Biology subjects

Velez, H.

Publications and source records attributed to Velez, H..

8 recordsLinked to original sources

bioRxiv2026

Uncovering bioactive metabolites from the Taxus wallichiana endophyte Annulohypoxylon purpureonitens using reverse metabolomics

Endophytic fungi associated with the Himalayan yew (Taxus wallichiana) represent an underexplored source of bioactive secondary metabolites. This study investigated the extracellular metabolites of Annulohypoxylon purpureonitens isolated from Nepalese T. wallichiana using bioactivity screening combined with LCMS/MS-based metabolomics. The fungal extract exhibited broad-spectrum antibacterial activity, showing the strongest inhibition against Staphylococcus aureusand Enterococcus faecalis (MIC = 500 ug/mL). It also displayed notable antioxidant capacity(DPPH, ABTS, TPC &TFC) and cytotoxicity against HeLa and MCF-7 cancer cell lines. Metabolite profiling via GNPS molecular networking, manual MS/MS validation, and MASST reverse metabolomics putatively identified diverse compounds, including hydroquinidine, chlorogenic acid, muramic acid, and cordycepin conjugates widely distributed across public microbial datasets. Overall, A. purpureonitens is a promising source of multifunctional metabolites, laying a foundation for future compound isolation and functional characterization.

pharmacology and toxicology↗

bioRxiv2026

IKKβ as a putative non-covalent and quinone-mediated covalent target of 4-methylcatechol in RANKL/NF-κB signaling: a combined computational and experimental analysis

Excessive osteoclast activity contributes to pathological bone loss in osteoporosis, rheumatoid arthritis, and osteolytic malignancies. The effects of small catechol derivatives on receptor activator of nuclear factor-{kappa}B ligand (RANKL)-induced osteoclastogenesis remain poorly understood. This study investigated the effects of 4-methylcatechol (4-MC) on RANKL-induced NF-{kappa}B activation and osteoclast differentiation. 4-MC reduced RANKL-induced NF-{kappa}B luciferase activity in HEK-293T/RANK cells. 4-MC also suppressed RANKL-induced TRAP activity in RAW264.7 cells in a concentration-dependent manner and reduced the number of TRAP-positive multinucleated osteoclasts, without affecting cell viability. Molecular docking predicted non-covalent binding of 4-MC within the ATP-binding hinge region of IKK{beta} (PDB: 4KIK), forming a close polar contact with Glu97, predicted hydrogen bonds with Cys99, and a hydrophobic contact with Ile165, within the pocket occupied by the co-crystallized inhibitor K252a. Covalent docking predicted that the oxidized quinone form of 4-MC engages Cys179 in the IKK{beta} activation loop. Quantum chemical calculations confirmed a markedly higher electrophilicity index for the oxidized quinone than for the parent catechol, supporting this mechanism. In silico ADMET profiling indicated favorable drug-likeness and safety. These findings identify IKK{beta} as a plausible molecular target of 4-MC through both non-covalent and covalent mechanisms. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=108 SRC="FIGDIR/small/741661v1_ufig1.gif" ALT="Figure 1"> View larger version (40K): org.highwire.dtl.DTLVardef@1d9f82eorg.highwire.dtl.DTLVardef@134a24borg.highwire.dtl.DTLVardef@8aeb91org.highwire.dtl.DTLVardef@6fb85d_HPS_FORMAT_FIGEXP M_FIG C_FIG

pharmacology and toxicology↗

bioRxiv2026

Asarinin Inhibits RANKL-Induced Osteoclast Differentiation by Targeting the p38/ERK-c-Fos-NFATc1 Axis

Excessive osteoclast formation is a key contributor to pathological bone loss in disorders such as osteoporosis and rheumatoid arthritis. Asarinin, a natural lignan, has not previously been examined in the context of osteoclast differentiation. Here, we investigated the anti-osteoclastogenic effects of asarinin using RANKL-stimulated RAW264.7 cells. Asarinin significantly suppressed TRAP-positive multinucleated osteoclast formation under the tested conditions. Mechanistically, asarinin selectively inhibited RANKL-induced phosphorylation of p38 and ERK MAPKs, leading to reduced c-Fos expression and inhibition of NFATc1 nuclear translocation. In addition, asarinin disrupted actin ring formation in mature osteoclasts. Collectively, these findings identify asarinin as a pathway-selective inhibitor of osteoclast differentiation, targeting the p38/ERK-c-Fos-NFATc1 axis while sparing parallel signaling pathways.

pharmacology and toxicology↗

bioRxiv2024

An experimental approach to study multi-species diseases interactions in wheat using machine learning-aided image analysis

Fusarium Head Blight (FHB) is a major disease of cereal crops present everywhere where wheat is produced. A complex of several, distinctly different, species from the genus Fusarium are responsible for causing the disease, with important taxa being F. graminearum, F. culmorum, and F. avenaceum. FHB is an adult stage, late season disease affecting wheat at anthesis. However, recent discoveries are now challenging the basic assumption that anthers and spikes are the only ecological niches relevant for resistance to FHB. Most prominently, it has been established that pathogens typically occurring earlier in the season, such as Zymoseptoria tritici, induce strong systemic changes in the plant immune system, that expand way beyond their primary ecological niche. Furthermore, taxa implicated in FHB can be isolated from virtually all wheat tissues, including typical blotch symptoms on wheat leaves. Strikingly, such important biological observations about the complex lifestyle of FHB causing taxa are overlooked as potential targets in resistance breeding. In this work we present a simplified approach allowing the dissection of the intricate lifestyles of the FHB causing Fusarium taxa. In doing so, we provide an experimental proof-of-concept that systemic signals from Z. tritici can affect the basic response of wheat to F. graminearum. We further demonstrate that differences in Fusarium species composition affect the outcome of the interaction in a genotype-specific manner. We argue that efforts to study hidden layers of the biology of FHB associated taxa are crucial to developing new resistance breeding strategies, based on a better understanding of the genetic drivers of the disease.

plant biology↗

bioRxiv2024

Genome sequence resources from three isolates of the apple canker pathogen Neonectria ditissima infecting forest trees.

Neonectria ditissima is a generalist ascomycete plant pathogen causing canker diseases on a variety of hardwood tree species and can cross-infect many of them. The fungus enters the plants through wounds throughout the year. N. ditissima is considered a major threat to apple production responsible for the fruit tree canker disease which damages trees and causes rotting of fruits in storage. Nearby forests and shelter belts can serve as source of inoculum for well-managed apple orchards. Thus, knowledge about the N. ditissima isolates infecting different host species is essential for designing integrated pest management strategies. Here, we describe the genomes of three N. ditissima isolates, Nd_iso34, Nd_iso35, and Nd_iso36, infecting European beech, American tulip tree, and American beech, respectively. We obtained genome assemblies of ca. 45 megabases for all isolates, covering 94% of the N. ditissima reference annotation, and 97% of the universal single-copy orthologs (BUSCOs). We conclude that these genome assemblies are a highly relevant resource considering the scarcity of genomic data available for N. ditissima.

genomics↗

bioRxiv2024

Survey of the wheat mycobiome associated with leaf blotch and head blight diseases in Sweden

Increasing the durability of crop resistance to plant pathogens has become a major concern in plant pathology. There are 32 diseases of agronomical importance in wheat, which makes disease management in this crop of worldwide importance extremely challenging. Two important groups of wheat pathogens driving the consumption of chemical fungicides in Sweden and worldwide are those causing head blight diseases and leaf blotch diseases. Swedish fields are regularly infested with head blight diseases typically driven by a complex of Fusarium and non-fusarium taxa including F. graminearum, F. culmorum, while leaf blotches are typically caused by Zymoseptoria tritici, Pyrenophora tritici-repentis, and Parastagonospora nodorum. In this work, we present a survey of the larger diversity of taxa associated with head blight and leaf blotch diseases in Sweden, with the primary aim to assess the usefulness of such an approach to develop new understanding and tools for disease diagnostics and management sensu lato. Here, we analyze nearly a thousand isolates collected from wheat fields across eight counties in Sweden and report the identification of pathogenic and non-pathogenic taxa as well as candidate biological control agents associated with head blight and leaf blotch diseases. We argue that such surveys represent an important tool for improving disease diagnostics, disease forecasting, and integrated management in wheat.

plant biology↗

bioRxiv2022

The phospholipase VlsPLA2 from the plant pathogen Verticillium longisporum is a virulence factor targeting host nuclei and suppressing PTI-related hypersensitive response

Phospholipases A2 (PLA2) are lipolytic enzymes, responsible for phospholipids hydrolysis. The role of PLA2 in various aspects of cell physiology has been shown, but their involvement in host-microbe interactions remains to be elucidated. The present study investigated the biological function of the secreted VIsPLA2 phospholipase in the phytopathogenic fungus Verticillium longisporum with emphasis on its role in host-microbe interactions. The VlsPLA2 was highly induced in V. longisporum during interaction with host plant Brassica napus, encoding an active phospholipase A2. VlsPLA2-overexpression V. longisporum strain showed an increased virulence on Arabidopsis plants, plausibly by inducing virulence factors. Furthermore, VIsPLA2 are transported to the nucleus, by hijacking VAMPA proteins, causing suppression of PTI-induced hypersensitive response, possibly by modulating the expression of genes involved in plant immunity. In summary, VlsPLA2 acts as a virulence factor by hydrolyzing the hosts nuclear envelope phospholipids, an action that induces signaling cascade, suppressing basal plant immunity responses.

microbiology↗

bioRxiv2020

Annulohypoxylon sp. strain MUS1, an Endophyte isolated from Taxus wallichiana Zucc. produces Taxol and Other Bioactive Metabolites

Endophytes are microbial colonizers that reside in plants by symbiotic association produces several biological classes of natural products. The current study focuses on the isolation and characterization of bioactive compounds produced by endophytic fungi isolated from the Himalayan yew (Taxus wallichiana) collected from the Mustang district of Nepal. The plant materials were collected from the Lower-Mustang region in the month of October 2016 and the endophytic fungi were isolated on artificial media from inner tissues of bark and needles. Antimicrobial and antioxidant activity, along with total phenolic- and flavonoid-content assays, were used in the evaluation of bioactivity of the fermented crude extracts along with the in vitro ability of the endophytes to produce the anticancer compound Taxol was analyzed. A total of 16 fungal morphotypes were obtained from asymptomatic inner tissues of the bark and needles of T. wallichiana. Among the 16 isolates, the ethyl acetate (EA) fraction of isolate MUS1, showed antibacterial and antifungal activity against all test-pathogens used, with significant inhibition against Pseudomonas aeruginosa ATCC 27853 (MIC: 250 {micro}g/ml) and the pathogenic yeast, Candida albicans (MIC: 125 {micro}g/ml). Antioxidant activity was also evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH). At a concentration of 100 {micro}g/ml, the % radical scavenging activity was 83.15{+/-}0.40, 81.62{+/-}0.11, and 62.36{+/-}0.29, for ascorbic acid, butylated hydroxytoluene (BHT) and the EA fraction of MUS1, respectively. The DPPH-IC50 value for the EA fraction was 81.52 {micro}g/ml, compared to BHT (62.87 {micro}g/ml) and ascorbic acid (56.15 {micro}g/ml). The total phenolic and flavonoid content in the EA fraction were 16.90{+/-}0.075 {micro}g gallic acid equivalent (GAE) and 11.59{+/-}0.148 {micro}g rutin equivalent (RE), per mg of dry crude extract, respectively. Isolate MUS1, identified as an Annulohypoxylon sp. by ITS sequencing, also produced Taxol (282.05 {micro}g/L) as shown by TLC and HPLC analysis. Having the ability to produce antimicrobial and antioxidant compounds, as well as the anticancer compound Taxol, makes Annulohypoxylon sp. strain MUS1, a promising candidate for further study given that naturally occurring bioactive compounds are of great interest to the pharmacological, food and cosmetic industries.

microbiology↗