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International audience; It has been recently shown that many proteins are lacking from reference databases used in mass spectrometry analysis, due to their translation templated on alternative open reading frames. This questions our current understanding of gene annotation and drastically expands the theoretical proteome complexity. The functions of these alternative proteins (AltProts) still remain largely unknown. We have developed a large-scale and unsupervised approach based on cross-linking mass spectrometry (XL-MS) followed by shotgun proteomics to gather information on the functional role of AltProts by mapping them back into known signalling pathways through the identification of their reference protein (RefProt) interactors. We have identified and profiled AltProts in a cancer cell reprogramming system: NCH82 human glioma cells after 0, 16, 24 and 48 h Forskolin stimulation. Forskolin is a protein kinase A activator inducing cell differentiation and epithelial-mesenchymal transition. Our data show that AltMAP2, AltTRNAU1AP and AltEPHA5 interactions with tropomyosin 4 are downregulated under Forskolin treatment. In a wider perspective, Gene Ontology and pathway enrichment analysis (STRING) revealed that RefProts associated with AltProts are enriched in cellular mobility and transfer RNA regulation. This study strongly suggests novel roles of AltProts in multiple essential cellular functions and supports the importance of considering them in future biological studies.

With the advent of novel molecular platforms for high-throughput/next-generation sequencing, the communities of commensal and pathogenic microorganisms that inhabit the human body have been defined in depth. In the last decade, the role of microbiota-host interactions in driving human cancer plasticity and malignant progression has been well documented. Germ-free preclinical models provided an invaluable tool to demonstrate that the human microbiota can confer susceptibility to various types of cancer and can also modulate the host response to therapeutic treatments. Of interest, besides the detrimental effects of dysbiosis on cancer etiopathogenesis, specific microorganisms have been shown to exert protective activities against cancer growth. This has strong clinical implications, as restoration of the physiologic microbiota is being rapidly implemented as a novel anticancer therapeutic strategy. Here, we reviewed past and recent literature depicting the role of microbiota-host interactions in modulating key molecular mechanisms that drive human cancer plasticity and lead to malignant progression. We analyzed microbiota-host interactions occurring in the gut as well as in other anatomic sites, such as oral and nasal cavities, lungs, breast, esophagus, stomach, reproductive tract, and skin. We revealed a common ground of biological alterations and pathways modulated by a dysbiotic microbiota and potentially involved in the control of cancer progression. The molecular mechanisms most frequently affected by the pathogenic microorganisms to induce malignant progression involve epithelial-mesenchymal transition- (EMT-) dependent barrier alterations and tumor-promoting inflammation. This evidence may pave the way to better stratify high-risk cancer patients based on unique microenvironmental/microbial signatures and to develop novel, personalized, biological therapies.

El objetivo general de la investigación fue conocer las prácticas relacionadas con la alimentación saludable y promoción de la salud que desarrollan los estudiantes y docentes de la UNLaM, y a su vez, desarrollar un análisis de la oferta y disposición institucional en cuanto a aspectos de promoción de la salud (habilidades personales y entornos saludables) y alimentación saludable. Se realizaron 346 encuestas a estudiantes y docentes de la UNLaM, y se indagó acerca de sus hábitos alimentarios, actividades vinculadas con la promoción de la salud, actividad física, consumo de sodio, alcohol y percepción acerca de su propia salud. Se indagó también sobre la presencia de espacios promotores de la salud dentro de la universidad, se observaron los espacios donde se ofrecen comidas y alimentos, y se definieron actores claves para ser entrevistados. Se identificó una prevalencia de exceso de peso cercana al 37%, y un bajo consumo de frutas y hortalizas. Más del 50% de las personas no realizan la cantidad suficiente de ejercicio físico diario. Por otro lado, los espacios institucionales que ofrecen alimentos no adecuaron su oferta a un estilo de vida saludable y promotor de la salud, ya que en proporción se ofrecen mayor cantidad de alimentos que no acompañan una alimentación saludable. Sin embargo, la UNLaM cuenta con un gran potencial para mejorar y adaptar la oferta de alimentos y combatir de este modo las altas prevalencias de exceso de peso y sedentarismo. Finalmente, se presentan una serie de recomendaciones generales e institucionales, así como materiales de educación para la salud. Fil: Klein, Karen. Universidad Nacional de La Matanza; Argentina. Fil: Clacheo, Rodrigo. Universidad Nacional de La Matanza; Argentina. Fil: Dakessian, María Andrea. Universidad Nacional de La Matanza; Argentina. Fil: Areces, Graciela. Universidad Nacional de La Matanza; Argentina. Fil: Fernández, Alicia. Universidad Nacional de La Matanza; Argentina. Fil: Sánchez, Claudio. Universidad Nacional de La Matanza; Argentina. Fil: Pukas, Silvia. Universidad Nacional de La Matanza; Argentina. Fil: Damato, Marina. Universidad Nacional de La Matanza; Argentina. Fil: Colombo, Celeste. Universidad Nacional de La Matanza; Argentina.

Microglia cells are the primary immune population of the central nervous system with a role in the regulation of several physiological and pathological conditions. Upon appropriate stimulation, microglia cells can be polarized in a pro-inflammatory M1-like or anti-inflammatory M2-like status. Biological processes and pathways engaged in microglia polarization are starting to be elucidated. To help clarify this, we used a liquid chromatography-mass spectrometry (LC-MS/MS) label free approach to characterize the proteomic profile of human microglia cell line (CHME-5) stimulated with gamma-interferon (IFN-&gamma, ) and interleukin-4 (IL-4) to induce a M1 or M2 phenotype, respectively. Outside the classical M1/M2 polarization markers, the M1 status appears to center around the activation of a classical inflammatory response and through the activation of multiple signaling pathways. M2 polarization resulted in a different pattern of protein modulation related to RNA and cellular metabolic processes. Together, our findings provide information regarding the protein changes specific to M1 and M2 activation states, and potentially link the polarization of microglia cells to the acquisition of a specific proteomic profile.

With the advent of novel molecular platforms for high-throughput/next-generation sequencing, the communities of commensal and pathogenic microorganisms that inhabit the human body have been defined in depth. In the last decade, the role of microbiota-host interactions in driving human cancer plasticity and malignant progression has been well documented. Germ-free preclinical models provided an invaluable tool to demonstrate that the human microbiota can confer susceptibility to various types of cancer and can also modulate the host response to therapeutic treatments. Of interest, besides the detrimental effects of dysbiosis on cancer etiopathogenesis, specific microorganisms have been shown to exert protective activities against cancer growth. This has strong clinical implications, as restoration of the physiologic microbiota is being rapidly implemented as a novel anticancer therapeutic strategy. Here, we reviewed past and recent literature depicting the role of microbiota-host interactions in modulating key molecular mechanisms that drive human cancer plasticity and lead to malignant progression. We analyzed microbiota-host interactions occurring in the gut as well as in other anatomic sites, such as oral and nasal cavities, lungs, breast, esophagus, stomach, reproductive tract, and skin. We revealed a common ground of biological alterations and pathways modulated by a dysbiotic microbiota and potentially involved in the control of cancer progression. The molecular mechanisms most frequently affected by the pathogenic microorganisms to induce malignant progression involve epithelial-mesenchymal transition- (EMT-) dependent barrier alterations and tumor-promoting inflammation. This evidence may pave the way to better stratify high-risk cancer patients based on unique microenvironmental/microbial signatures and to develop novel, personalized, biological therapies.