Publicaciones

Contrary to differentiated cells, cancer cells predominantly convert glucose to lactate even under conditions of adequate oxygen supply (“Warburg effect”). The initial enzyme implicated in this route is hexokinase, which transforms D-glucose into D-glucose-6-phosphate. We proposed the use of different polyphenols (resveratrol, epigallocatechin gallate, pterostilbene, phloretin) and their derivatives (α-glucosides and acylated α-glucosides) to inhibit this enzyme. For this study, we used Saccharomyces cerevisiae hexokinase, whose two isoforms show high resemblance at the active site with human hexokinase HK2. To monitor the reactions, a method of anion-exchange chromatography coupled with pulsed amperometric detection (HPAEC-PAD) was developed. Remarkably, most of the assayed compounds inhibited the enzyme more than 50 % in the standard assay. Among them, phloretin 4’-O-(6’’-O-octanoyl)-α-D-glucopyranoside showed the highest inhibition and was studied in depth to determine the inhibition pattern and inhibition constant. The Ki for glucose was calculated to be 22.1±0.4 μM. Computational models of inhibition were carried out with the three molecules displaying the highest inhibition, and correlated adequately with the observed inhibitory effects on the enzyme. The inhibitory effect of several of the assayed polyphenols on hexokinase and their lack of toxicity renders them promising candidates as adjuvant drugs for cancer therapy.

Mimicry, that is, the imitation of any unpalatable or defensive species by another, has been of central interest to evolutionary research since Darwin's lifetime. Two ant species, Camponotus guanchus Santschi, 1908 and Crematogaster alluaudi Emery, 1893, endemic to the Canary Islands, occur in two color-morphs: While the head of workers is always reddish and the gaster blackish, the mesosoma (inclusive waist) is either fully reddish or fully blackish. In addition to the obvious morphological and coloration similarities, we provide evidence of mimicry: (i) Ca. guanchus was found only within the area of Cr. alluaudi. (ii) Color morphs are geographically non-randomly distributed: Workers of both species from 16 localities of syntopic occurrences shared in eight cases a blackish and in eight cases a reddish mesosoma. Hence, Ca. guanchus mimics both local color-morphs of Cr. alluaudi. We consider a fascinating analogy with the Mediterranean mimicry system in Camponotus lateralis (Olivier, 1792) and its model species of the Crematogaster scutellaris (Olivier, 1792) group on an island scale. Additionally, we present two endemic bug species, Perenotus stysi (Ribes et al., 2008) and P. malobae Roca-Cusachs & Goula, 2016, as mimics of those Cr. alluaudi workers having a reddish mesosoma. Our distribution, coloration, frequency, and behavioral data as well as the analogy with Ca. lateralis and the Cr. scutellaris group suggest a Batesian-mimicry system in which Ca. guanchus, Perenotus stysi, and P. malobae mimic the unpalatable and aggressive Cr. alluaudi as an antipredator adaptation.

Primary amoebic meningoencephalitis is caused by the free-living amoeba Naegleria fowleri. The lack of standardized treatment has significantly contributed to the high fatality rates observed in reported cases. Therefore, this study aims to explore the anti-Naegleria activity of eight synthesized cyanoacrylamides and 5-iminopyrrol-2-ones. Notably, QOET-109, QOET-111, QOET-112, and QOET-114 exhibited a higher selectivity index against Naegleria compared to those of the rest of the compounds. Subsequently, these chemicals were assessed against the resistant stage of N. fowleri, demonstrating activity similar to that observed in the vegetative stage. Moreover, characteristic events of programmed cell death were evidenced, including chromatin condensation, increased plasma membrane permeability, mitochondrial damage, and heightened oxidative stress, among others. Finally, this research demonstrated the in vitro activity of the cyanoacrylamide and 5-iminopyrrol-2-one molecules, as well as the induction of metabolic event characteristics of regulated cell death in Naegleria fowleri.

A series of new hybrid compounds was prepared combining tetrahydropyran rings with different aromatic systems by means of a 1,2,3-triazole, using a building block strategy. The design of these structures was guided by Lead-Likeness and Molecular Analysis (LLAMA) software, adding modifications to our most potent scaffold (the tetrahydropyran ring) to generate promising “lead-like” candidates, which were subsequently compared against reported anticancer compounds. Our synthesized compounds demonstrated significant antiproliferative activity when compared with the standards cisplatin and 5-fluorouracil, across a panel of six different tumor cell lines. Moreover, compared with our group's previous hybrid compounds, these new structures exhibit similar activity while offering simpler synthesis and greater potential for structural diversification, a fact that was previously an issue. Further investigations on the most active compounds included assessments of reproductive cell survival, inhibition of cell migration, and effects on nuclear morphology, indicating potential diverse mechanisms of action for these compounds. Pharmacokinetic properties were also calculated for the whole series of compounds using the pkCSM online software.

The emergence of drug-resistant bacteria poses a significant challenge to modern medicine. In response, Artificial Intelligence (AI) and Machine Learning (ML) algorithms have emerged as powerful tools for combating antimicrobial resistance (AMR). This review aims to explore the role of AI/ML in AMR management, with a focus on identifying pathogens, understanding resistance patterns, predicting treatment outcomes, and discovering new antibiotic agents. Recent advancements in AI/ML have enabled the efficient analysis of large datasets, facilitating the reliable prediction of AMR trends and treatment responses with minimal human intervention. ML algorithms can analyze genomic data to identify genetic markers associated with antibiotic resistance, enabling the development of targeted treatment strategies. Additionally, AI/ML techniques show promise in optimizing drug administration and developing alternatives to traditional antibiotics. By analyzing patient data and clinical outcomes, these technologies can assist healthcare providers in diagnosing infections, evaluating their severity, and selecting appropriate antimicrobial therapies. While integration of AI/ML in clinical settings is still in its infancy, advancements in data quality and algorithm development suggest that widespread clinical adoption is forthcoming. In conclusion, AI/ML holds significant promise for improving AMR management and treatment outcome.

Martins, Anabela; Collart, Flavien; Sim-Sim, Manuela; Patiño, Jairo.

Ciguateric syndrome is a food poisoning associated with the consumption of some species of fish that have accumulated ciguatoxins (CTXs) in their tissues. The effects of the syndrome occur with nervous imbalances which have been described for quite some time, and mentioned in sailing literature for centuries. In the last decade, research has been focused on the implementation of analytical methods for toxin identification and the study of action modes of CTXs to design effective treatments. However, an important aspect is to determine the damage that CTXs caused in the organs of affected individuals. In this work, the damages observed in tissues of mice, mainly in the small intestine, were analyzed. The animals were fed with CTX-contaminated fish muscle at concentrations 10-times below the median lethal dose (LD50) for 10 weeks. The analysis of tissues derived from the oral treatment resulted in an increased occurrence of Paneth cells, presence of lymphoid tissue infiltrating the mucosa and fibrous lesions in the mucosal layer of the small intestine. A decreasing weight in animals fed with toxic muscle was observed.

Interferometric Synthetic Aperture Radar (InSAR) has catapulted our ability to detect, quantify, and characterize bio- and geophysical processes (e.g., aquifer dynamics, tectonic, and magmatic processes, etc.). During the last four decades, InSAR has imaged the complete Earth’s land surface and transformed our understanding of how Earth works. Such revolution has been underpinned by a relentless development of radar technology and processing methods and facilitated by free and open access to satellite missions’ data. Although satellite radar images represent electrical and geometrical properties of the illuminated ground surface, here I focus on the geometric information obtained from the phase delay (interferometric) patterns between two or more SAR images. After a brief overview of InSAR history, I review the fundamentals of the most popular interferometric methods and present a vision of how InSAR will deliver wide and easily accessible global high-resolution processed information, highlighting future challenges to monitor and understand Earth dynamics. Finally, I encourage further work on developing new radar mission concepts and harnessing big-data processing workflows deployed on energy-efficient and fast computing infrastructure, while minimizing our environmental footprint. To achieve such ambitious goals, I argue that researchers and technicians will have to collaborate in an inclusive environment, with a wide and diverse range of beneficiaries to achieve sustainability on a fast-changing Earth.

The Canary Islands is a Macaronesian volcanic archipelago with a depauperate community of three species of Kalotermitidae, including Kalotermes dispar. A total of 54 Kalotermes colonies were collected from Gran Canaria, Tenerife, La Gomera, La Palma, and El Hierro islands. Soldiers and imagos were morphologically examined and sequenced for four mitochondrial markers. Although morphological differences could not be detected, phylogenetic analysis of both cox1/tRNA/cox2 and rrnL markers revealed two distinct clades of K. dispar, suggesting cryptic diversity. The diversification within the Canary Kalotermes lineage most likely occurred around 7.5 Mya, while the divergence within the two clades was reconstructed at about 3.6 Mya and 1.9 Mya. Kalotermes approximatus from the southeastern Nearctic constitutes a sister to the Canary Kalotermes, while the Palearctic K. flavicollis, K. italicus, and K. phoenicae form a separate clade. It is hypothesized that a faunal exchange of Kalotermes from the Nearctic to the Canary Islands occurred via transoceanic rafting during the mid-Miocene.

Background

Current trends in Analytical Chemistry are highly focused on the introduction of new extraction materials with a high selectivity towards the target analytes, high extraction capacity as well as sustainable characteristics. In this context, the introduction of smart materials able to respond to an external stimulus constitutes a promising approach in the field. However, investigations regarding the development of such stimuli-responsive polymers have been basically centered on their synthesis and the control of their properties, and hardly on exploiting such properties to generate polymers that, once their extraction function is fulfilled, they can be degraded into fragments with little or negligible toxicity, or even into their constituent monomers for an efficient recycling.

Results

The applicability of a degradable and recyclable dynamic covalent polymer based on the use of tetrazine as a linker was assessed as sorbent for the extraction of a group of 37 persistent organic pollutants, including 10 polycyclic aromatic hydrocarbons, 11 organochlorine pesticides, 14 polychlorinated biphenyls, and 2 antibacterial agents, from water samples. A microdispersive solid-phase extraction procedure was developed for the selective extraction of the target analytes, while their separation, determination, and quantification were achieved by gas chromatography coupled to mass spectrometry. The optimized procedure was validated for seawater and wastewater obtaining mean relative recovery values between 72 and 112 % for almost all the analytes, with satisfactory relative standard deviation values (<18 %). After extraction, the polymer could be degraded by adding the amino acid L-tyrosine, being possible a quantitative recovery of the initial functional monomer.

Significance

A responsive polymer based on the chemical versatility of the tetrazine ring was used as sorbent in sample preparation providing excellent results, showing good physicochemical properties and the ability to be degraded after use. This polymer constitutes an interesting alternative to reduce chemical waste through the recycling of monomers, contributing to the development of more sustainable analytical methodologies.