Bone Marrow Mesenchymal Cell Contribution in Maintenance of Periodontal Ligament Homeostasis

In general, remodeling phenomenon of the periodontal ligament (PDL) is occurring in all times. Thus, in the chapter, the word “maintenance” was used, and the chapter title is “Maintenance of Periodontal Ligament Homeostasis.” Our experimental data on the remodeling of the PDL with cell acceleration at the furcation area in this experimental model are recovered using the cells in situ and the bone marrow-derived cells (BMCs). BMC migration into the PDL tissues using green fluorescent protein (GFP) bone marrow-transplanted model mouse was examined. BMCs have abilities of cell migration and differentiation into tissues/organs in the body. The immunohistochemistry revealed that GFP-positive cells were detected in the PDL. GFP-positive cells were also positive to CD31, CD68, and Runx2 suggesting that fibroblasts differentiated into osteoclasts and tissue macrophages. In this way, Notch signaling involvement considered in our tentative examinations revealed that the experimentally induced periodontal polyp was examined; the cytological dynamics of the cells in granulation tissue are mainly from migration of undifferentiated mesenchymal cells of the bone marrow and differentiate into the tissue-specified cells. Furthermore, the data suggest that cell differentiation is due to Notch signaling

Chapter 6 : Bone marrow masenchymal cell contribution in maintenance of periodontal ligament homeostasis.

In general, remodeling phenomenon of the periodontal ligament (PDL) is occurring in all times. Thus, in the chapter, the word “maintenance” was used, and the chapter title is “Maintenance of Periodontal Ligament Homeostasis.” Our experimental data on the remodeling of the PDL with cell acceleration at the furcation area in this experimental model are recovered using the cells in situ and the bone marrow-derived cells (BMCs).BMC migration into the PDL tissues using green Ěuorescent protein (GFP)bone　marrow-transplanted model mouse was examined. BMCs have abilities of　cell migration and diěerentiation into　tissues/organs in the body. The immunohistochemistry revealed that GFP-positive cells were detected in the PDL.GFP-positive cells were also positive to CD31, CD68, and Runx2 suggesting that ębroblasts diěerentiated into osteoclasts and tissue macrophages. In this　way, Notch signaling involvement considered in our tentative examinations revealed　that the experimentally induced periodontal polyp was examined; the cytological　dynamics of the cells in granulation tissue are mainly from migration of　undiěerentiated mesenchymal cells of the bone marrow and diěerentiate into the　tissue-specięed cells. Furthermore, the data suggest that cell diěerentiation is due to　Notch signaling.Edited by Thomas Heinbockel and Vonnie D.C. Shields : Published in London : IntechOpen, 2019

A novel transgenic chimaeric mouse system for the rapid functional evaluation of genes encoding secreted proteins

A major challenge of the post-genomic era is the functional characterization of anonymous open reading frames (ORFs) identified by the Human Genome Project. In this context, there is a strong requirement for the development of technologies that enhance our ability to analyze gene functions at the level of the whole organism. Here, we describe a rapid and efficient procedure to generate transgenic chimaeric mice that continuously secrete a foreign protein into the systemic circulation. The transgene units were inserted into the genomic site adjacent to the endogenous immunoglobulin (Ig) κ locus by homologous recombination, using a modified mouse embryonic stem (ES) cell line that exhibits a high frequency of homologous recombination at the Igκ region. The resultant ES clones were injected into embryos derived from a B-cell-deficient host strain, thus producing chimaerism-independent, B-cell-specific transgene expression. This feature of the system eliminates the time-consuming breeding typically implemented in standard transgenic strategies and allows for evaluating the effect of ectopic transgene expression directly in the resulting chimaeric mice. To demonstrate the utility of this system we showed high-level protein expression in the sera and severe phenotypes in human EPO (hEPO) and murine thrombopoietin (mTPO) transgenic chimaeras

A multi-ethnic meta-analysis identifies novel genes, including ACSL5, associated with amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a devastating progressive motor neuron disease that affects people of all ethnicities. Approximately 90% of ALS cases are sporadic and thought to have multifactorial pathogenesis. To understand the genetics of sporadic ALS, we conducted a genome-wide association study using 1,173 sporadic ALS cases and 8,925 controls in a Japanese population. A combined meta-analysis of our Japanese cohort with individuals of European ancestry revealed a significant association at the ACSL5 locus (top SNP p = 2.97 × 10−8). We validated the association with ACSL5 in a replication study with a Chinese population and an independent Japanese population (1941 ALS cases, 3821 controls; top SNP p = 1.82 × 10−4). In the combined meta-analysis, the intronic ACSL5 SNP rs3736947 showed the strongest association (p = 7.81 × 10−11). Using a gene-based analysis of the full multi-ethnic dataset, we uncovered additional genes significantly associated with ALS: ERGIC1, RAPGEF5, FNBP1, and ATXN3. These results advance our understanding of the genetic basis of sporadic ALS

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

Evolutionary Aspects and Regulation of Tetrapyrrole Biosynthesis in Cyanobacteria under Aerobic and Anaerobic Environments

Chlorophyll a (Chl) is a light-absorbing tetrapyrrole pigment that is essential for photosynthesis. The molecule is produced from glutamate via a complex biosynthetic pathway comprised of at least 15 enzymatic steps. The first half of the Chl pathway is shared with heme biosynthesis, and the latter half, called the Mg-branch, is specific to Mg-containing Chl a. Bilin pigments, such as phycocyanobilin, are additionally produced from heme, so these light-harvesting pigments also share many common biosynthetic steps with Chl biosynthesis. Some of these common steps in the biosynthetic pathways of heme, Chl and bilins require molecular oxygen for catalysis, such as oxygen-dependent coproporphyrinogen III oxidase. Cyanobacteria thrive in diverse environments in terms of oxygen levels. To cope with Chl deficiency caused by low-oxygen conditions, cyanobacteria have developed elaborate mechanisms to maintain Chl production, even under microoxic environments. The use of enzymes specialized for low-oxygen conditions, such as oxygen-independent coproporphyrinogen III oxidase, constitutes part of a mechanism adapted to low-oxygen conditions. Another mechanism adaptive to hypoxic conditions is mediated by the transcriptional regulator ChlR that senses low oxygen and subsequently activates the transcription of genes encoding enzymes that work under low-oxygen tension. In diazotrophic cyanobacteria, this multilayered regulation also contributes in Chl biosynthesis by supporting energy production for nitrogen fixation that also requires low-oxygen conditions. We will also discuss the evolutionary implications of cyanobacterial tetrapyrrole biosynthesis and regulation, because low oxygen-type enzymes also appear to be evolutionarily older than oxygen-dependent enzymes