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Alzheimer's disease (AD) is characterized by amyloid plaques and progressive cerebral atrophy. Here, we report FAM222A as a putative brain atrophy susceptibility gene. Our cross-phenotype association analysis of imaging genetics indicates a potential link between FAM222A and AD-related regional brain atrophy. The protein encoded by FAM222A is predominantly expressed in the CNS and is increased in brains of patients with AD and in an AD mouse model. It accumulates within amyloid deposits, physically interacts with amyloid-β (Aβ) via its N-terminal Aβ binding domain, and facilitates Aβ aggregation. Intracerebroventricular infusion or forced expression of this protein exacerbates neuroinflammation and cognitive dysfunction in an AD mouse model whereas ablation of this protein suppresses the formation of amyloid deposits, neuroinflammation and cognitive deficits in the AD mouse model. Our data support the pathological relevance of protein encoded by FAM222A in AD. In this study the authors identify a possible link between the gene FAM222A and brain atrophy. The protein it encodes is found to accumulate in plaques seen in Alzheimer's disease, and functional analysis suggests it interacts with amyloid-beta. [ABSTRACT FROM AUTHOR]

This image incorrectly showed the same sample as shown in the original Figure 4g, top row (A 1-42), under "0.5h". In the original version of the manuscript, the image shown in Figure 4g, bottom row (A 1-42 + rAggregatin), under "6h" was incorrect. [Extracted from the article]

Artemisinin, the endoperoxide sesquiterpene lactone, is an effective antimalarial drug isolated from the Chinese medicinal plant Artemisia annua L. Due to its effectiveness against multi-drug-resistant cerebral malaria, it becomes the essential components of the artemisinin-based combination therapies which are recommended by the World Health Organization as the preferred choice for malaria tropica treatments. To date, plant A. annua is still the main commercial source of artemisinin. Although semi-synthesis of artemisinin via artemisinic acid in yeast is feasible at present, another promising approach to reduce the price of artemisinin is using plant metabolic engineering to obtain a higher content of artemisinin in transgenic plants. In the past years, an Agrobacterium-mediated transformation system of A. annua has been established by which a number of genes related to artemisinin biosynthesis have been successfully transferred into A. annua plants. In this review, the progress on increasing artemisinin content in A. annua by transgenic approach and its future prospect are summarized and discussed. [ABSTRACT FROM AUTHOR]

Amorpha-4,11-diene synthase (ADS) is the first key enzyme of artemisinin biosynthetic pathway in Artemisia annua L. In this study, the promoter region of the ADS gene has been cloned and used to demonstrate the expression of GUS reporter gene in both glandular trichomes of A. annua and non-glandular trichomes of Arabidopsis thaliana following homologous and heterologous expression of ADS promoter- GUS fusion. Subsequently, 5′ sequential deletion analysis of the ADS promoter revealed that a short sequence, −350 upstream of the transcription start site, was sufficient for trichome-specific expression in A. thaliana and that the region from −350 to −300 contained essential elements for this observed specificity. However, frequencies of transgenic A. thaliana plants displaying trichome-specific expressions varied between different lines, and all the lines with deleted fragments of the ADS promoter showed lower frequencies than the line with full-length ADS promoter. Most lines with deleted ADS promoter- GUS fusions showed GUS expressions in the guard cells of stomata as well, which was not observed in A. thaliana plants transformed with the full-length ADS promoter. GUS activities varied among different transgenic lines as well, both in transiently transformed Nicotiana benthamiana and stably transformed A. thaliana, with promoter-deletion lines exhibiting higher GUS activities than the full-length ADS promoter line. [ABSTRACT FROM AUTHOR]

Artemisinin is widely used as an antimalarial drug around the world. Artemisinic aldehyde Δ11(13) reductase (DBR2) is a key enzyme which reduces artemisinic aldehyde to dihydroartemisinic aldehyde in the biosynthesis of artemisinin. In this study, two fragments encompassing a putative promoter of DBR2, designated as DBR2pro1 and DBR2pro2, were isolated using genomic DNA walking. The transcription start site and the putative cis-elements of each version of promoter were predicted using bioinformatic analysis. In order to study the function of the cloned promoter, Artemisia annua was transformed with β-glucuronidase (GUS) reporter gene driven by DBR2pro1 and DBR2pro2, respectively. GUS staining results demonstrated that both DBR2pro1 and DBR2pro2 were strongly expressed in glandular secretory trichomes (GSTs) of leaf primordia and flower buds, but were not obviously expressed in roots, stems, old leaves, and fully developed flowers, thus indicating that the two versions of promoter were functional and specifically expressed in GSTs. [ABSTRACT FROM AUTHOR]