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Feng, J. J.

Publications and source records attributed to Feng, J. J..

4 recordsLinked to original sources

Anatomical integrity of the human cochlea estimated with optical coherence tomography for future clinical application

The human cochlea is encased within the otic capsule, the densest bone in the body, posing significant challenges for anatomical imaging of cochlear structures. Because of difficult access and fragility of cochlear structures, our understanding of intracochlear anatomy has historically relied on postmortem histology. We thus have a limited understanding of human cochlear anatomy in its native, unfixed state. Clinical diagnostics for hearing loss, such as audiometry and otoacoustic emissions, offer functional assessments but fail to elucidate the often diverse underlying structural pathologies with any degree of precision. To address the critical need for assessing the human cochlear anatomy and associated pathologies without the risk of traumatizing cochlear structures, we imaged fresh cochleae in situ soon after death through the intact round window membrane with Optical Coherence Tomography (OCT) without inserting instruments inside or opening the cochlea. Micron-resolution OCT cross-sectional images of the human intracochlear structures were acquired and compared with corresponding histology systematically to aid in the identification of fine structural features and possible pathologies. With OCT imaging, we observed varied anatomy of the organ of Corti, and developed a cochlear "integrity" rating system to differentiate healthy appearing cochleae from various pathological states. These results demonstrate the capability of OCT to non-traumatically visualize cochlear integrity, highlighting its potential as a diagnostic tool. This work shows promise in translating the ability to determine the likelihood of existing or lack of hair cells and supporting cells in live patients, which would enable appropriate targeted treatments.

physiology↗

Exploring Mechanisms of Lipid Nanoparticle-Mucus Interactions in Healthy and Cystic Fibrosis Conditions

Mucus forms the first defense line of human lungs, and as such hampers the efficient delivery of therapeutics to the underlying epithelium. This holds particularly true for genetic cargo such as CRISPR-based gene editing tools which cannot readily surmount the mucosal barrier. While lipid nanoparticles (LNPs) emerged as versatile non-viral gene delivery systems that could help overcome the delivery challenge, many knowledge gaps remain, especially for diseased states such as cystic fibrosis (CF). This study provides fundamental insights into Cas9 mRNA or ribonucleoprotein-loaded LNP-mucus interactions in healthy and diseased states by assessing the impact of the genetic cargo, mucin sialylation, mucin concentration, ionic strength, pH, and polyethylene glycol (PEG) concentration and nature on LNP diffusivity leveraging experimental approaches and Brownian dynamics simulations. Taken together, this study identifies key mucus and LNP characteristics that are critical to enabling a rational LNP design for transmucosal delivery. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=100 SRC="FIGDIR/small/575680v1_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@10b1c0dorg.highwire.dtl.DTLVardef@5ebce4org.highwire.dtl.DTLVardef@1c34c1corg.highwire.dtl.DTLVardef@b9eb2d_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

Zasp52 strengthens whole embryo tissue integrity through supracellular actomyosin networks

During morphogenesis, large scale changes of tissue primordia occur that are all coordinated across an embryo. In Drosophila, several tissue primordia and embryonic regions are bordered or encircled by supracellular actomyosin cables, junctional actomyosin enrichments networked between many neighbouring cells. We show that the single Drosophila Alp/Enigma family protein Zasp52, which is most prominently found in Z-discs of muscles, is a component of many supracellular actomyosin structures during embryogenesis, including the ventral midline and the boundary of the salivary gland placode. Zasp52, we uncover, contains within its central coiled-coil region a type of actin-binding motif usually found in CapZbeta proteins, and this domain displays actin binding activity. Using endogenously-tagged lines we identify that Zasp52 interacts with a subset of junctional components, including APC2, Polychaetoid/ZO-1, and Sidekick, as well as actomyosin regulators. Analysis of zasp52 mutant embryos revealed that the severity of the embryonic defects observed scales inversely with the amount of functional protein left. Large tissue deformations occur at sites where actomyosin cables are found during embryogenesis, suggesting a model whereby supracellular cables containing Zasp52 aid to insulate morphogenetic changes from one another. This is further supported by the analysis of in vivo processes as well as by an in silico vertex model of morphogenetic domains separated by a stiffness boundary.

developmental biology↗

Dynamics of PAR proteins explain the oscillation and ratcheting mechanisms in dorsal closure

We present a vertex-based model for Drosophila dorsal closure that predicts the mechanics of cell oscillation and contraction from the dynamics of the PAR proteins. Based on experimental observations of how aPKC, Par-6 and Bazooka migrate from the circumference of the apical surface to the medial domain, and how they interact with each other and ultimately regulate the apicomedial actomyosin, we formulate a system of differential equations that capture the key features of the process. The oscillation in cell area in the early phase of dorsal closure results from an intracellular negative feedback loop that involves myosin, an actomyosin regulator, aPKC and Bazooka. In the slow phase, gradual sequestration of apicomedial aPKC into Bazooka clusters causes incomplete disassembly of the myosin network over each cycle of oscillation, thus producing the so-called ratchet. The fast phase of rapid cell and tissue contraction arises when medial myosin, no longer hindered by aPKC, builds up in time and produces sustained contraction. Thus, a minimal set of rules governing the dynamics of the PAR proteins, extracted from experimental observations, can account for all major mechanical outcomes of dorsal closure, including the transitions between its three distinct phases.\n\nInsert Received for publication Date and in final form Date

developmental biology↗