Efecto del resveratrol en el porcentaje y calidad de embriones in vitro generados por separación de blastómeras en bovinos

The oxidative state is an important factor that determines the development of bovine embryos. The objective in this study was to evaluate the effect of resveratrol on the quality of in vitro embryos generated by separation of blastomeres in cattle. Oocytes from the slaughterhouse were matured and fertilized in vitro by the conventional method. After 18 hours of fertilization, the zygotes were cultured for 3 days in synthetic oviductual fluid medium (SOF) for control and supplemented with 2 μM and 0.5 μM for the treatments. On day 3 they were stripped of their zona pellucida (ZP) to be cultivated at a rate of four blastomeres in well of the well (WOW) for 6 days in medium SOF supplemented with resveratrol. We evaluated percentage data of cleavage and embryonic division (8 to 10 blastomeres) after 3 days of culture, finding a significant difference p<0.05 with supplementation with 0.5 μM of resveratrol. At 6 days after blastomeres separation, percentage of embryos, number of total cells, live cells and dead cells were evaluated using Hoechst, FDA and PI staining respectively. There were no differences in the percentage of blastocysts between treatments; however, supplementation with 0.5 μM of resveratrol to the SOF medium had a greater amount of total cells and living cells (p<0.05). In conclusion, supplementation with resveratrol in the SOF medium does not increase the percentage of blastocysts but improves its quality using a concentration of 0.5 μM.El estado oxidativo es un factor importante que determina el desarrollo de embriones bovinos. El objetivo de este estudio fue evaluar el efecto del resveratrol en el porcentaje y calidad de embriones in vitro generados por separación de blastómeras en ganado bovino. Ovocitos provenientes de matadero fueron madurados y fecundados in vitro por el método convencional. Terminada las 18 horas de fecundación, los cigotos se cultivaron por 3 días en medio fluido oviductual sintético (SOF) para el control y suplementado con 2 µM y 0,5 µM para los tratamientos. Al día 3 se despojaron de su zona pelúcida (ZP) para ser cultivados a razón de cuatro blastómeras en well of thewell (WOW) por 6 días en medio SOF suplementado con resveratrol. Se evaluaron datos porcentuales de clivaje y división embrionaria (8 a 10 blastómeros) a los 3 días de cultivo superando la suplementación con 0.5µM de resveratrol (p<0,05). A los 6 días post separación de blastómeras se evaluó porcentaje de embriones, cantidad de células totales, células vivas y células muertas, utilizando la tinción Hoechst, FDA y PI respectivamente. No hubo diferencias en el porcentaje de blastocistos entre tratamientos; sin embargo, la suplementación con 0,5 µM de resveratrol al medio SOF tuvo mayor cantidad de células totales y células vivas (p<0,05). Finalmente la suplementación con resveratrol al medio SOF no aumenta el porcentaje de blastocistos pero sí mejora su calidad usando una concentración de 0,5 µM

Efecto del hongo entomopatógeno Beauveria bassiana en el control de garrapatosis en ganado bovino

This study was carried out to determine the effect of the entomopathogenic fungus Beauveria bassiana on the control of ticks in cattle. In total, 20 Fleckvieh female cattle were distributed in five treatments: T1 = control group, T2 = excipients (water + 0.6 ml of surfactant), T3 = 1.2x107 conidia (80 g of fungus + 0.2 ml surfactant), T4 = 2.4 x107 conidia (160 g of fungus + 0.4 ml of surfactant), T5 = 3.6x107 conidia (240 g of fungus + 0.6 ml of surfactant). The fungus was washed with water and surfactant to detach them from the substrate and then applied to the cattle by thick-drop spraying. The tick count was performed in six areas (neck table, groin, armpit) on days 0 (before treatment), 1, 2, 3, 5, 7, 9, 11 and 14. The significant decrease in the number of ticks were observed from day 7 on T3, T4, T5. The decrease in ticks on day 14 was 99% in T5, while in T3 and T4 it was 91 and 82%, respectively.La investigación fue realizada para determinar el efecto del hongo entomopatógeno Beauveria bassiana en el control de garrapatas en ganado bovino. Se trabajó con 20 bovinos hembra de raza Fleckvieh distribuidos en cinco tratamientos: T1= grupo control, T2= excipientes (agua + 0.6 ml de surfactante), T3= 1.2x107 conidias (80 g de hongo + 0.2 ml surfactante), T4= 2.4x107 conidias (160 g de hongo + 0.4 ml de surfactante), T5 = 3.6x107 conidias (240 g de hongo + 0.6 ml de surfactante). El hongo fue lavado con agua y surfactante, con el fin de desprenderlas del sustrato para luego ser aplicado a los bovinos por medio de aspersión por gota gruesa. El conteo de garrapatas se realizó en seis zonas (tabla del cuello, entrepierna, axila) los días 0 (antes del tratamiento), 1, 2, 3, 5, 7, 9, 11 y 14. La disminución significativa en el número de garrapatas se observó a partir del día 7 en T3, T4, T5. La disminución de garrapatas en el día 14 fue de 99% en T5, mientras que en T3 y T4 fue de 91 y 82%, respectivamente

Gut microbiome variation modulates the effects of dietary fiber on host metabolism

Background: There is general consensus that consumption of dietary fermentable fiber improves cardiometabolic health, in part by promoting mutualistic microbes and by increasing production of beneficial metabolites in the distal gut. However, human studies have reported variations in the observed benefits among individuals consuming the same fiber. Several factors likely contribute to this variation, including host genetic and gut microbial differences. We hypothesized that gut microbial metabolism of dietary fiber represents an important and differential factor that modulates how dietary fiber impacts the host. Results: We examined genetically identical gnotobiotic mice harboring two distinct complex gut microbial communities and exposed to four isocaloric diets, each containing different fibers: (i) cellulose, (ii) inulin, (iii) pectin, (iv) a mix of 5 fermentable fibers (assorted fiber). Gut microbiome analysis showed that each transplanted community preserved a core of common taxa across diets that differentiated it from the other community, but there were variations in richness and bacterial taxa abundance within each community among the different diet treatments. Host epigenetic, transcriptional, and metabolomic analyses revealed diet-directed differences between animals colonized with the two communities, including variation in amino acids and lipid pathways that were associated with divergent health outcomes. Conclusion: This study demonstrates that interindividual variation in the gut microbiome is causally linked to differential effects of dietary fiber on host metabolic phenotypes and suggests that a one-fits-all fiber supplementation approach to promote health is unlikely to elicit consistent effects across individuals. Overall, the presented results underscore the importance of microbe-diet interactions on host metabolism and suggest that gut microbes modulate dietary fiber efficacy. [MediaObject not available: see fulltext.]Fil: Murga Garrido, Sofia M.. Universidad Nacional Autónoma de México; México. University of Wisconsin; Estados UnidosFil: Hong, Qilin. University of Wisconsin; Estados UnidosFil: Cross, Tzu Wen L.. University of Wisconsin; Estados Unidos. Purdue University; Estados UnidosFil: Hutchison, Evan R.. University of Wisconsin; Estados UnidosFil: Han, Jessica. Wisconsin Institute for Discovery; Estados UnidosFil: Thomas, Sydney P.. Wisconsin Institute for Discovery; Estados UnidosFil: Vivas, Eugenio I.. University of Wisconsin; Estados UnidosFil: Denu, John. Wisconsin Institute for Discovery; Estados UnidosFil: Ceschin, Danilo Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina. Instituto Universitario de Ciencias Biomédicas de Córdoba; ArgentinaFil: Tang, Zheng Zheng. University of Wisconsin; Estados Unidos. Wisconsin Institute for Discovery; Estados UnidosFil: Rey, Federico E.. University of Wisconsin; Estados Unido

Epigenome-wide analysis of T-cell large granular lymphocytic leukemia identifies BCL11B as a potential biomarker

Background: The molecular pathogenesis of T-cell large granular lymphocytic leukemia (T-LGLL), a mature T-cell leukemia arising commonly from T-cell receptor alpha beta-positive CD8(+) memory cytotoxic T cells, is only partly understood. The role of deregulated methylation in T-LGLL is not well known. We analyzed the epigenetic profile of T-LGLL cells of 11 patients compared to their normal counterparts by array-based DNA methylation profiling. For identification of molecular events driving the pathogenesis of T-LGLL, we compared the differentially methylated loci between the T-LGLL cases and normal T cells with chromatin segmentation data of benign T cells from the BLUEPRINT project. Moreover, we analyzed gene expression data of T-LGLL and benign T cells and validated the results by pyrosequencing in an extended cohort of 17 patients, including five patients with sequential samples. Results: We identified dysregulation of DNA methylation associated with altered gene expression in T-LGLL. Since T-LGLL is a rare disease, the samples size is low. But as confirmed for each sample, hypermethylation of T-LGLL cells at various CpG sites located at enhancer regions is a hallmark of this disease. The interaction of BLC11B and C14orf64 as suggested by in silico data analysis could provide a novel pathogenetic mechanism that needs further experimental investigation. Conclusions: DNA methylation is altered in T-LGLL cells compared to benign T cells. In particular, BCL11B is highly significant differentially methylated in T-LGLL cells. Although our results have to be validated in a larger patient cohort, BCL11B could be considered as a potential biomarker for this leukemia. In addition, altered gene expression and hypermethylation of enhancer regions could serve as potential mechanisms for treatment of this disease. Gene interactions of dysregulated genes, like BLC11B and C14orf64, may play an important role in pathogenic mechanisms and should be further analyzed

Evidencias de la presencia Inca en el valle de Chicama: apachetas, huancas y cerámica en Cerro El Sapo, Costa Norte del Perú

In 1470 the Incas conquered the north coast of Peru. They administered and controlled new territories using a variety of strategies, such as the relocation of roadways in order to shor ten distances, the construction of walls that oriented travelers to a single direction, and the utilization of loyal, diversely specialized subjects to displace rebellious or intransigent groups. These new populations brought with them their native cultural practices; in the Chicama Valley, they introduced Southern Highland traditions that ultimately syncretized with local, coastal cultures. The discovery of five coastal apachetas associated with coast-highland routes provides new evidence of Inca presence in one of the most fertile valleys on the Peruvian coast.En 1470 d. C. los Incas conquistan la Costa Norte del Perú e inician la administración y control de nuevos territorios usando una variedad de estrategias, como la reubicación de trazos en los caminos, la construcción de diversas murallas que dirigían al transeúnte en una sola dirección y el uso de poblaciones leales polifuncionales que reemplazaban a los grupos desplazados, estos nuevos habitantes han traído consigo y practicado sus costumbres dejando como evidencia, en el valle de Chicama, tradiciones de la sierra sur que se sincretizaron con las tradiciones locales. El hallazgo de cinco apachetas costeñas asociadas a vías de comunicación Costa – Sierra y la presencia de nuevas formas y uso de vasijas asociadas a restos arquitectónicos en las laderas este y oeste de Cerro El Sapo son una nueva evidencia de la presencia Inca en la Costa Norte que aportará a entender cómo se desarrolló la administración y el control de uno de los valles más fértiles de la costa peruana

Metabolomics profiling reveals new aspects of dolichol biosynthesis in Plasmodium falciparum

The cis-polyisoprenoid lipids namely polyprenols, dolichols and their derivatives are linear polymers of several isoprene units. In eukaryotes, polyprenols and dolichols are synthesized as a mixture of four or more homologues of different length with one or two predominant species with sizes varying among organisms. Interestingly, co-occurrence of polyprenols and dolichols, i.e. detection of a dolichol along with significant levels of its precursor polyprenol, are unusual in eukaryotic cells. Our metabolomics studies revealed that cis-polyisoprenoids are more diverse in the malaria parasite Plasmodium falciparum than previously postulated as we uncovered active de novo biosynthesis and substantial levels of accumulation of polyprenols and dolichols of 15 to 19 isoprene units. A distinctive polyprenol and dolichol profile both within the intraerythrocytic asexual cycle and between asexual and gametocyte stages was observed suggesting that cis-polyisoprenoid biosynthesis changes throughout parasite’s development. Moreover, we confirmed the presence of an active cis-prenyltransferase (PfCPT) and that dolichol biosynthesis occurs via reduction of the polyprenol to dolichol by an active polyprenol reductase (PfPPRD) in the malaria parasite

Rpgrip1 is required for rod outer segment development and ciliary protein trafficking in zebrafish

The authors would like to thank the Royal Society of London, the National Eye Research Centre, the Visual Research Trust, Fight for Sight, the W.H. Ross Foundation, the Rosetrees Trust, and the Glasgow Children’s Hospital Charity for supporting this work. This work was also supported by the Deanship of Scientific Research at King Saud University for funding this research (Research Project) grant number ‘RGP – VPP – 219’.Mutations in the RPGR-interacting protein 1 (RPGRIP1) gene cause recessive Leber congenital amaurosis (LCA), juvenile retinitis pigmentosa (RP) and cone-rod dystrophy. RPGRIP1 interacts with other retinal disease-causing proteins and has been proposed to have a role in ciliary protein transport; however, its function remains elusive. Here, we describe a new zebrafish model carrying a nonsense mutation in the rpgrip1 gene. Rpgrip1homozygous mutants do not form rod outer segments and display mislocalization of rhodopsin, suggesting a role for RPGRIP1 in rhodopsin-bearing vesicle trafficking. Furthermore, Rab8, the key regulator of rhodopsin ciliary trafficking, was mislocalized in photoreceptor cells of rpgrip1 mutants. The degeneration of rod cells is early onset, followed by the death of cone cells. These phenotypes are similar to that observed in LCA and juvenile RP patients. Our data indicate RPGRIP1 is necessary for rod outer segment development through regulating ciliary protein trafficking. The rpgrip1 mutant zebrafish may provide a platform for developing therapeutic treatments for RP patients.Publisher PDFPeer reviewe

The Quijote CMB Experiment

We present the current status of the QUIJOTE (Q-U-I JOint TEnerife) CMB Experiment, a new instrument which will start operations early 2009 at Teide Observatory, with the aim of characterizing the polarization of the CMB and other processes of galactic and extragalactic emission in the frequency range 10-30 GHz and at large angular scales. QUIJOTE will be a valuable complement at low frequencies for the PLANCK mission, and will have the required sensitivity to detect a primordial gravitational-wave component if the tensor-to-scalar ratio is larger than r=0.05.Comment: 9 pages, 5 figures. To appear in "Highlights of Spanish Astrophysics V", Proceedings of the VIII Scientific Meeting of the Spanish Astronomical Society (SEA) held in Santander, 7-11 July, 2008. Edited by J. Gorgas, L. J. Goicoechea, J. I. Gonzalez-Serrano, J. M. Dieg

Distinct roles for PARP-1 and PARP-2 in c-Myc-driven B-cell lymphoma in mice

Dysregulation of the c-Myc oncogene occurs in a wide variety of hematologic malignancies, and its overexpression has been linked with aggressive tumor progression. Here, we show that poly (ADP-ribose) polymerase 1 (PARP-1) and PARP-2 exert opposing influences on progression of c-Myc-driven B-cell lymphoma. PARP-1 and PARP-2 catalyze the synthesis and transfer of ADP-ribose units onto amino acid residues of acceptor proteins in response to DNA strand breaks, playing a central role in the response to DNA damage. Accordingly, PARP inhibitors have emerged as promising new cancer therapeutics. However, the inhibitors currently available for clinical use are not able to discriminate between individual PARP proteins. We found that genetic deletion of PARP-2 prevents c-Myc-driven B-cell lymphoma, whereas PARP-1 deficiency accelerates lymphomagenesis in the E¿-Myc mouse model of aggressive B-cell lymphoma. Loss of PARP-2 aggravates replication stress in preleukemic E¿-Myc B cells, resulting in accumulation of DNA damage and concomitant cell death that restricts the c-Myc-driven expansion of B cells, thereby providing protection against B-cell lymphoma. In contrast, PARP-1 deficiency induces a proinflammatory response and an increase in regulatory T cells, likely contributing to immune escape of B-cell lymphoma, resulting in an acceleration of lymphomagenesis. These findings pinpoint specific functions for PARP-1 and PARP-2 in c-Myc-driven lymphomagenesis with antagonistic consequences that may help inform the design of new PARP-centered therapeutic strategies, with selective PARP-2 inhibition potentially representing a new therapeutic approach for the treatment of c-Myc-driven tumors.The J.Y. laboratory is funded by the Spanish Ministerio de Economía, Industria y Competitividad (grant SAF2017-83565-R), Spanish Ministerio de Ciencia e Innovación (grant PID2020-112526RB-I00), and Fundación Científica de la Asociación Española Contra el Cáncer (grant PROYEI6018YÉLA). Work in the J.E.S. laboratory is supported by a core grant to the Laboratory of Molecular Biology from the Medical Research Council (U105178808). The F.D. laboratory is supported by a Laboratory of Excellence grant (ANR-10-LABX-0034_Medalis) to Strasbourg University, Centre National de la Recherche Scientifique. The P.N. laboratory is supported by grants from the Spanish Ministry of Economy and Competitiveness/Instituto de Salud Carlos III–Fondo Europeo de Desarrollo Regional (FEDER; PI17/00199 and PI20/00625) and the Generalitat de Catalunya (2017-SGR-225). The P.M. laboratory acknowledges support from Centres de Recerca de Catalunya/Generalitat de Catalunya and Fundació Josep Carreras-Obra Social la Caixa for core support, the Spanish Ministry of Economy and Competitiveness (grant SAF-2019-108160-R), the Fundación Uno entre Cienmil, the Obra Social La Caixa (grant LCF/PR/HR19/52160011), and the German Josep Carreras Leukamie Stiftung. Work at the G.R. and P.M. laboratories are cofinanced by the European Regional Development Fund through the Interreg V-A Spain-France-Andorra Program (project PROTEOblood; grant EFA360/19). The O.F.-C. laboratory is funded by grants from the Spanish Ministry of Science, Innovation and Universities (RTI2018-102204-B-I00; cofinanced with European FEDER funds) and the European Research Council (ERC-617840). T.V.-H. was supported by a Marie Sklodowska Curie fellowship (GA792923). The A.B. laboratory is supported by the Spanish Ministry of Economy and Competitiveness (grant PID2019-104695RB-I00)

The MRN complex is transcriptionally regulated by MYCN during neural cell proliferation to control replication stress

The MRE11/RAD50/NBS1 (MRN) complex is a major sensor of DNA double strand breaks, whose role in controlling faithful DNA replication and preventing replication stress is also emerging. Inactivation of the MRN complex invariably leads to developmental and/or degenerative neuronal defects, the pathogenesis of which still remains poorly understood. In particular, NBS1 gene mutations are associated with microcephaly and strongly impaired cerebellar development, both in humans and in the mouse model. These phenotypes strikingly overlap those induced by inactivation of MYCN, an essential promoter of the expansion of neuronal stem and progenitor cells, suggesting that MYCN and the MRN complex might be connected on a unique pathway essential for the safe expansion of neuronal cells. Here, we show that MYCN transcriptionally controls the expression of each component of the MRN complex. By genetic and pharmacological inhibition of the MRN complex in a MYCN overexpression model and in the more physiological context of the Hedgehog-dependent expansion of primary cerebellar granule progenitor cells, we also show that the MRN complex is required for MYCN-dependent proliferation. Indeed, its inhibition resulted in DNA damage, activation of a DNA damage response, and cell death in a MYCN- and replication-dependent manner. Our data indicate the MRN complex is essential to restrain MYCN-induced replication stress during neural cell proliferation and support the hypothesis that replication-born DNA damage is responsible for the neuronal defects associated with MRN dysfunctions.Cell Death and Differentiation advance online publication, 12 June 2015; doi:10.1038/cdd.2015.81