Mughees Aizaz Alvi , Rana Muhammad Athar Ali , Li Li , Muhammad Saqib , Warda Qamar , Ali Hassan , Muzafar Ghafoor , Siddiq Ur Rahman , Muhammad Umar Zafar Khan , Bao-Quan Fu , Youyu Liu , Hong Yin , Hong-Bin Yan , Wan-Zhong Jia
{"title":"Phylogeny and population structure of Echinococcus granulosus (sensu stricto) based on full-length cytb-nad2-atp6 mitochondrial genes – First report from Sialkot District of Pakistan","authors":"Mughees Aizaz Alvi , Rana Muhammad Athar Ali , Li Li , Muhammad Saqib , Warda Qamar , Ali Hassan , Muzafar Ghafoor , Siddiq Ur Rahman , Muhammad Umar Zafar Khan , Bao-Quan Fu , Youyu Liu , Hong Yin , Hong-Bin Yan , Wan-Zhong Jia","doi":"10.1016/j.molbiopara.2022.111542","DOIUrl":"10.1016/j.molbiopara.2022.111542","url":null,"abstract":"<div><p><span><span>Cystic echinococcosis is a </span>zoonotic disease of livestock having serious economic setbacks. The etiological agents of the disease belong to </span><span><em>Echinococcus</em><em> granulosus</em></span> sensu lato. Despite of worldwide distribution of the disease, the molecular studies mainly employ amplification of <em>cox</em>1, <em>nad</em>1 and <em>nad</em><span>5 genes. To further strengthen the knowledge about significance of other molecular markers<span> and to investigate the genetic diversity and population structure of </span></span><em>Echinococcus</em> species in Pakistan, the current study was designed in which full length mitochondrial <em>cyt</em>b, <em>atp</em>6 and <em>nad</em>2 genes were amplified. Based on BLAST searches of the generated <em>cyt</em>b, <em>atp</em>6 and <em>nad</em>2 gene sequences from a total of 18 hydatid cysts collected from cattle, 12 isolates were identified as <em>E</em>. <em>granulousus</em> G3 and 6 as <em>E</em>. <em>granulosus</em><span> (G1). The phylogeny inferred by the Bayesian method using nucleotide sequences of </span><em>cyt</em>b-<em>atp</em>6-<em>nad</em>2 further confirmed their identity. The diversity indices indicated a high haplotype and a low nucleotide diversity. The negative values of Tajima’s D and Fu’s Fs test demonstrated deviation from neutrality suggesting a recent population expansion. To the best of our knowledge, the present study described the genetic variation of <em>E</em>. <em>granulosus</em> population for the first time in Pakistan using full-length <em>cyt</em>b, <em>atp</em>6 and <em>nad</em><span>2 mitochondrial genes. The findings on the genetic variation of </span><em>E</em>. <em>granulosus</em> in Pakistan will constitute useful baseline information for future studies on the prevalence and population structure of <em>E</em>. <em>granulosus</em> based on full-length <em>cyt</em>b, <em>atp</em>6 and <em>nad</em>2.</p></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":"253 ","pages":"Article 111542"},"PeriodicalIF":1.5,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10726588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Biophysical description of Bromosulfophthalein interaction with the 28-kDa glutathione transferase from Schistosoma japonicum","authors":"Kagiso Pooe, Monare Thulo, Hattie Makumbe, Blessing Akumadu, Oluwatobin Otun, Chinyere Aloke, Ikechukwu Achilonu","doi":"10.1016/j.molbiopara.2022.111524","DOIUrl":"10.1016/j.molbiopara.2022.111524","url":null,"abstract":"<div><p><span><span><span>Glutathione<span><span><span> transferases (GSTs) are major detoxification </span>enzymes vital for the survival and reproduction of </span>schistosomes<span> during infection in humans. Schistosoma encode two GST isoenzymes, the 26- and 28-kDa </span></span></span>isoforms<span>, that show different substrate specificities<span> and cellular localisations. Bromosulfophthalein (BSP) has been identified and characterised as a potent 26-kDa </span></span></span>Schistosoma japonicum<span> GST (Sj26GST) inhibitor with an anthelmintic<span><span> potential. This study describes the structure, function, and ligandin properties of the 28-kDa Schistosoma japonicum GST (Sj28GST) towards BSP. Enzyme kinetics show that BSP is a potent </span>enzyme inhibitor, with a specific activity decrease</span></span></span><del>s</del> from 60.4 µmol/min/mg to 0.0742 µmol/min/mg and an IC<sub>50</sub><span> in the micromolar range of 0.74 µM. Far-UV circular dichroism<span> confirmed that purified Sj28GST follows a typical GST fold, which is predominantly alpha-helical. Fluorescence spectroscopy<span> suggests that BSP binding occurs at a site distinct from the glutathione-binding site (G-site); however, the binding does not alter the local G-site environment. Isothermal titration calorimetry studies show that the binding of BSP to Sj28GST is exergonic (∆</span></span></span><em>G</em><span>°= −33 kJ/mol) and enthalpically-driven, with a stoichiometry of one BSP per dimer. The stability of Sj28GST (∆G</span><sub>(H2O)</sub> = 4.7 kcal/mol) is notably lower than Sj26GST, owing to differences in the enzyme’s dimeric interfaces. We conclude that Sj28GST shares similar biophysical characteristics with Sj26GST based on its kinetic properties and susceptibility to low concentrations of BSP. The study supports the potential benefits of re-purposing BSP as a potential drug or prodrug to mitigate the scourge of schistosomiasis.</p></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":"252 ","pages":"Article 111524"},"PeriodicalIF":1.5,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10451752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ranielly Araujo Nogueira , Maria Gabriela Sampaio Lira , Irlla Correia Lima Licá , Gleycka Cristine Carvalho Gomes Frazão , Vitor Augusto Ferreira dos Santos , Antonio Camilo Correia Mendes Filho , João Gustavo Mendes Rodrigues , Guilherme Silva Miranda , Rafael Cardoso Carvalho , Flávia Raquel Fernandes Nascimento
{"title":"Praziquantel: An update on the mechanism of its action against schistosomiasis and new therapeutic perspectives","authors":"Ranielly Araujo Nogueira , Maria Gabriela Sampaio Lira , Irlla Correia Lima Licá , Gleycka Cristine Carvalho Gomes Frazão , Vitor Augusto Ferreira dos Santos , Antonio Camilo Correia Mendes Filho , João Gustavo Mendes Rodrigues , Guilherme Silva Miranda , Rafael Cardoso Carvalho , Flávia Raquel Fernandes Nascimento","doi":"10.1016/j.molbiopara.2022.111531","DOIUrl":"10.1016/j.molbiopara.2022.111531","url":null,"abstract":"<div><p><span>Praziquantel<span> (PZQ) is the drug of choice for the treatment of all forms of schistosomiasis, although its mechanisms of action are not completely understood. PZQ acts largely on adult worms. This narrative literature review describes what is known about the mechanisms of action of PZQ against schistosomes from </span></span><em>in vitro</em> and <em>in vivo</em><span><span> studies and highlights the molecular targets in parasites and immune responses induced in definitive hosts by this drug. Moreover, new therapeutic uses of PZQ are discussed. Studies have demonstrated that in addition to impacting voltage-operated Ca2 + channels, PZQ may interact with other schistosome molecules, such as myosin regulatory light chain, glutathione S-transferase, and transient receptor potential<span><span> channels. Following PZQ administration, increased T regulatory type 1 (Tr1) cell differentiation and decreased inflammation were observed, indicating that PZQ promotes immunoregulatory pathways. Although PZQ is widely used in mass drug administration schemes, the existence of resistant parasites has not been proven; however, it is a concern that should be constantly investigated in human populations. In addition, we discuss studies that evaluate health applications of PZQ (other than </span>helminth infection), such as its effect in cancer therapy and its adjuvant action in vaccines against </span></span>viruses.</span></p></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":"252 ","pages":"Article 111531"},"PeriodicalIF":1.5,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10452049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rubens Emanoel Tavares da Rocha , Antônio Sérgio Alves de Almeida Júnior , Nairomberg Cavalcanti Portela Júnior , Amanda Vasconcelos do Nascimento , Nayara Maria Siqueira Leite , Jamerson Ferreira de Oliveira , Maria do Carmo Alves de Lima , Ana Paula Sampaio Feitosa , Maria Eliane Bezerra de Mélo , Fábio André Brayner , Luiz Carlos Alves
{"title":"Synthesis, in vitro schistosomicidal activity and ultrastructural alterations caused by thiosemicarbazones and thiazolidinones against juvenile and adult Schistosoma mansoni worms (Sambon, 1907)","authors":"Rubens Emanoel Tavares da Rocha , Antônio Sérgio Alves de Almeida Júnior , Nairomberg Cavalcanti Portela Júnior , Amanda Vasconcelos do Nascimento , Nayara Maria Siqueira Leite , Jamerson Ferreira de Oliveira , Maria do Carmo Alves de Lima , Ana Paula Sampaio Feitosa , Maria Eliane Bezerra de Mélo , Fábio André Brayner , Luiz Carlos Alves","doi":"10.1016/j.molbiopara.2022.111520","DOIUrl":"10.1016/j.molbiopara.2022.111520","url":null,"abstract":"<div><p>Schistosomiasis is a neglected disease that affects about 258 million people worldwide. Caused by <span><em>Schistosoma mansoni</em></span><span><span>, helminth which, in Brazil, it is present on 19 states and capital. </span>Praziquantel (PZQ) treatment presents low efficacy and adverse effects in parasites juvenile stages. Thiosemicarbazones and thiazolidinones are rising as potent chemical groups that have biological activity wide spectrum, and with radical modifications, they may become more effective and selective. Aiming to evaluate the action of these molecules against </span><em>S. mansoni</em><span><span><span>, JF series thiosemicarbazones and thiazolidinones (LqIT/UFPE) were synthesized: JF30, JF31, JF33, JF34, JF35, JF36, JF38, JF39, JF42 and JF43. Several parameters were evaluated, such as: their cytotoxicity in VERO cells, in vitro schistosomicidal activity for juvenile and adult worms and their action on worms through ultrastructural changes. Cytotoxicity indices ranged from 272 µM to 725 µM. When evaluating mortality rate, adult and juvenile worms showed 100 % mortality rate within 24 h and 48 h, respectively, when exposed to the compounds JF31 and JF43 at a dose of 200 µM. Also, motility, mortality and oviposition parameters were evaluated: JF31 and JF43 presented a score of 0 in 24 h, meaning total absence of movement, whereas no eggs and soft tissue damage were observed under </span>optical microscopy. Through scanning electron microscopy, integumentary alterations caused by the compounds JF31 and JF43 were observed, such as: exposure of the musculature, formation of integumentary bubbles, </span>integuments with abnormal morphology and destruction of tubercles and spikes. The results shoerd that the compound JF31 was 2.39 times more selective for adult worms and JF43 was 3.74 times more selective for juvenile worms. Thus, the compounds JF43 and JF31 are the most promising for presenting schistosomicidal activity of </span><em>S. mansoni</em>.</p></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":"252 ","pages":"Article 111520"},"PeriodicalIF":1.5,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10455840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Alpha-terthienyl increases filamentous actin of Entamoeba histolytica","authors":"Mayra Herrera-Martínez , Verónica Ivonne Hernández-Ramírez , Sarita Montaño , Bibiana Chávez-Munguía , Beatriz Hernández-Carlos , Patricia Talamás-Rohana","doi":"10.1016/j.molbiopara.2022.111512","DOIUrl":"10.1016/j.molbiopara.2022.111512","url":null,"abstract":"<div><p>This study aimed to know if alpha terthienyl (α-T) affects <span><em>E. histolytica</em></span><span> viability and to analyze its effect on the actin cytoskeleton. Trophozoites of </span><em>E. histolytica</em><span> HM1-IMSS were treated with α-T, then, cell viability<span><span> and morphology were evaluated using tetrazolium salts and scanning electron microscopy, respectively; while actin filaments (F-actin) were stained with rhodamine-phalloidin, observed by </span>confocal microscopy and quantified by fluorometry. Data showed that α-T inhibited cell viability of trophozoites (IC</span></span><sub>50</sub><span><span>, 19.43 µg / mL), affected the cell morphology, and increased the F-actin in a dose-dependent manner. Production of reactive oxygen species and RhoA-GTP levels remained normal in α-T-treated amebas. Two inhibitors that affect the organization of the trophozoites cytoskeleton, one that interacts directly with actin, Cytochalasin D (CD), and one that affects the Rho </span>signaling pathway by inhibiting the downstream effector Rock, Y27632, were tested. Y27632 did not affect the increase of polymerized actin observed with α-T, this compound partially ameliorates the potent disrupting effects of CD on actin filaments. Docking results suggest that α-T could be an antagonist of CD for the same interaction zone in actin, however, more studies are needed to define the action mechanism of this compound.</span></p></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":"252 ","pages":"Article 111512"},"PeriodicalIF":1.5,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10473231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lingyu Sun , Yaru Lu , Ningning Zhao , Yakun Wang , Bingxiang Wang , Huihui Li , Zhiyuan Wu , Hongmei Li , Xiao Zhang , Xiaomin Zhao
{"title":"Construction of constitutive expression of Eimeria tenella eukaryotic initiation factor U6L5H2 on the surface of Lactobacillus plantarum and evaluation of its immunoprotective efficiency against chicken coccidiosis","authors":"Lingyu Sun , Yaru Lu , Ningning Zhao , Yakun Wang , Bingxiang Wang , Huihui Li , Zhiyuan Wu , Hongmei Li , Xiao Zhang , Xiaomin Zhao","doi":"10.1016/j.molbiopara.2022.111527","DOIUrl":"10.1016/j.molbiopara.2022.111527","url":null,"abstract":"<div><p><span><em>Lactobacillus</em></span><span> strains exhibit preferable properties that make them attractive candidates for vaccine delivery systems because of their ability to regulate intestinal mucosal immunity in the body. To date, live </span><em>Lactobacillus</em> delivery vaccines reported for the defense against <span><em>Eimeria tenella</em></span> have been inducer-dependent systems whose applications are significantly limited due to their unattainable induction conditions in vivo. Here, a constitutive expression of <span><em>Lactobacillus plantarum</em></span> NC8 surface display system was constructed. Then, this system was used to prepare a live oral vaccine to constitutively express the <em>E. tenella</em> U6L5H2 (EtU6) protein on the NC8 surface and to evaluate its protective efficacy against <em>E. tenella</em> challenge in chickens. The results showed that the heterologous protein (EGFP or EtU6) was successfully expressed on the surface of <em>L. plantarum</em> NC8 without any inducer. The immunoprotection of EtU6 with constitutive expression in <em>L. plantarum</em> NC8 system (NC8/Pc-EtU6) was significantly stronger than that of EtU6 with induced expression of <em>L. plantarum</em><span> NC8 system (NC8/Pi-EtU6) (ACI: 168.28 vs. 152.74) as evidenced by increased body weight, decreased oocyst output and lesion scores. Furthermore, the constitutive system NC8/Pc-EtU6 produced higher levels of specific cecal SIgA, serum IgG, transcription of cytokines IFN-γ and IL-2, and lymphocyte proliferation than the induced system NC8/Pi-EtU6. These results indicate that, compared to the inducible system, the constitutive surface display system of </span><em>L. plantarum</em> has the advantages of continuously expressing antigens in vivo and stimulating the host immune system. It could be an ideal platform for vaccine expression. The live vector vaccine for coccidiosis constructed by this constitutive system greatly improves the application potential in chicken production and provides a novel platform for the prevention of coccidiosis in chickens.</p></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":"252 ","pages":"Article 111527"},"PeriodicalIF":1.5,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10798558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jiaqi Zhang , Xi Chen , Maohua Pan , Yucheng Qin , Hui Zhao , Qi Yang , Xinxin Li , Weilin Zeng , Zheng Xiang , Yanrui Wu , Mengxi Duan , Xiaosong Li , Xun Wang , Dominique Mazier , Yanmei Zhang , Wenya Zhu , Kemin Sun , Yiman Wu , Liwang Cui , Yaming Huang , Zhaoqing Yang
{"title":"Application of a low-cost, specific, and sensitive loop-mediated isothermal amplification (LAMP) assay to detect Plasmodium falciparum imported from Africa","authors":"Jiaqi Zhang , Xi Chen , Maohua Pan , Yucheng Qin , Hui Zhao , Qi Yang , Xinxin Li , Weilin Zeng , Zheng Xiang , Yanrui Wu , Mengxi Duan , Xiaosong Li , Xun Wang , Dominique Mazier , Yanmei Zhang , Wenya Zhu , Kemin Sun , Yiman Wu , Liwang Cui , Yaming Huang , Zhaoqing Yang","doi":"10.1016/j.molbiopara.2022.111529","DOIUrl":"10.1016/j.molbiopara.2022.111529","url":null,"abstract":"<div><h3>Background</h3><p>Chinese citizens traveling abroad bring back imported malaria cases to China. Current malaria diagnostic tests, including microscopy and antigen-detecting rapid tests, cannot reliably detect low-density infections. To complement existing diagnostic methods, we aimed to develop a new loop-mediated isothermal amplification (LAMP) assay to detect and identify <em>Plasmodium falciparum</em> in Chinese travelers returning from Africa.</p></div><div><h3>Methods</h3><p>We developed a miniaturized LAMP assay to amplify the <em>actin I</em> gene of <em>P. falciparum</em>. Each reaction consumed only 25% of the reagents used in a conventional LAMP assay and the same amount of DNA templates used in nested PCR. We evaluated this LAMP assay's performance and compared it to microscopy and a nested PCR assay using 466 suspected malaria cases imported from Africa. We assessed the sensitivity of the new LAMP assay using cultured <em>P. falciparum,</em> clinical samples, and a plasmid construct, allowing unprecedented precision when quantifying the limit of detection.</p></div><div><h3>Results</h3><p>The new LAMP assay was highly sensitive and detected two more malaria cases than nested PCR. Compared to nested PCR, the sensitivity and specificity of the novel LAMP assay were 100% [95% confidence interval (CI) 98.5–100%] and 99.1% (95% CI 96.7–99.9%), respectively. When evaluated using serial dilutions of the plasmid construct, the detection limit of the new LAMP was as low as 10<sup>2</sup> copies/μL, 10-fold lower than PCR. The LAMP assay detected 0.01 parasites/μL of blood (equal to 0.04 parasites/μL of DNA) using cultured <em>P. falciparum</em> and 1–7 parasites/μL of blood (4–28 parasites/μL of DNA) in clinical samples, which is as good as or better than previously reported and commercially licensed assays.</p></div><div><h3>Conclusion</h3><p>The novel LAMP assay based on the <em>P. falciparum actin I</em> gene was specific, sensitive, and cost-effective, as it consumes 1/4 of the reagents in a typical LAMP reaction.</p></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":"252 ","pages":"Article 111529"},"PeriodicalIF":1.5,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9890345/pdf/nihms-1865584.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10653861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Everett Cochrane, Joshua Foster, Mohammad Hassan Khatami, Hendrick W. de Haan, Sean G. Forrester
{"title":"Characterization of adjacent charged residues near the agonist binding site of the nematode UNC-49 GABA receptor","authors":"Everett Cochrane, Joshua Foster, Mohammad Hassan Khatami, Hendrick W. de Haan, Sean G. Forrester","doi":"10.1016/j.molbiopara.2022.111521","DOIUrl":"10.1016/j.molbiopara.2022.111521","url":null,"abstract":"<div><p><span><span>The UNC-49 receptor is a Cys-loop GABA receptor that is unique to the nematode phylum. The receptor differs from mammalian GABA receptors both in </span>amino acid sequence<span> and pharmacology which highlights its potential as a novel anthelmintic target. Sequence differences within and near the various ligand-binding loops of the nematode receptor suggest that there could be structural differences compared to mammalian receptors that result in different pharmacological and functional features. Here we investigated three residues in the UNC-49 receptor from the parasitic nematode </span></span><span><em>Haemonchus contortus</em></span><span><span>: K181, E183, and T230. Analysis of these residues was conducted via site-directed mutagenesis, electrophysiology, MD simulations, and mutant cycling analysis. In the UNC-49 receptor, E183 lies in close proximity to K181 where together they appear to play a role in GABA sensitivity and pharmacology, possibly interacting via an ionic bond. While the introduction of single </span>alanine residues at each position separately had a negative impact on GABA EC</span><sub>50</sub>, the double alanine mutant (K181A/E183A) exhibited wildtype-level GABA EC<sub>50</sub> and some differences in pharmacology. Overall, this study has revealed a potentially novel role for these two residues in nematode UNC-49 GABA receptors that could aid in understanding their function.</p></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":"252 ","pages":"Article 111521"},"PeriodicalIF":1.5,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10818007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Editorial - Strongyloides research in the post-genomics era","authors":"Louise E. Atkinson, Elissa A. Hallem","doi":"10.1016/j.molbiopara.2022.111522","DOIUrl":"10.1016/j.molbiopara.2022.111522","url":null,"abstract":"","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":"252 ","pages":"Article 111522"},"PeriodicalIF":1.5,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10451264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Profiling of metabolic alterations in mice infected with malaria parasites via high-resolution metabolomics","authors":"Jyoti Chhibber-Goel , Anurag Shukla , Dhanasekaran Shanmugam , Amit Sharma","doi":"10.1016/j.molbiopara.2022.111525","DOIUrl":"10.1016/j.molbiopara.2022.111525","url":null,"abstract":"<div><h3>Background</h3><p>Malaria infection can result in distinct clinical outcomes from asymptomatic to severe. The association between patho-physiological changes and molecular changes in the host, and their correlation with severity of malaria progression is not fully understood.</p></div><div><h3>Methods</h3><p>In this study, we addressed mass spectrometry-based temporal profiling of serum metabolite levels from mice infected with <em>Plasmodium berhgei</em> (strain ANKA).</p></div><div><h3>Results</h3><p>We show global perturbations and identify changes in specific metabolites in correlation with disease progression. While metabolome-wide changes were apparent in late-stage malaria, a subset of metabolites exhibited highly correlated changes with disease progression. These metabolites changed early on following infection and either continued or maintained the change as mice developed severe disease. Some of these have the potential to be sentinel metabolites for severe malaria. Moreover, glycolytic metabolites, purine nucleotide precursors, tryptophan<span><span> and its bioactive derivatives were many fold decreased in late-stage disease. Interestingly, uric acid, a metabolic waste reported to be elevated in severe human malaria, increased with disease progression, and subsequently appears to be detoxified into allantoin. This detoxification mechanism is absent in humans as they lack the </span>enzyme uricase.</span></p></div><div><h3>Conclusions</h3><p>We have identified candidate marker metabolites that may be of relevance in the context of human malaria.</p></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":"252 ","pages":"Article 111525"},"PeriodicalIF":1.5,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10451548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}