L-3, 4-dihydroxyphenylalanine (L-dopa) is the gold standard for symptomatic treatment of Parkinson's disease (PD), but long-term therapy is associated with the emergence of L-dopa-induced dyskinesia (LID). In the present study, L-dopa and benserazide were loaded by poly (lactic-co-glycolic acid) microspheres (LBM), which can release levodopa and benserazide in a sustained manner in order to continuous stimulate dopaminergic receptors. We investigated the role of striatal DR1/PKA/P-tau signal transduction in the molecular event underlying LID in the 6-OHDA-lesioned rat model of PD. We found that animals rendered dyskinetic by L-dopa treatment, administration of LBM prevented the severity of AIM score, as well as improvement in motor function. Moreover, we also showed L-dopa elicits profound alterations in the activity of three LID molecular markers, namely DR1/PKA/P-tau (ser396). These modifications are totally prevented by LBM treatment, a similar way to achieve continuous dopaminergic delivery (CDD). In conclusion, our experiments provided evidence that intermittent administration of L-dopa, but not continuous delivery, and DR1/PKA/p-tau (ser396) activation played a critical role in the molecular and behavioural induction of LID in 6-OHDA-lesioned rats. In addition, LBM treatment prevented the development of LID by inhibiting the expression of DR1/PKA/p-tau, as well as PPEB mRNA in dyskintic rats.

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Bark beetles and their associated fungi, which cause forest decline and sometimes high mortality in large areas around the world, are of increasing concern in terms of forest health. ThreeTomicusspp. (T.brevipilosus,T.minorandT.yunnanensis) infect branches and trunks ofPinusyunnanensisandP.kesiyain Yunnan Province, in south-western China.Tomicusspp. are well known as vectors of ophiostomatoid fungi and their co-occurrence could result in serious ecological and economic impact on local forest ecosystems. Nonetheless, knowledge about their diversity, ecology, including pathogenicity and potential economic importance is still quite rudimentary. Therefore, an extensive survey of ophiostomatoid fungi associated with theseTomicusspecies infestingP.yunnanensisandP.kesiyawas carried out in Yunnan. Seven hundred and seventy-two strains of ophiostomatoid fungi were isolated from the adult beetles and their galleries. The strains were identified based on comparisons of multiple DNA sequences, including the nuclear ribosomal large subunit (LSU) region, the internal transcribed spacer regions 1 and 2, together with the intervening 5.8S gene (ITS) and the partial genes of β-tubulin (TUB2), elongation factor 1α (TEF1-α) and calmodulin (CAL). Phylogenetic analyses were performed using maximum parsimony (MP) as well as maximum likelihood (ML). Combinations of culture features, morphological characters and temperature-dependent growth rates were also employed for species identification. Eleven species belonging to five genera were identified. These included six known species,Esteyavermicola,Leptographiumyunnanense,Ophiostomabrevipilosi,O.canum,O.minusandO.tingensand four novel taxa, described asGraphilbumanningense,O.aggregatum,SporothrixpseudoabietinaandS.macroconidia. A residual strain was left unidentified asOphiostomasp. 1. The overall ophiostomatoid community was by far dominated by three species, representing 87.3% of the total isolates; in decreasing order, these wereO.canum,O.brevipilosiandO.minus. Furthermore, the ophiostomatoid community of each beetle, although harbouring a diversity of ophiostomatoid species, was differentially dominated by a single fungal species;Ophiostomacanumwas preferentially associated with and dominated the ophiostomatoid community ofT.minor, whereasO.brevipilosiandO.minuswere exclusively associated with and dominated the ophiostomatoid communities ofT.brevipilosusandT.yunnanensis, respectively. Eight additional species, representing the remaining 12.7% of the total isolates, were marginal or sporadic. These results suggested that sympatricTomicuspopulations are dominated by distinct species showing some level of specificity or even exclusivity.

Hauser's engraver beetle, Ips hauseri, is a serious pest in spruce forest ecosystems in Central Asia. Its monoterpenoid signal production, transcriptome responses and potential regulatory mechanisms remain poorly understood. The quality and quantity of volatile metabolites in hindgut extracts of I. hauseri were found to differ between males and females and among three groups: beetles that were newly emerged, those with a topical application of juvenile hormone III (JHIII) and those that had been feeding for 24 h. Feeding males definitively dominated monoterpenoid signal production in I. hauseri, which uses (4S)-(−)-ipsenol and (S)-(−)-cis-verbenol to implement reproductive segregation from Ipstypographus and Ipsshangrila. Feeding stimulation induced higher expression of most genes related to the biosynthesis of (4S)-(−)-ipsenol than JHIII induction, and showed a male-specific mode in I. hauseri. JHIII stimulated males to produce large amounts of (−)-verbenone and also upregulated the expression of several CYP6 genes, to a greater extent in males than in females. The expression of genes involved in the metabolism of JHIII in females and males was also found to be upregulated. Our results indicate that a species-specific aggregation pheromone system for I. hauseri, consisting of (4S)-(−)-ipsenol and S-(−)-cis-verbenol, can be used to monitor population dynamics or mass trap killing. Our results also enable a better understanding of the bottom-up role of feeding behaviors in mediating population reproduction/aggregation and interspecific interactions.