ASK1-dependent recruitment and activation of macrophages induce hair growth in skin wounds

Apoptosis signal-regulating kinase 1 (ASK1) is a member of the mitogen-activated protein 3-kinase family that activates both c-Jun NH2-terminal kinase and p38 pathways in response to inflammatory cytokines and physicochemical stress. We report that ASK1 deficiency in mice results in dramatic retardation of wounding-induced hair regrowth in skin. Oligonucleotide microarray analysis revealed that expression of several chemotactic and activating factors for macrophages, as well as several macrophage-specific marker genes, was reduced in the skin wound area of ASK1-deficient mice. Intracutaneous transplantation of cytokine-activated bone marrow-derived macrophages strongly induced hair growth in both wild-type and ASK1-deficient mice. These findings indicate that ASK1 is required for wounding-induced infiltration and activation of macrophages, which play central roles in inflammation-dependent hair regrowth in skin

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Synthesis and photoreactivity of α-diketone-type precursors of acenes and their use in organic-device fabrication

Acenes are highly promising p-type organic semiconductors, and have been the subject of intense studies. However, acenes are often low in solubility and stability, which poses major obstacles in the synthesis and processing of this class of compounds. In order to overcome the problem, a series of α-diketone-type acene precursors have been developed. These precursors are generally more soluble and stable than the corresponding acene compounds, and their quantitative conversion can be achieved simply by photoirradiation both in solution and in the solid state. Further, the irreversible photoinduced removal of the α-diketone unit can be used to alter the optoelectronic properties of fluorophores. This review overviews the synthesis and photochemical properties of α-diketone-type acene precursors, as well as their use as intermediates in preparation of large acenes or highly functionalized acene derivatives. Computational studies on the mechanism of α-diketone photolysis and the use of α-diketone derivatives in fabrication of organic devices are also summarized in this review

Functional interaction between cyclooxygenase-2 and p53 in response to an endogenous electrophile

Cyclooxygenase-2 (Cox-2) is rapidly expressed by various stimuli and plays a key role in conversion of free arachidonic acid to prostaglandins. We have previously identified 4-hydroxy-2-nonenal (HNE), a lipid peroxidation-derived electrophile, as the potent Cox-2 inducer in rat epithelial RL34 cells and revealed that the HNE-induced Cox-2 expression resulted from the stabilization of Cox-2 mRNA that is mediated by the p38 mitogen-activated protein kinase signaling pathway. In the present study, we investigated an alternative regulatory mechanism of Cox-2 expression mediated by a transcription factor p53. In addition, to characterize the causal role for Cox-2, we examined the effects of Cox-2 overexpression in RL34 cells. To examine whether the HNE-induced Cox-2 expression was mechanistically linked to the p53 expression, we analyzed changes in Cox-2 and p53 expression levels in response to HNE and observed that the Cox-2 levels were inversely correlated with the p53 levels. Down-regulation of p53 followed by the activation of a transcription factor Sp1 was suggested to be involved in the HNE-induced Cox-2 gene expression. To characterize the effect of Cox-2 expression in the cells, we established the Cox-2-overexpressing derivatives of RL34 cells by stable transfection with Cox-2 cDNA. An oligonucleotide microarray analysis revealed a dramatic down-regulation of the proteasome subunit RC1 in the Cox-2 overexpressed cells compared to the empty-vector transfected control cells. Consistent with the Cox-2-mediated down-regulation of proteasome, a moderate reduction of the proteasome activities was observed. This proteasome dysfunction mediated by the Cox-2 overproduction was associated with the enhanced accumulation of p53 and ubiquitinated proteins, leading to the enhanced sensitivity toward electrophiles. These results suggest the existence of a causal link between Cox-2 and p53, which may represent a toxic mechanism of electrophilic lipid peroxidation products

Fecal Distribution Changes Using Colorectal Ultrasonography in Older People with Physical and Cognitive Impairment Living in Long-Term Care Facilities: A Longitudinal Observational Study

Nurses encounter difficulties evaluating constipation in elderly people with physical and cognitive impairment. Transabdominal ultrasonography (US) has been used to evaluate fecal impaction or fecal quality. However, it is unclear whether colorectal US can evaluate constipation symptoms in older people. Using colorectal US, we continuously observed the elderly and clarified the relationship between patterns of fecal distribution changes and constipation symptoms in older people with physical and cognitive impairment at long-term care facilities. This study included patients aged ≥65 years with oral intake. US was performed once a day until the next defecation, and fecal hardness was assessed. US images were extracted and categorized. Then, patterns of fecal distribution changes in the colorectum were classified. Multiple logistic regression analysis was performed to examine related factors associated with a constipation pattern. Among 101 patients, US images of 95 patients were analyzed. In 74.4% of the patients, US showed continuation of reflection with acoustic shadow in the rectum, which was significantly associated with defecation on the bed. Of the patients with a continuous crescent-shaped reflection pattern (R3), 92.9% had hard stool. R3 was found to be significantly associated with a Mini-Mental State Examination score of ≤10. In most of the patients, US detected a continuation of reflection with acoustic shadow in rectal patterns, indicating fecal retention in the rectum. Point-of-care US can be used by nurses to visualize rectal fecal retention as constipation patterns in the older people with physical and cognitive impairment at long-term care facilities