Metal-Specificity Divergence between Metallothioneins of Nerita peloronta (Neritimorpha,Gastropoda) Sets the Starting Point for a Novel Chemical MT Classification Proposal

Metallothioneins’ (MTs) biological function has been a matter of debate since their discovery. The importance to categorize these cysteine-rich proteins with high coordinating capacity into a specific group led to numerous classification proposals. We proposed a classification based on their metal-binding abilities, gradually sorting them from those with high selectivity towards Zn/Cd to those that are Cu-specific. However, the study of the NpeMT1 and NpeMT2isoforms of Nerita peloronta, has put a new perspective on this classification. N. peloronta has been chosen as a representative mollusk to elucidate the metal-binding abilities of Neritimorpha MTs, an order without any MTs characterized recently. Both isoforms have been recombinantly synthesized in cultures supplemented with Zn^II, Cd^II, or Cu^II, and the purified metal–MT complexes have been thoroughly characterized by spectroscopic and spectrometric methods, leading to results that confirmed that Neritimorpha share Cd-selective MTs with Caenogastropoda and Heterobranchia, solving a so far unresolved question. NpeMTs show high coordinating preferences towards divalent metal ions, although one of them (NpeMT1) shares features with the so-called genuine Zn-thioneins, while the other (NpeMT2) exhibits a higher preference for Cd. The dissimilarities between the two isoforms let a window open to a new proposal of chemical MT classification.     

Rescue of Vasopressin Synthesis in Magnocellular Neurons of the Supraoptic Nucleus Normalises Acute Stress-Induced Adrenocorticotropin Secretion and Unmasks an Effect on Social Behaviour in Male Vasopressin-Deficient Brattleboro Rats

The relevance of vasopressin (AVP) of magnocellular origin to the regulation of the endocrine stress axis and related behaviour is still under discussion. We aimed to obtain deeper insight into this process. To rescue magnocellular AVP synthesis, a vasopressin-containing adeno-associated virus vector (AVP-AAV) was injected into the supraoptic nucleus (SON) of AVP-deficient Brattleboro rats (di/di). We compared +/+, di/di, and AVP-AAV treated di/di male rats. The AVP-AAV treatment rescued the AVP synthesis in the SON both morphologically and functionally. It also rescued the peak of adrenocorticotropin release triggered by immune and metabolic challenges without affecting corticosterone levels. The elevated corticotropin-releasing hormone receptor 1 mRNA levels in the anterior pituitary of di/di-rats were diminished by the AVP-AAV-treatment. The altered c-Fos synthesis in di/di-rats in response to a metabolic stressor was normalised by AVP-AAV in both the SON and medial amygdala (MeA), but not in the central and basolateral amygdala or lateral hypothalamus. In vitro electrophysiological recordings showed an AVP-induced inhibition of MeA neurons that was prevented by picrotoxin administration, supporting the possible regulatory role of AVP originating in the SON. A memory deficit in the novel object recognition test seen in di/di animals remained unaffected by AVP-AAV treatment. Interestingly, although di/di rats show intact social investigation and aggression, the SON AVP-AAV treatment resulted in an alteration of these social behaviours. AVP released from the magnocellular SON neurons may stimulate adrenocorticotropin secretion in response to defined stressors and might participate in the fine-tuning of social behaviour with a possible contribution from the MeA.     

Experiences with SLALOM on the distributed Pleiades/ESP system

The paper describes experiences gained during the process of Implementing a standard serial benchmark (SLALOM) on a distributed computing system (Pleiades running ESP/C⁺⁺). Based on a real problem In computer graphics, SLALOM Is a timed benchmark that Includes problem set-up and I/O costs. The purpose of our experiments has been to maximize the speedup of a distributed implementation of SLALOM when compared to Its serial implementation. As a result of these experiments, we have developed several guidelines for adapting algorithms for distributed systems.     

Molecular Profiling and Novel Therapeutic Strategies for Mucosal Melanoma: A Comprehensive Review

Mucosal melanoma is a rare and aggressive subtype of melanoma. Unlike its cutaneous counterpart, mucosal melanoma has only gained limited benefit from novel treatment approaches due to the lack of actionable driver mutations and poor response to immunotherapy. Over the last years, whole-genome and exome sequencing techniques have led to increased knowledge on the molecular landscape of mucosal melanoma. Molecular studies have underlined noteworthy findings with potential therapeutic implications, including the presence of KIT mutations, which are potential targets of tyrosine kinase inhibitors currently in use in the clinic (imatinib), but also SF3B1 mutation, CDK4 amplifications, and CDKN2A gene deletions, which are presently under investigation in clinical trials. Recent results from a pooled analysis of patients with mucosal melanoma treated with immunotherapy have suggested that the combination of immune checkpoint inhibitors might improve survival outcomes in this subset of patients, as compared with single-agent immunotherapy. However, these results are not confirmed across different studies, and combo-immunotherapy correlates with a higher rate of adverse events. In this review, we describe the clinical, biological, and genetic features of mucosal melanoma. We also provide an update on the results of approved systemic treatment in this setting and overview the therapeutic strategies currently under investigation in clinical trials.     

Oxidation reactions with in situ generated oxidants

The main achievements and future prospects of in situ oxidations are discussed, focusing on the advantages and limits of the technique. This is based on hydrogen peroxide, peracids, metal peroxo and metal oxo species, generated in situ by oxygen and a reducing agent: hydrogen, carbon monoxide, metallic iron or zinc, hydrides, aldehydes and other organic reductants. Hydrogen peroxide and hydrogen, respectively, are preferred reagents for the inherent cleanliness of their use, producing only water as the byproduct. Examples are the epoxidation of propylene by air and alkylated anthrahydroquinones, catalysed by titanium silicalite (TS-1), and the hydroxylation of alkanes and aromatics on TS-1 and on other heterogeneous catalysts loaded with noble metals. The halogenation of phenol with hydrogen/oxygen/halogenidric acid mixtures on Pd/TS-1, has also been reported. Carbon monoxide was used to replace hydrogen in in situ oxidations occurring at higher temperatures. Reducing agents other than hydrogen and carbon monoxide lead to the formation of more than stoichiometric amounts of coproducts, which add complexity to the overall process for their separation and recycle/disposal. In the in situ oxidations by Gif^III/IV systems and by aldehyde/oxygen mixtures, large amounts of metallic wastes and carboxylic acid are co-produced, respectively, hindering their application in bulk chemicals production. Future developments might arise from the design of superior catalysts both for the in situ generation of hydrogen peroxide or peroxidic species from oxygen/hydrogen mixtures and for its subsequent efficient use. Oxygen/carbon monoxide and nitrous oxide can replace hydrogen/oxygen in oxidations at progressively higher temperatures, albeit no in situ oxidation with N₂O as yet has been reported. The general features of hydrogen peroxide and nitrous oxide are briefly compared and discussed.     

The impact of dietary mono‐ and poly‐unsaturated fatty acids on risk factors for atherosclerosis in humans

The fatty acid composition of the diet has various effects on atherosclerosis risk factors. Dietary saturated fatty acids (SFA) and trans‐unsaturated fatty acids increase the low‐density lipoprotein (LDL)‐/high‐density lipoprotein (HDL)‐cholesterol ratio in serum, while these fats do not have a significant bearing on serum triglyceride levels. By contrast, dietary monounsaturated fatty acids (MUFA), n‐6 polyunsaturated fatty acids (PUFA), and α‐linolenic acid (C18:3n‐3) similarly reduce LDL cholesterol concentrations, while their influence on serum HDL cholesterol and triglycerides is not appreciable. Dietary long‐chain n‐3 PUFA slightly increase serum LDL cholesterol concentrations, but are nevertheless considered salubrious with regard to serum lipids due to the distinct triglyceride‐lowering effects. MUFA‐rich compared to n‐6 PUFA‐rich diets strongly reduce the in vitro oxidizability of LDL. The available studies on this subject also suggest that n‐3 PUFA in the small amounts usually present in the diet are not unduly harmful. These findings are consistent with reports from observational studies: the amount of SFA is positively and the amount of MUFA and n‐6 PUFA in the diet is inversely associated with the risk of cardiovascular disease in most epidemiological studies. The available studies have had an impact on current dietary guidelines, which unanimously recommend that most of the dietary fat should be in the form of MUFA, while the amount of SFA and trans fatty acids in the diet should be as low as possible.     

Influence of ionic liquid on graphite/silver nanoparticles dispersion and antibacterial properties against Escherichia coli of PP/EPDM composite coatings

In this work, graphite doped with silver nanoparticles are synthesized and coated onto a PP/EPDM blend surface. Three nanoparticles deposition methods are used. In one method, the nanoparticles are directly deposited on previously corona discharge-treated TPO surface. Another method is by compression deposition of nanoparticles in a thin layer forming a segregated coating. In the last method, a nanoparticle-polymer composite is deposited and then treated by corona discharge to expose the deposited nanoparticles. These last two methods show excellent antimicrobial activity (R = 2.8 and 3.9, respectively) and higher inhibition values (85% and 89%, respectively) against Escherichia coli strains. The effect of using HMIMPF6 and BMIMBF4 ionic liquids on particle dispersion and antibacterial activity against E. coli is evaluated. Using ionic liquids enhance the antibacterial activity (from R = 3.9 to 5.4) and inhibition rates (from 89% to 99.8%) of the samples. As a result, a thermoplastic elastomer (TPE) material with enhanced antibacterial properties against E. coli is obtained using ionic liquids, which offer significant promise as a material for medical applications. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48714.     

Development of active cassava starch cellulose nanofiber-based films incorporated with natural antimicrobial tea tree essential oil

In the present study, a cassava starch-glycerol film with reinforcement of Pinus sp. nanofibers (NFC) incorporated with tea tree (Melaleuca alternifolia) essential oil (TTO) were prepared by casting technique. The physical (barrier, mechanical, and optical), structural, and antimicrobial properties of the films were evaluated and compared with the control films. Films with 0.08% TTO exhibited a significant increase in the tensile strength (TS) while films with 1.5% TTO showed a decrease in TS, suggesting a crosslinking effect. The addition of 1.5% TTO reduced the water vapor permeability values in 43% comparing to the control films. Analysis obtained by Fourier transform infrared spectroscopy showed bands related to the interaction between TTO and matrix for films with 1.5% TTO and 0.3% NFC. This film was effective against Staphylococcus aureus and Candida albicans which could be applied for several packaging purposes. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48726.