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The endothelin-1 (ET1) peptide has a pathological role in the activation of proliferation, survival and invasiveness pathways in different cancers. ET1's effects rely on its activation by the endothelin-converting enzyme-1 (ECE1), which is expressed as four isoforms, differing only in their cytoplasmic N-terminuses. We already demonstrated in colorectal cancer, glioblastoma, and preliminarily lung cancer, that the isoform ECE1c heightens aggressiveness by promoting cancer stem cell traits. This is achieved through a non-canonical ET1-independent mechanism of enhancement of ECE1c's stability upon CK2-dependent phosphorylation at S18 and S20. Here, a K6 residue is presumably responsible for ECE1c ubiquitination as its mutation to R impairs proteasomal degradation. However, how phosphorylation enhances ECE1c's stability and how this translates into aggressiveness are still open questions. In this brief report, by swapping residues to either phospho-mimetic or phospho-resistant amino acids, we propose that the N-terminus may also be phosphorylated at Y5 and/or T9 by an unknown kinase(s). In addition, N-terminus phosphorylation may lead to a blockage of K6 ubiquitination, increasing ECE1c's stability and presumably activating the Wnt/β-catenin signaling pathway. Thus, a novel CK2/ECE1c partnership may be emerging to promote aggressiveness and thus become a biomarker of poor prognosis and a potential therapeutic target for several cancers. [ABSTRACT FROM AUTHOR]

Millions of SARS-CoV-2 whole genome sequences have been generated to date. However, good quality data and adequate surveillance systems are required to contribute to meaningful surveillance in public health. In this context, the network of Spanish laboratories for coronavirus (RELECOV) was created with the main goal of promoting actions to speed up the detection, analyses, and evaluation of SARS-CoV-2 at a national level, partially structured and financed by an ECDC-HERA-Incubator action (ECDC/GRANT/2021/024). A SARS-CoV-2 sequencing quality control assessment (QCA) was developed to evaluate the network's technical capacity. QCA full panel results showed a lower hit rate for lineage assignment compared to that obtained for variants. Genomic data comprising 48,578 viral genomes were studied and evaluated to monitor SARS-CoV-2. The developed network actions showed a 36% increase in sharing viral sequences. In addition, analysis of lineage/sublineage-defining mutations to track the virus showed characteristic mutation profiles for the Delta and Omicron variants. Further, phylogenetic analyses strongly correlated with different variant clusters, obtaining a robust reference tree. The RELECOV network has made it possible to improve and enhance the genomic surveillance of SARS-CoV-2 in Spain. It has provided and evaluated genomic tools for viral genome monitoring and characterization that make it possible to increase knowledge efficiently and quickly, promoting the genomic surveillance of SARS-CoV-2 in Spain. [ABSTRACT FROM AUTHOR]

Copyright of Revista Española de Cirugía Oral y Maxilofacial is the property of Sociedad Espanola de Cirugia Oral y Maxilofacial (SECOM) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Revista Médica MD is the property of Comite Editorial de la Revista Medica MD and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

PLACNET is a graph-based tool for reconstruction of plasmids from next generation sequence pair-end datasets. PLACNET graphs contain two types of nodes (assembled contigs and reference genomes) and two types of edges (scaffold links and homology to references). Manual pruning of the graphs is a necessary requirement in PLACNET, but this is difficult for users without solid bioinformatic background. PLACNETw, a webtool based on PLACNET, provides an interactive graphic interface, automates BLAST searches, and extracts the relevant information for decision making. It allows a user with domain expertise to visualize the scaffold graphs and related information of contigs as well as reference sequences, so that the pruning operations can be done interactively from a personal computer without the need for additional tools. After successful pruning, each plasmid becomes a separate connected component subgraph. The resulting data are automatically downloaded by the user. [ABSTRACT FROM AUTHOR]

The bacteria Microbacterium sp. 8L and Exiguobacterium mexicanum 8N are known to improve the culture of Artemia franciscana using baker's yeast as food. Using spectrophotometry, sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE), substrate-SDS-PAGE and pH-stat in vitro-digestibility assays, the activity, molecular mass and hydrolysis on baker's yeast protein of proteases from extracellular polymeric substances (EPS) of the strains 8L and 8N along with the pathogenic strains Microbacterium sp. 8R and Vibrio parahaemolyticus 588 CECT (Vp) were studied. The EPSs of 8L and 8R showed one activity band, on which the serine inhibitor phenylmethylsulphonyl fluoride (PMSF) had no effect. The EPSs of 8N showed four bands; two were unaffected by PMSF, whereas one was affected, and the other was partially affected. The EPSs of Vp showed two bands, one partially inhibited by PMSF. No inhibitory effects from 1-chloro-3-tosylamido-7-amino-2-heptanone (trypsin inhibitor) were observed in the protease bands of the studied bacteria. The EPSs of 8L and 8N showed a similar degree of hydrolysis (pH-stat). The EPSs of 8L had the lowest Dice index of similarity of yeast protein profiles at 1 h of reaction. We conclude that the strain 8L could benefit A. franciscana by providing bacterial proteases for digestion of baker's yeast. [ABSTRACT FROM AUTHOR]

Abstract: Nine fish species, Gillichthys seta, Oligoplites saurus, Eucinostomus entomelas, Synodus scituliceps, Diplectrum pacificum, Pseudopeneus grandisquamis, Xenistius californiensis, Arius seemanni, and Orthopristis reddinig, caught as bycatch by shrimp commercial fleet of the Guaymas, Sonora, México, were processed to produce protein concentrates using three drying processes (freeze-drying and heating at 65 and 110°C). The soluble protein content from each process and species was evaluated. Significant differences were observed among processes. The composition of protein, observed by electrophoresis, was affected by temperature. Raw and freeze-dried protein from S. scituliceps showed high proteolytic activity and unwent auto-hydrolysis. The highest proteolytic activity was at 65°C and its optimum pH was 7.5. When assayed in the presence of several protease inhibitors, the enzymes were completely inactivated by soybean trypsin inhibitor. The in vitro digestibilities of the protein concentrates were higher when obtained by low-temperature methods. [Copyright &y& Elsevier]

Glioblastoma multiforme is one of the most malignant types of cancer. This is mainly due to a cell subpopulation with an extremely aggressive potential, called glioblastoma stem-like cells (GSCs). These cells produce high levels of extracellular adenosine which has been associated with increased chemoresistance, migration, and invasion in glioblastoma. In this study, we attempted to elucidate the mechanisms that control extracellular adenosine levels in GSC subtypes. By using primary and U87MG-derived GSCs, we associated increased extracellular adenosine with the mesenchymal phenotype. [3H]-adenosine uptake occurred mainly through the equilibrative nucleoside transporters (ENTs) in GSCs, but mesenchymal GSCs have lower expression and ENT1-mediated uptake activity than proneural GSCs. By analyzing expression and enzymatic activity, we determined that ecto-5′-nucleotidase (CD73) is predominantly expressed in proneural GSCs, driving AMPase activity. While in mesenchymal GSCs, both CD73 and Prostatic Acid Phosphatase (PAP) contribute to the AMP (adenosine monophosphate) hydrolysis. We did not observe significant differences between the expression of proteins involved in the metabolization of adenosine among the GCSs subtypes. In conclusion, the lower expression and activity of the ENT1 transporter in mesenchymal GSCs contributes to the high level of extracellular adenosine that these GSCs present. [ABSTRACT FROM AUTHOR]

Poor response to current treatments for glioblastoma has been attributed to the presence of glioblastoma stem-like cells (GSCs). GSCs are able to expel antitumor drugs to the extracellular medium using the multidrug resistance-associated protein 1 (MRP1) transporter. Tacrolimus (FK506) has been identified as an MRP1 regulator in differentiated glioblastoma (GBM) cells (non-GSCs); however, the effect of FK506 on GSCs is currently unknown. The objective of the following research is to evaluate the effect of FK506 on the MRP1-related chemo-resistant phenotype of GSCs. For this, U87MG and C6 glioma cell lines were used to generate non-GSCs and GSCs. mRNA and MRP1-positive cells were evaluated by RT-qPCR and flow cytometry, respectively. A Carboxyfluorescein Diacetate (CFDA)-retention assay was performed to evaluate the MRP1 activity. Apoptosis and MTT assays were employed to evaluate the cytotoxic effects of FK506 plus Vincristine (MRP1 substrate). GSC-derived subcutaneous tumors were generated to evaluate the in vivo effect of FK506/Vincristine treatment. No differences in transcript levels and positive cells for MRP1 were observed in FK506-treated cells. Lesser cell viability, increased apoptosis, and CFDA-retention in the FK506/Vincristine-treated cells were observed. In vivo, the FK506/Vincristine treatment decreased the tumor size as well as ki67, Glial Fibrillary Acidic Protein (GFAP), and nestin expression. We conclude that FK506 confers a chemo-sensitive phenotype to MRP1-drug substrate in GSCs. [ABSTRACT FROM AUTHOR]

Total enzyme activity of whole viscera, and partial characterization of acidic proteases from Monterey sardine viscera are presented. Major proteolytic activity in alkali (pH 10) and minor activity in acid (pH 3) were detected. From purified acidic proteases, six fractions with high activity were selected. One fraction (42) showed one band on SDS–PAGE and two bands on isoelectrofocusing, with pI close to 4.0 and 4.5, respectively. The optimal pH for acidic protease activity was 2.5, with high stability in the acid range and marked loss of activity at neutral and alkaline pH. The optimum temperature was 45 °C, and activity was high at 10 °C, whereas denaturation occurred above 55 °C. Activity was inhibited by Pepstatin A but not by SBTI or EDTA. The general characteristics of these enzymes resemble those of the digestive enzymes of other fish. Because Monterey sardine is abundant in Mexico, it is a potential source for biological reagent production. [Copyright &y& Elsevier]

Glomus tumors (GT) are very rare mesenchymal neoplasms arising from glomus bodies, arteriovenous structures located in the dermis and involved in thermoregulation. Although most are benign, they may occasionally present malignant histological features associated with aggressive clinical behavior, metastatic spread, and poor response to conventional chemotherapy. The BRAF V600E mutation has been identified in a subset of malignant GT, highlighting a promising therapeutic target. Here, we report the impressive clinical and morpho-metabolic response of a metastatic BRAF V600E-mutated glomangiosarcoma after treatment with encorafenib and binimetinib.

Glioblastoma (GBM) is the most common and deadly malignant brain tumor, with a median survival of 15 to 17 months for a patient. GBM contains a cellular subpopulation known as GBM stem-like cells (GSCs) that persist in hypoxic niches and are capable of infiltrating into healthy brain tissue. For this reason, GSCs are considered one of the main culprits for GBM recurrence. A hypoxic microenvironment increases extracellular adenosine levels, activating the low affinity A2B adenosine receptor (A 2B AR). Adenosine, through A 2B AR, is capable of modulating invasiveness. However, its role in the invasion/migration of hypoxic-GSCs is still unknown. This study aims to understand the importance of A 2B AR in modulating the migratory/invasive capacity of GSCs under hypoxia. Data analysis from The Cancer Genome Atlas (TCGA) program correlates A 2B AR expression with high-grade glioma and hypoxic necrotic areas. U87MG and primary culture-derived GSCs under hypoxic conditions (0.5% O 2 ) increased A 2B AR mRNA and protein levels. As expected, the migratory and invasive capacity of GSCs increased under hypoxia, which was counteracted by blocking A 2B AR, through the downregulation of MMP9 activity and epithelial-mesenchymal transition marker expression. Finally, in a xenograft mouse model, we demonstrate that treatment with MRS1754 did not affect the tumor volume but could decrease blood vessel formation and VEGF expression. Our results suggest that extracellular adenosine, through the activation of A 2B AR, enhances the migratory and invasive capacity of GSCs in vitro under hypoxic conditions. Targeting A 2B AR can be an effective therapy for GBM recurrence., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Erices, Niechi, Uribe-Ojeda, Toro, García-Romero, Carrión-Navarro, Monago-Sánchez, Ayuso-Sacido, Martin and Quezada-Monrás.)

Under a one health perspective and the worldwide antimicrobial resistance concern, we investigated extraintestinal pathogenic Escherichia coli (ExPEC), uropathogenic E. coli (UPEC), and multidrug resistant (MDR) E. coli from 197 isolates recovered from healthy dogs in Spain between 2013 and 2017. A total of 91 (46.2%) isolates were molecularly classified as ExPEC and/or UPEC, including 50 clones, among which (i) four clones were dominant (B2-CH14-180-ST127, B2-CH52-14-ST141, B2-CH103-9-ST372 and F-CH4-58-ST648) and (ii) 15 had been identified among isolates causing extraintestinal infections in Spanish and French humans in 2015 and 2016. A total of 28 (14.2%) isolates were classified as MDR, associated with B1, D, and E phylogroups, and included 24 clones, of which eight had also been identified among the human clinical isolates. We selected 23 ST372 strains, 21 from healthy dogs, and two from human clinical isolates for whole genome sequencing and built an SNP-tree with these 23 genomes and 174 genomes (128 from canine strains and 46 from human strains) obtained from public databases. These 197 genomes were segregated into six clusters. Cluster 1 comprised 74.6% of the strain genomes, mostly composed of canine strain genomes ( p < 0.00001). Clusters 4 and 6 also included canine strain genomes, while clusters 2, 3, and 5 were significantly associated with human strain genomes. Finding several common clones and clone-related serotypes in dogs and humans suggests a potentially bidirectional clone transfer that argues for the one health perspective., Competing Interests: The authors declare no conflict of interest.

The oral cavity constitutes a site of low prevalence for metastasis of malignant tumors. Nevertheless, it has a high prevalence for metastasis of renal origin. Besides the kidneys, there are other primary sites with high prevalence of metastasis to the oral mucosa, such as the lungs, skin and breasts. Metastasis is common in patients with a background of treated renal tumors, thereby, it is proper to determine the possibility of oral metastasis as part of the protocol of attention. However, it constitutes a diagnostic challenge when it presents in patients with no renal antecedents. It is in this type of patients that the diagnosis of carcinoma is achieved by means of a metastasis. Survival rate in these patients is short because at the time of the metastasis diagnosis, the general compromise is high. The following report describes a case referred from the Rheumatology Unit with an intraoral tumor, that was finally diagnosed as a Metastasic Renal Cell Carcinoma with multiple metastasis.

Beckwith Wiedemann Syndrome (BWS) is a rare congenital disease of low prevalence. However, it presents a high prevalence within the genetic pathologies of overgrowth. This syndrome presents typical manifestations such as macroglossia, macrosomy at birth, omphalocele and defects of the anterior abdominal wall. Its origin is known to be genetic, but its mechanism of generation is not clear. This syndrome has been the object of wide studies since investigators have established a relationship between the methods of assisted fertilization (assisted reproduction treatment, ART) and its appearance. Currently, research is oriented towards the improvement of the prenatal diagnostic techniques, which would allow a preparation of the multidisciplinary medical team to treat the pathologies with which these patients are born. Next we present the case of a 1 year-old child who consults this service with a diagnosis of macroglossia associated with BWS.

Decapod crustaceans synthesize highly active proteolytic enzymes in the midgut gland and release at least a part of them into the stomach where they facilitate the first step in peptide hydrolysis. The most common proteinases in the gastric fluid characterized so far are serine proteinases, that is, trypsin and chymotrypsin. These enzymes show highest activities at neutral or slightly alkaline conditions. The presence of acid proteinases, as they prevail in vertebrates, has been discussed contradictorily yet in invertebrates. In this study, we show that acid aspartic proteinases appear in the gastric fluid of several decapods. Lobsters Homarus gammarus showed the highest activity with a maximum at pH 3. These activities were almost entirely inhibited by pepstatin A, which indicates a high share of aspartic proteinases. In other species (Panulirus interruptus, Cancer pagurus, Callinectes arcuatus and Callinectes bellicosus), proteolytic activities were present at acid conditions but were distinctly lower than in H. gammarus. Zymograms at pH 3 showed in each of the studied species at least one, but mostly two-four bands of activity. The apparent molecular weight of the enzymes ranged from 17.8 to 38.6 kDa. Two distinct bands were identified which were inhibited by pepstatin A. Acid aspartic proteinases may play an important role in the process of extracellular digestion in decapod crustaceans. Activities were significantly higher in clawed lobster than in spiny lobster and three species of brachyurans. Therefore, it may be suggested that the expression of acid proteinases is favored in certain groups and reduced in others., (Copyright 2006 Wiley-Liss, Inc.)