Biology subjects

Dang, C.

Publications and source records attributed to Dang, C..

7 recordsLinked to original sources

bioRxiv2026

Ligand-specific endothelial Notch signaling coordinates brain pericyte specification and expansion

Pericyte specification and expansion must be coordinated with vascular growth to establish a functional cerebrovascular network, yet how endothelial signals control these distinct developmental transitions remains incompletely understood. Here, using genetic manipulation, single-cell transcriptomic analysis, and longitudinal in vivo imaging in zebrafish, we identify ligand-specific endothelial Notch signaling as a mechanism coordinating brain pericyte development. Endothelial Jag2b is required for efficient pericyte specification from pericerebral progenitor pools and subsequently promotes Notch-dependent pericyte proliferation and population expansion. By contrast, endothelial Dll4 restrains pericyte proliferation and functionally opposes Jag2b-dependent expansion, demonstrating that distinct endothelial Notch ligands generate different developmental outputs. Endothelial Notch activation increases jag2b expression, and genetic interaction analyses establish Jag2b as an important mediator of Notch-dependent pericyte expansion. Moreover, genetic disruption of piezo1 reduces brain pericyte abundance, whereas endothelial jag2b expression rescues this phenotype, placing Jag2b downstream of Piezo1-dependent hemodynamic signaling. Together, these findings reveal a ligand-specific endothelial Notch program that integrates hemodynamic cues with endothelial-pericyte communication to coordinate the specification and expansion of brain pericytes during cerebrovascular development.

developmental biology↗

bioRxiv2025

Rational Design of Immunogenic Nanoparticles as a Platform for Enhanced Ovarian Cancer Immunotherapy in Mice

Ovarian cancer immunotherapy remains a challenge based on the "cold" tumor microenvironment. Herein we present a rational design to create immunogenic nanoparticles as a multi-agent platform that promotes immune response in a mouse model of ovarian cancer. The hybrid lipid-silica nanosystem is capable of co-loading four types of cargo molecules including a model antigen, nucleic acid-based adjuvant Cytosine-p-linked to Guanine (CpG, TLR3/9 agonist), lipid-based adjuvant (MPLA, TLR4 agonist) integrated into the lipid coat, and optionally a small molecule drug, such as the chemotherapeutic agent oxaliplatin, a well-established treatment for ovarian cancer. The optimization of the nanoplatform in terms of lipid composition, functionalized silica dendritic core formation, and final charge, as well as their compatibility with the complex loading profile highlights an opportunity for enhanced survival of mice with advanced ovarian cancer compared to monotherapy. Furthermore, intraperitoneal administration led to preferential accumulation within tumor-burdened tissues with selective accumulation in myeloid cells. High myeloid cell cytotoxicity negated the benefits of oxaliplatin. The inclusion of CpG in the nanoparticle formulation enhanced the survival of mice with ovarian cancer. To interpret these outcomes and guide future design, we also developed a mathematical model of nanoparticle-driven immune activation, which quantified treatment efficacy and identified key parameters governing tumor response. The presented hybrid nanoparticle i tunable, enabling delivery of alternative molecules therefore, thereby highlighting a promising platform for the treatment of peritoneal cancers. Graphical TOC O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=69 SRC="FIGDIR/small/657862v1_ufig1.gif" ALT="Figure 1000"> View larger version (26K): org.highwire.dtl.DTLVardef@1434599org.highwire.dtl.DTLVardef@18e79e6org.highwire.dtl.DTLVardef@e5285corg.highwire.dtl.DTLVardef@bcc604_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2023

Longitudinal analysis of innate immune system in infants with perinatal HIV infection until 18 months of age

With the advent of antiretroviral therapy (ART), perinatal HIV infection is declining globally but prevalence in Sub-Saharan Africa is still greater than other nations. The relationship of HIV replication in early infancy and the developing immune system is not well understood. In this study, we investigated cellular components of the innate immune system including Natural Killer (NK) cells, monocytes, and Dendritic Cells (DC) in a cohort of HIV exposed infected (HEI) and age-matched HIV exposed uninfected (HEU) infants from Mozambique. Study entry was at the first visit after delivery at age 1-2 months for HIV diagnosis and initiation of ART. Phenotypic analysis by multi-parameter flow cytometry revealed an expansion of total NK cells and the dysfunctional, CD56-CD16+, NK cell subset; increased activation in monocytes and DC; and higher levels of inflammatory homing receptor CCR5 on circulating DC subsets in the HEI infants. NKG2A, an inhibitory receptor for NK cytolytic function, was reduced in HEI compared to HEU and positively correlated with pre-ART viral load (VL) while expression of CCR2, the inflammatory homing receptor, on NK was negatively correlated with VL. Other subsets exhibited positive correlations with VL including the frequency of intermediate monocytes amongst total monocytes. Longitudinal analysis of VL indicated suboptimal ART adherence in HEI. Regardless of level of viral suppression achieved, the frequencies of specific innate immune subsets in HEI were normalized to HEU by 18m. These data support the notion that in early life, NK cells play a role in virus control and should be explored for functional attributes that are effective against HIV at this time during development. Overall, our study provides high resolution overview of the innate immune system during perinatal HIV infection. Author SummaryVertical transmission of HIV has been reduced globally in recent years, however in utero exposure and acquisition of HIV continues to occur, especially in sub-Saharan Africa. Immediate ART initiation is recommended in infants diagnosed with HIV, but adherence is often suboptimal due to behavioral and sociological challenges. The impacts of perinatal HIV infection and ART on the developing immune system in infants are still unclear. Here, we evaluated a cohort of HIV exposed infected infants, and age-matched HIV exposed uninfected infants from Mozambique at pre-ART (age 1-2m) and post-ART longitudinally (up to 18m) specifically to compare the innate immune cellular components. We found that circulating innate immune cells including Natural Killer (NK) cells, monocytes, and Dendritic Cells (DC) exhibited altered distributions and more activated (inflammatory) phenotypes at pre-ART in infants with HIV suggesting the presence of a virus specific immune response. Despite suboptimal ART adherence in the cohort, differences in innate immune subsets between infected (suppressed and unsuppressed) and uninfected were not observed longitudinally pointing to normalized immune development despite HIV infection. Our study provides new insights into the early innate immune response during perinatal HIV.

immunology↗

bioRxiv2018

Abundance and community composition of comammox bacteria in different ecosystems by a universal primer set

Complete ammonia oxidizing bacteria (CAOB) have been recognized as a new member of ammonia-oxidizing microorganisms (AOMs) due to its single-step nitrification capability. However, the abundance and diversity of CAOB in environmental ecosystems were still far from known owing to the lack of specific molecular marker. Herein, a universal primer set specifically targeting the both clades of CAOB amoA gene with high specificity and coverage was successfully designed. Intriguingly, real-time quantitative PCR tests revealed that CAOB were ubiquitous and unexpectedly abundant in agricultural soils, river sediments, intertidal zones, drinking water and wastewater treatment systems. Phylogenetic analysis indicated that clade A existed in all the five types of ecosystems, while clade B were only detected in soil and sediment samples. Four sub-clusters were further classified within clade A, in which N. nitrosa cluster dominated CAOB amoA in activated sludge samples while the new recognized soil cluster was the primary constitute in soils. Moreover, the niche specialization between different CAOB species and the environmental conditions were supposed to be the primary driven force to shape the diversity and community of CAOB. This study provided a strong evidence in support of the ubiquities and high abundances of CAOB in various environmental ecosystems and highlighted the significance of including CAOB as the new member of AOMs to re-evaluate the biogeochemical nitrogen cycle.

microbiology↗

bioRxiv2018

A large-scale, standardized physiological survey reveals higher order coding throughout the mouse visual cortex

To understand how the brain processes sensory information to guide behavior, we must know how stimulus representations are transformed throughout the visual cortex. Here we report an open, large-scale physiological survey of neural activity in the awake mouse visual cortex: the Allen Brain Observatory Visual Coding dataset. This publicly available dataset includes cortical activity from nearly 60,000 neurons collected from 6 visual areas, 4 layers, and 12 transgenic mouse lines from 221 adult mice, in response to a systematic set of visual stimuli. Using this dataset, we reveal functional differences across these dimensions and show that visual cortical responses are sparse but correlated. Surprisingly, responses to different stimuli are largely independent, e.g. whether a neuron responds to natural scenes provides no information about whether it responds to natural movies or to gratings. We show that these phenomena cannot be explained by standard local filter-based models, but are consistent with multi-layer hierarchical computation, as found in deeper layers of standard convolutional neural networks.

neuroscience↗

bioRxiv2017

Eye-Movement Reinstatement and Neural Reactivation: Testing the Hebbian Theory of Mental Imagery

Half a century ago, Donald Hebb posited that mental imagery is a constructive process that emulates perception. Specifically, Hebb claimed that visual imagery results from the reactivation of neural activity associated with viewing images. He also argued that neural reactivation and imagery benefit from the re-enactment of eye movement patterns that first occurred at viewing (fixation reinstatement). To investigate these claims, we applied multivariate pattern analyses to functional MRI (fMRI) and eye-tracking data collected while healthy human participants repeatedly viewed and visualized complex images. We observed that the specificity of neural reactivation correlated positively with vivid imagery and with memory for stimulus image details. Moreover, neural reactivation correlated positively with fixation reinstatement, meaning that image-specific eye movements accompanied image-specific patterns of brain activity during visualization. These findings support the conception of mental imagery as a simulation of perception, and provide evidence of the supportive role of eye-movement in neural reactivation.

neuroscience↗

bioRxiv2016

Systematic assessment of multi-gene predictors of pan-cancer cell line sensitivity to drugs exploiting gene expression data

Selected gene mutations are routinely used to guide the selection of cancer drugs for a given patient tumour. Large pharmacogenomic data sets were introduced to discover more of these single-gene markers of drug sensitivity. Very recently, machine learning regression has been used to investigate how well cancer cell line sensitivity to drugs is predicted depending on the type of molecular profile. The latter has revealed that gene expression data is the most predictive profile in the pan-cancer setting. However, no study to date has exploited GDSC data to systematically compare the performance of machine learning models based on multi-gene expression data against that of widely-used single-gene markers based on genomics data.\n\nHere we present this systematic comparison using Random Forest (RF) classifiers exploiting the expression levels of 13,321 genes and an average of 501 tested cell lines per drug. To account for time-dependent batch effects in IC50 measurements, we employ independent test sets generated with more recent GDSC data than that used to train the predictors and show that this is a more realistic validation than K-fold cross-validation. Across 127 GDSC drugs, our results show that the single-gene markers unveiled by the MANOVA analysis tend to achieve higher precision than these RF-based multi-gene models, at the cost of generally having a poor recall (i.e. correctly detecting only a small part of the cell lines sensitive to the drug). Regarding overall classification performance, about two thirds of the drugs are better predicted by multi-gene RF classifiers. Among the drugs with the most predictive of these models, we found pyrimethamine, sunitinib and 17-AAG.

bioinformatics↗