIA, probably via inhibition of inflammatory cell recruitment. However, results from both CCR1-deficient mice and human synovial membranes suggest that, in some experimental settings, blocking CCR1 could enhance TNF production. British Journal of Pharmacology (2006) 149 , 666–675. doi:Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75213/1/sj.bjp.0706912.pd

Dendritic Cells in Multiple Sclerosis Lesions: Maturation Stage, Myelin Uptake, and Interaction With Proliferating T Cells

In multiple sclerosis (MS), dendritic cells (DCs) recruited to the central nervous system (CNS) are thought to be involved in the regulation of autoimmune responses directed against myelin antigens. To better understand the role of DCs in CNS inflammation, we performed a detailed immunohistochemical analysis of DC maturation markers and of DC relationship to CNS-infiltrating T cells in autopsy brain tissue of patients with MS. We also investigated the presence of DCs containing myelin debris in MS lesions. Myeloid DC subsets were identified using the following markers: CD1a for immature DCs; DC-SIGN for immature and mature DCs; and fascin, CD83, DC-LAMP, and CCR7 for mature DCs. The most common finding was the presence of cells expressing DC-SIGN and containing myelin components in the perivascular cuffs of early active and chronic (both active and inactive) MS lesions. Perivascular CD1a DCs were detected in active lesions in only one of 10 patients with MS who were examined. Although less numerous than DC-SIGN DCs, cells expressing mature DC markers were consistently detected in the inflamed meninges and perivascular cuffs of most active lesions examined. CCR7 immunostaining was predominantly confined to activated microglia at the lesion edges. Some perivascular DC-SIGN cells were found in close proximity to or contacting rare proliferating lymphocytes, most of which expressed the DC-SIGN ligand ICAM-3 and CD8. These data suggest that DCs recruited and maturing in MS lesions, where self-antigens are made available by continuous myelin destruction, may contribute to the local activation and expansion of presumably pathogenic T cells

Phosphoinositide-specific phospholipase C in health and disease

Phospholipases are widely occurring and can be found in several different organisms, including bacteria, yeast, plants, animals, and viruses. Phospholipase C (PLC) is a class of phospholipases that cleaves phospholipids on the diacylglycerol (DAG) side of the phosphodiester bond producing DAGs and phosphomonoesters. Among PLCs, phosphoinositide-specific PLC (PI-PLC) constitutes an important step in the inositide signaling pathways. The structures of PI-PLC isozymes show conserved domains as well as regulatory specific domains. This is important, as most PI-PLCs share a common mechanism, but each of them has a peculiar role and can have a specific cell distribution that is linked to a specific function. More importantly, the regulation of PLC isozymes is fundamental in health and disease, as there are several PLC-dependent molecular mechanisms that are associated with the activation or inhibition of important physiopathological processes. Moreover, PI-PLC alternative splicing variants can play important roles in complex signaling networks, not only in cancer but also in other diseases. That is why PI-PLC isozymes are now considered as important molecules that are essential for better understanding the molecular mechanisms underlying both physiology and pathogenesis, and are also potential molecular targets useful for the development of innovative therapeutic strategies.open