Search

For unknow reasons, the melanocyte stem cell (McSC) system fails earlier than other adult stem cell populations1, which leads to hair greying in most humans and mice2,3. Current dogma states that McSCs are reserved in an undifferentiated state in the hair follicle niche, physically segregated from differentiated progeny that migrate away following cues of regenerative stimuli4–8. Here we show that most McSCs toggle between transit-amplifying and stem cell states for both self-renewal and generation of mature progeny, a mechanism fundamentally distinct from those of other self-renewing systems. Live imaging and single-cell RNA sequencing revealed that McSCs are mobile, translocating between hair follicle stem cell and transit-amplifying compartments where they reversibly enter distinct differentiation states governed by local microenvironmental cues (for example, WNT). Long-term lineage tracing demonstrated that the McSC system is maintained by reverted McSCs rather than by reserved stem cells inherently exempt from reversible changes. During ageing, there is accumulation of stranded McSCs that do not contribute to the regeneration of melanocyte progeny. These results identify a new model whereby dedifferentiation is integral to homeostatic stem cell maintenance and suggest that modulating McSC mobility may represent a new approach for the prevention of hair greying.

Reports of true aneurysms of the lower leg are rare. Among them, cases involving young patients are all the more rare, and there are many unexplored aspects to this pathological condition.

Psoriasis is an autoinflammatory/autoimmune skin disease and the epitome of an exaggerated primary inflammatory response in the surface barrier tissue. Despite the efficacy of dimethyl fumarate, an electrophilic drug for psoriasis management, there is a paucity of mechanistic evidence in vivo. In response to electrophiles, the Kelch-like erythroid cell–derived protein with cap-n-collar homology–associated protein 1/nuclear factor erythroid 2-related factor 2 (NRF2) system mediates a myriad of cytoprotective mechanisms, including the regulation of excessive inflammatory response and epidermal differentiation. Because the psoriasiform tissue reaction comprises neutrophil infiltration and parakeratotic scaling, it is hypothesized that Nrf2 not only regulates inflammatory responses but also maintains epidermal differentiation, a hallmark of epidermal homeostasis. By using the imiquimod-induced cutaneous inflammation model, an exaggerated inflammatory response and impaired epidermal differentiation in Nrf2−/−mice was detected. Dimethyl fumarate treatment in Nrf2+/+mice attenuated a psoriasiform tissue reaction and rescued epidermal differentiation, which was not observed in Nrf2−/−mice. In accordance with the fact that psoriasis plaques form well-demarcated parakeratotic lesions in association with the psoriasiform tissue reaction, the lesional skin showed reduced expression levels of NRF2and its downstream target genes compared with nonlesional skin. In conclusion, Nrf2 attenuates the psoriasiform tissue reaction and underscores the mechanistic legitimacy of the electrophile-based approach for the management of psoriasis.

In the operation of a centrifugal compressor of turbocharger, instability phenomena such as rotating stall and surge are induced at a lower flow rate close to the maximum pressure ratio. In this study, the compressed air at the exit of centrifugal compressor was re-circulated and injected to the impeller inlet by using two injection nozzles in order to suppress the surge phenomenon. The most effective circumferential position was examined to reduce the flow rate at the surge inception. Moreover, the influences of the injection on the fluctuating property of the flow field before and after the surge inception were investigated by examining the frequency of static pressure fluctuation on the wall surface and visualizing the compressor wall surface by oil-film visualization technique.

Intravenous pacemaker lead implantation for small children is not performed routinely. Here, we report the case of a pediatric patient who underwent endocardial lead implantation and follow-up for 16 years. The patient was a 4-year-old boy who underwent total correction of pulmonary atresia with ventricular septal defect following several palliative operations. After the patient underwent total correction, atrial flutter was noted. Atrial flutter was successfully terminated by overdrive pacing. However, atrial flutter occurred again immediately after overdrive pacing. To treat atrial flutter caused by sick sinus syndrome, a screw-in type lead was attached to the free wall of the right atrium and an excess loop was left to allow for the patient's growth. During the 16-year follow-up, no adverse effects were observed except for a gradual increase in pacing threshold. The selection of a small-sized endocardial lead and an appropriate entry vein, with meticulous management of the leads, makes implantation of an endocardial lead for small children easier and safer.

Intravenous pacemaker lead implantation for small children is not performed routinely. Here, we report the case of a pediatric patient who underwent endocardial lead implantation and follow-up for 16 years. The patient was a 4-year-old boy who underwent total correction of pulmonary atresia with ventricular septal defect following several palliative operations. After the patient underwent total correction, atrial flutter was noted. Atrial flutter was successfully terminated by overdrive pacing. However, atrial flutter occurred again immediately after overdrive pacing. To treat atrial flutter caused by sick sinus syndrome, a screw-in type lead was attached to the free wall of the right atrium and an excess loop was left to allow for the patient's growth. During the 16-year follow-up, no adverse effects were observed except for a gradual increase in pacing threshold. The selection of a small-sized endocardial lead and an appropriate entry vein, with meticulous management of the leads, makes implantation of an endocardial lead for small children easier and safer.

The electronic excitation energy transfer between excitons in porous silicon and iodine molecules in an organic solution is studied. From the time-resolved photoluminescence the rate of the energy transfer is increased with approaching a wavelength region where the photoluminescence spectrum of porous silicon overlaps the absorption spectrum of iodine molecules, and with increasing the radiative recombination rate of porous silicon. We show that the dependence of the rate is well explained by Forster type dipole-dipole interaction mechanism in which the diffusion of the assemblies and molecules is taken into consideration. Furthermore, it is found that the efficiency of the energy transfer strongly depends on the emission wavelength at low iodine concentration.

The nitration mechanism of pyrene (PYH) by aerating NO2in solution was studied by varying the factors (concentration of NO2, addition of HNO3gas and H2O, 1-substituent on PYH, and solvent) affecting the nitration. Only 1-nitropyrene was formed. In acetonitrile, both the decrease in PYH and the increase in 1-nitropyrene depicted sigmoid curves, that is, their changes proceeded abruptly after an induction period, and finally approached to zero. The characteristic feature was reasonably explained by the facts that H+dissociated from HNO3, accumulated by aerating NO2into trace water-containing acetonitrile and released by the nitration, acted as an autocatalyst. The nitration proceeded electrophilically based on the 1-substituent effect of PYH, and accelerated with increasing polarity of the solvents. The nitration was studied kinetically and an ionic mechanism involving NO2+as an electrophile was proposed. The nitration mechanism of PYH in acetonitrile was different from that in the adsorbed water on silica gel.

Rat p38 mitogen‐activated protein (MAP) kinase cDNA was isolated from rat kidney cDNA library using a PCR cloning strategy. The deduced amino acid sequence consists of 360 amino acids and shares 95.3% similarity with human p38 MAP kinase. The message for rat p38 MAP kinase was about 3.4 kilobases and was highly expressed in the kidney. In water‐deprived rat kidneys, the steady‐state levels of p38 MAP kinase mRNA increased about 2.7‐fold as compared with those of control rats. This result suggests that p38 MAP kinase may play an important role in the osmoregulation in the kidney.

Seven different restriction fragment length polymorphisms (RFLPs) at the N-acetylgalactosamine-6-sulfate sulfatase (GALNS) locus were analyzed using Southern blotting and polymerase chain reaction based techniques to search for the frequency of each RFLP produced by StyI, SphI, HaeIII, StuI, HapII, XhoI, and BamHI restriction endonucleases, respectively, in 36 mutant alleles, including two sibling cases and 100 normal alleles. Calculation of heterozygosity indexes showed that these RFLPs were polymorphic, ranging from 0.31 to 0.69 in mucopolysaccharidosis IVA (MPS IVA) patients compared with 0.21 to 0.65 in normal individuals. There was some significant difference in several RFLPs and in the combination with four kinds of RFLPs (SphI, StuI, HapII, XhoI polymorphisms). The normal alleles were composed of 13 different RFLPs haplotypes; the most common among the Japanese population carrying normal alleles was haplotype 8 (bDEF1) (31.3%), the others being dispersed. The same haplotype 8 was the most frequent in the mutant alleles (44.4%), with seven further haplotypes. These findings revealed the striking variety of polymorphic haplotypes in the MPS IVA gene. By using these five kinds of RFLPs, we examined the theoretical informativity of haplotype analysis in heterozygote detection in nine unrelated MPS IVA families and ten unrelated normal families. All the members of the MPS IVA families studied were diagnosed as a patient, carrier, or noncarrier. We propose that prenatal diagnosis or family analysis in cases in which mutations have not been characterized is now feasible.

Cornification involves cytoskeletal cross-linkages in corneocytes (the brick) and the secretion of lipids/adhesion structures to the interstitial space (the mortar). Because the assembly of lipid envelopes precedes corneocyte maturation, loricrin is supposed to be dispensable for the protection against desiccation. Although the phenotypes of Lorknockout (LKO) mice are obscure, the antioxidative response on the KEAP1/NRF2 signaling pathway compensates for the structural defect in utero. In this study, we asked how the compensatory response is evoked after the defects are repaired. To this end, the postnatal phenotypes of LKO mice were analyzed with particular attention to the permeability barrier function primarily maintained by the mortar. Ultrastructural analysis revealed substantially thinner cornified cell envelopes and increased numbers of lamellar granules in LKO mice. Superficial epidermal damages triggered the adaptive repairing responses that evoke the NRF2-dependent upregulation of genes associated with lamellar granule secretion in LKO mice. We also found that corneodesmosomes are less degraded in LKO mice. The observation suggests that loricrin and NRF2 are important effectors of cornification, in which proteins need to be secreted, cross-linked, and degraded in a coordinated manner.

ABSTRACTKeratinization provides tolerance to desiccation and mechanical durability. Loricrin, which is an epidermal thiol-rich protein, efficiently stabilizes terminally differentiated keratinocytes and maintains redox homeostasis. The discovery of the largely asymptomatic loricrin knockout (LKO) phenotype decades ago was rather unpredicted. Nevertheless, when including redox-driven, NF-E2-related factor 2-mediated backup responses, LKO mice provide opportunities for the observation of altered or “quasi-normal” homeostasis. Specifically, given that the tissue structure, as well as the local metabolism, transmits immunological signals, we sought to dissect the consequence of truncated epidermal differentiation program from immunological perspectives. Through a review of the aggregated evidence, we have attempted to generate an integrated view of the regulation of the peripheral immune system, which possibly occurs within the squamous epithelial tissue with truncated differentiation. This synthesis might not only provide insights into keratinization but also lead to the identification of factors intrinsic to the epidermis that imprint the immune effector function.

The present report describes a simple modification to the reinforcement technique by Copeland et al. using autologous pericardium for the Bentall procedure. Our modified technique may decrease the probability of leaks at the aortic root. Further, this technique preserves the advantages of the Valsalva graft, including tension-free coronary anastomosis and anatomical adaptability.

The electronic excitation energy transfer between excitons in porous silicon and iodine molecules in an organic solution is studied. From the time-resolved photoluminescence the rate of the energy transfer is increased with approaching a wavelength region where the photoluminescence spectrum of porous silicon overlaps the absorption spectrum of iodine molecules, and with increasing the radiative recombination rate of porous silicon. We show that the dependence of the rate is well explained by Förster type dipole-dipole interaction mechanism in which the diffusion of the assemblies and molecules is taken into consideration. Furthermore, it is found that the efficiency of the energy transfer strongly depends on the emission wavelength at low iodine concentration.