BUSCADOR RECOLECTA

Relationship of other groups of methyltransferases to NNMT in cancers., Peer reviewed

2 tables, 2 figures, Supporting information for the article https://doi.org/10.3390/su14116472, Table S1 – Relative abundance of molecular species of fatty acids (expressed as % of total pool of fatty acids) of Hermetia illucens larvae fed with different substrates retrieved from the literature surveyed.-- Table S2: Dataset used on MetaboAnalist to perform the statistical analysis.-- Table S3 - Top 10 peer-reviewed scientific journals publishing scientific research addressing the fatty acid profile of Hermetia illucens retrieved from WoS™ and Scopus. (Journals publishing 5 or less articles on this topic were grouped as Others).-- Figure S1: Box plots and kernel density plots before and after normalization. The boxplots show at most 50 features due to space limitations. The density plots are based on all samples. Data transformation: Log Normalization; Data scaling: Autoscaling.-- Figure S2: Hierarchical clustering of substrates shown as dendrogram (distance measures using Euclidean, and clustering algorithm using Ward’s Distance).-- References, Peer reviewed

In melanoma NNMT expression is strongly anticorrelated with the histone methyltransferase-encoding gene SETDB1, a known driver of melanoma., Peer reviewed

Infiltration of specific immune cell types into primary tumours correlates positively with NNMT expression but does not strongly confound the HMT-NNMT relationship., Peer reviewed

Total histone methyltransferase expression is strongly anticorrelated with the activity of NNMT in cancers (related to Fig 1)., Peer reviewed

Supplementary material table and figures, Table S1. Bacteria, oomycete, fungi, phages, plasmids and oligonucleotides used in this study. Figure S1. Halos of antibiosis of filter-sterilized supernatants of Pantoea agglomerans 9Rz4 grown in different culture media. Growth inhibition of the ascomycete yeast Schizosaccharomyces pombe (herbicolin A sensitive) with culture supernatants of P. agglomerans 9Rz4 and the herbicolin A deficient mutant NB1 grown overnight in LB, minimal medium (MM), YE and Strobel medium (Strobel et al., 1999) at 25 ºC. For the bioassays, a S. pombe top agar lawn was prepared in YE-agar and 300 µl of filter-sterilized supernatants were added to holes punched in the S. pombe bioassay plates. The size of the inhibition halos is indicative of the susceptibility of S. pombe to herbicolin A. The bioassays were repeated three times and representative pictures are shown. Picture were taken after 48 h of incubation at 30 ºC. The radius of the halos from three biological replicas is 7.0 ± 0.2 mm (LB), 4.1 ± 0.1 (MM), 6 ± 0.1 mm (YE) and 1.8 ± 0.05 mm (Strobel medium). Bars, 5 mm. Figure S2. Pantoea agglomerans 9Rz4 maize root colonization and its effect on plant growth. A, Maize plants 10 days after inoculation with 9RZ4. Non-inoculated plants were included as control. B, Root weight of maize plants shown in Fig. S2A. Shown are mean and standard deviation of six different plants. No statistically significant differences in root weight were observed between inoculated and non-inoculated plants. C, Maize root colonization assays of P. agglomerans 9Rz4 and its mutant strain NB1. Shown are mean and standard deviation of six different plants. In A-C, sterilization, germination and inoculation of maize seeds was carried out as described previously (Matilla et al., 2007), with minor modifications. Briefly, sterile maize seeds were incubated for 45 min at 30 ºC with a 107 CFU/mL of Pantoea agglomerans 9Rz4 strains. Thereafter, seeds were rinsed with sterile deionized water and planted in 50 mL tubes containing 40 g of sterile washed silica sand and 10% (v/w) plant nutrient solution supplemented with Fe-EDTA and micronutrients, as described previously (Matilla et al., 2007). Plants were maintained at 24 ºC with a daily light period of 16 h for 10 days. Figure S3. Effect of plasmid carriage on the antifungal properties of P. agglomerans 9Rz4. Bioactivity against Verticillium dahliae of 9Rz4 and a 9Rz4 variant (9Rz4-W) lacking plasmid p9Rz4_1. Pictures were taken after 96 h of incubation at 25 °C. Figure S4. Herbicolins A and B production is reduced in the quorum sensing mutant defective in the acyl-homoserine lactone synthase PagI. Abundance of herbicolins A and B relative to the wild type 9Rz4 in the supernatants of the P. agglomerans 9Rz4 strains. Data are the mean and standard deviations from three biological replicates and correspond to the intensity (area under the peak) of “extracted ion chromatograms” (EIC) shown in Fig. 6B. Note that the areas derived from the EICs are not comparable between compounds (e.g. herbicolin A vs herbicolin B) as these areas depend on the ionization efficiency of each compound. As shown in Fig. 1A, herbicolin B is found at trace levels in the 9Rz4 supernatants based on LC-HRMS analyses. Figure S5: Complementation of herbicolins A and B production in the quorum sensing mutant defective in the acyl-homoserine lactone synthase PagI. A, Growth inhibition of Schizosaccharomyces pombe with culture supernatants of Pantoea agglomerans strains. For the assays, P. agglomerans strains were inoculated at an initial OD660 of 0.05 in 10 mL of LB medium containing 1 mL supernatants of overnight cultures of P. agglomerans NB1 (herbicolin A defective; wild type in acyl-homoserine lactone production) or P. agglomerans PagI (defective in the synthesis of acyl-homoserine lactones) grown in LB medium. Then, bacterial cultures were grown overnight at 25 ºC, at which time the supernatants were collected, filter-sterilized and characterized chemically and biologically. For the bioassays, a Schizosaccharomyces pombe top agar lawn was prepared and 300 µL of filter-sterilized supernatants were added to holes punched in the S. pombe bioassay plates. Pictures were taken after 48 h of incubation at 30 ºC. Numerical values indicate the mean and standard deviation of the radius of the inhibition halo of three biological replicates. Bars, 5 mm. B, Extracted ion chromatograms (EIC) corresponding to an m/z of 659.385 ± 0.005 (theoretical value for [M+2H]2+ in herbicolin A) and to an m/z of 569.845 ± 0.005 (theoretical value for [M+2H]2+ in herbicolin B). C, Abundance of herbicolins A and B relative to the wild type strain 9Rz4 in the supernatants of the P. agglomerans 9Rz4 strains through the measurement of peak areas in the EICs shown in Fig. S5B. In B and C, note that the areas derived from the EICs are not comparable between compounds (e.g. herbicolin A vs herbicolin B) as these areas depend on the ionization efficiency of each compound. As shown in Fig. 1A, herbicolin B is found at trace levels in the 9Rz4 supernatants based on LC-HRMS analyses., Peer reviewed

Two datasets are provided: general data on breeders (onset and end of the pre-breeding period) and newborn general information and biochemical data, Seahorses (Hippocampus spp.) are exceptional marine species considering their reproductive patterns and other features. Due to the iconic characteristics of these fishes, aquarium trade and research efforts have increased in the last years. Consequently, novel rearing techniques have been developed; however, there is a need for improvements on a series of issues, namely reproduction success enhancement. The tropical species Hippocampus reidi is the most traded seahorse but many aspects of breeding and its impact on the quality of neonates are still poorly understood. In the present study, we assessed the effects of two pre-breeding diets on newborn quality and viability considering biochemical characteristics, energetic status and ultrastructural aspects of muscular tissue. During the whole pre-breeding season (5 months), the breeders were fed on one of the following diets: M0 (adult non-enriched Artemia) and M5 (adult non-enriched Artemia + mysidaceans). From the onset of the reproduction period, all breeders were fed for 6 months on diet M5. Breeding success and energetic status (ATP, total adenylic nucleotides, AEC and NAD) of newborns resulted considerably enhanced in treatment M5. However, initial differences in neonates quality did not affect further newborn performance (survival and growth until day 7 after male’s pouch release) while gaining access to high-quality preys (copepods). Besides, morphological alterations in muscle tissue were not observed. The reproduction in the species followed a capital–income continuum pattern characterized by an initial mixed capital-income period (until 70-100 days since the onset of the breeding season) followed by an income breeding period with progressive exhaustion of body reserves, especially in M0-newborns. Interestingly, the effects of pre-breeding diets were also noticed in the second half of the breeding period. Our results seemed to indicate that the requirements in essential fatty acids in H. reidi are lower than in other seahorse species (e.g., H. guttulatus). Globally, the results achieved revealed that high-quality pre-breeding diets enhanced reproduction success and would likely result advantageous to improve newborn endurance in conditions of moderate starvation or sub-optimal feeding, Peer reviewed

6 figures, 3 tables, Supplementary material for the article https://doi.org/10.1016/j.marenvres.2021.105315, Figure S1. Results of Vtg mRNA expression in females after normalization process with a different number of reference genes.-- Figure S2. Results of Vtg mRNA expression in males after normalization process with a different number of reference genes.-- Figure S3. Individual observation of RT-qPCR data for female and male different Vtg domains normalized with different number of reference genes.-- Figure S4. Bioanalizer profiles of three samples of RNA selected to assess RNA quality.-- Figure S5. Melt curve analysis of reference genes and vitellogenin primer pairs.-- Figure S6. Results of 1% agarose gel electrophoresis of PCR product using all primer pairs tested.-- Table S1. Equations of standard curves for primers pair efficiency.-- Table S2. Power analysis showing the effect size that could be confidently detected (% change in comparison with control values) in our RT-qPCR analyses results using a sample size of 3, and the averaged observed standard deviation (SD) in our samples.-- Table S3. Results of Two-Way ANOVA performed in females and males respectively to evaluate the effect of factor "time” (t4 and t24), factor “chemical” (C, SC and EE2) and the interaction of the two factors on Vtg mNRA normalized expression levels with different number of reference genes.-- Zip mmc2. Sequences.-- Zip mmc3. Alignments, Peer reviewed

The astacins are a family of metallopeptidases (MPs) that has been extensively described from animals. They are multidomain extracellular proteins, which have a conserved core architecture encompassing a signal peptide for secretion, a prodomain or prosegment and a zinc-dependent catalytic domain (CD). This constellation is found in the archetypal name-giving digestive enzyme astacin from the European crayfish Astacus astacus. Astacin catalytic domains span ∼200 residues and consist of two subdomains that flank an extended active-site cleft. They share several structural elements including a long zinc-binding consensus sequence (HEXXHXXGXXH) immediately followed by an EXXRXDRD motif, which features a family-specific glutamate. In addition, a downstream SIMHY-motif encompasses a “Met-turn” methionine and a zinc-binding tyrosine. The overall architecture and some structural features of astacin catalytic domains match those of other more distantly related MPs, which together constitute the metzincin clan of metallopeptidases. We further analysed the structures of PRO-, MAM, TRAF, CUB and EGF-like domains, and described their essential molecular determinants. In addition, we investigated the distribution of astacins across kingdoms and their phylogenetic origin. Through extensive sequence searches we found astacin CDs in > 25,000 sequences down the tree of life from humans beyond Metazoa, including Choanoflagellata, Filasterea and Ichtyosporea. We also found < 400 sequences scattered across non-holozoan eukaryotes including some fungi and one virus, as well as in selected taxa of archaea and bacteria that are pathogens or colonizers of animal hosts, but not in plants. Overall, we propose that astacins originate in the root of Holozoa consistent with Darwinian descent and that the latter genes might be the result of horizontal gene transfer from holozoan donors., Peer reviewed

DLBCL are aggressive, rapidly proliferating tumors that critically depend on the ATF4-mediated integrated stress response (ISR) to adapt to stress caused by uncontrolled growth, such as hypoxia, amino acid deprivation, and accumulation of misfolded proteins. Here, we show that ISR hyperactivation is a targetable liability in DLBCL. We describe a novel class of compounds represented by BTM-3528 and BTM-3566, which activate the ISR through the mitochondrial protease OMA1. Treatment of tumor cells with compound leads to OMA1-dependent cleavage of DELE1 and OPA1, mitochondrial fragmentation, activation of the eIF2α-kinase HRI, cell growth arrest, and apoptosis. Activation of OMA1 by BTM-3528 and BTM-3566 is mechanistically distinct from inhibitors of mitochondrial electron transport, as the compounds induce OMA1 activity in the absence of acute changes in respiration. We further identify the mitochondrial protein FAM210B as a negative regulator of BTM-3528 and BTM-3566 activity. Overexpression of FAM210B prevents both OMA1 activation and apoptosis. Notably, FAM210B expression is nearly absent in healthy germinal center B-lymphocytes and in derived B-cell malignancies, revealing a fundamental molecular vulnerability which is targeted by BTM compounds. Both compounds induce rapid apoptosis across diverse DLBCL lines derived from activated B-cell, germinal center B-cell, and MYC-rearranged lymphomas. Once-daily oral dosing of BTM-3566 resulted in complete regression of xenografted human DLBCL SU-DHL-10 cells and complete regression in 6 of 9 DLBCL patient-derived xenografts. BTM-3566 represents a first-of-its kind approach of selectively hyperactivating the mitochondrial ISR for treating DLBCL., Peer reviewed