Chondroprotective effects of Salubrinal in a mouse model of osteoarthritis

OBJECTIVES: Salubrinal is a synthetic agent that elevates phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2α) and alleviates stress to the endoplasmic reticulum. Previously, we reported that in chondrocytes, Salubrinal attenuates expression and activity of matrix metalloproteinase 13 (MMP13) through downregulating nuclear factor kappa B (NFκB) signalling. We herein examine whether Salubrinal prevents the degradation of articular cartilage in a mouse model of osteoarthritis (OA). METHODS: OA was surgically induced in the left knee of female mice. Animal groups included age-matched sham control, OA placebo, and OA treated with Salubrinal or Guanabenz. Three weeks after the induction of OA, immunoblotting was performed for NFκB p65 and p-NFκB p65. At three and six weeks, the femora and tibiae were isolated and the sagittal sections were stained with Safranin O. RESULTS: Salubrinal suppressed the progression of OA by downregulating p-NFκB p65 and MMP13. Although Guanabenz elevates the phosphorylation level of eIF2α, it did not suppress the progression of OA. CONCLUSIONS: Administration of Salubrinal has chondroprotective effects in arthritic joints. Salubrinal can be considered as a potential therapeutic agent for alleviating symptoms of OA. Cite this article: Bone Joint Res 2015;4:84-92

Arginase from kiwifruit: properties and seasonal variation

The in vitro activity of arginase (EC 3.5.3.1) was investigated in youngest-mature leaves and roots (1-3 mm diameter) of kiwifruit vines (Actinidia deliciosa var. deliciosa) during an annual growth cycle, and enzyme from root material partially purified. No seasonal trend in the specific activity of arginase was observed in roots. Measurements in leaves, however, rose gradually during early growth and plateaued c. 17 weeks after budbreak. Changes in arginase activity were not correlated with changes in the concentration of arginine (substrate) or glutamine (likely end-product of arginine catabolism) in either tissue during the growth cycle. Purification was by (NH4)2SO4 precipitation and DEAE-cellulose chromatography. The kinetic properties of the enzyme, purified 60-fold over that in crude extracts, indicated a pH optimum of 8.8, and a Km (L-arginine) of 7.85 mM. Partially-purified enzyme was deactivated by dialysis against EDTA, and reactivated in the presence of Mn²⁺, Co²⁺, and Ni²⁺

Gauge Theory Description of Spin Ladders

A s=1/2 antiferromagnetic spin chain is equivalent to the two-flavor massless Schwinger model in an uniform background charge density in the strong coupling. The gapless mode of the spin chain is represented by a massless boson of the Schwinger model. In a two-leg spin ladder system the massless boson aquires a finite mass due to inter-chain interactions. The gap energy is found to be about .25 k |J'| when the inter-chain Heisenberg coupling J' is small compared with the intra-chain Heisenberg coupling. k is a constant of O(1). It is also shown that a cyclically symmetric N-leg ladder system is gapless or gapful for an odd or even N, respectively.Comment: 8 pages. CORRIGENDUM has been incorporated. (A factor 2 error has been corrected.

The free surface of superfluid 4He at zero temperature

The structure and energetics of the free surface of superfluid $^4$He are studied using the diffusion Monte Carlo method. Extending a previous calculation by Vall\'es and Schmidt, which used the Green's function Monte Carlo method, we study the surface of liquid $^4$He within a slab geometry using a larger number of particles in the slab and an updated interatomic potential. The surface tension is accurately estimated from the energy of slabs of increasing surface density and its value is close to one of the two existing experimental values. Results for the density profiles allow for the calculation of the surface width which shows an overall agreement with recent experimental data. The dependence on the transverse direction to the surface of other properties such as the two-body radial distribution function, structure factor, and one-body density matrix is also studied. The condensate fraction, extracted from the asymptotic behavior of the one-body density matrix, shows an unambiguous enhancement when approaching the surface.Comment: RevTex, 11 pages, accepted in Phys. Rev.

Temporal switching and cell-to-cell variability in Ca2+ release activity in mammalian cells

Genetically identical cells in a uniform external environment can exhibit different phenotypes, which are often masked by conventional measurements that average over cell populations. Although most studies on this topic have used microorganisms, differentiated mammalian cells have rarely been explored. Here, we report that only approximately 40% of clonal human embryonic kidney 293 cells respond with an intracellular Ca2+ increase when ryanodine receptor Ca2+ release channels in the endoplasmic reticulum are maximally activated by caffeine. On the other hand, the expression levels of ryanodine receptor showed a unimodal distribution. We showed that the difference in the caffeine sensitivity depends on a critical balance between Ca2+ release and Ca2+ uptake activities, which is amplified by the regenerative nature of the Ca2+ release mechanism. Furthermore, individual cells switched between the caffeine-sensitive and caffeine-insensitive states with an average transition time of approximately 65 h, suggestive of temporal fluctuation in endogenous protein expression levels associated with caffeine response. These results suggest the significance of regenerative mechanisms that amplify protein expression noise and induce cell-to-cell phenotypic variation in mammalian cells

Bipolar Charge Transport in Poly(3-hexyl thiophene)/Methanofullerene Blends: A Ratio Dependent Study

We investigated the charge carrier mobility in pristine poly(3-hexyl thiophene-2,5-diyl) (P3HT):[6,6]-phenyl-C61 butyric acid methyl ester (PCBM) blend devices by applying the time resolved photoconductivity experiment in dependence on the donor:acceptor ratio. We observe a bipolar transport in all studied samples ranging from pure polymer to polymer:fullerene with 90% PCBM content. For the ratios P3HT:PCBM 1:4 and 1:1 we observe two transit times in the electron current transients, as well as hole double transients for P3HT:PCBM 1:2. We find high hole and electron mobilities in the order of 10^(-3) - 10^(-2) cm^2/Vs for a concentration of 90% PCBM in the blend.Comment: 3 pages, 1 table, 2 figures, minor corrections include

Plasma membrane H⁺ -ATPase regulation is required for auxin gradient formation preceding phototropic growth.

Phototropism is a growth response allowing plants to align their photosynthetic organs toward incoming light and thereby to optimize photosynthetic activity. Formation of a lateral gradient of the phytohormone auxin is a key step to trigger asymmetric growth of the shoot leading to phototropic reorientation. To identify important regulators of auxin gradient formation, we developed an auxin flux model that enabled us to test in silico the impact of different morphological and biophysical parameters on gradient formation, including the contribution of the extracellular space (cell wall) or apoplast. Our model indicates that cell size, cell distributions, and apoplast thickness are all important factors affecting gradient formation. Among all tested variables, regulation of apoplastic pH was the most important to enable the formation of a lateral auxin gradient. To test this prediction, we interfered with the activity of plasma membrane H⁺ -ATPases that are required to control apoplastic pH. Our results show that H⁺ -ATPases are indeed important for the establishment of a lateral auxin gradient and phototropism. Moreover, we show that during phototropism, H⁺ -ATPase activity is regulated by the phototropin photoreceptors, providing a mechanism by which light influences apoplastic pH

A Sexually Conditioned Switch of Chemosensory Behavior in C. elegans

In sexually reproducing animals, mating is essential for transmitting genetic information to the next generation and therefore animals have evolved mechanisms for optimizing the chance of successful mate location. In the soil nematode C. elegans, males approach hermaphrodites via the ascaroside pheromones, recognize hermaphrodites when their tails contact the hermaphrodites' body, and eventually mate with them. These processes are mediated by sensory signals specialized for sexual communication, but other mechanisms may also be used to optimize mate location. Here we describe associative learning whereby males use sodium chloride as a cue for hermaphrodite location. Both males and hermaphrodites normally avoid sodium chloride after associative conditioning with salt and starvation. However, we found that males become attracted to sodium chloride after conditioning with salt and starvation if hermaphrodites are present during conditioning. For this conditioning, which we call sexual conditioning, hermaphrodites are detected by males through pheromonal signaling and additional cue(s). Sex transformation experiments suggest that neuronal sex of males is essential for sexual conditioning. Altogether, these results suggest that C. elegans males integrate environmental, internal and social signals to determine the optimal strategy for mate location

Arthrectomy for traumatic proximal interphalangeal arthritis in the lateral digit in a heifer

ΔΕΝ ΔΙΑΤΙΘΕΤΑΙ ΠΕΡΙΛΗΨΗInstructive information on the treatment for chronic deep infections of digital joints in a 9-month-old Holstein heifer is described in this report. Preoperative ultrasonographic and radiographic examinations revealed soft tissue swelling and subchondral bone lysis at the distal part of the proximal phalanx in the lateral digit. Arthrectomy was performed under xylazine sedation to remove infectious articular cartilage tissues. Immature callus formation was observed via radiography at the surgical site by the 28th postoperative day. On the 48th postoperative day, callus fellinto disrepair on the radiographs along with aggravation of the locomotion score. After the application of a half-limb cast, the immature callus formed again by the 62nd postoperative day (11 months), and bony callus formation was observed by the 74th postoperative day. Thereafter, the heifer could walk well with marked improvement in the locomotion score. The withers height of the heifer at 13 months (136 cm) was within the range of that in control heifers of the same age on this farm (133 ± 3 cm); however, the body weight (BW) of this heifer (322 kg) was lower than the BW of controls (384 ± 26 kg). The BW gain from 11 to 13 months of age seemed to be higher in the present heifer (+76 kg) than in controls (+55±20 kg), suggesting that BW of the present heifer was returning to the original BW. Based on these observations, we suggested that arthrectomy was an effective treatment option for the present case of digital joint arthritis