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Accumulating evidence indicates that abnormal deposition of amyloid-b (Ab) peptide in the brain is responsible for endothelial cell damage and consequently leads to bloodbrain barrier (BBB) leakage. However, the mechanisms underlying BBB disruption are not well described. We employed an monolayer BBB model comprising bEnd.3 cell and found that BBB leakage was induced by treatment with Ab 1-42, and the levels of tight junction (TJ) scaffold proteins (ZO-1, Claudin-5, and Occludin) were decreased. Through comparisons of the effects of the different components of Ab 1-42 , including monomer (Ab 1-42 -Mono), oligomer (Ab 1-42 -Oligo), and fibril (Ab 1-42 -Fibril), our data confirmed that Ab 1-42 -Oligo is likely to be the most important damage factor that results in TJ damage and BBB leakage in Alzheimer's disease. We found that the incubation of bEnd.3 cells with Ab 1-42 significantly up-regulated the level of receptor for advanced glycation end-products (RAGE). Co-incubation of a polyclonal antibody to RAGE and Ab 1-42 -Oligo in bEnd.3 cells blocked RAGE suppression of Ab 1-42 -Oligo-induced alterations in TJ scaffold proteins and reversed Ab 1-42 -Oligoinduced up-regulation of RAGE, matrix metalloproteinase (MMP)-2, and MMP-9. Furthermore, we found that these effects induced by Ab 1-42 -Oligo treatment were effectively suppressed by knockdown of RAGE using small interfering RNA (siRNA) transfection. We also found that GM 6001, a broad-spectrum MMP inhibitor, partially reversed the Ab 1-42 -Oligo-induced inhibitor effects in bEnd.3 cells. Thus, these

A series of novel vanadium silicates with open-framework and microporous structures has been synthesized under mild hydrothermal conditions. Ten distinct framework types have been identified that all have structures based on cross-linking single silicate sheets with square pyramidal V(IV)O(5) units to give compounds with the general formula A(r)[(VO)(s)(Si(2)O(5))(p)(SiO(2))(q)].tH(2)O, where A is Na, K, Rb, Cs, or a combination. The vanadosilicate (VSH-n) structures have free channel diameters up to 6.5 A and show good thermal stability, absorption, and ion-exchange properties, suggesting their potential for technological applications as molecular sieves or in catalysis.

Aristolochia, a genus in the magnoliid order Piperales, has been famous for centuries for its highly specialized flowers and wide medicinal applications. Here, we present a new, high-quality genome sequence of Aristolochia fimbriata, a species that, similar to Amborella trichopoda, lacks further whole-genome duplications since the origin of extant angiosperms. As such, the A. fimbriata genome is an excellent reference for inferences of angiosperm genome evolution, enabling detection of two novel whole-genome duplications in Piperales and dating of previously reported whole-genome duplications in other magnoliids. Genomic comparisons between A. fimbriata and other angiosperms facilitated the identification of ancient genomic rearrangements suggesting the placement of magnoliids as sister to monocots, whereas phylogenetic inferences based on sequence data we compiled yielded ambiguous relationships. By identifying associated homologues and investigating their evolutionary histories and expression patterns, we revealed highly conserved floral developmental genes and their distinct downstream regulatory network that may contribute to the complex flower morphology in A. fimbriata. Finally, we elucidated the genetic basis underlying the biosynthesis of terpenoids and aristolochic acids in A. fimbriata.

A very good host: The guest acid molecules of hydrothermally synthesized [V(O)(bdc)](H2bdc)0.71 (bdc=benzenedicarboxylate) are removed to give high‐quality single crystals of [V(O)(bdc)] (1). On absorption of guest molecules from the liquid phase, 1 undergoes crystal‐to‐crystal transformations (aniline: 2; thiophene: 3; acetone: 4). Furthermore, complex 1 also selectively absorbs thiophene and dimethyl sulfide from methane.

Accumulating evidence supports a key role for Wnt signaling in the development of the central nervous system (CNS) during embryonic development and in the regulation of the structure and function of the adult brain. Alzheimer's disease (AD) is the most common form of senile dementia, which is characterized by β-amyloid (Aβ) deposition in specific brain regions. However, the molecular mechanism underlying AD pathology remains elusive. Dysfunctional Wnt signaling is associated with several diseases such as epilepsy, cancer, metabolic disease, and AD. Increasing evidence suggests that downregulation of Wnt signaling, induced by Aβ, is associated with disease progression of AD. More importantly, persistent activation of Wnt signaling through Wnt ligands, or inhibition of negative regulators of Wnt signaling, such as Dickkopf-1 (DKK-1) and glycogen synthase kinase-3β (GSK-3β) that are hyperactive in the disease state, is able to protect against Aβ toxicity and ameliorate cognitive performance in AD. Together, these data suggest that Wnt signaling might be a potential therapeutic target of AD. Here, we review recent studies related to the progression of AD where Wnt signaling might be relevant and participate in the development of the disease. Then, we focus on the potential relevance of manipulating the Wnt signaling pathway for the treatment of AD.

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