Retinoic acid stimulates the cell cycle machinery in normal T cells: involvement of retinoic acid receptor-mediated IL-2 secretion

The mechanisms whereby vitamin A stimulates the immune system are poorly understood. In the current study, we attempted to elucidate the potential mechanisms of action of all-trans retinoic acid (atRA) on proliferation of human T lymphocytes. We found that physiological levels of atRA potently augmented T cell proliferation when added in combination with common T cell-stimulating agents. This was reflected in a time- and concentration-dependent stimulation of the cell cycle machinery. The presence of atRA led to elevated levels of cyclin D3, -E, and -A, decreased levels of p27(Kip1), increased activity of cyclin-dependent kinase 2, and enhanced phosphorylation of the retinoblastoma protein (pRB). The atRA-mediated changes in the cell cycle machinery were late events, appearing after 20 h of stimulation, indicating that the effects of atRA were indirect. atRA did not alter the expression of the high-affinity IL-2R. However, the level of IL-2 secreted by T cells was strongly enhanced by atRA. rIL-2 was able to substitute for the effects of atRA on the cell cycle machinery and on DNA synthesis, and blocking the IL-2R markedly inhibited atRA-induced cell proliferation and pRB phosphorylation. A retinoic acid receptor (RAR)-selective agonist and 9-cis-RA had the same potency as atRA on T cell proliferation and IL-2 secretion, whereas a retinoid X receptor-selective agonist had only marginal effects. Furthermore, a RAR-selective antagonist completely suppressed T cell proliferation and pRB phosphorylation induced by atRA. Taken together, these results suggest that atRA stimulates the cell cycle machinery and proliferation of normal human T cells by increasing IL-2 secretion through mechanisms involving RARs.     

Relationships between body size and sound‐producing structures in crickets: do large males have large harps?

Abstract. Male crickets produce conspicuous acoustic signals to attract mates and deter potential rivals. These signals are created when a male cricket closes his wings rapidly and a file and scraper mechanism causes several areas of the wing to vibrate. The harp is an area of the wing that is part of the resonating structure. Because the harp acts as part of a mechanical resonator, changes in harp area or mass could influence the frequency of sound produced. Because females exhibit stabilizing selection on the frequency used in male songs, we hypothesized that there would be a negative allometric relationship between body size and harp area. In addition, we examined the degree of asymmetry in the harp, wing, and tibia. We examined this in four different species of cricket: Acheta domesticus, Gryllus bimaculatus, Gryllus rubens , and Teleogryllus oceanicus. For each species, we measured pronotum width as an index of body size, tibia length, and the area of the forewing and harp. There were significant differences among species in their morphological characteristics. We observed consistent directional asymmetry in the harp area but not in the total wing area. When wings did exhibit directional asymmetry, it was in the opposite direction of the directional asymmetry observed in the harp. Within species, larger males typically had larger harps and the relationship between harp area and body size exhibited negative allometry. Wing area exhibited an isometric relationship with body size. Our data provide a potential mechanism linking decreases in song frequency with body size in male crickets, and suggest that sensory constraints might influence the morphology of signaling structures in a similar fashion as genitalia.     

Physiological responses to cadmium stress in strawberry treated with pomegranate peel-activated carbon

Many reports have already been published regarding the removal of heavy metals from aqueous solutions onto activated carbon. However, the biosorbents' effect on the plant response still needs further investigation. In this study, activated carbon derived from the pomegranate peel [pomegranate activated carbons (PAC)] was used to see the effects of the addition of PAC on growing strawberry in Cd-contaminated sand. Cd accumulation and toxicity to strawberry was investigated by measuring the concentration of Cd in plant tissues and various biochemical activities of plant. Our results suggested that PAC had a high sorption capacity for Cd. Strawberry plant tried to deal with the Cd-induced oxidative stress by strengthening its antioxidant competences and decreasing Cd absorption. In comparison with the control, PAC applied to the sand decreased the level of lipid peroxidation and enhanced the carotenoid content. The greater tolerance of strawberry toward the level of Cd due to the application of PAC was associated with improving the physical conditions of the soil, increasing the amounts of some essential elements and decreasing the level of Cd absorption. Gaviota strawberry cultivar exposed to 5 or 10 mg kg^?1 Cd was able to adopt a new metabolic equilibrium, allowing the plant to cope with this metal.     

Highly Stretchable,Sparse, Metallized Nanofiber Webs as Thin,Transferrable Transparent Conductors

The need for transparent conductors (TCs) that are capable of withstanding high mechanical deformation in comparison to the brittle indium tin oxide (ITO) films is paramount for roll‐to‐roll production of flexible and stretchable displays, signage systems, lighting devices and solar panels with stringent weatherability requirements. This paper reports a highly stretchable TC comprising of a web of core‐shell nanofibers, which mimics the fibrous structure of natural systems such as veins of a leaf or nerve systems. The TC web demonstrates high transparency, low sheet resistance, and unprecedented stretchability and stability over repeated stretching. The nanofiber TC web can be transferred to different substrates, which is manifested by the transfer onto an organic solar cell, demonstrating a photovoltaic performance comparable to that of a device with an ITO electrode. This work presents a technological platform, scalable for the manufacturing of large area transparent conductors for flexible and stretchable displays, electronics and solar cells on unconventional substrates such as rubber, fabric and paper.     

Lovastatin induces neuronal differentiation and apoptosis of embryonal carcinoma and neuroblastoma cells: enhanced differentiation and apoptosis in combination with dbcAMP

Vasodilator-stimulated phosphoprotein (VASP), an important substrate of PKA, plays a critical role in remodeling of actin cytoskeleton and actin-based cell motility. However, how PKA accurately transfers extracellular signals to VASP and then how phosphorylation of VASP regulates endothelial cell migration have not been clearly defined. Protein kinase A anchoring proteins (AKAPs) are considered to regulate intracellular-specific signal targeting of PKA via AKAP-mediated PKA anchoring. Thus, our study investigated the relationship among AKAP anchoring of PKA, PKA activity, and VASP phosphorylation, which is to clarify the exact role of VASP and its upstream regulatory mechanism in PKA-dependent migration. Our results show that chemotactic factor PDGF activated PKA, increased phosphorylation of VASP at Ser157, and enhanced ECV304 endothelial cell migration. However, phosphorylation site-directed mutation of VASP at Ser157 attenuated the chemotactic effect of PDGF on endothelial cells, suggesting phosphorylation of VASP at Ser157 promotes PKA-mediated endothelial cell migration. Furthermore, disrupting PKA anchoring to AKAP or PKA activity significantly attenuated the PKA activity, VASP phosphorylation, and subsequent cell migration. Meanwhile, disrupting PKA anchoring to AKAP abolished PDGF-induced lamellipodia formation and special VASP accumulation at leading edge of lamellipodia. These results indicate that PKA activation and PKA-mediated substrate responses in VASP phosphorylation and localization depend on PKA anchoring via AKAP in PDGF-induced endothelial cell migration. In conclusion, AKAP anchoring of PKA is an essential upstream event in regulation of PKA-mediated VASP phosphorylation and subsequent endothelial cell migration, which contributes to explore new methods for controlling endothelial cell migration related diseases and angiogenesis.     

Cannabinoids and Their Interactions with Diazepam on Modulation of Serum Corticosterone Concentration in Male Mice

Experimental results indicate a mutual interaction between cannabinoidergic and GABAergic systems; however, the interaction between these systems on corticosterone release has not been fully investigated. In this study, we treated male mice with either cannabinoid compounds alone or in combination with diazepam. Blood samples were collected at 60 min post-injection. The serum corticosterone (CORT) level was measured using ELISA technique. Acute treatment of mice by cannabinoid receptor agonist WIN55212-2 (2.5 mg/kg; i.p.) resulted in a significant reduction of CORT, while treatment with either endocannabinoid reuptake inhibitor AM404 or endocannabinoid degradation enzyme inhibitor URB597 increased CORT compared to control group. Co-administration of AM404 or URB597 with cannabinoid CB1 receptor antagonist AM251 blocked the effect of these compounds on CORT. Treatment of mice with different doses of diazepam alone did not alter CORT compared to control group. However, co-administration of diazepam and either AM404 or WIN55212-2 significantly reduced CORT compared to the respective group treated with cannabinoid compound alone. Co-administration of ineffective dose of URB597 and ineffective dose of diazepam increased CORT level compared to groups treated with each compound alone. In conclusion, our findings suggest that the endogenous cannabinoid system is active as a modulator of CORT in mice and diazepam can alter the effect of cannabinoid system in the modulation of neuroendocrine functions.     

Multivariate analysis of digital gene expression profiles identifies a xylem signature of the vascular tissue of white spruce (Picea glauca)

A collection of cDNA libraries from white spruce (Picea glauca) and interior spruce (P. glauca × engelmanii) vascular tissue were analyzed to identify a set of genes that could serve as tissue-related markers within the coniferous vascular system. Multivariate exploratory methods identified up to 128 genes co-expressed similarly among three xylem libraries. The majority (87) of these genes formed three distinctive meta-clusters, denoting putative gene cliques in xylem tissue. Of the selected genes, 33 (25%) exhibited no significant sequence homology in queries against any public databases, indicating the possibility of their unique expression in the xylem tissue of conifers. Another 38 genes (30%) had ambiguous annotation. Validation of the annotated genes with analog data, obtained from a wet-lab study utilizing microarray slides with 18,881 spots, resulted in a screened list of 29 genes as xylem-related markers. Response to stress was the predominant category to which the screened genes corresponded. Among the screened genes, elements of the phenolics biosynthesis, cinnamyl alcohol dehydrogenase and laccase, together with the fundamental enzyme of the cell wall biosynthesis, cellulose synthase, prominently delineated characteristics of the wood-forming tissue, xylem.     

Divergent Cortical Generators of MEG and EEG during Human Sleep Spindles Suggested by Distributed Source Modeling

Background

Sleep spindles are ∼1-second bursts of 10–15 Hz activity, occurring during normal stage 2 sleep. In animals, sleep spindles can be synchronous across multiple cortical and thalamic locations, suggesting a distributed stable phase-locked generating system. The high synchrony of spindles across scalp EEG sites suggests that this may also be true in humans. However, prior MEG studies suggest multiple and varying generators.

Methodology/Principal Findings

We recorded 306 channels of MEG simultaneously with 60 channels of EEG during naturally occurring spindles of stage 2 sleep in 7 healthy subjects. High-resolution structural MRI was obtained in each subject, to define the shells for a boundary element forward solution and to reconstruct the cortex providing the solution space for a noise-normalized minimum norm source estimation procedure. Integrated across the entire duration of all spindles, sources estimated from EEG and MEG are similar, diffuse and widespread, including all lobes from both hemispheres. However, the locations, phase and amplitude of sources simultaneously estimated from MEG versus EEG are highly distinct during the same spindles. Specifically, the sources estimated from EEG are highly synchronous across the cortex, whereas those from MEG rapidly shift in phase, hemisphere, and the location within the hemisphere.

Conclusions/Significance

The heterogeneity of MEG sources implies that multiple generators are active during human sleep spindles. If the source modeling is correct, then EEG spindles are generated by a different, diffusely synchronous system. Animal studies have identified two thalamo-cortical systems, core and matrix, that produce focal or diffuse activation and thus could underlie MEG and EEG spindles, respectively. Alternatively, EEG spindles could reflect overlap at the sensors of the same sources as are seen from the MEG. Although our results generally match human intracranial recordings, additional improvements are possible and simultaneous intra- and extra-cranial measures are needed to test their accuracy.