Selección de genotipos por comportamiento forrajero a partir de una progenie F2 de stylosanthes guianensis (fabaceae)

Stylosanthes guianensis (Aubl.) Sw. es una especie autógama de gran importancia forrajera en el norte de Argentina, ya que estudios previos han mostrado que se adapta bien a diferentes tipos de suelos y ambientes, siendo poco exigente en requerimientos de fósforo, además, tienen buen valor nutritivo comparado con otras especies tropicales. En Corrientes se han evaluado algunos de los cultivares comerciales, observándose una buena producción media durante 4 años. Sin embargo, la producción en período frío disminuye o se produce la muerte de las plantas debido a las bajas temperaturas. Sería de gran interés incorporar a Stylosanthes guianensis a un programa de mejoramiento genético. Con la finalidad de obtener genotipos que produjeran durante todo el año, sean tolerantes a las heladas y con mayor vigor. Con respecto a este punto, la cátedra de Forrajicultura de FCA UNNE cuenta con germoplasma de cuatro cultivares de S. guianensis (Endavour, Cook, CIAT 184 y Graham), los cuales fueron cultivados y caracterizados previamente. El objetivo del presente trabajo fue identificar y seleccionar genotipos deseables a partir de progenies segregantes (F2), provenientes de la hibridación de cultivares comerciales de Stylosanthes guianensis. Para ello se dispuso de un total de 390 plantas a campo, distribuidas en un diseño en bloques completos al azar con 3 repeticiones. Se realizaron mediciones relativas a la producción primaria, altura de plantas y diámetro, susceptibilidad a las enfermedades, tolerancia al frío y producción de semillas, como así también a observaciones del hábito de crecimiento y porte de la planta. Los resultados permiten identificar genotipos altamente favorables desde el punto de vista de la tolerancia al frío principalmente, logrando sobrevivir al invierno un total de 15 genotipos F2, pertenecientes a 8 familias, pero además 16 genotipos de padres o variedades comerciales. Lo cual daría un indicio de la factibilidad de la técnica de mejoramiento empleadaFil: Winter, Jonatan D.. Universidad Nacional del NordesteFil: Acuña, Carlos A.. Universidad Nacional del NordesteFil: Brugnoli, Elsa A.. Universidad Nacional del Nordest

Initiation of Pancreatic Cancer: The Interplay of Hyperglycemia and Macrophages Promotes the Acquisition of Malignancy-Associated Properties in Pancreatic Ductal Epithelial Cells

Pancreatic ductal adenocarcinoma (PDAC) is still one of the most aggressive solid malignancies with a poor prognosis. Obesity and type 2 diabetes mellitus (T2DM) are two major risk factors linked to the development and progression of PDAC, both often characterized by high blood glucose levels. Macrophages represent the main immune cell population in PDAC contributing to PDAC development. It has already been shown that pancreatic ductal epithelial cells (PDEC) undergo epithelial-mesenchymal transition (EMT) when exposed to hyperglycemia or macrophages. Thus, this study aimed to investigate whether concomitant exposure to hyperglycemia and macrophages aggravates EMT-associated alterations in PDEC. Exposure to macrophages and elevated glucose levels (25 mM glucose) impacted gene expression of EMT inducers such as IL-6 and TNF-α as well as EMT transcription factors in benign (H6c7-pBp) and premalignant (H6c7-kras) PDEC. Most strikingly, exposure to hyperglycemic coculture with macrophages promoted downregulation of the epithelial marker E-cadherin, which was associated with an elevated migratory potential of PDEC. While blocking IL-6 activity by tocilizumab only partially reverted the EMT phenotype in H6c7-kras cells, neutralization of TNF-α by etanercept was able to clearly impair EMT-associated properties in premalignant PDEC. Altogether, the current study attributes a role to a T2DM-related hyperglycemic, inflammatory micromilieu in the acquisition of malignancy-associated alterations in premalignant PDEC, thus providing new insights on how metabolic diseases might promote PDAC initiation

Chitosan nanoparticles as antigen vehicles to induce effective tumor specific T cell responses

Cancer vaccinations sensitize the immune system to recognize tumor-specific antigens de novo or boosting preexisting immune responses. Dendritic cells (DCs) are regarded as the most potent antigen presenting cells (APCs) for induction of (cancer) antigen-specific CD8+ T cell responses. Chitosan nanoparticles (CNPs) used as delivery vehicle have been shown to improve anti-tumor responses. This study aimed at exploring the potential of CNPs as antigen delivery system by assessing activation and expansion of antigen-specific CD8+ T cells by DCs and subsequent T cell-mediated lysis of pancreatic ductal adenocarcinoma (PDAC) cells. As model antigen the ovalbumin-derived peptide SIINFEKL was chosen. Using imaging cytometry, intracellular uptake of FITC-labelled CNPs of three different sizes and qualities (90/10, 90/20 and 90/50) was demonstrated in DCs and in pro- and anti-inflammatory macrophages to different extents. While larger particles (90/50) impaired survival of all APCs, small CNPs (90/10) were not toxic for DCs. Internalization of SIINFEKL-loaded but not empty 90/10-CNPs promoted a pro-inflammatory phenotype of DCs indicated by elevated expression of pro-inflammatory cytokines. Treatment of murine DC2.4 cells with SIINFEKL-loaded 90/10-CNPs led to a marked MHC-related presentation of SIINFEKL and enabled DC2.4 cells to potently activate SIINFEKL-specific CD8+ OT-1 T cells finally leading to effective lysis of the PDAC cell line Panc-OVA. Overall, our study supports the suitability of CNPs as antigen vehicle to induce potent anti-tumor immune responses by activation and expansion of tumor antigen-specific CD8+ T cells

Intramuscular oxytocin versus Syntometrine® versus carbetocin for prevention of primary postpartum haemorrhage after vaginal birth: a randomised double-blinded clinical trial of effectiveness, side effects and quality of life

Objective: To compare intramuscular oxytocin, Syntometrine® and carbetocin for prevention of postpartum haemorrhage after vaginal birth. Design: Randomised double-blinded clinical trial. Setting: Six hospitals in England. Population: A total of 5929 normotensive women having a singleton vaginal birth. Methods: Randomisation when birth was imminent. Main outcome measures: Primary: use of additional uterotonic agents. Secondary: weighed blood loss, transfusion, manual removal of placenta, adverse effects, quality of life. Results: Participants receiving additional uterotonics: 368 (19.5%) oxytocin, 298 (15.6%) Syntometrine and 364 (19.1%) carbetocin. When pairwise comparisons were made: women receiving carbetocin were significantly more likely to receive additional uterotonics than those receiving Syntometrine (odds ratio [OR] 1.28, 95% CI 1.08–1.51, P=0.004); the difference between carbetocin and oxytocin was non-significant (P=0.78); Participants receiving Syntometrine were significantly less likely to receive additional uterotonics than those receiving oxytocin (OR 0.75, 95% CI 0.65–0.91, P=0.002). Non-inferiority between carbetocin and Syntometrine was not shown. Use of Syntometrine reduced non-drug PPH treatments compared with oxytocin (OR 0.64, 95% CI 0.42–0.97) but not carbetocin (P=0.64). Rates of PPH and blood transfusion were not different. Syntometrine was associated with an increase in maternal adverse effects and reduced ability of the mother to bond with her baby. Conclusions: Non-inferiority of carbetocin to Syntometrine was not shown. Carbetocin is not significantly different to oxytocin for use of additional uterotonics. Use of Syntometrine reduced use of additional uterotonics and need for non-drug PPH treatments compared with oxytocin. Increased maternal adverse effects are a disadvantage of Syntometrine. Tweetable abstract: IM carbetocin does not reduce additional uterotonic use compared with IM Syntometrine or oxytocin

The Changing Fate of a Secretory Glycoprotein in Developing Maize Endosperm1[C][W]

Zeins are the major storage proteins in maize (Zea mays) endosperm, and their accumulation in zein bodies derived from the endoplasmic reticulum is well characterized. In contrast, relatively little is known about post-Golgi compartments or the trafficking of vacuolar proteins in maize endosperm, specifically the presence of globulins in structures resembling protein storage vacuoles that appear in early to mid-stage seed development. We investigated this pathway by expressing and analyzing a recombinant reporter glycoprotein during endosperm maturation, using a combination of microscopy and sensitive glycopeptide analysis. Specific N-glycan acceptor sites on the protein were followed through the stages of grain development, revealing a shift from predominantly paucimannosidic vacuolar glycoforms to predominantly trimmed glycan structures lacking fucose. This was accompanied by a change in the main subcellular localization of the protein from large protein storage vacuole-like post-Golgi organelles to the endoplasmic reticulum and zein bodies. The endogenous storage proteins corn α-globulin and corn legumin-1 showed a similar spatiotemporal profile both in transgenic plants expressing the reporter glycoprotein and in wild-type plants. This indicates that the shift of the intracellular trafficking route, as observed with our reporter glycoprotein, may be a common strategy in maize seed development

Stereochemistry Rules: A Single Stereocenter Changes the Conformation of a Cyclic Tetrapeptide

Two novel cyclo­(Boc-Cys-Pro-Leu-Cys-OMe) peptides <b>1</b> and <b>2</b> containing the enantiomeric amino acids d-Leu and l-Leu, respectively, were synthesized to investigate the effect of chiral centers on peptide conformations. By combining a variety of experimental techniques (X-ray crystallography, 2D NMR spectroscopy, temperature-dependent ¹H NMR and IR spectroscopy, and UV-CD spectroscopy) with replica exchange molecular dynamics (REMD) techniques and quantum mechanics/molecular dynamics (QM/MM) calculations, we establish that the stereochemistry of just one residue can noticeably influence the properties of the whole peptide and rationalize the origins of this effect, with potential implications for the rational design of peptides of chemical and biological relevance

Stereochemistry Rules: A Single Stereocenter Changes the Conformation of a Cyclic Tetrapeptide

Two novel cyclo­(Boc-Cys-Pro-Leu-Cys-OMe) peptides <b>1</b> and <b>2</b> containing the enantiomeric amino acids d-Leu and l-Leu, respectively, were synthesized to investigate the effect of chiral centers on peptide conformations. By combining a variety of experimental techniques (X-ray crystallography, 2D NMR spectroscopy, temperature-dependent ¹H NMR and IR spectroscopy, and UV-CD spectroscopy) with replica exchange molecular dynamics (REMD) techniques and quantum mechanics/molecular dynamics (QM/MM) calculations, we establish that the stereochemistry of just one residue can noticeably influence the properties of the whole peptide and rationalize the origins of this effect, with potential implications for the rational design of peptides of chemical and biological relevance