Multiple migrations to the Philippines during the last 50,000 years.

Island Southeast Asia has recently produced several surprises regarding human history, but the region's complex demography remains poorly understood. Here, we report ∼2.3 million genotypes from 1,028 individuals representing 115 indigenous Philippine populations and genome-sequence data from two ∼8,000-y-old individuals from Liangdao in the Taiwan Strait. We show that the Philippine islands were populated by at least five waves of human migration: initially by Northern and Southern Negritos (distantly related to Australian and Papuan groups), followed by Manobo, Sama, Papuan, and Cordilleran-related populations. The ancestors of Cordillerans diverged from indigenous peoples of Taiwan at least ∼8,000 y ago, prior to the arrival of paddy field rice agriculture in the Philippines ∼2,500 y ago, where some of their descendants remain to be the least admixed East Asian groups carrying an ancestry shared by all Austronesian-speaking populations. These observations contradict an exclusive "out-of-Taiwan" model of farming-language-people dispersal within the last four millennia for the Philippines and Island Southeast Asia. Sama-related ethnic groups of southwestern Philippines additionally experienced some minimal South Asian gene flow starting ∼1,000 y ago. Lastly, only a few lowlanders, accounting for <1% of all individuals, presented a low level of West Eurasian admixture, indicating a limited genetic legacy of Spanish colonization in the Philippines. Altogether, our findings reveal a multilayered history of the Philippines, which served as a crucial gateway for the movement of people that ultimately changed the genetic landscape of the Asia-Pacific region.

Peach Kernel Extracts Inhibit Lipopolysaccharide-Induced Activation of HSC-T6 Hepatic Stellate Cells.

There is an important role for hepatic stellate cells (HSCs) in liver fibrosis. As it stands, many traditional Chinese medicine formulations can effectively improve liver fibrosis, whether it is clinically used or in animal studies; however, the efficacy and mechanism of the main formulations remain unclear, including the peach kernel, which contains numerous phytochemicals with a wide range of biological activities. The purpose of this study was to investigate peach kernel's anti-liver fibrosis effects. In this study, peach kernel extracts inhibited lipopolysaccharide (LPS) activation in HSC-T6 cells and the expression of α-smooth muscle actin and connective tissue growth factor induced by LPS in HSC-T6 cells. Furthermore, peach kernel extracts inhibited signal transducers involving protein kinase B and mitogen-activated protein kinase, which regulate downstream genes associated with inflammation. As a result, peach kernel extracts inhibited inflammatory responses and subsequently inhibited LPS-induced transformation of activated HSC-T6 cells.

Correction to: Genetic diversity of the Thao people of Taiwan using Y-chromosome, mitochondrial DNA and HLA gene systems.

Following publication of the original article [1], we have been notified that Additional file 3 was published with track changes.

Genetic diversity of the Thao people of Taiwan using Y-chromosome, mitochondrial DNA and HLA gene systems.

BACKGROUND: Despite attempts in retracing the history of the Thao people in Taiwan using folktales, linguistics, physical anthropology, and ethnic studies, their history remains incomplete. The heritage of Thao has been associated with the Pazeh Western plains peoples and several other mountain peoples of Taiwan. In the last 400 years, their culture and genetic profile have been reshaped by East Asian migrants. They were displaced by the Japanese and the construction of a dam and almost faced extinction. In this paper, genetic information from mitochondrial DNA (mtDNA), Histoleucocyte antigens (HLA), and the non-recombining Y chromosome of 30 Thao individuals are compared to 836 other Taiwan Mountain and Plains Aborigines (TwrIP & TwPp), 384 Non-Aboriginal Taiwanese (non-TwA) and 149 Continental East Asians. RESULTS: The phylogeographic analyses of mtDNA haplogroups F4b and B4b1a2 indicated gene flow between Thao, Bunun, and Tsou, and suggested a common ancestry from 10,000 to 3000 years ago. A claim of close contact with the heavily Sinicized Pazeh of the plains was not rejected and suggests that the plains and mountain peoples most likely shared the same Austronesian agriculturist gene pool in the Neolithic. CONCLUSIONS: Having been moving repeatedly since their arrival in Taiwan between 6000 and 4500 years ago, the Thao finally settled in the central mountain range. They represent the last plains people whose strong bonds with their original culture allowed them to preserve their genetic heritage, despite significant gene flow from the mainland of Asia. Representing a considerable contribution to the genealogical history of the Thao people, the findings of this study bear on ongoing anthropological and linguistic debates on their origin.

The Luoping biota: exceptional preservation, and new evidence on the Triassic recovery from end-Permian mass extinction.

The timing and nature of biotic recovery from the devastating end-Permian mass extinction (252 Ma) are much debated. New studies in South China suggest that complex marine ecosystems did not become re-established until the middle-late Anisian (Middle Triassic), much later than had been proposed by some. The recently discovered exceptionally preserved Luoping biota from the Anisian Stage of the Middle Triassic, Yunnan Province and southwest China shows this final stage of community assembly on the continental shelf. The fossil assemblage is a mixture of marine animals, including abundant lightly sclerotized arthropods, associated with fishes, marine reptiles, bivalves, gastropods, belemnoids, ammonoids, echinoderms, brachiopods, conodonts and foraminifers, as well as plants and rare arthropods from nearby land. In some ways, the Luoping biota rebuilt the framework of the pre-extinction latest Permian marine ecosystem, but it differed too in profound ways. New trophic levels were introduced, most notably among top predators in the form of the diverse marine reptiles that had no evident analogues in the Late Permian. The Luoping biota is one of the most diverse Triassic marine fossil Lagerstätten in the world, providing a new and early window on recovery and radiation of Triassic marine ecosystems some 10 Myr after the end-Permian mass extinction.

Philippine Ayta possess the highest level of Denisovan ancestry in the world.

Multiple lines of evidence show that modern humans interbred with archaic Denisovans. Here, we report an account of shared demographic history between Australasians and Denisovans distinctively in Island Southeast Asia. Our analyses are based on ∼2.3 million genotypes from 118 ethnic groups of the Philippines, including 25 diverse self-identified Negrito populations, along with high-coverage genomes of Australopapuans and Ayta Magbukon Negritos. We show that Ayta Magbukon possess the highest level of Denisovan ancestry in the world-∼30%-40% greater than that of Australians and Papuans-consistent with an independent admixture event into Negritos from Denisovans. Together with the recently described Homo luzonensis, we suggest that there were multiple archaic species that inhabited the Philippines prior to the arrival of modern humans and that these archaic groups may have been genetically related. Altogether, our findings unveil a complex intertwined history of modern and archaic humans in the Asia-Pacific region, where distinct Islander Denisovan populations differentially admixed with incoming Australasians across multiple locations and at various points in time.

Cognitive improvements and reduction in amyloid plaque deposition by saikosaponin D treatment in a murine model of Alzheimer's disease.

Alzheimer's disease (AD), is a severe neurodegenerative disease that currently lacks an optimally effective therapeutic agent for its management. Saikosaponin D (SSD) is a component extracted from the herb Bupleurum falcatum that is commonly used in Chinese medicine. Although SSD has been reported to exert neuroprotective effects, its pharmacological role in AD has not been previously elucidated. Therefore, the aim of the present study was to investigate whether SSD treatment improves the cognitive function and pathological features of 3xTg mice, a triple-transgenic mouse model of AD that displays classical pathological features of AD. The effects of SSD treatment on the behavioral, histological and physiological features of the animal were quantified. Results from the behavioral experiments on the SSD-treated 3xTg mice identified a significant reduction in memory impairment. In addition, histological staining results indicated that SSD application could preserve the morphology of neurons, reduce apoptosis and significantly inhibit amyloid-ß deposition in the hippocampus of 3xTg mice. SSD treatment also decelerated the activation of microglia and astrocytes in the hippocampus of 3xTg mice, possibly via the inhibition of the NF-κB signal transduction pathway. Therefore, the present study demonstrated the protective effects of SSD against progressive neurodegeneration and identified the potential underlying pharmacological mechanism. It was speculated that SSD may serve as a possible therapeutic agent in AD treatment in the future.

A new stem group echinoid from the Triassic of China leads to a revised macroevolutionary history of echinoids during the end-Permian mass extinction.

The Permian-Triassic bottleneck has long been thought to have drastically altered the course of echinoid evolution, with the extinction of the entire echinoid stem group having taken place during the end-Permian mass extinction. The Early Triassic fossil record of echinoids is, however, sparse, and new fossils are paving the way for a revised interpretation of the evolutionary history of echinoids during the Permian-Triassic crisis and Early Mesozoic. A new species of echinoid, Yunnanechinus luopingensis n. sp. recovered from the Middle Triassic (Anisian) Luoping Biota fossil Lagerstätte of South China, displays morphologies that are not characteristic of the echinoid crown group. We have used phylogenetic analyses to further demonstrate that Yunnanechinus is not a member of the echinoid crown group. Thus a clade of stem group echinoids survived into the Middle Triassic, enduring the global crisis that characterized the end-Permian and Early Triassic. Therefore, stem group echinoids did not go extinct during the Palaeozoic, as previously thought, and appear to have coexisted with the echinoid crown group for at least 23 million years. Stem group echinoids thus exhibited the Lazarus effect during the latest Permian and Early Triassic, while crown group echinoids did not.

Increased risk of peripheral arterial disease in patients with alcohol intoxication: A population-based retrospective cohort study.

Previous studies have reported that light-to-moderate drinkers have a lower risk of peripheral arterial disease (PAD) than abstainers, and that heavy drinking increases the risk of PAD. However, reports of the effects of severe alcohol drinking on PAD are lacking within a population-based cohort. Alcohol intoxication is typically considered a medical emergency at clinics in Taiwan and is commonly attributed to excessive alcohol use. The present study aimed to investigate the association between alcohol intoxication and PAD risk. We conducted a retrospective, population-based, health insurance cohort study consisting of 56,544 adult patients with alcohol intoxication between January 1, 2000 and December 31, 2009, using claims data from the National Health Insurance Research Database (NHIRD) of Taiwan. This database included a control cohort of 226,176 residents without alcohol intoxication. The patients were age- and gender-matched. The incidence rate of PAD, after data regarding alcohol intoxication were obtained, was 12.8 per 10,000 person-years, and the adjusted hazard ratio (aHR) of PAD was 3.80 (95% confidence interval [CI] = 3.35-4.32, p < 0.05). The log-rank test showed that patients with alcohol intoxication had a considerably higher PAD cumulative incidence rate than those without alcohol intoxication. Alcohol intoxication was significantly associated with an increased risk of PAD in men (hazard ratio [HR] = 3.77, 95% CI = 3.30-4.31) and women (HR = 4.26, 95% CI = 2.60-6.97). The aHRs of PAD risk were 7.64 (95% CI = 4.39-13.3), 4.51 (95% CI = 3.83-5.29), and 2.16 (95% CI = 1.69-2.77) for patients with alcohol intoxication compared to participants of the control group aged <35 years, 35-64 years, and ≥65 years, respectively. The individuals with alcohol intoxication and without any comorbidities had a 3.77-fold increased risk of PAD in comparison to that of the control cohorts (HR = 3.77, 95% CI = 3.30-4.30). The aHR of PAD in patients with alcohol intoxication was 4.53 (95% CI = 2.51-8.16) in comparison to the control cohort, which consisted of patients with at least one existing comorbidity. Alcohol intoxication, along with the severe complications of excessive alcohol use, should be considered as major risk factors of PAD in the setting of a medical emergency. Further research needs to be performed to evaluate the quantitative effect of alcohol use on PAD.

A gigantic nothosaur (Reptilia: Sauropterygia) from the Middle Triassic of SW China and its implication for the Triassic biotic recovery.

The presence of gigantic apex predators in the eastern Panthalassic and western Tethyan oceans suggests that complex ecosystems in the sea had become re-established in these regions at least by the early Middle Triassic, after the Permian-Triassic mass extinction (PTME). However, it is not clear whether oceanic ecosystem recovery from the PTME was globally synchronous because of the apparent lack of such predators in the eastern Tethyan/western Panthalassic region prior to the Late Triassic. Here we report a gigantic nothosaur from the lower Middle Triassic of Luoping in southwest China (eastern Tethyan ocean), which possesses the largest known lower jaw among Triassic sauropterygians. Phylogenetic analysis suggests parallel evolution of gigantism in Triassic sauropterygians. Discovery of this gigantic apex predator, together with associated diverse marine reptiles and the complex food web, indicates global recovery of shallow marine ecosystems from PTME by the early Middle Triassic.