The Epithelial to Mesenchymal Transition in Colorectal Cancer Progression: The Emerging Role of Succinate Dehydrogenase Alterations and Succinate Accumulation.

Colorectal cancer (CRC) stands as the third most significant contributor to cancer-related mortality worldwide. A major underlying reason is that the detection of CRC usually occurs at an advanced metastatic stage, rendering therapies ineffective. In the progression from the in situ neoplasia stage to the advanced metastatic stage, a critical molecular mechanism involved is the epithelial-to-mesenchymal transition (EMT). This intricate transformation consists of a series of molecular changes, ultimately leading the epithelial cell to relinquish its features and acquire mesenchymal and stem-like cell characteristics. The EMT regulation involves several factors, such as transcription factors, cytokines, micro RNAs and long noncoding RNAs. Nevertheless, recent studies have illuminated an emerging link between metabolic alterations and EMT in various types of cancers, including colorectal cancers. In this review, we delved into the pivotal role played by EMT during CRC progression, with a focus on highlighting the relationship between the alterations of the tricarboxylic acid cycle, specifically those involving the succinate dehydrogenase enzyme, and the activation of the EMT program. In fact, emerging evidence supports the idea that elucidating the metabolic modifications that can either induce or inhibit tumor progression could be of immense significance for shaping new therapeutic approaches and preventative measures. We conclude that an extensive effort must be directed towards research for the standardization of drugs that specifically target proteins such as SDH and SUCNR1, but also TRAP1, PDH, ERK1/2, STAT3 and the HIF1-α catabolism.

Genome-Scale Mining of Acetogens of the Genus Clostridium Unveils Distinctive Traits in [FeFe]- and [NiFe]-Hydrogenase Content and Maturation.

Knowledge of the organizational and functional properties of hydrogen metabolism is pivotal to the construction of a framework supportive of a hydrogen-fueled low-carbon economy. Hydrogen metabolism relies on the mechanism of action of hydrogenases. In this study, we investigated the genomes of several industrially relevant acetogens of the genus Clostridium (C. autoethanogenum, C. ljungdahlii, C. carboxidivorans, C. drakei, C. scatologenes, C. coskatii, C. ragsdalei, C. sp. AWRP) to systematically identify their intriguingly diversified hydrogenases' repertoire. An entirely computational annotation pipeline unveiled common and strain-specific traits in the functional content of [NiFe]- and [FeFe]-hydrogenases. Hydrogenases were identified and categorized into functionally distinct classes by the combination of sequence homology, with respect to a database of curated nonredundant hydrogenases, with the analysis of sequence patterns characteristic of the mode of action of [FeFe]- and [NiFe]-hydrogenases. The inspection of the genes in the neighborhood of the catalytic subunits unveiled a wide agreement between their genomic arrangement and the gene organization templates previously developed for the predicted hydrogenase classes. Subunits' characterization of the identified hydrogenases allowed us to glean some insights on the redox cofactor-binding determinants in the diaphorase subunits of the electron-bifurcating [FeFe]-hydrogenases. Finally, the reliability of the inferred hydrogenases was corroborated by the punctual analysis of the maturation proteins necessary for the biosynthesis of [NiFe]- and [FeFe]-hydrogenases. IMPORTANCE Mastering hydrogen metabolism can support a sustainable carbon-neutral economy. Of the many microorganisms metabolizing hydrogen, acetogens of the genus Clostridium are appealing, with some of them already in usage as industrial workhorses. Having provided detailed information on the hydrogenase content of an unprecedented number of clostridial acetogens at the gene level, our study represents a valuable knowledge base to deepen our understanding of hydrogenases' functional specificity and/or redundancy and to develop a large array of biotechnological processes. We also believe our study could serve as a basis for future strain-engineering approaches, acting at the hydrogenases' level or at the level of their maturation proteins. On the other side, the wealth of functional elements discussed in relation to the identified hydrogenases is worthy of further investigation by biochemical and structural studies to ultimately lead to the usage of these enzymes as valuable catalysts.

Potential endocrine correlation with exposure to domoic acid in Southern Right Whale (Eubalaena australis) at the Península Valdés breeding ground.

In waters off Península Valdés (PV), Argentina, southern right whales (SRW, Eubalaena australis) are occasionally exposed to domoic acid (DA), a neurotoxin produced by diatoms of the genus Pseudo-nitzschia. Domoic acid toxicity in marine mammals can cause gastrointestinal and neurological clinical signs, alterations in hematologic and endocrine variables, and can be fatal in extreme cases. In this study, we validated an enzyme immunoassay to quantify fecal glucocorticoid metabolites (fGCm) in 16 SRW fecal samples from live and dead stranded whales in PV from 2013 to 2018 and assessed fGCm levels associated with DA exposure. Overall, fGCm levels were significantly lower in SRWs with detectable fecal DA (n = 3) as compared to SRWs with undetectable fecal DA levels (n = 13). The highest fecal DA was observed in a live lactating female, which had low fGCm compared to the other lactating females studied. The highest fGCm was observed in a lactating female with undetectable DA; interestingly, at the time of sample collection, this female was sighted with two calves, an extremely unusual occurrence in this species. Though the sample size of these exceptionally rare breeding-season fecal samples was unavoidably small, our study provides evidence of potential adrenal alterations in whales exposed to an environmental neurotoxin such as DA.

Electrophysiology of the Facultative Autotrophic Bacterium Desulfosporosinus orientis.

Electroautotrophy is a novel and fascinating microbial metabolism, with tremendous potential for CO2 storage and valorization into chemicals and materials made thereof. Research attention has been devoted toward the characterization of acetogenic and methanogenic electroautotrophs. In contrast, here we characterize the electrophysiology of a sulfate-reducing bacterium, Desulfosporosinus orientis, harboring the Wood-Ljungdahl pathway and, thus, capable of fixing CO2 into acetyl-CoA. For most electroautotrophs the mode of electron uptake is still not fully clarified. Our electrochemical experiments at different polarization conditions and Fe0 corrosion tests point to a H2- mediated electron uptake ability of this strain. This observation is in line with the lack of outer membrane and periplasmic multi-heme c-type cytochromes in this bacterium. Maximum planktonic biomass production and a maximum sulfate reduction rate of 2 ± 0.4 mM day-1 were obtained with an applied cathode potential of -900 mV vs. Ag/AgCl, resulting in an electron recovery in sulfate reduction of 37 ± 1.4%. Anaerobic sulfate respiration is more thermodynamically favorable than acetogenesis. Nevertheless, D. orientis strains adapted to sulfate-limiting conditions, could be tuned to electrosynthetic production of up to 8 mM of acetate, which compares well with other electroacetogens. The yield per biomass was very similar to H2/CO2 based acetogenesis. Acetate bioelectrosynthesis was confirmed through stable isotope labeling experiments with Na-H13CO3. Our results highlight a great influence of the CO2 feeding strategy and start-up H2 level in the catholyte on planktonic biomass growth and acetate production. In serum bottles experiments, D. orientis also generated butyrate, which makes D. orientis even more attractive for bioelectrosynthesis application. A further optimization of these physiological pathways is needed to obtain electrosynthetic butyrate production in D. orientis biocathodes. This study expands the diversity of facultative autotrophs able to perform H2-mediated extracellular electron uptake in Bioelectrochemical Systems (BES). We characterized a sulfate-reducing and acetogenic bacterium, D. orientis, able to naturally produce acetate and butyrate from CO2 and H2. For any future bioprocess, the exploitation of planktonic growing electroautotrophs with H2-mediated electron uptake would allow for a better use of the entire liquid volume of the cathodic reactor and, thus, higher productivities and product yields from CO2-rich waste gas streams.

Occurrence of Toxigenic Microalgal Species and Phycotoxin Accumulation in Mesozooplankton in Northern Patagonian Gulfs, Argentina.

In the Northern Patagonian gulfs of Argentina (Golfo Nuevo and Golfo San José), blooms of toxigenic microalgae and the detection of their associated phycotoxins are recurrent phenomena. The present study evaluated the transfer of phycotoxins from toxigenic microalgae to mesozooplankton in Golfo Nuevo and Golfo San José throughout an annual cycle (December 2014-2015 and January 2015-2016, respectively). In addition, solid-phase adsorption toxin tracking (SPATT) samplers were deployed for the first time in these gulfs, to estimate the occurrence of phycotoxins in the seawater between the phytoplankton samplings. Domoic acid was present throughout the annual cycle in SPATT samplers, whereas no paralytic shellfish poisoning toxins were detected. Ten toxigenic species were identified: Alexandrium catenella, Dinophysis acuminata, Dinophysis acuta, Dinophysis tripos, Dinophysis caudata, Prorocentrum lima, Pseudo-nitzschia australis, Pseudo-nitzschia calliantha, Pseudo-nitzschia fraudulenta, and Pseudo-nitzschia pungens. Lipophilic and hydrophilic toxins were detected in phytoplankton and mesozooplankton from both gulfs. Pseudo-nitzschia spp. were the toxigenic species most frequent in these gulfs. Consequently, domoic acid was the phycotoxin most abundantly detected and transferred to upper trophic levels. Spirolides were detected in phytoplankton and mesozooplankton for the first time in the study area. Likewise, dinophysistoxins were found in mesozooplankton from both gulfs, and this is the first report of the presence of these phycotoxins in zooplankton from the Argentine Sea. The dominance of calanoid copepods indicates that they were the primary vector of phycotoxins in the pelagic trophic web. Environ Toxicol Chem 2019;38:2209-2223. © 2019 SETAC.

Anodic microbial community analysis of microbial fuel cells based on enriched inoculum from freshwater sediment.

The characterization of anodic microbial communities is of great importance in the study of microbial fuel cells (MFCs). These kinds of devices mainly require a high abundance of anode respiring bacteria (ARB) in the anode chamber for optimal performance. This study evaluated the effect of different enrichments of environmental freshwater sediment samples used as inocula on microbial community structures in MFCs. Two enrichment media were compared: ferric citrate (FeC) enrichment, with the purpose of increasing the ARB percentage, and general enrichment (Gen). The microbial community dynamics were evaluated by polymerase chain reaction followed by denaturing gradient gel electrophoresis (PCR-DGGE) and real time polymerase chain reaction (qPCR). The enrichment effect was visible on the microbial community composition both during precultures and in anode MFCs. Both enrichment approaches affected microbial communities. Shannon diversity as well as ß-Proteobacteria and γ-Proteobacteria percentages decreased during the enrichment steps, especially for FeC (p < 0.01). Our data suggest that FeC enrichment excessively reduced the diversity of the anode community, rather than promoting the proliferation of ARB, causing a condition that did not produce advantages in terms of system performance.

Domoic acid in a marine pelagic food web: Exposure of southern right whales Eubalaena australis to domoic acid on the Península Valdés calving ground, Argentina.

The gulfs that surround Península Valdés (PV), Golfo Nuevo and Golfo San José in Argentina, are important calving grounds for the southern right whale Eubalaena australis. However, high calf mortality events in recent years could be associated with phycotoxin exposure. The present study evaluated the transfer of domoic acid (DA) from Pseudo-nitzschia spp., potential producers of DA, to living and dead right whales via zooplanktonic vectors, while the whales are on their calving ground at PV. Phytoplankton and mesozooplankton (primary prey of the right whales at PV and potential grazers of Pseudo-nitzschia cells) were collected during the 2015 whale season and analyzed for species composition and abundance. DA was measured in plankton and fecal whale samples (collected during whale seasons 2013, 2014 and 2015) using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). The genus Pseudo-nitzschia was present in both gulfs with abundances ranging from 4.4×102 and 4.56×105 cell l-1. Pseudo-nitzschia australis had the highest abundance with up to 4.56×105 cell l-1. DA in phytoplankton was generally low, with the exception of samples collected during a P. australis bloom. No clear correlation was found between DA in phytoplankton and mesozooplankton samples. The predominance of copepods in mesozooplankton samples indicates that they were the primary vector for the transfer of DA from Pseudo-nitzschia spp. to higher trophic levels. High levels of DA were detected in four whale fecal samples (ranging from 0.30 to 710µgg-1 dry weight of fecal sample or from 0.05 and 113.6µgg-1 wet weight assuming a mean water content of 84%). The maximum level of DA detected in fecal samples (710µg DA g-1 dry weight of fecal sample) is the highest reported in southern right whales to date. The current findings demonstrate for the first time that southern right whales, E. australis, are exposed to DA via copepods as vectors during their calving season in the gulfs of PV.

Microwave-Assisted Synthesis of Reduced Graphene Oxide/SnO2 Nanocomposite for Oxygen Reduction Reaction in Microbial Fuel Cells.

We report on an easy, fast, eco-friendly, and reliable method for the synthesis of reduced graphene oxide/SnO2 nanocomposite as cathode material for application in microbial fuel cells (MFCs). The material was prepared starting from graphene oxide that has been reduced to graphene during the hydrothermal synthesis of the nanocomposite, carried out in a microwave system. Structural and morphological characterizations evidenced the formation of nanocomposite sheets, with SnO2 crystals of few nanometers integrated in the graphene matrix. Physico-chemical analysis revealed the formation of SnO2 nanoparticles, as well as the functionalization of the graphene by the presence of nitrogen atoms. Electrochemical characterizations put in evidence the ability of such composite to exploit a cocatalysis mechanism for the oxygen reduction reaction, provided by the presence of both SnO2 and nitrogen. In addition, the novel composite catalyst was successfully employed as cathode in seawater-based MFCs, giving electrical performances comparable to those of reference devices employing Pt as catalyst.