Meat quality attributes of male and female broilers from 4 commercial strains processed for 2 market programs

ABSTRACT: In recent times, meat quality has become a key aspect of poultry production. In the current study, 2,400 sex separate broilers from 4 commercial strains were placed in 6 replications to evaluate various meat quality characteristics when grown to 2 market weights. Broilers were fed 1 of 2 diets with varying degrees of amino acid inclusion to evaluate meat quality of broiler raised on varying planes of nutrition. Birds were processed to meet 2 specified target weights (2.5 and 3.8 kg) representing small bird and big bird debone markets in the United States, respectively. Birds were processed using commercial methods, deboned at 3-h postmortem, and meat quality was assessed. Myopathies (woody breast, white striping, spaghetti meat, along with tenderloin quality), fillet dimensions, color, water-holding capacity (e.g., drip loss, cook loss), and Meullenet Owens Razor Shear was determined. Data were analyzed using the Mixed Model platform of JMP Pro 15.2 (SAS Institute, Cary, NC). Diet had no effect (P > 0.05) on the key quality responses; data were then pooled resulting in main effects of sex, strain, and target weight (noted as carcass size). On the day of processing, high yielding (HY) strains produced higher breast and tender yields (P < 0.05) when compared to standard yielding (SY) strains. In addition, and as expected, females exhibited higher breast and tender yields (P < 0.05) than males. However, males had significantly thicker (P < 0.05) and longer (P < 0.05) fillets, higher incidences (P < 0.05) of white striping, and higher (P < 0.05) cook loss when compared to females. Differences were also observed in tenderness as SY strain A produced the lowest shear values, whereas SY strain B produced the highest shear values across parameters (P < 0.05). SY strains in the small bird (SB) market performed better than SY strains in the big bird (BB) market as indicated by lower incidences of breast and tender myopathies white striping, woody breast, spaghetti meat, woody-like tender, and tender feathering and improved quality attributes (P < 0.05). Similar trends were observed (P < 0.05) in HY strains as SB carcasses produced a better overall product than BB. Differences in carcass size directly impacted quality (P < 0.05) as SB markets showed improvements in most parameters assessed, but broilers representing BB markets had greater breast yield. Although strain had minimal impacts on quality measures, carcass size, and sex had a greater impact on muscle myopathies, water-holding capacity, and shear properties

Identification of a Molecularly-Defined Subset of Breast and Ovarian Cancer Models that Respond to WEE1 or ATR Inhibition, Overcoming PARP Inhibitor Resistance

PARP inhibitors (PARPi) induce synthetic lethality in homologous recombination repair (HRR)-deficient tumors and are used to treat breast, ovarian, pancreatic, and prostate cancers. Multiple PARPi resistance mechanisms exist, most resulting in restoration of HRR and protection of stalled replication forks. ATR inhibition was highlighted as a unique approach to reverse both aspects of resistance. Recently, however, a PARPi/WEE1 inhibitor (WEE1i) combination demonstrated enhanced antitumor activity associated with the induction of replication stress, suggesting another approach to tackling PARPi resistance. We analyzed breast and ovarian patientderived xenoimplant models resistant to PARPi to quantify WEE1i and ATR inhibitor (ATRi) responses as single agents and in combination with PARPi. Biomarker analysis was conducted at the genetic and protein level. Metabolite analysis by mass spectrometry and nucleoside rescue experiments ex vivo were also conducted in patient-derived models. Although WEE1i response was linked to markers of replication stress, including STK11/RB1 and phospho-RPA, ATRi response associated with ATM mutation. When combined with olaparib, WEE1i could be differentiated from the ATRi/olaparib combination, providing distinct therapeutic strategies to overcome PARPi resistance by targeting the replication stress response. Mechanistically, WEE1i sensitivity was associated with shortage of the dNTP pool and a concomitant increase in replication stress. Targeting the replication stress response is a valid therapeutic option to overcome PARPi resistance including tumors without an underlying HRR deficiency. These preclinical insights are now being tested in several clinical trials where the PARPi is administered with either the WEE1i or the ATRi