50 research outputs found
MD simulations of complexes consisted of HIV reverse transcriptase and its potental inhibitors
No full textFyzikální ústav UKInstitute of Physics of Charles UniversityFaculty of Mathematics and PhysicsMatematicko-fyzikální fakult
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Modelling the effects of chemotherapy on the within-host dynamics of human malaria infection and immune response
Full text linkHost immunity and parasite stage specific sensitivity and resistance to antimalarial drugs are important determinants of the natural course of Plasmodium falciparum infections and the therapeutic response to antimalarial drugs. The relationship between these factors is incompletely understood. In this thesis, a series of discrete time mathematical models were developed to study the dynamics of P. falciparum parasites in malaria infected patients. The models were used to test two main hypotheses: 1) Host immunity regulates parasite load and can explain the plateauing of asexual stage parasitaemia observed during natural infection; 2) Deceleration of parasite clearance following artesunate treatment in patients infected with artemisinin resistant P. falciparum results from reduced drug eficacy against the ring stage of the asexual parasite lifecycle. To test the first hypothesis, detailed historical data from the era of malaria therapy for neurosyphilis were used. The model output predicted that increased peripheral blood parasite density was positively correlated with and resulted in an increase in host immunity over time. This host immunity subsequently contains the infection resulting in a sharp reduction in the parasite multiplication rate. This mathematical model was then adapted to examine the second hypothesis using data from detailed parasite clearance studies in patients treated with artesunate in Western Cambodia, an area of artemisinin resistance. The model output clearly supported that loss of ring stage sensitivity was the main factor explaining the overall deceleration in parasite clearance after artesunate treatment. This result prompted the development of ring-stage specific in-vitro artemisinin sensitivity tests, which further confirmed the hypothesis. Remaining questions include: whether gametocytogenesis can also explain the plateauing of parasitaemia and whether the level of splenic pitting is correlated with artemisinin resistance. To address this, future extensions of the model will include additional parasite life cycle stages, including sexual stages, as well as the interactions between parasites, erythrocytes and the spleen
The potential use of mitochondrial ribosomal genes (12S and 16S) in DNA barcoding and phylogenetic analysis of trematodes
Full text linkBackground: Genetic markers like the nuclear ribosomal RNA (rRNA) genes, internal transcribed spacer regions, mitochondrial protein-coding genes, and genomes have been utilized for molecular identification of parasitic trematodes. However, challenges such as the design of broadly applicable primers for the vast number of species within Digenea and the genetic markers’ ability to provide sufficient species-level resolution limited their utility. This study presented novel and broadly applicable primers using the mitochondrial 12S and 16S rRNA genes for Digenea and aimed to show their suitability as alternative genetic markers for molecular identification of orders Plagiorchiida, Echinostomida, and Strigeida.
Results: Our results revealed that the mitochondrial 12S and 16S rRNA genes are suitable for trematode molecular identification, with sufficient resolution to discriminate closely related species and achieve accurate species identification through phylogenetic placements. Moreover, the robustness of our newly designed primers to amplify medically important parasitic trematodes encompassing three orders was demonstrated through successful amplification. The convenience and applicability of the newly designed primers and adequate genetic variation of the mitochondrial rRNA genes can be useful as complementary markers for trematode molecular-based studies.
Conclusions: We demonstrated that the mitochondrial rRNA genes could be alternative genetic markers robust for trematode molecular identification and potentially helpful for DNA barcoding where our primers can be widely applied across the major Digenea orders. Furthermore, the potential of the mitochondrial rRNA genes for molecular systematics can be explored, enhancing their appeal for trematode molecular-based studies. The novelty of utilizing the mitochondrial rRNA genes and the designed primers in this study can potentially open avenues for species identification, discovery, and systematics in the future
Validating a web application’s use of genetic distance to determine helminth species boundaries and aid in identification
No full textAbstract Background Parasitic helminths exhibit significant diversity, complicating both morphological and molecular species identification. Moreover, no helminth-specific tool is currently available to aid in species identification of helminths using molecular data. To address this, we developed and validated a straightforward, user-friendly application named Applying Taxonomic Boundaries for Species Identification of Helminths (ABIapp) using R and the Shiny framework. Serving as a preliminary step in species identification, ABIapp is designed to assist in visualizing taxonomic boundaries for nematodes, trematodes, and cestodes. ABIapp employs a database of genetic distance cut-offs determined by the K-means algorithm to establish taxonomic boundaries for ten genetic markers. Validation of ABIapp was performed both in silico and with actual specimens to determine its classification accuracy. The in silico validation involved 591 genetic distances sourced from 117 publications, while the validation with actual specimens utilized ten specimens. ABIapp’s accuracy was also compared with other online platforms to ensure its robustness to assist in helminth identification. Results ABIapp achieved an overall classification accuracy of 76% for in silico validation and 75% for actual specimens. Additionally, compared to other platforms, the classification accuracy of ABIapp was superior, proving its effectiveness to determine helminth taxonomic boundaries. With its user-friendly interface, minimal data input requirements, and precise classification capabilities, ABIapp offers multiple benefits for helminth researchers and can aid in identification. Conclusions Built on a helminth-specific database, ABIapp serves as a pioneering tool for helminth researchers, offering an invaluable resource for determining species boundaries and aiding in species identification of helminths. The availability of ABIapp to the community of helminth researchers may further enhance research in the field of helminthology. To enhance ABIapp’s accuracy and utility, the database will be updated annually
Exploring the antimicrobial potential of crude peptide extracts from Allium sativum and Allium oschaninii against antibiotic-resistant bacterial strains
No full textContext Plant peptides garner attention for their potential antimicrobial properties amid the rising concern over antibiotic-resistant bacteria.Objective This study investigates the antibacterial potential of crude peptide extracts from 27 Thai plants collected locally.Materials and methods Peptide extracts from 34 plant parts, derived from 27 Thai plants, were tested for their antimicrobial efficacy against four highly resistant bacterial strains: Streptococcus aureus MRSA, Pseudomonas aeruginosa, Acinetobacter baumannii, and Escherichia coli. The stability of these peptide extracts was examined at different temperatures, and the synergistic effects of two selected plant peptide extracts were investigated. Additionally, the time-kill kinetics of the individual extracts and their combination were determined against the tested pathogens.Results Peptides from Allium sativum L. and Allium oschaninii O. Fedtsch (Amaryllidaceae) were particularly potent, inhibiting bacterial growth with MICs ranging from 1.43 to 86.50 µg/mL. The consistent MICs and MBCs of these extracts across various extraction time points highlight their reliability. Stability tests reveal that these peptides maintain their antimicrobial activity at −20 °C for over a month, emphasizing their durability for future exploration and potential applications in addressing antibiotic resistance. Time-kill assays elucidate the time and concentration-dependent nature of these antimicrobial effects, underscoring their potent initial activity and sustained efficacy over time.Discussion and conclusions This study highlights the antimicrobial potential of Allium-derived peptides, endorsing them for combating antibiotic resistance and prompting further investigation into their mechanisms
Additional file 1 of The potential use of mitochondrial ribosomal genes (12S and 16S) in DNA barcoding and phylogenetic analysis of trematodes
No full textAdditional file 1: Figure S1 to S3. Maximum likelihood phylogenetic trees for the nuclear 18S rRNA gene, 28S rRNA gene, ITS2 region, and the mitochondrial COI gene
Additional file 2 of The potential use of mitochondrial ribosomal genes (12S and 16S) in DNA barcoding and phylogenetic analysis of trematodes
No full textAdditional file 2: Figure S1 to S3. Maximum likelihood phylogenetic trees for the concatenated nuclear rRNA and mitochondrial rRNA genes
Sensitive and accurate DNA metabarcoding of parasitic helminth mock communities using the mitochondrial rRNA genes
Full text linkNext-generation sequencing technologies have accelerated the pace of helminth DNA metabarcoding research, enabling species detection in bulk community samples. However, finding suitable genetic markers with robust species-level resolution and primers targeting a broad species range among parasitic helminths are some of the challenges faced. This study aimed to demonstrate the potential use of the mitochondrial 12S and 16S rRNA genes for parasitic helminth (nematodes, trematodes, cestodes) DNA metabarcoding. To demonstrate the robustness of the 12S and 16S rRNA genes for DNA metabarcoding, we determined the proportion of species successfully recovered using mock helminth communities without environment matrix and mock helminth communities artificially spiked with environmental matrices. The environmental matrices are human fecal material, garden soil, tissue, and pond water. Our results revealed the robustness of the mitochondrial rRNA genes, through the high sensitivity of the 12S rRNA gene, and the effectiveness of the 12S and 16S primers targeting platyhelminths. With the mitochondrial rRNA genes, a broad range of parasitc helminths were successfully detected to the species level. The potential of the mitochondrial rRNA genes for helminth DNA metabarcoding was demonstrated, providing a valuable gateway for future helminth DNA metabarcoding applications like helminth detection and biodiversity studies
Additional file 3 of The potential use of mitochondrial ribosomal genes (12S and 16S) in DNA barcoding and phylogenetic analysis of trematodes
No full textAdditional file 3: Table S1. NCBI sequences generated in this study and trematode species used for phylogenetic analysis
Assessing the early stage of eHealth adoption: a case study from a community hospital in Thailand
Full text linkIn this paper, the authors implement and determine the success the eHealth adoption for queue management when it was first deployed for a community hospital setting in Thailand. The electronic queue system was first implemented to improve conventional operations; then extensive evaluations were conducted to measure the effectiveness for each stakeholder. The healthcare staff shared a common perception that the new system could reduce their workload and increase the efficacy of queue fairness. The overall patient satisfaction and actual waiting time patients spent at the nurse interview station improved significantly. The majority of the patients agreed that the notification for attention from the computerized system is more effective. The community healthcare has strong potential to adopt the eHealth system. Being more automated enabled a reduced burden of administration jobs and significantly reduced waiting times for patients. Patients responded that they had greater satisfaction after the introduction of the electronic queue system
