The role of different strain backgrounds in bacterial endotoxin-mediated sensitization to neonatal hypoxic-ischemic brain damage

Genetic background is known to influence the outcome in mouse models of human disease, and previous experimental studies have shown strain variability in the neonatal mouse model of hypoxia-ischemia. To further map out this variability, we compared five commonly used mouse strains: C57BL/6, 129SVJ, BALB/c, CD1 and FVB in a pure hypoxic-ischemic setup and following pre-sensitization with lipopolysaccharide (LPS). Postnatal day 7 pups were subjected to unilateral carotid artery occlusion followed by continuous 30 min 8% oxygen exposure at 36 °C. Twelve hours prior, a third of the pups received a single intraperitoneal LPS (0.6 μg/g) or a saline (vehicle) administration, respectively; a further third underwent hypoxia-ischemia alone without preceding injection. Both C57BL/6 and 129SVJ strains showed minimal response to 30min hypoxia-ischemia alone, BALB/c demonstrated a moderate response, and both CD1 and FVB revealed the highest brain damage. LPS pre-sensitization led to substantial increase in overall brain infarction, microglial and astrocyte response and cell death in four of the five strains, with exception of BALB/c that only showed a significant effect with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Saline administration prior to hypoxia-ischemia resulted in an increase in inflammatory-associated markers, particularly in the astroglial activation of C57BL/6 mice, and in combined microglial activation and neuronal cell loss in FVB mice. Finally, two of the four strongly affected strains--C57BL/6 and CD1--revealed pronounced contralateral astrogliosis with a neuroanatomical localization similar to that observed on the occluded hemisphere. Overall, the current findings demonstrate strain differences in response to hypoxia-ischemia alone, to stress associated with vehicle injection, and to LPS-mediated pre-sensitization, which partially explains the high variability seen in the neonatal mouse models of hypoxia-ischemia. These results can be useful in future studies of fetal/neonatal response to inflammation and reduced oxygen-blood supply

PIM1 kinase regulates cell death, tumor growth and chemotherapy response in triple-negative breast cancer

Triple-negative breast cancers (TNBCs) have poor prognosis and lack targeted therapies. Here we identified increased copy number and expression of the PIM1 proto-oncogene in genomic data sets of patients with TNBC. TNBC cells, but not nonmalignant mammary epithelial cells, were dependent on PIM1 for proliferation and protection from apoptosis. PIM1 knockdown reduced expression of the anti-apoptotic factor BCL2, and dynamic BH3 profiling of apoptotic priming revealed that PIM1 prevents mitochondrial-mediated apoptosis in TNBC cell lines. In TNBC tumors and their cellular models, PIM1 expression was associated with several transcriptional signatures involving the transcription factor MYC, and PIM1 depletion in TNBC cell lines decreased, in a MYC-dependent manner, cell population growth and expression of the MYC target gene MCL1. Treatment with the pan–PIM kinase inhibitor AZD1208 impaired the growth of both cell line and patient-derived xenografts and sensitized them to standard-of-care chemotherapy. This work identifies PIM1 as a malignant-cell-selective target in TNBC and the potential use of PIM1 inhibitors for sensitizing TNBC to chemotherapy-induced apoptotic cell death

Comparación de variables zoométricas en gallos de tres razas catalanas

Resumen de la comunicación presentada al III Congreso Ibérico sobre Recursos Genéticos Animale

Características de la carne de pollos del cruce F1 de dos razas españolas mejoradas en función de la edad de sacrificio

The present study analysed the meat characteristics of i) improved Castellana Negra chickens slaughtered at 18 weeks (CN-18) and ii) F1 crossbred chickens from improved Castellana Negra hens and improved Penedesenca Negracocks (CNPN) slaughtered at 12 weeks and 18 weeks of age (young and adult animals, respectively). Purebred andcrossbred specimens were compared at similar weights (CN-18 and CNPN-12) and ages (CN-18 and CNPN-18). The protein content of the meat was similar for the three types of animals; heavier animals (CNPN-18) had more fat thanthose slaughtered at lower weights (CNPN-12 and CN-18). Adults had a higher saturated fatty acid content and theyoung CNPN chickens had more monounsaturated fatty acids than CN chickens. In the CNPN adults, less water was lost during cooking, which is directly related to the juiciness of the meat. With regard to sensory analysis, a darker colour was observed in the meat as much as the internal fat of adult animals, in addition to greater colour uniformity. The meat of young CNPN birds was juicier, whereas that of the CN chickens was more fibrous. Therefore, we conclude that meat from CNPN chickens presents chemical, physical, and sensorial characteristics that make these animals a genetic base for alternative poultry production.En este trabajo se estudiaron las características de la carne de pollos mejorados de raza Castellana Negra sacrificados a las 18 semanas (CN-18) y de pollos del cruce F1 de gallinas mejoradas de raza Castellana Negra y gallos mejoradosde la raza Penedesenca Negra (tipo CNPN), sacrificados a las 12 y 18 semanas de vida (CNPN-12 y 18, animales jóvenes y adultos, respectivamente), con el fin de comparar la raza pura y el cruce sacrificados con peso similar (CN-18 y CNPN-12) y con la misma edad (CN-18 y CNPN-18). El contenido en proteína de la carne fue similar para los tres tipos de animales, y en grasa, los animales de mayor peso (CNPN-18) presentaron mayores contenidos que los sacrificados con pesos inferiores (CNPN-12 y CN-18). Los adultos presentaron mayor contenido en ácidos grasos saturados y el tipo CNPN joven mayor en monoinsaturados que el CN. En los tipo CNPN adultos se observaron unas menores pérdidas de agua por cocción, variable relacionada directamente con la jugosidad de la carne. Respecto al análisis sensorial, se observó un color más oscuro, tanto de la carne como de la grasa interna, en los animales adultos, así como una uniformidad mayor de ese color. La carne de los CNPN-12 resultó más jugosa, mientras que la de los CN-18 fue la más fibrosa. Así pues, podemos concluir que la carne de los pollos CNPN presenta unas características químicas, físicas y sensoriales, que hacen de estos animales una base genética adecuada para la producción avícola alternativa