The microRNA-455 Null Mouse Has Memory Deficit and Increased Anxiety,Targeting Key Genes Involved in Alzheimer’s Disease

The complete molecular mechanisms underlying the pathophysiology of Alzheimer’s disease (AD) remain to be elucidated. Recently, microRNA-455-3p has been identified as a circulating biomarker of early AD, with increased expression in post-mortem brain tissue of AD patients. MicroRNA-455-3p also directly targets and down-regulates APP, with the overexpression of miR-455-3p suppressing its toxic effects. Here, we show that miR-455-3p expression decreases with age in the brains of wild-type mice. We generated a miR-455 null mouse utilising CRISPR-Cas9 to explore its function further. Loss of miR-455 resulted in increased weight gain, potentially indicative of metabolic disturbances. Furthermore, performance on the novel object recognition task diminished significantly in miR-455 null mice (p = 0.004), indicating deficits in recognition memory. A slight increase in anxiety was also captured on the open field test. BACE1 and TAU were identified as new direct targets for miR-455-3p, with overexpression of miR-455-3p leading to a reduction in the expression of APP, BACE1 and TAU in neuroblastoma cells. In the hippocampus of miR-455 null mice at 14 months of age, the levels of protein for APP, BACE1 and TAU were all increased. Such findings reinforce the involvement of miR-455 in AD progression and demonstrate its action on cognitive performance.     

Inhaled PYY(3–36) dry-powder formulation for appetite suppression

Objective: Peptide YY3–36 [PYY(3–36)] has shown efficacy in appetite suppression when dosed by injection modalities (intraperitoneal (IP)/subcutaneous). Transitioning to needle-free delivery, towards inhalation, often utilizes systemic pharmacokinetics as a key endpoint to compare different delivery methods and doses. Systemic pharmacokinetics were evaluated for PYY3–36 when delivered by IP, subcutaneous, and inhalation, the systemic pharmacokinetics were then used to select doses in an appetite suppression pharmacodynamic study.

Methods: Dry-powder formulations were manufactured by spray drying and delivered to mice via nose only inhalation. The systemic plasma, lung tissue, and bronchoalveolar lavage fluid pharmacokinetics of different inhalation doses of PYY(3–36) were compared to IP and subcutaneous efficacious doses. Based on these pharmacokinetic data, inhalation doses of 70:30 PYY(3–36):Dextran T10 were evaluated in a mouse model of appetite suppression and compared to IP and subcutaneous data.

Results: Inhalation pharmacokinetic studies showed that plasma exposure was similar for a 2?×?higher inhalation dose when compared to subcutaneous and IP delivery. Inhalation doses of 0.22 and 0.65?mg/kg were for efficacy studies. The results showed a dose-dependent (not dose proportional) decrease in food consumption over 4?h, which is similar to IP and subcutaneous delivery routes.

Conclusions: The pharmacokinetic and pharmacodynamics results substantiate the ability of pharmacokinetic data to inform pharmacodynamics dose selection for inhalation delivery of the peptide PYY(3–36). Additionally, engineered PYY(3–36):Dextran T10 particles delivered to the respiratory tract show promise as a non-invasive therapeutic for appetite suppression.     

中央通过《关于设立知识产权法院的方案》

6月6日，中央全面深化改革领导小组第三次会议召开，会议审议通过了“关于设立知识产权法院的方案》等方案。     

Seasonal bacterial community dynamics in a full-scale enhanced biological phosphorus removal plant

Activated sludge is one of the most abundant and effective wastewater treatment process used to treat wastewater, and has been used in developed countries for nearly a century. In all that time, several hundreds of studies have explored the bacterial communities responsible for treatment, but most studies were based on a handful of samples and did not consider temporal dynamics. In this study, we used the DNA fingerprinting technique called automated ribosomal intergenic spacer region analysis (ARISA) to study bacterial community dynamics over a two-year period in two different treatment trains. We also used quantitative PCR to measure the variation of five phylogenetically-defined clades within the Accumulibacter lineage, which is a model polyphosphate accumulating organism. The total bacterial community exhibited seasonal patterns of change reminiscent of those observed in lakes and oceans. Surprisingly, all five Accumulibacter clades were present throughout the study, and the total Accumulibacter community was relatively stable. However, the abundance of each clade did fluctuate through time. Clade IIA dynamics correlated positively with temperature (ρ = 0.65, p < 0.05) while Clade IA dynamics correlated negatively with temperature (ρ = −0.35, p < 0.05). This relationship with temperature hints at the mechanisms that may be driving the seasonal patterns in overall bacterial community dynamics and provides further evidence for ecological differentiation among clades within the Accumulibacter lineage. This work provides a valuable baseline for activated sludge bacterial community variation.     

Technology adoption as process: a case of integrating an information-intensive website into a patient education helpline

This study followed the introduction of the Arthritis Source website into the existing teaching practices of Arthritis Foundation Helpline volunteers. The goal was to examine what factors may affect a particular group of educators adopt a potentially valuable Internet tool into an existing instructional environment. Defining the possible uses of the website in reference to the volunteers' actual job duties helped provide a clearer understanding of how the volunteers might use this new technology. The researchers used qualitative techniques to focus on three volunteers who experienced different physical, environmental and cognitive means that impacted their use of the new tool. Each volunteer experienced varying levels of motivation in areas of learning, satisfaction and responses to outside influences. Each volunteer also had varying amounts of opportunity prompts in which to interact or refer the website. Consequently, Helpline volunteers experienced different rates of adopting the information-intensive website into their traditional work system.     

Retracted: Temperature affects flavour intensity and quality of aroma in fresh basil (Ocimum basilicum L.) leaves

Retraction: The following article from the Journal of the Science of Food and Agriculture , ‘Temperature affects flavour intensity and quality of aroma in fresh basil (Ocimum basilicum L.) leaves’ by Xianmin Chang, Peter G Alderson, Tracey A Hollowood, Louise Hewson, and Charles J Wright, published online on 19 October 2005 in Wiley InterScience (www.interscience.wiley.com), has been retracted by agreement between the authors, the journal Editor in Chief, David S. Reid and John Wiley & Sons, Ltd. The retraction has been agreed due to overlap between this article and the following article published in the The Journal of Horticultural Science & Biotechnology ; ‘Effect of temperature integration on the growth and volatile oil content of Basil (Ocimum basilicum L.)’ by Xianmin Chang, Peter G Alderson and Charles J Wright. Volume 80 Issue 5, 2005, pages 593 – 598     

Isolation of the third capsule-associated gene, CAP60, required for virulence in Cryptococcus neoformans

A polysaccharide capsule is one of the most important virulence factors for the pathogenic fungus Cryptococcus neoformans. We previously characterized two capsule-associated genes, CAP59 and CAP64. To further dissect the molecular mechanism of capsule synthesis, 16 acapsular mutants induced by 4-nitroquinoline-1-oxide were obtained. The acapsular phenotype of one of these mutants was complemented. The cloned gene was designated CAP60, and deletion of this newly described capsule-associated gene resulted in an acapsular phenotype. The proposed 67-kDa Cap60p contains 592 amino acids and appears to have a putative transmembrane domain close to the N terminus. DNA sequence analysis revealed that CAP60 has similarity to CAP59 at the center portion of its coding regions. Contour-clamped homogeneous electric field blot analysis suggested that these two genes are on the same chromosome. CAP60 and CAP59, however, could not be functionally substituted for each other by direct complementation or by domain swap experiments. In addition, CAP60 is closely linked to a gene which is similar to a cellulose growth-specific gene of Agaricus bisporus, CEL1. Immunogold electron microscopy studies of the epitope-tagged CAP60 gene revealed that Cap60p was primarily localized to the nuclear membrane. Animal model studies indicated that CAP60 is essential for virulence. Thus, CAP60 is required for both capsule formation and virulence.