Biology subjects

Yip, L.

Publications and source records attributed to Yip, L..

7 recordsLinked to original sources

bioRxiv2025

Cognitive Mode Detectable with Task-Based fMRI: Default Mode B (DMB)

In the context of task-based functional magnetic resonance imaging (fMRI), cognitive modes can be defined as task-general cognitive/sensory/motor processes which reliably elicit specific blood-oxygen-level-dependent (BOLD) signal pattern configurations. A number of cognitive modes are detectable with task-based fMRI, and here we focus on Default Mode B (DMB), a task-negative and late-trial peaking cognitive mode. The BOLD signal configurations associated with DMB are modulated by a range of tasks, and here we present eight. For each task, we report: (1) specific pattern-based (as opposed to coordinate-based) anatomical details essential for distinguishing DMB from other BOLD-based cognitive modes, and (2) task-induced BOLD signal changes associated with DMB over a range of task conditions. In order to facilitate recognition, we nick-named the anatomical patterns specific to DMB as follows: (1) In Flight, (2) Medial Temporal Dots, (3) Snowman Nose, (4) Angel Wings, and (5) Tripod. Evidence for DMB was derived from the timing and magnitude of task-induced BOLD signal changes induced by the following tasks: working memory, spatial capacity, semantic association, evidence integration, Ravens matrices, autobiographical event simulation, meditation and social perception. It was observed that deactivations in DMB were sensitive to cognitive load during attention to specific features of the external environment, based on evidence from working memory, spatial capacity, semantic association, evidence integration, and Ravens matrices. It was also observed that activations in DMB involved a cognitive process for engaging in mental projection into self-relevant social narratives, based on evidence from autobiographical event simulation, meditation, and social perception. Future research may explore DMB activation over a wider range of tasks in larger samples.

neuroscience↗

bioRxiv2022

Optimized path planning surpasses human efficiency in cryo-EM imaging

Cryo-electron microscopy (cryo-EM) represents a powerful technology for determining atomic models of biological macromolecules(Kuhlbrandt, 2014). Despite this promise, human-guided cryo-EM data collection practices limit the impact of cryo-EM because of a path planning problem: cryo-EM datasets typically represent 2-5% of the total sample area. Here, we address this fundamental problem by formalizing cryo-EM data collection as a path planning optimization from low signal data. Within this framework, we incorporate reinforcement learning (RL) and deep regression to design an algorithm that uses distributed surveying of cryo-EM samples at low magnification to learn optimal cryo-EM data collection policies. Our algorithm - cryoRL - solves the problem of path planning on cryo-EM grids, allowing the algorithm to maximize data quality in a limited time without human intervention. A head-to-head comparison of cryoRL versus human subjects shows that cryoRL performs in the top 10% of test subjects, surpassing the majority of users in collecting high-quality images from the same sample. CryoRL establishes a general framework that will enable human-free cryo-EM data collection to increase the impact of cryo-EM across life sciences research.

biophysics↗

bioRxiv2022

First detection of SARS-CoV-2 infection in Canadian wildlife identified in free-ranging white-tailed deer (Odocoileus virginianus) from southern Quebec, Canada

White-tailed deer are susceptible to SARS-CoV-2 and represent a highly important species for surveillance. Nasal swabs and retropharyngeal lymph nodes from white-tailed deer (n=258) collected in November 2021 from Quebec, Canada were analyzed for SARS-CoV-2 RNA. We employed viral genomics and transcriptomics to further characterize infection and investigate host response to infection. We detected Delta SARS-CoV-2 (AY.44) in deer from the Estrie region; sequences clustered with human sequences from GISAID collected in October 2021 from Vermont, USA, which borders this region. Mutations in the S-gene and a deletion in ORF8 encoding a truncated protein were detected. Host expression patterns in SARS-CoV-2 infected deer were associated with the innate immune response, including signalling pathways related to anti-viral, pro- and anti-inflammatory signalling, and host damage. Our findings provide preliminary insights of host response to SARS-CoV-2 infection in deer and underscores the importance of ongoing surveillance of key wildlife species for SARS-CoV-2.

microbiology↗

bioRxiv2021

SARS-CoV-2 wildlife surveillance in Ontario and Quebec, Canada

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the COVID-19 pandemic, is capable of infecting a variety of wildlife species. Wildlife living in close contact with humans are at an increased risk of SARS-CoV-2 exposure and if infected have the potential to become a reservoir for the pathogen, making control and management more difficult. ObjectiveTo conduct SARS-CoV-2 surveillance in urban wildlife from Ontario and Quebec, Canada, increasing our knowledge of the epidemiology of the virus and our chances of detecting spillover from humans into wildlife. MethodsUsing a One Health approach, we leveraged activities of existing research, surveillance, and rehabilitation programs among multiple agencies to collect samples from 776 animals from 17 different wildlife species between June 2020 and May 2021. Samples from all animals were tested for the presence of SARS-CoV-2 viral RNA, and a subset of samples from 219 animals across 3 species (raccoons, Procyon lotor; striped skunks, Mephitis mephitis; and mink, Neovison vison) were also tested for the presence of neutralizing antibodies. ResultsNo evidence of SARS-CoV-2 viral RNA or neutralizing antibodies was detected in any of the tested samples. ConclusionAlthough we were unable to identify positive SARS-CoV-2 cases in wildlife, continued research and surveillance activities are critical to better understand the rapidly changing landscape of susceptible animal species. Collaboration between academic, public and animal health sectors should include experts from relevant fields to build coordinated surveillance and response capacity.

pathology↗

bioRxiv2021

Preclinical evaluation of a SARS-CoV-2 mRNA vaccine PTX-COVID19-B

Safe and effective vaccines are needed to end the COVID-19 pandemic caused by SARS-CoV-2. Here we report the preclinical development of a lipid nanoparticle (LNP) formulated SARS-CoV-2 mRNA vaccine, PTX-COVID19-B. PTX-COVID19-B was chosen among three candidates after the initial mouse vaccination results showed that it elicited the strongest neutralizing antibody response against SARS-CoV-2. Further tests in mice and hamsters indicated that PTX-COVID19-B induced robust humoral and cellular immune responses and completely protected the vaccinated animals from SARS-CoV-2 infection in the lung. Studies in hamsters also showed that PTX-COVID19-B protected the upper respiratory tract from SARS-CoV-2 infection. Mouse immune sera elicited by PTX-COVID19-B vaccination were able to neutralize SARS-CoV-2 variants of concern (VOCs), including the B.1.1.7, B.1.351 and P.1 lineages. No adverse effects were induced by PTX-COVID19-B in both mice and hamsters. These preclinical results indicate that PTX-COVID19-B is safe and effective. Based on these results, PTX-COVID19-B was authorized by Health Canada to enter clinical trials in December 2020 with a phase 1 clinical trial ongoing (ClinicalTrials.gov number: NCT04765436). One Sentence SummaryPTX-COVID19-B is a SARS-CoV-2 mRNA vaccine that is highly immunogenic, safe, and effective in preventing SARS-CoV-2 infection in mice and hamsters and is currently being evaluated in human clinical trials.

immunology↗

bioRxiv2020

Early temporal dynamics of cellular responses to SARS-CoV-2

Type I interferons (IFNs) are our first line of defence against a virus. Protein over-expression studies have suggested the ability of SARS-CoV-2 proteins to block IFN responses. Emerging data also suggest that timing and extent of IFN production is associated with manifestation of COVID-19 severity. In spite of progress in understanding how SARS-CoV-2 activates antiviral responses, mechanistic studies into wildtype SARS-CoV-2-mediated induction and inhibition of human type I IFN responses are lacking. Here we demonstrate that SARS-CoV-2 infection induces a mild type I IFN response in vitro and in moderate cases of COVID-19. In vitro stimulation of type I IFN expression and signaling in human airway epithelial cells is associated with activation of canonical transcriptions factors, and SARS-CoV-2 is unable to inhibit exogenous induction of these responses. Our data demonstrate that SARS-CoV-2 is not adept in blocking type I IFN responses and provide support for ongoing IFN clinical trials. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/158154v2_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@193c540org.highwire.dtl.DTLVardef@7b106forg.highwire.dtl.DTLVardef@1741cfforg.highwire.dtl.DTLVardef@1bde68_HPS_FORMAT_FIGEXP M_FIG GRAPHICAL SUMMARY C_FIG

immunology↗

bioRxiv2020

Sequence, infectivity and replication kinetics of SARS-CoV-2 isolated from COVID-19 patients in Canada

SARS-CoV-2 emerged in December 2019 in Wuhan, China and has since infected over 1.5 million people, of which over 107,000 have died. As SARS-CoV-2 spreads across the planet, speculations remain about the range of human cells that can be infected by SARS-CoV-2. In this study, we report the isolation of SARS-CoV-2 from two COVID-19 patients in Toronto, Canada. We determined the genomic sequences of the two isolates and identified single nucleotide changes in representative populations of our virus stocks. More importantly, we tested a wide range of human immune cells for productive infection with SARS-CoV-2. Here we confirm that human primary peripheral blood mononuclear cells (PBMCs) are not permissive to SARS-CoV-2. As SARS-CoV-2 continues to spread globally, it is essential to monitor small nucleotide polymorphisms in the virus and to continue to isolate circulating viruses to determine cell susceptibility and pathogenicity using in vitro and in vivo infection models.

microbiology↗