network stability
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The present study has undertaken the isolation of marine yeasts from mangrove sediment samples and their ability to produce alkaline protease enzymes. A total of 14 yeast isolates were recovered on yeast-malt agar (YMA) and yeast extract peptone dextrose (YEPD) agar medium. After screening for proteolytic activity on skim milk agar, marine yeast isolate, AKB-1 exhibited a hydrolysis zone of 18 mm. Optimal conditions for the enzyme production from yeast isolate AKB-1 were at 30 °C, pH 8, fructose as carbon source, potassium nitrate as nitrogen source, and 25% saline concentration. Under the optimal conditions, the protease enzyme activity of the isolate AKB-1 was observed to be 978 IU/mL. The structural and functional analysis was carried out through FTIR and HPLC analysis for the extracted protease enzyme. Furthermore, the enzyme produced was partially purified by solvent extraction using ethyl acetate and ammonium sulfate precipitation (3.4-fold) followed by dialysis (56.8-fold). The molecular weight of the purified enzyme was observed to be around 60 kDa using SDS-PAGE. The extracted protein showed good antibacterial activity against six different clinical bacterial pathogens and the highest against Bacillus cereus (16 ± 0.5 mm). The extracted protease enzyme was revealed to remove blood stains from cloth within 20 min of application similar to the commercial detergent. The marine yeast isolate was further identified as Candida orthopsilosis AKB-1 (Accession number KY348766) through 18S rRNA sequencing, and a phylogenetic tree was generated.
- MeSH
- antibakteriální látky farmakologie metabolismus chemie izolace a purifikace MeSH
- Bacillus cereus účinky léků MeSH
- bakteriální proteiny * chemie farmakologie metabolismus izolace a purifikace MeSH
- Candida * enzymologie izolace a purifikace genetika klasifikace MeSH
- endopeptidasy * chemie metabolismus izolace a purifikace farmakologie MeSH
- fylogeneze MeSH
- geologické sedimenty mikrobiologie MeSH
- koncentrace vodíkových iontů MeSH
- kultivační média chemie MeSH
- mikrobiální testy citlivosti MeSH
- molekulová hmotnost MeSH
- stabilita enzymů MeSH
- teplota MeSH
- Publikační typ
- časopisecké články MeSH
The honeybee (Apis mellifera) is a key pollinator critical to global agriculture, facing threats from various stressors, including the ectoparasitic Varroa mite (Varroa destructor). Previous studies have identified shared bacteria between Varroa mites and honeybees, yet it remains unclear if these bacteria assemble similarly in both species. This study builds on existing knowledge by investigating co-occurrence patterns in the microbiomes of both Varroa mites and honeybees, shedding light on potential interactions. Leveraging 16S rRNA datasets, we conducted co-occurrence network analyses, explored Core Association Networks (CAN) and assess network robustness. Comparative network analyses revealed structural differences between honeybee and mite microbiomes, along with shared core features and microbial motifs. The mite network exhibited lower robustness, suggesting less resistance to taxa extension compared to honeybees. Furthermore, analyses of predicted functional profiling and taxa contribution revealed that common central pathways in the metabolic networks have different taxa contributing to Varroa mites and honeybee microbiomes. The results show that while both microbial systems exhibit functional redundancy, in which different taxa contribute to the functional stability and resilience of the ecosystem, there is evidence for niche specialization resulting in unique contributions to specific pathways in each part of this host-parasite system. The specificity of taxa contribution to key pathways offers targeted approaches to Varroa microbiome management and preserving honeybee microbiome. Our findings provide valuable insights into microbial interactions, aiding farmers and beekeepers in maintaining healthy and resilient bee colonies amid increasing Varroa mite infestations.
- MeSH
- Bacteria * klasifikace genetika izolace a purifikace MeSH
- mikrobiota * MeSH
- RNA ribozomální 16S genetika MeSH
- Varroidae * mikrobiologie MeSH
- včely mikrobiologie parazitologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Neurodegenerative disorders (NDs) are typically characterized by progressive loss of neuronal function and the deposition of misfolded proteins in the brain and peripheral organs. They are molecularly classified based on the specific proteins involved, underscoring the critical role of protein-processing systems in their pathogenesis. Alpha-synuclein (α-syn) is a neural protein that is crucial in initiating and progressing various NDs by directly or indirectly regulating other ND-associated proteins. Therefore, reducing the α-syn aggregation can be an excellent option for combating ND initiation and progression. This study presents an in silico phytochemical-based approach for discovering novel neuroprotective agents from bioactive compounds of the Lamiaceae family, highlighting the potential of computational methods such as functional networking, pathway enrichment analysis, molecular docking, and simulation in therapeutic discovery. Functional network and enrichment pathway analysis established the direct or indirect involvement of α-syn in various NDs. Furthermore, molecular docking interaction and simulation studies were conducted to screen 85 major bioactive compounds of the Lamiaceae family against the α-syn aggregation. The results showed that five compounds (α-copaene, γ-eudesmol, carnosol, cedryl acetate, and spathulenol) had a high binding affinity towards α-syn with potential inhibitory activity towards its aggregation. MD simulations validated the stability of the molecular interactions determined by molecular docking. In addition, in silico pharmacokinetic analysis underscores their potential as promising drug candidates, demonstrating excellent blood-brain barrier (BBB) permeability, bioactivity, and reduced toxicity. In summary, this study identifies the most suitable compounds for targeting the α-syn aggregation and recommends these compounds as potential therapeutic agents against various NDs, pending further in vitro and in vivo validation.
- Publikační typ
- časopisecké články MeSH
Changes in cellular physiology and proteomic homeostasis accompanied the initiation and progression of colorectal cancer. Thus, ubiquitination represents a central regulatory mechanism in proteome dynamics. However, the complexity of the ubiquitinating network involved in carcinogenesis remains unclear. This study revealed the tumor-suppressive role of the ubiquitin ligase Cullin4A (CUL4A) in the intestine. We showed that simultaneous loss of CUL4A and hyperactivation of the Wnt pathway promotes tumor development in the distal colon. This tumor development is caused by an accumulation of the inactive SMAD3, a TGF-β pathway mediator. Depletion of CUL4A resulted in stabilization of HUWE1, which attenuated SMAD3 function. We showed a correlation between the intracellular localization of CUL4A and colorectal cancer progression, where nuclear CUL4A localization correlates with advanced colorectal cancer progression. In summary, we identified CUL4A as an important regulator of SMAD3 signal transduction competence in a HUWE1-dependent manner and demonstrated a critical role for the crosstalk between ubiquitination and the Wnt/TGF-β signaling pathways in gastrointestinal homeostasis.
- MeSH
- HCT116 buňky MeSH
- kolorektální nádory * patologie genetika metabolismus MeSH
- kulinové proteiny * metabolismus genetika MeSH
- lidé MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- nádorové supresorové proteiny * metabolismus genetika MeSH
- protein Smad3 * metabolismus genetika MeSH
- regulace genové exprese u nádorů MeSH
- signální dráha Wnt MeSH
- ubikvitinace MeSH
- ubikvitinligasy * metabolismus genetika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Telomeres, essential for maintaining genomic stability, are typically preserved through the action of telomerase, a ribonucleoprotein complex that synthesizes telomeric DNA. One of its two core components, telomerase RNA (TR), serves as the template for this synthesis, and its evolution across different species is both complex and diverse. This review discusses recent advancements in understanding TR evolution, with a focus on plants (Viridiplantae). Utilizing novel bioinformatic tools and accumulating genomic and transcriptomic data, combined with corresponding experimental validation, researchers have begun to unravel the intricate pathways of TR evolution and telomere maintenance mechanisms. Contrary to previous beliefs, a monophyletic origin of TR has been demonstrated first in land plants and subsequently across the broader phylogenetic megagroup Diaphoretickes. Conversely, the discovery of plant-type TRs in insects challenges assumptions about the monophyletic origin of TRs in animals, suggesting evolutionary innovations coinciding with arthropod divergence. The review also highlights key challenges in TR identification and provides examples of how these have been addressed. Overall, this work underscores the importance of expanding beyond model organisms to comprehend the full complexity of telomerase evolution, with potential applications in agriculture and biotechnology.
- MeSH
- fylogeneze MeSH
- molekulární evoluce * MeSH
- RNA * genetika metabolismus MeSH
- rostliny genetika MeSH
- telomerasa * genetika metabolismus MeSH
- telomery * metabolismus genetika MeSH
- Viridiplantae genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
PURPOSE: Liver transplantation (LTx) is performed in individuals with urea cycle disorders when medical management (MM) insufficiently prevents the occurrence of hyperammonemic events. However, there is a paucity of systematic analyses on the effects of LTx on health-related outcome parameters compared to individuals with comparable severity who are medically managed. METHODS: We investigated the effects of LTx and MM on validated health-related outcome parameters, including the metabolic disease course, linear growth, and neurocognitive outcomes. Individuals were stratified into "severe" and "attenuated" categories based on the genotype-specific and validated in vitro enzyme activity. RESULTS: LTx enabled metabolic stability by prevention of further hyperammonemic events after transplantation and was associated with a more favorable growth outcome compared with individuals remaining under MM. However, neurocognitive outcome in individuals with LTx did not differ from the medically managed counterparts as reflected by the frequency of motor abnormality and cognitive standard deviation score at last observation. CONCLUSION: Whereas LTx enabled metabolic stability without further need of protein restriction or nitrogen-scavenging therapy and was associated with a more favorable growth outcome, LTx-as currently performed-was not associated with improved neurocognitive outcomes compared with long-term MM in the investigated urea cycle disorders.
Satellite DNAs (satDNAs) are abundant components of eukaryotic genomes, playing pivotal roles in chromosomal organization, genome stability, and evolution. Here, we combined cytogenetic and genomic methods to characterize the satDNAs in the genomes of Leptidea butterflies. Leptidea is characterized by the presence of a high heterochromatin content, large genomes, and extensive chromosomal reshuffling as well as the occurrence of cryptic species. We show that, in contrast to other Lepidoptera, satDNAs constitute a considerable proportion of Leptidea genomes, ranging between 4.11% and 11.05%. This amplification of satDNAs, together with the hyperactivity of transposable elements, contributes to the substantial genome expansion in Leptidea. Using chromosomal mapping, we show that, particularly LepSat01-100 and LepSat03-167 satDNAs, are preferentially localized in heterochromatin exhibiting variable distribution that may have contributed to the highly diverse karyotypes within the genus. The satDNAs also exhibit W-chromosome accumulation, suggesting their involvement in sex chromosome evolution. Our results provide insights into the dynamics of satDNAs in Lepidoptera genomes and highlight their role in genome expansion and chromosomal organization, which could influence the speciation process. The high proportion of repetitive DNAs in the genomes of Leptidea underscores the complex evolutionary dynamics revealing the interplay between repetitive DNAs and genomic architecture in the genus.
The FGF system is the most complex of all receptor tyrosine kinase signaling networks with 18 FGF ligands and four FGFRs that deliver morphogenic signals to pattern most embryonic structures. Even when a single FGFR is expressed in the tissue, different FGFs can trigger dramatically different biological responses via this receptor. Here we show both quantitative and qualitative differences in the signaling of one of the FGF receptors, FGFR1c, in response to different FGFs. We provide an overview of the recent discovery that FGFs engage in biased signaling via FGFR1c. We discuss the concept of ligand bias, which represents qualitative differences in signaling as it is a measure of differential ligand preferences for different downstream responses. We show how FGF ligand bias manifests in functional data in cultured chondrocyte cells. We argue that FGF-ligand bias contributes substantially to FGF-driven developmental processes, along with known differences in FGF expression levels, FGF-FGFR binding coefficients and differences in FGF stability in vivo.
- MeSH
- chondrocyty metabolismus MeSH
- fibroblastové růstové faktory * metabolismus MeSH
- lidé MeSH
- ligandy MeSH
- receptor fibroblastových růstových faktorů, typ 1 * metabolismus MeSH
- receptory fibroblastových růstových faktorů * metabolismus MeSH
- signální transdukce * MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- MeSH
- chaperoniny chemie MeSH
- hydrofobní a hydrofilní interakce MeSH
- metabolické sítě a dráhy MeSH
- oxygenasy chemie MeSH
- proteindisulfidisomerasy chemie MeSH
- sbalování proteinů * MeSH
- sekundární struktura proteinů MeSH
- stabilita proteinů MeSH
- statická elektřina MeSH
- vodíková vazba MeSH
- Publikační typ
- přehledy MeSH
Tannase-producing filamentous fungi residing alongside tannin-rich ambient in the Northwest Himalayas were isolated at laboratory conditions and further identified by 18S ribosomal RNA gene sequencing. Five most potent tannase producing strains (EI ≥ 2.0), designated Aspergillus fumigatus AN1, Fusarium redolens AN2, Penicillium crustosum AN3, Penicillium restrictum AN4, and Penicillium commune AN5, were characterized. The strain Penicillium crustosum AN3 exhibited a maximum zone dia (25.66 mm ± 0.38). During solid-state fermentation, a maximal amount of tannase was attained with Penicillium crustosum AN3 using pine needles (substrate) by adopting response surface methodology for culture parameter optimization. Gel filtration chromatography yielded 46.48% of the partially purified enzyme with 3.94-fold of tannase purification. We found two subunits in enzyme-117.76 KDa and 88.51 KDa, respectively, in the SDS-PAGE. Furthermore, the characterization of partially purified tannase revealed a maximum enzyme activity of 8.36 U/mL at 30 °C using a substrate concentration (methyl gallate) of 10 mM. To broaden the knowledge of crude enzyme application, dye degradation studies were subjected to extracellular crude tannase from Penicillium crustosum AN3 where the maximum degradation achieved at a low enzyme concentration (5 ppm).
- MeSH
- barvicí látky metabolismus chemie MeSH
- fermentace MeSH
- fungální proteiny genetika metabolismus izolace a purifikace chemie MeSH
- Fusarium enzymologie genetika MeSH
- fylogeneze MeSH
- houby enzymologie genetika MeSH
- karboxylesterhydrolasy * metabolismus genetika izolace a purifikace chemie MeSH
- kultivační média chemie MeSH
- molekulová hmotnost MeSH
- Penicillium * enzymologie genetika MeSH
- RNA ribozomální 18S genetika MeSH
- stabilita enzymů MeSH
- substrátová specifita MeSH
- teplota MeSH
- Publikační typ
- časopisecké články MeSH
