MicroRNAs as new player in rheumatoid arthritis

MicroRNAs (miRNAs) are small noncoding RNA molecules that negatively regulate gene expression at the post-transcriptional level. Currently, there are 939 mature human miRNA sequences listed in the Sanger updated miRNA registry. There are approximately 1500 predicted miRNAs in the human genome that may regulate the expression of one third of our genes. By controlling the accumulation of the target protein(s) in cells, these regulatory RNA molecules participate in key functions in many physiological networks and their deregulation has been implicated in the pathogenesis of serious human disorders, such as cancer and infection. The implication of miRNAs in immune-mediated disorders such as rheumatoid arthritis (RA) has recently emerged suggesting that miRNA-based therapeutic approaches may have a promising potential in these diseases. Here, we provide an overview of the state-of-the-art on miRNAs in RA, focusing on both systemic and local features of the pathology

Inferring phytoplankton carbon and eco-physiological rates from diel cycles of spectral particulate beam-attenuation coefficient

The diurnal fluctuations in solar irradiance impose a fundamental frequency on ocean biogeochemistry. Observations of the ocean carbon cycle at these frequencies are rare, but could be considerably expanded by measuring and interpreting the inherent optical properties. A method is presented to analyze diel cycles in particulate beam-attenuation coefficient (<i>c</i><sub>p</sub>) measured at multiple wavelengths. The method is based on fitting observations with a size-structured population model coupled to an optical model to infer the particle size distribution and physiologically relevant parameters of the cells responsible for the measured diel cycle in <i>c</i><sub>p</sub>. Results show that the information related to size and contained in the spectral data can be exploited to independently estimate growth and loss rates during the day and night. In addition, the model can characterize the population of particles affecting the diel variability in <i>c</i><sub>p</sub>. Application of this method to spectral <i>c</i><sub>p</sub> measured at a station in the oligotrophic Mediterranean Sea suggests that most of the observed variations in <i>c</i><sub>p</sub> can be ascribed to a synchronized population of cells with an equivalent spherical diameter around 4.6±1.5 μm. The inferred carbon biomass of these cells was about 5.2–6.0 mg m<sup>−3</sup> and accounted for approximately 10% of the total particulate organic carbon. If successfully validated, this method may improve our in situ estimates of primary productivity

Inferring phytoplankton carbon and eco-physiological rates from diel cycles of spectral particulate beam-attenuation coefficient

The diurnal fluctuations in solar irradiance impose a fundamental frequency on ocean biogeochemistry. Observations of the ocean carbon cycle at these frequencies are rare, but could be considerably expanded by measuring and interpreting the inherent optical properties. A method is presented to analyze diel cycles in particulate beam-attenuation coefficient (cp) measured at multiple wavelengths. The method is based on fitting observations with a size-structured population model coupled to an optical model to infer the particle size distribution and physiologically relevant parameters of the cells responsible for the measured diel cycle in cp. Results show that the information related to size and contained in the spectral data can be exploited to independently estimate growth and loss rates during the day and night. In addition, the model can characterize the population of particles affecting the diel variability in cp. Application of this method to spectral cp measured at a station in the oligotrophic Mediterranean Sea suggests that most of the observed variations in cp can be ascribed to a synchronized population of cells with an equivalent spherical diameter around 4.6-1.5 1/4μm. The inferred carbon biomass of these cells was about 5.2-6.0 mg mg -\u273 and accounted for approximately 10% of the total particulate organic carbon. If successfully validated, this method may improve our in situ estimates of primary productivity

Cytosolic phospholipase A2α gene silencing in monocytes alters development of Th1 responses and reduces autoimmune arthritis

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3-D Ultrastructure of O. tauri: Electron Cryotomography of an Entire Eukaryotic Cell

The hallmark of eukaryotic cells is their segregation of key biological functions into discrete, membrane-bound organelles. Creating accurate models of their ultrastructural complexity has been difficult in part because of the limited resolution of light microscopy and the artifact-prone nature of conventional electron microscopy. Here we explored the potential of the emerging technology electron cryotomography to produce three-dimensional images of an entire eukaryotic cell in a near-native state. Ostreococcus tauri was chosen as the specimen because as a unicellular picoplankton with just one copy of each organelle, it is the smallest known eukaryote and was therefore likely to yield the highest resolution images. Whole cells were imaged at various stages of the cell cycle, yielding 3-D reconstructions of complete chloroplasts, mitochondria, endoplasmic reticula, Golgi bodies, peroxisomes, microtubules, and putative ribosome distributions in-situ. Surprisingly, the nucleus was seen to open long before mitosis, and while one microtubule (or two in some predivisional cells) was consistently present, no mitotic spindle was ever observed, prompting speculation that a single microtubule might be sufficient to segregate multiple chromosomes

Robustness of circadian clocks to daylight fluctuations: hints from the picoeucaryote Ostreococcus tauri

The development of systemic approaches in biology has put emphasis on identifying genetic modules whose behavior can be modeled accurately so as to gain insight into their structure and function. However most gene circuits in a cell are under control of external signals and thus quantitative agreement between experimental data and a mathematical model is difficult. Circadian biology has been one notable exception: quantitative models of the internal clock that orchestrates biological processes over the 24-hour diurnal cycle have been constructed for a few organisms, from cyanobacteria to plants and mammals. In most cases, a complex architecture with interlocked feedback loops has been evidenced. Here we present first modeling results for the circadian clock of the green unicellular alga Ostreococcus tauri. Two plant-like clock genes have been shown to play a central role in Ostreococcus clock. We find that their expression time profiles can be accurately reproduced by a minimal model of a two-gene transcriptional feedback loop. Remarkably, best adjustment of data recorded under light/dark alternation is obtained when assuming that the oscillator is not coupled to the diurnal cycle. This suggests that coupling to light is confined to specific time intervals and has no dynamical effect when the oscillator is entrained by the diurnal cycle. This intringuing property may reflect a strategy to minimize the impact of fluctuations in daylight intensity on the core circadian oscillator, a type of perturbation that has been rarely considered when assessing the robustness of circadian clocks

Macrophages retain hematopoietic stem cells in the spleen via VCAM-1

Splenic myelopoiesis provides a steady flow of leukocytes to inflamed tissues, and leukocytosis correlates with cardiovascular mortality. Yet regulation of hematopoietic stem cell (HSC) activity in the spleen is incompletely understood. Here, we show that red pulp vascular cell adhesion molecule 1 (VCAM-1)[superscript +] macrophages are essential to extramedullary myelopoiesis because these macrophages use the adhesion molecule VCAM-1 to retain HSCs in the spleen. Nanoparticle-enabled in vivo RNAi silencing of the receptor for macrophage colony stimulation factor (M-CSFR) blocked splenic macrophage maturation, reduced splenic VCAM-1 expression and compromised splenic HSC retention. Both, depleting macrophages in CD169 iDTR mice or silencing VCAM-1 in macrophages released HSCs from the spleen. When we silenced either VCAM-1 or M-CSFR in mice with myocardial infarction or in ApoE[superscript −/−] mice with atherosclerosis, nanoparticle-enabled in vivo RNAi mitigated blood leukocytosis, limited inflammation in the ischemic heart, and reduced myeloid cell numbers in atherosclerotic plaques

Inferring phytoplankton carbon and eco-physiological rates from diel cycles of spectral particulate beam-attenuation coefficient

The diurnal fluctuations in solar irradiance impose a fundamental frequency on ocean biogeochemistry. Observations of the ocean carbon cycle at these frequencies are rare, but could be considerably expanded by measuring and interpreting the inherent optical properties. A method is presented to analyze diel cycles in particulate beam-attenuation coefficient (c[subscript p]) measured at multiple wavelengths. The method is based on fitting observations with a size-structured population model coupled to an optical model to infer the particle size distribution and physiologically relevant parameters of the cells responsible for the measured diel cycle in c[subscript p]. Results show that the information related to size and contained in the spectral data can be exploited to independently estimate growth and loss rates during the day and night. In addition, the model can characterize the population of particles affecting the diel variability in c[subscript p]. Application of this method to spectral c[subscript p] measured at a station in the oligotrophic Mediterranean Sea suggests that most of the observed variations in c[subscript p] can be ascribed to a synchronized population of cells with an equivalent spherical diameter around 4.6±1.5 μm. The inferred carbon biomass of these cells was about 5.2–6.0 mg m⁻³ and accounted for approximately 10% of the total particulate organic carbon. If successfully validated, this method may improve our in situ estimates of primary productivity

In Silico and Biochemical Analysis of Physcomitrella patens Photosynthetic Antenna: Identification of Subunits which Evolved upon Land Adaptation

Background. In eukaryotes the photosynthetic antenna system is composed of subunits encoded by the light harvesting complex (Lhc) multigene family. These proteins play a key role in photosynthesis and are involved in both light harvesting and photoprotection. The moss Physcomitrella patens is a member of a lineage that diverged from seed plants early after land colonization and therefore by studying this organism, we may gain insight into adaptations to the aerial environment. Principal Findings. In this study, we characterized the antenna protein multigene family in Physcomitrella patens, by sequence analysis as well as biochemical and functional investigations. Sequence identification and analysis showed that some antenna polypeptides, such as Lhcb3 and Lhcb6, are present only in land organisms, suggesting they play a role in adaptation to the sub-aerial environment. Our functional analysis which showed that photo-protective mechanisms in Physcomitrella patens are very similar to those in seed plants fits with this hypothesis. In particular, Physcomitrella patens also activates Non Photochemical Quenching upon illumination, consistent with the detection of an ortholog of the PsbS protein. As a further adaptation to terrestrial conditions, the content of Photosystem I low energy absorbing chlorophylls also increased, as demonstrated by differences in Lhca3 and Lhca4 polypeptide sequences, in vitro reconstitution experiments and low temperature fluorescence spectra. Conclusions. This study highlights the role of Lhc family members in environmental adaptation and allowed proteins associated with mechanisms of stress resistance to be identified within this large family