Explore the vast range of titles available.

The deprotection step is crucial in order to secure a good quality product in Fmoc solid phase peptide synthesis. 9-Fluorenylmethoxycarbonyl (Fmoc) removal is achieved by a two-step mechanism reaction favored by the use of cyclic secondary amines; however, the efficiency of the reaction could be affected by side reactions and by-product formation. Several aspects have to be taken into consideration when selecting a deprotection reagent: its physicochemical behavior, basicity (pKa) and polarity, concentration, and time of reaction, toxicity and disposability of residues and, finally, availability of reagents. This report presents a comparison of the performance of three strategies for deprotection using microwave-assisted Fmoc peptide synthesis. Four peptide sequences were synthesized using Rink amide resin with a Liberty Blue™ automated synthesizer and 4-methylpiperidine (4MP), piperidine (PP), and piperazine (PZ) as Fmoc removal reagents. In the first instance all three reagents behaved similarly. A detailed analysis showed a correlation between the hydrophobicity and size of the peptide with the yield and purity of the obtained product. The three reagents are interchangeable, and replacement of piperidine could be advantageous regarding toxicity and reagent handling.

Peptide synthesis is an area with a wide field of application, from biomedicine to nanotechnology, that offers the option of simultaneously synthesizing a large number of sequences for the purpose of preliminary screening, which is a powerful tool. Nevertheless, standard protocols generate large volumes of solvent waste. Here, we present a protocol for the multiple Fmoc solid-phase peptide synthesis in tea bags, where reagent recycling steps are included. Fifty-two peptides with wide amino acid composition and seven to twenty amino acid residues in length were synthesized in less than three weeks. A clustering analysis was performed, grouping the peptides by physicochemical features. Although a relationship between the overall yield and the physicochemical features of the sequences was not established, the process showed good performance despite sequence diversity. The recycling system allowed to reduce N, N-dimethylformamide usage by 25–30% and reduce the deprotection reagent usage by 50%. This protocol has been optimized for the simultaneous synthesis of a large number of peptide sequences. Additionally, a reagent recycling system was included in the procedure, which turns the process into a framework of circular economy, without affecting the quality of the products obtained.

Pancreatic ductal adenocarcinoma (PDAC) remains a major clinical challenge due to late detection and limited treatment responsiveness. To better evaluate complex immunotherapies in a human‐relevant setting, we developed an integrated organoid–immune co‐culture pipeline using PDAC patient‐derived organoids (PDOs) and matched HLA immune cells. As a proof of concept, we assessed an MSLN‐targeted nanovaccine (Mesovac), alone and in combination with FOLFIRINOX chemotherapy and Atezolizumab. We evaluated Mesovac across a multi‐stage pipeline, including T‐cell stimulation, ex vivo expansion, and PDO‐immune co‐cultures, to assess immune activation, specificity, and synergy with combinatorial treatments. MSLN‐stimulated T‐cells, derived from PDAC patients, showed increased IFN‐γ production and selective infiltration into MSLN‐expressing PDOs. Artificial antigen‐presenting cells (aAPCs) boosted the expansion of reactive T‐cells, enhancing antitumor responses. Notably, combining Mesovac with FOLFIRINOX and Atezolizumab maintained PD‐L1+ T‐cell levels and reduced cancer stem cells and aggressive PDAC subsets. Using this advanced in vitro workflow, we highlight that this platform, using human organoid–immune cell co‐cultures, enables the evaluation of complex processes related to nanovaccine strategies that would not be possible in vivo. Pancreatic ductal adenocarcinoma remains difficult to treat. We establish an organoid–immune co‐culture using patient‐derived organoids and matched T‐cells to assess cancer vaccines. A mesothelin‐targeted nanovaccine activates antigen‐specific T‐cells, increases IFN‐γ, and targets MSLN+ organoids. Combined with FOLFIRINOX and Atezolizumab, it reduces stemness and maintains immune activity, enabling personalized ex vivo vaccine evaluation.

El objeto de este trabajo es analizar los elementos que dan forma a la noción militar de seguridad nacional en México. La formulación original del concepto de seguridad nacional, y las nociones relacionadas, como la de poder nacional, se encuentra en los trabajos de académicos universitarios en Estados Unidos (EE.UU.) que datan de las décadas de 1930 y 1940. Se estudian los antecedentes de la noción de seguridad interior que pueden rastrearse, para el caso de México, a la monarquía española en la época colonial, pasando por el constitucionalismo de los siglos XIX y XX. Se destaca la forma en que la propuesta de desarrollo anexada a la doctrina se convirtió en axioma en las versiones latinoamericanas, justificando la intervención de militares en funciones consideradas de naturaleza civil. Por último, se examina cómo la doctrina de seguridad nacional sirvió para justificar la reconfiguración de relaciones civiles-militares en los países de la región, incluyendo México. Se trata de un esfuerzo de revisión de un marco teórico que no ha cambiado en lo esencial desde su formulación a inicios de la década de 1980. This paper analyzes the elements that constitute Mexico’s military notion of national security. The original formulation of the concept of national security and related notions, such as national power, is found in the works of university academics in the United States between the 1930s and 1940s. In the case of Mexico, the background of the notion of internal security is studied and traced to the Spanish monarchy in the colonial era, passing through the 19th and 20th centuries constitutionalism. The article highlights how the development proposal attached to the doctrine became an axiom in the Latin American versions, justifying the intervention of military personnel in functions considered of a civil nature. Finally, how the doctrine of national security served to justify a reconfiguration of civil-military relations in the region’s countries, including Mexico, is examined. This work is an initial effort to review a theoretical framework that has not essentially changed since its formulation in the early 1980s.

Background/Objectives: Immunotherapy has shown promising results in some cancers, but its efficacy remains limited in pancreatic ductal adenocarcinoma (PDAC). Vaccines in nanoparticle form (nanovaccines) can incorporate immunostimulating components to induce a potent immune response. As mesothelin (MSLN) is a tumor-associated antigen overexpressed in PDAC, we evaluated the effect of MSLN nanovaccine in a syngeneic orthotopic KPC-PDAC mouse model. Methods: An MSLN peptide combining three MSLN epitopes and two adjuvants, poly I:C and R848, was encapsulated in PLGA–chitosan nanoparticles to generate the nanovaccine. Results: The MSLN nanovaccine was successfully taken up by dendritic cells in vitro and was found in inguinal lymph nodes 24 h after subcutaneous injection into C57BL/6 mice. Nanovaccine re-stimulation of splenocytes from vaccinated mice led to increased levels of interferon-γ in vitro compared to unstimulated splenocytes. Higher levels of MSLN-specific IgM and IgG antibodies were detected in the serum of vaccinated mice compared to that of control mice. Three vaccination regimens were tested: a prophylactic scheme that included vaccination before tumor induction and two therapeutic schemes involving early and late vaccination after tumor cell inoculation. MSLN nanovaccination inhibited KPC tumor progression and metastasis and induced higher CD8+ T cell infiltration in the tumor that developed in response to prophylactic and early therapeutic schedules but not in response to a later vaccination approach. Although the nanovaccine treatment elicited higher humoral and cellular antigen-specific responses in tumor-bearing mice for both vaccination strategies, the therapeutic vaccination also increased the expression of exhaustion markers in CD8+ T cells. Conclusions: Our results support the relevance of an MSLN-based nanovaccine as a new immunotherapy treatment for PDAC and propose an innovative method of vaccine delivery using NPs.

Cyclotides are circular peptides found in various plant families. A cyclized backbone, together with multiple disulfide bonds, confers the peptides’ exceptional stability against protease digestion and thermal denaturation. In addition, the features of these antimicrobial molecules make them suitable for use in animal farming, such as aquaculture. Fmoc solid phase peptide synthesis on 2-chlorotrityl chlorine (CTC) resin using the “tea-bag” approach was conducted to generate the VarvA cyclotide identified previously from Viola arvensis. MALDI-TOF mass spectrometry determined the correct peptide amino acid sequence and the cyclization sites-critical in this multicyclic compound. The cyclotide showed antimicrobial activity against various Gram-negative bacteria, including recurrent pathogens present in Chilean aquaculture. The highest antimicrobial activity was found to be against Flavobacterium psychrophilum. In addition, membrane blebbing on the bacterial surface after exposure to the cyclotide was visualized by SEM microscopy and the Sytox Green permeabilization assay showed the ability to disrupt the bacterial membrane. We postulate that this compound can be proposed for the control of fish farming infections.

Several factors have influenced the increasing presence of peptides as an important class of Active Pharmaceutical Ingredients. One is the continued development of synthetic methodologies for peptide synthesis. Herein, we investigated the Fmoc removal step, using the tea-bag strategy. In this regard, three different secondary amines: piperidine, 4-methylpiperidine, and piperazine, were evaluated. As a result of this study, 4-methyl piperidine showed to be an excellent alternative to the usually used piperidine in terms of purity and compliance with green chemistry principles as well.

The aim of this work was to synthesize peptides that would perform two functions in the potential treatment of two types of cancer.The first group of peptides was used as the antigenic component of a nanovaccine formulation that represents an immunotherapeutic approach to treating pancreatic ductal adenocarcinoma. In some cases, the peptides were modified at the N-terminus through palmitoylation and PEGylation, with the objective of enhancing their immunogenic potential. Additionally, they were synthesized as single epitopes or as multi-epitope constructs derived from tumor-associated antigen proteins. The peptides were formulated in poly(lactic-co-glycolic) acid-based nanoparticles, and the resulting nanoformulation was tested in a mouse model to assess its immunogenic activity. Two multiepitope peptides demonstrated a markedly positive response in vitro. These were the PalmitoylPLTVAEVQKLLGPHVKKALPLDLLLFLKKSLLFLLFSL-NH2 peptide and the HKVYLRVRPLLKKSYGVLLWEIKKRFVPDGNRI-NH2 peptide. These findings suggest that long multi-epitope constructs are the most effective alternative for use as nanovaccine components, as single epitope peptides were demonstrated to lack immunogenicity. However, preliminary in vivo assays of the two multi-epitope peptides exhibited minimal activity against the tumor in a mouse model. Additional validation is necessary through the repetition of these assays.The second group of peptides served as targeting units in a quatsome nanovesicle delivery system that is designed to carry a therapeutic nucleic acid for the treatment of neuroblastoma. The peptides were initially synthesized with fluorescein as a probe. In parallel, a small molecule ligand, a thiolated paminobenzylguanidine derivative, was also synthesized, labeled and evaluated in conjunction with the targeting peptide moieties to determine their internalization capability in a neuroblastoma cell line.A sequence targeting the GD2 receptor in neuroblastoma cells (H-WHWRLPSGGGC-NH2) and the thiolated p-aminobenzylguanidine derivative, demonstrated the greatest capacity to internalize into these cells and were therefore selected for the development of a conjugation methodology in quatsome nanovesicles using a thiol-maleimide click reaction. The methodology was successfully developed, and the optimal conditions were identified as a pH of 7.5, a reaction time of two hours, the presence of a reducing agent and a clean-up methodology of size exclusion chromatography in Sephadex G50 and aqueous elution followed by mild acidic elution. This allowed for the separation of nanovesicles from unreacted ligands and the indirect estimation of the conjugated targeting moiety in the nanovesicle. The methodology yielded conjugation estimates of 50% to 65% for both the GD2- binding peptide and the thiolated p-aminobenzylguanidine derivative. Furthermore, this formulation was demonstrated to have the capacity to deliver a nucleic acid to a neuroblastoma cell line. However, a switch of the PEGyl moiety carrying the maleimide function from PEG2000 to PEG1000 is required to achieve quantitative internalization.Furthermore, a study was conducted to evaluate the suitability of five different carbodiimides for use in solid-phase peptide synthesis, the methodology employed for the production of all peptide compounds in this research. The objective of this comparative study was to identify an optimal alternative to N,N'-diisopropylcarbodiimide (DIC) that can prevent the formation of the toxic compound hydrogen cyanide, which can occur when the reaction is conducted in the presence of oxyma. The study demonstrated that 1-tert-butyl-3-ethylcarbodiimide is an effective alternative to DIC. It exhibited comparable synthetic performance in the production of two peptide models and an antigenic peptide, while reducing the occurrence of hydrogen cyanide by threefold compared to DIC.

El estudio de la biodiversidad marina se está convirtiendo no solo en una actividad académica que ayuda a conocer en mayor detalle las faunas y floras, sino en una urgencia social dada nuestra dependencia de los recursos naturales para poder mantener un nivel de vida aceptable. La llamada \"crisis de la biodiversidad\", que resulta del uso indiscriminado de los servicios ambientales que nos provee la naturaleza, en el fondo refleja la gran preocupación de múltiples sectores sobre el poco promisorio futuro que espera a la humanidad si los principios del desarrollo sustentable no son puestos en práctica con el fin de mejorar las condiciones del entorno natural, y en paralelo impulsar un desarrollo social más equitativo. Este libro se considera un aporte en este sentido, y presenta seis colaboraciones originales basadas en el trabajo de investigación de los miembros del Cuerpo Académico de Biología de la Conservación de la Universidad Autónoma de Baja California Sur, así como de una serie de investigadores asociados y catedráticos Conacyt, quienes se han especializado en diversos campos del estudio de la biodiversidad marina. Los capítulos presentan aportes que permiten establecer el nivel actual de conocimiento sobre el ecosistema de manglar en el estado de Baja California Sur y la importancia de conocer la distribución de los peces arrecifales, tiburones y aves terrestres residentes del golfo de California y la Península de Baja California, con el fin de apoyar su conservación. También se publican dos ensayos: uno dirigido a llamar la atención a la problemática del plástico en los océanos, y un segundo enfocado a describir la utilidad de una nueva herramienta tecnológica (los vehículos aéreos no tripulados), para mapear diversos aspectos de las poblaciones de aves y mamíferos residentes en la zona costera. Esperamos sinceramente que las contribuciones que conforman esta obra sean de utilidad para cualquier interesado en el bienestar de la biodiversidad marina, pero en especial que llamen la atención de estudiantes de todos los niveles académicos con el fin que en el futuro cercano puedan realizar nuevas investigaciones y acciones de vinculación que aumenten el conocimiento y la conciencia de la sociedad regional sobre la importancia de la conservación de los océanos.

Para la Presidencia de la Republica CANDIDATOVOTOSPORCENTAJE Vicente Fox93856.5 Francisco Labastida40724.5 [Gilberto Rincon Gallardo]17910.8 [Cuauhtemoc Cardenas]704.2 [Porfirio Munoz Ledo]563.33 [Manuel Camacho]30.12 Votos nulos70.58 Total1660100 Para el DF Santiago Creel Miranda66139.8 [Jesus Silva Herzog]62137.4 [Andres M. Lopez Obrador]32019.3 [Tere Vale]271.6 [Alejandro Ordorica]20.12 Total166098.22 Para la Presidencia de la Republica CANDIDATOVOTOSPORCENTAJE Vicente Fox216070 Francisco Labastida41313 Cuauhtemoc Cardenas2137 Gilberto Rincon Gallardo2127 Porfirio Munoz Ledo772 Manuel Camacho171 Total3092100 Para la Presidencia de la Republica CANDIDATOVOTOSPORCENTAJE Vicente Fox86763.23 Francisco Labastida18213.27 Cuauhtemoc Cardenas16712.18 Gilberto Rincon Gallardo987.14 Porfirio Munoz Ledo443.20 Manuel Camacho50.36 Votos nulos80.58 Total1371100 Para el DF CANDIDATOVOTOSPORCENTAJE Santiago Creel Miranda56540.70 Anres M. Lopez Obrador40028.81 Jesus Silva Herzog34725.00 Tere Vale402.88 Alejandro Ordorica120.86 Votos nulos241.72 Total1388100