Food-borne outbreak of norovirus infection in a French military parachuting unit, April 2011.

On 13 April 2011 the medical service of a French military parachuting unit reported an outbreak of acute gastroenteritis involving 147 persons among the military personnel. Meals suspected to have caused the outbreak (pasta and some raw vegetables) were tested for norovirus by PCR. The same norovirus (genogroup I) was found in some of the food items consumed by the cases and in a cook who prepared the meals.

The human NTERA2 neural cell line generates neurons on growth under neural stem cell conditions and exhibits characteristics of radial glial cells.

NTERA2 cells are a human neural cell line generating neurons after exposure to retinoic acid and, as such, are widely used as a model of neurogenesis. We report that these cells form spheres when grown in serum-free medium supplemented with basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF). These spheres were found to express markers of radial glial cells such as, Pax6, glutamate transporter (GLAST), tenascin C, brain lipid-binding protein (BLBP), and the 3CB2 antigen. On plating on an adhesive substrate, NTERA2 spheres generate a large percentage of immature neurons (30-50%) together with a minority of cells of the oligodendrocyte lineage. Thus NTERA2 cells share properties with neural stem cells. However, at variance with the latter, we found that they produce their own bFGF implicated in an autocrine or paracrine proliferative loop and that they do not generate astrocytes after differentiation. These results provide an interesting model to study radial glial cells and their role in human neurogenesis.

Mitochondrial activity is involved in the regulation of myoblast differentiation through myogenin expression and activity of myogenic factors.

To characterize the regulatory pathways involved in the inhibition of cell differentiation induced by the impairment of mitochondrial activity, we investigated the relationships occurring between organelle activity and myogenesis using an avian myoblast cell line (QM7). The inhibition of mitochondrial translation by chloramphenicol led to a potent block of myoblast differentiation. Carbonyl cyanide p-(trifluoromethoxy) phenylhydrazone and oligomycin, which affect the organelle at different levels, exerted a similar influence. In addition, we provided evidence that this phenomenon was not the result of an alteration in cell viability. Conversely, overexpression of the mitochondrial T3 receptor (p43) stimulated organelle activity and strongly potentiated myoblast differentiation. The involvement of mitochondrial activity in an actual regulation of myogenesis is further supported by results demonstrating that the muscle regulatory gene myogenin, in contrast to CMD1 (chicken MyoD) and myf5, is a specific transcriptional target of mitochondrial activity. Whereas myogenin mRNA and protein levels were down-regulated by chloramphenicol treatment, they were up-regulated by p43 overexpression, in a positive relationship with the expression level of the transgene. We also found that myogenin or CMD1 overexpression in chloramphenicol-treated myoblasts did not restore differentiation, thus indicating that an alteration in mitochondrial activity interferes with the ability of myogenic factors to induce terminal differentiation.

A variant form of the nuclear triiodothyronine receptor c-ErbAalpha1 plays a direct role in regulation of mitochondrial RNA synthesis.

In earlier research, we identified a 43-kDa c-ErbAalpha1 protein (p43) in the mitochondrial matrix of rat liver. In the present work, binding experiments indicate that p43 displays an affinity for triiodothyronine (T3) similar to that of the T3 nuclear receptor. Using in organello import experiments, we found that p43 is targeted to the organelle by an unusual process similar to that previously reported for MTF1, a yeast mitochondrial transcription factor. DNA-binding experiments demonstrated that p43 specifically binds to four mitochondrial DNA sequences with a high similarity to nuclear T3 response elements (mt-T3REs). Using in organello transcription experiments, we observed that p43 increases the levels of both precursor and mature mitochondrial transcripts and the ratio of mRNA to rRNA in a T3-dependent manner. These events lead to stimulation of mitochondrial protein synthesis. In transient-transfection assays with reporter genes driven by the mitochondrial D loop or two mt-T3REs located in the D loop, p43 stimulated reporter gene activity only in the presence of T3. All these effects were abolished by deletion of the DNA-binding domain of p43. Finally, p43 overexpression in QM7 cells increased the levels of mitochondrial mRNAs, thus indicating that the in organello influence of p43 was physiologically relevant. These data reveal a novel hormonal pathway functioning within the mitochondrion, involving a truncated form of a nuclear receptor acting as a potent mitochondrial T3-dependent transcription factor.

BTG1: a triiodothyronine target involved in the myogenic influence of the hormone.

The product of the B-cell translocation gene 1 (BTG1), a member of an antiproliferative protein family including Tis-21/PC3 and Tob, is thought to play an important role in the regulation of cell cycle progression. We have shown in a previous work that triiodothyronine (T3) stimulates quail myoblast differentiation, partly through a cAMP-dependent mechanism involved in the stimulation of cell cycle withdrawal. Furthermore, we found that T3 or 8-Br-cAMP increases BTG1 nuclear accumulation in confluent myoblast cultures. In this study, we report that BTG1 is essentially expressed at cell confluence and in differentiated myotubes. Whereas neither T3 nor cAMP exerted a direct transcriptional control upon BTG1 expression, we found that AP-1 activity, a crucial target involved in the triiodothyronine myogenic influence, repressed BTG1 expression, thus probably explaining the low BTG1 expression level in proliferating myoblasts. In transient transfection studies, we demonstrated that an AP-1-like sequence located in the BTG1 promoter was involved in this negative regulation. Our present data also bring evidence that the stimulation of BTG1 nuclear accumulation by T3 or 8-Br-cAMP probably results from an increased nuclear import or retention in the nucleus. Lastly, BTG1 overexpression in quail myoblasts mimicked the T3 or 8-Br-cAMP myogenic influence: (i) inhibition of myoblast proliferation due to an increased rate of myoblast withdrawal from the cell cycle; and (ii) stimulation of terminal differentiation. These data suggest that BTG1 is probably involved in T3 and cAMP myogenic influences. In conclusion, BTG1 is a T3 target involved in the regulation of myoblast differentiation.