Biology subjects

Pei, P.

Publications and source records attributed to Pei, P..

4 recordsLinked to original sources

bioRxiv2024

Natural selection exerted by historical coronavirus epidemic(s): comparative genetic analysis in China Kadoorie Biobank and UK Biobank

BackgroundPathogens have been one of the primary sources of natural selection affecting modern humans. The footprints of historical selection events - "selective sweeps" - can be detected in the genomes of present-day individuals. Previous analyses of 629 samples from the 1000 Genomes Project suggested that an ancient coronavirus epidemic [~]20,000 years ago drove multiple selective sweeps in the ancestors of present-day East Asians, but not in other worldwide populations. ResultsUsing a much larger genetic dataset of 76,719 unrelated individuals from each of the China Kadoorie Biobank (CKB) and UK Biobank (UKB) to identify regions of long-range linkage disequilibrium, we further investigated signatures of past selective sweeps and how they reflect previous viral epidemics. Using independently-curated lists of human host proteins which interact physically or functionally with viruses (virus-interacting proteins; VIPs), we found enrichment in CKB for regions of long-range linkage disequilibrium at genes encoding VIPs for coronaviruses, but not DNA viruses. By contrast, we found no clear evidence for any VIP enrichment in UKB. These findings were supported by additional analyses using saltiLASSi, a selection-scan method robust to false positives caused by demographic events. By contrast, for GWAS signals for SARS-Cov2 susceptibility (critical illness, hospitalisation, and reported infection), there was no difference between UKB and CKB in the number located at or near signals of selection, as expected for a novel virus which has had no opportunity to impact the CKB/UKB study populations. ConclusionsTogether, these results provide evidence of selection events consistent with historical coronavirus epidemic(s) originating in East Asia. These results show how biobank-scale datasets and evolutionary genomics theory can provide insight into the study of past epidemics. The results also highlights how historic infectious diseases epidemics can shape the genetic architecture of present-day human populations.

genomics↗

bioRxiv2023

Heparan sulfate dependent phase separation of CCL5 and its chemotactic activity

Secreted chemokines form concentration gradients in target tissues to control migratory directions and patterns of immune cells in response to inflammatory stimulation; however, how the gradients are formed is much debated. Heparan sulfate (HS) binds to chemokines and modulates their activities. In this study, we investigated the roles of HS in the gradient formation and chemoattractant activity of CCL5 that is known to bind to HS. CCL5 and heparin underwent liquid-liquid phase separation (LLPS) and formed gradient, which was confirmed using CCL5 immobilized on heparin-beads. The biological implication of HS in CCL5 gradient formation was established in CHO-K1 (wild type) and CHO-677 (lacking HS) cells by Transwell assay. The effect of HS on CCL5 chemoattractant activity was further proved by Transwell assay of human peripheral blood cells. Finally, peritoneal injection of the chemokines into mice showed reduced recruitment of inflammatory cells either by mutant CCL5 (lacking heparin binding sequence) or by addition of heparin to wild type CCL5. Our experimental data propose that co-phase separation of CCL5 with HS establishes a specific chemokine concentration gradient to trigger directional cell migration. The results warrant further investigation on other heparin binding chemokines and allows for a more elaborate insight into disease process and new treatment strategies.

cell biology↗

bioRxiv2022

Diversity and ecological function of urease-producing bacteria in the cultivation environment of Gracilariopsis lemaneiformis

Urease-producing bacteria (UPB) provide inorganic nitrogen for primary producers by hydrolysis of urea. They play an important role in marine nitrogen cycle. However, there is still incomplete understanding of UPB and their ecological functions in the cultivation environment of red macroalage Gracilariopsis lemaneiformis. This study comprehensively analyzed the diversity of culturable UPB and explored their effects on urea uptake by G. lemaneiformis. Total 34 isolates belonging to four main bacterial phyla i.e. Proteobacteria, Bacteroidetes, Firmicutes, and Actinobacteria were identified through 16S rRNA sequencing and were screened for UPB by urea agar chromogenic medium assay and ureC gene cloning. Our data revealed that only 8 strains were found containing urease. These all UPB exhibited different urease activities by Berthelot reaction colorimetry assay. Furthermore, UPB with highest urease activity was selected to use as co-culture with G. lemaneiformis to explore its role in terms of promotion or inhibition of nitrogen uptake by G. lemaneiformis. The results showed that the urea consumption in culture media and the total cellular nitrogen in G. lemaneiformis found increased significantly in the UPB-co culture group than control i.e. in the sterile group (p < 0.05). Similarity, isotopic assay revealed that {delta}15N contents of G. lemaneiformis was significant higher in the UPB-co culture than in the control where {delta}15N-urea was the only nitrogen source in the culture media, indicating the UPB helped G. lemaneiformis to absorb more nitrogen from urea. Moreover, the highest content of {delta}15N was found in G. lemaneiformis with epiphytic bacteria, as compared to sterilized (control) showing that epiphytic bacteria along with UPB have compound effects in helping G. lemaneiformis absorb more nitrogen in urea. Taken together, these results provide unique insight into the ecological role of UPB and suggest that urease from macroalgae environment-associated bacteria might be important player in the marine nitrogen cycling. ImportanceTo the best of our knowledge, this is the first study ever conducted to isolate the culturable UPB from the cultivation environment of G. lemaneiformis by urea agar chromogenic medium assay, and also evaluate the effects of UPB on urea utilization in G. lemaneiformis by stable isotopic tracer technique. This study provides a new insight into the mechanism of organic nitrogen uptake and utilization in G. lemaneiformis, and is of great significance for a better understanding of the ecological role of functional bacteria (e.g. urease-producing bacteria) in the marine nitrogen cycling.

microbiology↗

bioRxiv2022

Pathogen-Host Adhesion between SARS-CoV-2 S Proteins from Different Variants and Human ACE2 Probed at Single-Molecule and Single-Cell Levels

Pathogen-Host adhesion is considered the first step of infection for many pathogens such as bacteria and virus. The binding of the receptor binding domain (RBD) of SARS-CoV-2 Spike protein (S protein) onto human angiotensin-converting enzyme 2 (ACE2) is considered as the first step for the SARS-CoV-2 to adhere onto the host cells during the infection. Within three years, a number of variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been found all around the world. Here, we investigated the adhesion of S Proteins from different variants and ACE2 using atomic force microscopy (AFM)-based single-molecule force spectroscopy (SMFS) and single-cell force spectroscopy (SCFS). We found that the unbinding force and binding probability of the S protein from Delta variant to the ACE2 was the highest among the variants tested in our study at both single-molecule and single-cell levels. Molecular dynamics simulation showed that ACE2-RBD (Omicron) complex is destabilized by the E484A and Y505H mutations and stabilized by S477N and N501Y mutations, when compared with Delta variant. In addition, a neutralizing antibody, produced by immunization with wild type RBD of S protein, could effectively inhibit the binding of S proteins from wild type, Delta and Omicron variants onto ACE2. Our results provide new insight for the molecular mechanism of the adhesive interactions between S protein and ACE2 and suggest that effective monoclonal antibody can be prepared using wild type S protein against the different variants.

biophysics↗