Ancient History

Anthropogenic pressures on the Earth System have reached a scale where abrupt global environmental change can no longer be excluded. We propose a new approach to global sustainability in which we define planetary boundaries within which we expect that humanity can operate safely. Transgressing one or more planetary boundaries may be deleterious or even catastrophic due to the risk of crossing thresholds that will trigger non-linear, abrupt environmental change within continental-to planetary-scale systems.

Acute respiratory distress syndrome (ARDS), the most severe form of acute lung injury, is a devastating clinical syndrome with a high mortality rate (30-60%) (refs 1-3). Predisposing factors for ARDS are diverse 1,3 and include sepsis, aspiration, pneumonias and infections with the severe acute respiratory syndrome (SARS) coronavirus 4,5 . At present, there are no effective drugs for improving the clinical outcome of ARDS 1-3 . Angiotensin-converting enzyme (ACE) and ACE2 are homologues with different key functions in the renin-angiotensin system 6-8 . ACE cleaves angiotensin I to generate angiotensin II, whereas ACE2 inactivates angiotensin II and is a negative regulator of the system. ACE2 has also recently been identified as a potential SARS virus receptor and is expressed in lungs 9,10 . Here we report that ACE2 and the angiotensin II type 2 receptor (AT 2 ) protect mice from severe acute lung injury induced by acid aspiration or sepsis. However, other components of the renin-angiotensin system, including ACE, angiotensin II and the angiotensin II type 1a receptor (AT 1 a), promote disease pathogenesis, induce lung oedemas and impair lung function. We show that mice deficient for Ace show markedly improved disease, and also that recombinant ACE2 can protect mice from severe acute lung injury. Our data identify a critical function for ACE2 in acute lung injury, pointing to a possible therapy for a syndrome affecting millions of people worldwide every year.

The discovery of antibiotics more than 70years ago initiated a period of drug innovation and implementation in human and animal health and agriculture. These discoveries were tempered in all cases by the emergence of resistant microbes. This history has been interpreted to mean that antibiotic resistance in pathogenic bacteria is a modern phenomenon; this view is reinforced by the fact that collections of microbes that predate the antibiotic era are highly susceptible to antibiotics. Here we report targeted metagenomic analyses of rigorously authenticated ancient DNA from 30,000-year-old Beringian permafrost sediments and the identification of a highly diverse collection of genes encoding resistance to β-lactam, tetracycline and glycopeptide antibiotics. Structure and function studies on the complete vancomycin resistance element VanA confirmed its similarity to modern variants. These results show conclusively that antibiotic resistance is a natural phenomenon that predates the modern selective pressure of clinical antibiotic use.

Striding bipedalism is a key derived behaviour of hominids that possibly originated soon after the divergence of the chimpanzee and human lineages. Although bipedal gaits include walking and running, running is generally considered to have played no major role in human evolution because humans, like apes, are poor sprinters compared to most quadrupeds. Here we assess how well humans perform at sustained long-distance running, and review the physiological and anatomical bases of endurance running capabilities in humans and other mammals. Judged by several criteria, humans perform remarkably well at endurance running, thanks to a diverse array of features, many of which leave traces in the skeleton. The fossil evidence of these features suggests that endurance running is a derived capability of the genus Homo, originating about 2 million years ago, and may have been instrumental in the evolution of the human body form. M ost research on the evolution of human locomotion has focused on walking. There are a few indications that the earliest-known hominids were bipeds 1,2 , and there is abundant fossil evidence that australopithecines habitually walked by at least 4.4 million years (Myr) ago 3,4 . Many researchers interpret the evolution of an essentially modern human-like body shape, first apparent in early Homo erectus, as evidence for improved walking performance in more open habitats that came at the expense of retained adaptations in the australopithecine postcranium for arboreal locomotion (for example, refs 5-8). Although the biomechanics of running, the other human gait, is well studied, only a few researchers (see refs 9, 10 for example) have considered whether running was a mode of locomotion that influenced human evolution. This lack of attention is largely because humans are mediocre runners in several respects. Even elite human sprinters are comparatively slow, capable of sustaining maximum speeds of only 10.2 m s 21 for less than 15 s. In contrast, mammalian cursorial specialists such as horses, greyhounds and pronghorn antelopes can maintain maximum galloping speeds of 15-20 m s 21 for several minutes 11 . Moreover, running is more costly for humans than for most mammals, demanding roughly twice as much metabolic energy per distance travelled than is typical for a mammal of equal body mass 12 . Finally, human runners are less manoeuvrable and lack many structural modifications characteristic of most quadrupedal cursors such as elongate digitigrade feet and short proximal limb segments.

The covariation of carbon dioxide (CO(2)) concentration and temperature in Antarctic ice-core records suggests a close link between CO(2) and climate during the Pleistocene ice ages. The role and relative importance of CO(2) in producing these climate changes remains unclear, however, in part because the ice-core deuterium record reflects local rather than global temperature. Here we construct a record of global surface temperature from 80 proxy records and show that temperature is correlated with and generally lags CO(2) during the last (that is, the most recent) deglaciation. Differences between the respective temperature changes of the Northern Hemisphere and Southern Hemisphere parallel variations in the strength of the Atlantic meridional overturning circulation recorded in marine sediments. These observations, together with transient global climate model simulations, support the conclusion that an antiphased hemispheric temperature response to ocean circulation changes superim...

Herbs and spices have a traditional history of use, with strong roles in cultural heritage, and in the appreciation of food and its links to health. Demonstrating the benefits of foods by scientific means remains a challenge, particularly when compared with standards applied for assessing pharmaceutical agents. Pharmaceuticals are small-molecular-weight compounds consumed in a purified and concentrated form. Food is eaten in combinations, in relatively large, unmeasured quantities under highly socialised conditions. The real challenge lies not in proving whether foods, such as herbs and spices, have health benefits, but in defining what these benefits are and developing the methods to expose them by scientific means. The place of herbs and spices in the diet needs to be considered in reviewing health benefits. This includes definitions of the food category and the way in which benefits might be viewed, and therefore researched. Research may focus on identifying bioactive substances ...

In 1967 the Kibish Formation in southern Ethiopia yielded hominid cranial remains identified as early anatomically modern humans, assigned to Homo sapiens. However, the provenance and age of the fossils have been much debated. Here we confirm that the Omo I and Omo II hominid fossils are from similar stratigraphic levels in Member I of the Kibish Formation, despite the view that Omo I is more modern in appearance than Omo II. 40Ar/39Ar ages on feldspar crystals from pumice clasts within a tuff in Member I below the hominid levels place an older limit of 198 +/- 14 kyr (weighted mean age 196 +/- 2 kyr) on the hominids. A younger age limit of 104 +/- 7 kyr is provided by feldspars from pumice clasts in a Member III tuff. Geological evidence indicates rapid deposition of each member of the Kibish Formation. Isotopic ages on the Kibish Formation correspond to ages of Mediterranean sapropels, which reflect increased flow of the Nile River, and necessarily increased flow of the Omo River. Thus the 40Ar/39Ar age measurements, together with the sapropel correlations, indicate that the hominid fossils have an age close to the older limit. Our preferred estimate of the age of the Kibish hominids is 195 +/- 5 kyr, making them the earliest well-dated anatomically modern humans yet described.

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Currently, it is widely accepted that only one hominin genus, Homo, was present in Pleistocene Asia, represented by two species, Homo erectus and Homo sapiens. Both species are characterized by greater brain size, increased body height and smaller teeth relative to Pliocene Australopithecus in Africa. Here we report the discovery, from the Late Pleistocene of Flores, Indonesia, of an adult hominin with stature and endocranial volume approximating 1 m and 380 cm 3 , respectively-equal to the smallest-known australopithecines. The combination of primitive and derived features assigns this hominin to a new species, Homo floresiensis. The most likely explanation for its existence on Flores is long-term isolation, with subsequent endemic dwarfing, of an ancestral H. erectus population. Importantly, H. floresiensis shows that the genus Homo is morphologically more varied and flexible in its adaptive responses than previously thought.

High-throughput direct sequencing techniques have recently opened the possibility to sequence genomes from Pleistocene organisms. Here we analyze DNA sequences determined from a Neandertal, a mammoth, and a cave bear. We show that purines are overrepresented at positions adjacent to the breaks in the ancient DNA, suggesting that depurination has contributed to its degradation. We furthermore show that substitutions resulting from miscoding cytosine residues are vastly overrepresented in the DNA sequences and drastically clustered in the ends of the molecules, whereas other substitutions are rare. We present a model where the observed substitution patterns are used to estimate the rate of deamination of cytosine residues in single-and doublestranded portions of the DNA, the length of single-stranded ends, and the frequency of nicks. The results suggest that reliable genome sequences can be obtained from Pleistocene organisms.

The past decade has witnessed a quantum leap in our understanding of the origins, diffusion, and impact of early agriculture in the Mediterranean Basin. In large measure these advances are attributable to new methods for documenting domestication in plants and animals. The initial steps toward plant and animal domestication in the Eastern Mediterranean can now be pushed back to the 12th millennium cal B.P. Evidence for herd management and crop cultivation appears at least 1,000 years earlier than the morphological changes traditionally used to document domestication. Different species seem to have been domesticated in different parts of the Fertile Crescent, with genetic analyses detecting multiple domestic lineages for each species. Recent evidence suggests that the expansion of domesticates and agricultural economies across the Mediterranean was accomplished by several waves of seafaring colonists who established coastal farming enclaves around the Mediterranean Basin. This process also involved the adoption of domesticates and domestic technologies by indigenous populations and the local domestication of some endemic species. Human environmental impacts are seen in the complete replacement of endemic island faunas by imported mainland fauna and in today's anthropogenic, but threatened, Mediterranean landscapes where sustainable agricultural practices have helped maintain high biodiversity since the Neolithic.

Loss of seed shattering was a key event in the domestication of major cereals. We revealed that the qSH1 gene, a major quantitative trait locus of seed shattering in rice, encodes a BEL1-type homeobox gene and demonstrated that a single-nucleotide polymorphism (SNP) in the 5 ¶ regulatory region of the qSH1 gene caused loss of seed shattering owing to the absence of abscission layer formation. Haplotype analysis and association analysis in various rice collections revealed that the SNP was highly associated with shattering among japonica subspecies of rice, implying that it was a target of artificial selection during rice domestication.

Warfare and dislocation are obvious features of the break-up of the late Roman West, but this crucial period of change was characterised also by communication and diplomacy. The great events of the late antique West were determined by the quieter labours of countless envoys, who travelled between emperors, kings, generals, high officials, bishops, provincial councils, and cities. This book examines the role of envoys in the period from the establishment of the first 'barbarian kingdoms' in the West, to the eve of Justinian's wars of reconquest. It shows how ongoing practices of Roman imperial administration shaped new patterns of political interaction in the novel context of the earliest medieval states. Close analysis of sources with special interest in embassies offers insight into a variety of genres: chronicles, panegyrics, hagiographies, letters, and epitaphs. This study makes a significant contribution to the developing field of ancient and medieval communications. andrew g i l let t is Research Fellow in the First published in print format isbn-13 978-0-521-81349-5 hardback isbn-13 978-0-511-07322-9 eBook (EBL)

There is intense debate about whether all Native Americans stem from one migration or multiple waves of migration from Asia. In addition, little is known about the principal settlement routes and patterns of population diversification within the Americas. We assembled a dataset of 55 Native American and 19 Siberian populations typed at over 370,000 polymorphisms, the most comprehensive survey of genetic diversity in Native Americans to date, and masked out segments of recent European or African ancestry. Along with providing genetic support for controversial linguistic evidence for three episodes of migration from Asia, the data provide strong evidence for a southward population expansion (facilitated by the coast) with sequential splits and little gene flow after divergence. An important exception to this pattern is the history of Chibchanspeakers around the Panama isthmus, who our data suggest derive from a >5,000 year old mixture of South American and North American lineages, highlighting the isthmus as a region of genetic interaction between both hemispheres. Our results refute recent interpretations of mitochondrial DNA (mtDNA) positing a single settlement wave. They also highlight how genome-wide analyses of data directly accounting for the confounder of non-Native admixture can be used to document previously unknown historical events.

Biomaterials, traditionally defined as materials used in medical devices, have been used since antiquity, but recently their degree of sophistication has increased significantly. Biomaterials made today are routinely information rich and incorporate biologically active components derived from nature. In the future, biomaterials will assume an even greater role in medicine and will find use in a wide variety of non-medical applications through biologically inspired design and incorporation of dynamic behaviour.

Global climate and the atmospheric partial pressure of carbon dioxide (p CO atm 2 ) are correlated over recent glacial cycles, with lower p CO atm 2 during ice ages, but the causes of the p CO atm 2 changes are unknown. The modern Southern Ocean releases deeply sequestered CO 2 to the atmosphere. Growing evidence suggests that the Southern Ocean CO 2 'leak' was stemmed during ice ages, increasing ocean CO 2 storage. Such a change would also have made the global ocean more alkaline, driving additional ocean CO 2 uptake. This explanation for lower ice-age p CO atm 2 , if correct, has much to teach us about the controls on current ocean processes.

We show that DNA molecules amplified by PCR from DNA extracted from animal bones and teeth that vary in age between 25 000 and over 50 000 years carry C→T and G→A substitutions. These substitutions can reach high proportions among the molecules amplified and are due to the occurrence of modified deoxycytidine residues in the template DNA. If the template DNA is treated with uracil N-glycosylase, these substitutions are dramatically reduced. They are thus likely to result from deamination of deoxycytidine residues. In addition, 'jumping PCR', i.e. the occurrence of template switching during PCR, may contribute to these substitutions. When DNA sequences are amplified from ancient DNA extracts where few template molecules initiate the PCR, precautions such as DNA sequence determination of multiple clones derived from more than one independent amplification are necessary in order to reduce the risk of determination of incorrect DNA sequences. When such precautionary measures are taken, errors induced by damage to the DNA template are unlikely to be more frequent than ∼0.1% even under the unlikely scenario where each amplification starts from a single template molecule.

Methadone, a full mu-opioid agonist, is the recommended treatment for opioid dependence during pregnancy. However, prenatal exposure to methadone is associated with a neonatal abstinence syndrome (NAS) characterized by central nervous system hyperirritability and autonomic nervous system dysfunction, which often requires medication and extended hospitalization. Buprenorphine, a partial mu-opioid agonist, is an alternative treatment for opioid dependence but has not been extensively studied in pregnancy.

In face recognition tasks, the dimension of the sample space is typically larger than the number of the samples in the training set. As a consequence, the within-class scatter matrix is singular and the Linear Discriminant Analysis (LDA) method cannot be applied directly. This problem is known as the "small sample size" problem. In this paper, we propose a new face recognition method called the Discriminative Common Vector method based on a variation of Fisher's Linear Discriminant Analysis for the small sample size case. Two different algorithms are given to extract the discriminative common vectors representing each person in the training set of the face database. One algorithm uses the within-class scatter matrix of the samples in the training set while the other uses the subspace methods and the Gram-Schmidt orthogonalization procedure to obtain the discriminative common vectors. Then, the discriminative common vectors are used for classification of new faces. The proposed method yields an optimal solution for maximizing the modified Fisher's Linear Discriminant criterion given in the paper. Our test results show that the Discriminative Common Vector method is superior to other methods in terms of recognition accuracy, efficiency, and numerical stability.

has clear implications for our understanding of the tempo and mode of important transitions in evolution. But the controversy over the molecular clock is not just the concern of evolutionary theorists: the practical benefits of the molecular clock are immense. For example, molecular clock dates that place the last common ancestor of the main pandemic strain of human immunodeficiency virus (HIV) in the 1930s have been used to counter claims that the virus was spread through the distribution of contaminated polio vaccine in the 1950s (allegedly manufactured using tissue from chimpanzees infected with simian immunodeficiency virus) 2 .

The grape is one of the earliest domesticated fruit crops and, since antiquity, it has been widely cultivated and prized for its fruit and wine. Here, we characterize genome-wide patterns of genetic variation in over 1,000 samples of the domesticated grape, Vitis vinifera subsp. vinifera, and its wild relative, V. vinifera subsp. sylvestris from the US Department of Agriculture grape germplasm collection. We find support for a Near East origin of vinifera and present evidence of introgression from local sylvestris as the grape moved into Europe. High levels of genetic diversity and rapid linkage disequilibrium (LD) decay have been maintained in vinifera, which is consistent with a weak domestication bottleneck followed by thousands of years of widespread vegetative propagation. The considerable genetic diversity within vinifera, however, is contained within a complex network of close pedigree relationships that has been generated by crosses among elite cultivars. We show that first-degree relationships are rare between wine and table grapes and among grapes from geographically distant regions. Our results suggest that although substantial genetic diversity has been maintained in the grape subsequent to domestication, there has been a limited exploration of this diversity. We propose that the adoption of vegetative propagation was a double-edged sword: Although it provided a benefit by ensuring true breeding cultivars, it also discouraged the generation of unique cultivars through crosses. The grape currently faces severe pathogen pressures, and the long-term sustainability of the grape and wine industries will rely on the exploitation of the grape's tremendous natural genetic diversity. genomics | SNP array | positive selection | genome-wide association

Tissue engineering and regenerative medicine research is being aggressively pursued in attempts to develop biological substitutes to replace lost tissue or organs. Remarkable degrees of success have been achieved in the generation of a variety of tissues and organs as a result of concerted contributions by multidisciplinary groups in the field of biotechnology. Engineering of an organ is a complex process which is initiated by appropriate sourcing of cells and their controlled proliferation to achieve critical numbers for seeding on biodegradable scaffolds in order to create cell-scaffold constructs, which are thereafter maintained in bioreactors to generate tissues identical to those required for replacement. Extensive efforts in understanding the characteristics of cells and their interaction with specifically tailored scaffolds holds the key to their attachment, controlled proliferation and differentiation, intercommunication, and organization to form tissues. The demand for tissue-engineered organs is enormous and this technology holds the promise to supply customized organs to overcome the severe shortages that are currently faced by the pediatric patient, especially due to organ-size mismatch. The contemporary state of tissue-engineering technology presented in this review summarizes the advances in the various areas of regenerative medicine and addresses issues that are associated with its future implementation in the pediatric surgical patient.

The histories of crop domestication and breeding are recorded in genomes. Although tomato is a model species for plant biology and breeding, the nature of human selection that altered its genome remains largely unknown. Here we report a comprehensive analysis of tomato evolution based on the genome sequences of 360 accessions. We provide evidence that domestication and improvement focused on two independent sets of quantitative trait loci (QTLs), resulting in modern tomato fruit ∼100 times larger than its ancestor. Furthermore, we discovered a major genomic signature for modern processing tomatoes, identified the causative variants that confer pink fruit color and precisely visualized the linkage drag associated with wild introgressions. This study outlines the accomplishments as well as the costs of historical selection and provides molecular insights toward further improvement.

Modern economics tantalizes historians, promising them a set of simple verbal and mathematical formulas to explain and even retrospectively predict historical actions and choices. Colin P. Elliott challenges economic historians to rethink the way they use economic theory. Building upon the approaches of Max Weber, R. G. Collingwood, Ludwig von Mises and others, Elliott reconceptualizes economic theories such as the quantity theory of money and Gresham’s law as heuristic constructs – constructs which help historians identify and understand the unique modes of thought and embedding contexts which characterized economic action in the Roman Empire. The book offers novel analyses of key events in Roman monetary history, from Augustus’ triumph over Mark Antony and Cleopatra, to third-century AD coinage debasements. Roman history has long been a battleground for polarizing methodological debates, but this book’s accessible style and conciliatory tone invites historians, economists, sociologists and other scholars to use economic theory for understanding.

Role of basal ganglia: Vesalius and Piccolomini distinguished subcortical nuclei from cortex and white matter in the 16th century. Willis' mistaken concept in the late 17th century that the corpus striatum was the seat of motor power persisted for 200 years and formed the basis of mid-19th-century localizations of movement disorders to the striatum (chorea by Broadbent and Jackson, and athetosis by Hammond). By the late 19th century, many movement disorders were described but for most no pathologic correlate was known. Tremor: Descriptions of tremors progressed from Galen's definition in the 2nd century; to Galileo's physiologic tremor in 1610; separation of involuntary movements during action and at rest in the 17th and 18th centuries by de la Boë Sylvius and van Sweiten; description of Parkinson's disease by Parkinson, discrimination of the rest tremor of Parkinson's disease from the intention tremor of multiple sclerosis by Charcot, and recognition of familial...