ESC pre-test probability estimates for obstructive coronary artery disease: can they be used in Brazil?

Aims: Cardiovascular disease, primarily coronary artery disease (CAD), is the leading cause of mortality worldwide. Accurate diagnosis of CAD often requires pre-test probability (PTP) estimation, traditionally performed using scoring systems like the Diamond-Forrester (DF) and European Society of Cardiology (ESC) models. However, the applicability of such models in specific populations may vary. This study compares the performance of DF and PTP scores in the Brazilian context, using coronary computed tomography angiography (CCTA) as a reference standard. Methods and results: PTP for obstructive CAD was calculated using DF and ESC scores in 409 symptomatic patients without known CAD who underwent CCTA between 2019 and 2022. Predicted PTP was compared with actual CAD prevalence. DF overestimated CAD prevalence across age and symptom categories, while ESC showed better alignment with actual prevalence. Conclusion: Our study confirms that the ESC PTP model is more appropriate than the DF model for determining PTP in the Brazilian population.

LYP regulates SLP76 and other adaptor proteins in T cells.

BACKGROUND: The LYP tyrosine phosphatase presents a SNP (1858C > T) that increases the risk of developing autoimmune diseases such as type I diabetes and arthritis. It remains unclear how this SNP affects LYP function and promotes the development of these diseases. The scarce information about LYP substrates is in part responsible for the poor understanding of LYP function. RESULTS: In this study, we identify in T lymphocytes several adaptor proteins as potential substrates targeted by LYP, including FYB, SLP-76, HS-1, Vav, SKAP1 and SKAP2. We also show that LYP co-localizes with SLP76 in microclusters, upon TCR engagement. CONCLUSIONS: These data indicate that LYP may modulate T cell activation by dephosphorylating several adaptor proteins, such as FYB, SLP-76, HS-1, Vav, SKAP1 and SKAP2 upon TCR engagement.

Protein tyrosine phosphatase 1B (PTP1B) function, structure, and inhibition strategies to develop antidiabetic drugs.

Tyrosine protein phosphatase non-receptor type 1 (PTP1B; also known as protein tyrosine phosphatase 1B) is a member of the protein tyrosine phosphatase (PTP) family and is a soluble enzyme that plays an essential role in different physiological processes, including the regulation of metabolism, specifically in insulin and leptin sensitivity. PTP1B is crucial in the pathogenesis of type 2 diabetes mellitus and obesity. These biological functions have made PTP1B validated as an antidiabetic and anti-obesity, and potentially anticancer, molecular target. Four main approaches aim to inhibit PTP1B: orthosteric, allosteric, bidentate inhibition, and PTPN1 gene silencing. Developing a potent and selective PTP1B inhibitor is still challenging due to the enzyme's ubiquitous expression, subcellular location, and structural properties. This article reviews the main advances in the study of PTP1B since it was first isolated in 1988, as well as recent contextual information related to the PTP family to which this protein belongs. Furthermore, we offer an overview of the role of PTP1B in diabetes and obesity, and the challenges to developing selective, effective, potent, bioavailable, and cell-permeable compounds that can inhibit the enzyme.

Differences in the expression of the phosphatase PTP-1B in patients with localized prostate cancer with and without adverse pathological features.

Introduction: Patients with adverse pathological features (APF) at radical prostatectomy (RP) for prostate cancer (PC) are candidates for adjuvant treatment. Clinicians lack reliable markers to predict these APF preoperatively. Protein tyrosine phosphatase 1B (PTP-1B) is involved in migration and invasion of PC, and its expression could predict presence of APF. Our aim was to compare PTP-1B expression in patients with and without APF, and to explore PTP-1B expression as an independent prognostic factor. Methods: Tissue microarrays (TMAs) were constructed using RP archival specimens for immunohistochemical staining of PTP-1B; expression was reported with a standardized score (0-9). We compared median PTP-1B score between cases with and without APF. We constructed two logistic regression models, one to identify the independence of PTP-1B score from biologically associated variables (metformin use and type 2 diabetes mellitus [T2DM]) and the second to seek independence of known risk factors (Gleason score and prostate specific antigen [PSA]). Results: A total of 73 specimens were suitable for TMA construction. Forty-four (60%) patients had APF. The median PTP-1B score was higher in those with APF: 8 (5-9) vs 5 (3-8) (p=0.026). In the logistic regression model including T2DM and metformin use, the PTP-1B score maintained statistical significance (OR 1.21, 95% CI 1.01-1.45, p=0.037). In the model including PSA and Gleason score; the PTP-1B score showed no independence (OR 1.68, 95% CI 0.97-1.41, p=0.11). The area under the curve to predict APF for the PTP-1B score was 0.65 (95% CI 0.52-0.78, p=0.03), for PSA+Gleason 0.71 (95% CI 0.59-0.82, p=0.03), and for PSA+Gleason+PTP-1B score 0.73 (95% CI 0.61-0.84, p=0.001). Discussion: Patients with APF after RP have a higher expression of PTP-1B than those without APF, even after adjusting for T2DM and metformin exposure. PTP-1B has a good accuracy for predicting APF but does not add to known prognostic factors.

Discovery of inhibitors of protein tyrosine phosphatase 1B contained in a natural products library from Mexican medicinal plants and fungi using a combination of enzymatic and in silico methods*.

This work aimed to discover protein tyrosine phosphatase 1B (PTP1B) inhibitors from a small molecule library of natural products (NPs) derived from selected Mexican medicinal plants and fungi to find new hits for developing antidiabetic drugs. The products showing similar IC50 values to ursolic acid (UA) (positive control, IC50 = 26.5) were considered hits. These compounds were canophyllol (1), 5-O-(ß-D-glucopyranosyl)-7-methoxy-3',4'-dihydroxy-4-phenylcoumarin (2), 3,4-dimethoxy-2,5-phenanthrenediol (3), masticadienonic acid (4), 4',5,6-trihydroxy-3',7-dimethoxyflavone (5), E/Z vermelhotin (6), tajixanthone hydrate (7), quercetin-3-O-(6″-benzoyl)-ß-D-galactoside (8), lichexanthone (9), melianodiol (10), and confusarin (11). According to the double-reciprocal plots, 1 was a non-competitive inhibitor, 3 a mixed-type, and 6 competitive. The chemical space analysis of the hits (IC50 < 100 µM) and compounds possessing activity (IC50 in the range of 100-1,000 µM) with the BIOFACQUIM library indicated that the active molecules are chemically diverse, covering most of the known Mexican NPs' chemical space. Finally, a structure-activity similarity (SAS) map was built using the Tanimoto similarity index and PTP1B absolute inhibitory activity, which allows the identification of seven scaffold hops, namely, compounds 3, 5, 6, 7, 8, 9, and 11. Canophyllol (1), on the other hand, is a true analog of UA since it is an SAR continuous zone of the SAS map.

SPdel: A pipeline to compare and visualize species delimitation methods for single-locus datasets.

An accurate species delimitation is critical for biological studies. In this context, the use of molecular techniques along with species delimitation methods would help to a rapid and accurate biodiversity assessment. The species delimitation methods cluster data sets of orthologous sequences in molecular operational taxonomic units (MOTU). In particular, the methods based on a single gene are easily integrated with the widely used DNA barcoding approach. We developed SPdel a user-friendly pipeline to integrate different single-gene species delimitation methods. SPdel is designed to calculate and compare MOTUs obtained by different species delimitation approaches. SPdel also outputs diverse ready-to-publish quality figures, that facilitate the interpretation of results. SPdel aims to help researchers use species delimitation methods that would improve biodiversity studies.

Comparison between p-distance and single-locus species delimitation models for delineating reproductively tested strains of pennate diatoms (Bacillariophyceae) using cox1, rbcL and ITS.

Several automated molecular methods have emerged for distinguishing eukaryote species based on DNA sequence data. However, there are knowledge gaps around which of these single-locus methods is more accurate for the identification of microalgal species, such as the highly diverse and ecologically relevant diatoms. We applied genetic divergence, Automatic Barcode Gap Discovery for primary species delimitation (ABGD), Assemble Species by Automatic Partitioning (ASAP), Statistical Parsimony Network Analysis (SPNA), Generalized Mixed Yule Coalescent (GMYC) and Poisson Tree Processes (PTP) using partial cox1, rbcL, 5.8S + ITS2, ITS1 + 5.8S + ITS2 markers to delineate species and compare to published polyphasic identification data (morphological features, phylogeny and sexual reproductive isolation) to test the resolution of these methods. ASAP, ABGD, SPNA and PTP models resolved species of Eunotia, Seminavis, Nitzschia, Sellaphora and Pseudo-nitzschia corresponding to previous polyphasic identification, including reproductive isolation studies. In most cases, these models identified diatom species in similar ways, regardless of sequence fragment length. GMYC model presented smallest number of results that agreed with previous published identification. Following the recommendations for proper use of each model presented in the present study, these models can be useful tools to identify cryptic or closely related species of diatoms, even when the datasets have relatively few sequences.

A survey of aquatic macroinvertebrates in a river from the dry corridor of Nicaragua using biological indices and DNA barcoding.

Aquatic macroinvertebrates are widely used as indicators for water quality assessment around the world. Modern strategies for environmental assessment implement molecular analysis to delimitate species of aquatic macroinvertebrates. Delimitation methods have been established to determine boundaries between species units using sequencing data from DNA barcodes and serve as first exploratory tools for taxonomic revisions. This is useful in regions such as the neotropics where aquatic macroinvertebrate habitats are threatened by human interference and DNA databases remain understudied. We asked whether the biodiversity of aquatic macroinvertebrates in a stream in Nicaragua, within the Central American Dry Corridor, could be characterized with biological indices and DNA barcoding. In this study, we combined regional biological indices (BMWP-CR, IBF-SV-2010) along with distance-based (ASAP, BIN) and tree-based (GMYC, bPTP) delimitation methods, as well as nucleotide BLAST in public barcode databases. We collected samples from the upper, middle, and low reaches of the Petaquilla river. The three sites presented excellent water quality with the BMWP-CR index, but evidence of high organic pollution was found in the middle reach with the IBF-SV-2010 index. We report a total of 219 COI sequences successfully generated from 18 families and 8 orders. Operational taxonomic units (OTUs) designation ranged from 69 to 73 using the four methods, with a congruency of 92% for barcode assignation. Nucleotide BLAST identified 14 species (27.4% of barcodes) and 33 genera (39.3% of barcodes) from query sequences in GenBank and BOLD system databases. This small number of identified OTUs may be explained by the paucity of molecular data from the Neotropical region. Our study provides valuable information about the characterization of macroinvertebrate families that are important biological indicators for the assessment of water quality in Nicaragua. The application of molecular approaches will allow the study of local diversity and further improve the application of molecular techniques for biomonitoring.

Protein tyrosine phosphatase 1B (PTP1B) as a potential therapeutic target for neurological disorders.

Protein tyrosine phosphatase 1B (PTP1B) is a typical member of the PTP family, considered a direct negative regulator of several receptor and receptor-associated tyrosine kinases. This widely localized enzyme has been involved in the pathophysiology of several diseases. More recently, PTP1B has attracted attention in the field of neuroscience, since its activation in brain cells can lead to schizophrenia-like behaviour deficits, anxiety-like effects, neurodegeneration, neuroinflammation and depression. Conversely, PTP1B inhibition has been shown to prevent microglial activation, thus exerting a potent anti-inflammatory effect and has also shown potential to increase the cognitive process through the stimulation of hippocampal insulin, leptin and BDNF/TrkB receptors. Notwithstanding, most research on the clinical efficacy of targeting PTP1B has been developed in the field of obesity and type 2 diabetes mellitus (TD2M). However, despite the link existing between these metabolic alterations and neurodegeneration, no clinical trials assessing the neurological advantages of PTP1B inhibition have been performed yet. Preclinical studies, though, have provided strong evidence that targeting PTP1B could allow to reach different pathophysiological mechanisms at once. herefore, specific interventions or trials should be designed to modulate PTP1B activity in brain, since it is a promising strategy to decelerate or prevent neurodegeneration in aged individuals, among other neurological diseases. The present paper fails to include all neurological conditions in which PTP1B could have a role; instead, it focuses on those which have been related to metabolic alterations and neurodegenerative processes. Moreover, only preclinical data is discussed, since clinical studies on the potential of PTP1B inhibition for treating neurological diseases are still required.

Computational Methods in Cooperation with Experimental Approaches to Design Protein Tyrosine Phosphatase 1B Inhibitors in Type 2 Diabetes Drug Design: A Review of the Achievements of This Century.

Protein tyrosine phosphatase 1B (PTP1B) dephosphorylates phosphotyrosine residues and is an important regulator of several signaling pathways, such as insulin, leptin, and the ErbB signaling network, among others. Therefore, this enzyme is considered an attractive target to design new drugs against type 2 diabetes, obesity, and cancer. To date, a wide variety of PTP1B inhibitors that have been developed by experimental and computational approaches. In this review, we summarize the achievements with respect to PTP1B inhibitors discovered by applying computer-assisted drug design methodologies (virtual screening, molecular docking, pharmacophore modeling, and quantitative structure-activity relationships (QSAR)) as the principal strategy, in cooperation with experimental approaches, covering articles published from the beginning of the century until the time this review was submitted, with a focus on studies conducted with the aim of discovering new drugs against type 2 diabetes. This review encourages the use of computational techniques and includes helpful information that increases the knowledge generated to date about PTP1B inhibition, with a positive impact on the route toward obtaining a new drug against type 2 diabetes with PTP1B as a molecular target.

Mitochondrial Dysfunction and the Glycolytic Switch Induced by Caveolin-1 Phosphorylation Promote Cancer Cell Migration, Invasion, and Metastasis.

Cancer cells often display impaired mitochondrial function, reduced oxidative phosphorylation, and augmented aerobic glycolysis (Warburg effect) to fulfill their bioenergetic and biosynthetic needs. Caveolin-1 (CAV1) is a scaffolding protein that promotes cancer cell migration, invasion, and metastasis in a manner dependent on CAV1 phosphorylation on tyrosine-14 (pY14). Here, we show that CAV1 expression increased glycolysis rates, while mitochondrial respiration was reduced by inhibition of the mitochondrial complex IV. These effects correlated with increased reactive oxygen species (ROS) levels that favored CAV1-induced migration and invasion. Interestingly, pY14-CAV1 promoted the metabolic switch associated with increased migration/invasion and augmented ROS-inhibited PTP1B, a phosphatase that controls pY14 levels. Finally, the glycolysis inhibitor 2-deoxy-D-glucose reduced CAV1-enhanced migration in vitro and metastasis in vivo of murine melanoma cells. In conclusion, CAV1 promotes the Warburg effect and ROS production, which inhibits PTP1B to augment CAV1 phosphorylation on tyrosine-14, thereby increasing the metastatic potential of cancer cells.

Coalescent-based species delimitation in North American pinyon pines using low-copy nuclear genes and plastomes.

PREMISE: Accurate species delimitation is essential for evolutionary biology, conservation, and biodiversity management. We studied species delimitation in North American pinyon pines, Pinus subsection Cembroides, a natural group with high levels of incomplete lineage sorting. METHODS: We used coalescent-based methods and multivariate analyses of low-copy number nuclear genes and nearly complete high-copy number plastomes generated with the Hyb-Seq method. The three coalescent-based species delimitation methods evaluated were the Generalized Mixed Yule Coalescent (GMYC), Poisson Tree Process (PTP), and Trinomial Distribution of Triplets (Tr2). We also measured admixture in populations with possible introgression. RESULTS: Our results show inconsistencies among GMYC, PTP, and Tr2. The single-locus based GMYC analysis of plastid DNA recovered a higher number of species (up to 24 entities, including singleton lineages and clusters) than PTP and the multi-locus coalescent approach. The PTP analysis identified 10 species whereas Tr2 recovered 13, which agreed closely with taxonomic treatments. CONCLUSIONS: We found that PTP and GMYC identified species with low levels of ILS and high morphological divergence (P. maximartinezii, P. pinceana, and P. rzedowskii). However, GMYC method oversplit species by identification of more divergent samples as singletons. Moreover, both PTP and GMYC were incapable of identifying some species that are readily identified morphologically. We suggest that the divergence times between lineages within North American pinyon pines are so disparate that GMYC results are unreliable. Results of the Tr2 method coincided well with previous delimitations based on morphology, DNA, geography, and secondary chemistry.

Crystal structure of the Cys-NO modified YopH tyrosine phosphatase.

Protein tyrosine phosphatases (PTPs) are key virulence factors in pathogenic bacteria, consequently, they have become important targets for new approaches against these pathogens, especially in the fight against antibiotic resistance. Among these targets of interest YopH (Yersinia outer protein H) from virulent species of Yersinia is an example. PTPs can be reversibly inhibited by nitric oxide (NO) since the oxidative modification of cysteine residues may influence the protein structure and catalytic activity. We therefore investigated the effects of NO on the structure and enzymatic activity of Yersinia enterocolitica YopH in vitro. Through phosphatase activity assays, we observe that in the presence of NO YopH activity was inhibited by 50%, and that this oxidative modification is partially reversible in the presence of DTT. Furthermore, YopH S-nitrosylation was clearly confirmed by a biotin switch assay, high resolution mass spectrometry (MS) and X-ray crystallography approaches. The crystal structure confirmed the S-nitrosylation of the catalytic cysteine residue, Cys403, while the MS data provide evidence that Cys221 and Cys234 might also be modified by NO. Interestingly, circular dichroism spectroscopy shows that the S-nitrosylation affects secondary structure of wild type YopH, though to a lesser extent on the catalytic cysteine to serine YopH mutant. The data obtained demonstrate that S-nitrosylation inhibits the catalytic activity of YopH, with effects beyond the catalytic cysteine. These findings are helpful for designing effective YopH inhibitors and potential therapeutic strategies to fight this pathogen or others that use similar mechanisms to interfere in the signal transduction pathways of their hosts.

Design, synthesis, kinetic, molecular dynamics, and hypoglycemic effect characterization of new and potential selective benzimidazole derivatives as Protein Tyrosine Phosphatase 1B inhibitors.

Protein-tyrosine phosphatase 1B (PTP1B) is a negative regulator of insulin signaling pathway and has been validated as a therapeutic target for type 2 diabetes. A wide variety of scaffolds have been included in the structure of PTP1B inhibitors, one of them is the benzimidazole nucleus. Here, we report the design and synthesis of a new series of di- and tri- substituted benzimidazole derivatives including their kinetic and structural characterization as PTP1B inhibitors and hypoglycemic activity. Results show that compounds 43, 44, 45, and 46 are complete mixed type inhibitors with a Ki of 12.6 µM for the most potent (46). SAR type analysis indicates that a chloro substituent at position 6(5), a ß-naphthyloxy at position 5(6), and a p-benzoic acid attached to the linker 2-thioacetamido at position 2 of the benzimidazole nucleus, was the best combination for PTP1B inhibition and hypoglycemic activity. In addition, molecular dynamics studies suggest that these compounds could be potential selective inhibitors from other PTPs such as its closest homologous TCPTP, SHP-1, SHP-2 and CDC25B. Therefore, the compounds reported here are good hits that provide structural, kinetic, and biological information that can be used to develop novel and selective PTP1B inhibitors based on benzimidazole scaffold.

Protein tyrosine phosphatase 1B targets focal adhesion kinase and paxillin in cell-matrix adhesions.

Protein tyrosine phosphatase 1B (PTP1B, also known as PTPN1) is an established regulator of cell-matrix adhesion and motility. However, the nature of substrate targets at adhesion sites remains to be validated. Here, we used bimolecular fluorescence complementation assays, in combination with a substrate trapping mutant of PTP1B, to directly examine whether relevant phosphotyrosines on paxillin and focal adhesion kinase (FAK, also known as PTK2) are substrates of the phosphatase in the context of cell-matrix adhesion sites. We found that the formation of catalytic complexes at cell-matrix adhesions requires intact tyrosine residues Y31 and Y118 on paxillin, and the localization of FAK at adhesion sites. Additionally, we found that PTP1B specifically targets Y925 on the focal adhesion targeting (FAT) domain of FAK at adhesion sites. Electrostatic analysis indicated that dephosphorylation of this residue promotes the closed conformation of the FAT 4-helix bundle and its interaction with paxillin at adhesion sites.

Short-Term Strength Exercise Reduces Hepatic Insulin Resistance in Obese Mice by Reducing PTP1B Content, Regardless of Changes in Body Weight.

Obesity is closely related to insulin resistance and type 2 diabetes genesis. The liver is a key organ to glucose homeostasis since insulin resistance in this organ increases hepatic glucose production (HGP) and fasting hyperglycemia. The protein-tyrosine phosphatase 1B (PTP1B) may dephosphorylate the IR and IRS, contributing to insulin resistance in this organ. Aerobic exercise is a great strategy to increase insulin action in the liver by reducing the PTP1B content. In contrast, no study has shown the direct effects of strength training on the hepatic metabolism of PTP1B. Therefore, this study aims to investigate the effects of short-term strength exercise (STSE) on hepatic insulin sensitivity and PTP1B content in obese mice, regardless of body weight change. To achieve this goal, obese Swiss mice were submitted to a strength exercise protocol lasting 15 days. The results showed that STSE increased Akt phosphorylation in the liver and enhanced the control of HGP during the pyruvate tolerance test. Furthermore, sedentary obese animals increased PTP1B content and decreased IRS-1/2 tyrosine phosphorylation; however, STSE was able to reverse this scenario. Therefore, we conclude that STSE is an important strategy to improve the hepatic insulin sensitivity and HGP by reducing the PTP1B content in the liver of obese mice, regardless of changes in body weight.

Treat Me Well or Will Resist: Uptake of Mobile Genetic Elements Determine the Resistome of Corynebacterium striatum.

Corynebacterium striatum, a bacterium that is part of the normal skin microbiota, is also an opportunistic pathogen. In recent years, reports of infections and in-hospital and nosocomial outbreaks caused by antimicrobial multidrug-resistant C. striatum strains have been increasing worldwide. However, there are no studies about the genomic determinants related to antimicrobial resistance in C. striatum. This review updates global information related to antimicrobial resistance found in C. striatum and highlights the essential genomic aspects in its persistence and dissemination. The resistome of C. striatum comprises chromosomal and acquired elements. Resistance to fluoroquinolones and daptomycin are due to mutations in chromosomal genes. Conversely, resistance to macrolides, tetracyclines, phenicols, beta-lactams, and aminoglycosides are associated with mobile genomic elements such as plasmids and transposons. The presence and diversity of insertion sequences suggest an essential role in the expression of antimicrobial resistance genes (ARGs) in genomic rearrangements and their potential to transfer these elements to other pathogens. The present study underlines that the resistome of C. striatum is dynamic; it is in evident expansion and could be acting as a reservoir for ARGs.

The role of vascular endothelial protein tyrosine phosphatase on nitric oxide synthase function in diabetes: from molecular biology to the clinic.

Endothelial nitric oxide synthase (eNOS) and receptor-type vascular endothelial protein tyrosine phosphatase (VE-PTP) are one of the majors signaling pathways related to endothelial health in diabetes. Several reports have shown that the inhibition of VE-PTP can lead the nitric oxide production, although repeated studies showed that VE-PTP regulated the eNOS exclusive at Ser1177 in indirect-manner. A recent, exciting paper (Siragusa et al. in Cardiovasc Res, 2020. https://doi.org/10.1093/cvr/cvaa213 ), showing that VE-PTP regulates eNOS in a direct-manner, dephosphorylating eNOS at Tyr81 and indirect at Ser1177 and the effects of a VE-PTP inhibitor, AKB-9778, in the blood pressure from diabetic patients.

Are vanadium complexes druggable against the main protease Mpro of SARS-CoV-2? - A computational approach.

In silico techniques helped explore the binding capacities of the SARS-CoV-2 main protease (Mpro) for a series of metalloorganic compounds. Along with small size vanadium complexes a vanadium-containing derivative of the peptide-like inhibitor N3 (N-[(5-methylisoxazol-3-yl)carbonyl]alanyl-l-valyl-N1-((1R,2Z)-4-(benzyloxy)-4-oxo-1-{[(3R)-2-oxopyrrolidin-3-yl] methyl }but-2-enyl)-l-leucinamide) was designed from the crystal structure with PDB entry code 6LU7. On theoretical grounds our consensus docking studies evaluated the binding affinities at the hitherto known binding site of Chymotrypsin-like protease (3CLpro) of SARS-CoV-2 for existing and designed vanadium complexes. This main virus protease (Mpro) has a Cys-His dyad at the catalytic site that is characteristic of metal-dependent or metal-inhibited hydrolases. Mpro was compared to the human protein-tyrosine phosphatase 1B (hPTP1B) with a comparable catalytic dyad. HPTP1B is a key regulator at an early stage in the signalling cascade of the insulin hormone for glucose uptake into cells. The vanadium-ligand binding site of hPTP1B is located in a larger groove on the surface of Mpro. Vanadium constitutes a well-known phosphate analogue. Hence, its study offers possibilities to design promising vanadium-containing binders to SARS-CoV-2. Given the favourable physicochemical properties of vanadium nuclei, such organic vanadium complexes could become drugs not only for pharmacotherapy but also diagnostic tools for early infection detection in patients. This work presents the in silico design of a potential lead vanadium compound. It was tested along with 20 other vanadium-containing complexes from the literature in a virtual screening test by docking to inhibit Mpro of SARS-CoV-2.

Use of species delimitation approaches to tackle the cryptic diversity of an assemblage of high Andean butterflies (Lepidoptera: Papilionoidea).

Cryptic biological diversity has generated ambiguity in taxonomic and evolutionary studies. Single-locus methods and other approaches for species delimitation are useful for addressing this challenge, enabling the practical processing of large numbers of samples for identification and inventory purposes. This study analyzed an assemblage of high Andean butterflies using DNA barcoding and compared the identifications based on the current morphological taxonomy with three methods of species delimitation (automatic barcode gap discovery, generalized mixed Yule coalescent model, and Poisson tree processes). Sixteen potential cryptic species were recognized using these three methods, representing a net richness increase of 11.3% in the assemblage. A well-studied taxon of the genus Vanessa, which has a wide geographical distribution, appeared with the potential cryptic species that had a higher genetic differentiation at the local level than at the continental level. The analyses were useful for identifying the potential cryptic species in Pedaliodes and Forsterinaria complexes, which also show differentiation along altitudinal and latitudinal gradients. This genetic assessment of an entire assemblage of high Andean butterflies (Papilionoidea) provides baseline information for future research in a region characterized by high rates of endemism and population isolation.