An abnormal neuronal activity in the amygdala is involved in the pathogenesis of anxiety disorders. However, little is known about the mechanisms. High-anxiety mice and low-anxiety mice, representing ...the innate extremes of anxiety-related behaviors, were first grouped according to their anxiety levels in the elevated plus maze test. We found that the mRNA for endothelin-1 (ET1) and ET1 B-type receptors (ETBRs) in the amygdala was down-regulated in high-anxiety mice compared with low-anxiety mice. Knocking down basolateral amygdala (BLA) ET1 expression enhanced anxiety-like behaviors, whereas over-expressing ETBRs, but not A-type receptors (ETARs), had an anxiolytic effect. The combined down-regulation of ETBR and ET1 had no additional anxiogenic effect compared to knocking down the ETBR gene alone, suggesting that BLA ET1 acts through ETBRs to regulate anxiety-like behaviors. To explore the mechanism underlying this phenomenon further, we verified that most of the ET1 and the ET1 receptors in the BLA were expressed in pyramidal neurons. The ET1-ETBR signaling pathway decreased the firing frequencies and threshold currents for the action potentials of BLA pyramidal neurons but did not alter BLA synaptic neurotransmission. Together, these results indicate that amygdalar ET1-ETBR signaling could attenuate anxiety-like behaviors by directly decreasing the excitability of glutamatergic neurons.
Magnetic Resonance Imaging (MRI) has been widely used to acquire structural and functional information about the brain. In a group- or voxel-wise analysis, it is essential to correct the bias field ...of the radiofrequency coil and to extract the brain for accurate registration to the brain template. Although automatic methods have been developed, manual editing is still required, particularly for echo-planar imaging (EPI) due to its lower spatial resolution and larger geometric distortion. The needs of user interventions slow down data processing and lead to variable results between operators. Deep learning networks have been successfully used for automatic postprocessing. However, most networks are only designed for a specific processing and/or single image contrast (e.g., spin-echo or gradient-echo). This limitation markedly restricts the application and generalization of deep learning tools. To address these limitations, we developed a deep learning network based on the generative adversarial net (GAN) to automatically correct coil inhomogeneity and extract the brain from both spin- and gradient-echo EPI without user intervention. Using various quantitative indices, we show that this method achieved high similarity to the reference target and performed consistently across datasets acquired from rodents. These results highlight the potential of deep networks to integrate different postprocessing methods and adapt to different image contrasts. The use of the same network to process multimodality data would be a critical step toward a fully automatic postprocessing pipeline that could facilitate the analysis of large datasets with high consistency.
Recent studies have found gut microbiota to be closely associated with onset and perpetuation of UC. Currently, studies about gut microbiota have mainly covered samples collected from the intestinal ...lumen. However, the luminal flora is only part of the gut microbiota. Studies of the changes in mucosal flora under pathological conditions have been lacking. In this study, we investigated the correlation between the onset of UC and flora changes in different intestinal layers.
The dextran sulfate sodium(DSS)-induced UC model was established by exposing mice to cycles of DSS. The luminal contents, an inner mucus layer, and outer mucus layer were harvested under sterile conditions. The samples were then analyzed using high-throughput sequencing of 16S rRNA V3 + V4 amplicons. The colonic microbiota composition and diversity were analyzed and compared using MetaStat, LefSe, multivariate analysis of variance, and spatial statistics.
The DSS-induced UC mouse model was successfully established. The diversity of the microbiota from luminal content, the outer mucus layer, and inner mucus layer were significantly different in both control and UC model groups. The statistically different OTUs belonged to Lachnospiraceae and Ruminococcaceae families within the order Clostridiales were mainly localized to the outer mucus layer.
The alterations in flora composition and diversity mainly occurred in the colonic outer mucus layer. The change of flora in the colonic mucus layers is of great significance in the understanding of common features of gut flora in IBD and the understanding of the relationship between gut flora and disease progression.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
O-linked N -acetylglucosamine (GlcNAc) transferase (OGT) is the only known enzyme that catalyzes the O-GlcNAcylation of proteins at the Ser or Thr side chain hydroxyl group. OGT participates in ...transcriptional and epigenetic regulation, and dysregulation of OGT has been implicated in diseases such as cancer. However, the underlying mechanism is largely unknown. Here we show that OGT is required for the trimethylation of histone 3 at K27 to form the product H3K27me3, a process catalyzed by the histone methyltransferase enhancer of zeste homolog 2 (EZH2) in the polycomb repressive complex 2 (PRC2). H3K27me3 is one of the most important histone modifications to mark the transcriptionally silenced chromatin. We found that the level of H3K27me3, but not other H3 methylation products, was greatly reduced upon OGT depletion. OGT knockdown specifically down-regulated the protein stability of EZH2, without altering the levels of H3K27 demethylases UTX and JMJD3, and disrupted the integrity of the PRC2 complex. Furthermore, the interaction of OGT and EZH2/PRC2 was detected by coimmunoprecipitation and cosedimentation experiments. Importantly, we identified that serine 75 is the site for EZH2 O-GlcNAcylation, and the EZH2 mutant S75A exhibited reduction in stability. Finally, microarray and ChIP analysis have characterized a specific subset of potential tumor suppressor genes subject to repression via the OGT–EZH2 axis. Together these results indicate that OGT-mediated O-GlcNAcylation at S75 stabilizes EZH2 and hence facilitates the formation of H3K27me3. The study not only uncovers a functional posttranslational modification of EZH2 but also reveals a unique epigenetic role of OGT in regulating histone methylation.
Type Ib diamonds emit bright fluorescence at 550-800 nm from nitrogen-vacancy point defects, (N-V)⁰ and (N-V)⁻, produced by high-energy ion beam irradiation and subsequent thermal annealing. The ...emission, together with noncytotoxicity and easiness of surface functionalization, makes nano-sized diamonds a promising fluorescent probe for single-particle tracking in heterogeneous environments. We present the result of our characterization and application of single fluorescent nanodiamonds as cellular biomarkers. We found that, under the same excitation conditions, the fluorescence of a single 35-nm diamond is significantly brighter than that of a single dye molecule such as Alexa Fluor 546. The latter photobleached in the range of 10 s at a laser power density of 10⁴ W/cm², whereas the nanodiamond particle showed no sign of photobleaching even after 5 min of continuous excitation. Furthermore, no fluorescence blinking was detected within a time resolution of 1 ms. The photophysical properties of the particles do not deteriorate even after surface functionalization with carboxyl groups, which form covalent bonding with polyL-lysines that interact with DNA molecules through electrostatic forces. The feasibility of using surface-functionalized fluorescent nanodiamonds as single-particle biomarkers is demonstrated with both fixed and live HeLa cells.
The prevalence of myopia is increasing globally. Complications of myopia are associated with huge economic and social costs. It is believed that high myopia in adulthood can be traced back to school ...age onset myopia. Therefore, it is crucial and urgent to implement effective measures of myopia control, which may include preventing myopia onset as well as retarding myopia progression in school age children. The mechanism of myopia is still poorly understood. There are some evidences to suggest excessive expansion of Bruch's membrane, possibly in response to peripheral hyperopic defocus, and it may be one of the mechanisms leading to the uncontrolled axial elongation of the globe. Atropine is currently the most effective therapy for myopia control. Recent clinical trials demonstrated low-dose atropine eye drops such as 0.01% resulted in retardation of myopia progression, with significantly less side effects compared to higher concentration preparation. However, there remain a proportion of patients who are poor responders, in whom the optimal management remains unclear. Proposed strategies include stepwise increase of atropine dosing, and a combination of low-dose atropine with increase outdoor time. This review will focus on the current understanding of epidemiology, pathophysiology in myopia and highlight recent clinical trials using atropine in the school-aged children, as well as the treatment strategy in clinical implementation in hyperopic, pre-myopic and myopic children.
Much of the current understanding of thermal effects in biological systems is based on macroscopic measurements. There is little knowledge about the local thermostability or heat tolerance of ...subcellular components at the nanoscale. Herein, we show that gold nanorod–fluorescent nanodiamond (GNR‐FND) hybrids are useful as a combined nanoheater/nanothermometer in living cells. With the use of a 594 nm laser for both heating and probing, we measure the temperature changes by recording the spectral shifts of the zero‐phonon lines of negatively charged nitrogen‐vacancy centers in FNDs. The technique allows us to determine the rupture temperatures of individual membrane nanotubes in human embryonic kidney cells, as well as to generate high temperature gradients on the cell membrane for photoporation and optically controlled hyperthermia. Our results demonstrate a new paradigm for hyperthermia research and application.
Heating up: Gold nanorod–fluorescent nanodiamond (GNR‐FND) hybrids are shown to be useful as a combined nanoheater/nanothermometer in living cells. A temperature difference of up to 10 °C in the damage threshold between local and global heating of intercellular membrane nanotubes was found. These hybrid devices open new opportunities in hyperthermia research.
Scientific drilling in active faults after a large earthquake is ideal to study earthquake mechanisms. The Wenchuan earthquake Fault Scientific Drilling project (WFSD) is an extremely rapid response ...to the 2008 Ms 8.0 Wenchuan earthquake, which happened along the Longmenshan fault, eastern margin of the Tibetan Plateau. In order to better understand the fault mechanism and the physical and chemical characteristics of the rocks, the WFSD project will eventually drill 5 boreholes along the two main faults. This paper focuses on the first hole (WFSD-1), which started just 178days after the earthquake, down to a final depth of 1201.15m. Petrological and structural analyses of the cores allowed the identification of fault-related rocks in the Yingxiu–Beichuan fault (fault gouge, cataclasite, and fault breccia), and the Principle Slip Zone (PSZ) location of the Wenchuan earthquake was determined.
We found 12 fault zones in the entire core profile, with at least 10, including the Yingxiu–Beichuan fault zone, with a multiple cores structure and minimum width of ~100m. The co-seismic slip plane of the Wenchuan earthquake at depth (corresponding to the Yingxiu–Beichuan fault zone at the outcrop), as well as its PSZ, was expected to be located at the bottom of the fault zone (at 759m-depth). Instead, it was found at ~590m-depth with 1cm-wide fresh fault gouge, as determined by logging data such as temperature, natural gamma ray, p-wave velocity and resistivity, combined with the fresh appearance, magnetic susceptibility, and microstructure of the gouge. The Wenchuan earthquake slip plane has a dip angle of ~65°, showing the high-angle thrust feature. The distribution of fault gouge with several meters thick, the location of the Wenchuan earthquake's PSZ and the thickness of fresh gouge all imply a correlation between the width of the fault zone and the number of seismic events.
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► WFSD-1 borehole started shortly (178days) after the Wenchuan earthquake down to 1201m-depth ► The Wenchuan earthquake alone produced ~1cm thick fresh fault gouge ► At least 12 fault cores/zones were discovered and constitute the Yingxiu–Beichuan fault zone with multiple cores structure (~100m-wide) ► The principal slip zone is located at ~590m-depth, with a slope of 65° ► The fault gouge is 3.79m-thick, attesting the long-term high seismic activity of the fault
Biofouling is a common challenge for underwater sensors, especially for long-term in situ monitoring in marine environments. In this study, we assessed the antifouling efficacy of a paint containing ...a natural product camptothecin (CPT) on six materials (316 L stainless steel, TC4 titanium alloy, 7075 aluminum alloy, polyoxymethylene, polyvinyl chloride, and Teflon), which are frequently used in the construction of underwater sensor housings. Additionally, a buoy-based sea-trial was performed to test the antifouling performance of the CPT-based paint on housings of three in situ sensors used for practical seawater monitoring applications, namely a spectrophotometer for chemical oxygen demand (COD) measurements and two fluorimeters for biochemical oxygen demand (BOD) and chlorophyll a (Chl a) concentration measurements. The results showed significantly lower macrofouling coverage on the areas painted with the CPT-based paint compared to the unpainted areas for each tested material over 9 months of seawater immersion. The CPT-based paint exhibited different antifouling performance for the different materials; in particular, it exhibited better antifouling performance on the plastic materials compared to the metal materials. Furthermore, when applied on submersible sensor housings in the sea-trial test, the CPT-based paint kept the housings of the COD sensor and the Chl a sensor clean for over 4 months. In addition, the paint prevented fouling of the BOD sensor housing even after 6 months of seawater immersion. Thus, our results suggest that the CPT-based paint could be used as a potential solution to control the biofouling of sensor housings for long-term in situ applications in marine environments.
•The CPT-based paint prevented biofouling on 6 materials used for sensor housings.•The CPT-based paint kept the housings of 3 sensors clean for >4 months in the sea.•The CPT-based paint provides an antifouling solution for marine sensor housings.
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