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.

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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.

BackgroundInfluenza is a common infectious disease caused by influenza viruses. Annual epidemics cause severe illnesses, deaths, and economic loss around the world. To better defend against influenza viral infection, it is essential to understand its mechanisms and associated host responses. Many studies have been conducted to elucidate these mechanisms, however, the overall picture remains incompletely understood. A systematic understanding of influenza viral infection in host cells is needed to facilitate the identification of influential host response mechanisms and potential drug targets.DescriptionWe constructed a comprehensive map of the influenza A virus (‘IAV’) life cycle (‘FluMap’) by undertaking a literature-based, manual curation approach. Based on information obtained from publicly available pathway databases, updated with literature-based information and input from expert virologists and immunologists, FluMap is currently composed of 960 factors (i.e., proteins, mRNAs etc.) and 456 reactions, and is annotated with ~500 papers and curation comments. In addition to detailing the type of molecular interactions, isolate/strain specific data are also available. The FluMap was built with the pathway editor CellDesigner in standard SBML (Systems Biology Markup Language) format and visualized as an SBGN (Systems Biology Graphical Notation) diagram. It is also available as a web service (online map) based on the iPathways+ system to enable community discussion by influenza researchers. We also demonstrate computational network analyses to identify targets using the FluMap.ConclusionThe FluMap is a comprehensive pathway map that can serve as a graphically presented knowledge-base and as a platform to analyze functional interactions between IAV and host factors. Publicly available webtools will allow continuous updating to ensure the most reliable representation of the host-virus interaction network. The FluMap is available at http://www.influenza-x.org/flumap/.

It has been widely accepted that the initial steps in the formation of atherosclerotic lesions involve the adherence of circulating leukocytes to dysfunctional endothelium and their subsequent transmigration into the arterial intima [1±3]. The recruitment of leukocytes into the tissues is dependent on a multistep cascade of events mediated by distinct adhesion molecules such as the selectin family, immunoglobulin superfamily and integrin family [3,4]. Substantially, vascular cell adhesion molecule-1 (VCAM-1) has been found in rabbit atherosclerotic lesions [5] and intercellular adhesion molecule-1 (ICAM-1) has been expressed in human atherosclerotic plaques [6] and carotid bifurcations [7]. Also, the soluble form of adhesion molecules has recently been found in serum and increased levels have been re- Diabetologia (1998) Summary The purpose of this study was to investigate the relationship between complications arising from silent cerebral infarction (SCI) and changes in the levels of serum-soluble adhesion molecules in 82 elderly diabetic patients aged 60 years and older. SCI was found in 43 % of the 82 patients, with incidence increasing in relation to age. The prevalence of SCI was higher in subjects with hypertension, poor metabolic control and increased fibrinolysis. The levels of soluble intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1) and E-selectin (sE-selectin) were higher in diabetic patients than in non-diabetic subjects (p < 0.05, p < 0.001, and p < 0.05, respectively). Also, sICAM-1 and sVCAM-1 were found at increased levels in diabetic patients with SCI compared to those without SCI (p < 0.01 and p < 0.05, respectively). In particular, the level of sICAM-1 was increased in patients with SCI due to perforating arterial occlusion, while the level of sVCAM-1 was increased in patients with SCI due to cortical arterial occlusion. However, no significant difference was found in sE-selectin levels. Overall average of the intima and media thickness (IMT) of the common carotid arteries increased with age. IMT proved to be greater in patients with SCI than in patients without SCI (p < 0.05), and showed a weak but significant positive correlation with sVCAM-1, while no correlation was found with either sICAM-1 or sE-selectin levels. In conclusion, measurement of serum adhesion molecules may be useful for diagnosing the early stages of brain damage and for prophylactic treatment which may prevent the onset or progression of SCI. [Diabetologia (1998) 41: 911±917]