Investigating the modern human settlement of Mainland Southeast Asia using mitochondrial DNA

Many questions remain about the settlement of anatomically modern humans in Mainland Southeast Asia (MSEA). During the last Ice Age, the Sunda shelf was exposed and the Sunda continent connected MSEA with western ISEA (Java, Sumatra and Borneo), but global warming after about 20,000 years ago (20ka) led to rises in sea levels which flooded a large part of Sundaland. This region is a key area of initial settlement of anatomically modern humans, who likely expanded along the coastal route from the Horn of Africa via Arabia and South Asia towards Australasia. In this work, I aimed to investigate the first arrival of modern populations in MSEA, clarify the timing and process, and study the subsequent demographic history of its populations from the perspective of the maternal line of descent. I have studied phylogeographic and phylogenetic relationships of populations in North, South, and Southeast Asia using mitochondrial DNA (mtDNA) genome variation, using both control-region sequence and whole mitogenomes, in order to gain a more comprehensive insight into the evolutionary history of the MSEA population. Using next-generation sequencing I have analysed 909 new complete mtDNA sequences from MSEA population, including 506 Lao, 387 Vietnamese and 16 Burmese samples in the context of the available published world-wide database. Most of the basal lineages within the major non-African founders, the roots of haplogroups M and R, represent the indigenous inhabitants who first arrived in the region from the west. The founder ages for M and R were dated by maximum likelihood in this study to ~61 ka and ~64ka, with a 95% confidence range of 55 ka to 73 ka, confirming that this was most likely and shortly after the volcanic eruption of Mount Toba in Sumatra at 74 ka, with MSEA and ISEA beginning to diverge as early as ~54 ka. I have used founder analysis with the new mitogenomes in order to quantify the fraction of maternal lineages that arrived at various times throughout prehistory. This showed that approximately 11-21% of modern mtDNA lineages date to the first settlement, with several subsequent major waves of arrival, mainly from the north in what is now South China, since the Last Glacial Maximum. These subsequent events are primarily focused on three time intervals, and suggest a strong demographic impact from climatic changes following the end of the last Ice Age. The first is the Late Glacial, ~13 ka, at the time of the first major sea-level rise (17-19% of modern mtDNAs), but the largest fraction dates to the early postglacial, at the time of the final major sea-level rise, ~7 ka (36-37%). This early Holocene process corresponds to the middle Neolithic, or coastal Neolithic, a dispersal of primarily hunter-gatherer groups adapted to coastal resources and possibly practising early forms of horticulture and/or arboriculture. Only a minority of lineages, amounting to 18-24%, date to the spread of late Neolithic rice agriculture from South China ~4 ka

Biomolecular insights into North African-related ancestry, mobility and diet in eleventh-century Al-Andalus.

Funder: Helmholtz Zentrum München – German Research Center for Environmental HealthFunder: Leverhulme TrustHistorical records document medieval immigration from North Africa to Iberia to create Islamic al-Andalus. Here, we present a low-coverage genome of an eleventh century CE man buried in an Islamic necropolis in Segorbe, near Valencia, Spain. Uniparental lineages indicate North African ancestry, but at the autosomal level he displays a mosaic of North African and European-like ancestries, distinct from any present-day population. Altogether, the genome-wide evidence, stable isotope results and the age of the burial indicate that his ancestry was ultimately a result of admixture between recently arrived Amazigh people (Berbers) and the population inhabiting the Peninsula prior to the Islamic conquest. We detect differences between our sample and a previously published group of contemporary individuals from Valencia, exemplifying how detailed, small-scale aDNA studies can illuminate fine-grained regional and temporal differences. His genome demonstrates how ancient DNA studies can capture portraits of past genetic variation that have been erased by later demographic shifts-in this case, most likely the seventeenth century CE expulsion of formerly Islamic communities as tolerance dissipated following the Reconquista by the Catholic kingdoms of the north

Study of effect of inhaled versus oral corticosteroids on sputum granzyme B in patients with moderate persistent bronchial asthma

Background: Asthma is a major public health problem with a high economic burden. It involves several inflammatory cells and multiple mediators. Granzyme B is an inflammatory mediator expressed and secreted by both immune and non immune cells. Recently it was found to play a role in the pathogenesis of asthma. The aim of this work: was to evaluate the effect of both inhaled and oral corticosteroids on sputum granzyme B in asthmatic patients with moderate severity. Methods: The study included 25 patients with moderate persistent asthma plus 15 healthy subjects as a control group. Granzyme B was measured before treatment with corticosteroids then after inhalation therapy and oral therapy. Results: It was found that expected pulmonary function parameters were significantly lower in asthmatic patients than in controls. Sputum granzyme B levels were significantly higher in asthmatic patients than in controls. Sputum granzyme B levels were significantly lower after treatment with inhaled corticosteroids than basal levels. Oral corticosteroids further significantly lowered granzyme B, but the lowering effect of inhaled steroids was significantly higher than that of oral drugs. There was no statistically significant correlation between granzyme B and PFTs in asthmatic patients. Conclusion: Granzyme B levels are elevated in bronchial asthma. Granzyme B could play a role in the pathogenesis of bronchial asthma. Both inhaled and oral corticosteroids lowered granzyme B levels significantly. The lowering effect of inhaled corticosteroids on sputum granzyme B is more than that of the oral corticosteroids