Control of Dog Mediated Human Rabies in Haiti: No Time to Spare

The American region has pledged to eliminate dog-mediated human rabies by 2015. As part of these efforts, we describe the findings of a desk and field mission review of Haiti’s rabies situation by the end of 2013. While government officials recognize the importance of dog-mediated rabies control, and the national rabies plan adequately contemplates the basic capacities to that effect, regular and sufficient implementation, for example, of dog vaccination, is hampered by limited funding. Compounding insufficient funding and human resources, official surveillance figures do not accurately reflect the risk to the population, as evidenced by the large number of rabid dogs detected by focalized and enhanced surveillance activities conducted by the Ministry of Agriculture, Natural Resources and Rural Development (MARNDR) and the Health and Population Ministry (MSPP) with the technical assistance of the United States Centers for Disease Control and Prevention. Although international support is common, either in the form of on-the-ground technical support or donations of immunobiologicals, it is not comprehensive. In addition, there is limited coordination with MARNDR/MSPP and with other actors at the strategic or operational level due to human resources limitations. Given these findings, the 2015 elimination goal in the region is compromised by the situation in Haiti where control of the disease is not yet in sight despite the best efforts of the resolute national officials. More importantly, dog-mediated rabies is still a threat to the Haitian population.     

Assignment of the human stromelysin 3 (STMY3) gene to the q11.2 region of chromosome 22.

The human stromelysin 3 (STMY3) gene, a new member of the matrix metalloproteinase (MMP) gene family, may contribute to breast cancer cell invasion, and has been localized by in situ hybridization to the long arm of chromosome 22. As demonstrated using a panel of somatic cell hybrids, the STMY3 gene is in band 22q11.2, in close proximity to the BCR gene involved in chronic myeloid leukemia, but far from the (11;22) translocation breakpoint observed in Ewing sarcoma. This position differs from that reported on chromosomes 11 and 16 for the other MMP genes, suggesting that stromelysin 3 could be a member of a new MMP subfamily.     

Inactivation of yeast nucleotidyl transferase and its effect on the integrity of the aminoacid acceptor end of transfer RNA

Yeast tRNA nucleotidyl transferase rapidly inactivates (half life c. 2 hr) upon nitrogen starvation of exponentially growing cells. The inactivation does not occur when glucose together with the nitrogen source is removed or when glucose is replaced by ethanol. The transferase activity reappears shortly after replenishment of the nitrogen source and this appearance of the enzymatic activity is blocked by cycloheximide, indicating the need for protein biosynthesis during the process. The nucleotidyl transferase activity is also very low in stationary phase yeast cells. A ten fold decrease in the transferase activity is not paralleled by loss of the integrity of the 3' end of the tRNA chains. It seems that there is a large excess of enzymatic activity over that needed to keep the tRNA chains complete. The observed lack of the 3' end of tRNAs from late stationary phase yeast cannot be accounted for by the observed drop in transferase activity in these cells.     

TRAF4 Is a Novel Phosphoinositide-Binding Protein Modulating Tight Junctions and Favoring Cell Migration

Tumor necrosis factor (TNF) receptor-associated factor 4 (TRAF4) is frequently overexpressed in carcinomas, suggesting a specific role in cancer. Although TRAF4 protein is predominantly found at tight junctions (TJs) in normal mammary epithelial cells (MECs), it accumulates in the cytoplasm of malignant MECs. How TRAF4 is recruited and functions at TJs is unclear. Here we show that TRAF4 possesses a novel phosphoinositide (PIP)-binding domain crucial for its recruitment to TJs. Of interest, this property is shared by the other members of the TRAF protein family. Indeed, the TRAF domain of all TRAF proteins (TRAF1 to TRAF6) is a bona fide PIP-binding domain. Molecular and structural analyses revealed that the TRAF domain of TRAF4 exists as a trimer that binds up to three lipids using basic residues exposed at its surface. Cellular studies indicated that TRAF4 acts as a negative regulator of TJ and increases cell migration. These functions are dependent from its ability to interact with PIPs. Our results suggest that TRAF4 overexpression might contribute to breast cancer progression by destabilizing TJs and favoring cell migration.     

Circulating Cell-Free DNA from Colorectal Cancer Patients May Reveal High KRAS or BRAF Mutation Load

Our data might suggest a very high variation in the proportion of malignant cells in colorectal tumors and/or low tumor cell clonogenicity. However, the direct relationship between these data and the proportion of malignant cells is currently uncertain as the mechanism of ccfDNA release determines the yield (necrosis, apoptosis, or active release). Therefore, interindividual comparison of the proportion of mutant allele determined from circulating DNA could appear somewhat more difficult to interpret; however, this parameter could be an efficient biomarker for monitoring or following up CRC patients and could be combined with size fraction analysis, as demonstrated in this study, to provide a deeper examination toward this goal.     

shape In vitro effects of diacetoxyscirpenol (DAS) on human and rat granulo-monocytic progenitors

Diacetoxyscirpenol (DAS) is a trichothecene mycotoxin produced by various species of fungi. Trichothecenes are known as major contaminants of cereals and cereal-containing foods. DAS has been detected in agricultural products worldwide and persists in products after processing. In human as well as in animals, DAS consumption has been shown to induce haematological disorders (neutropenia, aplastic anemia). Granulo-monocytic progenitors (CFU-GM) from human umbilical cord blood and rat bone marrow have been cultured in the presence of DAS (from 10^-8 M to 5 × 10^-10 M) for 14 days. Study of concentration and effect relationships have shown a sharp effect of DAS on rat CFU-GM between 10^-7 M and 10^-8 M, while human CFU-GM are able to grow in the presence of 10^-8 M of the toxin. IC₅₀ values on day 14 are respectively, 7.6 × 10^-9 M for human CFU-GM and 6.2 × 10^-9 M for rat CFU-GM. This revised version was published online in June 2006 with corrections to the Cover Date.