Enhanced branched-chain amino acid metabolism improves age-related reproduction in C. elegans.

Reproductive ageing is one of the earliest human ageing phenotypes, and mitochondrial dysfunction has been linked to oocyte quality decline; however, it is not known which mitochondrial metabolic processes are critical for oocyte quality maintenance with age. To understand how mitochondrial processes contribute to Caenorhabditis elegans oocyte quality, we characterized the mitochondrial proteomes of young and aged wild-type and long-reproductive daf-2 mutants. Here we show that the mitochondrial proteomic profiles of young wild-type and daf-2 worms are similar and share upregulation of branched-chain amino acid (BCAA) metabolism pathway enzymes.

Enhanced Branched-Chain Amino Acid Metabolism Improves Age-Related Reproduction in .

Reproductive aging is one of the earliest human aging phenotypes, and mitochondrial dysfunction has been linked to oocyte quality decline. However, it is not known which mitochondrial metabolic processes are critical for oocyte quality maintenance with age. To understand how mitochondrial processes contribute to oocyte quality, we characterized the mitochondrial proteomes of young and aged wild-type and long-reproductive mutants.

Lab, a microfluidic platform for the study of life history traits, reveals metformin and SGK-1 regulation of longevity and reproductive span.

The potential to carry out high-throughput assays in a whole organism in a small space is one of the benefits of , but worm assays often require a large sample size with frequent physical manipulations, rendering them highly labor-intensive. Microfluidic assays have been designed with specific questions in mind, such as analysis of behavior, embryonic development, lifespan, and motility. While these devices have many advantages, current technologies to automate worm experiments have several limitations that prevent widespread adoption, and most do not allow analyses of reproduction-linked traits.

Lab, a Microfluidic Platform for the Study of Life History Traits, reveals Metformin and SGK-1 regulation of Longevity and Reproductive Span.

The potential to carry out high-throughput assays in a whole organism in a small space is one of the benefits of , but worm assays often require a large sample size with frequent physical manipulations, rendering them highly labor-intensive. Microfluidic assays have been designed with specific questions in mind, such as analysis of behavior, embryonic development, lifespan, and motility. While these devices have many advantages, current technologies to automate worm experiments have several limitations that prevent widespread adoption, and most do not allow analyses of reproduction-linked traits.

Oocyte mitophagy is critical for extended reproductive longevity.

Women's reproductive cessation is the earliest sign of human aging and is caused by decreasing oocyte quality. Similarly, C. elegans' reproduction declines in mid-adulthood and is caused by oocyte quality decline.

Novel elasticity measurements reveal C. elegans cuticle stiffens with age and in a long-lived mutant.

Changes in biomechanical properties have profound impacts on human health. C. elegans might serve as a model for studying the molecular genetics of mammalian tissue decline.

CeAid: a smartphone application for logging and plotting Caenorhabditis elegans assays.

Caenorhabditis elegans is used as a model organism to study a wide range of topics in molecular and cellular biology. Conventional C. elegans assays often require a large sample size with frequent manipulations, rendering them labor-intensive.

Oleic Acid Protects Mothers From Mating-Induced Death and the Cost of Reproduction.

Reproduction comes at a cost, including accelerated death. Previous studies of the interconnections between reproduction, lifespan, and fat metabolism in were predominantly performed in low-reproduction conditions. To understand how increased reproduction affects lifespan and fat metabolism, we examined mated worms; we find that a Δ9 desaturase, FAT-7, is significantly up-regulated.

High-throughput behavioral screen in C. elegans reveals Parkinson's disease drug candidates.

We recently linked branched-chain amino acid transferase 1 (BCAT1) dysfunction with the movement disorder Parkinson's disease (PD), and found that RNAi-mediated knockdown of neuronal bcat-1 in C. elegans causes abnormal spasm-like 'curling' behavior with age. Here we report the development of a machine learning-based workflow and its application to the discovery of potentially new therapeutics for PD.

Metformin rescues Parkinson's disease phenotypes caused by hyperactive mitochondria.

Metabolic dysfunction occurs in many age-related neurodegenerative diseases, yet its role in disease etiology remains poorly understood. We recently discovered a potential causal link between the branched-chain amino acid transferase and the neurodegenerative movement disorder Parkinson's disease (PD). RNAi-mediated knockdown of is known to recapitulate PD-like features, including progressive motor deficits and neurodegeneration with age, yet the underlying mechanisms have remained unknown.

An integrative tissue-network approach to identify and test human disease genes.

Effective discovery of causal disease genes must overcome the statistical challenges of quantitative genetics studies and the practical limitations of human biology experiments. Here we developed diseaseQUEST, an integrative approach that combines data from human genome-wide disease studies with in silico network models of tissue- and cell-type-specific function in model organisms to prioritize candidates within functionally conserved processes and pathways. We used diseaseQUEST to predict candidate genes for 25 different diseases and traits, including cancer, longevity, and neurodegenerative diseases.

Label-free sorting of soft microparticles using a bioinspired synthetic cilia array.

Isolating cells of interest from a heterogeneous population has been of critical importance in biological studies and clinical applications. In this study, a novel approach is proposed for utilizing an active ciliary system in microfluidic devices to separate particles based on their physical properties. In this approach, the bottom of the microchannel is covered with an equally spaced cilia array of various patterns which is actuated by an external stimuli.

Modeling thermal inkjet and cell printing process using modified pseudopotential and thermal lattice Boltzmann methods.

Pseudopotential lattice Boltzmann methods (LBMs) can simulate a phase transition in high-density ratio multiphase flow systems. If coupled with thermal LBMs through equation of state, they can be used to study instantaneous phase transition phenomena with a high-temperature gradient where only one set of formulations in an LBM system can handle liquid, vapor, phase transition, and heat transport. However, at lower temperatures an unrealistic spurious current at the interface introduces instability and limits its application in real flow system.

Numerical simulation of cell squeezing through a micropore by the immersed boundary method.

The deformability of cells has been used as a biomarker to detect circulating tumor cells (CTCs) from patient blood sample using microfluidic devices with microscale pores. Successful separations of CTCs from a blood sample requires careful design of the micropore size and applied pressure. This paper presented a parametric study of cell squeezing through micropores with different size and pressure.

Finite Element Analysis of the Implantation Process of Overlapping Stents.

Overlapping stents are widely used in vascular stent surgeries. However, the rate of stent fractures (SF) and in-stent restenosis (ISR) after using overlapping stents is higher than that of single stent implantations. Published studies investigating the nature of overlapping stents rely primarily on medical images, which can only reveal the effect of the surgery without providing insights into how stent overlap influences the implantation process.

Acoustic Patterning for 3D Embedded Electrically Conductive Wire in Stereolithography.

In this paper, we reported a new approach for particle assembly with acoustic tweezer during three-dimensional (3D) printing for the fabrication of embedded conductive wire with 3D structures. A hexagon shaped acoustic tweezer was incorporated with Digital Light Processing (DLP) based stereolithography (SLA) printer to pattern conductive lines via aligning and condensing conductive nanoparticles. The effect of filler content on electrical resistivity and pattern thickness were studied for copper, magnetite nanoparticles, and carbon nanofiber reinforced nanocomposite samples.

Characterization of vascular permeability using a biomimetic microfluidic blood vessel model.

The inflammatory response in endothelial cells (ECs) leads to an increase in vascular permeability through the formation of gaps. However, the dynamic nature of vascular permeability and external factors involved is still elusive. In this work, we use a biomimetic blood vessel (BBV) microfluidic model to measure in real-time the change in permeability of the EC layer under culture in physiologically relevant flow conditions.

Characterization of Nanoparticle Dispersion in Red Blood Cell Suspension by the Lattice Boltzmann-Immersed Boundary Method.

Nanodrug-carrier delivery in the blood stream is strongly influenced by nanoparticle (NP) dispersion. This paper presents a numerical study on NP transport and dispersion in red blood cell (RBC) suspensions under shear and channel flow conditions, utilizing an immersed boundary fluid-structure interaction model with a lattice Boltzmann fluid solver, an elastic cell membrane model and a particle motion model driven by both hydrodynamic loading and Brownian dynamics. The model can capture the multiphase features of the blood flow.

A Cellular Model of Shear-Induced Hemolysis.

A novel model is presented to study red blood cell (RBC) hemolysis at cellular level. Under high shear rates, pores form on RBC membranes through which hemoglobin (Hb) leaks out and increases free Hb content of plasma leading to hemolysis. By coupling lattice Boltzmann and spring connected network models through immersed boundary method, we estimate hemolysis of a single RBC under various shear rates.

Nanoparticle transport and delivery in a heterogeneous pulmonary vasculature.

Quantitative understanding of nanoparticles delivery in a complex vascular networks is very challenging because it involves interplay of transport, hydrodynamic force, and multivalent interactions across different scales. Heterogeneous pulmonary network includes up to 16 generations of vessels in its arterial tree. Modeling the complete pulmonary vascular system in 3D is computationally unrealistic.

Shear induced alignment of short nanofibers in 3D printed polymer composites.

3D printing of composite materials offers an opportunity to combine the desired properties of composite materials with the flexibility of additive manufacturing in geometric shape and complexity. In this paper, the shear-induced alignment of aluminum oxide nanowires during stereolithography printing was utilized to fabricate a nanowire reinforced polymer composite. To align the fibers, a lateral oscillation mechanism was implemented and combined with wall pattern printing technique to generate shear flow in both vertical and horizontal directions.

The Configuration of Copolymer Ligands on Nanoparticles Affects Adhesion and Uptake.

Nanoparticles (NPs) are promising carriers for targeted drug delivery, photodynamic therapy, and imaging probes. A fundamental understanding of the dynamics of polymeric NP targeting to bilayer membranes is important to enhance the design of NPs for higher adhesion, binding percentage, and efficiency. In this study, dissipative particle dynamics simulations are applied to investigate the adhesion and uptake processes of the rod, spherical, and striped NPs to cell membranes.

Mechanical Properties of Nanoworm Assembled by DNA and Nanoparticle Conjugates.

Recently, DNA-nanoparticle conjugates have been widely used as building blocks for assembling complex nanostructures, due to their programmable recognitions, high cellular uptake and enhanced binding capabilities. In this study, a nanoworm structure, which can be applied in fields of drug targeting, image probing and thermal therapies, has been assembled by DNA-nanoparticle conjugates. Subsequently, its mechanical properties have been investigated due to their importance on the structural stability, transport and circulations of the nanoworm.

Characterization of nanoparticle binding dynamics in microcirculation using an adhesion probability function.

Quantitative understanding of nanoparticles transport and adhesion dynamic in microcirculation is very challenging due to complexity of fluid dynamics and imaging setup. In-vitro experiments within microfluidic channels showed the significant influence of shear rate, carrier size, particle-substrate chemistry and vessel geometry on particle deposition rate. However, there are few theoretical models that can accurately predict experimental results.