Publications by authors named "David Mankus"

Cholestasis, or disruption in bile flow, is a common yet poorly understood feature of many liver diseases and injuries. Despite this, many engineered human tissue models of liver disease fail to recapitulate physiological bile flow. Here, we present a 3D multicellular spheroid-based model of the human hepatobiliary junction, the interface between hepatocytes and cholangiocytes often disrupted in liver disease that is required for directing bile excreted by hepatocytes into the biliary ductal system.

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All cells are subject to geometric constraints, including the surface area-to-volume (SA/V) ratio, which can limit nutrient uptake, maximum cell size, and cell shape changes. Like the SA/V ratio of a sphere, it is generally assumed that the SA/V ratio of cells decreases as cell size increases. However, the structural complexity of the plasma membrane makes studies of the surface area challenging in cells that lack a cell wall.

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Lithium-metal batteries employing solid electrolytes (ceramics or polymers) could surpass the energy and power densities of current state-of-the-art lithium-ion batteries. Unfortunately, ceramic electrolyte/electrode interfaces suffer from poor interfacial contact, and polymer electrolytes show insufficient ionic conductivities for practical uses. Composite solid electrolytes, comprised of mixtures of ceramic and polymer electrolytes, could mitigate these challenges by combining high ionic conductivity with good interfacial contact.

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  • Deep brain stimulation has greatly advanced the treatment of neurological and psychiatric disorders, and there's interest in finding less invasive alternatives.
  • The study focuses on magnetoelectric nanodiscs (MENDs) that can convert magnetic fields into electric signals to modulate neurons remotely, showing effective results even below traditional stimulation thresholds.
  • When injected into specific brain regions of mice, MENDs can control behaviors related to reward and movement, paving the way for new applications in neuroscience research and therapy.
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  • The study examined the role of the MECP2 gene in astrocyte (AST) development using human embryonic stem cells, highlighting a shift from traditional neuron-focused research.
  • Significant findings showed that RTT (Rett Syndrome) hESC-derived cerebral organoids had smaller mitochondria in astrocytes compared to controls, indicating cellular dysfunction linked to MECP2 mutations.
  • Lastly, the altered mitochondrial function in RTT astrocytes, including increased reactive oxygen species and disrupted metabolism, suggests that these changes may negatively impact neuronal health and contribute to RTT-related brain issues.
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All cells are subject to geometric constraints, including the surface area-to-volume (SA/V) ratio, which can limit nutrient uptake, maximum cell size, and cell shape changes. Like the SA/V ratio of a sphere, it is generally assumed that the SA/V ratio of cells decreases as cell size increases. However, the structural complexity of the plasma membrane makes studies of the surface area challenging in cells that lack a cell wall.

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  • The study introduces a new injectable and self-healing hydrogel made from liposomes, designed for controlled release of low molecular weight hydrophilic drugs, which helps maintain high drug concentrations at specific target sites.
  • The hydrogel achieves slow drug release by encapsulating drugs either in the liposomes' aqueous cores or the surrounding space, addressing the common issue of rapid drug diffusion typically seen in hydrogels.
  • This innovative approach offers a promising solution for improved drug delivery, demonstrating high mechanical strength, minimal swelling, and a favorable tissue reaction when tested in vivo.
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  • The interaction between excitons and photons is crucial for developing technologies like molecular lasers and photonic circuits.
  • Two main factors influencing this interaction are the exciton's binding energy and the orientation of its dipole in relation to the photon field.
  • The study demonstrates a metal-organic framework (MOF) that can control exciton dipole directions, leading to distinct light emissions that could enhance future exciton-photonic applications.
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  • Nuclear pore complexes (NPCs) facilitate transport between the nucleus and cytoplasm and consist of around thirty different proteins called nucleoporins, organized in distinct rings.
  • Using advanced imaging techniques on human cells, researchers created a detailed structural model revealing that the inner ring of the NPC is wider than previously thought, increasing the central transport channel's volume by 75%.
  • The study also shows that the dynamics between the nucleoporins are crucial for maintaining the structure and asymmetry of the NPC, emphasizing how the environment affects its size and shape.
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Patchy particle interactions are predicted to facilitate the controlled self-assembly and arrest of particles into phase-stable and morphologically tunable "equilibrium" gels, which avoids the arrested phase separation and subsequent aging that is typically observed in traditional particle gels with isotropic interactions. Despite these promising traits of patchy particle interactions, such tunable equilibrium gels have yet to be realized in the laboratory due to experimental limitations associated with synthesizing patchy particles in high yield. Here, we introduce a supramolecular metal-coordination platform consisting of metallic nanoparticles linked by telechelic polymer chains, which validates the predictions associated with patchy particle interactions and facilitates the design of equilibrium particle hydrogels through limited valency interactions.

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  • The study presents a method for 3D visualization of vitrified cells, which allows for observing subcellular structures without the need for chemical fixation or staining.
  • The approach combines three imaging techniques—cryo-fluorescence confocal microscopy, volume cryo-focused ion beam SEM, and transmission cryo-electron tomography—to examine the same specimen at various scales under cryogenic conditions.
  • This workflow effectively revealed the 3D arrangement of organelles and protein inclusions in heat-shocked yeast cells and has the potential for broader applications in studying other cell types in different conditions.
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Lesion and electrode location verification are traditionally done via histological examination of stained brain slices, a time-consuming procedure that requires manual estimation. Here, we describe a simple, straightforward method for quantifying lesions and locating electrodes in the brain that is less laborious and yields more detailed results. Whole brains are stained with osmium tetroxide, embedded in resin, and imaged with a micro-CT scanner.

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Lesion verification and quantification is traditionally done via histological examination of sectioned brains, a time-consuming process that relies heavily on manual estimation. Such methods are particularly problematic in posterior cortical regions (e.g.

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Resolving patterns of synaptic connectivity in neural circuits currently requires serial section electron microscopy. However, complete circuit reconstruction is prohibitively slow and may not be necessary for many purposes such as comparing neuronal structure and connectivity among multiple animals. Here, we present an alternative strategy, targeted reconstruction of specific neuronal types.

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This study provides evidence for the Golgi-like activity of the multilayered interlaced network (MIN) and new ultrastructural observations of the MIN in the sporoplasm of Anncaliia algerae, a microsporidium that infects both insects and humans. The MIN is attached to the end of the polar tubule upon extrusion from the germinating spore. It surrounds the sporoplasm, immediately below its plasma membrane, and most likely maintains the integrity of the sporoplasm, as it is pulled through the everting polar tube.

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