Post-transcriptional modification of RNA is an important determinant of RNA quality control, translational efficiency, RNA-protein interactions and stress response. This is illustrated by the ...observation of toxicant-specific changes in the spectrum of tRNA modifications in a stress-response mechanism involving selective translation of codon-biased mRNA for crucial proteins. To facilitate systems-level studies of RNA modifications, we developed a liquid chromatography-mass spectrometry (LC-MS) technique for the quantitative analysis of modified ribonucleosides in tRNA. The protocol includes tRNA purification by HPLC, enzymatic hydrolysis, reversed-phase HPLC resolution of the ribonucleosides, and identification and quantification of individual ribonucleosides by LC-MS via dynamic multiple reaction monitoring (DMRM). In this approach, the relative proportions of modified ribonucleosides are quantified in several micrograms of tRNA in a 15-min LC-MS run. This protocol can be modified to analyze other types of RNA by modifying the steps for RNA purification as appropriate. By comparison, traditional methods for detecting modified ribonucleosides are labor- and time-intensive, they require larger RNA quantities, they are modification-specific or require radioactive labeling.
In clinical assessments, the correlation between atmospheric air pollution and respiratory damage is highly complicated. Epidemiological studies show that atmospheric air pollution is largely ...responsible for the global proliferation of pulmonary disease. This is particularly significant, since most Computational Fluid Dynamics (CFD) studies to date have used monodisperse particles, which may not accurately reflect realistic inhalation patterns, since atmospheric aerosols are mostly polydisperse. The aim of this study is to investigate the anatomy and turbulent effects on polydisperse particle transport and deposition (TD) in the upper airways. The Euler-Lagrange approach is used for polydisperse particle TD prediction in both laminar and turbulent conditions. Various anatomical models are adopted to investigate the polydisperse particle TD under different flow conditions. Rossin-Rammler diameter distribution is used for the distribution of the initial particle diameter. The numerical results illustrate that airflow rate distribution at the right lung of a realistic model is higher than a non-realistic model. The CFD study also shows that turbulence effects on deposition are higher for larger diameter particles than with particles of smaller diameter. A significant amount of polydisperse particles are also shown to be deposited at the tracheal wall for CT-based model, whereas particles are mostly deposited at the carinal angle for the non-realistic model. A comprehensive, polydisperse particle TD analysis would enhance understanding of the realistic deposition pattern and decrease unwanted therapeutic aerosol deposition at the extrathoracic airways.
•Anaesthesia/surgery altered the gut microbiome in aged mice.•Dysbacteriosis induced by anaesthesia/surgery impaired reference memory in aged mice.•Probiotics alleviated reference memory impairment ...induced by anaesthesia/surgery.
Postoperative cognitive dysfunction (POCD) is associated with increased morbidity and mortality and has become a major concern for patients and caregivers. POCD is most common in older patients. Previous studies demonstrated that the gut microbiome affects cognitive function and behaviour, and perioperative factors, including the operation itself, antibiotics, opioids or acid-inducing drugs, affect the gut microbiome. Thus, we hypothesised that intestinal dysbacteriosis caused by anaesthesia/surgery induces POCD.
Tibial fracture internal fixation was performed in 18-month-old C57BL/6 mice under isoflurane anaesthesia to establish the POCD model. The Morris water maze was used to measure reference memory after anaesthesia/surgery. High-throughput sequencing of 16S rRNA from faecal samples was used to investigate changes in the abundance of intestinal bacteria after anaesthesia/surgery. To confirm the role of the gut microbiome in POCD, we pretreated mice with compound antibiotics or mixed probiotics (VSL#3). Anaesthesia/surgery impaired reference memory and induced intestinal dysbacteriosis in aged mice.
The 16S rRNA sequencing data revealed 37 genera (18 families) of bacteria that changed in abundance after anaesthesia/surgery. Pretreating mice with compound antibiotics or mixed probiotics (VSL#3) prevented the learning and memory deficits induced by anaesthesia/surgery. We further conducted quantitative real-time polymerase chain reaction (qRT-PCR) of 22 common types of bacteria among the 37 total types to verify the results of bacterial flora changes after anaesthesia/surgery. Numbers of 8 types of bacteria changed after anaesthesia/surgery but returned to normal after treatment with a mix of probiotics.
Our data suggest that deficits in reference memory induced by anaesthesia/surgery are mediated by intestinal dysbacteriosis.
Viral and host factors can shape SARS-CoV-2 evolution. However, little is known about lineage-specific and vaccination-specific mutations that occur within individuals. Here, we analysed deep ...sequencing data from 2,820 SARS-CoV-2 respiratory samples with different viral lineages to describe the patterns of within-host diversity under different conditions, including vaccine-breakthrough infections. In unvaccinated individuals, variant of Concern (VOC) Alpha, Delta, and Omicron respiratory samples were found to have higher within-host diversity and were under neutral to purifying selection at the full genome level compared to non-VOC SARS-CoV-2. Breakthrough infections in 2-dose or 3-dose Comirnaty and CoronaVac vaccinated individuals did not increase levels of non-synonymous mutations and did not change the direction of selection pressure. Vaccine-induced antibody or T cell responses did not appear to have significant impact on within-host SARS-CoV-2 sequence diversification. Our findings suggest that vaccination does not increase exploration of SARS-CoV-2 protein sequence space and may not facilitate emergence of viral variants.
Future Physics Programme of BESIII Ahmed, S.; Amoroso, A.; Bennett, J. V. ...
Chinese physics C,
04/2020, Letnik:
44, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Abstract
There has recently been a dramatic renewal of interest in hadron spectroscopy and charm physics. This renaissance has been driven in part by the discovery of a plethora of charmonium-like
...XYZ
states at BESIII and
B
factories, and the observation of an intriguing proton-antiproton threshold enhancement and the possibly related
X
(1835) meson state at BESIII, as well as the threshold measurements of charm mesons and charm baryons.
We present a detailed survey of the important topics in tau-charm physics and hadron physics that can be further explored at BESIII during the remaining operation period of BEPCII. This survey will help in the optimization of the data-taking plan over the coming years, and provides physics motivation for the possible upgrade of BEPCII to higher luminosity.
Transmission of SARS-CoV-2 from humans to other mammals, including pet animals, has been reported. However, with the exception of farmed mink, there is no previous evidence that these infected ...animals can infect humans, resulting in sustained human-to-human transmission. Following a confirmed SARS-CoV-2 infection of a pet shop worker, animals in the shop and the warehouse supplying it were tested for evidence of SARS-CoV-2 infection.
In this case study, viral swabs and blood samples were collected from animals in a pet shop and its corresponding warehouse in Hong Kong. Nasal swab or saliva samples from human COVID-19 patients epidemiologically linked to the pet shop and from subsequent local cases confirmed to be infected by SARS-CoV-2 delta variant were collected. Oral swabs were tested by quantitative RT-PCR (RT-qPCR) for SARS-CoV-2 and blood samples were serologically tested by a surrogate virus neutralisation test and plaque reduction neutralisation test. The SARS-CoV-2 RT-qPCR positive samples were sequenced by next generation viral full genome sequencing using the ISeq sequencing platform (Illumina), and the viral genomes were phylogenetically analysed.
Eight (50%) of 16 individually tested Syrian hamsters in the pet shop and seven (58%) of 12 Syrian hamsters in the corresponding warehouse were positive for SARS-CoV-2 infection in RT-qPCR or serological tests. None of the dwarf hamsters (n=75), rabbits (n=246), guinea pigs (n=66), chinchillas (n=116), and mice (n=2) were confirmed positive for SARS-CoV-2 in RT-qPCR tests. SARS-CoV-2 viral genomes deduced from human and hamster cases in this incident all belong to the delta variant of concern (AY.127) that had not been circulating locally before this outbreak. The viral genomes obtained from hamsters were phylogenetically related with some sequence heterogeneity. Phylogenetic dating suggests infection in these hamsters occurred around Oct 14, 2021 (95% CI Sept 15 to Nov 9, 2021). Multiple zoonotic transmission events to humans were detected, leading to onward human-to-human transmission.
Pet hamsters can be naturally infected with SARS-CoV-2. The virus can circulate among hamsters and lead to human infections. Both genetic and epidemiological results strongly suggest that there was more than one hamster-to-human transmission event in this study. This incident also led to onward human transmission. Importation of SARS-CoV-2-infected hamsters was a likely source of this outbreak.
US National Institutes of Health, Research Grants Council of Hong Kong, Food and Health Bureau, and InnoHK.
Abstract
In the absence of solar radiation, precipitating electrons from the solar wind (SW) are generally thought to be the dominant source of energy deposition in the nightside Martian upper ...atmosphere, creating a patchy ionosphere and possibly also affecting the nightside thermal budget of various neutral and ionized species. Previous model calculations have not taken into account in situ heating via SW electron impact. In the present study, we utilize extensive measurements made by several instruments on board the Mars Atmosphere and Volatile Evolution spacecraft, in order to perform data-driven computations of the nightside neutral, ion, and electron heating rates. Considering the large range of energetic electron intensity observed on the nightside of Mars, we divide the entire data set into two subsamples, either with or without energetic electron depletion, a notable feature of the nightside Martian ionosphere. Our calculations indicate that in situ nightside neutral heating is dominated by exothermic chemistry and Maxwell interaction with thermal ions for regions with depletion, and by direct SW impact for regions without. Collisional quenching of excited state species produced from a variety of channels, such as electron impact excitation, dissociation, and ionization, as well as
dissociative recombination, makes a substantial contribution to neutral heating, except during depletion. For comparison, nightside ion heating is mainly driven by energetic ion production under all circumstances, which occurs mainly via ion-neutral reaction O
+
+ CO
2
and CO
2
+
predissociation.
The cross section of the process e+e−→K+K− is measured at a number of center-of-mass energies s from 2.00 to 3.08 GeV with the BESIII detector at the Beijing Electron Positron Collider (BEPCII). The ...results provide the best precision achieved so far. A resonant structure around 2.2 GeV is observed in the cross section line shape. A Breit-Wigner fit yields a mass of M=2239.2±7.1±11.3 MeV/c2 and a width of Γ=139.8±12.3±20.6 MeV, where the first uncertainties are statistical and the second ones are systematic. In addition, the timelike electromagnetic form factor of the kaon is determined at the individual center-of-mass energy points.
Hypoxia inducible factor 2α (HIF-2α) is critical for primordial germ cell (PGC) survival as knockout of HIF-2α (HIF-2α−/−) decreases both expression of Oct-4 and PGC number in genital ridge. Hypoxia ...is known to stabilize HIF-2α protein from proteasomal degradation. However, little is known about the hypoxia-associated endocrinal signaling in HIF-2α expression. The current work demonstrates a role for an endocrine insulin-like growth factor-I receptor (IGF-IR)-PI3K/Akt-mTOR-HIF-2α regulatory loop in the proliferation and Oct-4 maintenance of PGC-like alkaline phosphatase positive mouse germline stem cells (AP+GSCs). We found that hypoxia greatly increased the cell proliferation and the levels of nuclear Oct-4/HIF-2α protein of AP+GSCs. The hypoxic-AP+GSCs presented stronger stemness ability for germ cell differentiation than normoxic, with expressions of c-KIT (differentiation germ cell marker), VASA (differentiation germ cell marker) and SCP3 (meiotic marker) using a renal capsule transplantation assay. Meanwhile, hypoxia significantly increased the expression levels of secreted-IGF-I and IGF-IR. The IGF-I dose dependently increased the HIF-2α expression levels in AP+GSCs; and, the inhibition of IGF-IR by RNA interference (shIGF-IR) or LY294002 (PI3K inhibitor)/Rapamycin (mTOR inhibitor) effectively suppressed the IGF-I- and/or hypoxia-induced HIF-2α and Oct-4 expression, suggesting that the IGF-IR and its downstream Akt/mTOR signaling are involved in the IGF-I/hypoxia effects. Additionally, knockdown of HIF-2α dramatically suppressed Oct-4 and IGF-IR protein levels in AP+GSC cells. In conclusion, the present study demonstrates a regulatory loop of IGF-IR-PI3K/Akt-mTOR-HIF-2α in proliferation and Oct-4 maintenance of PGC-like AP+GSCs under hypoxia. This finding provides insights into the niche endocrinology underlying early germ cell development.
The understanding of complex inhalation and transport processes of pollutant particles through the human respiratory system is important for investigations into dosimetry and respiratory health ...effects in various settings, such as environmental or occupational health. The studies over the last few decades for micro- and nanoparticle transport and deposition have advanced the understanding of drug-aerosol impacts in the mouth-throat and the upper airways. However, most of the Lagrangian and Eulerian studies have utilized the non-realistic symmetric anatomical model for airflow and particle deposition predictions. Recent improvements to visualization techniques using high-resolution computed tomography (CT) data and the resultant development of three dimensional (3-D) anatomical models support the realistic representation of lung geometry. Yet, the selection of different modelling approaches to analyze the transitional flow behavior and the use of different inlet and outlet conditions provide a dissimilar prediction of particle deposition in the human lung. Moreover, incorporation of relevant physical and appropriate boundary conditions are important factors to consider for the more accurate prediction of transitional flow and particle transport in human lung. This review critically appraises currently available literature on airflow and particle transport mechanism in the lungs, as well as numerical simulations with the aim to explore processes involved. Numerical studies found that both the Euler-Lagrange (E-L) and Euler-Euler methods do not influence nanoparticle (particle diameter ≤50 nm) deposition patterns at a flow rate ≤25 L/min. Furthermore, numerical studies demonstrated that turbulence dispersion does not significantly affect nanoparticle deposition patterns. This critical review aims to develop the field and increase the state-of-the-art in human lung modelling.
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