• Molecules and Cells
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• v.43 no.4
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• pp.331-339
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• 2020

Genetic modifications in noncoding regulatory regions are likely critical to human evolution. Human-accelerated noncoding elements are highly conserved noncoding regions among vertebrates but have large differences across humans, which implies human-specific regulatory potential. In this study, we found that human-accelerated noncoding elements were frequently coupled with DNase I hypersensitive sites (DHSs), together with monomethylated and trimethylated histone H3 lysine 4, which are active regulatory markers. This coupling was particularly pronounced in fetal brains relative to adult brains, non-brain fetal tissues, and embryonic stem cells. However, fetal brain DHSs were also specifically enriched in deeply conserved sequences, implying coexistence of universal maintenance and human-specific fitness in human brain development. We assessed whether this coexisting pattern was a general one by quantitatively measuring evolutionary rates of DHSs. As a result, fetal brain DHSs showed a mixed but distinct signature of regional conservation and outlier point acceleration as compared to other DHSs. This finding suggests that brain developmental sequences are selectively constrained in general, whereas specific nucleotides are under positive selection or constraint relaxation simultaneously. Hence, we hypothesize that human- or primate-specific changes to universally conserved regulatory codes of brain development may drive the accelerated, and most likely adaptive, evolution of the regulatory network of the human brain.

• Animal cells and systems
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• v.5 no.3
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• pp.231-236
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• 2001

SINE-R retroposons have been derived from human endogenous retrovirus HERV-K family and found to be hominoid specific. Both SINE-R retroposons and HERV-K family are potentially capable of affecting the expression of closely located genes. From cDNA library of human fetal brain, we identified seven SINE-R retroposons and compared them with sequences derived from GenBank database. The SINE-R retroposons from human feta1 brain showed 85∼97% sequence similarities with the human-specific retroposon SINE-R.C2. They also showed 88∼96% sequence similarities with the sequence of the schizo-cDNA clone that derived from postmortem frontal cortex tissue of a schizophrenic patient. Phylogenetic analysis using the neiqhbor-joining method revealed that the seven new SINE-R retroposons from cDNA library of the human feta1 brain have proliferated independently during human evolution. The data indicate that such SINE-R retroposons are expressed in human fetal brain and deserve further investigation as potential leads to understanding of neuropsychiatric diseases.

• Journal of Life Science
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• v.11 no.4
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• pp.379-384
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• 2001

Long terminal repeats(LTRs) of the human endogenous retrovirus(HERV) heve been found to be coexpresed with genes located nearby. It has been suggested that the LTR elements have contributed to the genetic variation of human genome connected to various diseases. Recently, HERV-W family was identified in the cerebrospinal fluids and brains of individuals with schizophrenia. Using cHNA library derived from human fetal brain, we performed PCR amplification and identified seven new HERV-W LTR elements. Those LTR elements showed a high degree of sequence similarity(98∼99%) with HERV-W (AF072500). A phylogentic tree obtained by the neighbor-joining method revealed that seven new HERV-W LTR elements(FB-1, 2, 4, 8, 9, 10, 12) were closely related to the AX000960, AF072504, and AF072506 from Gen Bank database. Our data suggest that several copy numbers of the HERV-W LTR elements are expressed in human feta brain and may contribute to an understanding of biological function connected to neuropsychiatric diseases.

• BMB Reports
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• v.32 no.4
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• pp.409-413
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• 1999

The cDNA encoding CMP-NeuAc:lactosylceramide ${\alpha}2$,3-sialyltransferase (GM3 synthase) was isolated from a human fetal brain cDNA library using sequence information obtained from amino acid sequences found in the conserved regions of the previously-cloned mouse GM3 synthase (mST3Gal V) and human sialyltransferases. The cDNA sequence included an open reading frame coding for 362 amino acids, and the primary structure of this enzyme predicted all the structural features characteristic of other sialyltransferases, including a type II membrane protein topology and both sialylmotifs. Comparative analysis of this cDNA with mST3Gal V showed 85% and 86% identity of the nucleotide and amino acid residues, respectively. The expression of this gene is highly restricted in both human fetal and adult tissues.

• Journal of Life Science
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• v.13 no.3
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• pp.291-297
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• 2003

A human endogenous retroviral family (HERV-W) has recently been described that is related to multiple sclerosis-associated retrovirus (MSRV) sequences that have been identified in particles recovered from monocyte cultures from patients with multiple sclerosis. Two pol fragments (HWP-FB10 and HWP-FBl2) of HERV-W family were identified and analysed by the PCR approach with cDNA library of human fetal brain. They showed 89 percent nucleotide sequence similarity with that of the HERV-W (accession no. AF009668). Deletion/insertion or point mutation in the coding region of the pol fragments from human fetal brain resulted in amino acid frameshift that induced a mutated protein. Phylogenetic analysis of the HERV-W family from GenBank database indicates that the HWP-FB10 is very closely related to the AC000064 derived from human chromosome 7q21-q22. Further studies on the genetic relationship with neighbouring genes and functional role of these new HERV-W pol sequences are indicated.

• BMB Reports
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• v.52 no.10
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• pp.577-588
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• 2019

DNA methylation at CpG sites is an essential epigenetic mark that regulates gene expression during mammalian development and diseases. Methylome refers to the entire set of methylation modifications present in the whole genome. Over the last several years, an increasing number of reports on brain DNA methylome reported the association between aberrant methylation and the abnormalities in the expression of critical genes known to have critical roles during aging and neurodegenerative diseases. Consequently, the role of methylation in understanding neurodegenerative diseases has been under focus. This review outlines the current knowledge of the human brain DNA methylomes during aging and neurodegenerative diseases. We describe the differentially methylated genes from fetal stage to old age and their biological functions. Additionally, we summarize the key aspects and methylated genes identified from brain methylome studies on neurodegenerative diseases. The brain methylome studies could provide a basis for studying the functional aspects of neurodegenerative diseases.

• Journal of Nutrition and Health
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• v.10 no.2
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• pp.5-11
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• 1977

The mature human braun contains over 10 billion nerve cells (neurons), whose functions are directly related to the acquisition, transfer, processing, analysis, and utilization of all the information. There are also billions of glial cells, which serve primarily to support and to maintain the integrity of the neuron network and to synthesize an essential fatty strucfure, myelin. In the human brain DNA content therefore cell number rises rapidly until birth and then more slowly until $5{\sim}6$ months of age, when it reaches a maximum. While glial cells may be replaced, the more important nerve cell neurons can never be replaced once they are formed. Humans are born with their full complement of neurons and every neuron is as old as each individual. Thus prenatal malnutrition can seriously affect a person's entire life by severely inhibiting the production of neurons before birth.It has been demonstrated that in humans severe malnutrition during the fetal period and in infancy is associated with intellectual impairment. Severely malnourished children have brains smaller than average size and have been found to have $15{\sim}20%$ fewer brain cells than wellnourished childen. There is growing body of literature pointing to malnutrition as a cause of abnormal behavior as evidence that suggests these abnormalities may produce chromosomal damage that may persist forever. Although cognitive development in children is affected by multiple environmental factors, nutrition certainly deaerves more attention than it has received.

• Asian-Australasian Journal of Animal Sciences
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• v.27 no.12
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• pp.1671-1677
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• 2014

Ras homolog enriched in brain (Rheb) and FK506 binding protein 38 (FKBP38) are two important regulatory proteins in the mammalian target of rapamycin (mTOR) pathway. There are contradictory data on the interaction between Rheb and FKBP38 in human cells, but this association has not been examined in cashmere goat cells. To investigate the interaction between Rheb and FKBP38, we overexpressed goat Rheb and FKBP38 in goat fetal fibroblasts, extracted whole proteins, and performed coimmunoprecipitation to detect them by western blot. We found Rheb binds directly to FKBP38. Then, we constructed bait vectors (pGBKT7-Rheb/FKBP38) and prey vectors (pGADT7-Rheb/FKBP38), and examined their interaction by yeast two-hybrid assay. Their direct interaction was observed, regardless of which plasmid served as the prey or bait vector. These results indicate that the 2 proteins interact directly in vivo. Novel evidence is presented on the mTOR signal pathway in Cashmere goat cells.

• Development and Reproduction
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• v.3 no.1
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• pp.101-105
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• 1999

N-Methylpurine-DNA glycosylase (MPG) removes N-methylpurine and other damaged purines in DNA. RT-PCR analysis revealed MPG mRNA expression at various tissues of fetal development from day 8 to day 18 fetus and day 400 mature adult. The MPG transcripts were abundant during fetal development in mice. In placenta, the MPG mRNA was continuously decreased from day 8 post coitum (p.c) to day 18 p.c. fetus. The high level of mRNA in fetal brain and liver was drastically declined in day 400 mature adult. The expression of MPG, originally characterized by its highest level of expression in the epididymis of adult mouse, was detected with high level in several other reproductive organ, including the ovary, oviduct, testis, vas deference, uterus, and seminal vesicles. These results demonstrate developmental stage- and tissue-specific variation of MPG gene expression.

• Journal of Veterinary Clinics
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• v.36 no.2
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• pp.116-118
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• 2019

A 2-year-old female Persian cat weighing 2.95 kg was admitted for dystocia. The levels of white blood cells and thrombocytes were decreased in blood analysis. In radiography and ultrasonography, there were four fetuses with no remarkable signs of blood flow and heartbeat. In particular, one of them showed symptom of Spalding's sign, which is a rare symptom that indicated overriding of the fetal cranial bones and shrinkage of the head with a decreased volume. It was reported that Spalding's sign is one of the strong indication of fetal death in human uterus and it occurs rarely with normal fetus without apparent reason prior to labor in human. This is the first report to provide the Spalding's sign in domestic cats and this will be applied in a strong presumptive evidence that fetal death has occurred with brain disruption sequence while pregnancy in domestic animals.