Northern China harbored the world's earliest complex societies based on millet farming, in two major centers in the Yellow (YR) and West Liao (WLR) River basins. Until now, their genetic histories have remained largely unknown. Here we present 55 ancient genomes dating to 7500-1700 BP from the YR, WLR, and Amur River (AR) regions. Contrary to the genetic stability in the AR, the YR and WLR genetic profiles substantially changed over time. The YR populations show a monotonic increase over time in their genetic affinity with present-day southern Chinese and Southeast Asians. In the WLR, intensification of farming in the Late Neolithic is correlated with increased YR affinity while the inclusion of a pastoral economy in the Bronze Age was correlated with increased AR affinity. Our results suggest a link between changes in subsistence strategy and human migration, and fuel the debate about archaeolinguistic signatures of past human migration.

We sequenced 15 complete mitochondrial genomes and performed comprehensive molecular phylogenetic analyses to study the origin and phylogeny of the Hynobiidae, an ancient lineage of living salamanders. Our phylogenetic analyses show that the Hynobiidae is a clade with well resolved relationships, and our results contrast with a morphology-based phylogenetic hypothesis. These salamanders have low vagility and are limited in their distribution primarily by deserts, mountains, and oceans. Our analysis suggests that the relationships among living hynobiids have been shaped primarily by geography. We show that four-toed species assigned to Batrachuperus do not form a monophyletic group, and those that occur in Afghanistan and Iran are transferred to the resurrected Paradactylodon. Convergent morphological characters in different hynobiid lineages are likely produced by similar environmental selective pressures. Clock-independent molecular dating suggests that hynobiids originated in the Middle Cretaceous [Ϸ110 million years ago (Mya)]. We propose an ''out of North China'' hypothesis for hynobiid origins and hypothesize an ancestral stream-adapted form. Given the particular distributional patterns and our molecular dating estimates, we hypothesize that: (i) the interior desertification from Mongolia to Western Asia began Ϸ50 Mya; (ii) the Tibetan plateau (at least on the eastern fringe) experienced rapid uplift Ϸ40 Mya and reached an altitude of at least 2,500 m; and (iii) the Ailao-Red River shear zone underwent the most intense orogenic movement Ϸ24 Mya.mitochondrial DNA ͉ phylogenetics ͉ homoplasy ͉ Tibetan Plateau T he Asiatic Salamanders, Hynobiidae, represent an early branch of the caudate lineage (1). All living species (Ϸ50, in seven to nine genera; http:͞͞amphibiaweb.org) occur in Asia. Hynobiids are closely related to the family Cryptobranchidae, with which they form the suborder Cryptobranchoidea. In comparison with other living salamanders, hynobiids are thought to resemble the most recent common ancestor of all salamanders because of three traits that are regarded as ancestral: external fertilization, an angular bone in the lower jaw, and large numbers of microchromosomes (1-3). Although usually thought to be monophyletic, the Hynobiidae also has been considered a paraphyletic stem group (4). Fossil hynobiids are known from the Late Miocene [Ϸ5 million years ago (Mya)] (5), whereas their relatives, cryptobranchids, can be traced back to the Jurassic (Ϸ160 Mya) (6). Remarkably, recent fossil findings of salamanders from the Early Cretaceous of North China show strong similarities with the Hynobiidae with respect to many skeletal features (7-9). This finding raises the questions of where and when hynobiids originated and what relationship there is between them and their fossil relatives. To answer these questions, a robust phylogenetic hypothesis of living hynobiids is required. Apart from a tentative phylogeny based on 23 morphological characters ( Fig. 1; ref. 10), and another based on an unpublished data...

Establishing the relationships among modern amphibians (lissamphibians) and their ancient relatives is necessary for our understanding of early tetrapod evolution. However, the phylogeny is still intractable because of the highly specialized anatomy and poor fossil record of lissamphibians. Paleobiologists are still not sure whether lissamphibians are monophyletic or polyphyletic, and which ancient group (temnospondyls or lepospondyls) is most closely related to them. In an attempt to address these problems, eight mitochondrial genomes of living amphibians were determined and compared with previously published amphibian sequences. A comprehensive molecular phylogenetic analysis of nucleotide sequences yields a highly resolved tree congruent with the traditional hypotheses (Batrachia). By using a molecular clock-independent approach for inferring dating information from molecular phylogenies, we present here the first molecular timescale for lissamphibian evolution, which suggests that lissamphibians first emerged about 330 million years ago. By observing the fit between molecular and fossil times, we suggest that the temnospondyl-origin hypothesis for lissamphibians is more credible than other hypotheses. Moreover, under this timescale, the potential geographic origins of the main living amphibian groups are discussed: (i) advanced frogs (neobatrachians) may possess an Africa-India origin; (ii) salamanders may have originated in east Asia; (iii) the tropic forest of the Triassic Pangaea may be the place of origin for the ancient caecilians. An accurate phylogeny with divergence times can be also helpful to direct the search for "missing" fossils, and can benefit comparative studies of amphibian evolution.

Purpose: To determine the possibility of synergistic antileukemic activity and the underlying molecular mechanisms associated with cytarabine combined with valproic acid (VPA; a histone deacetylase inhibitor and a Food and Drug Administration-licensed drug for treating both children and adults with epilepsy) in pediatric acute myeloid leukemia (AML).Experimental Design: The type and extent of antileukemic interactions between cytarabine and VPA in clinically relevant pediatric AML cell lines and diagnostic blasts from children with AML were determined by MTT assays and standard isobologram analyses. The effects of cytarabine and VPA on apoptosis and cell cycle distributions were determined by flow cytometry analysis and caspase enzymatic assays. The effects of the two agents on DNA damage and Bcl-2 family proteins were determined by Western blotting.Results: We showed synergistic antileukemic activities between cytarabine and VPA in four pediatric AML cell lines and nine diagnostic AML blast samples. t(8;21) AML blasts were significantly more sensitive to VPA and showed far greater sensitivities to combined cytarabine and VPA than non-t(8;21) AML cases. Cytarabine and VPA cooperatively induced DNA double-strand breaks, reflected in induction of γH2AX and apoptosis, accompanied by activation of caspase-9 and caspase-3. Further, VPA induced Bim expression and short hairpin RNA knockdown of Bim resulted in significantly decreased apoptosis induced by cytarabine and by cytarabine plus VPA.Conclusions: Our results establish global synergistic antileukemic activity of combined VPA and cytarabine in pediatric AML and provide compelling evidence to support the use of VPA in the treatment of children with this deadly disease. Clin Cancer Res; 16(22); 5499-510. ©2010 AACR.