Synuclein Proteins in Cancer Development and Progression.

Synucleins are a family of small, soluble proteins mainly expressed in neural tissue and in certain tumors. Since their discovery, tens of thousands of scientific reports have been published about this family of proteins as they are associated with severe human diseases. Although the physiological function of these proteins is still elusive, their relationship with neurodegeneration and cancer has been clearly described over the years. In this review, we summarize data connecting synucleins and cancer, going from the structural description of these molecules to their involvement in tumor-related processes, and discuss the putative use of these proteins as cancer molecular biomarkers.

Binucleating Hydrazonic Ligands and Their µ-Hydroxodicopper(II) Complexes as Promising Structural Motifs for Enhanced Antitumor Activity.

Very few inorganic antineoplastic drugs have entered the clinic in the last decades, mainly because of toxicity issues. Because copper is an essential trace element of ubiquitous occurrence, decreased side effects could be expected in comparison with the widely used platinum anticancer compounds. In the present work, two novel hydrazonic binucleating ligands and their µ-hydroxo dicopper(II) complexes were prepared and fully characterized. They differ by the nature of the aromatic group present in their aroylhydrazone moieties: while H3L1 and its complex, 1, possess a thiophene ring, H3L2 and 2 contain the more polar furan heterocycle. X-ray diffraction indicates that both coordination compounds are very similar in structural terms and generate dimeric arrangements in the solid state. Positive-ion electrospray ionization mass spectrometry analyses confirmed that the main species present in a 10% dimethyl sulfoxide (DMSO)/water solution should be [Cu2(HL)(OH)]+ and the DMSO-substituted derivative [Cu2(L)(DMSO)]+. Scattering techniques [dynamic light scattering (DLS) and small-angle X-ray scattering] suggest that the complexes and their free ligands interact with bovine serum albumin (BSA) in a reversible manner. The binding constants to BSA were determined for the complexes through fluorescence spectroscopy. Moreover, to gain insight into the mechanism of action of the compounds, calf thymus DNA binding studies by UV-visible and DLS measurements using plasmid pBR322 DNA were also performed. For the complexes, DLS data seem to point to the occurrence of DNA cleavage to Form III (linear). Both ligands and their dicopper(II) complexes display potent antiproliferative activity in a panel of four cancer cell lines, occasionally even in the submicromolar range, with the complexes being more potent than the free ligands. Our data on cellular models correlate quite well with the DNA interaction experiments. The results presented herein show that aroylhydrazone-derived binucleating ligands, as well as their dinuclear µ-hydroxodicopper(II) complexes, may represent a promising structural starting point for the development of a new generation of highly active potential antitumor agents.

Metagenomics unveils the attributes of the alginolytic guilds of sediments from four distant cold coastal environments.

Alginates are abundant polysaccharides in brown algae that constitute an important energy source for marine heterotrophic bacteria. Despite the key role of alginate degradation processes in the marine carbon cycle, little information is available on the bacterial populations involved in these processes. The aim of this work was to gain a better understanding of alginate utilization capabilities in cold coastal environments. Sediment metagenomes from four high-latitude regions of both Hemispheres were interrogated for alginate lyase gene homologue sequences and their genomic context. Sediments contained highly abundant and diverse bacterial assemblages with alginolytic potential, including members of Bacteroidetes and Proteobacteria, as well as several poorly characterized taxa. The microbial communities in Arctic and Antarctic sediments exhibited the most similar alginolytic profiles, whereas brackish sediments showed distinct structures with a higher proportion of novel genes. Examination of the gene neighbourhood of the alginate lyase homologues revealed distinct patterns depending on the potential lineage of the scaffolds, with evidence of evolutionary relationships among alginolytic gene clusters from Bacteroidetes and Proteobacteria. This information is relevant for understanding carbon fluxes in cold coastal environments and provides valuable information for the development of biotechnological applications from brown algae biomass.

Efecto de las condiciones de crecimiento y composición del medio de cultivo sobre la producción de bacteriocina de Enterococcus mundtii Tw56 / Effect of growth conditions and culture medium composition on bacteriocin production by Enterococcus mundtii Tw56

Enterococcus mundtii Tw56 es una cepa productora de bacteriocina que fue aislada del contenido intestinal de pejerrey (Odontesthes sp.). El objetivo del presente trabajo fue determinar los factores fisicoquímicos y la composición del medio de cultivo para lograr un mayor rendimiento de células viables y producción de bacteriocina. No se observaron cambios en la producción del antimicrobiano cuando la glucosa fue sustituida por fructosa o maltosa en la formulación del medio MRS. Por el contrario, la mayor actividad de las bacteriocinas se obtuvo cuando se utilizó el extracto de carne como fuente única de nitrógeno. Mientras que la máxima biomasa se alcanzó a 35 °C, las temperaturas óptimas para la producción de bacteriocina se observaron a 25 y 30 °C. El pH inicial óptimo para el crecimiento celular y bioactividad fue 6,5, ambos parámetros disminuyeron cuando la experiencia comenzó a pH 6,0 o 5,5. La formación de biomasa y la producción de bacteriocina disminuyeron en presencia de cloruro de sodio. La cepa comenzó a producir bacteriocina en la fase exponencial tardía. La actividad aumentó en función de la masa celular y alcanzó el máximo al final de la fase exponencial (12 h). Una disminución de la actividad antimicrobiana se observó en la fase estacionaria (16 h), posiblemente debido a la degradación por enzimas proteolíticas.

Enterococcus mundtii Tw56 is a bacteriocin-producing strain that was isolated from intestinal content of silverside (Odontesthes sp.). The aim of the present work was to determine physicochemical factors and culture medium composition for higher yield of viable cells and bacteriocin production. No changes were observed in the antimicrobial production when glucose was replaced by fructose or maltose in the MRS medium formulation. On the other hand, highest bacteriocin activity was obtained when meat extract was used as a sole nitrogen source. While the maximun biomass was achieved at 35 ºC, the optimal temperatures for bacteriocin production were observed at 25 and 30 ºC. The optimal initial pH for cell growth and bioactivity was 6.5, both parameters dropped when the experience started at pH 6.0 or 5.5. Biomass formation and bacteriocin production decreased in the presence of sodium chloride. The strain started producing the bacteriocin at the late exponential phase. The activity increased as a function of the cell mass and reached the maximun at the end of exponential phase (12 h). A decrease of antimicrobial activity was observed in the stationary phase (16 h), possibly due to degradation by proteolitic enzimes.