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.
Intestinal IgA, which is regulated by gut microbiota, has a crucial role in maintenance of intestinal homeostasis and in protecting the intestines from inflammation. However, the means by which ...microbiota promotes intestinal IgA responses remain unclear. Emerging evidence suggests that the host can sense gut bacterial metabolites in addition to pathogen-associated molecular patterns and that recognition of these small molecules influences host immune response in the intestines and beyond. We reported here that microbiota metabolite short-chain fatty acid acetate promoted intestinal IgA responses, which was mediated by "metabolite-sensing" GPR43. GPR43
mice demonstrated lower levels of intestinal IgA and IgA
gut bacteria compared with those in wild type (WT) mice. Feeding WT but not GPR43
mice acetate but not butyrate promoted intestinal IgA response independent of T cells. Acetate promoted B-cell IgA class switching and IgA production in vitro in the presence of WT but not GPR43
dendritic cells (DCs). Mechanistically, acetate-induced DC expression of Aldh1a2, which converts Vitamin A into its metabolite retinoic acid (RA). Moreover, blockade of RA signaling inhibited the acetate induction of B-cell IgA production. Our studies thus identified a new pathway by which microbiota promotes intestinal IgA response through its metabolites.
Summary
Sarcopenia was reported to be significantly associated with osteoporosis. In this study, we reported for the first time that sarcopenia was an independent risk predictor of osteoporotic ...vertebral compression refractures (OVCRFs). Other risk factors of OVCRFs are low bone mass density T-scores, female sex, and advanced age.
Introduction
The purpose of this study was to investigate the association between osteoporotic vertebral compression refractures (OVCRFs) and sarcopenia, and to identify other risk factors of OVCRFs.
Methods
We evaluated 237 patients with osteoporotic vertebral compression fracture who underwent percutaneous kyphoplasty (PKP) in our hospital from August 2016 to December 2017. To diagnose sarcopenia, a cross-sectional computed tomography (CT) image at the inferior aspect of the third lumbar vertebra (L3) was selected for estimating muscle mass. Grip strength was used to assess muscle strength. Possible risk factors, such as age, sex, body mass index (BMI), bone mineral density (BMD), location of the treated vertebra, anterior-posterior ratio (AP ratio) of the fractured vertebra, cement leakage, and vacuum clefts, were assessed. The multivariable analysis was used to determine the risk factors of OVCRFs.
Results
During the follow-up period, OVCRFs occurred in 64 (27.0%) patients. Sarcopenia was present in 48 patients (20.3%), including 21 OVCRFs and 27 non-OVCRFs patients. Sarcopenia was significantly correlated with advanced age, lower BMI, lower BMD, and hypoalbuminemia. Compared with non-sarcopenic patients, sarcopenic patients had higher OVCRFs risk. In univariate analysis, sarcopenia (
p
= 0.003), female (
p
= 0.024), advanced age (≥ 75 years;
p
< 0.001), lower BMD (
p
< 0.001), lower BMI (
p
= 0.01), TL junction (vertebral levels at the thoracolumbar junction) (
p
= 0.01), cardiopulmonary comorbidity (
p
= 0.042), and hypoalbuminemia (
p
= 0.003) were associated with OVCRFs. Multivariable analysis revealed that sarcopenia (OR 2.271; 95% CI 1.069–4.824,
p
= 0.033), lower BMD (OR 1.968; 95% CI 1.350–2.868,
p
< 0.001), advanced age (≥ 75 years; OR 2.431; 95% CI 1.246–4.744,
p
= 0.009), and female sex (OR 4.666; 95% CI 1.400–15.552,
p
= 0.012) were independent risk predictors of OVCRFs.
Conclusions
Sarcopenia is an independent risk predictor of osteoporotic vertebral compression refractures. Other factors affecting OVCRFs are low BMD T-scores, female sex, and advanced age.
Aims
The presence of viable but nonculturable (VBNC) bacterial pathogens which often fail to be detected by cultivation and can regain the cultivability if the living conditions improve were ...reported. The objective of this study was to determine the occurrence of VBNC Salmonella spp. and Shigella spp. in the biosolids during anaerobic digestion and its reactivation during the cake storage.
Methods and Results
The occurrence of VBNC Salmonella spp. and Shigella spp. during mesophilic, temperature‐phased, thermophilic anaerobic digestion of sewage sludge and the subsequent storage were studied by RT‐qPCR and most probable number (MPN) method. The VBNC incidence of Salmonella spp. and Shigella spp. during thermophilic digestion was four orders of magnitude higher than those of mesophilic digestion. Accordingly, higher resuscitation ratio of VBNC pathogens was also achieved in thermophilic digested sludge. As a result, the culturable Salmonella typhimurium contents in thermophilic digested sludge after cake storage were two orders of magnitude higher than mesophilic digestion. Both quantitive PCR and reverse transcription quantitative PCR assay results showed the two bacterial counting numbers remained stable throughout the cake storage.
Conclusions
The results indicate that the increase in the culturable Salmonella spp. and Shigella spp. after centrifugal dewatering was attributed to the resuscitation from the VBNC state to the culturable state.
Significance and Impact of the Study
Thermophilic anaerobic digestion mainly induced Salmonella spp. and Shigella spp. into VBNC state rather than killed them, suggesting that the biological safety of sewage sludge by temperature‐phased anaerobic digestion should be carefully assessed.
In this study, we quantify the contribution of individual large‐scale waves to ionospheric electrodynamics and examine the dependence of the ionospheric perturbations on solar activity. We focus on ...migrating diurnal tide (DW1) plus mean winds, migrating semidiurnal tide (SW2), quasi‐stationary planetary wave one (QSPW1), and nonmigrating semidiurnal westward wave one (SW1) under northern winter conditions, when QSPW1 and SW1 are climatologically strong. From thermosphere‐ionosphere‐mesosphere electrodynamics general circulation model simulations under solar minimum conditions, it is found that the mean winds and DW1 produce a wave two pattern in equatorial vertical E×Bdrift that is upward in the morning and around dusk. The modeled SW2 also produces a wave two pattern in the ionospheric vertical drift that is nearly a half wave cycle out of phase with that due to mean winds and DW1. SW1 can cause large vertical drifts around dawn, while QSPW1 does not have any direct impact on the vertical drift. Wind components of both SW2 and SW1 become large at middle to high latitudes in the E‐region, and kernel functions obtained from numerical experiments reveal that they can significantly affect the equatorial ion drift, likely through modulating the E‐region wind dynamo. The most evident changes of total ionospheric vertical drift when solar activity is increased are seen around dawn and dusk, reflecting the more dominant role of large F‐region Pedersen conductivity and of the F‐region dynamo under high solar activity. Therefore, the lower atmosphere driving of the ionospheric variability is more evident under solar minimum conditions, not only because variability is more identifiable in a quieter background but also because the E‐region wind dynamo is more significant. These numerical experiments also demonstrate that the amplitudes, phases, and latitudinal and vertical structures of large‐scale waves are important in quantifying the ionospheric responses.
Key PointsContributions of individual tides to ionospheric vertical drift are quantified.Semidiurnal tides can strongly affect E-region dynamo at mid/high latitudes.Ionospheric responses to waves are dependent on solar activity.
During the minimum of solar cycles 23–24, the Sun was extremely quiet; however, tropospheric deep convection was strong and active. In this paper, we model the gravity waves (GWs) excited by deep ...convective plumes globally during 15–27 June in 2009 and in 2000 (previous solar maximum). We ray trace the GWs into the thermosphere and calculate the body force/heatings which result where they dissipate. We input these force/heatings into a global dynamical model and study the neutral and plasma changes that result. The body forces induce horizontal wind (uH′) and temperature (T′) perturbations, while the heatings primarily induce T′. We find that the forces create much larger T′ than the heatings. uH′ consists of clockwise and counterclockwise circulations and “jet”‐like winds that are highly correlated with deep convection, with |uH′|∼50–200m/s. uH′ and T′ are much larger during 2009 than 2000. uH′ decreases slightly (significantly) with altitude from z∼150 to 400 km during 2009 (2000). T′ perturbations at z=350km primarily propagate westward at ∼460 m/s, consistent with migrating tides. It was found that planetary‐scale diurnal and semidiurnal tides are generated in situ in the thermosphere, with amplitudes ∼10–40m/s at z=250 km. The largest‐amplitude in situ tides are DW1, D0, DW2, SW2, SW3, and SW5. Smaller‐amplitude in situ tides are S0, SE2, and SW3. Total electron content (TEC′) perturbations of 1–2.5 (2–3.5) total electron content units (TECU, where 1 TECU = 1016 el m−2) during 2009 (2000) are created in the upper atmosphere above nearby regions of deep tropical convection. For a given local time (LT), there are 2 to 3 TEC′ peaks in longitude around the Earth.
Key Points
The dissipation of GWs creates global changes to the thermosphere and ionosphere
The present study was performed to investigate the effects of a commercially available probiotic product (compound probiotic) containing Bacillus subtilis 7.0 × 109 CFU g−1, Bacillus licheniformis ...3.0 × 109 CFU g−1, Lactobacillus spp. 5.0 × 108 CFU g−1 and Arthrobacter spp. 1.0 × 108 CFU g−1 on the growth performance, non‐specific immunity and protection against Vibrio harveyi infection in cobia (Rachycentron canadum). Fish were fed diets containing six graded levels of compound probiotic (0.0, 1.0, 2.0, 3.0, 4.0 and 5.0 g kg−1) for 8 weeks. The results showed that the survival rate ranged from 81.1% to 84.4% with no significant difference among dietary treatments (P > 0.05) after feeding experiment. Dietary compound probiotic significantly increased the specific growth rate (SGR), serum lysozyme, alternative complement pathway (ACP) activity, phagocytosis percentage (PP) and respiratory burst activity of head‐kidney macrophages of cobia. Moreover, feeding of supplemented diets containing compound probiotic resulted in significantly lower mortality against the pathogens Vibrio harveyi compared with the control group. To elevate the growth and immune resistance ability of cobia, an optimal dose of dietary compound probiotic administration determined by second‐order polynomial regression analysis was 3.3 g kg−1, on the basis of the SGR and mortality after challenge with V. harveyi.
Using the TIMED Doppler interferometer (TIDI) mesospheric and lower thermospheric neutral‐wind multiyear data set (2002–2007) and NCAR TIME General Circulation Models (GCM) 1.2 annual run results ...(2002–2005) at the TIDI sampling points, we study the migrating diurnal tide's global distribution, interannual, and seasonal variations in connection with the mean zonal wind interannual variations. A strong quasi‐biennial oscillation (QBO) effect on the diurnal tide was observed in the TIDI data and reproduced to a lesser degree in the TIME‐GCM run. The migrating diurnal tide amplitude is larger during the eastward phase of the stratospheric QBO and weaker during the westward phase. Westward mesospheric equatorial mean zonal winds appeared during the eastward phase of the stratospheric QBO (in 2002, 2004, and 2006). The strongest QBO effect on both the migrating diurnal tide and mean zonal winds was observed during the March equinox. The stronger tides may be related to the weaker gravity wave filtering in the stratosphere during the eastward phase stratospheric QBO. The TIDI data also exhibit large interhemispheric asymmetry. The westward mean zonal winds in the mesosphere appeared to be associated with the enhanced diurnal tide. The TIME‐GCM 1.2 diurnal tide amplitudes are in general smaller than those observed by the TIDI instrument. Limited vertical spatial resolution for the TIME‐CGM 1.2 is suggested as the cause. Future improvements are expected with a higher spatial resolution in the model.
The Whole Atmosphere Community Climate Model eXtended is used to investigate the extent to which neglecting the realistic day‐to‐day lower atmospheric variability introduces uncertainty in the ...ionosphere response to an idealized geomagnetic storm. A 10‐member ensemble is generated by adding small temperature perturbations in the lower atmosphere 30 days prior to the imposed geomagnetic storm. Chaotic divergence, and internal atmospheric variability, leads to the geomagnetic storm occurring under an arbitrarily different, though climatically similar, atmospheric state for each ensemble member. The intra‐ensemble variability, which we characterize by the ensemble standard deviation, of the day‐to‐day change in total electron content is generally ∼10%–20% during geomagnetically quiet time. During an idealized storm with a Kp of 7 the ensemble standard deviation of the change in total electron content increases to ∼20%–40% at low and middle latitudes, with localized regions exceeding 100%. Examination of individual ensemble members illustrates that they all capture the same large‐scale features of the storm time changes in the ionosphere but can exhibit notable (50%) differences regionally, especially during later stages of the storm. The results thus demonstrate that in order to accurately capture smaller‐scale features of the upper atmosphere response to geomagnetic storms, it is necessary to include the effects of lower atmosphere variability.
Plain Language Summary
Geomagnetic storms are an important driver of variability in Earth's ionosphere and can have significant societal impacts through the ionosphere's impact on communications and navigation systems (e.g., Global Positioning System). Numerical simulations are a common tool for the specification and forecasting of the ionosphere variability driven by geomagnetic storms. Simulations have historically only used a climatological spectrum of waves propagating upward from the lower atmosphere (i.e., troposphere, stratosphere, and mesosphere; 0–100 km). This neglect of the day‐to‐day variability of wave forcing from the lower atmosphere is a potential source of uncertainty when simulating the ionosphere variability during geomagnetic storms. The present study uses a whole atmosphere model, extending from the surface to ∼500 km, to understand the uncertainty in the ionosphere response to a geomagnetic storm that is due to the day‐to‐day variability of the lower atmosphere. It is found that omitting lower atmosphere variability leads to an uncertainty in the ionosphere response to a geomagnetic storm that is typically ∼20%–40% but can be as large as 100% regionally. Incorporating the day‐to‐day variability of the lower atmosphere is thus an important factor for reducing the uncertainty in numerical models that are used to specify and forecast the near‐Earth space environment.
Key Points
WACCM‐X simulations demonstrate the impact of lower atmosphere variability during a geomagnetic storm
Uncertainty in TEC response to a geomagnetic storm due to neglecting lower atmosphere forcing is 20–40%
Simulations, and observational analyses, should account for the effects of lower atmosphere forcing
Abstract
As a novel X-ray focusing technology, lobster-eye micropore optics (MPO) feature both a wide observing field of view and true imaging capability, promising sky monitoring with significantly ...improved sensitivity and spatial resolution in soft X-rays. Since first proposed by Angel, the optics have been extensively studied, developed and trialed over the past decades. In this Letter, we report on the first-light results from a flight experiment of the Lobster Eye Imager for Astronomy, a pathfinder of the wide-field X-ray telescope of the Einstein Probe mission. The piggyback imager, launched in 2022 July, has a mostly unvignetted field of view of 18.°6 × 18.°6. Its spatial resolution is in the range of 4′–7′ in FWHM and the focal spot effective area is 2–3 cm
2
, both showing only mild fluctuations across the field of view. We present images of the Galactic center region, Sco X-1, and the diffuse Cygnus Loop nebular taken in snapshot observations over 0.5–4 keV. These are truly wide-field X-ray images of celestial bodies observed, for the first time, by a focusing imaging telescope. Initial analyses of the in-flight data show excellent agreement between the observed images and the on-ground calibration and simulations. The instrument and its characterization are briefly described, as well as the flight experiment. The results provide a solid basis for the development of the present and proposed wide-field X-ray missions using lobster-eye MPO.
PDF
