PML-RARA-associated cooperating mutations belong to a transcriptional network that is deregulated in myeloid leukemias.

It has been shown that individual acute myeloid leukemia (AML) patients are characterized by one of few initiating DNA mutations and 5-10 cooperating mutations not yet defined among hundreds identified by massive sequencing of AML genomes. We report an in vivo insertional-mutagenesis screen for genes cooperating with one AML initiating mutations (PML-RARA, oncogene of acute promyelocytic leukemia, APL), which allowed identification of hundreds of genetic cooperators. The cooperators are mutated at low frequency in APL or AML patients but are always abnormally expressed in a cohort of 182 APLs and AMLs analyzed. These deregulations appear non-randomly distributed and present in all samples, regardless of their associated genomic mutations. Reverse-engineering approaches showed that these cooperators belong to a single transcriptional gene network, enriched in genes mutated in AMLs, where perturbation of single genes modifies expression of others. Their gene-ontology analysis showed enrichment of genes directly involved in cell proliferation control. Therefore, the pool of PML-RARA cooperating mutations appears large and heterogeneous, but functionally equivalent and deregulated in the majority of APLs and AMLs. Our data suggest that the high heterogeneity of DNA mutations in APLs and AMLs can be reduced to patterns of gene expression deregulation of a single 'mutated' gene network.

Investigation on Opisthorchis felineus occurrence and life cycle in Italy.

Opisthorchiasis is a fish borne parasitic infection caused by helminths of the genus Opisthorchis (Digenea, Opisthorchiidae), affecting humans and other fish-eating mammals. Despite Opisthorchis felineus was first described in Italy in 1884, no cases of human opisthorchiasis were reported in this country until 2004; from then on, 4 outbreaks due to this species have been recorded in Central Italy. Following the more relevant of these outbreaks, involving 34 people in August 2007, snails, fishes and fecal samples collected from the Bolsena and Bracciano lakes (Central Italy) were analyzed in order to define the cycle of O. felineus in the area and investigate its prevalence in the different hosts. Pools of 20-40 snails each (4983 specimens altogether) of the genus Bithynia were analyzed by PCR for parasite DNA detection. Eight hundred and ninety-four fish belonging to 12 species were collected from the two lakes and tested for metacercariae both by muscle compression and digestion techniques. Eighty-seven fecal samples of 5 putative definitive host species were collected very close to the two lakes and tested for parasite eggs detection by formalin-ethyl acetate concentration technique. Identification at the species level of metacercariae and eggs, respectively, from fish and stool was confirmed by PCR analysis and sequencing. O. felineus DNA was detected in 0.08% (overall minimum infection rate) of snails of the genus Bithynia from the two lakes. The tench, Tinca tinca, was the only fish found infested in both lakes (prevalence 88.5%). O. felineus eggs were found only in cat feces (prevalence 46.4%). The tench represents the only threat for the human consumption in the study area while Coregonus sp., the most economically important species for the local fishery and frequently consumed raw marinated, resulted to be not infected. The high prevalence recorded both in fish and in definitive host suggests a widespread and massive presence of the parasite in the area. Further studies are needed to better investigate the possible role of some cyprinids species as intermediate hosts, in order to check their safety for human consumption.

Occurrence of Salmonella in swine in the Latium Region (central Italy) from 1980 to 1989: a retrospective study.

An extensive survey was carried out on 849 biological samples (dead animals, organs and viscera, faeces, and rectal swabs) from pigs in the Latium Region (Central Italy) throughout the years 1980-1989. In total, 46 of the samples (5.4%) were found to be bacteriologically positive for salmonellae. Among dead animals, typical gross lesions were observed in 6 clinically infected animals. As far as serotypes are concerned, 11 different ones were isolated, with a predominance of Salmonella typhimurium (26.1%), S. anatum (21.7%), S. bovis-morbificans (15.2%), and S. heidelberg (10.8%). According to Kauffmann-White's classification scheme, 39.1% of the isolated strains belonged to serogroup B, 13% to serogroup C1, 17.4% tot serogroup C2, 6.5% to serogroup D, and 23.9% to serogroup E1. In conclusion, the authors speculate that the relatively low Salmonella isolation frequency (5.4%) reported in this study was not dependent upon the cultural procedures used, since different enrichment and plating methods were used, but rather upon the great number of rural-type herds which were investigated over the decade compared to industrial-type herds. Other factors such as stress conditions, which are particularly pronounced in industrial-type herds, and overall climatic situations, which tend to be characterised by warm, dry and long summers in the Latium Region, are also considered in this respect.