Fonsecaea pedrosoi-induced Th17-cell differentiation in mice is fostered by Dectin-2 and suppressed by Mincle recognition

Funded by NIH. Grant Number: R01 AI093553 Wellcome TrustPeer reviewedPublisher PD

Sentiment and Topic Modeling Analysis on Twitter Reveals Concerns over Cannabis-Containing Food after Cannabis Legalization in Thailand

Objectives Twitter has been used to express a diverse range of public opinions about cannabis legalization in Thailand. The purpose of this study was to observe changes in sentiments after cannabis legalization and to investigate health-related topics discussed on Twitter. Methods Tweets in Thai and English related to cannabis were scraped from Twitter between May 1 and June 13, 2022, during cannabis legalization in Thailand. Sentiment and topic-modeling analyses were used to compare the content of tweets before and after legalization. Health-related topics were manually grouped into categories by their content and rated according to the number of corresponding tweets. Results We collected 21,242 and 6,493 tweets, respectively, for Thai and English search terms. A sharp increase in the number of tweets related to cannabis legalization was detected at the time of its public announcement. Sentiment analysis in the Thai search group showed a significant change (p < 0.0001) in sentiment distribution after legalization, with increased negative and decreased positive sentiments. A significant change was not found in the English search group (p = 0.4437). Regarding cannabis-containing food as a leading issue, topic-modeling analysis revealed public concerns after legalization in the Thai search group, but not the English one. Topics related to cannabis tourism surfaced only in the English search group. Conclusions Since cannabis legalization, the primary health-related concern has been cannabis-containing food. Education and clear regulations on cannabis use are required to strengthen oversight of cannabis in the Thai population, as well as among medical tourists

DNA Repair Biosensor-Identified DNA Damage Activities of Endophyte Extracts from Garcinia cowa

Recent developments in chemotherapy focus on target-specific mechanisms, which occur only in cancer cells and minimize the effects on normal cells. DNA damage and repair pathways are a promising target in the treatment of cancer. In order to identify novel compounds targeting DNA repair pathways, two key proteins, 53BP1 and RAD54L, were tagged with fluorescent proteins as indicators for two major double strand break (DSB) repair pathways: non-homologous end-joining (NHEJ) and homologous recombination (HR). The engineered biosensor cells exhibited the same DNA repair properties as the wild type. The biosensor cells were further used to investigate the DNA repair activities of natural biological compounds. An extract from Phyllosticta sp., the endophyte isolated from the medicinal plant Garcinia cowa Roxb. ex Choisy, was tested. The results showed that the crude extract induced DSB, as demonstrated by the increase in the DNA DSB marker &gamma;H2AX. The damaged DNA appeared to be repaired through NHEJ, as the 53BP1 focus formation in the treated fraction was higher than in the control group. In conclusion, DNA repair-based biosensors are useful for the preliminary screening of crude extracts and biological compounds for the identification of potential targeted therapeutic drugs

Transcriptome analysis reveals pathogenicity and evolutionary history of the pathogenic oomycete Pythium insidiosum

Oomycetes form a unique group of microorganisms that share hyphal morphology with fungi. Most of pathogenic oomycetes infect plants, while some species are capable of infecting animals. Pythium insidiosum is the only oomycete that can infect both humans and animals, and causes a life-threatening infectious disease, called 'pythiosis'. Controlling an infection caused by P. insidiosum is problematic because effective antimicrobial drugs are not available. Information on the biology and pathogenesis of P. insidiosum is limited. We generated a P. insidiosum transcriptome of 26735 unigenes, using the 454 sequencing platform. As adaptations to increased temperature inside human hosts are required for a successful pathogen, we generated P. insidiosum transcriptomes at 28°C and 37°C and identified 625 up-regulated and 449 down-regulated genes at 37°C. Comparing the proteomes of oomycetes, fungi, and parasites provided clues on the evolutionary history of P. insidiosum. Potential virulence factors of P. insidiosum, including putative effectors, were identified. Pythium insidiosum harbored an extensive repertoire of ~300 elicitin domain-containing proteins. The transcriptome, presented herein, provides an invaluable resource for exploring P. insidiosum's biology, pathogenesis, and evolution.14 page(s

The elicitin-like glycoprotein, ELI025, is secreted by the pathogenic oomycete Pythium insidiosum and evades host antibody responses.

Pythium insidiosum is a unique oomycete that can infect humans and animals. Patients with a P. insidiosum infection (pythiosis) have high rates of morbidity and mortality. The pathogen resists conventional antifungal drugs. Information on the biology and pathogenesis of P. insidiosum is limited. Many pathogens secrete proteins, known as effectors, which can affect the host response and promote the infection process. Elicitins are secretory proteins and are found only in the oomycetes, primarily in Phytophthora and Pythium species. In plant-pathogenic oomycetes, elicitins function as pathogen-associated molecular pattern molecules, sterol carriers, and plant defense stimulators. Recently, we reported a number of elicitin-encoding genes from the P. insidiosum transcriptome. The function of elicitins during human infections is unknown. One of the P. insidiosum elicitin-encoding genes, ELI025, is highly expressed and up-regulated at body temperature. This study aims to characterize the biochemical, immunological, and genetic properties of the elicitin protein, ELI025. A 12.4-kDa recombinant ELI025 protein (rELI025) was expressed in Escherichia coli. Rabbit anti-rELI025 antibodies reacted strongly with the native ELI025 in P. insidiosum's culture medium. The detected ELI025 had two isoforms: glycosylated and non-glycosylated. ELI025 was not immunoreactive with sera from pythiosis patients. The region near the transcriptional start site of ELI025 contained conserved oomycete core promoter elements. In conclusion, ELI025 is a small, abundant, secreted glycoprotein that evades host antibody responses. ELI025 is a promising candidate for development of diagnostic and therapeutic targets for pythiosis

Cloning and expression of <i>ELI025</i>.

<p>(<b>A</b>) Plasmid DNA map of pET28b-ELI025 shows the cloning sites (<i>Nde-</i>I and <i>EcoR-</i>I) of <i>ELI025</i>. Expression of <i>ELI025</i> is under the control of the T7 promoter. The numbers in parentheses indicate a location of each plasmid component; (<b>B</b>) Protein structure of ELI025 shows a signal peptide (SP; amino acid position 1–20), an elicitin domain (amino acid position 25–110), three disulfide bonds (C1, cysteine position 27 and 91; C2, cysteine position 47 and 76; C3, cysteine position 71 and 110), two predicted N-linked glycosylation sties (N; amino acid position, 22 and 87), and three predicted O-linked glycosylation sties (O; amino acid position 49, 51, and 54).</p