Search

SUMMARY: In automotive and industrial fields, pressure sensors are a key component for precisely controlling the mechanical systems. Conventional micro electro mechanical system (MEMS)‐based pressure sensors have an advantage in noise resistance, because both strain gauges and control circuits are integrated in one chip. However, the MEMS‐based pressure sensors are generally fabricated on an Si substrate, and have a low stability against various active gases. Thus, we have newly proposed a pressure sensor which consists of an Si‐based strain sensor set on a stainless steel diaphragm with a high stability against the active gases. The key technology is that a Koval plate is inserted between the strain sensor and the stainless steel diaphragm, for preventing the breakage or the delamination of the strain sensor at the bonding interface due to a difference in thermal expansion. Structure of the sensor including the shape and the size of Koval plate and the assembly position of the strain sensor were designed using structural simulation and experiments. Eventually, the 2.8 mm wide and 0.17 mm thick Koval beam was bridged on the stainless steel diaphragm for efficiently transmitting the diaphragm deformation to the strain sensor. The strain sensor was assembled at the edge of Koval beam with a glass bonding technique. Consequently, the developed pressure sensor has achieved a small dispersion of less than 1% F. S. in a temperature range from 0 °C to 85 °C. [ABSTRACT FROM AUTHOR]

The article cites a study which uses the tools of molecular anthropology to investigate the origin and cultural reversion of the Mlabri people of Southeast Asia. The study was conducted by researcher Mark Stoneking and colleagues. The Mlabri lived mostly as nomadic hunter-gatherers in the forests of northeastern Thailand and western Laos. It also compares the genetic diversity of the Mlabri with that of six other agriculture-based hill tribes by analyzing specific regions of each population's mitochondrial DNA (mtDNA), Y chromosomes, and autosomes. mtDNA and Y chromosomes can help uncover clues to evolutionary origins because both are in effect haploid systems and so do not undergo recombination.

Abstract Background Routine trichromatic color vision is a characteristic feature of catarrhines (humans, apes and Old World monkeys). This is enabled by L and M opsin genes arrayed on the X chromosome and an autosomal S opsin gene. In non-human catarrhines, genetic variation affecting the color vision phenotype is reported to be absent or rare in both L and M opsin genes, despite the suggestion that gene conversion has homogenized the two genes. However, nucleotide variation of both introns and exons among catarrhines has only been examined in detail for the L opsin gene of humans and chimpanzees. In the present study, we examined the nucleotide variation of gibbon (Catarrhini, Hylobatidae) L and M opsin genes. Specifically, we focused on the 3.6~3.9-kb region that encompasses the centrally located exon 3 through exon 5, which encode the amino acid sites functional for the spectral tuning of the genes. Results Among 152 individuals representing three genera (Hylobates, Nomascus and Symphalangus), all had both L and M opsin genes and no L/M hybrid genes. Among 94 individuals subjected to the detailed DNA sequencing, the nucleotide divergence between L and M opsin genes in the exons was significantly higher than the divergence in introns in each species. The ratio of the inter-LM divergence to the intra-L/M polymorphism was significantly lower in the introns than that in synonymous sites. When we reconstructed the phylogenetic tree using the exon sequences, the L/M gene duplication was placed in the common ancestor of catarrhines, whereas when intron sequences were used, the gene duplications appeared multiple times in different species. Using the GENECONV program, we also detected that tracts of gene conversions between L and M opsin genes occurred mostly within the intron regions. Conclusions These results indicate the historical accumulation of gene conversions between L and M opsin genes in the introns in gibbons. Our study provides further support for the homogenizing role of gene conversion between the L and M opsin genes and for the purifying selection against such homogenization in the central exons to maintain the spectral difference between L and M opsins in non-human catarrhines.

Abstract Background Within-species genome diversity has been best studied in humans. The international HapMap project has revealed a tremendous amount of single-nucleotide polymorphisms (SNPs) among humans, many of which show signals of positive selection during human evolution. In most of the cases, however, functional differences between the alleles remain experimentally unverified due to the inherent difficulty of human genetic studies. It would therefore be highly useful to have a vertebrate model with the following characteristics: (1) high within-species genetic diversity, (2) a variety of gene-manipulation protocols already developed, and (3) a completely sequenced genome. Medaka (Oryzias latipes) and its congeneric species, tiny fresh-water teleosts distributed broadly in East and Southeast Asia, meet these criteria. Findings Using Oryzias species from 27 local populations, we conducted a simple screening of nonsynonymous SNPs for 11 genes with apparent orthology between medaka and humans. We found medaka SNPs for which the same sites in human orthologs are known to be highly differentiated among the HapMap populations. Importantly, some of these SNPs show signals of positive selection. Conclusion These results indicate that medaka is a promising model system for comparative population genomics exploring the functional and adaptive significance of allelic differentiations.

Humans have long pondered their genesis. The answer to the great question of where Homo sapiens come from has evolved in conjunction with biotechnologies that have allowed us to more brightly illuminate our distant past. The "Multiregional Evolution" model was once the hegemonic theory of Homo sapiens origins, but in the last 30 years, it has been supplanted by the "Out of Africa" model. Here, we review the major findings that have resulted in this paradigmatic shift. These include hominin brain expansion, classical insight from the mitochondrial genome (mtDNA) regarding the timing of the divergence point between Africans and non-Africans, and next-generation sequencing (NGS) of the Neanderthal and Denisovan genomes. These findings largely bolstered the "Out of Africa" model, although they also revealed a small degree of introgression of the Neanderthal and Denisovan genomes into those of non-African Homo sapiens. We also review paleogenomic studies for which migration route, north or south, early migrants to East Eurasia most likely traversed. Whichever route was taken, the migrants moved to higher latitudes, which necessitated adaptation for lower light conditions, colder clines, and pro-adipogenic mechanisms to counteract food scarcity. Further genetic and epigenetic investigations of these physiological adaptations constitute an integral aspect of the story of human origins and human migration to East Asia., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests., (© 2025. The Author(s).)

As humans' closest living relatives, chimpanzees offer valuable insights into human evolution. However, technical and ethical limitations hinder investigations into the molecular and cellular foundations that distinguish chimpanzee and human traits. Recently, induced pluripotent stem cells (iPSCs) have emerged as a novel model for functional comparative studies and provided a non-invasive alternative for studying embryonic phenomena. In this study, we generated five new chimpanzee iPSC lines from peripheral blood cells and skin fibroblasts with SeV vectors carrying four reprogramming factors (human OCT3/4, SOX2, KLF4, and L-MYC) and characterized their pluripotency and differentiation potential. We also examined the expression of a human-specific non-coding RNA, HSTR1, which is predicted to be involved in human brain development. Our results show that the chimpanzee iPSCs possess pluripotent characteristics and can differentiate into various cell lineages. Moreover, we found that HSTR1 is expressed in human iPSCs and their neural derivatives but not in chimpanzee counterparts, supporting its possible role in human-specific brain development. As iPSCs are inherently variable due to genetic and epigenetic differences in donor cells or reprogramming procedures, it is essential to expand the number of chimpanzee iPSC lines to comprehensively capture the molecular and cellular properties representative of chimpanzees. Hence, our cells provide a valuable resource for investigating the function and regulation of human-specific transcripts such as HSTR1 and for understanding human evolution more generally., (© 2024. The Society for In Vitro Biology.)

Coprolites contain various kinds of ancient DNAs derived from gut micro-organisms, viruses, and foods, which can help to determine the gut environment of ancient peoples. Their genomic information should be helpful in elucidating the interaction between hosts and microbes for thousands of years, as well as characterizing the dietary behaviors of ancient people. We performed shotgun metagenomic sequencing on four coprolites excavated from the Torihama shell-mound site in the Japanese archipelago. The coprolites were found in the layers of the Early Jomon period, corresponding stratigraphically to 7000 to 5500 years ago. After shotgun sequencing, we found that a significant number of reads showed homology with known gut microbe, viruses, and food genomes typically found in the feces of modern humans. We detected reads derived from several types of phages and their host bacteria simultaneously, suggesting the coexistence of viruses and their hosts. The food genomes provide biological evidence for the dietary behavior of the Jomon people, consistent with previous archaeological findings. These results indicate that ancient genomic analysis of coprolites is useful for understanding the gut environment and lifestyle of ancient peoples., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Nishimura et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Yersinia enterocolitica is a causative agent of food poisoning and has been isolated from pork and stream water, causing Yersinia enterocolitica in humans. The bacterium is divided into multiple serotypes and biotypes, among which serotypes O3 and O8 and biotypes 1B, 3, and 4 are frequently isolated in Japan. Biotype 3 can be classified as [VP+, Suc+], [VP-, Suc+], [VP-, Suc-] based on the biochemical properties. Among them, [O3, 3, VP-, Suc-] has been reported to be identified as Yersinia kristensenii in a simple identification kit. An increasing number of facilities in the field of microbiological testing are currently using mass spectrometers to identify species of microorganisms. However, there are many facilities where mass spectrometers have not yet been installed and microbial identification and susceptibility testing devices are used to identify bacterial species. No reports have described how the [O3, 3, VP-, Suc-] type, which is identified as Y. kristensenii in the simple identification kit, is identified by the microbial identification and susceptibility testing devices. In this study, 15 strains of Y. enterocolitica , which were previously isolated, serotyped, and biotyped from fecal culture tests at our hospital, were analyzed to see how these strains were identified in RAISUS S4, Microscan WalkAway, VITEK2 Blue, and BD Phoenix. [O3, 3, VP-, Suc-] was identified as Y. kristensenii in RAISUS S4, Microscan WalkAway, and VITEK2 Blue and as Y. enterocolitica in BD Phoenix. [O3, 3, VP-, Suc+], [O3, 4] and [O8, 1B] were identified as Y. enterocolitica . Therefore, when a sample was identified as Y. kristensenii by RAISUS S4, Microscan WalkAway, or VITEK2 Blue, the possibility that it was actually [O3, 3, VP-, Suc-] could not be ruled out. The possibility of Y. enterocolitica should be informed to attending physicians.

An unsolved archaeological puzzle of the East Asian Upper Palaeolithic is why the southward expansion of an innovative lithic technology represented by microblades stalled at the Qinling-Huaihe Line. It has been suggested that the southward migration of foragers with microblades stopped there, which is consistent with ancient DNA studies showing that populations to the north and south of this line had differentiated genetically by 19 000 years ago. Many infectious pathogens are believed to have been associated with hominins since the Palaeolithic, and zoonotic pathogens in particular are prevalent at lower latitudes, which may have produced a disease barrier. We propose a mathematical model to argue that mortality due to infectious diseases may have arrested the wave-of-advance of the technologically advantaged foragers from the north.

When lowlanders are exposed to environments inducing hypobaric hypoxia (HH) such as high mountains, hemodynamic changes occur to maintain oxygen levels in the body. However, changes to other physiological functions under such conditions have yet to be clarified. This study investigated changes in endocrine, inflammatory and immune parameters and individual differences during acute HH exposure using a climatic chamber (75 min of exposure to conditions mimicking 3500 m) in healthy lowlanders. Aldosterone and cortisol were significantly decreased and interleukin (IL)-6, IL-8 and white blood cell (WBC) counts were significantly increased after HH. Lower peripheral oxygen saturation (SpO 2 ) was associated with higher IL-6 and WBC counts, and higher IL-8 was associated with higher cortisol. These findings suggest that endocrine, inflammatory and immune responses are evoked even with a short 75-min exposure to HH and individuals with lower SpO 2 seemed to show more pronounced responses. Our results provide basic data for understanding the physiological responses and interactions of homeostatic systems during acute HH., (© 2023. Springer Nature Limited.)

In new drug development, cells or animals are treated with the selected candidate compound to confirm its efficacy and safety in nonclinical studies. Clinical laboratory tests are carried out using samples from experimental animals in these studies. The clinical laboratory test method validation in nonclinical fields should be conducted keeping in mind that the circumstances differ from those in clinical settings. However, the validation procedures have not been systematically integrated into any standard. The considerations in this paper set out systematically practical guidance for the validation of quantitative analytical methods for fluid samples collected from animal studies, for the purpose of ensuring that laboratory test method validation is conducted in nonclinical fields at an enough level.

Transient receptor potential cation channel subfamily V member 1 (TRPV1)-targeted compounds were synthesized by modifying the structure of SB366791, a pharmaceutically representative TRPV1 antagonist. To avoid amide-iminol tautomerization, structurally supported N -methylated amides ( i.e. , 3-alkoxy-substitued N -meythylamide derivatives of SB366791) were evaluated using a Ca 2+ influx assay, in which cells expressed recombinant TRPV1 in the presence of 1.0 μM capsaicin. The antagonistic activities of N -(3-methoxyphenyl)- N -methyl-4-chlorocinnamamide (2) (RLC-TV1004) and N -{3-(3-fluoropropoxy)phenyl}- N -methyl-4-chlorocinnamamide (4) (RLC-TV1006) were found to be approximately three-fold higher (IC 50 : 1.3 μM and 1.1 μM, respectively) than that of SB366791 (IC 50 : 3.7 μM). These results will help reinvigorate the potential of SB366791 in medicinal chemistry applications. The 3-methoxy and 3-fluoroalkoxy substituents were used to obtain radioactive [ 11 C]methoxy- or [ 18 F]fluoroalkoxy-incorporated tracers for in vivo positron emission tomography (PET). Using the 11 C- or 18 F-labeled derivatives, explorative PET imaging trials were performed in rats., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The transition to agriculture occurred relatively late in Eastern Europe, leading researchers to debate whether it was a gradual, interactive process or a colonisation event. In the forest and forest-steppe regions of Ukraine, farming appeared during the fifth millennium BCE, associated with the Cucuteni-Trypillia cultural complex (CTCC, ~ 5000-3000 BCE). Across Europe, the Neolithisation process was highly variable across space and over time. Here, we investigate the population dynamics of early agriculturalists from the eastern forest-steppe region based on the analyses of 20 ancient genomes from the site of Verteba Cave (3935-825 cal BCE). Results reveal that the CTCC individuals' ancestry is related to both western hunter-gatherers and Near Eastern farmers, has no local ancestry associated with Ukrainian Neolithic hunter-gatherers and has steppe ancestry. An Early Bronze Age individual has an ancestry profile related to the Yamnaya expansions but with 20% of ancestry related to the other Trypillian individuals, which suggests admixture between the Trypillians and the incoming populations carrying steppe-related ancestry. A Late Bronze Age individual dated to 980-825 cal BCE has a genetic profile indicating affinity to Beaker-related populations, detected close to 1000 years after the end of the Bell Beaker phenomenon during the third millennium BCE., (© 2022. The Author(s).)

The origin and early dispersal of speakers of Transeurasian languages-that is, Japanese, Korean, Tungusic, Mongolic and Turkic-is among the most disputed issues of Eurasian population history 1-3 . A key problem is the relationship between linguistic dispersals, agricultural expansions and population movements 4,5 . Here we address this question by 'triangulating' genetics, archaeology and linguistics in a unified perspective. We report wide-ranging datasets from these disciplines, including a comprehensive Transeurasian agropastoral and basic vocabulary; an archaeological database of 255 Neolithic-Bronze Age sites from Northeast Asia; and a collection of ancient genomes from Korea, the Ryukyu islands and early cereal farmers in Japan, complementing previously published genomes from East Asia. Challenging the traditional 'pastoralist hypothesis' 6-8 , we show that the common ancestry and primary dispersals of Transeurasian languages can be traced back to the first farmers moving across Northeast Asia from the Early Neolithic onwards, but that this shared heritage has been masked by extensive cultural interaction since the Bronze Age. As well as marking considerable progress in the three individual disciplines, by combining their converging evidence we show that the early spread of Transeurasian speakers was driven by agriculture., (© 2021. The Author(s).)

Recent studies on paleogenomics have reported some Paleolithic and Neolithic genomes that have provided new insights into the human population history in East and Northeast Asia. However, there remain some cases where more recent migration events need to be examined to elucidate the detailed formation process of local populations. Although the area around northern Japan is one of the regions archaeologically suggested to have been affected by migration waves after the Neolithic period, the genetic source of these migrations are still unclear. Thus, genomic data from such past migrant populations would be highly informative to clarify the detailed formation process of local populations in this region. Here, we report the genome sequence of a 900-year-old adult female (NAT002) belonging to the prehistoric Okhotsk people, who have been considered to be the past migrants to northern Japan after the Neolithic period. We found a close relationship between NAT002 and modern Lower Amur populations and past admixture events between the Amur, Jomon, and Kamchatka ancestries. The admixture dating suggested migration of Amur-related ancestry at approximately 1,600 BP, which is compatible with the archaeological evidence regarding the settlement of the Okhotsk people. Our results also imply migration of Kamchatka-related ancestry at approximately 2,000 BP. In addition, human leukocyte antigen (HLA) typing detected the HLA-B*40 allele, which is reported to increase the risk of arthritis, suggesting the genetic vulnerability of NAT002 to hyperostosis, which was observed around her chest clavicle., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)

Background: Ring finger protein 213 (RNF213) is a susceptibility gene of moyamoya disease (MMD). A previous case-control study and a family analysis demonstrated a strong association of the East Asian-specific variant, R4810K (rs112735431), with MMD. Our aim is to uncover evolutionary history of R4810K in East Asian populations., Methods: The RNF213 locus of 24 MMD patients in Japan were sequenced using targeted-capture sequencing. Based on the sequence data, we conducted population genetic analysis and estimated the age of R4810K using coalescent simulation., Results: The diversity of the RNF213 gene was higher in Africans than non-Africans, which can be explained by bottleneck effect of the out-of-Africa migration. Coalescent simulation showed that the risk variant was born in East Asia 14,500-5100 years ago and came to the Japanese archipelago afterward, probably in the period when the known migration based on archaeological evidences occurred., Conclusions: Although clinical data show that the symptoms varies, all sequences harboring the risk allele are almost identical with a small number of exceptions, suggesting the MMD phenotypes are unaffected by the variants of this gene and rather would be more affected by environmental factors., (© 2021 The Authors. Annals of Human Genetics published by University College London (UCL) and John Wiley & Sons Ltd.)

Culture evolves in ways that are analogous to, but distinct from, genomes. Previous studies examined similarities between cultural variation and genetic variation (population history) at small scales within language families, but few studies have empirically investigated these parallels across language families using diverse cultural data. We report an analysis comparing culture and genomes from in and around northeast Asia spanning 11 language families. We extract and summarize the variation in language (grammar, phonology, lexicon), music (song structure, performance style), and genomes (genome-wide SNPs) and test for correlations. We find that grammatical structure correlates with population history (genetic history). Recent contact and shared descent fail to explain the signal, suggesting relationships that arose before the formation of current families. Our results suggest that grammar might be a cultural indicator of population history while also demonstrating differences among cultural and genetic relationships that highlight the complex nature of human history., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Anatomically modern humans reached East Asia more than 40,000 years ago. However, key questions still remain unanswered with regard to the route(s) and the number of wave(s) in the dispersal into East Eurasia. Ancient genomes at the edge of the region may elucidate a more detailed picture of the peopling of East Eurasia. Here, we analyze the whole-genome sequence of a 2,500-year-old individual (IK002) from the main-island of Japan that is  characterized with a typical Jomon culture. The phylogenetic analyses support multiple waves of migration, with IK002 forming a basal lineage to the East and Northeast Asian genomes examined, likely representing some of the earliest-wave migrants who went north from Southeast Asia to East Asia. Furthermore, IK002 shows strong genetic affinity with the indigenous Taiwan aborigines, which may support a coastal route of the Jomon-ancestry migration. This study highlights the power of ancient genomics to provide new insights into the complex history of human migration into East Eurasia.

Animal sex-determining genes, which bifurcate for female and male development, are diversified even among closely related species. Most of these genes emerged independently from various sex-related genes during species diversity as neofunctionalization-type genes. However, the common mechanisms of this divergent evolution remain poorly understood. Here, we compared the molecular evolution of two sex-determining genes, the medaka dmy and the clawed frog dm-W, which independently evolved from the duplication of the transcription factor-encoding masculinization gene dmrt1. Interestingly, we detected parallel amino acid substitutions, from serine (S) to threonine (T), on the DNA-binding domains of both ancestral DMY and DM-W, resulting from positive selection. Two types of DNA-protein binding experiments and a luciferase reporter assay demonstrated that these S-T substitutions could strengthen the DNA-binding abilities and enhance the transcriptional regulation function. These findings suggest that the parallel S-T substitutions may have contributed to the establishment of dmy and dm-W as sex-determining genes., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

We encountered a fetal pig with eventration of the diaphragm and pulmonary hypoplasia accompanied by phrenic nerve agenesis. The fetal pig was female measuring 34 cm in crown-rump length and about 1500 g in body weight. The diaphragm was a complete continuous sheet, but comprised a translucent membrane with residual muscular tissue only at the dorsolateral area of the right leaf of the diaphragm. The left leaf protruded extraordinarily toward the thoracic cavity. The left phrenic nerve was completely absent, while there was a slight remnant of the right phrenic nerve that supplied the dorsolateral muscular area of the right leaf. Both lungs were small, and the number of smaller bronchioles arising from the bronchioles was decreased to about half of that of the normal lung. Additionally, the right and left subclavius muscles and nerves could not be identified. These findings imply that the diaphragm, the subclavius muscle and nerves innervating them comprise a developmental module, which would secondarily affect lung development. It is considered that the present case is analogous to the animal model of congenital eventration of the diaphragm in humans.

Medaka is a model organism in medicine, genetics, developmental biology and population genetics. Lab stocks composed of more than 100 local wild populations are available for research in these fields. Thus, medaka represents a potentially excellent bioresource for screening disease-risk- and adaptation-related genes in genome-wide association studies. Although the genetic population structure should be known before performing such an analysis, a comprehensive study on the genome-wide diversity of wild medaka populations has not been performed. Here, we performed genotyping-by-sequencing (GBS) for 81 and 12 medakas captured from a bioresource and the wild, respectively. Based on the GBS data, we evaluated the genetic population structure and estimated the demographic parameters using an approximate Bayesian computation (ABC) framework. The genome-wide data confirmed that there were substantial differences between local populations and supported our previously proposed hypothesis on medaka dispersal based on mitochondrial genome (mtDNA) data. A new finding was that a local group that was thought to be a hybrid between the northern and the southern Japanese groups was actually an origin of the northern Japanese group. Thus, this paper presents the first population-genomic study of medaka and reveals its population structure and history based on chromosomal genetic diversity., (Copyright © 2019 by the Genetics Society of America.)

A 68-year-old female with severe aplastic anemia (SAA) refractory to initial immunosuppressive therapy, including anti-thymocyte globulin (ATG) and cyclosporine, received a reduced-intensity cord blood transplant (CBT) in June 2015. Tacrolimus (TAC) and mycophenolate mofetil were administered for graft-versus-host disease (GVHD) prophylaxis, and she received prolonged TAC and prednisolone to treat chronic GVHD. The patient presented with progressive ataxia 14 months after CBT. A brain magnetic resonance image (MRI, FLAIR) detected a high-intensity lesion in the left cerebellar hemisphere, which suggested infarction. Her consciousness level gradually continued to deteriorate and another brain MRI (T2) revealed that the size of the cerebellar lesion had increased and had involved the pons. A cerebrospinal fluid (CSF) examination showed normal cell count and protein levels; however, polymerase chain reaction (PCR) analysis of CSF was positive for JC virus (JCV). Therefore, she was eventually diagnosed with progressive multifocal leukoencephalopathy (PML) and treated with mefloquine. The symptoms were reduced after 3 months, and JCV in CSF disappeared without new lesions after 6 months. This is an unusual case of PML initially involving the cerebellum, and we report here PML after an immunosuppressive therapy and CBT in the patient with SAA.

To analyze a specific genome region using next-generation sequencing technologies, the enrichment of DNA libraries with targeted capture methods has been standardized. For enrichment of mitochondrial genome, a previous study developed an original targeted capture method that use baits constructed from long-range polymerase chain reaction (PCR) amplicons, common laboratory reagents, and equipment. In this study, a new targeted capture method is presented, that of bacterial artificial chromosome (BAC) double capture (BDC), modifying the previous method, but using BAC libraries as baits for sequencing a relatively large gene. We applied the BDC approach for the 214 kb autosomal region, ring finger protein 213, which is the susceptibility gene of moyamoya disease (MMD). To evaluate the reliability of BDC, cost and data quality were compared with those of a commercial kit. While the ratio of duplicate reads was higher, the cost was less than that of the commercial kit. The data quality was sufficiently the same as that of the kit. Thus, BDC can be an easy, low-cost, and useful method for analyzing individual genome regions with substantial length., Competing Interests: The authors have declared that no competing interests exist.

The human occupation history of Southeast Asia (SEA) remains heavily debated. Current evidence suggests that SEA was occupied by Hòabìnhian hunter-gatherers until ~4000 years ago, when farming economies developed and expanded, restricting foraging groups to remote habitats. Some argue that agricultural development was indigenous; others favor the "two-layer" hypothesis that posits a southward expansion of farmers giving rise to present-day Southeast Asian genetic diversity. By sequencing 26 ancient human genomes (25 from SEA, 1 Japanese Jōmon), we show that neither interpretation fits the complexity of Southeast Asian history: Both Hòabìnhian hunter-gatherers and East Asian farmers contributed to current Southeast Asian diversity, with further migrations affecting island SEA and Vietnam. Our results help resolve one of the long-standing controversies in Southeast Asian prehistory., (Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Lamin is an intermediate protein underlying the nuclear envelope and it plays a key role in maintaining the integrity of the nucleus. A defect in the processing of its precursor by a metalloprotease, ZMPSTE24, results in the accumulation of farnesylated prelamin in the nucleus and causes various diseases, including Hutchinson-Gilford progeria syndrome (HGPS). However, the role of lamin processing is unclear in fish species. Here, we generated zmpste24-deficient medaka and evaluated their phenotype. Unlike humans and mice, homozygous mutants did not show growth defects or lifespan shortening, despite lamin precursor accumulation. Gonadosomatic indices, blood glucose levels, and regenerative capacity of fins were similar in 1-year-old mutants and their wild-type (WT) siblings. Histological examination showed that the muscles, subcutaneous fat tissues, and gonads were normal in the mutants at the age of 1 year. However, the mutants showed hypersensitivity to X-ray irradiation, although p53target genes, p21 and mdm2, were induced 6 h after irradiation. Immunostaining of primary cultured cells from caudal fins and visualization of nuclei using H2B-GFP fusion proteins revealed an abnormal nuclear shape in the mutants both in vitro and in vivo. The telomere lengths were significantly shorter in the mutants compared to WT. Taken together, these results suggest that zmpste24-deficient medaka phenocopied HGPS only partially and that abnormal nuclear morphology and lifespan shortening are two independent events in vertebrates., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

Humans have spread out all over the world adapting to many different cold environments. Recent worldwide genome analyses and animal experiments have reported dozens of genes associated with cold adaptation. The uncoupling protein 1 (UCP1) gene enhances thermogenesis reaction in a physiological process by blocking ATP (adenosine triphosphate) synthesis on a mitochondrial membrane in brown adipose tissues. To our knowledge, no previous studies have shown an association between variants of the UCP1 gene and physiological phenotypes concerning non-shivering thermogenesis (NST) under the condition of low temperature in humans. We showed that the degree of NST for healthy subjects in an artificial climate chamber is significantly different among UCP1 genotypes. Defining the haplotypes covering the UCP1 region (39.4 kb), we found that the frequency of the haplotype with the highest NST was significantly correlated with latitudes and ambient temperature. Thus, the data in this study provide the first evidence that the UCP1 genotype alters the efficiency of NST in humans, and likely supports the hypothesis that the UCP1 gene has been related to cold adaptation in human evolutionary history.

Humans show various responses to the environmental stimulus in individual levels as "physiological variations." However, it has been unclear if these are caused by genetic variations. In this study, we examined the association between the physiological variation of response to light-stimulus and genetic polymorphisms. We collected physiological data from 43 subjects, including light-induced melatonin suppression, and performed haplotype analyses on the clock genes, PER2 and PER3, exhibiting geographical differentiation of allele frequencies. Among the haplotypes of PER3, no significant difference in light sensitivity was found. However, three common haplotypes of PER2 accounted for more than 96% of the chromosomes in subjects, and 1 of those 3 had a significantly low-sensitive response to light-stimulus (P < 0.05). The homozygote of the low-sensitive PER2 haplotype showed significantly lower percentages of melatonin suppression (P < 0.05), and the heterozygotes of the haplotypes varied their ratios, indicating that the physiological variation for light-sensitivity is evidently related to the PER2 polymorphism. Compared with global haplotype frequencies, the haplotype with a low-sensitive response was more frequent in Africans than in non-Africans, and came to the root in the phylogenetic tree, suggesting that the low light-sensitive haplotype is the ancestral type, whereas the other haplotypes with high sensitivity to light are the derived types. Hence, we speculate that the high light-sensitive haplotypes have spread throughout the world after the Out-of-Africa migration of modern humans.

Crohn's disease (CD) involves chronic inflammation in the gastrointestinal tract due to dysregulation of the host immune response to the gut microbiome. Even though the host-microbiome interactions are likely contributors to the development of CD, a few studies have detected genetic variants that change bacterial compositions and increase CD risk. We focus on one of the well-replicated susceptible genes, tumor necrosis factor superfamily member 15 (TNFSF15), and apply statistical analyses for personal profiles of genotypes and salivary microbiota collected from CD cases and controls in the Ryukyu Islands, southernmost islands of the Japanese archipelago. Our association test confirmed the susceptibility of TNFSF15 in the Ryukyu Islands. We found that the recessive model was supported to fit the observed genotype frequency of risk alleles slightly better than the additive model, defining the genetic effect on CD if a pair of the chromosomes in an individual consists of all risk alleles. The combined analysis of haplotypes and salivary microbiome from a small set of samples showed a significant association of the genetic effect with the increase of Prevotella, which led to a significant increase of CD risk. However, the genetic effect on CD disappeared if the abundance of Prevotella was low, suggesting the genetic contribution to CD is conditionally independent given a fixed amount of Prevotella. Although our statistical power is limited due to the small sample size, these results support an idea that the genetic susceptibility of TNFSF15 to CD may be confounded, in part, by the increase of Prevotella.

Objectives: A cline of frequencies of the derived allele of the ALDH2 gene, which causes a deficiency of an enzyme and "facial flushing" in humans who drink alcohol, has been known among the people of the Japanese archipelago. This cline is conventionally explained by admixture with immigrants from the Asian continent occurring during the Yayoi period. Previous studies lack sufficient data from the peripheral regions of the indigenous Jomon people, and those data the ADH1B gene that is involved in the Class I ADH gene cluster and contains another variant leading to a functional change., Methods: We focused on the southwestern-most people from the Ryukyu Islands (n = 218) and those from northern Kyushu (n = 21) where the Yayoi immigrants likely arrived. We investigated both the Class I ADH and ALDH2 loci, as well as neutral genetic markers., Results: In the Ryukyu Islands, the frequencies of the ancestral alleles in both loci were always higher than those in mainland Japan, while the frequencies of ADH1B were less than those of the derived allele. A haplotype block was not observed in ALDH2 but was in Class I ADH., Discussion: Our data suggest that the derived allele of ALDH2 came with the Yayoi immigrants from the Asian continent to the Japanese archipelago. However, the derived allele of ADH1B is unlikely to be related to the Yayoi migration. Therefore, we postulate that the expansion of the derived allele of ADHIB in East Asia could be traced back to the last glacial period., (© 2016 Wiley Periodicals, Inc.)