scholarly journals Single Extracellular Vesicles (EV) Proteomic Profiling Altered and Identifies Co-Localization of SARS-CoV-2 Nucleocapsid Protein with CD81/Integrin-Rich EV Subpopulation in Sputum Samples of COVID-19 Patients

Author(s):  
Ruiting Sun ◽  
Yanling Cai ◽  
Yumin Zhou ◽  
Ge Bai ◽  
Airu Zhu ◽  
...  

Abstract Understanding the pathogenesis of SARS-CoV-2 is crucial to respond to the current coronavirus disease 2019 (COVID-19) pandemic. Sputum samples from 20 COVID-19 patients and healthy controls were collected, respectively. During the isolation of infectious SARS-CoV-2 virus, EV-like vesicles were associated with virions under a transmission electron microscope. Next, the expression of IL6 and TGF-β increased in EVs derived from the sputum of patients, and these were highly correlated with the expression of the SARS-CoV-2 N protein. Further, proximity barcoding assay (PBA) was used to investigate the immune-related proteins in the EVs, and the relationship between EVs and SARS-CoV-2 N protein in COVID-19 patients’ samples. Particularly, to investigate the differential contribution of the specific EV subsets, the protein expression of a single EV was detected and analyzed for the first time. Among the 40 EV subpopulations, 18 were found to have significant differences. The EV subpopulation regulated by CD81 were most likely to correlate with the changes in the pulmonary microenvironment after SARS-CoV-2 infection. This study provides evidence on the association between EVs and the SARS-CoV-2 virus, give a deep insight into the possible pathogenesis of SARS-CoV-2 infection and the possibility of nanoparticles drug intervention in viral infection.

1998 ◽  
Vol 112 (2-3) ◽  
pp. 104-126
Author(s):  
Frank Van Der Ploeg

AbstractThis article examines the relationship between the Brussels painter Jan 11 van Coninxloo (ca. 1489-1561 or later) and the Benedictine convent of Groot-Bijgaarden. In earlier publications by J. Maquet-Tombu the link between certain members of the Van Coninxloo family and the Vorst convent have already been pointed out. A new chapter can now be added. In the archive of Groot-Bijgaarden convent are two books in which payments made by the prioresses Françoise and Catherine van Straten for the dccoration of the convent and the church are recorded. The books list a separate item for painting and polychrome work. Here, for the first time, the name Jan van Coninxloo crops up in connection with a sum paid for painting the side panels of the main altar. Van Coninxloo was also paid for painting organ doors, a vaulted ceiling and for 'rough painting'. Four triptychs by Van Coninxloo have also been preserved; they were commissions from women of noble birth who had taken the veil. The names of three of these nuns are known: Anthonine de Locquenghien, Berbel van dcr Noot and Marie Brant. The fourth was called Barbara (Berbel). In view of all this material it may be concluded that Van Coninxloo played a significant part in the decorative appearance of the convent church. He was responsible for triptychs on altars dedicated to St. Anne, St. John and St. Benedict. He also painted the smaller triptych with the Seven Sorrows of the Virgin, the panels of the high altar, doors for an organ and (part of) the ceiling decorations. The article offers a new insight into the context of a group of paintings and adds a number of works to Jan 11 van Coninxloo's oeuvre.


Author(s):  
Angela S. Chiu

In 1976, Hans Penth, pioneering scholar of Lanna, published a catalogue of over three hundred Buddha statues bearing inscriptions and dating from the fifteenth through twentieth centuries found in central Chiang Mai monasteries. This invaluable record is here analyzed in depth as a whole for the first time. It provides further insight into the relationship between Buddha images and donors. Statues were often sponsored through collaboration, reflecting the image’s role in materializing sociokarmic groupings seen as extending through the future. Donor resolutions reflect the significance of producing Buddha statues for Buddhism’s future prosperity as well as for donors’ individual spiritual and material aspirations. Images are often described by material and size, reflecting the relation between financial donation and merit generated. Also, refurbishments to statues indicate how they were never seen as finished, nor their appearance seen as sacrosanct; a statue is a palimpsest of its interactions with devotees through time.


2020 ◽  
Vol 37 (9) ◽  
pp. 2520-2530 ◽  
Author(s):  
Christian Brion ◽  
Claudia Caradec ◽  
David Pflieger ◽  
Anne Friedrich ◽  
Joseph Schacherer

Abstract To explore the origin of the diversity observed in natural populations, many studies have investigated the relationship between genotype and phenotype. In yeast species, especially in Saccharomyces cerevisiae, these studies are mainly conducted using recombinant offspring derived from two genetically diverse isolates, allowing to define the phenotypic effect of genetic variants. However, large genomic variants such as interspecies introgressions are usually overlooked even if they are known to modify the genotype–phenotype relationship. To have a better insight into the overall phenotypic impact of introgressions, we took advantage of the presence of a 1-Mb introgressed region, which lacks recombination and contains the mating-type determinant in the Lachancea kluyveri budding yeast. By performing linkage mapping analyses in this species, we identified a total of 89 loci affecting growth fitness in a large number of conditions and 2,187 loci affecting gene expression mostly grouped into two major hotspots, one being the introgressed region carrying the mating-type locus. Because of the absence of recombination, our results highlight the presence of a sexual dimorphism in a budding yeast for the first time. Overall, by describing the phenotype–genotype relationship in the Lachancea kluyveri species, we expanded our knowledge on how genetic characteristics of large introgression events can affect the phenotypic landscape.


2020 ◽  
Author(s):  
Christian Brion ◽  
Claudia Caradec ◽  
David Pflieger ◽  
Anne Friedrich ◽  
Joseph Schacherer

AbstractTo explore the origin of the diversity observed in natural populations, many studies have investigated the relationship between genotype and phenotype. In yeast species, especially in Saccharomyces cerevisiae, these studies are mainly conducted using recombinant offspring derived from two genetically diverse isolates, allowing to define the phenotypic effect of genetic variants. However, large genomic variants such as interspecies introgressions are usually overlooked even if they are known to modify the genotype-phenotype relationship. To have a better insight into the overall phenotypic impact of introgressions, we took advantage of the presence of a 1-Mb introgressed region, which lacks recombination and contains the mating-type determinant in the Lachancea kluyveri budding yeast. By performing linkage mapping analyses in this species, we identified a total of 89 loci affecting growth fitness in a large number of conditions and 2,187 loci affecting gene expression mostly grouped into two major hotspots, one being the introgressed region carrying the mating-type locus. Because of the absence of recombination, our results highlight the presence of a sexual dimorphism in a budding yeast for the first time. Overall, by describing the phenotype-genotype relationship in the L. kluyveri species, we expanded our knowledge on how genetic characteristics of large introgression events can affect the phenotypic landscape.


2020 ◽  
Author(s):  
Noah Avery Schuster

An initial outbreak of coronavirus disease 2019 (COVID-19) in China has resulted in a massive global pandemic causing well over 16,500,000 cases and 650,000 deaths worldwide. The virus responsible, SARS-CoV-2, has been found to possess a very close association with Bat-CoV RaTG13 and Pangolin-CoV MP789. The nucleocapsid protein can serve as a decent model for determining phylogenetic, evolutionary, and structural relationships between coronaviruses. Therefore, this study uses the nucleocapsid gene and protein to further investigate the relationship between SARS-CoV-2 and closely related bat and pangolin coronaviruses. Sequence and phylogenetic analyses have revealed the nucleocapsid gene and protein in SARS-CoV-2 are both closely related to those found in Bat-CoV RaTG13 and Pangolin-CoV MP789. Evidence of recombination was detected within the N gene, along with the presence of a double amino acid insertion found in the N-terminal region. Homology modeling for the N-Terminal Domain revealed similar structures but distinct electrostatic surfaces and topological variations in the β-hairpin that likely reflect specific adaptive functions. In respect to SARS-CoV-2, two amino acids (S37 and A267) were found to exist only in its N protein, along with an extended β-hairpin that bends towards the nucleotide binding site. Collectively, this study strengthens the relationship among SARS-CoV-2, Bat-CoV RaTG13, and Pangolin-CoV MP789, providing additional insights into the structure and adaptive nature of the nucleocapsid protein found in these coronaviruses. Furthermore, these data will enhance our understanding of the complete history behind SARS-CoV-2 and help assist in antiviral and vaccine development.


2017 ◽  
Vol 27 (3) ◽  
pp. 413-432
Author(s):  
Andrzej Rozwadowski

One of the aspects of the relationship between rock art and shamanism, which has been supposed to be of a universal nature, inspired by trance experience, concerns the intentional integration of the images with rock. Rock surface therefore has been interpreted, in numerous shamanic rock-art contexts, as a veil beyond which the otherworld could be encountered. Such an idea was originally proposed in southern Africa, then within Upper Palaeolithic cave art and also other rock-art traditions in diverse parts of the world. This paper for the first time discusses the relevance of this observation from the perspective of unquestionable shamanic culture in Siberia. It shows that the idea of the otherworld to be found on the other side of the rock actually is a widespread motif of shamanic beliefs in Siberia, and that variants of this belief provide a new mode of insight into understanding the semantics of Siberian rock art. Siberian data therefore support previous hypotheses of the shamanic nature of associating rock images with rock surface.


2017 ◽  
Vol 83 (15) ◽  
Author(s):  
Robert J. Dorosky ◽  
Jun Myoung Yu ◽  
Leland S. Pierson ◽  
Elizabeth A. Pierson

ABSTRACT R-type tailocins are high-molecular-weight bacteriocins that resemble bacteriophage tails and are encoded within the genomes of many Pseudomonas species. In this study, analysis of the P. chlororaphis 30-84 R-tailocin gene cluster revealed that it contains the structural components to produce two R-tailocins of different ancestral origins. Two distinct R-tailocin populations differing in length were observed in UV-induced lysates of P. chlororaphis 30-84 via transmission electron microscopy. Mutants defective in the production of one or both R-tailocins demonstrated that the killing spectrum of each tailocin is limited to Pseudomonas species. The spectra of pseudomonads killed by the two R-tailocins differed, although a few Pseudomonas species were either killed by or insusceptible to both tailocins. Tailocin release was disrupted by deletion of the holin gene within the tailocin gene cluster, demonstrating that the lysis cassette is required for the release of both R-tailocins. The loss of functional tailocin production reduced the ability of P. chlororaphis 30-84 to compete with an R-tailocin-sensitive strain within biofilms and rhizosphere communities. Our study demonstrates that Pseudomonas species can produce more than one functional R-tailocin particle sharing the same lysis cassette but differing in their killing spectra. This study provides evidence for the role of R-tailocins as determinants of bacterial competition among plant-associated Pseudomonas in biofilms and the rhizosphere. IMPORTANCE Recent studies have identified R-tailocin gene clusters potentially encoding more than one R-tailocin within the genomes of plant-associated Pseudomonas but have not demonstrated that more than one particle is produced or the ecological significance of the production of multiple R-tailocins. This study demonstrates for the first time that Pseudomonas strains can produce two distinct R-tailocins with different killing spectra, both of which contribute to bacterial competition between rhizosphere-associated bacteria. These results provide new insight into the previously uncharacterized role of R-tailocin production by plant-associated Pseudomonas species in bacterial population dynamics within surface-attached biofilms and on roots.


Author(s):  
Yanhao Zhang ◽  
Xiuxing Jiang ◽  
Qin Deng ◽  
Ziyi Gao ◽  
Xiangyu Tang ◽  
...  

Abstract Background MYO1C, an actin-based motor protein, is involved in the late stages of autophagosome maturation and fusion with the lysosome. The molecular mechanism by which MYO1C regulates autophagosome-lysosome fusion remains largely unclear. Methods Western blotting was used to determine the expression of autophagy-related proteins. Transmission electron microscopy (TEM) was used to observe the ultrastructural changes. An immunoprecipitation assay was utilized to detect protein-protein interactions. Immunofluorescence analysis was used to detect autophagosome-lysosome fusion and colocalization of autophagy-related molecules. An overexpression plasmid or siRNA against MYO1C were sequentially introduced into human breast cancer MDA-MB-231 cells. Results We show here that cepharanthine (CEP), a novel autophagy inhibitor, inhibited autophagy/mitophagy through blockage of autophagosome-lysosome fusion in human breast cancer cells. Mechanistically, we found for the first time that MYO1C was downregulated by CEP treatment. Furthermore, the interaction/colocalization of MYO1C and F-actin with either LC3 or LAMP1 was inhibited by CEP treatment. Knockdown of MYO1C further decreased the interaction/colocalization of MYO1C and F-actin with either LC3 or LAMP1 inhibited by CEP treatment, leading to blockade of autophagosome-lysosome fusion. In contrast, overexpression of MYO1C significantly restored the interaction/colocalization of MYO1C and F-actin with either LC3 or LAMP1 inhibited by CEP treatment. Conclusion These findings highlight a key role of MYO1C in the regulation of autophagosome-lysosome fusion through F-actin remodeling. Our findings also suggest that CEP could potentially be further developed as a novel autophagy/mitophagy inhibitor, and a combination of CEP with classic chemotherapeutic drugs could become a promising treatment for breast cancer.


2021 ◽  
Vol 12 ◽  
Author(s):  
Feng Dai ◽  
Pengfei Yu ◽  
Zhenhan Yu ◽  
Hong Jiang ◽  
Zhijia Ma ◽  
...  

Autophagy has been proved to occur in rats with intervertebral disc degeneration (IVDD). Yiqi Huoxue recipe (YQHXR), an effective therapy of traditional Chinese medicine, was widely used for ruptured lumbar disc herniation under clinical observation. More importantly, YQHXR positively regulated the expression of autophagy-related proteins. However, little is known about the significance of YQHXR in the pathologic process of IVDD. Therefore, this study explored the protective effect of YQHXR based on IVDD rat model through magnetic resonance imaging and histopathologic analysis. Then we evaluated the formation of autophagosomes in the degenerated intervertebral disc by transmission electron microscope. Real-time PCR was used to detect the changes of autophagy-related genes. Western blot and immunoprecipitation were used to assess the protein expression of the autophagy-related pathway. We found that YQHXR-induced autophagy attenuated the release of inflammatory factors. In addition, YQHXR promoted the formation of Beclin1-VPS34 complex to activate autophagy through not only activation of the upstream protein AMPK and upregulation of the deubiquitinase USP13, thus in turn alleviating the development of IVDD. We proposed the potential molecular mechanism of YQHXR on autophagy for the first time, so as to provide a theoretical and experimental basis for the clinical application of YQHXR in the treatment of IVDD-related diseases.


eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Sven Schenk ◽  
Stephanie C Bannister ◽  
Fritz J Sedlazeck ◽  
Dorothea Anrather ◽  
Bui Quang Minh ◽  
...  

Many marine animals, ranging from corals to fishes, synchronise reproduction to lunar cycles. In the annelid Platynereis dumerilii, this timing is orchestrated by an endogenous monthly (circalunar) clock entrained by moonlight. Whereas daily (circadian) clocks cause extensive transcriptomic and proteomic changes, the quality and quantity of regulations by circalunar clocks have remained largely elusive. By establishing a combined transcriptomic and proteomic profiling approach, we provide first systematic insight into the molecular changes in Platynereis heads between circalunar phases, and across sexual differentiation and maturation. Whereas maturation elicits large transcriptomic and proteomic changes, the circalunar clock exhibits only minor transcriptomic, but strong proteomic regulation. Our study provides a versatile extraction technique and comprehensive resources. It corroborates that circadian and circalunar clock effects are likely distinct and identifies key molecular brain signatures for reproduction, sex and circalunar clock phase. Examples include prepro-whitnin/proctolin and ependymin-related proteins as circalunar clock targets.


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