Project description:<p>Parasites can manipulate host behavior to facilitate parasite transmission. One such host-pathogen interaction occurs between the fungus Ophiocordyceps sinensis (O. sinensis) and the ghost moth Thitarodes xiaojinensis. O. sinensis is involved in the mummification process of infected host larvae. However, the underlying molecular and chemical mechanism for this phenomenon is unknown. We characterized the small molecules regulating host behavior and the altered metabolites in infected and mummified host larvae. Lipid-related metabolites, such as phosphatidylcholine (PC) were identified in infected and mummified larvae. Decreased levels of the neurotransmitter acetylcholine (ACh) and elevated choline levels were observed in the brains of both the infected and mummified larvae. The aberrant activity of acetylcholinesterase (AChE) and relative mRNA expression of ACE2 (acetylcholinesterase) may mediate the altered transformation between ACh and choline, leading to the brain dysfunction of mummified larvae. Caspofungin treatment inhibited the mummification of infected larvae and the activity of AChE. These findings indicate the importance of ACh in the mummification of host larvae after O. sinensis infection.</p><p><br></p><p><strong>Lipidome data</strong> is reported in the current study <a href='https://www.ebi.ac.uk/metabolights/MTBLS9930' rel='noopener noreferrer' target='_blank'><strong>MTBLS9930</strong></a>.</p><p><strong>Metabolome data</strong> is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS9929' rel='noopener noreferrer' target='_blank'><strong>MTBLS9929</strong></a>.</p>
Project description:<p>Parasites can manipulate host behavior to facilitate parasite transmission. One such host-pathogen interaction occurs between the fungus Ophiocordyceps sinensis (O. sinensis) and the ghost moth Thitarodes xiaojinensis. O. sinensis is involved in the mummification process of infected host larvae. However, the underlying molecular and chemical mechanism for this phenomenon is unknown. We characterized the small molecules regulating host behavior and the altered metabolites in infected and mummified host larvae. Lipid-related metabolites, such as phosphatidylcholine (PC) were identified in infected and mummified larvae. Decreased levels of the neurotransmitter acetylcholine (ACh) and elevated choline levels were observed in the brains of both the infected and mummified larvae. The aberrant activity of acetylcholinesterase (AChE) and relative mRNA expression of ACE2 (acetylcholinesterase) may mediate the altered transformation between ACh and choline, leading to the brain dysfunction of mummified larvae. Caspofungin treatment inhibited the mummification of infected larvae and the activity of AChE. These findings indicate the importance of ACh in the mummification of host larvae after O. sinensis infection.</p><p><br></p><p><strong>Metabolome data</strong> is reported in the current study <a href='https://www.ebi.ac.uk/metabolights/MTBLS9929' rel='noopener noreferrer' target='_blank'><strong>MTBLS9929</strong></a>.</p><p><strong>Lipidome data</strong> is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS9930' rel='noopener noreferrer' target='_blank'><strong>MTBLS9930</strong></a>.</p>
2024-08-05 | MTBLS9929 | MetaboLights
Project description:Gut microbiota on Tibetan plateau and low-altitude aritificial rearing ghost moth
Project description:Recurring genetic abnormalities have been identified in Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL). Among them, IKZF1 deletion was associated with poor prognosis in patients treated with imatinib-based or dasatinib-based regimens. However, the molecular determinants for clinical outcomes in ponatinib-treated patients remain unknown. We systematically analyzed genetic alterations in adults with Ph-positive ALL uniformly treated in clinical trials with dasatinib-based regimens or a ponatinib-based regimen and investigated the molecular determinants for treatment outcomes using pretreatment specimens collected from adults with Ph-positive ALL treated with Hyper-CVAD plus dasatinib or ponatinib. DNA sequencing and SNP microarray were performed and recurrent genetic abnormalities were found in 84% of the patients, among whom IKZF1 deletion was most frequently detected (60%). IKZF1 deletion frequently co-occurred with other copy-number abnormalities (IKZF1plus, 46%) and was significantly associated with unfavorable overall survival (OS) (false discovery rate < 0.1) and increased cumulative incidence of relapse (p = 0.01). In a multivariate analysis, dasatinib therapy, lack of achievement of 3-month complete molecular response, and the presence of IKZF1plus status were significantly associated with poor OS. The differential impact of IKZF1plus was largely restricted to patients given Hyper-CVAD plus ponatinib; dasatinib-based regimens had unfavorable outcomes regardless of the molecular abnormalities.
Project description:Recurring genetic abnormalities have been identified in Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL). Among them, IKZF1 deletion was associated with poor prognosis in patients treated with imatinib-based or dasatinib-based regimens. However, the molecular determinants for clinical outcomes in ponatinib-treated patients remain unknown. We systematically analyzed genetic alterations in adults with Ph-positive ALL uniformly treated in clinical trials with dasatinib-based regimens or a ponatinib-based regimen and investigated the molecular determinants for treatment outcomes using pretreatment specimens collected from adults with Ph-positive ALL treated with Hyper-CVAD plus dasatinib or ponatinib. DNA sequencing and SNP microarray were performed and recurrent genetic abnormalities were found in 84% of the patients, among whom IKZF1 deletion was most frequently detected (60%). IKZF1 deletion frequently co-occurred with other copy-number abnormalities (IKZF1plus, 46%) and was significantly associated with unfavorable overall survival (OS) (false discovery rate < 0.1) and increased cumulative incidence of relapse (p = 0.01). In a multivariate analysis, dasatinib therapy, lack of achievement of 3-month complete molecular response, and the presence of IKZF1plus status were significantly associated with poor OS. The differential impact of IKZF1plus was largely restricted to patients given Hyper-CVAD plus ponatinib; dasatinib-based regimens had unfavorable outcomes regardless of the molecular abnormalities.