The association between urinary Alzheimer-associated neuronal thread protein and cognitive impairment in late-life depression: A controlled pilot study

Accumulation of tau protein is associated with both Alzheimer’s disease (AD) and late-life depression (LLD). Alzheimer-associated neuronal thread protein (AD7c-NTP), which is closely linked with the tau protein, is elevated in the cerebrospinal fluid and urine of AD patients. This study examined the association between urinary AD7c-NTP and late-life depression with cognitive impairment. One hundred and thirty-eight subjects were recruited into late-life depression with cognitive impairment (LLD-CI, n=52), late-life depression without cognitive impairment (LLD-NCI, n=29), AD (n=27), and healthy control (HC, n=30) groups. The level of urinary AD7c-NTP was measured using the enzyme-linked immunosorbent assay method. The Montreal Cognitive Assessment scale (MoCA), Hamilton Rating Scale for Depression (HRSD) and Hamilton Anxiety Rating Scale (HAMA) were used to assess cognitive functions and depressive and anxiety symptoms in the AD and LLD groups. Urinary levels of AD7c-NTP in the LLD-CI group (1.0±0.7ng/ml) were significantly higher than both the LLD-NCI (0.5±0.3ng/ml) and HC groups (0.5±0.3ng/ml), but lower than in the AD group (1.6±1.7 ng/ml). No significant associations were found in the level of urinary AD7c-NTP in relation to age, gender, education and MoCA in the LLD-CI group. The level of urinary AD7c-NTP appears to be associated with cognitive impairment in late-life depression and may be a potential biomarker for early identification of cognitive impairment in LLD

Tissue inhibitor of metalloproteinases-3 mediates the death of immature oligodendrocytes via TNF-α/TACE in focal cerebral ischemia in mice

Abstract Background and Purpose Oligodendrocyte (OL) death is important in focal cerebral ischemia. TIMP-3 promotes apoptosis in ischemic neurons by inhibiting proteolysis of TNF-α superfamily of death receptors. Since OLs undergo apoptosis during ischemia, we hypothesized that TIMP-3 contributes to OL death. Methods Middle cerebral artery occlusion (MCAO) was induced in Timp-3 knockout (KO) and wild type (WT) mice with 24 or 72 h of reperfusion. Cell death in white matter was investigated by stereology and TUNEL. Mature or immature OLs were identified using antibodies against glutathione S-transferase-π (GST-π) and galactocerebroside (GalC), respectively. Expression and level of proteins were examined using immunohistochemistry and immunoblotting. Protein activities were determined using a FRET peptide. Results Loss of OL-like cells was detected at 72 h only in WT ischemic white matter where TUNEL showed greater cell death. TIMP-3 expression was increased in WT reactive astrocytes. GST-π was reduced in ischemic white matter of WT mice compared with WT shams with no difference between KO and WT at 72 h. GalC level was significantly increased in both KO and WT ischemic white matter at 72 h. However, the increase in GalC in KO mice was significantly higher than WT; most TUNEL-positive cells in ischemic white matter expressed GalC, suggesting TIMP-3 deficiency protects the immature OLs from apoptosis. There were significantly higher levels of cleaved caspase-3 at 72 h in WT white matter than in KO. Greater expression of MMP-3 and -9 was seen in reactive astrocytes and/or microglia/macrophages in WT at 72 h. We found more microglia/macrophages in WT than in KO, which were the predominant source of increased TNF-α detected in the ischemic white matter. TACE activity was significantly increased in ischemic WT white matter, which was expressed in active microglia/macrophages and OLs. Conclusions Our results suggested that focal ischemia leads to proliferation of immature OLs in white matter and that TIMP-3 contributes to a caspase-3-dependent immature OL death via TNF-α-mediated neuroinflammation. Future studies will be needed to delineate the role of MMP-3 and MMP-9 that were increased in the Timp-3 wild type

Effects of charge doping and constrained magnetization on the electronic structure of an FeSe monolayer

The electronic structural properties in the presence of constrained magnetization and a charged background are studied for a monolayer of FeSe in non-magnetic, checkerboard-, and striped-antiferromagnetic (AFM) spin configurations. First principles techniques based on the pseudopotential density functional approach and the local spin density approximation are utilized. Our findings show that the experimentally observed shape of the Fermi surface is best described by the checkerboard AFM spin pattern. To explore the underlying pairing mechanism, we study the evolution of the non-magnetic to the AFM-ordered structures under constrained magnetization. We estimate the strength of electronic coupling to magnetic excitations involving an increase in local moment and, separately, a partial moment transfer from one Fe atom to another. We also show that the charge doping in the FeSe can lead to an increase in the density of states at the Fermi level and possibly produce higher superconducting transition temperatures

Orientation Effects in Ballistic High-Strained P-type Si Nanowire FETs

In order to design and optimize high-sensitivity silicon nanowire-field-effect transistor (SiNW FET) pressure sensors, this paper investigates the effects of channel orientations and the uniaxial stress on the ballistic hole transport properties of a strongly quantized SiNW FET placed near the high stress regions of the pressure sensors. A discrete stress-dependent six-band k.p method is used for subband structure calculation, coupled to a two-dimensional Poisson solver for electrostatics. A semi-classical ballistic FET model is then used to evaluate the ballistic current-voltage characteristics of SiNW FETs with and without strain. Our results presented here indicate that [110] is the optimum orientation for the p-type SiNW FETs and sensors. For the ultra-scaled 2.2 nm square SiNW, due to the limit of strong quantum confinement, the effect of the uniaxial stress on the magnitude of ballistic drive current is too small to be considered, except for the [100] orientation. However, for larger 5 nm square SiNW transistors with various transport orientations, the uniaxial tensile stress obviously alters the ballistic performance, while the uniaxial compressive stress slightly changes the ballistic hole current. Furthermore, the competition of injection velocity and carrier density related to the effective hole masses is found to play a critical role in determining the performance of the nanotransistors

The GB Virus C (GBV-C) NS3 Serine Protease Inhibits HIV-1 Replication in a CD4+ T Lymphocyte Cell Line without Decreasing HIV Receptor Expression

Introduction: Persistent infection with GBV-C (GB Virus C), a non-pathogenic virus related to hepatitis C virus (HCV), prolongs survival in HIV infection. Two GBV-C proteins, NS5A and E2, have been shown previously to inhibit HIV replication in vitro. We investigated whether the GBV-C NS3 serine protease affects HIV replication. Results: GBV-C NS3 protease expressed in a human CD4+ T lymphocyte cell line significantly inhibited HIV replication. Addition of NS4A or NS4A/4B coding sequence to GBV-C NS3 increased the effect on HIV replication. Inhibition of HI

Longer telomere length in peripheral white blood cells is associated with risk of lung cancer and the rs2736100 (CLPTM1L-TERT) polymorphism in a prospective cohort study among women in China.

A recent genome-wide association study of lung cancer among never-smoking females in Asia demonstrated that the rs2736100 polymorphism in the TERT-CLPTM1L locus on chromosome 5p15.33 was strongly and significantly associated with risk of adenocarcinoma of the lung. The telomerase gene TERT is a reverse transcriptase that is critical for telomere replication and stabilization by controlling telomere length. We previously found that longer telomere length measured in peripheral white blood cell DNA was associated with increased risk of lung cancer in a prospective cohort study of smoking males in Finland. To follow up on this finding, we carried out a nested case-control study of 215 female lung cancer cases and 215 female controls, 94% of whom were never-smokers, in the prospective Shanghai Women's Health Study cohort. There was a dose-response relationship between tertiles of telomere length and risk of lung cancer (odds ratio (OR), 95% confidence interval [CI]: 1.0, 1.4 [0.8-2.5], and 2.2 [1.2-4.0], respectively; P trend = 0.003). Further, the association was unchanged by the length of time from blood collection to case diagnosis. In addition, the rs2736100 G allele, which we previously have shown to be associated with risk of lung cancer in this cohort, was significantly associated with longer telomere length in these same study subjects (P trend = 0.030). Our findings suggest that individuals with longer telomere length in peripheral white blood cells may have an increased risk of lung cancer, but require replication in additional prospective cohorts and populations

Photonic chip-based low noise microwave oscillator

Numerous modern technologies are reliant on the low-phase noise and exquisite timing stability of microwave signals. Substantial progress has been made in the field of microwave photonics, whereby low noise microwave signals are generated by the down-conversion of ultra-stable optical references using a frequency comb. Such systems, however, are constructed with bulk or fiber optics and are difficult to further reduce in size and power consumption. Our work addresses this challenge by leveraging advances in integrated photonics to demonstrate low-noise microwave generation via two-point optical frequency division. Narrow linewidth self-injection locked integrated lasers are stabilized to a miniature Fabry-P\'{e}rot cavity, and the frequency gap between the lasers is divided with an efficient dark-soliton frequency comb. The stabilized output of the microcomb is photodetected to produce a microwave signal at 20 GHz with phase noise of -96 dBc/Hz at 100 Hz offset frequency that decreases to -135 dBc/Hz at 10 kHz offset--values which are unprecedented for an integrated photonic system. All photonic components can be heterogeneously integrated on a single chip, providing a significant advance for the application of photonics to high-precision navigation, communication and timing systems

How to design high quality acupuncture trials—a consensus informed by evidence

An international panel including patients, clinicians, researchers, acupuncture and surgery trialists, statisticians, and experts in clinical epidemiology and methodology have developed new guidance for randomised controlled trials in acupuncture. It addresses the most prevalent and critical concerns of current acupuncture trials and will help funding agencies, trial registers, and journal editors to evaluate the relevance, importance, and quality of submitted trial proposals and completed trial