Prenatal Exposure of Rats to Staphylococcal Enterotoxin B Alters the Expression of Th1 and Th2 Cytokines via Decreased Methylation in the Spleen of Adult but not Neonatal Offspring.

Background: The methylation of IFN-γ and IL-4 genes is regarded as an epigenetic regulation that maintains the Th1 or Th2 phenotype.

Objective: To explore the influence of prenatal administration of the staphylococcal enterotoxin B (SEB) in pregnant rats, on the IFN-γ or IL-4 expression in the offspring spleen.

Methods: The SEB or PBS was administered intravenously to pregnant rats on the embryo-day 16.

Exposure of pregnant rats to staphylococcal enterotoxin B increases offspring splenic Treg number and function via decreasing FoxP3 methylation.

Staphylococcus aureus is an infectious pathogen that is relatively common, but that can cause severe disease in pregnant women and their fetus. We previously demonstrated that exposing pregnant rats to staphylococcal enterotoxin B (SEB) altered splenic CD4/CD8 T cell frequencies in their offspring. Whether prenatal SEB exposure impacts Tregs in these offspring, however, remains to be determined.

High-energy femtosecond amplifier-similariton Er-doped fiber oscillator.

We demonstrated high-energy femtosecond amplifier-similariton oscillators with predominant Er-doped fibers of normal dispersion. Stably mode-locked pulses of ~3 ps, 33 nJ were produced at 720 mW pump power, while a double-pass grating pair of 36% efficiency compressed the pulses to 156 fs and 47 kW peak power (a new record). Broad mode-locked spectra supporting transform-limited pulsewidths down to 60 fs were obtained by adjusting the intracavity waveplates and filter.

Famitinib in metastatic renal cell carcinoma: a single center study.

Background: Famitinib is a novel and potent multitargeting receptor tyrosine kinase inhibitor. The phase I clinical study showed that famitinib was well tolerated and had a broad anti-tumor spectrum. The purpose of this study was to examine the efficacy and safety of famitinib for the treatment of metastatic renal cell carcinoma (mRCC).

Translational control of C-terminal Src kinase (Csk) expression by PRL3 phosphatase.

Phosphatase of regenerating liver 3 (PRL3) is up-regulated in cancer metastases. However, little is known of PRL3-mediated cellular signaling pathways. We previously reported that elevated PRL3 expression increases Src kinase activity, which likely contributes to the increased tumorigenesis and metastasis potential of PRL3.

The unfolded protein response of B-lymphocytes: PERK-independent development of antibody-secreting cells.

When B-lymphocytes differentiate into plasma cells, immunoglobulin (Ig) heavy and light chain synthesis escalates and the entire secretory apparatus expands to support high-rate antibody secretion. These same events occur when murine B-cells are stimulated with lipopolysaccharide (LPS), providing an in vitro model in which to investigate the differentiation process. The unfolded protein response (UPR), a multi-pathway signaling response emanating from the endoplasmic reticulum (ER) membrane, allows cells to adapt to increasing demands on the protein folding capacity of the ER.

The eukaryotic initiation factor-2 kinase pathway facilitates differential GADD45a expression in response to environmental stress.

Phosphorylation of eukaryotic initiation factor-2 (eIF2) regulates general and gene-specific translation in response to diverse environmental stresses. Central to gene expression induced by eIF2 phosphorylation is the preferential translation of ATF4, a basic zipper transcription activator. Phosphorylation of eIF2 and its attendant induction of ATF4 can lead to different patterns of gene expression depending on the environmental stress.

Aggregation and porin-like channel activity of a beta sheet peptide.

Beta sheet peptides (e.g., amyloid beta) are known to form ion channels in lipid bilayers possibly through aggregation, though the channel structure is not clear.

IMPACT, a protein preferentially expressed in the mouse brain, binds GCN1 and inhibits GCN2 activation.

Translational control directed by the eukaryotic translation initiation factor 2 alpha-subunit (eIF2alpha) kinase GCN2 is important for coordinating gene expression programs in response to nutritional deprivation. The GCN2 stress response, conserved from yeast to mammals, is critical for resistance to nutritional deficiencies and for the control of feeding behaviors in rodents. The mouse protein IMPACT has sequence similarities to the yeast YIH1 protein, an inhibitor of GCN2.

Phosphorylation of the alpha-subunit of the eukaryotic initiation factor-2 (eIF2alpha) reduces protein synthesis and enhances apoptosis in response to proteasome inhibition.

Protein ubiquitination and subsequent degradation by the proteasome are important mechanisms regulating cell cycle, growth and differentiation, and apoptosis. Recent studies in cancer therapy suggest that drugs that disrupt the ubiquitin/proteasome pathway induce apoptosis and sensitize malignant cells and tumors to conventional chemotherapy. In this study we addressed the role of phosphorylation of the alpha-subunit eukaryotic initiation factor-2 (eIF2), and its attendant regulation of gene expression, in the cellular stress response to proteasome inhibition.

GCN2 phosphorylation of eIF2alpha activates NF-kappaB in response to UV irradiation.

In response to UV irradiation, mammalian cells elicit a gene expression programme designed to repair damage and control cell proliferation and apoptosis. Important members of this stress response include the NF-kappaB (nuclear factor-kappaB) family. However, the mechanisms by which UV irradiation activates NF-kappaB are not well understood.

B-Myb represses vascular smooth muscle cell collagen gene expression and inhibits neointima formation after arterial injury.

Objective: The function of B-Myb, a negative regulator of vascular smooth muscle cell (SMC) matrix gene transcription, was analyzed in the vasculature.

Methods And Results: Mice were generated in which the human B-myb gene was driven by the basal cytomegalovirus promoter, and 3 founders were identified. Mice appeared to develop normally, and human B-myb was expressed in the aortas.

Activating transcription factor 3 is integral to the eukaryotic initiation factor 2 kinase stress response.

In response to environmental stress, cells induce a program of gene expression designed to remedy cellular damage or, alternatively, induce apoptosis. In this report, we explore the role of a family of protein kinases that phosphorylate eukaryotic initiation factor 2 (eIF2) in coordinating stress gene responses. We find that expression of activating transcription factor 3 (ATF3), a member of the ATF/CREB subfamily of basic-region leucine zipper (bZIP) proteins, is induced in response to endoplasmic reticulum (ER) stress or amino acid starvation by a mechanism requiring eIF2 kinases PEK (Perk or EIF2AK3) and GCN2 (EIF2AK4), respectively.

Phosphorylation of the alpha subunit of eukaryotic initiation factor 2 is required for activation of NF-kappaB in response to diverse cellular stresses.

Nuclear factor kappaB (NF-kappaB) serves to coordinate the transcription of genes in response to diverse environmental stresses. In this report we show that phosphorylation of the alpha subunit of eukaryotic initiation factor 2 (eIF2) is fundamental to the process by which many stress signals activate NF-kappaB. Phosphorylation of this translation factor is carried out by a family of protein kinases that each respond to distinct stress conditions.