Background and purpose
Previous studies suggested that the overall burden of prior infections contributes to cardiovascular diseases and stroke. In the present study, the association between ...infectious burden (IB) and Alzheimer's disease (AD) was examined.
Methods
Antibody titers to common infectious pathogens including cytomegalovirus (CMV), herpes simplex virus type 1 (HSV‐1), Borrelia burgdorferi, Chlamydophila pneumoniae and Helicobacter pylori were measured by enzyme‐linked immunosorbent assay in 128 AD patients and 135 healthy controls. IB was defined as a composite serological measure of exposure to these common pathogens.
Results
Seropositivities toward zero−two, three and four−five of these pathogens were found in 44%, 40% and 16% of healthy controls but in 20%, 44% and 36% of AD patients, respectively. IB, bacterial burden and viral burden were independently associated with AD after adjusting for age, gender, education, APOE genotype and various comorbidities. Mini‐Mental State Examination scores were negatively correlated with IB in all cases. Serum beta‐amyloid protein (Aβ) levels (i.e. Aβ40, Aβ42 and total Aβ) and inflammatory cytokines (i.e. interferon‐γ, tumor necrosis factor α, interleukin‐1β and interleukin‐6) in individuals exposed to four−five infectious pathogens were significantly higher than those exposed to zero−two or three pathogens.
Conclusions
IB consisting of CMV, HSV‐1, B. burgdorferi, C. pneumoniae and H. pylori is associated with AD. This study supports the role of infection/inflammation in the etiopathogenesis of AD.
Click here to view the accompanying paper in this issue. Videocasts of this article are available in: English: http://player.polyv.net/videos/player.swf?vid=f6ee5715d9808c7a481b7ae727da00dd_f Mandarin: http://player.polyv.net/videos/f6ee5715d98ae743a9b0509d0900c91f_f.swf
To evaluate a reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay for detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and compare it with RT-PCR.
...We designed primers specific to the orf1ab and S genes of SARS-CoV-2. Total viral RNA was extracted using the QIAamp Viral RNA Mini Kit. We optimized the RT-LAMP assay, and evaluated it for its sensitivity and specificity of detection using real-time turbidity monitoring and visual observation.
The primer sets orf1ab-4 and S-123 amplified the genes in the shortest times, the mean (±SD) times were 18 ± 1.32 min and 20 ± 1.80 min, respectively, and 63°C was the optimum reaction temperature. The sensitivities were 2 × 101 copies and 2 × 102 copies per reaction with primer sets orf1ab-4 and S-123, respectively. This assay showed no cross-reactivity with 60 other respiratory pathogens. To describe the availability of this method in clinical diagnosis, we collected 130 specimens from patients with clinically suspected SARS-CoV-2 infection. Among them, 58 were confirmed to be positive and 72 were negative by RT-LAMP. The sensitivity was 100% (95% CI 92.3%–100%), specificity 100% (95% CI 93.7%–100%). This assay detected SARS-CoV-2 in a mean (±SD) time of 26.28 ± 4.48 min and the results can be identified with visual observation.
These results demonstrate that we developed a rapid, simple, specific and sensitive RT-LAMP assay for SARS-CoV-2 detection among clinical samples. It will be a powerful tool for SARS-CoV-2 identification, and for monitoring suspected patients, close contacts and high-risk groups.
Kinetic‐scale magnetic dips (KSMDs), with a significant depression in magnetic field strength, and scale length close to and less than one proton gyroradius, were reported in the turbulent plasmas ...both in recent observation and numerical simulation studies. These KSMDs likely play important roles in energy conversion and dissipation. In this study, we present observations of the KSMDs that are labeled whistler mode waves, electrostatic solitary waves, and electron cyclotron waves in the magnetosheath. The observations suggest that electron temperature anisotropy or beams within KSMD structures provide free energy to generate these waves. In addition, the occurrence rates of the waves are higher in the center of the magnetic dips than at their edges, implying that the KSMDs might be the origin of various kinds of waves. We suggest that the KSMDs could provide favorable conditions for the generation of waves and transfer energy to the waves in turbulent magnetosheath plasmas.
Plain Language Summary
The Earth's magnetosheath is a turbulent plasma environment where energy conversion, particle acceleration, and mass and momentum transport take place. Many of these key processes involve kinetic‐scale physics. However, in‐depth studies from previous missions are limited by their lower spacecraft data resolution. The recent Magnetospheric Multiscale (MMS) mission provides us with a large amount of high‐temporal cadence data for studying kinetic‐scale physics in the magnetosheath. In this study, we report whistler mode waves, electrostatic solitary waves and electron cyclotron waves within kinetic‐scale magnetic dips (KSMDs) that can be generated in the turbulent magnetosheath. These waves could be excited by electron temperature anisotropy or beams. As is well known, plasma waves are important processes in converting energy, accelerating and scattering electrons and ions, and modifying the distributions of charged particles. If plasma instabilities develop within the KSMDs, the resulting waves could absorb free energy from plasma particles and may propagate out of the KSMDs. Thus, our discoveries could significantly advance the understanding of energy conversion and dissipation for kinetic‐scale turbulence. This study provides a new reference not only for observations in space physics but also for related basic plasma theories and numerical simulations.
Key Points
MMS observations reveal KSMDs coupled with whistler mode waves, electrostatic solitary waves, and electron cyclotron waves
These waves are excited by different plasma distributions, and the ESWs could affect the electron distributions in kinetic scale
Statistical results indicate that the KSMDs in the magnetosheath are a possible origin for various kinds of waves
Reduced expression of brain-derived neurotrophic factor (BDNF) has a crucial role in the pathogenesis of Alzheimer's disease (AD), which is characterized with the formation of neuritic plaques ...consisting of amyloid-beta (Aβ) and neurofibrillary tangles composed of hyperphosphorylated tau protein. A growing body of evidence indicates a potential protective effect of BDNF against Aβ-induced neurotoxicity in AD mouse models. However, the direct therapeutic effect of BDNF supplement on tauopathy in AD remains to be established. Here, we found that the BDNF level was reduced in the serum and brain of AD patients and P301L transgenic mice (a mouse model of tauopathy). Intralateral ventricle injection of adeno-associated virus carrying the gene encoding human BDNF (AAV-BDNF) achieved stable expression of BDNF gene and restored the BDNF level in the brains of P301L mice. Restoration of the BDNF level attenuated behavioral deficits, prevented neuron loss, alleviated synaptic degeneration and reduced neuronal abnormality, but did not affect tau hyperphosphorylation level in the brains of P301L mice. Long-term expression of AAV-BDNF in the brain was well tolerated by the mice. These findings suggest that the gene delivery of BDNF is a promising treatment for tau-related neurodegeneration for AD and other neurodegenerative disorders with tauopathy.
In Alzheimer's disease (AD), neurodegenerative signals such as amyloid-beta (Aβ) and the precursors of neurotrophins, outbalance neurotrophic signals, causing synaptic dysfunction and ...neurodegeneration. The neurotrophin receptor p75 (p75NTR) is a receptor of Aβ and mediates Aβ-induced neurodegenerative signals. The shedding of its ectodomain from the cell surface is physiologically regulated; however, the function of the diffusible p75NTR ectodomain (p75ECD) after shedding remains largely not known. Here, we show that p75ECD levels in cerebrospinal fluid and in the brains of Alzheimer's patients and amyloid-beta precursor protein (APP)/PS1 transgenic mice were significantly reduced, due to inhibition of the sheddase-tumor necrosis factor-alpha-converting enzyme by Aβ. Restoration of p75ECD to the normal level by brain delivery of the gene encoding human p75ECD before or after Aβ deposition in the brain of APP/PS1 mice reversed the behavioral deficits and AD-type pathologies, such as Aβ deposit, apoptotic events, neuroinflammation, Tau phosphorylation and loss of dendritic spine, neuronal structures and synaptic proteins. Furthermore, p75ECD can also reduce amyloidogenesis by suppressing β-secretase expression and activities. Our data demonstrate that p75ECD is a physiologically neuroprotective molecule against Aβ toxicity and would be a novel therapeutic target and biomarker for AD.
Covering: 2010 to 2014.
Advances in isolation, synthesis and screening strategies have made many bioactive substances available. However, in most cases their putative biological targets remain ...unknown. Herein, we highlight recent advances in target identification of natural products and bioactive compounds by using affinity-based probes. Aided by photoaffinity labelling, this strategy can capture potential cellular targets (on and off) of a natural product or bioactive compound in live cells directly, even when the compound-target interaction is reversible with moderate affinity. The knowledge of these targets may help uncover molecular pathways and new therapeutics for currently untreatable diseases. In this highlight, we will introduce the development of various photoactivatable groups, their synthesis and applications in target identification of natural products and bioactive compounds, with a focus on work done in recent years and from our laboratory. We will further discuss the strengths and weaknesses of each group and the outlooks for this novel proteome-wide profiling strategy.
Direct capture of drug-target complexes
in situ
by using affinity-based probes allows target identification of natural products and bioactive compounds, even if the binding is reversible with moderate affinity.
Cancer/testis (CT) antigens are protein antigens with normal expression restricted to adult testicular germ cells, and yet are aberrantly activated and expressed in a proportion of various types of ...human cancer. At least a subset of this group of antigens has been found to elicit spontaneous humoral and cell‐mediated immune responses in cancer patients, raising the possibility that these antigens could be cancer vaccine targets. More than 100 CT antigen genes have been reported in the literature, with approximately 30 being members of multigene families on the X chromosome, so‐called CT‐X genes. Most CT‐X genes are expressed at the spermatogonia stage of spermatogenesis, and their functions are mostly unknown. In cancer, the frequency of CT antigen expression is highly variable among different tumor types, but is more often expressed in high‐grade late‐stage cases in general. Cancer vaccine trials based on CT antigens MAGE‐A3 and NY‐ESO‐1 are currently ongoing, and these antigens may also play a role in antigen‐specific adoptive T‐cell transfer and in the immunomodulation approach of cancer therapy. (Cancer Sci 2009)
A grand challenge underlies the entire field of topology-enabled quantum logic and information science: how to establish topological control principles driven by quantum coherence and understand the ...time dependence of such periodic driving. Here we demonstrate a few-cycle THz-pulse-induced phase transition in a Dirac semimetalZrTe5that is periodically driven by vibrational coherence due to excitation of the lowest Raman active mode. Above a critical THz-pump field threshold, there emerges a long-lived metastable phase, approximately 100 ps, with unique Raman phonon-assisted topological switching dynamics absent for optical pumping. The switching also manifests itself by distinct features: nonthermal spectral shape, relaxation slowing near the Lifshitz transition where the critical Dirac point occurs, and diminishing signals at the same temperature that the Berry-curvature-induced anomalous Hall effect magnetoresistance vanishes. These results, together with first-principles modeling, identify a mode-selective Raman coupling that drives the system from strong to weak topological insulators with a Dirac semimetal phase established at a critical atomic displacement controlled by the phonon coherent pumping. Harnessing of vibrational coherence can be extended to steer symmetry-breaking transitions, i.e., Dirac to Weyl ones, with implications for THz topological quantum gate and error correction applications.
Hybrid organic–inorganic halide perovskite semiconductors are attractive candidates for optoelectronic applications, such as photovoltaics, light-emitting diodes, and lasers. Perovskite nanocrystals ...are of particular interest, where electrons and holes can be confined spatially, promoting radiative recombination. However, nanocrystalline films based on traditional colloidal nanocrystal synthesis strategies suffer from the use of long insulating ligands, low colloidal nanocrystal concentration, and significant aggregation during film formation. Here, we demonstrate a facile method for preparing perovskite nanocrystal films in situ and that the electroluminescence of light-emitting devices can be enhanced up to 40-fold through this nanocrystal film formation strategy. Briefly, the method involves the use of bulky organoammonium halides as additives to confine crystal growth of perovskites during film formation, achieving CH3NH3PbI3 and CH3NH3PbBr3 perovskite nanocrystals with an average crystal size of 5.4 ± 0.8 nm and 6.4 ± 1.3 nm, respectively, as confirmed through transmission electron microscopy measurements. Additive-confined perovskite nanocrystals show significantly improved photoluminescence quantum yield and decay lifetime. Finally, we demonstrate highly efficient CH3NH3PbI3 red/near-infrared LEDs and CH3NH3PbBr3 green LEDs based on this strategy, achieving an external quantum efficiency of 7.9% and 7.0%, respectively, which represent a 40-fold and 23-fold improvement over control devices fabricated without the additives.
A new inventory of air pollutant emissions in Asia in the year 2006 is developed to support the Intercontinental Chemical Transport Experiment-Phase B (INTEX-B) funded by the National Aeronautics and ...Space Administration (NASA). Emissions are estimated for all major anthropogenic sources, excluding biomass burning. We estimate total Asian anthropogenic emissions in the year 2006 as follows: 47.1 Tg SO2, 36.7 Tg NOx, 298.2 Tg CO, 54.6 Tg NMVOC, 29.2 Tg PM10, 22.2 Tg PM2.5, 2.97 Tg BC, and 6.57 Tg OC. We emphasize emissions from China because they dominate the Asia pollutant outflow to the Pacific and the increase of emissions from China since 2000 is of great concern. We have implemented a series of improved methodologies to gain a better understanding of emissions from China, including a detailed technology-based approach, a dynamic methodology representing rapid technology renewal, critical examination of energy statistics, and a new scheme of NMVOC speciation for model-ready emissions. We estimate China's anthropogenic emissions in the year 2006 to be as follows: 31.0 Tg SO2, 20.8 Tg NOx, 166.9 Tg CO, 23.2 Tg NMVOC, 18.2 Tg PM10, 13.3 Tg PM2.5, 1.8 Tg BC, and 3.2 Tg OC. We have also estimated 2001 emissions for China using the same methodology and found that all species show an increasing trend during 2001–2006: 36% increase for SO2, 55% for NOx, 18% for CO, 29% for VOC, 13% for PM10, and 14% for PM2.5, BC, and OC. Emissions are gridded at a resolution of 30 min×30 min and can be accessed at our web site (http://mic.greenresource.cn/intex-b2006).
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