Genome-wide analysis reveals that Smad3 and JMJD3 HDM co-activate the neural developmental program

Neural development requires crosstalk between signaling pathways and chromatin. In this study, we demonstrate that neurogenesis is promoted by an interplay between the TGFβ pathway and the H3K27me3 histone demethylase (HDM) JMJD3. Genome-wide analysis showed that JMJD3 is targeted to gene promoters by Smad3 in neural stem cells (NSCs) and is essential to activate TGFβ-responsive genes. In vivo experiments in chick spinal cord revealed that the generation of neurons promoted by Smad3 is dependent on JMJD3 HDM activity. Overall, these findings indicate that JMJD3 function is required for the TGFβ developmental program to proceed.     

Effect of range of motion on muscle strength and thickness

The purpose of this investigation was to compare partial range-of-motion vs. full range-of-motion upper-body resistance training on strength and muscle thickness (MT) in young men. Volunteers were randomly assigned to 3 groups: (a) full range of motion (FULL; n = 15), (b) partial range of motion (PART; n = 15), or (c) control (CON; n = 10). The subjects trained 2 d · wk(-1) for 10 weeks in a periodized program. Primary outcome measures included elbow flexion maximal strength measured by 1 repetition maximum (1RM) and elbow flexors MT measured by ultrasound. The results indicated that elbow flexion 1RM significantly increased (p < 0.05) for the FULL (25.7 ± 9.6%) and PART groups (16.0 ± 6.7%) but not for the CON group (1.7 ± 5.5%). Also, FULL 1RM strength was significantly greater than the PART 1RM after the training period. Average elbow flexor MT significantly increased for both training groups (9.65 ± 4.4% for FULL and 7.83 ± 4.9 for PART). These data suggest that muscle strength and MT can be improved with both FULL and PART resistance training, but FULL may lead to greater strength gains.     

Rosmarinic acid prevents lipid peroxidation and increase in acetylcholinesterase activity in brain of streptozotocin‐induced diabetic rats

We investigated the efficacy of rosmarinic acid (RA) in preventing lipid peroxidation and increased activity of acetylcholinesterase (AChE) in the brain of streptozotocin‐induced diabetic rats. The animals were divided into six groups (n = 8): control, ethanol, RA 10 mg/kg, diabetic, diabetic/ethanol and diabetic/RA 10 mg/kg. After 21 days of treatment with RA, the cerebral structures (striatum, cortex and hippocampus) were removed for experimental assays. The results demonstrated that the treatment with RA (10 mg/kg) significantly reduced the level of lipid peroxidation in hippocampus (28%), cortex (38%) and striatum (47%) of diabetic rats when compared with the control. In addition, it was found that hyperglycaemia caused significant increased in the activity of AChE in hippocampus (58%), cortex (46%) and striatum (30%) in comparison with the control. On the other hand, the treatment with RA reversed this effect to the level of control after 3 weeks. In conclusion, the present findings showed that treatment with RA prevents the lipid peroxidation and consequently the increase in AChE activity in diabetic rats, demonstrating that this compound can modulate cholinergic neurotransmission and prevent damage oxidative in brain in the diabetic state. Thus, we can suggest that RA could be a promising compound in the complementary therapy in diabetes. Copyright © 2013 John Wiley & Sons, Ltd.     

Trypanosoma cruzi: the effects of zinc supplementation during experimental infection

It is well recognized that zinc is an essential trace element, influencing growth and affecting the development and integrity of the immune system. The use of oligoelements as zinc can be considered a tool in modulating the effectiveness of the immune response. In this work zinc was daily and orally supplied in male Wistar rats infected with the Y strain of Trypanosoma cruzi. Parasitemia was evaluated and a significant reduction on blood parasites was observed. In order to check some immunological parameters peritoneal macrophages were counted revealing higher percentages for zinc supplied group. Consequently enhanced concentrations of IFN-gamma was found and for the first time NO was evaluated in T. cruzi infected animals under the influence of zinc therapy, revealing enhanced concentrations when compared to unsupplied counterparts. We conclude that zinc is able to up-regulate the host's immune response against parasite replication.     

Trypanosoma cruzi: orchiectomy and dehydroepiandrosterone therapy in infected rats

The ability of gonadal hormones to influence and induce diverse immunological functions during the course of a number of parasitic infections has been extensively studied in the latest decades. Dehydroepiandrosterone and its sulfate are the most abundant steroid hormones secreted by the human adrenal cortex and are considered potent immune-activators. The effects of orchiectomy on the course of Trypanosoma cruzi infection in rats, treated and untreated with DHEA were examined, by comparing blood and cardiac parasitism, macrophage numbers, nitric oxide and IFN-γ levels. Orchiectomy enhanced resistance against infection with elevated numbers of macrophages, enhanced concentrations of NO and IFN-γ and reduced amastigote burdens in heart when compared to control animals. DHEA replacement exerted a synergistic effect, up-modulating the immune response. Male sex steroids appear to play fundamental role in determining the outcome of disease, through the regulation and modulation of the activity of the immune response.     

Effects of chlorogenic acid,caffeine, and coffee on behavioral and biochemical parameters of diabetic rats

Mesenchymal stem cells (MSCs) represent a potential therapeutic target for glioma. We determined the molecular mechanism of inhibitory effect of human umbilical cord-derived MSCs (hUC-MSCs) on the growth of C6 glioma cells. We demonstrated that hUC-MSCs inhibited C6 cell growth and modulated the cell cycle to G0/G1 phase. The expression of β-catenin and c-Myc was downregulated in C6 cells by conditioned media from hUC-MSCs, and the levels of secreted DKK1 were positively correlated with concentrations of hUCMSCs-CM. The inhibitory effect of hUC-MSCs on C6 cell proliferation was enhanced as the concentration of DKK1 in hUCMSCs-CM increased. When DKK1 was neutralized by anti-DKK1 antibody, the inhibitory effect of hUC-MSCs on C6 cells was attenuated. Furthermore, we found that conditioned media from hUC-MSCs transfection with siRNA targeting DKK1 mRNA or pEGFPN1-DKK1 plasmid lost or enhanced the abilities to regulate the Wnt signaling in C6 cells. Therefore, hUC-MSCs inhibited C6 glioma cell growth via secreting DKK1, an inhibitor of Wnt pathway, may represent a novel therapeutic strategy for malignant glioma.     

Exercise training prevents ecto-nucleotidases alterations in platelets of hypertensive rats

Mechano-growth factor (MGF) has emerged as an important mechanosensitive player in bone repair, but understanding of MGF function is hampered by the fact that MGF receptor and the underlying pathways remain unknown. In this study, fluorescein isothiocyanate (FITC)-labeled MGF-Ct24E (FITC-MGF) was used to determine the subcellular localization of MGF receptor in osteoblasts. After the primary osteoblasts were exposed to stretch with the strain at 10?%, and/or loaded with 50?ng/ml exogenous MGF-Ct24E, cells were incubated with the different concentrations of FITC-MGF (0.01, 0.1, and 1?mg/ml) followed by flow cytometry and laser scanning confocal microscope analysis. Our results showed that the fluorescence intensity and cell population internalizing FITC-MGF increased with the concentration of FITC-MGF. And all the cells were labeled with fluorescence at 1?mg/ml. Notably, FITC-MGF had nuclear localization when osteoblasts were exposed to stretch and/or 50?ng/ml MGF-Ct24E added, compared to the evident cytoplasmic localization in the static culture group. The nuclear localization of FITC-MGF in response to mechanical loading was found to associate with high expression of proliferating cell nuclear antigen, suggesting MGF and its receptor could serve as potential messengers that replay information in nuclei to control cell proliferation.     

4-HPR-mediated leukemia cell cytotoxicity is triggered by ceramide-induced mitochondrial oxidative stress and is regulated downstream by Bcl-2

We have previously reported that, in leukemia cells, the cytotoxicity of the anticancer agent N-(4-hydroxyphenyl)retinamide (4-HPR) is mediated by mitochondria-derived reactive oxygen species (ROS) and cardiolipin peroxidation. Here, we have analyzed at greater depth the 4-HPR-triggered molecular events, demonstrating that 4-HPR induces an early (15 min) increase in ceramide levels by sphingomyelin hydrolysis and later (from 1 h) by de novo synthesis. Using specific inhibitors of both pathways, we demonstrate that ceramide accumulation is responsible for early ROS generation, which act as apoptotic signalling intermediates leading to conformational activation of Bak and Bax, loss of mitochondrial membrane potential (ΔΨm), mitochondrial membrane permeabilization (MMP) and cell death. Enforced expression of Bcl-2 has no effect on 4-HPR-induced oxidative stress, but notably prevents mitochondrial alterations and apoptosis, indicating that Bcl-2 functions by regulating events downstream of ROS generation. In conclusion, our study delineates for the fist time the sequence and timing of the principal events induced by 4-HPR in leukemia cells and points to the potential use of modulators of ceramide metabolism as enhancers in 4-HPR-based therapies.     

LORACS: JAVA software for modeling landscape connectivity and matrix permeability

GIS tools and remote sensing products have opened the possibility to model the impacts of matrix permeability on a broad range of ecological phenomena. LORACS (Landscape ORganization and Connectivity Survey) is JAVA software containing a GUI interface and an API for easy extensibility. The user inputs maps with the relative costs to move within each pixel and the location of source and target patches. The software outputs Multiple Shortest Paths and Conditional Minimum Transit Cost maps. One key feature is the derivation of uncertainty estimates around path length, cost, and spatial distribution. We use data from the Brazilian Atlantic Forest to illustrate how LORACS can be used to translate assumptions about habitat quality into landscape connectivity patterns.