Genome-wide translation control analysis of developing human neurons.

During neuronal differentiation, neuroprogenitor cells become polarized, change shape, extend axons, and form complex dendritic trees. While growing, axons are guided by molecular cues to their final destination, where they establish synaptic connections with other neuronal cells. Several layers of regulation are integrated to control neuronal development properly. Although control of mRNA translation plays an essential role in mammalian gene expression, how it contributes temporarily to the modulation of later stages of neuronal differentiation remains poorly understood. Here, we investigated how translation control affects pathways and processes essential for neuronal maturation, using H9-derived human neuro progenitor cells differentiated into neurons as a model. Through Ribosome Profiling (Riboseq) combined with RNA sequencing (RNAseq) analysis, we found that translation control regulates the expression of critical hub genes. Fundamental synaptic vesicle secretion genes belonging to SNARE complex, Rab family members, and vesicle acidification ATPases are strongly translationally regulated in developing neurons. Translational control also participates in neuronal metabolism modulation, particularly affecting genes involved in the TCA cycle and glutamate synthesis/catabolism. Importantly, we found translation regulation of several critical genes with fundamental roles regulating actin and microtubule cytoskeleton pathways, critical to neurite generation, spine formation, axon guidance, and circuit formation. Our results show that translational control dynamically integrates important signals in neurons, regulating several aspects of its development and biology.

Translational Control during Mammalian Neocortex Development and Postembryonic Neuronal Function.

The control of mRNA translation has key roles in the regulation of gene expression and biological processes such as mammalian cellular differentiation and identity. Methodological advances in the last decade have resulted in considerable progress towards understanding how translational control contributes to the regulation of diverse biological phenomena. In this review, we discuss recent findings in the involvement of translational control in the mammalian neocortex development and neuronal biology. We focus on regulatory mechanisms that modulate translational efficiency during neural stem cells self-renewal and differentiation, as well as in neuronal-related processes such as synapse, plasticity, and memory.

Decrease of Pericytes is Associated With Liver Disease Caused by Ligature-Induced Periodontitis in Rats.

BACKGROUND: Damage caused by periodontitis not only affects periodontal tissues, but also increases the severity of various illnesses such as rheumatoid arthritis, diabetes, and liver diseases. The aim of this study is to investigate the association between induced periodontitis and damage caused through its systemic effects on the liver. METHODS: Twenty rats were divided into two groups: control and periodontitis. The following parameters were evaluated: gingival bleeding index (GBI), probing depth (PD), myeloperoxidase (MPO) activity, alveolar bone loss (ABL) for periodontal tissues; histopathologic examination of gingival and liver tissues; immunohistochemistry to cells positive for neural/glial antigen 2 (NG2) expressed in hepatic pericytes, glutathione (GSH), and malondialdehyde (MDA) concentrations in liver; and serum levels of alanine aminotransferase and aspartate aminotransferase. RESULTS: GBI, PD, MPO, ABL, and histopathologic examinations demonstrated the development of periodontitis. There was a significant increase in microvesicular steatosis accompanied by a marked reduction in NG2+ pericytes in the periodontitis group compared with the control group. The periodontitis group had significantly lower GSH and higher MDA concentration in the liver compared with the control group. CONCLUSIONS: The present study results link the systemic effects of induced periodontitis with changes in hepatic tissues such as microvesicular steatosis, likely caused by an increase in oxidative stress and lipid peroxidation. The findings from the present study implicate an association between a decrease of pericytes and liver disease caused by ligature-induced periodontitis in rats.

Effects of titanium surface anodization with CaP incorporation on human osteoblastic response.

In this study we investigated whether anodization with calcium phosphate (CaP) incorporation (Vulcano®) enhances growth factors' secretion, osteoblast-specific gene expression, and cell viability, when compared to acid etched surfaces (Porous®) and machined surfaces (Screw®) after 3 and 7days. Results showed significant cell viability for Porous and Vulcano at day 7, when compared with Screw (p=0.005). At the same time point, significant differences regarding runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP) and bone sialoprotein (BSP) expression were found for all surfaces (p<0.05), but with greater fold induction for Porous and Vulcano. The secretion of transforming growth factor ß1 (TGF-ß1) and bone morphogenetic protein 2 (BMP-2) was not significantly affected by surface treatment in any experimental time (p>0.05). Although no significant correlation was found for growth factors' secretion and Runx2 expression, a significant positive correlation between this gene and ALP/BSP expression showed that their strong association is independent on the type of surface. The incorporation of CaP affected the biological parameters evaluated similar to surfaces just acid etched. The results presented here support the observations that roughness also may play an important role in determining cell response.

Cytotoxic response of two cell lines exposed in vitro to four endodontic sealers

Aim: To investigate the cytotoxicity of four endodontic sealers with different bases – Epiphany(EPH), AH Plus (AHP), Sealer 26 (S26) and Endofill (ENF) – on human foreskin fibroblasts(HFF) and mouse macrophages (J774/G8). Methods: Cells were placed in direct contact withfreshly prepared endodontic sealers in polypropylene tubes. The cells were incubated for 24, 48and 72 h. Cytotoxicity was assessed using the MTT assay (cell viability) and Griess reagent (NOrelease). Results: On the HFF cultures, EPH showed the lowest viability levels of all four sealersat 24 h (p<0.05), but over time (72h), EPH lessened its toxic levels in a similar pattern as the otherthree materials (p>0.05). The viability of all four sealers on the macrophage cultures showed nostatistically significant difference over time, except between EPH and AHP at 72 h (p<0.05).Although uniformity was not detected in macrophage and fibroblast release of NO in response tosealers over time, a trend of increased NO levels for EPH (p<0.05) was observed. Conclusions:The response pattern varied depending on time and type of cell line used for analysis, althoughthe results indicate a higher cytotoxicity for EPH in short-term tests.