Fibroblast-like synoviocytes orchestrate daily rhythmic inflammation in arthritis

Rheumatoid arthritis is a chronic inflammatory disease that shows characteristic diurnal variation in symptom severity, where joint resident fibroblast-like synoviocytes (FLS) act as important mediators of arthritis pathology. We investigate the role of FLS circadian clock function in directing rhythmic joint inflammation in a murine model of inflammatory arthritis. We demonstrate FLS time-of-day-dependent gene expression is attenuated in arthritic joints, except for a subset of disease-modifying genes. The deletion of essential clock gene Bmal1 in FLS reduced susceptibility to collagen-induced arthritis but did not impact symptomatic severity in affected mice. Notably, FLS Bmal1 deletion resulted in loss of diurnal expression of disease-modulating genes across the joint, and elevated production of MMP3, a prognostic marker of joint damage in inflammatory arthritis. This work identifies the FLS circadian clock as an influential driver of daily oscillations in joint inflammation, and a potential regulator of destructive pathology in chronic inflammatory arthritis

Photorespiration: metabolic pathways and their role in stress protection

Photorespiration results from the oxygenase reaction catalysed by ribulose-1,5-bisphosphate carboxylase/ oxygenase. In this reaction glycollate-2-phosphate is produced and subsequently metabolized in the photorespiratory pathway to form the Calvin cycle intermediate glycerate-3-phosphate. During this metabolic process, CO2 and NH3 are produced and ATP and reducing equivalents are consumed, thus making photorespiration a wasteful process. However, precisely because of this ine¤ciency, photorespiration could serve as an energy sink preventing the overreduction of the photosynthetic electron transport chain and photoinhibition, especially under stress conditions that lead to reduced rates of photosynthetic CO2 assimilation. Furthermore, photorespiration provides metabolites for other metabolic processes, e.g. glycine for the synthesis of glutathione, which is also involved in stress protection. In this review, we describe the use of photorespiratory mutants to study the control and regulation of photorespiratory pathways. In addition, we discuss the possible role of photorespiration under stress conditions, such as drought, high salt concentrations and high light intensities encountered by alpine plants

Efficient algorithms for estimating the width of nearly normal distributions

Typical physics data samples often conform to Gaussian distributions with admixtures of more slowly varying backgrounds. Under such circumstances the standard deviation is known to be a poor statistical measure of distribution width. As an alternative, the performance of Gini's mean difference is compared with the standard deviation and the mean deviation. Variants which sum over subsets of all possible pairs are shown to have statistical efficiencies comparable to the mean difference and mean deviation but do not require extensive data storage or a priori knowledge of the sample mean. These statistics are reasonable candidates for monitoring the distribution width of a real time data stream.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25187/1/0000626.pd

Temperature regulates NF-κB dynamics and function through timing of A20 transcription

NF-κB signaling plays a pivotal role in control of the inflammatory response. We investigated how the dynamics and function of NF-κB were affected by temperature within the mammalian physiological range (34 °C to 40 °C). An increase in temperature led to an increase in NF-κB nuclear/cytoplasmic oscillation frequency following Tumor Necrosis Factor alpha (TNFα) stimulation. Mathematical modeling suggested that this temperature sensitivity might be due to an A20-dependent mechanism, and A20 silencing removed the sensitivity to increased temperature. The timing of the early response of a key set of NF-κB target genes showed strong temperature dependence. The cytokine-induced expression of many (but not all) later genes was insensitive to temperature change (suggesting that they might be functionally temperature-compensated). Moreover, a set of temperature- and TNFα-regulated genes were implicated in NF-κB cross-talk with key cell-fate–controlling pathways. In conclusion, NF-κB dynamics and target gene expression are modulated by temperature and can accurately transmit multidimensional information to control inflammation

Generic flow profiles induced by a beating cilium

We describe a multipole expansion for the low Reynolds number fluid flows generated by a localized source embedded in a plane with a no-slip boundary condition. It contains 3 independent terms that fall quadratically with the distance and 6 terms that fall with the third power. Within this framework we discuss the flows induced by a beating cilium described in different ways: a small particle circling on an elliptical trajectory, a thin rod and a general ciliary beating pattern. We identify the flow modes present based on the symmetry properties of the ciliary beat.Comment: 12 pages, 6 figures, to appear in EPJ

Susceptibility sets and the final outcome of collective Reed–Frost epidemics

This paper is concerned with exact results for the final outcome of stochastic SIR (susceptible → infective → recovered) epidemics among a closed, finite and homogeneously mixing population. The factorial moments of the number of initial susceptibles who ultimately avoid infection by such an epidemic are shown to be intimately related to the concept of a susceptibility set. This connection leads to simple, probabilistically illuminating proofs of exact results concerning the total size and severity of collective Reed–Frost epidemic processes, in terms of Gontcharoff polynomials, first obtained in a series of papers by Claude Lef`evre and Philippe Picard. The proofs extend easily to include general final state random variables defined on SIR epidemics, and also to multitype epidemics