Comprehensive MicroRNAome Analysis of the Relationship Between Alzheimer Disease and Cancer in Double-Knockout Mice

Purpose Presenilins are functionally important components of γ-secretase, which cleaves a number of transmembrane proteins. Manipulations of PSEN1 and PSEN2 have been separately studied in Alzheimer disease (AD) and cancer because both involve substrates of γ-secretase. However, numerous clinical studies have reported an inverse correlation between AD and cancer. Interestingly, AD is a neurodegenerative disorder, whereas cancer is characterized by the proliferation of malignant cells. However, this inverse correlation in the PSEN double-knockout (PSEN dKO) mouse model of AD has been not elucidated, although doing so would shed light onto the relationship between AD and cancer. Methods To investigate the inverse relationship of AD and cancer under conditions of PSEN loss, we used the hippocampus of 7-month-old and 18-month-old PSEN dKO mice for a microRNA (miRNA) microarray analysis, and explored the tumorsuppressive or oncogenic role of differentially-expressed miRNAs. Results The total number of miRNAs that showed changes in expression level was greater at 18 months of age than at 7 months. Most of the putative target genes of the differentially-expressed miRNAs involved Cancer pathways. Conclusions Based on literature reviews, many of the miRNAs involved in Cancer pathways were found to be known tumorsuppressive miRNAs, and their target genes were known or putative oncogenes. In conclusion, the expression levels of known tumor-suppressive miRNAs increased at 7 and 18 months, in the PSEN dKO mouse model of AD, supporting the negative correlation between AD and cancer

Three Cases of Descemet's Membrane Detachment after Cataract Surgery

Descemet's membrane detachment (DMD) is an uncommon condition with a wide range of etiologies. More than likely, the most common cause is a localized detachment occurring after cataract surgery. We report three cases of Descemet's membrane detachment that occurred after uncomplicated phacoemulsification cataract surgeries. The first patient was managed without surgical intervention, the second patient was treated using an intracameral air injection, and the last patient was treated with an intracameral perfluoropropane (C3F8) gas injection. All three patients recovered their vision following the reattachment of Descemet's membrane. The three patients were treated according to the extent of the detachment

Natural Form of Noncytolytic Flexible Human Fc as a Long-Acting Carrier of Agonistic Ligand, Erythropoietin

Human IgG1 Fc has been widely used as a bioconjugate, but exhibits shortcomings, such as antibody- and complement-mediated cytotoxicity as well as decreased bioactivity, when applied to agonistic proteins. Here, we constructed a nonimmunogenic, noncytolytic and flexible hybrid Fc (hyFc) consisting of IgD and IgG4, and tested its function using erythropoietin (EPO) conjugate, EPO-hyFc. Despite low amino acid homology (20.5%) between IgD Fc and IgG4 Fc, EPO-hyFc retained “Y-shaped” structure and repeated intravenous administrations of EPO-hyFc into monkeys did not generate EPO-hyFc-specific antibody responses. Furthermore, EPO-hyFc could not bind to FcγR I and C1q in contrast to EPO-IgG1 Fc. In addition, EPO-hyFc exhibited better in vitro bioactivity and in vivo bioactivity in rats than EPO-IgG1 Fc, presumably due to the high flexibility of IgD. Moreover, the mean serum half-life of EPO-hyFc(H), a high sialic acid content form of EPO-hyFc, was approximately 2-fold longer than that of the heavily glycosylated EPO, darbepoetin alfa, in rats. More importantly, subcutaneous injection of EPO-hyFc(H) not only induced a significantly greater elevation of serum hemoglobin levels than darbepoetin alfa in both normal rats and cisplatin-induced anemic rats, but also displayed a delayed time to maximal serum level and twice final area-under-the-curve (AUClast). Taken together, hyFc might be a more attractive Fc conjugate for agonistic proteins/peptides than IgG1 Fc due to its capability to elongate their half-lives without inducing host effector functions and hindering bioactivity of fused molecules. Additionally, a head-to-head comparison demonstrated that hyFc-fusion strategy more effectively improved the in vivo bioactivity of EPO than the hyperglycosylation approach

mRNA microarray within hippocampus and cortex brain regions of PSEN12 double knockout mice

The wild type and PSEN dKO mice were sacrificed at the ages of 7 and 18 months. The complete mouse brain structure was removed and immediately prepared by being frozen on dry ice. The cortex and hippocampus were dissected and stored at -80°C until RNA isolation. Total RNA was isolated using the Trizol reagent. Messenger RNA expression profiling was performed using Affymetrix Mouse Genome 430 2.0 array chip containing 764,885 probe sets from 28,132 genes (Ensembl) or from 19,734 putative full-length transcripts (GenBank and Ref Seq)

Data from: Comprehensive MicroRNAome analysis of the relationship between Alzheimer disease and cancer in PSEN double-knockout mice

Purpose: Presenilins are functionally important components of γ-secretase, which cleaves a number of transmembrane proteins. Manipulations of PSEN1 and PSEN2 have been separately studied in Alzheimer disease (AD) and cancer because both involve substrates of γ-secretase. However, numerous clinical studies have reported an inverse correlation between AD and cancer. Interestingly, AD is a neurodegenerative disorder, whereas cancer is characterized by the proliferation of malignant cells. However, this inverse correlation in the PSEN double-knockout (PSEN dKO) mouse model of AD has been not elucidated, although doing so would shed light onto the relationship between AD and cancer. Methods: To investigate the inverse relationship of AD and cancer under conditions of PSEN loss, we used the hippocampus of 7-month-old and 18-month-old PSEN dKO mice for a microRNA (miRNA) microarray analysis, and explored the tumorsuppressive or oncogenic role of differentially-expressed miRNAs. Results: The total number of miRNAs that showed changes in expression level was greater at 18 months of age than at 7 months. Most of the putative target genes of the differentially-expressed miRNAs involved Cancer pathways. Conclusions: Based on literature reviews, many of the miRNAs involved in Cancer pathways were found to be known tumorsuppressive miRNAs, and their target genes were known or putative oncogenes. In conclusion, the expression levels of known tumor-suppressive miRNAs increased at 7 and 18 months, in the PSEN dKO mouse model of AD, supporting the negative correlation between AD and cancer

Baicalein prevents 6-hydroxydopamine-induced dopaminergic dysfunction and lipid peroxidation in mice

The effects of baicalein on 6-hydroxydopamine (6-OHDA)-induced neurotoxicity were evaluated. Intracerebroventricularly (i.c.v.) injection of 6-OHDA was done to young mice. Baicalein was administered intraperitoneally 30 min before and 90 min after i.c.v. injection. Animals received further injection of bacalein daily for 3 consecutive days. Rotarod performance was assessed, tyrosine hydroxylase (TH) Western blotting was performed, and dopamine (DA) levels and peroxidation were determined. High dose of baicalein effectively improved rotarod performance and prevented the reduction of striatal DA levels and TH contents in the striatum and subtantia nigra (SN). In addition, lipid peroxidation level was decreased by baicalein at 3 and 7 days after 6-OHDA injection. These results showed that baicalein effectively prevents the 6-OHDA-induced dopaminergic dysfunction through an antioxidative action

1/f-Noise in AlGaN/GaN Nanowire Omega-FinFETs

International audienceThe low-frequency noise (LFN) characteristics of AlGaN/GaN FinFETs with omega-gate and combined two-dimensional electron gas (2DEG) and MOS conduction are investigated. It is found that LFN is dominated by carrier number fluctuations whatever the width of the fin. Charge trapping in narrow devices is one order of magnitude lower than in wide fin device. In narrow devices, the sidewall conduction prevails and the noise mainly stems from the carrier trapping in the sidewall Al2O3 gate dielectric. Instead, in wide fin devices, the top gate AlGaN/GaN HEMT structure dominates and the LFN is mostly governed by the carrier trapping in the GaN layer close to 2DEG channel

Performance enhancement of AlGaN/GaN nanochannel omega-FinFET

International audienceNovel AlGaN/GaN omega-shaped nanochannel FinFETs with fin width of 50 nm were successfully fabricated using TMAH lateral wet etching with ALD HfO2 sidewall spacer. This fin structure apparently exhibited the current spreading in the access region, which results in the suppression of the drain lag effect at high drain voltage and sharp switching performance with subthreshold swing of 57–65 mV/decade. Excellent on- and off-state state performances for the fabricated device prove that the omega-shaped gate structure not only exhibits excellent gate controllability, but also decouples the active nano-channel region from the underlying thick buffer. The proposed device is very promising candidate for high-performance device applications

Melatonin protects against neuronal damage induced by 3-nitropropionic acid in rat striatum

In this study, the protective effects of melatonin were evaluated against 3-nitropropionic acid (3-NP)-induced striatal neuronal damage in rats. Lesions were induced in the right striatum of Sprague-Dawley rats by stereotaxic injection with 3-NP and melatonin was intraperitoneally administered both 30 min before and 60 min after 3-NP injection. And rats continuously received melatonin daily for 3 days. As indicators of oxidative damage, lipid peroxidation and protein oxidation in the lesioned striatum were measured at 1 day after 3-NP injection. Levels of malondialdehyde (MDA) and protein carbonyl were significantly increased by 3-NP injection, but reduced in the melatonin-treated rats. Four days post-lesion, large lesions and extensive neuronal damage were produced in the 3-NP-injected striata, as revealed by 2,3,5-triphenyltetrazolium chloride (TTC) staining. In addition, marked ipsilateral rotational behavior following apomorphine challenge and a decrease of dopamine content in the lesioned striatum were observed in the 3-NP-injected rats. However, melatonin treatment significantly attenuated the 3-NP-induced neuronal damage, reduced the degree of asymmetric rotational behavior, and restored the dopamine level in the lesioned striatum. The present results indicate that melatonin effectively protects against the neuronal damage caused by 3-NP in vivo and that the neuroprotective effects of melatonin may be related to antioxidant action