Nasopharyngeal swabs (NPSs) are being widely used as specimens for multiplex real-time reverse transcription (RT)-PCR for respiratory virus detection. However, it remains unclear whether NPS ...specimens are optimal for all viruses targeted by multiplex RT-PCR. In addition, the procedure to obtain NPS specimens causes coughing in most patients, which possibly increases the risk of nosocomial spread of viruses. In this study, paired NPS and saliva specimens were collected from 236 adult male patients with suspected acute respiratory illnesses. Specimens were tested for 16 respiratory viruses by multiplex real-time RT-PCR. Among the specimens collected from the 236 patients, at least 1 respiratory virus was detected in 183 NPS specimens (77.5%) and 180 saliva specimens (76.3%). The rates of detection of respiratory viruses were comparable for NPS and saliva specimens (P = 0.766). Nine virus species and 349 viruses were isolated, 256 from NPS specimens and 273 from saliva specimens (P = 0.1574). Adenovirus was detected more frequently in saliva samples (P < 0.0001), whereas influenza virus type A and human rhinovirus were detected more frequently in NPS specimens (P = 0.0001 and P = 0.0289, respectively). The possibility of false-positive adenovirus detection from saliva samples was excluded by direct sequencing. In conclusion, neither of the sampling methods was consistently more sensitive than the other. We suggest that these cost-effective methods for detecting respiratory viruses in mixed NPS-saliva specimens might be valuable for future studies.
As Charles Darwin anticipated, living fossils provide excellent opportunities to study evolutionary questions related to extinction, competition, and adaptation. Ginkgo (Ginkgo biloba L.) is one of ...the oldest living plants and a fascinating example of how people have saved a species from extinction and assisted its resurgence. By resequencing 545 genomes of ginkgo trees sampled from 51 populations across the world, we identify three refugia in China and detect multiple cycles of population expansion and reduction along with glacial admixture between relict populations in the southwestern and southern refugia. We demonstrate multiple anthropogenic introductions of ginkgo from eastern China into different continents. Further analyses reveal bioclimatic variables that have affected the geographic distribution of ginkgo and the role of natural selection in ginkgo's adaptation and resilience. These investigations provide insights into the evolutionary history of ginkgo trees and valuable genomic resources for further addressing various questions involving living fossil species.
The RIG-I–like receptors (RLRs) retinoic acid–inducible gene I protein (RIG-I) and melanoma differentiation–associated protein 5 (MDA5) are cytosolic pattern recognition receptors that recognize ...specific viral RNA products and initiate antiviral innate immunity. Severe fever with thrombocytopenia syndrome virus (SFTSV) is a highly pathogenic member of the Bunyavirales. RIG-I, but not MDA5, has been suggested to sense some bunyavirus infections; however, the roles of RLRs in anti-SFTSV immune responses remain unclear. Here, we show that SFTSV infection induces an antiviral response accompanied by significant induction of antiviral and inflammatory cytokines and that RIG-I plays a main role in this induction by recognizing viral 5′-triphosphorylated RNAs and by signaling via the adaptor mitochondrial antiviral signaling protein. Moreover, MDA5 may also sense SFTSV infection and contribute to IFN induction, but to a lesser extent. We further demonstrate that the RLR-mediated anti-SFTSV signaling can be antagonized by SFTSV nonstructural protein (NSs) at the level of RIG-I activation. Protein interaction and MS-based analyses revealed that NSs interacts with the host protein tripartite motif–containing 25 (TRIM25), a critical RIG-I–activating ubiquitin E3 ligase, but not with RIG-I or Riplet, another E3 ligase required for RIG-I ubiquitination. NSs specifically trapped TRIM25 into viral inclusion bodies and inhibited TRIM25-mediated RIG-I-Lys-63–linked ubiquitination/activation, contributing to suppression of RLR-mediated antiviral signaling at its initial stage. These results provide insights into immune responses to SFTSV infection and clarify a mechanism of the viral immune evasion, which may help inform the development of antiviral therapeutics.
Gut dysbiosis has been reported implicated in ankylosing spondylitis (AS), a common chronic inflammatory disease mainly affects sacroiliac joints and spine. Utilizing deep sequencing on the feces of ...untreated AS patients, our study aimed at providing an in-depth understanding of AS gut microbiota.
We analyzed the fecal metagenome of 85 untreated AS patients and 62 healthy controls by metagenomic shotgun sequencing, and 23 post-treatment feces of those AS patients were collected for comparison. Comparative analyses among different cohorts including AS, rheumatoid arthritis and Behcet's disease were performed to uncover some common signatures related to inflammatory arthritis. Molecular mimicry of a microbial peptide was also demonstrated by ELISpot assay.
We identified AS-enriched species including Bacteroides coprophilus, Parabacteroides distasonis, Eubacterium siraeum, Acidaminococcus fermentans and Prevotella copri. Pathway analysis revealed increased oxidative phosphorylation, lipopolysaccharide biosynthesis and glycosaminoglycan degradation in AS gut microbiota. Microbial signatures of AS gut selected by random forest model showed high distinguishing accuracy. Some common signatures related to autoimmunity, such as Bacteroides fragilis and type III secretion system (T3SS), were also found. Finally, in vitro experiments demonstrated an increased amount of IFN-γ producing cells triggered by a bacterial peptide of AS-enriched species, mimicking type II collagen.
These findings collectively indicate that gut microbiota was perturbed in untreated AS patients with diagnostic potential, and some AS-enriched species might be triggers of autoimmunity by molecular mimicry. Additionally, different inflammatory arthritis shared some common microbial signatures.
•Gut microbiota was perturbed in untreated ankylosing spondylitis patients.•Distinctive species and pathways were found and correlated with clinical indices.•A diagnostic classifier was made based on differently expressed gut microbes.•Common gut microbial signatures of inflammatory arthritis were revealed.•A microbial peptide can trigger IFN-γ secretion by mimicking type II collagen.
Cell type-specific expression of optogenetic molecules allows temporally precise manipulation of targeted neuronal activity. Here we present a toolbox of four knock-in mouse lines engineered for ...strong, Cre-dependent expression of channelrhodopsins ChR2-tdTomato and ChR2-EYFP, halorhodopsin eNpHR3.0 and archaerhodopsin Arch-ER2. All four transgenes mediated Cre-dependent, robust activation or silencing of cortical pyramidal neurons in vitro and in vivo upon light stimulation, with ChR2-EYFP and Arch-ER2 demonstrating light sensitivity approaching that of in utero or virally transduced neurons. We further show specific photoactivation of parvalbumin-positive interneurons in behaving ChR2-EYFP reporter mice. The robust, consistent and inducible nature of our ChR2 mice represents a significant advance over previous lines, and the Arch-ER2 and eNpHR3.0 mice are to our knowledge the first demonstration of successful conditional transgenic optogenetic silencing. When combined with the hundreds of available Cre driver lines, this optimized toolbox of reporter mice will enable widespread investigations of neural circuit function with unprecedented reliability and accuracy.
As biological signals are mainly based on ion transport, the differences in signal carriers have become a major issue for the intimate communication between electrical devices and biological areas. ...In this respect, an ionic device which can directly interpret ionic signals from biological systems needs to be designed. Particularly, it is also required to amplify the ionic signals for effective signal processing, since the amount of ions acquired from biological systems is very small. Here, we report the signal amplification in ionic systems as well as sensing through the modified design of polyelectrolyte hydrogel-based ionic diodes. By designing an open-junction structure, ionic signals from the external environment can be directly transmitted to an ionic diode. Moreover, the minute ionic signals injected into the devices can also be amplified to a large amount of ions. The signal transduction mechanism of the ion-to-ion amplification is suggested and clearly verified by revealing the generation of breakdown ionic currents during an ion injection. Subsequently, various methods for enhancing the amplification are suggested.
The main building block and readout unit of the planned CDF Run IIb silicon detector is a "stave," a highly integrated mechanical, thermal, and electrical structure. One of its characteristic ...features is a copper-on-Kapton flexible cable for power, high voltage, data transmission, and control signals that is placed directly below the silicon microstrip sensors. The dense packaging makes deadtime-less operation of the stave a challenge since coupling of bus cable activity into the silicon sensors must be suppressed efficiently. The stave design features relevant for deadtime-less operation are discussed. The electrical performance achieved with stave prototypes is presented.
We report detections of two 1.2 mm continuum sources (\(S_\mathrm{1.2mm}\) ~ 0.6 mJy) without any counterparts in the deep \(H\)- and/or \(K\)-band image (i.e., \(K\)-band magnitude \(\gtrsim\) 26 ...mag). These near-infrared-dark faint millimeter sources are uncovered by ASAGAO, a deep and wide-field (\(\simeq\) 26 arcmin\(^2\)) Atacama Large Millimeter/submillimeter Array (ALMA) 1.2 mm survey. One has a red IRAC (3.6 and 4.5 \(\mu\)m) counterpart, and the other has been independently detected at 850 and 870 \(\mu\)m using SCUBA2 and ALMA Band 7, respectively. Their optical to radio spectral energy distributions indicate that they can lie at \(z \gtrsim\) 3-5 and can be in the early phase of massive galaxy formation. Their contribution to the cosmic star formation rate density is estimated to be ~ 1 \(\times\) 10\(^{-3}\) \(M_\odot\) yr\(^{-1}\) Mpc\(^{-3}\) if they lie somewhere in the redshift range of \(z\) ~ 3-5. This value can be consistent with, or greater than that of bright submillimeter galaxies (\(S_\mathrm{870\mu m}>\) 4.2 mJy) at \(z\) ~ 3-5. We also uncover 3 more candidates near-infrared-dark faint ALMA sources without any counterparts (\(S_\mathrm{1.2mm}\) ~ 0.45-0.86 mJy). These results show that an unbiased ALMA survey can reveal the dust-obscured star formation activities, which were missed in previous deep optical/near-infrared surveys.
Medial arterial calcification (MAC), a systemic vascular disease different from atherosclerosis, is associated with an increased incidence of cardiovascular events. Several studies have demonstrated ...that ambient temperature is one of the most important factors affecting cardiovascular events. However, there has been limited research on the effect of different ambient temperatures on MAC. In the present study, we showed that cold temperature exposure (CT) in mice slowed down the formation of vitamin D (VD)-induced vascular calcification compared with room temperature exposure (RT). To investigate the mechanism involved, we isolated plasma-derived exosomes from mice subjected to CT or RT for 30 days (CT-Exo or RT-Exo, respectively). Compared with RT-Exo, CT-Exo remarkably alleviated the calcification/senescence formation of vascular smooth muscle cells (VSMCs) and promoted autophagy by activating the phosphorylation of AMP-activated protein kinase (p-AMPK) and inhibiting phosphorylation of mammalian target of rapamycin (p-mTOR). At the same time, CT-Exo promoted autophagy in β-glycerophosphate (β-GP)-induced VSMCs. The number of autophagosomes and the expression of autophagy-related proteins ATG5 and LC3B increased, while the expression of p62 decreased. Based on a microRNA chip microarray assay and real-time polymerase chain reaction, miR-320a-3p was highly enriched in CT-Exo as well as thoracic aortic vessels in CT mice. miR-320a-3p downregulation in CT-Exo using AntagomiR-320a-3p inhibited autophagy and blunted its anti-calcification protective effect on VSMCs. Moreover, we identified that programmed cell death 4 (PDCD4) is a target of miR-320a-3p, and silencing PDCD4 increased autophagy and decreased calcification in VSMCs. Treatment with CT-Exo alleviated the formation of MAC in VD-treated mice, while these effects were partially reversed by GW4869. Furthermore, the anti-arterial calcification protective effects of CT-Exo were largely abolished by AntagomiR-320a-3p in VD-induced mice. In summary, we have highlighted that prolonged cold may be a good way to reduce the incidence of MAC. Specifically, miR-320a-3p from CT-Exo could protect against the initiation and progression of MAC via the AMPK/mTOR autophagy pathway.
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