Plasticity of Intestinal Epithelium: Stem Cell Niches and Regulatory Signals

The discovery of Lgr5+ intestinal stem cells (ISCs) triggered a breakthrough in the field of ISC research. Lgr5+ ISCs maintain the homeostasis of the intestinal epithelium in the steady state, while these cells are susceptible to epithelial damage induced by chemicals, pathogens, or irradiation. During the regeneration process of the intestinal epithelium, more quiescent +4 stem cells and short-lived transit-amplifying (TA) progenitor cells residing above Lgr5+ ISCs undergo dedifferentiation and act as stem-like cells. In addition, several recent reports have shown that a subset of terminally differentiated cells, including Paneth cells, tuft cells, or enteroendocrine cells, may also have some degree of plasticity in specific situations. The function of ISCs is maintained by the neighboring stem cell niches, which strictly regulate the key signal pathways in ISCs. In addition, various inflammatory cytokines play critical roles in intestinal regeneration and stem cell functions following epithelial injury. Here, we summarize the current understanding of ISCs and their niches, review recent findings regarding cellular plasticity and its regulatory mechanism, and discuss how inflammatory cytokines contribute to epithelial regeneration.     

Effect of polyethyleneimine-fatty acid complex type dispersant structure on the overall processing chain of Si3N4 ceramics using multicomponent non-aqueous slurries

The effect of fatty acid structure of polyethyleneimine (PEI)-fatty acid complex, which was designed as a polymer dispersant for multi-component non-aqueous slurries, on the overall processing chain of Si₃N₄ ceramics involving slurry stabilization, spray drying, compaction, and liquid sintering was investigated using PEI-oleic acid (PEI-OA) and PEI-isostearic (PEI-ISA) complexes. Si₃N₄-Y₂O₃-Al₂O₃-AlN-TiO₂/toluene slurries were selected as a real model for Si₃N₄-based multicomponent slurries. It was observed that both PEI-OA and PEI-ISA can stabilize Si₃N₄-Y₂O₃-Al₂O₃-AlN-TiO₂/toluene slurries; however, the PEI-ISA system tended to have slightly higher slurry viscosity, which was suspected to be due to the interactions between protruded PEI segments among short ISA chains. The spray-dried granules from PEI-ISA-stabilized slurry were observed to have filled structures with higher surface roughness whereas those prepared from PEI-OA-stabilized slurry were observed to have hollow-structured granules. The granules prepared from PEI-OA slurry had improved flow and compaction properties with higher relative density of green compacts compared with those prepared from PEI-ISA-stabilized slurry, whereas the relative density and microstructural homogeneity of S₃N₄ ceramics sintered at 1600?°C for 2?h were observed to be higher for the PEI-ISA system. It is suspected that PEI-OA effectively improved the dispersion stability of multicomponent slurries and flow/compaction properties of granules; however, the inhomogeneous microstructures of green compacts induced by the hollow-structured granules had an adverse effect on the sintering of Si₃N₄ ceramics.     

Chemical reaction kinetics dataset of Cs-I-B-Mo-O-H system for evaluation of fission product chemistry under LWR severe accident conditions

In order to improve LWR source term under severe accident conditions, the first version of a fission product chemistry database named ‘ECUME’ was developed. The ECUME is intended to include several datasets of major chemical reactions and their effective kinetic constants for representative severe accident sequences. It is expected that the ECUME can serve as a fundamental basis from which fission product chemical models can be elaborated for use in the severe accident analysis codes. The implemented chemical reactions in the first version were those for representative gas species in Cs-I-B-Mo-O-H system from 300 to 3000 K. The chemical reaction kinetic constants were evaluated from either literature data or calculated values using ab-initio calculations. The sample chemical reaction calculation using the presently constructed dataset showed meaningful kinetics effects at 1000 K. Comparison of the chemical equilibrium compositions by using the dataset with those by chemical equilibrium calculations has shown rather good consistency for the representative Cs-I-B-Mo-O-H species. From these results, it was concluded that the present dataset should be useful to evaluate fission product chemistry in Cs-I-B-Mo-O-H system under LWR severe accident conditions, where kinetics effects should be considered.     

Aerobic Exercise Ameliorates Cancer Cachexia-Induced Muscle Wasting through Adiponectin Signaling

Cachexia is a multifactorial syndrome characterized by muscle loss that cannot be reversed by conventional nutritional support. To uncover the molecular basis underlying the onset of cancer cachectic muscle wasting and establish an effective intervention against muscle loss, we used a cancer cachectic mouse model and examined the effects of aerobic exercise. Aerobic exercise successfully suppressed muscle atrophy and activated adiponectin signaling. Next, a cellular model for cancer cachectic muscle atrophy using C2C12 myotubes was prepared by treating myotubes with a conditioned medium from a culture of colon-26 cancer cells. Treatment of the atrophic myotubes with recombinant adiponectin was protective against the thinning of cells through the increased production of p-mTOR and suppression of LC3-II. Altogether, these findings suggest that the activation of adiponectin signaling could be part of the molecular mechanisms by which aerobic exercise ameliorates cancer cachexia-induced muscle wasting.     

Measurement of vertical and horizontal vibrations of a probe for acoustic evaluation of food texture

Two‐dimensional (vertical and horizontal) vibrations of a wedge‐type probe upon food rupture were evaluated separately using two accelerometers placed perpendicular to a guide rod of a swing‐arm device for texture evaluation of the flesh of three varieties of apples and three types of potato chips. Voltage signals from the accelerometers were filtered using a half‐octave band‐pass filter. The energy texture index (ETI), based on kinetic energy of the vertical or horizontal probe vibrations, was calculated over low to high frequency bands (no. 1–21). The spectra for the flesh of the three varieties of apples included two common peaks for vertical ETI at band no. 11 (1,120–1,600 Hz) and 19 (17,920–25,600 Hz) and horizontal ETI at band no. 1 (0–10 Hz) and 15 (4,480–6,400 Hz). The spectra for the three types of potato chips had a common ETI peak at band no. 11 (1,120–1,600 Hz) for horizontal ETI and at no. 15 (4,480–6,400 Hz) for vertical ETI. The three apple varieties gave rise to different intensities of vertical and horizontal ETIs while the two peaks were maintained. The thick potato chip type had higher vertical and horizontal ETIs than the thin and soft varieties in most bands; however, the thin type had the highest vertical ETIs only in lower bands (0–200 Hz). The soft type had the lowest vertical and horizontal ETI. The above results suggest that different food textures can be distinguished by two‐dimensional vibration analyses of probe insertion into a food sample based on frequency bands.     

Dimeric C34 Derivatives Linked through Disulfide Bridges as New HIV-1 Fusion Inhibitors

C34, a 34-mer fragment peptide, is contained in the HIV-1 envelope protein gp41. A dimeric derivative of C34 linked through a disulfide bridge at its C terminus was synthesized and found to display potent anti-HIV activity, comparable with that of a previously reported PEGylated dimer of C34REG. The reduction in the size of the linker moiety for dimerization was thus successful, and this result might shed some light on the mechanism of the suppression of six-helix bundle formation by these C34 dimeric derivatives. Addition of a Gly-Cys(CH₂CONH₂)-Gly-Gly motif at the N-terminal position of a C34 monomeric derivative significantly increased the anti-HIV-1 activity. This moiety functions as a new pharmacophore, and this might provide a useful insight into the design of potent HIV-1 fusion inhibitors.     

Investigation on the Interactions between Self-Assembled β-Sheet Peptide Nanofibers and Model Cell Membranes

Self-assembled peptide nanofibers (NFs) obtained from β-sheet peptides conjugated with drugs, including antigenic peptides, have recently attracted significant attention. However, extensive studies on the interactions of β-sheet peptide NFs with model cell membranes have not been reported. In this study, we investigated the interactions between three types of NFs, composed of PEG-peptide conjugates with different ethylene glycol (EG) lengths (6-, 12- and 24-mer), and dipalmitoylphosphatidylcholine (DPPC) Langmuir membranes. When increasing the EG chain length, those interactions significantly decreased considering measurements in the presence of the NFs of: (i) changes in surface pressure of the DPPC Langmuir monolayers and (ii) surface pressure–area (π–A) compression isotherms of DPPC. Because the observed trend was similar to the EG length dependency with regard to cellular association and cytotoxicity of the NFs that was reported previously, the interaction of NFs with phospholipid membranes represented a crucial factor to determine the cellular association and toxicity of the NFs. In contrast to NFs, no changes were observed with varying EG chain length on the interaction of the building block peptide with the DPPC membrane. The results obtained herein can provide a design guideline on the formulation of β-sheet peptide NFs, which may broaden its potential.     

Nonzero repair times dependent on the failure hazard

It is common in the literature on the reliability and maintenance of repairable systems to model the repair times as instantaneous. However, this is an unreasonable assumption for some complex systems, especially those requiring a high level of reliability, and such systems may spend a significant proportion of their lifetimes under maintenance and repair. We model the ageing of such a system with alternating stochastic processes. Operational times are generated at random and may have an increasing failure rate. Repair times are generated from a random process where the repair time is related to the hazard rate at failure. This yields lengthened repair times at late stages in a system subject to an increasing failure hazard rate but also accommodates long repair times at young ages in systems with a bathtub-shaped hazard rate function. We derive analytic results for a set of special cases of the model, show how simulation and inference can be carried out, and apply our method to real data from a large car manufacturer.