A High-Throughput Microphysiological Liver Chip System to Model Drug-Induced Liver Injury Using Human Liver Organoids.

Background And Aims: Drug-induced liver injury (DILI) is a major failure mode in pharmaceutical development. This study aims to address the limitations of existing preclinical models by assessing a high-throughput, microfluidic liver-on-a-chip system, termed "Curio Barrier Liver Chips," and its capacity to recapitulate the effects of chronic hepatotoxic drug treatment through metabolic and phenotypic characterization.

Methods: Curio Barrier liver chips (Curiochips), fabricated in an 8 × 2 well configuration, were utilized to establish three dimensional liver organoid cultures.

Stromal Fibroblasts Drive Host Inflammatory Responses That Are Dependent on Chlamydia trachomatis Strain Type and Likely Influence Disease Outcomes.

ocular strains cause a blinding disease known as trachoma. These strains rarely cause urogenital infections and are not found in the upper genital tract or rectum. Urogenital strains are responsible for a self-limited conjunctivitis and the sequelae of infertility, ectopic pregnancy, and hemorrhagic proctitis.

A role for glutamine 183 in the folate oxidative half-reaction of methylenetetrahydrofolate reductase from Escherichia coli.

The flavoprotein methylenetetrahydrofolate reductase (MTHFR) from Escherichia coli catalyzes a ping-pong reaction with NADH and 5,10-methylenetetrahydrofolate (CH-Hfolate) to produce NAD and 5-methyltetrahydrofolate (CH-Hfolate). This work focuses on the function of the invariant, active-site aminoacyl residue Gln183. X-ray structures of the enzyme complexes E(wild-type)•NADH and E(Glu28Gln)•CH-Hfolate indicate that Gln183 makes key hydrogen-bonding interactions with both NADH and folate in their respective half-reactions, suggesting roles in binding each substrate.

Corneal surface glycosylation is modulated by IL-1R and challenge but is insufficient for inhibiting bacterial binding.

Cell surface glycosylation is thought to be involved in barrier function against microbes at mucosal surfaces. Previously we showed that the epithelium of healthy mouse corneas becomes vulnerable to adhesion if it lacks the innate defense protein MyD88 (myeloid differentiation primary response gene 88), or after superficial injury by blotting with tissue paper. Here we explored their effect on corneal surface glycosylation using a metabolic label, tetra-acetylated -azidoacetylgalactosamine (AcGalNAz).

A Genome-wide RNAi Screen for Microtubule Bundle Formation and Lysosome Motility Regulation in Drosophila S2 Cells.

Long-distance intracellular transport of organelles, mRNA, and proteins ("cargo") occurs along the microtubule cytoskeleton by the action of kinesin and dynein motor proteins, but the vast network of factors involved in regulating intracellular cargo transport are still unknown. We capitalize on the Drosophila melanogaster S2 model cell system to monitor lysosome transport along microtubule bundles, which require enzymatically active kinesin-1 motor protein for their formation. We use an automated tracking program and a naive Bayesian classifier for the multivariate motility data to analyze 15,683 gene phenotypes and find 98 proteins involved in regulating lysosome motility along microtubules and 48 involved in the formation of microtubule filled processes in S2 cells.

Bidirectional intracellular transport: utility and mechanism.

Bidirectional transport of intracellular cargo along microtubule tracks is the subject of intense debate in the motility field. In the present review, we provide an overview of the models describing the possible mechanisms driving intracellular saltatory transport, taking into account current experimental results that may at first seem contradictory. We examine the phenomenon of saltatory motion, in an attempt to interpret the mechanistic debate in terms of the utility of saltatory motion.

Cytoplasmic microtubule sliding: An unconventional function of conventional kinesin.

There are well known examples in nature of microtubules dramatically changing their function by re-organizing their structure. Most interphase animal cells rely on the radial organization of the microtubule network for precise cargo delivery. Dividing cells re-organize microtubules with the help of motor proteins to form the spindle and drive the segregation of chromosomes into daughter cells.

Kinesin-1 heavy chain mediates microtubule sliding to drive changes in cell shape.

Microtubules are typically observed to buckle and loop during interphase in cultured cells by an unknown mechanism. We show that lateral microtubule movement and looping is a result of microtubules sliding against one another in interphase Drosophila S2 cells. RNAi of the kinesin-1 heavy chain (KHC), but not dynein or the kinesin-1 light chain, eliminates these movements.