Gut microbiota play an important part in the pathogenesis of mucosal inflammation, such as inflammatory bowel disease (IBD). However, owing to the complexity of the gut microbiota, our understanding ...of the roles of commensal and pathogenic bacteria in the maintenance of immune homeostasis in the gut is evolving only slowly. Here, we evaluated the role of gut microbiota and their secreting extracellular vesicles (EV) in the development of mucosal inflammation in the gut. Experimental IBD model was established by oral application of dextran sulfate sodium (DSS) to C57BL/6 mice. The composition of gut microbiota and bacteria-derived EV in stools was evaluated by metagenome sequencing using bacterial common primer of 16S rDNA. Metagenomics in the IBD mouse model showed that the change in stool EV composition was more drastic, compared to the change of bacterial composition. Oral DSS application decreased the composition of EV from Akkermansia muciniphila and Bacteroides acidifaciens in stools, whereas increased EV from TM7 phylum, especially from species DQ777900_s and AJ400239_s. In vitro pretreatment of A. muciniphila-derived EV ameliorated the production of a pro-inflammatory cytokine IL-6 from colon epithelial cells induced by Escherichia coli EV. Additionally, oral application of A. muciniphila EV also protected DSS-induced IBD phenotypes, such as body weight loss, colon length, and inflammatory cell infiltration of colon wall. Our data provides insight into the role of gut microbiota-derived EV in regulation of intestinal immunity and homeostasis, and A. muciniphila-derived EV have protective effects in the development of DSS-induced colitis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Most secreted and membrane proteins are targeted to and translocated across the endoplasmic reticulum (ER) membrane through the Sec61 protein-conducting channel. Evolutionarily conserved Sec62 and ...Sec63 associate with the Sec61 channel, forming the Sec complex and mediating translocation of a subset of proteins. For the last three decades, it has been thought that ER protein targeting and translocation occur via two distinct pathways: signal recognition particle (SRP)-dependent co-translational or SRP-independent, Sec62/Sec63 dependent post-translational translocation pathway. However, recent studies have suggested that ER protein targeting and translocation through the Sec translocon are more intricate than previously thought. This review summarizes the current understanding of the molecular functions of Sec62/Sec63 in ER protein translocation.
In this study, the size effect of copper particles on the flash light sintering of copper (Cu) ink was investigated using Cu nanoparticles (20-50 nm diameter) and microparticles (2 m diameter). Also, ...the mixed Cu nano- micro-inks were fabricated, and the synergetic effects between the Cu nano-ink and micro-ink on flash light sintering were assessed. The ratio of nanoparticles to microparticles in Cu ink and the several flash light irradiation conditions (irradiation energy density, pulse number, on-time, and off-time) were optimized to obtain high conductivity of Cu films. In order to precisely monitor the milliseconds-long flash light sintering process, in situ monitoring of electrical resistance and temperature changes of Cu films was conducted during the flash light irradiation using a real-time Wheatstone bridge electrical circuit, thermocouple-based circuit, and a high-rate data acquisition system. Also, several microscopic and spectroscopic characterization techniques such as scanning electron microscopy, x-ray diffraction, x-ray photoelectron spectroscopy, and Fourier transform infrared spectroscopy were used to characterize the flash light sintered Cu nano- micro-films. In addition, the sheet resistance of Cu film was measured using a four-point probe method. This work revealed that the optimal ratio of nanoparticles to microparticles is 50:50 wt%, and the optimally fabricated and flash light sintered Cu nano- micro-ink films have the lowest resistivity (80 cm) among nano-ink, micro-ink, or nano-micro mixed films.
Mitochondrial stress releases mitochondrial DNA (mtDNA) into the cytosol, thereby triggering the type Ι interferon (IFN) response. Mitochondrial outer membrane permeabilization, which is required for ...mtDNA release, has been extensively studied in apoptotic cells, but little is known about its role in live cells. We found that oxidatively stressed mitochondria release short mtDNA fragments via pores formed by the voltage-dependent anion channel (VDAC) oligomers in the mitochondrial outer membrane. Furthermore, the positively charged residues in the N-terminal domain of VDAC1 interact with mtDNA, promoting VDAC1 oligomerization. The VDAC oligomerization inhibitor VBIT-4 decreases mtDNA release, IFN signaling, neutrophil extracellular traps, and disease severity in a mouse model of systemic lupus erythematosus. Thus, inhibiting VDAC oligomerization is a potential therapeutic approach for diseases associated with mtDNA release.
Graphene oxide and silver nanowires were bar coated onto PET substrates and then welded using an ultraviolet (UV)-assisted flash light irradiation process to achieve both high electrical conductivity ...and low haze. The irradiation process connected adjacent silver nanowires by welding, while simultaneously reducing the graphene oxide to graphene. This process was performed using a custom UV-assisted flash light welding system at room temperature under ambient conditions and was extremely rapid, with processing time of several milliseconds. The effects of varying the weight fractions of the silver nanowires and graphene oxide and of varying the UV-assisted flash light welding conditions (light energy and pulse duration) were investigated. The surface morphologies of the welded silver nanowire/graphene films were analyzed using scanning electron microscopy. Optical characterizations, including transmittance and haze measurements, were also conducted using a spectrophotometer. To test their resistance to oxidation, the welded silver nanowire/graphene films were subjected to high temperature in a furnace (100 °C), and their sheet resistances were measured every hour. The flash light welding process was found to yield silver nanowire/graphene films with high oxidation resistance, high conductivity (14.35 Ω·sq
–1
), high transmittance (93.46%), and low haze (0.9%). This material showed uniform temperature distribution when applied as a resistive heating film.
Flexible/stretchable electrodes based on conductive polymers are used in various fields, including wearable devices and human body sensors. However, the durability of flexible/stretchable electrodes ...is insufficient. In this study, a carbon nanotube (CNT) electrode layer was formed on a polydimethylsiloxane (PDMS) surface with a controlled precuring time using a simple spray-coating method. The electrical properties and durability of the CNT-based conductive polymers were evaluated. To evaluate the durability of the electrodes, bending, stretching, tribo, and scratch tests were performed. The degree of embedding of the CNT electrode layer on the PDMS surface differed according to the PDMS precuring time, which showed a difference in durability. The case in which the CNTs were coated at a precuring time of approximately 8–12 h had the best durability. It was verified that CNT-embedded PDMS electrodes fabricated under optimal conditions can be attached to the skin of human joints and used as human-body-attachable wearable sensors that measure changes in electrical resistance according to joint movement, resulting in excellent elasticity, durability, and performance.
•CNT electrodes were sprayed onto the surface of PDMS to create a CNT-embedded PDMS coating.•CNT layer thickness, conductivity, and durability varied with embedding conditions.•The ideal human-body-attachable wearable sensor coated with CNT-embedded PDMS showed excellent durability and sensing performance.
Non-alcoholic fatty liver disease (NAFLD) has emerged as a significant liver ailment attributed to factors like obesity and diabetes. While ongoing research explores treatments for NAFLD, further ...investigation is imperative to address this escalating health concern. NAFLD manifests as hepatic steatosis, precipitating insulin resistance and metabolic syndrome. This study aims to validate the regenerative potential of chimeric fibroblast growth factor 21 (FGF21) and Hepatocyte Growth Factor Receptor (HGFR) in NAFLD-afflicted liver cells. AML12, a murine hepatocyte cell line, was utilized to gauge the regenerative effects of chimeric FGF21/HGFR expression. Polysaccharide accumulation was affirmed through Periodic acid-Schiff (PAS) staining, while LDL uptake was microscopically observed with labeled LDL. The expression of FGF21/HGFR and NAFLD markers was analyzed by mRNA analysis with RT-PCR, which showed a decreased expression in acetyl-CoA carboxylase 1 (
) and sterol regulatory element binding protein (
) cleavage-activating protein (
) with increased expression of hepatocellular growth factor (
), hepatocellular nuclear factor 4 alpha (
), and albumin (
). These findings affirm the hepato-regenerative properties of chimeric FGF21/HGFR within AML12 cells, opening novel avenues for therapeutic exploration in NAFLD.
Coulomb attraction between electrons and holes in a narrow-gap semiconductor or a semimetal is predicted to lead to an elusive phase of matter dubbed excitonic insulator. However, direct observation ...of such electronic instability remains extremely rare. Here, we report the observation of incipient divergence in the static excitonic susceptibility of the candidate material Ta2NiSe5 using Raman spectroscopy. Critical fluctuations of the excitonic order parameter give rise to quasi-elastic scattering of B2g symmetry, whose intensity grows inversely with temperature toward the Weiss temperature of TW ≈ 241 K, which is arrested by a structural phase transition driven by an acoustic phonon of the same symmetry at TC = 325 K. Concurrently, a B2g optical phonon becomes heavily damped to the extent that its trace is almost invisible around TC, which manifests a strong electron-phonon coupling that has obscured the identification of the low-temperature phase as an excitonic insulator for more than a decade. Our results unambiguously reveal the electronic origin of the phase transition.Concominant structural and electronic phase transitions in the excitonic insulator candidate Ta2NiSe5 make the identification of the driving mechanism of the transition challenging. Here, the authors report evidence for electronically-driven transition via Raman susceptibility measurements.
In the present study, we explore the observational characteristics of Electromagnetic Ion Cyclotron (EMIC) wave propagation from the source region to the ground. We use magnetometers aboard ...Geostationary Operational Environment Satellite (GOES) 13, the geosynchronous orbit satellite at 75°W, and at Sanikiluaq ground station (SNK, 79.14°W and 56.32°N in geographic coordinates, and L ∼ 6.0 in a dipole magnetic field) which is located in northern Canada. Using these magnetically conjugate observatories, simultaneous EMIC wave observations are carried out. We found a total of 295 coincident and 248 non‐coincident EMIC wave events between GOES 13 and the SNK station. Our statistical analysis reveals that the coincident events are predominantly observed on the dayside. The wave normal angles are slightly higher for the non‐coincident events than for coincident events. However, the coincidence of the waves is mostly governed by the intensity and duration of the wave. This is confirmed by the geomagnetic environment which shows higher auroral electrojet (AE) and Kp indices for the coincident events. We also found that some events show high‐frequency (f > 0.4 Hz) wave filtering. The statistics of the high‐frequency filtered and non‐filtered wave events show that there are clear magnetic local time (MLT) and F10.7 index differences between the two groups, as well as in ionospheric electron density measurements. In addition, we also found differences in the wave properties which possibly indicate that the propagation in the magnetosphere also plays an important role in the wave filtering.
Key Points
Coincidence of the Electromagnetic Ion Cyclotron wave observation is studied using conjugate space Geostationary Operational Environment Satellite (GOES) 13 and ground (SNK ground magnetometer) observations
The Coincidence of the waves is primarily dominated by wave power and duration
The high‐frequency wave filtering is complicated by both magnetospheric and ionospheric wave propagation
Glioblastoma (GBM) is a devastating and incurable brain tumour, with a median overall survival of fifteen months
. Identifying the cell of origin that harbours mutations that drive GBM could provide ...a fundamental basis for understanding disease progression and developing new treatments. Given that the accumulation of somatic mutations has been implicated in gliomagenesis, studies have suggested that neural stem cells (NSCs), with their self-renewal and proliferative capacities, in the subventricular zone (SVZ) of the adult human brain may be the cells from which GBM originates
. However, there is a lack of direct genetic evidence from human patients with GBM
. Here we describe direct molecular genetic evidence from patient brain tissue and genome-edited mouse models that show astrocyte-like NSCs in the SVZ to be the cell of origin that contains the driver mutations of human GBM. First, we performed deep sequencing of triple-matched tissues, consisting of (i) normal SVZ tissue away from the tumour mass, (ii) tumour tissue, and (iii) normal cortical tissue (or blood), from 28 patients with isocitrate dehydrogenase (IDH) wild-type GBM or other types of brain tumour. We found that normal SVZ tissue away from the tumour in 56.3% of patients with wild-type IDH GBM contained low-level GBM driver mutations (down to approximately 1% of the mutational burden) that were observed at high levels in their matching tumours. Moreover, by single-cell sequencing and laser microdissection analysis of patient brain tissue and genome editing of a mouse model, we found that astrocyte-like NSCs that carry driver mutations migrate from the SVZ and lead to the development of high-grade malignant gliomas in distant brain regions. Together, our results show that NSCs in human SVZ tissue are the cells of origin that contain the driver mutations of GBM.
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