Biology subjects

Li, B.

Publications and source records attributed to Li, B..

At least 361 records · Page 20Linked to original sources

bioRxiv2023

Computational Modelling of Immune Interaction and Epidermal Homeostasis in Psoriasis

Psoriasis is an incurable chronic inflammatory skin disease characterised by immune cytokine-stimulated epidermal hyperproliferation. This results in the skin becoming red with scaly plaques that can appear anywhere on the body, decreasing the quality of life for patients. Previous modelling studies of psoriasis have been limited to 2D models and lacked cell-cell interactions. We have developed a 3D agent-based model of epidermal cell dynamics to gain insights into how immune cytokine stimuli induces hyperproliferation in psoriasis to better understand disease formation and structural changes. Three main keratinocytes, stem, transit-amplifying (TA), differentiated and T cells, are modelled with proliferation and division governed by various nutrients and immune cytokines. Each cell has a set of attributes (growth rate, division probability, position, etc) whose values are governed by processes such as monod-based cellular growth model, probability-based division based on calcium and cytokine concentration and various forces to form the epidermal layers. The model has 2 steady states, healthy (non-lesional) and psoriatic (lesional) skin. Transition from healthy to psoriatic state is triggered by a temporary cytokine stimulus which causes hyperproliferation to occur, a hallmark of psoriasis. This results in the deepening of rete ridges and thickening of the epidermal structure. Model outputs has been validated against population ratios of stem, TA, differentiated, and T cells, cell cycle and turnover times in vivo. The model simulates the structural properties of epidermis, including layer stratification, formation of wave-like rete ridges, change in epidermal height and length of rete ridges from healthy to psoriasis. This has provided some insights on the complex spatio-temporal changes when transitioning between the 2 steady states and how a shot of temporary cytokine stimulus can induce different severity of psoriasis and alters proliferation between healthy and psoriatic skin in line with known literature. This provides the basis to study different cytokine simulation variations of psoriasis development and tracking of cell proliferation in the lab. It also provides a baseline to model the effects of psoriasis treatments such as narrowband-ultraviolet B (NB-UVB) or biologics and predict potential treatment outcomes for patients.

physiology↗

bioRxiv2023

Oncogenic KrasG12D specific non-covalent small molecule inhibitor reprograms tumor microenvironment and reverses early precursor lesions and in combination with immunotherapy regresses advanced PDAC in a CD8+ T cells dependent manner

Pancreatic ductal adenocarcinoma (PDAC) is associated with mutations in Kras, a known oncogenic driver of PDAC; and the KRASG12D mutation is present in nearly half of PDAC patients. Recently, a non-covalent small molecule inhibitor (MRTX1133) was identified with specificity to the KrasG12D mutant protein. Here we explore the impact of KrasG12D inhibition by MRTX1133 on advanced PDAC and its influence on the tumor microenvironment. Employing different orthotopic xenograft and syngeneic tumor models, eight different PDXs, and two different autochthonous genetic models, we demonstrate that MRTX1133 reverses early PDAC growth, increases intratumoral CD8+ effector T cells, decreases myeloid infiltration, and reprograms cancer associated fibroblasts. Autochthonous genetic mouse models treated with MRTX1133 leads to regression of both established PanINs and advanced PDAC. Regression of advanced PDAC requires CD8+ T cells and immune checkpoint blockade therapy (iCBT) synergizes with MRTX1133 to eradicate PDAC and prolong overall survival. Mechanistically, inhibition of mutant Kras in advanced PDAC and human patient derived organoids (PDOs) induces Fas expression in cancer cells and facilitates CD8+T cell mediated death. These results demonstrate the efficacy of MRTX1133 in different mouse models of PDAC associated with reprogramming of stromal fibroblasts and a dependency on CD8+ T cell mediated tumor clearance. Collectively, this study provides a rationale for a synergistic combination of MRTX1133 with iCBT in clinical trials.

cancer biology↗

bioRxiv2023

Fiberbots: Robotic fibers for high-precision minimally invasive surgery

Technologies that rely on the fundamental principle of thermal expansion have demonstrated high-precision, a growing demand in fields driven by miniaturization. However, scalable production of high aspect ratio devices that harness this capability while facilitating flexibility in design and functionality remains a challenge. We employed the high-throughput fiber thermal drawing technique to readily fabricate multimaterial fiberbots that can precisely and omnidirectionally move by asymmetric thermal expansion. These millimeter-scale fibers (< 2 mm) show excellent repeatability and linearity, negligible hysteresis, and can achieve micron-level resolution over four orders of magnitude motion range. By integrating these robotic fibers with medical devices that can perform cellular-level tissue imaging, diagnosis, and manipulation, we showcase their versatility through benchtop and preclinical animal studies and their overall potential impact on medicine, biomedical engineering, robotics, and beyond. One Sentence SummaryScalable manufacturing and integration of robotic fibers that deliver high-precision motion when heated.

bioengineering↗

bioRxiv2023

SynEcoSys: a multifunctional platform of large-scale single-cell omics data analysis

Next generation sequencing technologies enable the analysis of the transcriptomes of individual cells, providing a higher resolution of gene expression and function at the single cell level. Various single-cell data are continuously generated every year, covering fields from scientific research to clinical development. The fast-growing public datasets are collected by distinctive platforms, which are designed to facilitate biological discoveries, disease diagnosis, and new treatments. However, these platforms are hard to meet the urgency of having a unified data integration pipeline to improve comparability between datasets. Here we present SynEcoSys, an online multifunctional platform for single-cell transcriptomic data analysis, visualization, and exploration. SynEcoSys by Singleron Biotechnologies currently provides a massive collection of publicly available single-cell sequencing dataset, involving 46,326,175 cells from 731 datasets across multiple platforms and species. All datasets are generated with a strict and uniform data analysis pipeline and cell marker-based manual annotation, thus facilitating more comprehensive and reliable data mining. SynEcoSys is available at: https://www.synecosys.com.

bioinformatics↗

bioRxiv2023

Electroacupuncture prevents astrocyte atrophy to alleviate depression

Astrocyte atrophy is the main histopathological hallmark of the major depressive disorder (MDD) in humans and in animal models of depression. Here we show that electroacupuncture prevents astrocyte atrophy in the prefrontal cortex and alleviates depressive-like behaviour in mice subjected to the chronic unpredictable mild stress (CUMS). Treatment of mice with CUMS induced depressive-like phenotypes as confirmed by sucrose preference test, tail suspension test, and forced swim test. These behavioural changes were paralleled with morphological atrophy of astrocytes in the prefrontal cortex, revealed by analysis of 3D reconstructions of confocal Z-stack images of mCherry expressing astrocytes. This morphological atrophy was accompanied with a decrease in expression of cytoskeletal linker Ezrin, associated with formation of astrocytic leaflets, which form astroglial synaptic cradle. Electroacupuncture at the acupoint ST36 as well as treatment with anti-depressant fluoxetine prevented depressive-like behaviours, astrocytic atrophy and down-regulation of astrocytic ezrin. In conclusion, our data further strengthen the notion of a primary role of astrocytic atrophy in depression and reveal astrocytes as cellular target for electroacupuncture in treatment of depressive disorders.

neuroscience↗

bioRxiv2023

Aerobic exercise reverses aging-induced depth-dependent decline in cerebral microcirculation

Aging is a major risk factor for cognitive impairment. Aerobic exercise benefits brain function and may promote cognitive health in older adults. However, underlying biological mechanisms across cerebral gray and white matter are poorly understood. Selective vulnerability of the white matter to small vessel disease and a link between white matter health and cognitive function suggests a potential role for responses in deep cerebral microcirculation. Here, we tested whether aerobic exercise modulates cerebral microcirculatory changes induced by aging. To this end, we carried out a comprehensive quantitative examination of changes in cerebral microvascular physiology in cortical gray and subcortical white matter in mice (3-6 vs. 19-21 months old), and asked whether and how exercise may rescue age-induced deficits. In the sedentary group, aging caused a more severe decline in cerebral microvascular perfusion and oxygenation in deep (infragranular) cortical layers and subcortical white matter compared with superficial (supragranular) cortical layers. Five months of voluntary aerobic exercise partly renormalized microvascular perfusion and oxygenation in aged mice in a depth-dependent manner, and brought these spatial distributions closer to those of young adult sedentary mice. These microcirculatory effects were accompanied by an improvement in cognitive function. Our work demonstrates the selective vulnerability of the deep cortex and subcortical white matter to aging-induced decline in microcirculation, as well as the responsiveness of these regions to aerobic exercise.

neuroscience↗

bioRxiv2023

GLI1 facilitates rheumatoid arthritis by collaborative regulation of DNA methyltransferases

Rheumatoid arthritis (RA) is characterized by joint synovitis and bone destruction, the etiology of which remains to be explored. Overactivation of M1 macrophages and osteoclasts has been thought a direct cause of joint inflammation and bone destruction. Glioma-associated oncogene homolog 1 (GLI1) has been revealed to be closely linked to bone metabolism. In this study, GLI1-expression in synovial tissue of RA patients showed to be positively correlated with RA-related scores and was highly expressed in collagen-induced arthritis (CIA) mouse articular macrophage-like cells. The decreased expression and inhibition of nuclear transfer of GLI1 downregulated macrophage M1 polarization and osteoclast activation, the effect of which was achieved by modulation of DNA methyltransferases (DNMTs) via transcriptional regulation and protein interaction ways. By pharmacological inhibition of GLI1, the proportion of proinflammatory macrophages and the number of osteoclasts were significantly reduced, and the joint inflammatory response and bone destruction in CIA mice were alleviated. This study clarified the mechanism of GLI1 in macrophage phenotypic changes and activation of osteoclasts, suggesting potential applications of GLI1 inhibitor in the clinical treatment of RA.

cell biology↗

bioRxiv2023

FarmGTEx TWAS-server: an interactive web server for customized TWAS analysis in both human and farm animals

Transcriptome-wide association study (TWAS) is a powerful strategy for elucidating the molecular mechanisms behind the genetic loci of complex phenotypes. However, TWAS analysis is still daunting in many species due to the complication of the TWAS analysis pipeline, including the construction of the gene expression reference panel, gene expression prediction, and the subsequent association analysis in the large cohorts of genome-wide association study (GWAS). Farm animals are major protein sources and biomedical models for humans. To facilitate the translation of genetic findings across species, here we provide an interactive and easy-to-use multi-species TWAS web server for the entire community, called the FarmGTEx TWAS-server (http://twas.farmgtex.org), which is based on the GTEx and FarmGTEx projects. It includes gene expression data from 49, 34, and 23 tissues in 838 humans, 5,457 pigs, and 4,889 cattle, representing 38,180, 21,037, and 17,942 distinct eGenes in prediction models for humans, pigs, and cattle, respectively. It allows users to conduct gene expression prediction for any individuals with genotypes, GWAS summary statistics imputation, customized TWAS, and popular downstream functional annotation. It also provides 479,203, 1,208, and 657 tissue-gene-trait association trios for the research community, representing 1,129 human traits, 41 cattle traits, and 11 pig traits. In summary, the FarmGTEx TWAS-server is a one-stop solution for performing TWAS analysis for researchers without programming skills in both human and farm animal research communities. It will be maintained and updated timely within the FarmGTEx project to facilitate gene mapping and phenotype prediction within and across species.

bioinformatics↗

bioRxiv2023

Mitochondrial Genome Analysis and Phylogeny and Divergence Time Evaluation of the Strix aluco

In this study, a complete mitochondrial genome of the Strix aluco was reported for the first time, with a total length of 18,632 bp. There were 37 genes, including 22 tRNAs, 2 rRNAs, 13 protein-coding genes (PCGs), and 2 non-coding control regions (D-loop). The second-generation sequencing of the complete mitochondrial genome of the S. aluco was conducted using the Illumina platform, and then Tytoninae was used as the out-group, PhyloSuite software was applied to build the ML-tree and BI-tree of the Strigiformes, and finally, the divergence time tree was constructed using Beast2.6.7 software, the age of Miosurnia diurna fossil-bearing sediments (6.0-9.5 Ma) was set as the internal correction point. The common ancestor of the Strix was confirmed to have diverged during the Pleistocene(2.59~0.01Ma). The dramatic uplift of the Qinling Mountains in the Middle Pleistocene and the climate oscillation of the Pleistocene together caused Strix divergence between the northern and southern parts of mainland China. The isolation of glacial-interglacial rotation and glacier refuge was the main reason for the divergence of the common ancestor of the Strix uralensis and the S. aluco during this period. This study provides a reference for the evolution history of the Strix. Summary statementThis study was the first time to assemble the complete mitochondrial genome of Strix aluco, and report the divergence time of Strix. A full discussion was made, and it was inferred that the uplift of the Qinling Mountains and the glacial refuge led to the differentiation of this genus.

evolutionary biology↗

bioRxiv2023

FedDP: Secure Federated Learning for Disease Prediction with Imbalanced Genetic Data

It is challenging to share and aggregate biomedical data distributed among multiple institutions or computing resources due to various concerns including data privacy, security, and confidentiality. The federated Learning (FL) schema can effectively enable multiple institutions jointly perform machine learning by training a robust model with local data to satisfy the requirement of user privacy protection as well as data security. However, conventional FL methods are exposed to the risk of gradient leakage and cannot be directly applied to genetic data since they cannot address the unique challenges of data imbalance typically seen in genomics. To provide secure and efficient disease prediction based on genetic data distributed across multiple parties, we propose an FL framework enhanced with differential privacy (FedDP) on trained model parameters. In FedDP, local models can be trained among multiple local-hold genetic data with efficient secure and privacy-preserving techniques. The key idea of FedDP is to deploy differential privacy on compressed intermediate gradients that are computed and transmitted by optimizers from local parties. In addition, the unique weighted minmax loss in FedDP is able to address the difficulties of prediction for highly imbalanced genetic datasets. Our experiments on multiple genetic datasets demonstrate that FedDP provides a powerful tool to implement and evaluate various strategies in support of privacy preservation and model performance guarantee to overcome data imbalance.

bioinformatics↗

bioRxiv2023

Area postrema neurons mediate interleukin-6 function in cancer-associated cachexia

Interleukin-6 (IL-6) has been long considered a key player in cancer-associated cachexia1-15. It is believed that sustained elevation of IL-6 production during cancer progression causes brain dysfunctions, which ultimately result in cachexia16-20. However, how peripheral IL-6 influences the brain remains poorly understood. Here we show that neurons in the area postrema (AP), a circumventricular structure in the hindbrain, mediate the function of IL-6 in cancer-associated cachexia in mice. We found that circulating IL-6 can rapidly enter the AP and activate AP neurons. Peripheral tumor, known to increase circulating IL-61-5,15,18,21-23, leads to elevated IL-6 and neuronal hyperactivity in the AP, and causes potentiated excitatory synaptic transmission onto AP neurons. Remarkably, neutralization of IL-6 in the brain of tumor-bearing mice with an IL-6 antibody prevents cachexia, reduces the hyperactivity in an AP network, and markedly prolongs lifespan. Furthermore, suppression of Il6ra, the gene encoding IL-6 receptor, specifically in AP neurons with CRISPR/dCas9 interference achieves similar effects. Silencing of Gfral-expressing AP neurons also ameliorates the cancer-associated cachectic phenotypes and AP network hyperactivity. Our study identifies a central mechanism underlying the function of peripheral IL-6, which may serve as a target for treating cancer-associated cachexia.

neuroscience↗

bioRxiv2023

High frequency soil polarization can phenotype crop roots noninvasively

Noninvasive and nondestructive root phenotyping techniques under field conditions are sorely needed to advance plant root science. Soil polarization measured by electrical capacitance (ECsoil) has the potential to meet this requirement, but whether it specifically detects root properties remains unexplored. We carried out manipulative experiments where wheat (Triticum aestivum L.) and maize (Zea mays L.) roots were buried in soil or immersed in hydroponic solution combined with pot trials to reveal the mechanism of root trait detection by ECsoil, while a field experiment was conducted to test its feasibility to determine root depth distribution. We found that ECsoil measured at low current frequency (< 1 kHz) was not significantly affected by the addition of roots to the system either by burying roots in soil or immersing them in solution. At frequency greater than10 kHz a shift occurred, and root polarization contributed more to ECsoil which was positively correlated with root volume. When ECsoil was measured at high frequency (30 kHz -100 kHz) it was well correlated with root volume vertical distribution in the field. The measurement error after soil moisture calibration at depths of 10 cm, 20 cm, 30 cm and 40 cm was 0.4%, 12.0%, 1% and 34%, respectively. Our results demonstrate that ECsoil is a robust method to measure in situ root distribution and we believe the newly available high frequency measurement equipment combined with novel root prediction models will enable ECsoil to be widely used for root phenotyping in the future.

plant biology↗

bioRxiv2022

Prenatal Carotenoid Supplementation with Lutein or Zeaxanthin Ameliorates Oxygen-Induced Retinopathy (OIR) in Bco2-/- Macular Pigment Mice

PurposePremature infants at risk of retinopathy of prematurity (ROP) miss placental transfer of carotenoids, lutein (L) and zeaxanthin (Z), during the third trimester. We previously demonstrated that prenatal L and Z supplementation raises carotenoid levels in infants at birth in the Lutein and Zeaxanthin in Pregnancy (L-ZIP) study (NCT03750968). Based on their antioxidant effects and bioavailability, we hypothesized that prenatal maternal supplementation with macular carotenoids would reduce risk of ROP. To test this hypothesis, we utilized "macular pigment mice" genetically engineered to take up L and Z into the retina in a model of oxygen-induced retinopathy (OIR). MethodsPregnant Bco2-/- mice were divided into nine experimental subgroups based on the type of supplementation (L, Z, or placebo) and on maternal supplementation start date corresponding to the three trimesters of human fetal development (E0, E11, and P1). Pups and nursing mothers were exposed to 75% O2 for 5 days (P7-12) and returned to room air for 5 days (P12-17). Pups were sacrificed at P12 and P17, and their retinas were analyzed for vaso-obliteration (VO) and intravitreal neovascularization (INV). ResultsPups of pregnant mice supplemented with L or Z had significant reductions in VO and INV areas compared to placebo. Prenatal carotenoid supplementation starting at E0 or E11 was significantly more protective against OIR than postnatal supplementation starting at P1. ConclusionPrenatal supplementation with L and Z was beneficial in a mouse OIR model. We recommend testing prenatal L and Z supplementation in future human clinical trials to prevent ROP.

biochemistry↗

bioRxiv2022

Retrieving the near-complete genome of a threatened bird from wild frozen samples

Conservation genomics often relies on non-invasive methods to obtain DNA fragments which limit the power of multi-omic analyses for threatened species. Collecting samples from frozen dead animals in the wild provides an alternative approach to obtaining high-quality nucleic acids. Here, we report multi-omic analyses based on a well-preserved great bustard individual (Otis tarda, Otidiformes) of a recent death found in the mountainous region in Gansu, China. We generated a near-complete genome assembly (OTswu) having only 18 gaps scattering in 8 out of the 40 assembled chromosomes. Unlikely most other bird genome assemblies, OTswu contains complete chromosome models (2n = 80). We demonstrated that the great bustard genome likely retained the ancestral avian karyotype. We also characterized the DNA methylation landscapes of OTswu which are strongly correlated with GC content and gene expression. Our phylogenomic analysis suggested Otidiformes and Musophagiformes were sister groups that diverged from each other 46.3 million years ago. The genetic diversity of great bustard was found the lowest among the four available Otidiformes genomes, possibly due to population declines during past glacial periods. As one of the heaviest migratory birds, great bustard possesses several expanded gene families related to cardiac contraction, actin contraction, calcium ion signaling transduction, as well as positively selected genes enriching for metabolism. Finally, we identified an extremely young evolutionary stratum on the sex chromosome, a rare case among Neoaves. Together, our study combining long-read sequencing and RNA-seq technology provides a working strategy for conducting multi-omic analyses for threatened species by retrieving high-quality nucleic acids from dead animals frozen in the wild.

genomics↗

bioRxiv2022

Bovine blastocyst like structures derived from stem cell cultures

Understanding blastocyst formation and implantation is critical for improving farm animal reproduction but is hampered by a limited supply of embryos. We developed an efficient method to generate bovine blastocyst-like structures (termed blastoids) via the assembly of trophoblast stem cells and expanded potential stem cells. Bovine blastoids resemble blastocysts in morphology, cell composition, single-cell transcriptomes, and represent an accessible in vitro model for studying bovine embryogenesis.

developmental biology↗

bioRxiv2022

Prewhitening and Normalization Help Detect a Strong Cross-Correlation Between Daily Wastewater SARS-CoV-2 RNA Abundance and COVID-19 Cases in a Community

Wastewater surveillance is a promising technology for real-time tracking and even early detection of COVID-19 infections in communities. Although correlation analysis between wastewater surveillance data and the daily clinical COVID-19 case numbers has been frequently conducted, the importance of stationarity of the time-series data has not been well addressed. In this study, we demonstrated that strong yet spurious correlation could arise from non-stationary time-series data in wastewater surveillance, and data prewhitening to remove trends helped to reveal distinct cross-correlation patterns between daily clinical case numbers and daily wastewater SARS-CoV-2 concentration during a lockdown period in 2020 in Honolulu, Hawaii. Normalization of wastewater SARS-CoV-2 concentration by the endogenous fecal viral markers in the same samples significantly improved the cross-correlation, and the best correlation was detected at a two-day lag of the daily clinical case numbers. The detection of a significant correlation between daily wastewater SARS-CoV-2 RNA abundance and clinical case numbers also suggests that disease burden fluctuation in the community should not be excluded as a contributor to the often observed weekly cyclic patterns of clinical cases. Water impactWastewater surveillance represents an emerging water technology with significant human health benefits. The study demonstrated that non-stationary time-series data could lead to spurious correlation, highlighting the need for prewhitening. Normalization strategies could alleviate variations in sample collection and analyses, which is useful for detecting actual underlying relationships between wastewater surveillance data and clinical data.

microbiology↗

bioRxiv2022

cpSRP54 and FtsH cooperate thylakoid membrane associated proteostasis during de-etiolation in Arabidopsis thaliana

The thylakoid membrane protein quality control, which requires the coordination of membrane protein translocation and degradation of unassembled proteins, determines the chloroplast development during de-etiolation. Despite numerous efforts, the regulation of this progress in land plants is largely unknown. Here, we reported the isolation and characterization of pga4 mutants with defects in chloroplast development during de-etiolation. Map-based cloning and complementation assay confirmed that PGA4 encodes the chloroplast signal recognition particle 54 kDa protein (cpSRP54). A heterogeneous LhcB2-GFP was generated as an indicative substrate for cpSRP54-mediated thylakoid translocation. LhcB2-GFP were not assembled into functional complexes, and degraded to a short form dLhcB2-GFP during de-etiolation, through an N-terminal degradation initiated on thylakoid membranes. Further biochemical and genetic evidences demonstrated that the degradation of LhcB2-GFP to dLhcB2-GFP was disrupted in pga4, and var2 mutants caused by mutations in the VAR2/AtFtsH2 subunit of thylakoid FtsH. The yeast two-hybrid assay showed that the N-terminus of LhcB2-GFP which was degraded consequently, interacts with the protease domain of VAR2/AtFtsH2 in yeasts. Moreover, the over-accumulated LhcB2-GFP in pga4 and var2, formed protein aggregates, which were insoluble in mild nonionic detergents. Genetically, cpSRP54 is a new suppressor locus for the leaf variegation phenotype of var2. Those together demonstrated the coordination of cpSRP54 and thylakoid FtsH in maintenance of thylakoid membrane protein quality control during the assembly of photosynthetic complexes, and provided a trackable substrate and product for monitoring the cpSRP54-dependent protein translocation and the FtsH-dependent protein degradation. One Sentence SummaryWe revealed the coordination of cpSRP54 and FtsH in thylakoid membrane protein quality control, and provided a trackable marker for monitoring the activity of cpSRP54 and thylakoid FtsH protease.

plant biology↗

bioRxiv2022

Proteomic Analysis Defines the Interactome of Telomerase in the Protozoan Parasite, Trypanosoma brucei

Telomerase is a ribonucleoprotein enzyme responsible for maintaining the telomeric end of the chromosome. The telomerase enzyme requires two main components to function: the telomerase reverse transcriptase (TERT) and the telomerase RNA (TR), which provides the template for telomeric DNA synthesis. TR is a long noncoding RNA, which forms the basis of a large structural scaffold upon which many accessory proteins can bind and form the complete telomerase holoenzyme. These accessory protein interactions are required for telomerase activity and regulation inside cells. The interacting partners of TERT have been well studied in yeast, human, and Tetrahymena models, but not in lower eukaryotes, including clinically relevant human parasites. Here, using the protozoan parasite, Trypanosoma brucei (T. brucei) as a model, we have identified the interactome of T. brucei TERT (TbTERT) using a mass spectrometry-based approach. We identified previously known and unknown interacting factors of TbTERT, highlighting unique features of T. brucei telomerase biology. These unique interactions with TbTERT, suggest mechanistic differences in telomere maintenance between T. brucei and other eukaryotes.

molecular biology↗