Nucleophosmin 1 promotes mucosal immunity by supporting mitochondrial oxidative phosphorylation and ILC3 activity.

Nucleophosmin 1 (NPM1) is commonly mutated in myelodysplastic syndrome (MDS) and acute myeloid leukemia. Concurrent inflammatory bowel diseases (IBD) and MDS are common, indicating a close relationship between IBD and MDS. Here we examined the function of NPM1 in IBD and colitis-associated colorectal cancer (CAC).

A high-throughput microfluidic diploid yeast long-term culturing (DYLC) chip capable of bud reorientation and concerted daughter dissection for replicative lifespan determination.

Background: Budding yeast, Saccharomyces cerevisiae, has been extensively favored as a model organism in aging and age-related studies, thanks to versatile microfluidic chips for cell dynamics assay and replicative lifespan (RLS) determination at single-cell resolution. However, previous microfluidic structures aiming to immobilize haploid yeast may impose excessive spatial constraint and mechanical stress on cells, especially for larger diploid cells that sprout in a bipolar pattern.

Results: We developed a high-throughput microfluidic chip for diploid yeast long-term culturing (DYLC), optical inspection and cell-aging analysis.

A microfluidic single-cell array for in situ laminar-flow-based comparative culturing of budding yeast cells.

To facilitate in situ comparative culturing of budding yeast cells in a precisely controlled microenvironment, we developed a microfluidic single-cell array (MiSCA) with 96 traps (16 rows × 6 columns) for single-cell immobilization. Through optimization of the distances between neighboring traps and the applied flow rates by using a hydraulic equivalent circuit of the fluidic network, yeast cells were delivered to each column of the array by laminar focused flows and reliably captured at the traps by hydrodynamic forces with about 90% efficiency of cell immobilization. Immobilized cells in different columns within the same device can then be cultured in parallel while being exposed to different media and compounds delivered by laminar flows.

Design and 3D modeling investigation of a microfluidic electrode array for electrical impedance measurement of single yeast cells.

High-resolution microscopic imaging may cause intensive image processing and potential impact of light irradiation on yeast replicative lifespan (RLS). Electrical impedance spectroscopy (EIS) could be alternatively used to perform high-throughput and label-free yeast RLS assays. Prior to fabricating EIS-integrated microfluidic devices for yeast RLS determination, systematic modeling and theoretical investigation are crucial for device design and optimization.

Functional consequences of a rare missense BARD1 c.403G>A germline mutation identified in a triple-negative breast cancer patient.

We identified a rare missense germline mutation in BARD1 (c.403G>A or p.Asp135Asn) as pathogenic using integrated genomics and transcriptomics profiling of germline and tumor samples from an early-onset triple-negative breast cancer patient who later was administrated with a PARP inhibitor for 2 months.

Design and fabrication of an integrated heart-on-a-chip platform for construction of cardiac tissue from human iPSC-derived cardiomyocytes and in situ evaluation of physiological function.

In vitro model of the human cardiac tissues generated from human induced pluripotent stem cells (hiPSCs) could facilitate drug discovery and patient-specific studies of physiology and disease. However, the immature state of hiPSC-derived cardiomyocytes (hiPSC-CMs) compared to adult myocardium is a key defect that must be overcome to enable the potential applications of hiPSC-CMs in drug testing. For this purpose, we developed a heart-on-a-chip device that contains microfluidic channels for long-term dynamic culture of cells, platinum wire electrodes for electrical stimulation of hiPSC-CMs, and gold electrode arrays as acquisition electrodes for real-time recording electrophysiological signals of cardiac tissues.

Investigation of daughter cell dissection coincidence of single budding yeast cells immobilized in microfluidic traps.

Microfluidic methodologies allow for automatic and high-throughput replicative lifespan (RLS) determination of single budding yeast cells. However, the resulted RLS is highly impacted by the robustness of experimental conditions, especially the microfluidic yeast-trapping structures, which are designed for cell retention, growth, budding, and daughter cell dissection. In this work, four microfluidic yeast-trapping structures, which were commonly used to immobilize mother cells and remove daughter cells for entire lifespan of budding yeast, were systematically investigated by means of finite element modeling (FEM).

High-throughput discovery of genetic determinants of circadian misalignment.

Circadian systems provide a fitness advantage to organisms by allowing them to adapt to daily changes of environmental cues, such as light/dark cycles. The molecular mechanism underlying the circadian clock has been well characterized. However, how internal circadian clocks are entrained with regular daily light/dark cycles remains unclear.

A Bubble-Free Microfluidic Device for Easy-to-Operate Immobilization, Culturing and Monitoring of Zebrafish Embryos.

The development of miniaturized devices for studying zebrafish embryos has been limited due to complicated fabrication and operation processes. Here, we reported on a microfluidic device that enabled the capture and culture of zebrafish embryos and real-time monitoring of dynamic embryonic development. The device was simply fabricated by bonding two layers of polydimethylsiloxane (PDMS) structures replicated from three-dimensional (3D) printed reusable molds onto a flat glass substrate.

Multiplexing microelectrodes for dielectrophoretic manipulation and electrical impedance measurement of single particles and cells in a microfluidic device.

This work presents a microfluidic device, which was patterned with (i) microstructures for hydrodynamic capture of single particles and cells, and (ii) multiplexing microelectrodes for selective release via negative dielectrophoretic (nDEP) forces and electrical impedance measurements of immobilized samples. Computational fluid dynamics (CFD) simulations were performed to investigate the fluidic profiles within the microchannels during the hydrodynamic capture of particles and evaluate the performance of single-cell immobilization. Results showed uniform distributions of velocities and pressure differences across all eight trapping sites.

A p53-based genetic tracing system to follow postnatal cardiomyocyte expansion in heart regeneration.

In the field of heart regeneration, the proliferative potential of cardiomyocytes in postnatal mice is under intense investigation. However, solely relying on immunostaining of proliferation markers, the long-term proliferation dynamics and potential of the cardiomyocytes cannot be readily addressed. Previously, we found that a promoter-driving reporter predominantly marked the proliferating lineages in mice.

Correlated evolution between CK1δ Protein and the Serine-rich Motif Contributes to Regulating the Mammalian Circadian Clock.

Understanding the mechanism underlying the physiological divergence of species is a long-standing issue in evolutionary biology. The circadian clock is a highly conserved system existing in almost all organisms that regulates a wide range of physiological and behavioral events to adapt to the day-night cycle. Here, the interactions between hCK1ϵ/δ/DBT (Drosophila ortholog of CK1δ/ϵ) and serine-rich (SR) motifs from hPER2 (ortholog of Drosophila per) were reconstructed in a Drosophila circadian system.

Post-transcriptional Regulation of Nkx2-5 by RHAU in Heart Development.

RNA G-quadruplexes (G4s) play important roles in RNA biology. However, the function and regulation of mRNA G-quadruplexes in embryonic development remain elusive. Previously, we identified RHAU (DHX36, G4R1) as an RNA helicase that resolves mRNA G-quadruplexes.

Targeted Gene Delivery to Macrophages by Biodegradable Star-Shaped Polymers.

In this report, two biodegradable star-shaped polyasparamide derivatives and four analogues modified with either mannose or folic acid moiety for preferential targeting of a difficult-to-transfect immune cell type, i.e., macrophage, have been synthesized.

The DEAH-box helicase RHAU is an essential gene and critical for mouse hematopoiesis.

The DEAH helicase RHAU (alias DHX36, G4R1) is the only helicase shown to have G-quadruplex (G4)-RNA resolvase activity and the major source of G4-DNA resolvase activity. Previous report showed RHAU mRNA expression to be elevated in human lymphoid and CD34(+) BM cells, suggesting a potential role in hematopoiesis. Here, we generated a conditional knockout of the RHAU gene in mice.

Normal erythropoiesis but severe polyposis and bleeding anemia in Smad4-deficient mice.

The tumor suppressor Smad4 mediates signaling by the transforming growth factor beta (TGF-beta) superfamily of ligands. Previous studies showed that several TGF-beta family members exert important functions in hematopoiesis. Here, we studied the role of Smad4 in adult murine hematopoiesis using the inducible Mx-Cre/loxP system.

Extensive polymorphism and different evolutionary patterns of intron 2 were identified in the HLA-DQB1 gene.

Exon 2 and intron 2 of the HLA DQB1 gene from 20 individuals were cloned and sequenced and eight alleles were obtained. Based on our analysis, the nucleotide diversity of the 5' end of intron 2 was higher than the synonymous nucleotide diversity of exon 2, which may be due to the lower GC content and the 'hitch-hiking effect'. In contrast, the opposite phenomenon was observed for the 3' end of intron 2, which may be the result of the recombination between the 3' end and 5' end of intron 2 and the subsequent genetic drift.

[Comparative study of HLA-DQA1 and HLA-DRB1 allele in patients with endometriosis and adenomyosis].

Objective: To make a comparative study of HLA-DQA1 and HLA-DRB1 allele frequencies in the cases of endometriosis and adeonmyosis.

Methods: The allelic types of HLA-DQA1 and HLA-DRB1 were detected by polymerase chain reaction-sequence specific primers (PCR-SSP) technique in 51 cases of endometriosis, 45 cases of adenomyosis, and 44 normal individuals as the control.

Results: The frequencies of HLA-DQA1*0401(7.