Systematic analysis of intrinsic enhancer-promoter compatibility in the mouse genome.

Gene expression is in part controlled by cis-regulatory elements (CREs) such as enhancers and repressive elements. Anecdotal evidence has indicated that a CRE and a promoter need to be biochemically compatible for promoter regulation to occur, but this compatibility has remained poorly characterized in mammalian cells. We used high-throughput combinatorial reporter assays to test thousands of CRE-promoter pairs from three Mb-sized genomic regions in mouse cells. This revealed that CREs vary substantially in their promoter compatibility, ranging from striking specificity to broad promiscuity. More than half of the tested CREs exhibit significant promoter selectivity. Housekeeping promoters tend to have similar CRE preferences, but other promoters exhibit a wide diversity of compatibilities. Higher-order transcription factors (TF) motif combinations may account for compatibility. CRE-promoter selectivity does not correlate with looping interactions in the native genomic context, suggesting that chromatin folding and compatibility are two orthogonal mechanisms that confer specificity to gene regulation.

Effect of probiotics administration at different levels on the productive parameters of guinea pigs for fattening (Cavia porcellus).

Background: For more than 50 years, antibiotics have been used to maintain animal welfare and improve efficiency. Recently, antibiotics were found in the muscle, liver, and kidney of guinea pig carcasses put up for sale and human consumption, which is a public health issue. Probiotics are supplements of live microorganisms that, when administered in adequate doses, could replace growth-promoting antibiotics. Aim: This study analyzed the effect of the administration of an oral probiotic mixture on the guinea pigs productive performance (Cavia porcellus). Methods: Fifty male guinea pigs, weaned at 14 days of age, were distributed in a completely randomized design of five treatments with ten repetitions for each group. The treatments were CONTROL group without probiotic; PROB 1 given 1 ml of probiotic; PROB 2 with 2 ml of probiotic; PROB 3 with 3 ml of probiotic; and antibiotic growth promoter (AGP) was given 300 ppm zinc bacitracin. The microorganisms used in the probiotic were Enterococcus hirae, Lactobacillus reuteri, Lactobacillus frumenti, Lactobacillus johnsoni, Streptococcus thoraltensis, and Bacillus pumilus. Productive parameters were evaluated from weaning to 70 days of age. Results: No statistically significant difference was found between the treatments on forage dry matter intake (DMI), concentrateconcentrate DMI, or total concentrate DMI (p > 0.05). Similarly, no statistical difference was found between the treatments in terms of final weight or weight gain (p > 0.05). Regarding the feed conversion ratio (FCR), there was a significant difference between treatments (p = 0.045); the CONTROL group had the highest FCR, followed by the AGP group, with the best FCR observed in the PROB 3 group (p < 0.05). In addition, significant statistical differences were found between CONTROL and PROB 2 (p < 0.05). Likewise, a significant linear effect of increasing doses of the probiotic was found (p = 0.01), which indicated that the feed conversion was better with a higher dose. Conclusion: The treatments evaluated in this study significantly impacted the FCR in guinea pigs for fattening. Increasing doses of probiotics had a linear effect on FCR.

Double-Edged Lipid Nanoparticles Combining Liposome-Bound TRAIL and Encapsulated Doxorubicin Showing an Extraordinary Synergistic Pro-Apoptotic Potential.

Although TRAIL (TNF-related apoptosis-inducing ligand, also known as Apo2L) was described as capable of inducing apoptosis in transformed cells while sparing normal cells, limited results obtained in clinical trials has limited its use as an anti-tumor agent. Consequently, novel TRAIL formulations with enhanced bioactivity are necessary for overcoming resistance to conventional soluble TRAIL (sTRAIL) exhibited by many primary tumors. Our group has generated artificial liposomes with sTRAIL anchored on their surface (large unilamellar vesicle (LUV)-TRAIL), which have shown a greater cytotoxic activity both in vitro and in vivo when compared to sTRAIL against distinct hematologic and epithelial carcinoma cells. In this study, we have improved LUV-TRAIL by loading doxorubicin (DOX) in its liposomal lumen (LUVDOX-TRAIL) in order to improve their cytotoxic potential. LUVDOX-TRAIL killed not only to a higher extent, but also with a much faster kinetic than LUV-TRAIL. In addition, the concerted action of the liposomal DOX and TRAIL was specific of the liposomal DOX and was not observed when with soluble DOX. The cytotoxicity induced by LUVDOX-TRAIL was proven to rely on two processes due to different molecular mechanisms: a dynamin-mediated internalization of the doxorubicin-loaded particle, and the strong activation of caspase-8 exerted by the liposomal TRAIL. Finally, greater cytotoxic activity of LUVDOX-TRAIL was also observed in vivo in a tumor xenograft model. Therefore, we developed a novel double-edged nanoparticle combining the cytotoxic potential of DOX and TRAIL, showing an exceptional and remarkable synergistic effect between both agents.

Depresión y factores asociados en la población peruana adulta mayor según la ENDES 2014-2015 / Depression and associated factors in the Peruvian elderly population according to ENDES 2014-2015

Objetivos: Estimar la prevalencia y los factores asociados a la depresión en la población peruana adulta mayor según los resultados de la Encuesta Demográfica y de Salud Familiar (ENDES) 2014-2015. Diseño: Estudio observacional, transversal y analítico. Institucion: UNMSM. Participantes: Adultos mayores. Intervenciones: Muestra probabilística de 11 411 adultos mayores que respondieron a la ENDES 2014-2015. Principales Medidas de Resultados: Prevalencias, promedios, desviaciones estándar y cálculos de OR con un IC 95%. Resultados: La prevalencia estimada fue de 14%. Respecto a los factores de riesgo para la depresión, se identificaron la condición de mujer [OR 1,92 (1,72 2,15)]; ser mayor de 75 años [OR 1,56 (1,40 1,74)]; el carecer de instrucción [OR 2,63 (2,35 2,95)]; el vivir sin pareja [OR 1,32 (1,19 1,47)]; el residir en área rural [OR 2,12 (1,91 2,36)]; el ser pobre [OR 2,30 (2,06 2,56)] y el tener alguna discapacidad [OR 2,63 (2,29 3,02)]. Conclusiones: La prevalencia de depresión en adultos mayores es sustancial. Los factores de riesgo identificados para la presencia de depresión en el adulto mayor, fueron la condición de mujer, ser mayor de 75 años, la carencia de instrucción, el vivir sin pareja, vivir en área rural, la pobreza y la discapacidad física.

Objectives: The study aims to estimate the prevalence and associated factors of depression in the peruvian older adults using the results of the Demographic and Family Health Survey 2014-2015 (ENDES). Design: The study was observational, transversal and analytic. Institution: UNMSM. Participants: Olders adults. Interventions: Probabilistic sample of 11411 older adults who participated in the ENDES 2014-2015. Main Outcomes: Prevalence estimates, means, standard deviations and OR with 95% confidence probability and p-values. Results: Depression prevalence was estimated as 14%. Identified risk factors for depression were being female [OR 1.92 (1.72 2.15)]; being ≥ 75 years old (OR 1.56 (1.40 1.74)]; lack of education (OR 2.63 (2.35 2.95)]; living without a couple [OR 1.32 (1.19 1.45)]; living in rural areas [OR 2.12 (1.90 2.36)]; being poor [OR 2.30 (2.06 2.56)] and having physical disabilities. Conclusions: Depression prevalence in peruvian older adults is substantial. Risk factors were being female, being older, lacking education, living without a couple, living in rural areas, poverty, and physical disabilities.