Publication Title: 
The Journal of Neuroscience: The Official Journal of the Society for Neuroscience

Spinal muscular atrophy (SMA), a recessive neurodegenerative disease, is characterized by the selective loss of spinal motor neurons. No available therapy exists for SMA, which represents one of the leading genetic causes of death in childhood. SMA is caused by a mutation of the survival-of-motor-neuron 1 (SMN1) gene, leading to a quantitative defect in the survival-motor-neuron (SMN) protein expression. All patients retain one or more copies of the SMN2 gene, which modulates the disease severity by producing a small amount of stable SMN protein.

Branchu, Julien
Biondi, Olivier
Chali, Farah
Collin, Thibault
Leroy, Felix
Mamchaoui, Kamel
Makoukji, Joelle
Pariset, Claude
Lopes, Philippe
Massaad, Charbel
Chanoine, Christophe
Charbonnier, FrÈdÈric
Publication Title: 
The Journal of Biological Chemistry

Estrogen receptors (ER alpha/ER beta) are expressed in neuronal cells and exhibit a variety of activities in the central nervous system. ER activity is regulated in a ligand-dependent manner and by co-regulatory factors. Caveolin-1 is a recently identified co-activator of ER alpha mediating the ligand-independent activation of this steroid receptor. Here the influence of ERs on caveolin expression in human neuroblastoma SK-N-MC cells as well as in rodent brain was investigated.

Zschocke, J¸rgen
Manthey, Dieter
Bayatti, Nadhim
van der Burg, Bart
Goodenough, Sharon
Behl, Christian
Publication Title: 
Applied Microbiology and Biotechnology

In comparison to other bacteria Bacillus subtilis emits the volatile compound isoprene in high concentrations. Isoprene is the smallest representative of the natural product group of terpenoids. A search in the genome of B. subtilis resulted in a set of genes with yet unknown function, but putatively involved in the methylerythritol phosphate (MEP) pathway to isoprene. Further identification of these genes would give the possibility to engineer B. subtilis as a host cell for the production of terpenoids like the valuable plant-produced drugs artemisinin and paclitaxel.

Julsing, Mattijs K.
Rijpkema, Michael
Woerdenbag, Herman J.
Quax, Wim J.
Kayser, Oliver
Publication Title: 
The Journal of Biological Chemistry

The roles of MEK, ERK, the epsilon and alpha isoforms of protein kinase C (PKC), and caveolin-1 in regulating collagen expression were studied in normal lung fibroblasts. Knocking down caveolin-1 gave particularly striking results. A 70% decrease caused a 5-fold increase in MEK/ERK activation and collagen expression. The combined data reveal a branched signaling pathway. In its central portion MEK activates ERK, leading to increased collagen expression. Two branches converge on MEK/ERK. In one, increased PKCepsilon leads to MEK/ERK activation.

Tourkina, Elena
Gooz, Pal
Pannu, Jaspreet
Bonner, Michael
Scholz, Dimitri
Hacker, Sharon
Silver, Richard M.
Trojanowska, Maria
Hoffman, Stanley
Publication Title: 
Toxicology and Applied Pharmacology

CD40 is a costimulatory molecule linking innate and adaptive immune responses to bacterial stimuli, as well as a critical regulator of functions of other costimulatory molecules. The mechanisms regulating lipopolysaccharide (LPS)-induced CD40 expression have not been adequately characterized in human monocytic cells. In this study we used a human monocytic cell line, THP-1, to investigate the possible mechanisms of CD40 expression following LPS exposure. Exposure to LPS resulted in a dose- and time-dependent increase in CD40 expression.

Wu, Weidong
Alexis, Neil E.
Chen, Xian
Bromberg, Philip A.
Peden, David B.
Publication Title: 

OBJECTIVES: Prostaglandin E2 (PGE2) is a product of cyclooxygenase (COX) and PGE synthase (PGES) and deactivated by 15-hydroxyprostaglandin dehydrogenase (PGDH). Down-regulation of PGDH contributes to PGE2 accumulation in lung and colon cancers but has not been identified in pancreatic cancer.

Pham, Hung
Chen, Monica
Li, Aihua
King, Jonathan
Angst, Eliane
Dawson, David W.
Park, Jenny
Reber, Howard A.
Hines, O. Joe
Eibl, Guido
Publication Title: 
PloS One

BACKGROUND: During inflammation, adhesion molecules regulate recruitment of leukocytes to inflamed tissues. It is reported that vascular cell adhesion molecule-1 (VCAM-1) activates extracellular regulated kinases 1 and 2 (ERK1/2), but the mechanism for this activation is not known. Pharmacological inhibitors of ERK1/2 partially inhibit leukocyte transendothelial migration in a multi-receptor system but it is not known whether VCAM-1 activation of ERK1/2 is required for leukocyte transendothelial migration (TEM) on VCAM-1.

Abdala-Valencia, Hiam
Berdnikovs, Sergejs
Cook-Mills, Joan M.
Publication Title: 
Hepatology (Baltimore, Md.)

RNA-binding proteins (RBPs) play a major role in the control of messenger RNA (mRNA) turnover and translation rates. We examined the role of the RBP, human antigen R (HuR), during cholestatic liver injury and hepatic stellate cell (HSC) activation. HuR silencing attenuated fibrosis development in vivo after BDL, reducing liver damage, oxidative stress, inflammation, and collagen and alpha smooth muscle actin (α-SMA) expression. HuR expression increased in activated HSCs from bile duct ligation mice and during HSC activation in vitro, and HuR silencing markedly reduced HSC activation.

Woodhoo, Ashwin
Iruarrizaga-Lejarreta, Marta
Beraza, Naiara
García-Rodríguez, Juan L.
Embade, Nieves
Fernández-Ramos, David
Martínez-López, Nuria
Gutierrez-de Juan, Virginia
Arteta, Beatriz
Caballeria, Juan
Lu, Shelly C.
Mato, José M.
Varela-Rey, Marta
Martínez-Chantar, María L.
Publication Title: 
Journal of Neuroimmunology

Zymosan has previously been reported to have both pro-inflammatory and anti-inflammatory effects. Here we demonstrate that low dose zymosan prevented or reversed chronic and relapsing paralysis in EAE. In suppressing CNS autoimmune inflammation, zymosan not only regulated APC costimulator and MHC class II expression, but also promoted differentiation of regulatory T cells. Following adoptive transfer of zymosan-primed CD4(+) T cells, recipient mice were protected from EAE. In contrast, a MAPK inhibitor and a blocker of β-glucan, reversed the effects of zymosan.

Li, Hongmei
Gonnella, Patricia
Safavi, Farinaz
Vessal, Ghazal
Nourbakhsh, Bardia
Zhou, Fang
Zhang, Guang-Xian
Rostami, Abdolmohamad
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