From the Cover: Genomic and cranial phenotype data support multiple modern human dispersals from Africa and a southern route into Asia

Despite broad consensus on Africa as the main place of origin for anatomically modern humans, their dispersal pattern out of the continent continues to be intensely debated. In extant human populations, the observation of decreasing genetic and phenotypic diversity at increasing distances from sub-Saharan Africa has been interpreted as evidence for a single dispersal, accompanied by a series of founder effects. In such a scenario, modern human genetic and phenotypic variation was primarily generated through successive population bottlenecks and drift during a rapid worldwide expansion out of Africa in the Late Pleistocene. However, recent genetic studies, as well as accumulating archaeological and paleoanthropological evidence, challenge this parsimonious model. They suggest instead a “southern route” dispersal into Asia as early as the late Middle Pleistocene, followed by a separate dispersal into northern Eurasia. Here we test these competing out-of-Africa scenarios by modeling hypothetical geographical migration routes and assessing their correlation with neutral population differentiation, as measured by genetic polymorphisms and cranial shape variables of modern human populations from Africa and Asia. We show that both lines of evidence support a multiple-dispersals model in which Australo-Melanesian populations are relatively isolated descendants of an early dispersal, whereas other Asian populations are descended from, or highly admixed with, members of a subsequent migration event.Paleontological and genetic data indicate a common ancestral population of modern humans residing in Africa between ∼100–200 ka (1–4). The timing and pattern of the modern human African diaspora continues to be strongly debated. Competing hypotheses center on either a single Late Pleistocene dispersal into Eurasia between ∼50–75 ka or multiple dispersals beginning as early as the Middle Pleistocene ∼130 ka (5–8). The observed pattern of decreasing genetic (9, 10) and cranial (11) diversity at increasing distances from sub-Saharan Africa has been interpreted as evidence for a single dispersal, characterized by a series of founder effects during global expansion. In its simplest form, a single dispersal scenario follows a series of founder events in an eastward expansion (EE) model that conforms to terrestrial routes mostly along a latitudinal axis across Asia (10, 12).Another interpretation consistent with decreasing biological diversity from Africa is to consider multiple dispersals (MD) out of the continent. In an MD model, an initial dispersal between ∼50–100 ka occurs primarily along a coastal route through the southern Arabian Peninsula and is followed by a second dispersal through the Levant at ∼50 ka and into northern Eurasia (13, 14). This model proposes that extant, isolated populations in Asia could retain the biological signal of the initial, “southern route” dispersal. Such hypothetical, “relic” populations could include Australians, Melanesians, Papuans, Dravidian speakers of South Asia, and short-statured “Negrito” populations of Southeast Asia. A recent genetic study proposed that living Australians are direct descendants of the southern route dispersal, whereas Papuans, Melanesians, and Philippine Aeta “Negrito” populations also retain a signal of the southern route, but one that is obscured owing to admixture with members of the second dispersal (8). In this model of multiple dispersals with isolation (MDI), a southern route dispersal out of Africa commences between ∼62–75 ka and is followed by a second dispersal between ∼25–38 ka. An alternative chronology for the MDI model posits a southern route dispersal as early as the late Middle Pleistocene ∼130 ka (MDI-MP), rather than the Late Pleistocene (MDI-LP), and is based primarily on archaeological evidence in the Arabian Peninsula (6, 15).Growing consensus on the southern route dispersal has been strengthened by the study of SNPs in hypothetical relic populations (8, 16–18). However, whether this reflects evidence of multiple dispersals from Africa continues to be debated (8, 16). A reconciling view, therefore, has been that a single dispersal from Africa might have taken place in the Late Pleistocene ∼75 ka, followed by divergence into separate migration waves outside the continent, likely in Southwest Asia (7). Like the MD and MDI models, migration into Southeast Asia is via a “beachcomber” single dispersal (BSD) route along the coast. Unlike the EE model, the BSD model implies substantial migration along a longitudinal axis in East Asia.Because temporal and spatial dimensions are explicit in these competing out-of-Africa models, distinguishing them can be achieved by assessing the correlation of predicted spatial and temporal distances and observed neutral biological distances between modern human populations. Such a biogeographical approach accounts for the primary drivers of recent human evolution: migration, mutation, and drift. We used this test for 10 populations sampled from Africa and Asia using genetic and cranial phenotype data (19, 20). For both lines of evidence we used the same quantitative evolutionary framework to assess biological distances between our sampled populations (21).

Table 1.

Populations, sample size, and geography

High-precision radiocarbon dating shows recent and rapid initial human colonization of East Polynesia

The 15 archipelagos of East Polynesia, including New Zealand, Hawaii, and Rapa Nui, were the last habitable places on earth colonized by prehistoric humans. The timing and pattern of this colonization event has been poorly resolved, with chronologies varying by >1000 y, precluding understanding of cultural change and ecological impacts on these pristine ecosystems. In a meta-analysis of 1,434 radiocarbon dates from the region, reliable short-lived samples reveal that the colonization of East Polynesia occurred in two distinct phases: earliest in the Society Islands A.D. ～1025-1120, four centuries later than previously assumed; then after 70-265 y, dispersal continued in one major pulse to all remaining islands A.D. ～1190-1290. We show that previously supported longer chronologies have relied upon radiocarbon-dated materials with large sources of error, making them unsuitable for precise dating of recent events. Our empirically based and dramatically shortened chronology for the colonization of East Polynesia resolves longstanding paradoxes and offers a robust explanation for the remarkable uniformity of East Polynesian culture, human biology, and language. Models of human colonization, ecological change and historical linguistics for the region now require substantial revision.     

Human remains from Zhirendong, South China, and modern human emergence in East Asia

The 2007 discovery of fragmentary human remains (two molars and an anterior mandible) at Zhirendong (Zhiren Cave) in South China provides insight in the processes involved in the establishment of modern humans in eastern Eurasia. The human remains are securely dated by U-series on overlying flowstones and a rich associated faunal sample to the initial Late Pleistocene, >100 kya. As such, they are the oldest modern human fossils in East Asia and predate by >60,000 y the oldest previously known modern human remains in the region. The Zhiren 3 mandible in particular presents derived modern human anterior symphyseal morphology, with a projecting tuber symphyseos, distinct mental fossae, modest lateral tubercles, and a vertical symphysis; it is separate from any known late archaic human mandible. However, it also exhibits a lingual symphyseal morphology and corpus robustness that place it close to later Pleistocene archaic humans. The age and morphology of the Zhiren Cave human remains support a modern human emergence scenario for East Asia involving dispersal with assimilation or populational continuity with gene flow. It also places the Late Pleistocene Asian emergence of modern humans in a pre-Upper Paleolithic context and raises issues concerning the long-term Late Pleistocene coexistence of late archaic and early modern humans across Eurasia.     

Impact of poverty on the prevalence of diabetes and its complications in urban southern India.

AIM: The impact of poverty on the profile of diabetes and its complications was studied. METHODS: A comparative study of low income group (LIG) (family income Rs. < 30,000/annum (approx. 432 pounds sterling) and high income group (HIG) (family income Rs. greater-than-or-equal 60,000/annum (approx. pounds sterling) subjects of > or = 40 years was done in Madras, India. By screening 1748 LIG subjects (M/W 844/904) 301 diabetic subjects were identified and 218 underwent tests for diabetic complications. Population data available in 635 (M/W 309/326) HIG subjects from the survey were used for comparison of glucose tolerance profile. Complications were studied in 221 diabetic HIG subjects. RESULTS: Age-standardized prevalences of diabetes (12.6% vs. 25.5%; chi(2) = 56.9, P < 0.0001) and impaired glucose tolerance (IGT) (8.9% vs. 19.0%) were significantly lower (chi(2) = 57.7; P < 0.0001) in the LIG. Hypertension was more common in LIG (53.7% vs. 40.0% in HIG; chi(2) = 34.9; P < 0.0001). LIG subjects were more physically active; 73.8% did not go to school. Parameters significantly associated with diabetes were body mass index (BMI), age, higher income, waist--hip ratio and physical inactivity. Higher income, BMI and age were associated with IGT. Diabetic LIG subjects had a higher prevalence of cardiac disease, neuropathy and cataract and a lower prevalence of retinopathy than HIG subjects. The risk variables such as hyperglycaemia, dyslipidaemia, hypertension, smoking and alcohol consumption were more in the LIG group. CONCLUSIONS: The urban poor in the developing world has a lower prevalence of diabetes than the urban poor in developed societies. However, they have higher rates of complications of diabetes.     

Intertidal snail-trematode communities on the southern Thailand before and after the South Asia tsunami

Intertidal snail-trematode communities in southern Thailand were examined before and after the South Asia tsunami. Infection rates and species diversity of cercaria in the host snail Cerithidea in tidal zones did not change significantly from one year before to one month after the tsunami. However, the host snails C. quadrata, C. alata and C. obtusa disappeared from greatly damaged sites. It is important to follow up on the intertidal snail-trematode community recovery process after destruction of the intertidal ecosystem.     

Late Middle Eocene primate from Myanmar and the initial anthropoid colonization of Africa

Reconstructing the origin and early evolutionary history of anthropoid primates (monkeys, apes, and humans) is a current focus of paleoprimatology. Although earlier hypotheses frequently supported an African origin for anthropoids, recent discoveries of older and phylogenetically more basal fossils in China and Myanmar indicate that the group originated in Asia. Given the Oligocene-Recent history of African anthropoids, the colonization of Africa by early anthropoids hailing from Asia was a decisive event in primate evolution. However, the fossil record has so far failed to constrain the nature and timing of this pivotal event. Here we describe a fossil primate from the late middle Eocene Pondaung Formation of Myanmar, Afrasia djijidae gen. et sp. nov., that is remarkably similar to, yet dentally more primitive than, the roughly contemporaneous North African anthropoid Afrotarsius. Phylogenetic analysis suggests that Afrasia and Afrotarsius are sister taxa within a basal anthropoid clade designated as the infraorder Eosimiiformes. Current knowledge of eosimiiform relationships and their distribution through space and time suggests that members of this clade dispersed from Asia to Africa sometime during the middle Eocene, shortly before their first appearance in the African fossil record. Crown anthropoids and their nearest fossil relatives do not appear to be specially related to Afrotarsius, suggesting one or more additional episodes of dispersal from Asia to Africa. Hystricognathous rodents, anthracotheres, and possibly other Asian mammal groups seem to have colonized Africa at roughly the same time or shortly after anthropoids gained their first toehold there.     

Self-harm and self-poisoning in southern India: choice of poisoning agents and treatment

Objective  To record cases of suicide and attempted suicide among a population of 108 000 people living in a primarily rural area of southern India, with the aim of guiding policies and strategies to restrict access to poisonous compounds at community level.
Method  Community-based surveillance over a period of 2 years.
Results and conclusion  The overall suicide rate was 71.4 per 100 000 population; the highest burden was among men. Most people died through hanging (81, 54%) and self-poisoning (46, 31%). Of the 46 who died from self-poisoning, 78.3% had taken pesticides and 19.7% had eaten poisonous plants. Eighty per cent of the self-poisoning cases obtained the poisonous substance in or in close proximity to the home, highlighting the importance of safe storage in the domestic environment. Of the 110 fatal and non-fatal self-poisoning cases, 87 (57.5%) were taken for treatment; 50 (57.4%) went to government hospitals and 37 (42.5%) to private facilities. This indicates the importance of including the private sector in the efforts to improve case management. Furthermore, the fact that 31 (67%) of the self-poisoning patients, who eventually died, were alive after 4 h provides an incentive to focus on improved case management and access to health services.     

Sickle cell anemia and trait in a population of southern india

In an ethnic group in southern India, the Irula, seven individuals with sickle cell anemia were found to manifest only mild illness. Although a relatively high level of fetal hemoglobin was present in one, none of the factors thought to ameliorate the course of sickling disorders could be identified in the remaining six. In a random population survey, sickle hemoglobin was found in 90 of 292 Irula (31%). In those with sickle cell trait, the proportion of sickle hemoglobin in hemolysates (mean = 26%, range 19–32%) was substantially lower than that reported for any other population.     

Prevalence and clinical features of chronic pancreatitis in southern india

We have conducted a field study in India in the state of Kerala involving 28,567 inhabitants to determine the prevalence and clinical features of chronic pancreatitis of the tropics (CPT), an illness that is endemic in several regions of India. Selection criteria for the present study included:

Review of varicella zoster seroepidemiology in India and South-east Asia

Summary Varicella zoster virus (VZV) predominantly affects children in temperate countries, with near-universal seroconversion occurring by late childhood. However, in tropical regions, VZV infection is common in adolescents and adults. This review identifies age-related VZV seroprevalence patterns in a number of Asian countries which indicate that seroconversion in tropical countries occurs at a later age than in temperate countries. Seasonal and regional variations in acute disease within some Asian countries suggest that temperate climates might favour transmission of the varicella virus, with incidence peaking during cooler months and in cooler, more temperate regions. VZV infection is often more severe in adults than in children, suggesting that tropical countries may be at risk of greater morbidity and mortality as a result of later-age seroconversion. Susceptibility of pregnant women and their infants, and of people infected with HIV/AIDS is also cause for concern. Vaccination may be beneficial in reducing the impact of VZV in Asian populations.     

Genetic absolute dating based on microsatellites and the origin of modern humans.

We introduce a new genetic distance for microsatellite loci, incorporating features of the stepwise mutation model, and test its performance on microsatellite polymorphisms in humans, chimpanzees, and gorillas. We find that it performs well in determining the relations among the primates, but less well than other distance measures (not based on the stepwise mutation model) in determining the relations among closely related human populations. However, the deepest split in the human phylogeny seems to be accurately reconstructed by the new distance and separates African and non-African populations. The new distance is independent of population size and therefore allows direct estimation of divergence times if the mutation rate is known. Based on 30 microsatellite polymorphisms and a recently reported average mutation rate of 5.6 x 10(-4) at 15 dinucleotide microsatellites, we estimate that the deepest split in the human phylogeny occurred about 156,000 years ago. Unlike most previous estimates, ours requires no external calibration of the rate of molecular evolution. We can use such calibrations, however, to test our estimate.     

Taeniasis and cysticercosis in Asia and the Pacific: present state of knowledge and perspectives

Several topics on taeniasis and cysticercosis in Asia and the Pacific are overviewed. In Asia and the Pacific, three human taeniid species have been recognized: Taenia solium, Taenia saginata and Taenia asiatica. The first topic is on evolution of T. solium. Mitochondrial DNA polymorphisms of T. solium worldwide are discussed with emphasis of two specific genotypes: American-African and Asian. The second topic is recent major advances in sero- and molecular-diagnosis of T. solium cysticercosis in humans, pigs and dogs. The third is the present situation of T. solium taeniasis/cysticercosis in Papua (Irian Jaya), Indonesia. The forth is the present situation of T. solium cysticercosis and T. saginata taeniasis in Bali, Indonesia. The fifth is the present situation of T. asiatica taeniasis in Asia and the Pacific and in North Sumatra, Indonesia. The sixth is on the debate of the exact definition of T. asiatica. Because T. asiatica can not be differentiated from T. saginata morphologically, it is time to re-evaluate T. saginata in Asia and the Pacific. New and broad-based surveys across this region are necessary from epidemiological and public health perspectives, based on evidence.     

Asthma in Asia: Physician perspectives on control,inhaler use and patient communications

Objective: We examined the physician perspectives on asthma management in Asia. Methods: An online/face-to-face, questionnaire-based survey of respiratory specialists and primary care physicians from eight Asian countries/region was carried out. The survey explored asthma control, inhaler selection, technique and use; physician-patient communications and asthma education. Inclusion criteria were >50% of practice time spent on direct patient care; and treated >30 patients with asthma per month, of which >60% were aged >12 years. Results: REALISE Asia (Phase 2) involved 375 physicians with average 15.9(±6.8) years of clinical experience. 89.1% of physicians reporting use of guidelines estimated that 53.2% of their patients have well-controlled (GINA-defined) asthma. Top consideration for inhaler choice was asthma severity (82.4%) and lowest, socio-economic status (32.5%). Then 54.7% of physicians checked their patients’ inhaler techniques during consultations but 28.2(±19.1)% of patients were using their inhalers incorrectly; 21.1–57.9% of physicians could spot improper inhaler techniques in video demonstrations. And 79.6% of physicians believed combination inhalers could increase adherence because of convenience (53.7%), efficacy (52.7%) and usability (18.9%). Initial and follow-up consultations took 16.8(±8.4) and 9.2(±5.3) minutes, respectively. Most (85.1%) physicians used verbal conversations and least (24.5%), video demonstrations of inhaler use; 56.8% agreed that patient attitudes influenced their treatment approach. Conclusion: Physicians and patients have different views of ‘well-controlled’ asthma. Although physicians informed patients about asthma and inhaler usage, they overestimated actual usage and patients’ knowledge was sub-optimal. Physician-patient interactions can be augmented with understanding of patient attitudes, visual aids and ancillary support to perform physical demonstrations to improve treatment outcomes.     

Prevalence and correlates of psychosocial conditions among people living with HIV in southern India

Psychosocial conditions such as depression, intimate partner violence (IPV), and history of childhood sexual abuse (CSA) have been associated with poor HIV-related outcomes. In India, which has the third largest HIV epidemic in the world, little is understood about the impact of psychosocial conditions on people living with HIV (PLHIV). We aimed to understand the prevalence and correlates of psychosocial conditions among PLHIV entering into HIV care at the Y.R. Gaitonde Centre for AIDS Research and Education in Chennai, India. Thirteen questions were added to the standard voluntary counseling and testing questionnaire, including the Patient Health Questionnaire-9 (a depression scale) and questions assessing for CSA and IPV. We fitted logistic regression models, stratified by gender, with psychosocial condition as the outcome of interest and substance use variables and socio-demographic variables as the correlates of interest. Three hundred and eighty-three persons were enrolled into the study; of these, 253 (66%) tested positive for HIV, including 149 men and 104 women, and were included in the models. More than one-quarter (28%) of the men and 19% of the women reported at least one psychosocial condition (probable depression, CSA, or IPV). In adjusted analysis, current alcohol use was associated with greater than two times higher odds of a psychosocial condition (Adjusted Odds Ratio?=?2.24, 95% CI, 1.04–4.85) among men. In conclusion, we estimated the prevalence of probable depression, CSA, and IPV among PLHIV presenting for HIV care in southern India and found that, among male PLHIV, alcohol use was associated with a markedly higher odds of reporting a psychosocial condition. Further study is needed to characterize alcohol use among male PLHIV and the possible deleterious impact of psychosocial conditions and alcohol use on HIV-related outcomes in India.     

Influence of doxycycline on the normal human flora and colonization of the oral cavity and colon

Doxycycline was given orally in doses of 100 mg every 24 h for 7 days to 10 subjects. Salivary and faecal specimens were taken up to 16 days for cultivation of aerobic and anaerobic microorganisms and for assay of doxycycline. Doxycycline was detected in both saliva and faeces. Only minor changes were observed regarding the number of aerobic and anaerobic microorganisms in the oral cavity. In the faecal flora a decrease in the number of aerobic microorganisms was observed in most subjects, while only minor changes in the number of anaerobic bacteria were noticed. A marked increase in doxycycline-resistant aerobic and anaerobic bacterial strains was noticed both in the oral cavity and the colon. Only a few patients were colonized with potentially pathogenic microorganisms.     

Interventional applications of intravascular ultrasound imaging: initial experience and future perspectives

Intravascular ultrasound imaging offers the potential to provide more detailed information about vessel and lesion morphology and physiology than is currently available from angiography. The greatest impact of intravascular ultrasound upon clinical decisions may be in the area of cardiac and vascular interventions. To evaluate the utility of intravascular ultrasound, we prospectively studied 45 patients, 11 of whom underwent interventional procedures. Intravascular ultrasound imaging was performed before and after interventions using a 20 MHz, mechanically rotating transducer on either 6.5 Fr or 8.0 Fr catheter systems. Interventions included seven peripheral vessel balloon angioplasties (Femoral artery-two, Renal artery-two, Arteriovenous fistula-two, Aortic coarctation-one), two Femoral artery rotational atherectomies, and two balloon valvuloplasties (Pulmonic valve-1, Mitral valve-1). Intravascular ultrasound and digital angiography provided similar information about vessel size. However, morphological information about the vessel wall, plaque composition, plaque topography, luminal thrombus, and vessel dissections was better appreciated by intravascular ultrasound. Intravascular ultrasound was determined to have provided unique and clinically useful information in 10/11 (91%) interventions. These preliminary data illustrate the potential value of intravascular ultrasound for the evaluation of the vascular system and in particular its value in interventional procedures.     

Juvenile hominoid cranium from the late Miocene of southern China and hominoid diversity in Asia

The fossil ape Lufengpithecus is known from a number of late Miocene sites in Yunnan Province in southern China. Along with other fossil apes from South and Southeast Asia, it is widely considered to be a relative of the extant orangutan, Pongo pygmaeus. It is best represented at the type site of Shihuiba (Lufeng) by several partial to nearly complete but badly crushed adult crania. There is, however, an additional, minimally distorted cranium of a young juvenile from a nearly contemporaneous site in the Yuanmou Basin, which affords the opportunity to better assess the relationships between Lufengpithecus and Pongo. Comparison with similarly aged juvenile skulls of extant great apes reveals no features suggesting clear affinities to orangutans, and instead reveals a morphological pattern largely consistent with a stem member of the hominid (great ape and human) clade. The existence at this time of other hominids in South Asia (Sivapithecus) and Southeast Asia (Khoratpithecus) with clear craniofacial affinities to Pongo suggests both more diversity among Asian Late Miocene apes and more complex patterns of dispersal than previously supposed. Major differences in the associated mammal faunas from the southern China sites and those from South and Southeast Asia are consistent with these findings and suggest more than one dispersal route of apes into East Asia earlier in the Miocene.     

Factors that mediate colonization of the human stomach by Helicobacter pylori

Helicobacter pylori(H.pylori)colonizes the stomach of humans and causes chronic infection.The majority of bacteria live in the mucus layer overlying the gastric epithelial cells and only a small proportion of bacteria are found interacting with the epithelial cells.The bacteria living in the gastric mucus may act as a reservoir of infection for the underlying cells which is essential for the development of disease.Colonization of gastric mucus is likely to be key to the establishment of chronic infection.How H.pylori manages to colonise and survive in the hostile environment of the human stomach and avoid removal by mucus flow and killing by gastric acid is the subject of this review.We also discuss how bacterial and host factors may together go some way to explaining the susceptibility to colonization and the outcome of infection in different individuals.H.pylori infection of the gastric mucosa has become a paradigm for chronic infection.Understanding of why H.pylori is such a successful pathogen may help us understand how other bacterial species colonise mucosal surfaces and cause disease.