Interleukin-23 is critical for full-blown expression of a non-autoimmune destructive arthritis and regulates interleukin-17A and RORγt in γδ T cells

Introduction  

Interleukin (IL)-23 is essential for the development of various experimental autoimmune models. However, the role of IL-23 in non-autoimmune experimental arthritis remains unclear. Here, we examined the role of IL-23 in the non-autoimmune antigen-induced arthritis (AIA) model. In addition, the regulatory potential of IL-23 in IL-17A and retinoic acid-related orphan receptor gamma t (RORγt) expression in CD4⁺ and TCRγδ⁺ T cells was evaluated systemically as well as at the site of inflammation.     

Alignment of genetic maps and QTLs between inter- and intra-specific sorghum populations

To increase the value of associated molecular tools and also to begin to explore the degree to which interspecific and intraspecific genetic variation in Sorghum is attributable to corresponding genetic loci, we have aligned genetic maps derived from two sorghum populations that share one common parent (Sorghum bicolor L. Moench accession BTx623) but differ in morphological and evolutionarily distant alternate parents (S. propinquum or S. bicolor accession IS3620C). A total of 106 well-distributed DNA markers provide for map alignment, revealing only six nominal differences in marker order that are readily explained by sampling variation or mapping of paralogous loci. We also report a total of 61 new QTLs detected from 17 traits in these crosses. Among eight corresponding traits (some new, some previously published) that could be directly compared between the two maps, QTLs for two (tiller height and tiller number) were found to correspond in a non-random manner (P<0.05). For several other traits, correspondence of subsets of QTLs narrowly missed statistical significance. In particular, several QTLs for leaf senescence were near loci previously mapped for ‘stay-green’ that have been implicated by others in drought tolerance. These data provide strong validation for the value of molecular tools developed in the interspecific cross for utilization in cultivated sorghum, and begin to separate QTLs that distinguish among Sorghum species from those that are informative within the cultigen (S. bicolor). Electronic Supplementary Material Supplementary material is available for this article at and is accessible for authorized users. K.F. Schertz: deceased     

A cellular solid model of the lamina cribrosa: mechanical dependence on morphology

The biomechanics of the optic nerve head (ONH) may underlie many of the potential mechanisms that initiate the characteristic vision loss associated with primary open angle glaucoma. Therefore, it is important to characterize the physiological levels of stress and strain in the ONH and how they may change in relation to material properties, geometry, and microstructure of the tissue. An idealized, analytical microstructural model of the ONH load bearing tissues was developed based on an octagonal cellular solid that matched the porosity and pore area of morphological data from the lamina cribrosa (LC). A complex variable method for plane stress was applied to relate the geometrically dependent macroscale loads in the sclera to the microstructure of the LC, and the effect of different geometric parameters, including scleral canal eccentricity and laminar and scleral thickness, was examined. The transmission of macroscale load in the LC to the laminar microstructure resulted in stress amplifications between 2.8 and 24.5xIOP. The most important determinants of the LC strain were those properties pertaining to the sclera and included Young's modulus, thickness, and scleral canal eccentricity. Much larger strains were developed perpendicular to the major axis of an elliptical canal than in a circular canal. Average strain levels as high as 5% were obtained for an increase in IOP from 15 to 50 mm Hg.     

Phagocytosis of apoptotic cells

Removal of apoptotic cells by phagocytes plays an important role in many biological processes, including embryological development and tissue remodelling. In addition, it has become apparent that one of the key mechanisms for the successful resolution of inflammation is the orchestrated clearance of apoptotic inflammatory cells by phagocytes (e.g., macrophages and dendritic cells) and other cells known to have phagocytic capacity (e.g., hepatocytes, endothelial cells, epithelial cells, etc.). Furthermore, phagocytosis of apoptotic cells is an active and highly regulated process that not only serves to remove potentially histotoxic cells from the inflammatory milieu, but also directs the phenotype of the phagocytic cell to be anti-inflammatory. Convincing evidence has been presented that reduced or dysregulated phagocytosis of apoptotic cells contributes to the development and propagation of inflammatory disorders. Conversely, enhanced phagocytosis of apoptotic cells may be exploited for therapeutic gain. Indeed, powerful anti-inflammatory drugs such as the glucocorticoids have been shown to augment clearance of apoptotic cells which may contribute to their therapeutic effectiveness. In this chapter, we describe methods for studying phagocytosis of apoptotic cells.     

Yoga as steadiness training: effects on motor variability in young adults

Exercise training programs can increase strength and improve submaximal force control, but the effects of yoga as an alternative form of steadiness training are not well described. The purpose was to explore the effect of a popular type of yoga (Bikram) on strength, steadiness, and balance. Young adults performed yoga training (n = 10, 29 +/- 6 years, 24 yoga sessions in 8 weeks) or served as controls (n = 11, 26 +/- 7 years). Yoga sessions consisted of 1.5 hours of supervised, standardized postures. Measures before and after training included maximum voluntary contraction (MVC) force of the elbow flexors (EF) and knee extensors (KE), steadiness of isometric EF and KE contractions, steadiness of concentric (CON) and eccentric (ECC) KE contractions, and timed balance. The standard deviation (SD) and coefficient of variation (CV, SD/mean force) of isometric force and the SD of acceleration during CON and ECC contractions were measured. After yoga training, MVC force increased 14% for KE (479 +/- 175 to 544 +/- 187 N, p < 0.05) and was unchanged for the EF muscles (219 +/- 85 to 230 +/- 72 N, p > 0.05). The CV of force was unchanged for EF (1.68 to 1.73%, p > 0.05) but was reduced in the KE muscles similarly for yoga and control groups (2.04 to 1.55%, p < 0.05). The variability of CON and ECC contractions was unchanged. For the yoga group, improvement in KE steadiness was correlated with pretraining steadiness (r = -0.62 to -0.84, p < 0.05); subjects with the greatest KE force fluctuations before training experienced the greatest reductions with training. Percent change in balance time for individual yoga subjects averaged +228% (19.5 +/- 14 to 34.3 +/- 18 seconds, p < 0.05), with no change in controls. For young adults, a short-term yoga program of this type can improve balance substantially, produce modest improvements in leg strength, and improve leg muscle control for less-steady subjects.     

B-type natriuretic peptide (BNP) attenuates the L-type calcium current and regulates ventricular myocyte function

A fundamental question in physiology is how hormones regulate the functioning of a cell or organ. It was therefore the aim of this study to investigate the effect(s) of BNP-32 on calcium handling by ventricular myocytes obtained from the rat left ventricle. We specifically tested the hypothesis that BNP-32 decreased the L-type calcium current (I(Ca,L)). Perforated patch clamp technique was used to record I(Ca,L) and action potential (AP) in voltage and current clamp mode, respectively. Myocyte shortening was measured using a photodiode array edge-detection system and intracellular calcium transients were measured by fluorescence photometry. Western blotting was used to determine the relative change in the expression of proteins. At the concentrations tested, BNP-32 significantly decreased cell shortening in a dose-dependent manner; increased the phase II slope of the AP by 53.0%; increased the APD(50) by 16.9%; reduced the I(Ca,L) amplitude with a 22.9% decrease in the peak amplitude and reduced Ca(2+)-dependent inactivation; increased the V(1/2) activation of the L-type calcium channel by 51.1% and decreased V(1/2) inactivation by 31.8%; and, intracellular calcium transient amplitude was significantly decreased by 32.0%, whereas the time to peak amplitude and T(1/2) were both significantly increased by 38.7% and 89.4% respectively. Sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2a) protein expression was reduced by BNP-32. These data suggest that BNP-32 regulates ventricular myocyte function by attenuating I(Ca,L), altering the AP and reducing SERCA2a activity and/or expression. This study suggests a novel constitutive mechanism for the autocrine action of BNP on the L-type calcium channel in ventricular myocytes.     

Modeling spinal muscular atrophy in Drosophila

Spinal Muscular Atrophy (SMA), a recessive hereditary neurodegenerative disease in humans, has been linked to mutations in the survival motor neuron (SMN) gene. SMA patients display early onset lethality coupled with motor neuron loss and skeletal muscle atrophy. We used Drosophila, which encodes a single SMN ortholog, survival motor neuron (Smn), to model SMA, since reduction of Smn function leads to defects that mimic the SMA pathology in humans. Here we show that a normal neuromuscular junction (NMJ) structure depends on SMN expression and that SMN concentrates in the post-synaptic NMJ regions. We conducted a screen for genetic modifiers of an Smn phenotype using the Exelixis collection of transposon-induced mutations, which affects approximately 50% of the Drosophila genome. This screen resulted in the recovery of 27 modifiers, thereby expanding the genetic circuitry of Smn to include several genes not previously known to be associated with this locus. Among the identified modifiers was wishful thinking (wit), a type II BMP receptor, which was shown to alter the Smn NMJ phenotype. Further characterization of two additional members of the BMP signaling pathway, Mothers against dpp (Mad) and Daughters against dpp (Dad), also modify the Smn NMJ phenotype. The NMJ defects caused by loss of Smn function can be ameliorated by increasing BMP signals, suggesting that increased BMP activity in SMA patients may help to alleviate symptoms of the disease. These results confirm that our genetic approach is likely to identify bona fide modulators of SMN activity, especially regarding its role at the neuromuscular junction, and as a consequence, may identify putative SMA therapeutic targets.     

AC Electrokinetic Phenomena Generated by Microelectrode Structures

The field of AC electrokinetics is rapidly growing due to its ability to perform dynamic fluid and particle manipulation on the micro- and nano-scale, which is essential for Lab-on-a-Chip applications. AC electrokinetic phenomena use electric fields to generate forces that act on fluids or suspended particles (including those made of dielectric or biological material) and cause them to move in astonishing ways^{1, 2}. Within a single channel, AC electrokinetics can accomplish many essential on-chip operations such as active micro-mixing, particle separation, particle positioning and micro-pattering. A single device may accomplish several of those operations by simply adjusting operating parameters such as frequency or amplitude of the applied voltage. Suitable electric fields can be readily created by micro-electrodes integrated into microchannels. It is clear from the tremendous growth in this field that AC electrokinetics will likely have a profound effect on healthcare diagnostics^3-5, environmental monitoring⁶ and homeland security⁷.In general, there are three AC Electrokinetic phenomena (AC electroosmosis, dielectrophoresis and AC electrothermal effect) each with unique dependencies on the operating parameters. A change in these operating parameters can cause one phenomena to become dominant over another, thus changing the particle or fluid behavior. It is difficult to predict the behavior of particles and fluids due to the complicated physics that underlie AC electrokinetics. It is the goal of this publication to explain the physics and elucidate particle and fluid behavior. Our analysis also covers how to fabricate the electrode structures that generate them, and how to interpret a wide number of experimental observations using several popular device designs. This video article will help scientists and engineers understand these phenomena and may encourage them to start using AC Electrokinetics in their research.Download video file.^{(251M, mp4)}