Chronic brain hypoperfusion (CBH) is a common clinical feature of Alzheimer's disease and vascular dementia, but the underlying molecular mechanism is unclear. Our previous study reported that the down-regulation of promotes amyloidogenesis via regulation of amyloid precursor protein and b-site amyloid precursor protein cleaving enzyme 1 (BACE1) expression at the post-transcriptional level in CBH rats with bilateral common carotid artery occlusion (2VO). CBH owing to unilateral common carotid artery occlusion (UCCAO) increases tau phosphorylation levels at multiple phosphorylation sites in the brain, but the molecular mechanism is poorly understood. The purpose of this study was to investigate whether miR-195 could both deregulate amyloid metabolism and indirectly deregulate tau phosphorylation in CBH. We observed that 2VO leads to tau hyperphosphorylation at Ser202/Thr205, Ser262, Thr231, and Ser422 and to the conversion from cyclin-dependent kinase 5 (Cdk5)/ p35 to Cdk5/p25 in rat hippocampi. Endogenous miR-195 was knocked down using over-expression of its antisense molecule (pre-AMO-miR-195) via a lentivirus (lenti-pre-AMO-miR-195); this knockdown increased the tau phosphorylation at Ser202/ Thr205, Ser262, Thr231, Ser422, and the Cdk5/p25 activation, but over-expression of miR-195 using lenti-pre-miR-195 decreased the tau phosphorylation and Cdk5/p25 activation. Further in vitro studies demonstrated that miR-195 overexpression prevented tau hyperphosphorylation and Cdk5/p35 activity, which were increased by miR-195 inhibition. A dual luciferase reporter assay showed that miR-195 bound to the Cdk5r1 gene, which encodes p35 protein, in the 3 0 UTR and inhibited p35 expression. We concluded that tau hyperphosphorylation involves the down-regulation of miR-195, which is mediated by Cdk5/p25 activation in 2VO rats. Our findings demonstrated that down-regulation of miR-195 led to increased vulnerability via the regulation of multiple targets.

No abstract

a b s t r a c t Selenium (Se) is one of contaminants required to be regulated during drinking water treatment, however, little information has been collected to date regarding Se removal by coagulation. In this study, the performance of Se removal by coagulation has been evaluated with respect to the dependence on Se species, coagulant type, water pH and interfering ions. The results showed that a Fe-based coagulant was much more efficient than Al-based coagulants in Se removal. The removal of selenite (Se(IV)) by coagulation was much more pronounced than that of selenate (Se(VI)). With an FC dosage of more than 0.4 mM Fe/L, Se(IV) removal efficiency of more than 98% could be achieved when the initial Se(IV) concentration was 250 lg/L. For Al-based coagulants (AlCl 3 (AC) and polyaluminum chloride (PACl)) Se removal efficiency was positively correlated with the content of Al 13 species during the coagulation process. Adsorption onto hydroxide flocs was the most active coagulation mechanism for Se removal and precipitation also played specific roles at low dosage, especially for Se(IV) removal and with Fe coagulant. High coagulant dosage and weakly acidic pH could enhance the formation of hydroxide flocs having more active adsorption sites and high zeta potential, and thus favored Se removal. These findings are important to understand the efficiency and mechanisms of Se removal by coagulation.

No abstract

No abstract

Adeno-associated viruses are members of the genus dependoviruses of the parvoviridae family. AAV vectors are considered promising vectors for gene therapy and genetic vaccination as they can be easily produced, are highly stable and non-pathogenic. Nevertheless, transduction of cells in vitro and in vivo by AAV in the absence of a helper virus is comparatively inefficient requiring high multiplicity of infection. Several bottlenecks for AAV transduction have previously been described, including release from endosomes, nuclear transport and conversion of the single stranded DNA into a double stranded molecule. We hypothesized that the bottlenecks in AAV transduction are, in part, due to the presence of host cell restriction factors acting directly or indirectly on the AAV-mediated gene transduction. In order to identify such factors we performed a whole genome siRNA screen which identified a number of putative genes interfering with AAV gene transduction. A number of factors, yielding the highest scores, were identified as members of the SUMOylation pathway. We identified Ubc9, the E2 conjugating enzyme as well as Sae1 and Sae2, enzymes responsible for activating E1, as factors involved in restricting AAV. The restriction effect, mediated by these factors, was validated and reproduced independently. Our data indicate that SUMOylation targets entry of AAV capsids and not downstream processes of uncoating, including DNA single strand conversion or DNA damage signaling. We suggest that transiently targeting SUMOylation will enhance application of AAV in vitro and in vivo.

A bola-type supra-amphiphile assembled from a water-soluble pillar[5]arene host (WP5) and a rod-coil guest molecule (G) containing a photoactive 9,10-dialkoxyanthracene group was successfully constructed, which could further assemble into a monolayer supramolecular vesicle. Interestingly, the photodecomposition rate of G was remarkably promoted after its aggregation with WP5, accompanied by the disassembly of the formed supramolecular vesicle, especially with the coassembly of a photosensitizer eosin Y, which has potential applications in phototherapy.

A rotor-based fluorescent probe to label exosomes in living cells.