Triangulation supports agricultural spread of the Transeurasian languages.

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 history1-3. A key problem is the relationship between linguistic dispersals, agricultural expansions and population movements4,5. 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.

Ancient lipids document continuity in the use of early hunter-gatherer pottery through 9,000 years of Japanese prehistory.

The earliest pots in the world are from East Asia and date to the Late Pleistocene. However, ceramic vessels were only produced in large numbers during the warmer and more stable climatic conditions of the Holocene. It has long been assumed that the expansion of pottery was linked with increased sedentism and exploitation of new resources that became available with the ameliorated climate, but this hypothesis has never been tested. Through chemical analysis of their contents, we herein investigate the use of pottery across an exceptionally long 9,000-y sequence from the Jomon site of Torihama in western Japan, intermittently occupied from the Late Pleistocene to the mid-Holocene. Molecular and isotopic analyses of lipids from 143 vessels provides clear evidence that pottery across this sequence was predominantly used for cooking marine and freshwater resources, with evidence for diversification in the range of aquatic products processed during the Holocene. Conversely, there is little indication that ruminant animals or plants were processed in pottery, although it is evident from the faunal and macrobotanical remains that these foods were heavily exploited. Supported by other residue analysis data from Japan, our results show that the link between pottery and fishing was established in the Late Paleolithic and lasted well into the Holocene, despite environmental and socio-economic change. Cooking aquatic products in pottery represents an enduring social aspect of East Asian hunter-gatherers, a tradition based on a dependable technology for exploiting a sustainable resource in an uncertain and changing world.

Inland sea as a unit for environmental history: East Asian inland seas from prehistory to future.

The boundaries of landscape policies often coincide with political or economic boundaries, thus creating a situation where a unit of landscape protection or management reflects more its present political status than its historico-geographical situation, its historical function and formation. At the same time, it is evident that no unit can exist independently of the context that has given birth to it and that environmental protection in isolated units cannot be very effective. The present paper will discuss inland sea as a landscape unit from prehistory to modern days and its implications for future landscape planning, using EastAsian inland sea (Japan Sea and East China Sea) rim as an example. Historically an area of active communication, EastAsian inland sea rim has become a politically very sharply divided area. The authors will bring examples to demonstrate how cultural communication on the inland sea level has influenced the formation of several landscape features that are now targets for local or national landscape protection programs, and how a unified view could benefit the future of landscape policies in the whole region.

The identification of zebrafish mutants showing alterations in senescence-associated biomarkers.

There is an interesting overlap of function in a wide range of organisms between genes that modulate the stress responses and those that regulate aging phenotypes and, in some cases, lifespan. We have therefore screened mutagenized zebrafish embryos for the altered expression of a stress biomarker, senescence-associated beta-galactosidase (SA-beta-gal) in our current study. We validated the use of embryonic SA-beta-gal production as a screening tool by analyzing a collection of retrovirus-insertional mutants. From a pool of 306 such mutants, we identified 11 candidates that showed higher embryonic SA-beta-gal activity, two of which were selected for further study. One of these mutants is null for a homologue of Drosophila spinster, a gene known to regulate lifespan in flies, whereas the other harbors a mutation in a homologue of the human telomeric repeat binding factor 2 (terf2) gene, which plays roles in telomere protection and telomere-length regulation. Although the homozygous spinster and terf2 mutants are embryonic lethal, heterozygous adult fish are viable and show an accelerated appearance of aging symptoms including lipofuscin accumulation, which is another biomarker, and shorter lifespan. We next used the same SA-beta-gal assay to screen chemically mutagenized zebrafish, each of which was heterozygous for lesions in multiple genes, under the sensitizing conditions of oxidative stress. We obtained eight additional mutants from this screen that, when bred to homozygosity, showed enhanced SA-beta-gal activity even in the absence of stress, and further displayed embryonic neural and muscular degenerative phenotypes. Adult fish that are heterozygous for these mutations also showed the premature expression of aging biomarkers and the accelerated onset of aging phenotypes. Our current strategy of mutant screening for a senescence-associated biomarker in zebrafish embryos may thus prove to be a useful new tool for the genetic dissection of vertebrate stress response and senescence mechanisms.

Populations dynamics in Northern Eurasian forests: a long-term perspective from Northeast Asia.

The 'Northern Eurasian Greenbelt' (NEG) is the northern forest zone stretching from the Japanese Archipelago to Northern Europe. The NEG has created highly productive biomes for humanity to exploit since the end of the Pleistocene. This research explores how the ecological conditions in northern Eurasia contributed to and affected human migrations and cultural trajectories by synthesizing the complimentary viewpoints of environmental archaeology, Geographic Information Science (GIS), genetics and linguistics. First, the environmental archaeology perspective raises the possibility that the NEG functioned as a vessel fostering people to develop diverse cultures and engage in extensive cross-cultural exchanges. Second, geographical analysis of genomic data on mitochondrial DNA using GIS reveals the high probability that population dynamics in the southeastern NEG promoted the peopling of the Americas at the end of the Pleistocene. Finally, a linguistic examination of environmental- and landscape-related vocabulary of the proto-Turkic language groups enables the outline of their original cultural landscape and natural conditions, demonstrating significant cultural spheres, i.e. from southern Siberia to eastern Inner Mongolia during Neolithization. All of these results combine to suggest that the ecological complex in the southern edge of the NEG in northeast Asia played a significant role in peopling across the continents during prehistory.

Zebrafish as a genetic model in biological and behavioral gerontology: where development meets aging in vertebrates--a mini-review.

Understanding the molecular mechanisms of aging in vertebrates is a major challenge of modern biology and biomedical science. This is due, in part, to the complexity of the aging process and its multifactorial nature, the paucity of animal models that lend themselves to unbiased high-throughput screening for aging phenotypes, and the difficulty of predicting such phenotypes at an early age. We suggest that the zebrafish genetic model offers a unique opportunity to fill in this gap and contributes to advances in biological and behavioral gerontology. Our recent studies demonstrated that this diurnal vertebrate with gradual senescence is an excellent model in which to study age-dependent changes in musculoskeletal and eye morphology, endocrine factors, gene expression, circadian clock, sleep and cognitive functions. Importantly, we have also found that the presence of a senescence-associated biomarker ('senescence-associated beta-galactosidase') can be documented during early zebrafish development and is predictive of premature aging phenotypes later in adult life. The availability of mutant 'genotypes' with identified aging 'phenotypes' in zebrafish, in combination with a wealth of information about zebrafish development and genetics, and the existence of multiple mutant and transgenic lines, should significantly facilitate the use of this outstanding vertebrate model in deciphering the mechanisms of aging, and in developing preventive and therapeutic strategies to prolong the productive life span ('health span') in humans.

Common carp aquaculture in Neolithic China dates back 8,000 years.

Despite the growing importance of farmed fish for contemporary economies, the origins of aquaculture are poorly known. Although it is widely assumed that fish domestication began much later than the domestication of land animals, the evidence is largely negative. Here, we use age-mortality and species-selection profiles of fish bones from prehistoric East Asia to show that managed aquaculture of common carp (Cyprinus carpio) was present at the Early Neolithic Jiahu site, Henan Province, China, by around 6000 BC.

Publisher Correction: Common carp aquaculture in Neolithic China dates back 8,000 years.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Differential effects of genotoxic stress on both concurrent body growth and gradual senescence in the adult zebrafish.

Among vertebrates, fish and mammals show intriguing differences in their growth control properties with age. The potential for unlimited or indeterminate growth in a variety of fish species has prompted many questions regarding the senescent phenomena that appear during the aging process in these animals. Using zebrafish as our model system, we have attempted in our current study to examine the growth phenomena in fish in relation to the onset of senescence-associated symptoms, and to evaluate the effects of genotoxic stress on these processes. We observed in the course of these analyses that the zebrafish undergoes continuous growth, irrespective of age, past the point of sexual maturation with gradually decreasing growth rates at later stages. Animal population density, current body size and chronological age also play predominant roles in regulating zebrafish growth and all inversely influence the growth rate. Interestingly, the induction of genotoxic stress by exposure to ionizing radiation (IR) did not adversely affect this body growth ability in zebrafish. However, IR was found to chronically debilitate the regeneration of amputated caudal fins and thereby induce high levels of abnormal fin regeneration in the adult zebrafish. In addition, by resembling and mimicking the natural course of aging, IR treatments likewise enhanced several other symptoms of senescence, such as a decline in reproductive abilities, increased senescence-associated beta-galactosidase activity and a reduction in melatonin secretion. Our current data thus suggest that during the lifespan of zebrafish, the onset of senescence-associated symptoms occurs in parallel with continuous growth throughout mid-adulthood. Moreover, our present findings indicate that genotoxic DNA damage may play a role as a rate-limiting factor during the induction of senescence, but not in the inhibition of continuous, density-dependent growth in adult zebrafish.

The zebrafish as a vertebrate model of functional aging and very gradual senescence.

The zebrafish (Danio rerio) has been developed as a powerful model for genetic studies in developmental biology, which also gives insights into several diseases of adult humans such as cardiovascular disease and cancer. Because aging processes affect these and many other human diseases, it is important to compare zebrafish and other mammalian aging. However, the aging process of zebrafish remains largely unexplored, and little is known about its functional aging and senescence. In a survey of aging in zebrafish, we detected senescence-associated beta-galactosidase activity in skin and oxidized protein accumulation in muscle. However, we did not observe lipofuscin granules ('aging pigments'), which commonly accumulate in postmitotic cells of other vertebrates. This absence of lipofuscins may be consistent with the existence of continuously proliferating myocytes that incorporated BrdU in muscle tissues of aged zebrafish. Moreover, we demonstrated that zebrafish have constitutively abundant telomerase activity in somatic tissues from embryos to aged adults. Although some stress-associated markers are upregulated and minor histological changes are observed during the aging process of zebrafish, our studies together with other evidence of remarkable reproductive and regenerative abilities suggest that zebrafish show very gradual or sub-negligible senescence in vivo.

A non-canonical function of zebrafish telomerase reverse transcriptase is required for developmental hematopoiesis.

Although it is clear that telomerase expression is crucial for the maintenance of telomere homeostasis, there is increasing evidence that the TERT protein can have physiological roles that are independent of this central function. To further examine the role of telomerase during vertebrate development, the zebrafish telomerase reverse transcriptase (zTERT) was functionally characterized. Upon zTERT knockdown, zebrafish embryos show reduced telomerase activity and are viable, but develop pancytopenia resulting from aberrant hematopoiesis. The blood cell counts in TERT-depleted zebrafish embryos are markedly decreased and hematopoietic cell differentiation is impaired, whereas other somatic lineages remain morphologically unaffected. Although both primitive and definitive hematopoiesis is disrupted by zTERT knockdown, the telomere lengths are not significantly altered throughout early development. Induced p53 deficiency, as well as overexpression of the anti-apoptotic proteins Bcl-2 and E1B-19K, significantly relieves the decreased blood cells numbers caused by zTERT knockdown, but not the impaired blood cell differentiation. Surprisingly, only the reverse transcriptase motifs of zTERT are crucial, but the telomerase RNA-binding domain of zTERT is not required, for rescuing complete hematopoiesis. This is therefore the first demonstration of a non-canonical catalytic activity of TERT, which is different from "authentic" telomerase activity, is required for during vertebrate hematopoiesis. On the other hand, zTERT deficiency induced a defect in hematopoiesis through a potent and specific effect on the gene expression of key regulators in the absence of telomere dysfunction. These results suggest that TERT non-canonically functions in hematopoietic cell differentiation and survival in vertebrates, independently of its role in telomere homeostasis. The data also provide insights into a non-canonical pathway by which TERT functions to modulate specification of hematopoietic stem/progenitor cells during vertebrate development. (276 words).