Loss of LZAP inactivates p53 and regulates sensitivity of cells to DNA damage in a p53-dependent manner.

Chemotherapy and radiation, the two most common cancer therapies, exert their anticancer effects by causing damage to cellular DNA. However, systemic treatment damages DNA not only in cancer, but also in healthy cells, resulting in the progression of serious side effects and limiting efficacy of the treatment. Interestingly, in response to DNA damage, p53 seems to play an opposite role in normal and in the majority of cancer cells-wild-type p53 mediates apoptosis in healthy tissues, attributing to the side effects, whereas mutant p53 often is responsible for acquired cancer resistance to the treatment. Here, we show that leucine zipper-containing ARF-binding protein (LZAP) binds and stabilizes p53. LZAP depletion eliminates p53 protein independently of its mutation status, subsequently protecting wild-type p53 cells from DNA damage-induced cell death, while rendering cells expressing mutant p53 more sensitive to the treatment. In human non-small-cell lung cancer, LZAP levels correlated with p53 levels, suggesting that loss of LZAP may represent a novel mechanism of p53 inactivation in human cancer. Our studies establish LZAP as a p53 regulator and p53-dependent determinative of cell fate in response to DNA damaging treatment.

Decontamination of beef subprimal cuts intended for blade tenderization or moisture enhancement.

The prevalence of Escherichia coli O157:H7 on beef subprimal cuts intended for mechanical tenderization was evaluated. This evaluation was followed by the assessment of five antimicrobial interventions at minimizing the risk of transferring E. coli O157:H7 to the interior of inoculated subprimal cuts during blade tenderization (BT) or moisture enhancement (ME). Prevalence of E. coli O157:H7 on 1,014 uninoculated beef subprimals collected from six packing facilities was 0.2%. Outside round pieces inoculated with E. coli O157:H7 at 10(4) CFU/100 cm2 were treated with (i) no intervention, (ii) surface trimming, (iii) hot water (82 degrees C), (iv) warm 2.5% lactic acid (55 degrees C), (v) warm 5.0% lactic acid (55 degrees C), or (vi) 2% activated lactoferrin followed by warm 5.0% lactic acid (55 degrees C) and then submitted to BT or ME. Prevalence (n=196) of internalized (BT and ME) E. coli O157:H7 was 99%. Enumeration of E. coli 0157:H7 (n=192) revealed mean surface reductions of 0.93 to 1.10 log CFU/100 cm2 for all antimicrobial interventions. E. coli O157:H7 was detected on 3 of the 76 internal BT samples and 73 of the 76 internal ME samples. Internal ME samples with no intervention had significantly higher mean E. coli O157:H7 populations than did those internal samples treated with an intervention, but there were no significant differences in E. coli O157:H7 populations among internal BT samples. Results of this study demonstrate that the incidence of E. coli O157:H7 on the surface of beef subprimal cuts is low and that interventions applied before mechanical tenderization can effectively reduce the transfer of low concentrations of E. coli O157:H7 to the interior of beef subprimal cuts.

Formation of Neu/ErbB2-induced mammary tumors is unaffected by loss of ErbB4.

The four members of the ErbB family of receptor tyrosine kinases are involved in development and tumorigenesis of the mammary gland. Whereas the epidermal growth factor receptor, ErbB2 and ErbB3 are positively associated with various cancers, clinical studies of ErbB4 in breast cancer are contradictory. Results from tissue culture analyses and some clinical studies suggested that ErbB4 is either a tumor suppressor or is a negative regulator of ErbB2-driven tumors. Neu-Cre-ErbB4(flox/null) mice in which ErbB4 was inactivated by Cre-lox-mediated recombination in the mammary gland developed MMTV-Neu-driven mammary tumors with a similar latency period to mice with one or two wild-type ErbB4 alleles. Moreover, there was no difference in the histologies of tumors that developed, nor in the propensity to form lung metastases. Taken together these results suggest that ErbB4 is not a potent, highly penetrant tumor suppressor, nor is it a factor in Neu-mediated tumorigenesis in this model.

Extent of microbial contamination in United States pork retail products.

To determine the extent of microbiological contamination of U.S. pork, 384 samples of retail pork were collected from 24 stores in six cities, including (i) whole-muscle, store-packaged pork; (ii) fresh, store-packaged ground pork and/or pork sausage; (iii) prepackaged ground pork and/or pork sausage; and (iv) whole-muscle, enhanced (injected or marinated; 60% store-packaged, 40% prepackaged) pork. Additional samples (n = 120) of freshly ground pork and/or pork sausage were collected from two hot-boning sow/boar sausage plants, two slaughter and fabrication plants, and two further-processing plants. Samples were analyzed for aerobic plate counts (APC), total coliform counts (TCC), Escherichia coli counts (ECC), and incidences of Salmonella spp., Listeria monocytogenes, Campylobacter jejuni, Campylobacter coli, and Yersinia enterocolitica. Mean log APC and TCC were highest (P < 0.05) for store-ground pork, while whole-muscle, enhanced products and prepackaged ground products had the lowest (P < 0.05) APC. Mean log APC and TCC were higher (P < 0.05) in samples from the slaughter and fabrication plants than in samples from hot-boning and further processing plants. Mean log ECC were lower (P < 0.05) in samples from further-processing plants compared to slaughter and fabrication plants and hot-boning, sow and boar sausage plants. L. monocytogenes was detected in 26.7% of plant samples and 19.8% of retail samples and was present more frequently in ground products. Y. enterocolitica was detected most often in whole-muscle, store-packaged cuts (19.8%) and in store-ground product (11.5%). Salmonella spp. were found in 9.6% of retail samples and 5.8% of plant samples, while C. jejuni and C. coli were found in 1.3% of retail samples and 6.7% of plant samples. Pork products exposed to the most handling and processing appeared to be of the poorest microbiological quality. These results should be useful in risk assessments that are directed at the identification of actions that could enhance food safety.

Microbiological contamination of raw beef trimmings and ground beef.

To survey the microbiological quality of beef trimmings and final-ground beef, samples were collected from eight commercial grinding facilities, including trimmings from fed-cattle, culled-beef cows, culled-dairy cows, imported-beef trimmings and finished-ground products. Trim samples (core and purge) and ground product samples (n=586) were evaluated for aerobic plate (APC), total coliform (TCC), Escherichia coli (ECC) and Staphylococcus aureus counts and the presence of Salmonella spp. and Listeria monocytogenes. As fat content in the trimmings increased, APC also increased. Trimmings from fed-cattle had higher (P<0.05) APC and TCC than trimmings from culled-beef cows, culled-dairy cows and imported trimmings. Purge samples produced higher (P<0.05) APC, TCC and ECC than core samples, but there were no difference (P>0.05) across fat percentages in APC, TCC, ECC or S. aureus counts. Final-ground beef samples had a 13.6 and 1.5 % incidence of L. monocytogenes and Salmonella spp., respectively. The results of this study indicate specific areas of potential that ground beef processors could capitalize upon to further improve the microbiological quality of their finished product. Ground beef processors should focus their efforts on reducing the microbial counts on incoming raw materials, especially those containing large proportions of subcutaneous fat, and processors should no longer incorporate the purge component of raw materials into ground beef. From this study, it is also apparent that ground beef processors should implement sanitation and manufacturing procedures that address L. monocytogenes contamination.

Sources and extent of microbiological contamination of beef carcasses in seven United States slaughtering plants.

This study determined microbiological loads of beef carcasses at different stages during the slaughtering to chilling process in seven (four steer/heifer and three cow/bull) plants. Potential sources of contamination (feces, air, lymph nodes) were also tested. Each facility was visited twice, once in November through January (wet season) and again in May through June (dry season). Carcasses were sampled by aseptic excision of surface tissue (100 cm2) from the brisket, flank, and rump (30 samples each) after hide removal (pre-evisceration), after final carcass washing, and after 24-h carcass chilling. The samples were analyzed individually by standard procedures for aerobic plate counts (APC), total coliform counts (TCC), Escherichia coli biotype I counts (ECC), and presence of Salmonella. Incidence of Salmonella was higher on dry feces of older compared to younger animals, fresh feces of younger compared to older animals, and on cow/bull carcasses compared to steer/heifer carcasses. Most factors and their interactions had significant (P < or = 0.05) effects on the bacterial counts obtained. Depending on plant and season, APC, TCC, and ECC were < or =10(4), < or =10(2), and < or =10(1) CFU/cm2 in 46.7 to 93.3, 50.0 to 100.0, and 74.7 to 100.0% of the samples, respectively. TCC exceeded 10(3) CFU/cm2 in 2.5% (wet season) and 1.5% (dry season) of the samples. ECC exceeded 10(2) CFU/cm2 in 8.7%, 0.3%, and 1.5% of the pre-evisceration, final carcass-washing, and 24-h carcass-chilling samples, respectively, during the wet season; the corresponding numbers during the dry season were 3.5%, 2.2%, and 3.0%, respectively. These data should serve as a baseline for future comparisons in measuring the microbiological status of beef carcasses, as the new inspection requirements are implemented.