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Sample records for early human ancestors

  1. An early modern human from Romania with a recent Neanderthal ancestor

    PubMed Central

    Fu, Qiaomei; Hajdinjak, Mateja; Moldovan, Oana Teodora; Constantin, Silviu; Mallick, Swapan; Skoglund, Pontus; Patterson, Nick; Rohland, Nadin; Lazaridis, Iosif; Nickel, Birgit; Viola, Bence; Prüfer, Kay; Meyer, Matthias; Kelso, Janet; Reich, David; Pääbo, Svante

    2015-01-01

    Neanderthals are thought to have disappeared in Europe ~39,000–41,000 years ago but they have contributed one to three percent of the DNA of present-day people in Eurasia1. Here, we analyze DNA from a 37,000–42,000-year-old2 modern human from Peştera cu Oase, Romania. Although the specimen contains small amounts of human DNA, we use an enrichment strategy to isolate sites that are informative about its relationship to Neanderthals and present-day humans. We find that on the order of six to nine percent of the genome of the Oase individual is derived from Neanderthals, more than any other modern human sequenced to date. Three chromosomal segments of Neanderthal ancestry are over 50 centimorgans in size, indicating that this individual had a Neanderthal ancestor as recently as four to six generations back. However, the Oase individual does not share more alleles with later Europeans than with East Asians, suggesting that the Oase population did not contribute substantially to later humans in Europe. PMID:26098372

  2. An early modern human from Romania with a recent Neanderthal ancestor.

    PubMed

    Fu, Qiaomei; Hajdinjak, Mateja; Moldovan, Oana Teodora; Constantin, Silviu; Mallick, Swapan; Skoglund, Pontus; Patterson, Nick; Rohland, Nadin; Lazaridis, Iosif; Nickel, Birgit; Viola, Bence; Prüfer, Kay; Meyer, Matthias; Kelso, Janet; Reich, David; Pääbo, Svante

    2015-08-13

    Neanderthals are thought to have disappeared in Europe approximately 39,000-41,000 years ago but they have contributed 1-3% of the DNA of present-day people in Eurasia. Here we analyse DNA from a 37,000-42,000-year-old modern human from Peştera cu Oase, Romania. Although the specimen contains small amounts of human DNA, we use an enrichment strategy to isolate sites that are informative about its relationship to Neanderthals and present-day humans. We find that on the order of 6-9% of the genome of the Oase individual is derived from Neanderthals, more than any other modern human sequenced to date. Three chromosomal segments of Neanderthal ancestry are over 50 centimorgans in size, indicating that this individual had a Neanderthal ancestor as recently as four to six generations back. However, the Oase individual does not share more alleles with later Europeans than with East Asians, suggesting that the Oase population did not contribute substantially to later humans in Europe. PMID:26098372

  3. Virtual ancestor reconstruction: Revealing the ancestor of modern humans and Neandertals.

    PubMed

    Mounier, Aurélien; Mirazón Lahr, Marta

    2016-02-01

    The timing and geographic origin of the common ancestor of modern humans and Neandertals remain controversial. A poor Pleistocene hominin fossil record and the evolutionary complexities introduced by dispersals and regionalisation of lineages have fuelled taxonomic uncertainty, while new ancient genomic data have raised completely new questions. Here, we use maximum likelihood and 3D geometric morphometric methods to predict possible morphologies of the last common ancestor of modern humans and Neandertals from a simplified, fully resolved phylogeny. We describe the fully rendered 3D shapes of the predicted ancestors of humans and Neandertals, and assess their similarity to individual fossils or populations of fossils of Pleistocene age. Our results support models of an Afro-European ancestral population in the Middle Pleistocene (Homo heidelbergensis sensu lato) and further predict an African origin for this ancestral population. PMID:26852813

  4. Diet and the evolution of the earliest human ancestors

    PubMed Central

    Teaford, Mark F.; Ungar, Peter S.

    2000-01-01

    Over the past decade, discussions of the evolution of the earliest human ancestors have focused on the locomotion of the australopithecines. Recent discoveries in a broad range of disciplines have raised important questions about the influence of ecological factors in early human evolution. Here we trace the cranial and dental traits of the early australopithecines through time, to show that between 4.4 million and 2.3 million years ago, the dietary capabilities of the earliest hominids changed dramatically, leaving them well suited for life in a variety of habitats and able to cope with significant changes in resource availability associated with long-term and short-term climatic fluctuations. PMID:11095758

  5. Diet and the evolution of the earliest human ancestors.

    PubMed

    Teaford, M F; Ungar, P S

    2000-12-01

    Over the past decade, discussions of the evolution of the earliest human ancestors have focused on the locomotion of the australopithecines. Recent discoveries in a broad range of disciplines have raised important questions about the influence of ecological factors in early human evolution. Here we trace the cranial and dental traits of the early australopithecines through time, to show that between 4.4 million and 2.3 million years ago, the dietary capabilities of the earliest hominids changed dramatically, leaving them well suited for life in a variety of habitats and able to cope with significant changes in resource availability associated with long-term and short-term climatic fluctuations. PMID:11095758

  6. Stride lengths, speed and energy costs in walking of Australopithecus afarensis: using evolutionary robotics to predict locomotion of early human ancestors

    PubMed Central

    Sellers, William I; Cain, Gemma M; Wang, Weijie; Crompton, Robin H

    2005-01-01

    This paper uses techniques from evolutionary robotics to predict the most energy-efficient upright walking gait for the early human relative Australopithecus afarensis, based on the proportions of the 3.2 million year old AL 288-1 ‘Lucy’ skeleton, and matches predictions against the nearly contemporaneous (3.5–3.6 million year old) Laetoli fossil footprint trails. The technique creates gaits de novo and uses genetic algorithm optimization to search for the most efficient patterns of simulated muscular contraction at a variety of speeds. The model was first verified by predicting gaits for living human subjects, and comparing costs, stride lengths and speeds to experimentally determined values for the same subjects. Subsequent simulations for A. afarensis yield estimates of the range of walking speeds from 0.6 to 1.3 m s−1 at a cost of 7.0 J kg−1 m−1 for the lowest speeds, falling to 5.8 J kg−1 m−1 at 1.0 m s−1, and rising to 6.2 J kg−1 m−1 at the maximum speed achieved. Speeds previously estimated for the makers of the Laetoli footprint trails (0.56 or 0.64 m s−1 for Trail 1, 0.72 or 0.75 m s−1 for Trail 2/3) may have been underestimated, substantially so for Trail 2/3, with true values in excess of 0.7 and 1.0 m s−1, respectively. The predictions conflict with suggestions that A. afarensis used a ‘shuffling’ gait, indicating rather that the species was a fully competent biped. PMID:16849203

  7. The vertebral formula of the last common ancestor of African apes and humans.

    PubMed

    McCollum, Melanie A; Rosenman, Burt A; Suwa, Gen; Meindl, Richard S; Lovejoy, C Owen

    2010-03-15

    The modal number of lumbar vertebrae in modern humans is five. It varies between three and four in extant African apes (mean=3.5). Because both chimpanzees (Pan troglodytes) and gorillas (Gorilla gorilla) possess the same distributions of thoracic, lumbar, and sacral vertebrae, it has been assumed from parsimony that the last common ancestor (LCA) of African apes and humans possessed a similarly short lower back. This "short-backed LCA" scenario has recently been viewed favorably in an analysis of the intra- and interspecific variation in axial formulas observed among African apes and humans (Pilbeam, 2004. J Exp Zool 302B:241-267). However, the number of bonobo (Pan paniscus) specimens in that study was small (N=17). Here we reconsider vertebral type and number in the LCA in light of an expanded P. paniscus sample as well as evidence provided by the human fossil record. The precaudal (pre-coccygeal) axial column of bonobos differs from those of chimpanzees and gorillas in displaying one additional vertebra as well as significantly different combinations of sacral, lumbar, and thoracic vertebrae. These findings, along with the six-segmented lumbar column of early Australopithecus and early Homo, suggest that the LCA possessed a long axial column and long lumbar spine and that reduction in the lumbar column occurred independently in humans and in each ape clade, and continued after separation of the two species of Pan as well. Such an explanation is strongly congruent with additional details of lumbar column reduction and lower back stabilization in African apes. PMID:19688850

  8. A hominid from the lower Pleistocene of Atapuerca, Spain: possible ancestor to Neandertals and modern humans.

    PubMed

    Bermúdez de Castro, J M; Arsuaga, J L; Carbonell, E; Rosas, A; Martínez, I; Mosquera, M

    1997-05-30

    Human fossil remains recovered from the TD6 level (Aurora stratum) of the lower Pleistocene cave site of Gran Dolina, Sierra de Atapuerca, Spain, exhibit a unique combination of cranial, mandibular, and dental traits and are suggested as a new species of Homo-H. antecessor sp. nov. The fully modern midfacial morphology of the fossils antedates other evidence of this feature by about 650, 000 years. The midfacial and subnasal morphology of modern humans may be a retention of a juvenile pattern that was not yet present in H. ergaster. Homo antecessor may represent the last common ancestor for Neandertals and modern humans. PMID:9162001

  9. Scapular shape of extant hominoids and the African ape/modern human last common ancestor.

    PubMed

    Green, David J; Spiewak, Ted A; Seitelman, Brielle; Gunz, Philipp

    2016-05-01

    Newly discovered early hominin fossil scapulae have bolstered investigations of scapular shape, which have long been used to interpret behavioral variation among primates. However, unexpected similarities between Pongo and Homo - particularly in scapular spine orientation - have raised questions about the functional utility of scapular morphology and its phylogenetic context in the hominin lineage. Not surprisingly, significant disagreement surrounds disparate morphological reconstructions of the modern human/African ape last common ancestor (LCA). Our study utilizes geometric morphometric (GM) approaches - two employing homologous, anatomical landmarks and a "spine-free" alternative using 98 sliding semilandmarks along the boundary of the subscapular fossa. The landmark-based "wireframe" GM analysis principally sorted groups by spine orientation: Homo and Pongo were similar to one another with more transversely-oriented spines as compared to Hylobates and the African apes. In contrast, Homo and Gorilla clustered together in our semilandmark analysis with superoinferiorly broad blades. Pan scapulae were similar, but had more mediolaterally compressed blades and laterally-positioned superior angles. Hylobates was superoinferiorly narrow, yet obliquely expanded relative to the vertebral border. Pongo scapulae were unique among hominoids in being nearly as broad as they were long. Previously documented 'convergence' of Homo and Pongo scapulae appears to be principally driven by similarities in spine orientation, rather than overall blade shape. Therefore, we contend that it is more parsimonious to reconstruct the African ape/Homo LCA scapula as being Gorilla-like, especially in light of similar characterizations of certain fossil hominin scapulae. Accordingly, the evolution of Pan (highly oblique spine and laterally-situated superior angle) and Homo (transversely-oriented spine) scapular morphology would have involved relatively minor shifts from this ancestral

  10. Fossil hominin shoulders support an African ape-like last common ancestor of humans and chimpanzees

    PubMed Central

    Young, Nathan M.; Capellini, Terence D.; Roach, Neil T.; Alemseged, Zeresenay

    2015-01-01

    Reconstructing the behavioral shifts that drove hominin evolution requires knowledge of the timing, magnitude, and direction of anatomical changes over the past ∼6–7 million years. These reconstructions depend on assumptions regarding the morphotype of the Homo–Pan last common ancestor (LCA). However, there is little consensus for the LCA, with proposed models ranging from African ape to orangutan or generalized Miocene ape-like. The ancestral state of the shoulder is of particular interest because it is functionally associated with important behavioral shifts in hominins, such as reduced arboreality, high-speed throwing, and tool use. However, previous morphometric analyses of both living and fossil taxa have yielded contradictory results. Here, we generated a 3D morphospace of ape and human scapular shape to plot evolutionary trajectories, predict ancestral morphologies, and directly test alternative evolutionary hypotheses using the hominin fossil evidence. We show that the most parsimonious model for the evolution of hominin shoulder shape starts with an African ape-like ancestral state. We propose that the shoulder evolved gradually along a single morphocline, achieving modern human-like configuration and function within the genus Homo. These data are consistent with a slow, progressive loss of arboreality and increased tool use throughout human evolution. PMID:26351685

  11. Fossil hominin shoulders support an African ape-like last common ancestor of humans and chimpanzees.

    PubMed

    Young, Nathan M; Capellini, Terence D; Roach, Neil T; Alemseged, Zeresenay

    2015-09-22

    Reconstructing the behavioral shifts that drove hominin evolution requires knowledge of the timing, magnitude, and direction of anatomical changes over the past ∼6-7 million years. These reconstructions depend on assumptions regarding the morphotype of the Homo-Pan last common ancestor (LCA). However, there is little consensus for the LCA, with proposed models ranging from African ape to orangutan or generalized Miocene ape-like. The ancestral state of the shoulder is of particular interest because it is functionally associated with important behavioral shifts in hominins, such as reduced arboreality, high-speed throwing, and tool use. However, previous morphometric analyses of both living and fossil taxa have yielded contradictory results. Here, we generated a 3D morphospace of ape and human scapular shape to plot evolutionary trajectories, predict ancestral morphologies, and directly test alternative evolutionary hypotheses using the hominin fossil evidence. We show that the most parsimonious model for the evolution of hominin shoulder shape starts with an African ape-like ancestral state. We propose that the shoulder evolved gradually along a single morphocline, achieving modern human-like configuration and function within the genus Homo. These data are consistent with a slow, progressive loss of arboreality and increased tool use throughout human evolution. PMID:26351685

  12. No known hominin species matches the expected dental morphology of the last common ancestor of Neanderthals and modern humans

    PubMed Central

    Gómez-Robles, Aida; Bermúdez de Castro, José María; Arsuaga, Juan-Luis; Carbonell, Eudald; Polly, P. David

    2013-01-01

    A central problem in paleoanthropology is the identity of the last common ancestor of Neanderthals and modern humans ([N-MH]LCA). Recently developed analytical techniques now allow this problem to be addressed using a probabilistic morphological framework. This study provides a quantitative reconstruction of the expected dental morphology of the [N-MH]LCA and an assessment of whether known fossil species are compatible with this ancestral position. We show that no known fossil species is a suitable candidate for being the [N-MH]LCA and that all late Early and Middle Pleistocene taxa from Europe have Neanderthal dental affinities, pointing to the existence of a European clade originated around 1 Ma. These results are incongruent with younger molecular divergence estimates and suggest at least one of the following must be true: (i) European fossils and the [N-MH]LCA selectively retained primitive dental traits; (ii) molecular estimates of the divergence between Neanderthals and modern humans are underestimated; or (iii) phenotypic divergence and speciation between both species were decoupled such that phenotypic differentiation, at least in dental morphology, predated speciation. PMID:24145426

  13. The facial skeleton of the chimpanzee-human last common ancestor

    PubMed Central

    Cobb, Samuel N

    2008-01-01

    This review uses the current morphological evidence to evaluate the facial morphology of the hypothetical last common ancestor (LCA) of the chimpanzee/bonobo (panin) and human (hominin) lineages. Some of the problems involved in reconstructing ancestral morphologies so close to the formation of a lineage are discussed. These include the prevalence of homoplasy and poor phylogenetic resolution due to a lack of defining derived features. Consequently the list of hypothetical features expected in the face of the LCA is very limited beyond its hypothesized similarity to extant Pan. It is not possible to determine with any confidence whether the facial morphology of any of the current candidate LCA taxa (Ardipithecus kadabba, Ardipithecus ramidus, Orrorin tugenensis and Sahelanthropus tchadensis) is representative of the LCA, or a stem hominin, or a stem panin or, in some cases, a hominid predating the emergence of the hominin lineage. The major evolutionary trends in the hominin lineage subsequent to the LCA are discussed in relation to the dental arcade and dentition, subnasal morphology and the size, position and prognathism of the facial skeleton. PMID:18380866

  14. Maize Domestication and Anti-Herbivore Defences: Leaf-Specific Dynamics during Early Ontogeny of Maize and Its Wild Ancestors

    PubMed Central

    Maag, Daniel; Erb, Matthias; Bernal, Julio S.; Wolfender, Jean-Luc; Turlings, Ted C. J.; Glauser, Gaétan

    2015-01-01

    As a consequence of artificial selection for specific traits, crop plants underwent considerable genotypic and phenotypic changes during the process of domestication. These changes may have led to reduced resistance in the cultivated plant due to shifts in resource allocation from defensive traits to increased growth rates and yield. Modern maize (Zea mays ssp. mays) was domesticated from its ancestor Balsas teosinte (Z. mays ssp. parviglumis) approximately 9000 years ago. Although maize displays a high genetic overlap with its direct ancestor and other annual teosintes, several studies show that maize and its ancestors differ in their resistance phenotypes with teosintes being less susceptible to herbivore damage. However, the underlying mechanisms are poorly understood. Here we addressed the question to what extent maize domestication has affected two crucial chemical and one physical defence traits and whether differences in their expression may explain the differences in herbivore resistance levels. The ontogenetic trajectories of 1,4-benzoxazin-3-ones, maysin and leaf toughness were monitored for different leaf types across several maize cultivars and teosinte accessions during early vegetative growth stages. We found significant quantitative and qualitative differences in 1,4-benzoxazin-3-one accumulation in an initial pairwise comparison, but we did not find consistent differences between wild and cultivated genotypes during a more thorough examination employing several cultivars/accessions. Yet, 1,4-benzoxazin-3-one levels tended to decline more rapidly with plant age in the modern maize cultivars. Foliar maysin levels and leaf toughness increased with plant age in a leaf-specific manner, but were also unaffected by domestication. Based on our findings we suggest that defence traits other than the ones that were investigated are responsible for the observed differences in herbivore resistance between teosinte and maize. Furthermore, our results indicate

  15. The universal ancestor

    NASA Technical Reports Server (NTRS)

    Woese, C.

    1998-01-01

    A genetic annealing model for the universal ancestor of all extant life is presented; the name of the model derives from its resemblance to physical annealing. The scenario pictured starts when "genetic temperatures" were very high, cellular entities (progenotes) were very simple, and information processing systems were inaccurate. Initially, both mutation rate and lateral gene transfer levels were elevated. The latter was pandemic and pervasive to the extent that it, not vertical inheritance, defined the evolutionary dynamic. As increasingly complex and precise biological structures and processes evolved, both the mutation rate and the scope and level of lateral gene transfer, i.e., evolutionary temperature, dropped, and the evolutionary dynamic gradually became that characteristic of modern cells. The various subsystems of the cell "crystallized," i.e., became refractory to lateral gene transfer, at different stages of "cooling," with the translation apparatus probably crystallizing first. Organismal lineages, and so organisms as we know them, did not exist at these early stages. The universal phylogenetic tree, therefore, is not an organismal tree at its base but gradually becomes one as its peripheral branchings emerge. The universal ancestor is not a discrete entity. It is, rather, a diverse community of cells that survives and evolves as a biological unit. This communal ancestor has a physical history but not a genealogical one. Over time, this ancestor refined into a smaller number of increasingly complex cell types with the ancestors of the three primary groupings of organisms arising as a result.

  16. The Universal Ancestor

    NASA Astrophysics Data System (ADS)

    Woese, Carl

    1998-06-01

    A genetic annealing model for the universal ancestor of all extant life is presented; the name of the model derives from its resemblance to physical annealing. The scenario pictured starts when ``genetic temperatures'' were very high, cellular entities (progenotes) were very simple, and information processing systems were inaccurate. Initially, both mutation rate and lateral gene transfer levels were elevated. The latter was pandemic and pervasive to the extent that it, not vertical inheritance, defined the evolutionary dynamic. As increasingly complex and precise biological structures and processes evolved, both the mutation rate and the scope and level of lateral gene transfer, i.e., evolutionary temperature, dropped, and the evolutionary dynamic gradually became that characteristic of modern cells. The various subsystems of the cell ``crystallized,'' i.e., became refractory to lateral gene transfer, at different stages of ``cooling,'' with the translation apparatus probably crystallizing first. Organismal lineages, and so organisms as we know them, did not exist at these early stages. The universal phylogenetic tree, therefore, is not an organismal tree at its base but gradually becomes one as its peripheral branchings emerge. The universal ancestor is not a discrete entity. It is, rather, a diverse community of cells that survives and evolves as a biological unit. This communal ancestor has a physical history but not a genealogical one. Over time, this ancestor refined into a smaller number of increasingly complex cell types with the ancestors of the three primary groupings of organisms arising as a result.

  17. Phylogenomic Analyses Indicate that Early Fungi Evolved Digesting Cell Walls of Algal Ancestors of Land Plants

    PubMed Central

    Chang, Ying; Wang, Sishuo; Sekimoto, Satoshi; Aerts, Andrea L.; Choi, Cindy; Clum, Alicia; LaButti, Kurt M.; Lindquist, Erika A.; Yee Ngan, Chew; Ohm, Robin A.; Salamov, Asaf A.; Grigoriev, Igor V.; Spatafora, Joseph W.; Berbee, Mary L.

    2015-01-01

    As decomposers, fungi are key players in recycling plant material in global carbon cycles. We hypothesized that genomes of early diverging fungi may have inherited pectinases from an ancestral species that had been able to extract nutrients from pectin-containing land plants and their algal allies (Streptophytes). We aimed to infer, based on pectinase gene expansions and on the organismal phylogeny, the geological timing of the plant–fungus association. We analyzed 40 fungal genomes, three of which, including Gonapodya prolifera, were sequenced for this study. In the organismal phylogeny from 136 housekeeping loci, Rozella diverged first from all other fungi. Gonapodya prolifera was included among the flagellated, predominantly aquatic fungal species in Chytridiomycota. Sister to Chytridiomycota were the predominantly terrestrial fungi including zygomycota I and zygomycota II, along with the ascomycetes and basidiomycetes that comprise Dikarya. The Gonapodya genome has 27 genes representing five of the seven classes of pectin-specific enzymes known from fungi. Most of these share a common ancestry with pectinases from Dikarya. Indicating functional and sequence similarity, Gonapodya, like many Dikarya, can use pectin as a carbon source for growth in pure culture. Shared pectinases of Dikarya and Gonapodya provide evidence that even ancient aquatic fungi had adapted to extract nutrients from the plants in the green lineage. This implies that 750 million years, the estimated maximum age of origin of the pectin-containing streptophytes represents a maximum age for the divergence of Chytridiomycota from the lineage including Dikarya. PMID:25977457

  18. The Distribution and Most Recent Common Ancestor of the 17q21 Inversion in Humans

    PubMed Central

    Donnelly, Michael P.; Paschou, Peristera; Grigorenko, Elena; Gurwitz, David; Mehdi, Syed Qasim; Kajuna, Sylvester L.B.; Barta, Csaba; Kungulilo, Selemani; Karoma, N.J.; Lu, Ru-Band; Zhukova, Olga V.; Kim, Jong-Jin; Comas, David; Siniscalco, Marcello; New, Maria; Li, Peining; Li, Hui; Manolopoulos, Vangelis G.; Speed, William C.; Rajeevan, Haseena; Pakstis, Andrew J.; Kidd, Judith R.; Kidd, Kenneth K.

    2010-01-01

    The polymorphic inversion on 17q21, sometimes called the microtubular associated protein tau (MAPT) inversion, is an ∼900 kb inversion found primarily in Europeans and Southwest Asians. We have identified 21 SNPs that act as markers of the inverted, i.e., H2, haplotype. The inversion is found at the highest frequencies in Southwest Asia and Southern Europe (frequencies of ∼30%); elsewhere in Europe, frequencies vary from < 5%, in Finns, to 28%, in Orcadians. The H2 inversion haplotype also occurs at low frequencies in Africa, Central Asia, East Asia, and the Americas, though the East Asian and Amerindian alleles may be due to recent gene flow from Europe. Molecular evolution analyses indicate that the H2 haplotype originally arose in Africa or Southwest Asia. Though the H2 inversion has many fixed differences across the ∼900 kb, short tandem repeat polymorphism data indicate a very recent date for the most recent common ancestor, with dates ranging from 13,600 to 108,400 years, depending on assumptions and estimation methods. This estimate range is much more recent than the 3 million year age estimated by Stefansson et al. in 2005.1 PMID:20116045

  19. Hairless mutation: a driving force of humanization from a human–ape common ancestor by enforcing upright walking while holding a baby with both hands

    PubMed Central

    Sutou, Shizuyo

    2012-01-01

    Three major characteristics distinguish humans from other primates: bipedality, practical nakedness, and the family as a social unit. A hairless mutation introduced into the chimpanzee/human last common ancestor (CLCA) 6 million years ago (Mya) diverged hairless human and hairy chimpanzee lineages. All primates except humans can carry their babies without using their hands. A hairless mother would be forced to stand and walk upright. Her activities would be markedly limited. The male partner would have to collect food and carry it to her by hand to keep her and their baby from starving; irresponsible and selfish males could not have left their offspring. The mother would have sexually accepted her partner at any time as a reward for food. Sexual relations irrespective of estrus cycles might have strengthened the pair bond. Molecular and paleontological dating indicates that CLCA existed 6 Mya, and early hominin fossils show that they were bipeds, indicating that humanization from CLCA occurred rapidly. A single mutation in animals with scalp hair is known to induce hairless phenotype (ectodermal dysplasia). Bipedalism and hairlessness are disadvantageous traits; only those who could survive trials and tribulations in cooperation with family members must have been able to evolve as humans. PMID:22404045

  20. Strong Selective Sweeps on the X Chromosome in the Human-Chimpanzee Ancestor Explain Its Low Divergence.

    PubMed

    Dutheil, Julien Y; Munch, Kasper; Nam, Kiwoong; Mailund, Thomas; Schierup, Mikkel H

    2015-08-01

    The human and chimpanzee X chromosomes are less divergent than expected based on autosomal divergence. We study incomplete lineage sorting patterns between humans, chimpanzees and gorillas to show that this low divergence can be entirely explained by megabase-sized regions comprising one-third of the X chromosome, where polymorphism in the human-chimpanzee ancestral species was severely reduced. We show that background selection can explain at most 10% of this reduction of diversity in the ancestor. Instead, we show that several strong selective sweeps in the ancestral species can explain it. We also report evidence of population specific sweeps in extant humans that overlap the regions of low diversity in the ancestral species. These regions further correspond to chromosomal sections shown to be devoid of Neanderthal introgression into modern humans. This suggests that the same X-linked regions that undergo selective sweeps are among the first to form reproductive barriers between diverging species. We hypothesize that meiotic drive is the underlying mechanism causing these two observations. PMID:26274919

  1. Strong Selective Sweeps on the X Chromosome in the Human-Chimpanzee Ancestor Explain Its Low Divergence

    PubMed Central

    Dutheil, Julien Y.; Munch, Kasper; Nam, Kiwoong; Mailund, Thomas; Schierup, Mikkel H.

    2015-01-01

    The human and chimpanzee X chromosomes are less divergent than expected based on autosomal divergence. We study incomplete lineage sorting patterns between humans, chimpanzees and gorillas to show that this low divergence can be entirely explained by megabase-sized regions comprising one-third of the X chromosome, where polymorphism in the human-chimpanzee ancestral species was severely reduced. We show that background selection can explain at most 10% of this reduction of diversity in the ancestor. Instead, we show that several strong selective sweeps in the ancestral species can explain it. We also report evidence of population specific sweeps in extant humans that overlap the regions of low diversity in the ancestral species. These regions further correspond to chromosomal sections shown to be devoid of Neanderthal introgression into modern humans. This suggests that the same X-linked regions that undergo selective sweeps are among the first to form reproductive barriers between diverging species. We hypothesize that meiotic drive is the underlying mechanism causing these two observations. PMID:26274919

  2. Human Diversity and the Genealogy of Languages: Noah as the Founding Ancestor of the Chinese

    ERIC Educational Resources Information Center

    Hutton, Christopher

    2008-01-01

    The characteristics which were held to define the Chinese language within the Western intellectual tradition placed it for a time at the centre in discussions of the genealogy of mankind. The dominant premodern paradigm for the explanation of human linguistic diversity was Biblical exegesis, as discussed and elaborated within the framework of…

  3. Ancient horizontal transfers of retrotransposons between birds and ancestors of human pathogenic nematodes.

    PubMed

    Suh, Alexander; Witt, Christopher C; Menger, Juliana; Sadanandan, Keren R; Podsiadlowski, Lars; Gerth, Michael; Weigert, Anne; McGuire, Jimmy A; Mudge, Joann; Edwards, Scott V; Rheindt, Frank E

    2016-01-01

    Parasite host switches may trigger disease emergence, but prehistoric host ranges are often unknowable. Lymphatic filariasis and loiasis are major human diseases caused by the insect-borne filarial nematodes Brugia, Wuchereria and Loa. Here we show that the genomes of these nematodes and seven tropical bird lineages exclusively share a novel retrotransposon, AviRTE, resulting from horizontal transfer (HT). AviRTE subfamilies exhibit 83-99% nucleotide identity between genomes, and their phylogenetic distribution, paleobiogeography and invasion times suggest that HTs involved filarial nematodes. The HTs between bird and nematode genomes took place in two pantropical waves, >25-22 million years ago (Myr ago) involving the Brugia/Wuchereria lineage and >20-17 Myr ago involving the Loa lineage. Contrary to the expectation from the mammal-dominated host range of filarial nematodes, we hypothesize that these major human pathogens may have independently evolved from bird endoparasites that formerly infected the global breadth of avian biodiversity. PMID:27097561

  4. Ancient horizontal transfers of retrotransposons between birds and ancestors of human pathogenic nematodes

    PubMed Central

    Suh, Alexander; Witt, Christopher C.; Menger, Juliana; Sadanandan, Keren R.; Podsiadlowski, Lars; Gerth, Michael; Weigert, Anne; McGuire, Jimmy A.; Mudge, Joann; Edwards, Scott V.; Rheindt, Frank E.

    2016-01-01

    Parasite host switches may trigger disease emergence, but prehistoric host ranges are often unknowable. Lymphatic filariasis and loiasis are major human diseases caused by the insect-borne filarial nematodes Brugia, Wuchereria and Loa. Here we show that the genomes of these nematodes and seven tropical bird lineages exclusively share a novel retrotransposon, AviRTE, resulting from horizontal transfer (HT). AviRTE subfamilies exhibit 83–99% nucleotide identity between genomes, and their phylogenetic distribution, paleobiogeography and invasion times suggest that HTs involved filarial nematodes. The HTs between bird and nematode genomes took place in two pantropical waves, >25–22 million years ago (Myr ago) involving the Brugia/Wuchereria lineage and >20–17 Myr ago involving the Loa lineage. Contrary to the expectation from the mammal-dominated host range of filarial nematodes, we hypothesize that these major human pathogens may have independently evolved from bird endoparasites that formerly infected the global breadth of avian biodiversity. PMID:27097561

  5. Ancient gene flow from early modern humans into Eastern Neanderthals.

    PubMed

    Kuhlwilm, Martin; Gronau, Ilan; Hubisz, Melissa J; de Filippo, Cesare; Prado-Martinez, Javier; Kircher, Martin; Fu, Qiaomei; Burbano, Hernán A; Lalueza-Fox, Carles; de la Rasilla, Marco; Rosas, Antonio; Rudan, Pavao; Brajkovic, Dejana; Kucan, Željko; Gušic, Ivan; Marques-Bonet, Tomas; Andrés, Aida M; Viola, Bence; Pääbo, Svante; Meyer, Matthias; Siepel, Adam; Castellano, Sergi

    2016-02-25

    It has been shown that Neanderthals contributed genetically to modern humans outside Africa 47,000-65,000 years ago. Here we analyse the genomes of a Neanderthal and a Denisovan from the Altai Mountains in Siberia together with the sequences of chromosome 21 of two Neanderthals from Spain and Croatia. We find that a population that diverged early from other modern humans in Africa contributed genetically to the ancestors of Neanderthals from the Altai Mountains roughly 100,000 years ago. By contrast, we do not detect such a genetic contribution in the Denisovan or the two European Neanderthals. We conclude that in addition to later interbreeding events, the ancestors of Neanderthals from the Altai Mountains and early modern humans met and interbred, possibly in the Near East, many thousands of years earlier than previously thought. PMID:26886800

  6. Ancient gene flow from early modern humans into Eastern Neanderthals

    PubMed Central

    Kuhlwilm, Martin; Gronau, Ilan; Hubisz, Melissa J.; de Filippo, Cesare; Prado-Martinez, Javier; Kircher, Martin; Fu, Qiaomei; Burbano, Hernán A.; Lalueza-Fox, Carles; de la Rasilla, Marco; Rosas, Antonio; Rudan, Pavao; Brajkovic, Dejana; Kucan, Željko; Gušic, Ivan; Marques-Bonet, Tomas; Andrés, Aida M.; Viola, Bence; Pääbo, Svante; Meyer, Matthias; Siepel, Adam; Castellano, Sergi

    2016-01-01

    It has been shown that Neanderthals contributed genetically to modern humans outside Africa 47,000–65,000 years ago. Here, we analyze the genomes of a Neanderthal and a Denisovan from the Altai Mountains in Siberia together with the sequences of chromosome 21 of two Neanderthals from Spain and Croatia. We find that a population that diverged early from other modern humans in Africa contributed genetically to the ancestors of Neanderthals from the Altai Mountains roughly 100,000 years ago. By contrast, we do not detect such a genetic contribution in the Denisovan or the two European Neanderthals. We conclude that in addition to later interbreeding events, the ancestors of Neanderthals from the Altai Mountains and of modern humans met and interbred, possibly in the Near East, many thousands of years earlier than previously reported. PMID:26886800

  7. Duplication of the gamma-globin gene mediated by L1 long interspersed repetitive elements in an early ancestor of simian primates.

    PubMed Central

    Fitch, D H; Bailey, W J; Tagle, D A; Goodman, M; Sieu, L; Slightom, J L

    1991-01-01

    Regions surrounding the single gamma-globin gene of galago and the duplicated gamma 1- and gamma 2-globin genes of gibbon, rhesus monkey, and spider monkey were sequenced and aligned with those from humans. Contrary to previous studies, spider monkey was found to have not one but two gamma-globin genes, only one of which (gamma 2) is functional. The reconstructed evolutionary history of the gamma-globin genes and their flanking sequences traces their origin to a tandem duplication of a DNA segment approximately 5.5 kilobases long that occurred before catarrhine primates (humans, apes, and Old World monkeys) diverged from platyrrhines (New World monkeys), much earlier than previously thought. This reconstructed molecular history also reveals that the duplication resulted from an unequal homologous crossover between two related L1 long interspersed repetitive elements, one upstream and one downstream of the single ancestral gamma-globin gene. Perhaps facilitated by the redundancy resulting from the duplication, the gamma-globin genes escaped the selective constraints of embryonically functioning genes and evolved into fetally functioning genes. This view is supported by the finding that a burst of nonsynonymous substitutions occurred in the gamma-globin genes while they became restructured for fetal expression in the common ancestor of platyrrhines and catarrhines. PMID:1908094

  8. Non-Darwinian estimation: My ancestors, my genes' ancestors

    PubMed Central

    Weiss, Kenneth M.; Long, Jeffrey C.

    2009-01-01

    There is widespread interest in characterizing the organization of human genetic variation around the world from a population perspective. Related to this are attempts to describe the pattern of genetic variation in the human species generally, including “recreational” genomics, the genome-based estimation of the ancestry of individuals. These approaches rest on subtle concepts of variation, time, and ancestry that are perhaps not widely appreciated. They share the idea that there are, or were, discrete panmictic human populations such that every person is either a member of such a population or is an admixed descendant of them. Ancestry fraction estimation is biased by assumptions about past and present human population structure, as when we trace ancestry to hypothetical unmixed ancestral populations, or assign an individual's ancestry to continental populations that are indistinguishable from classical “races.” Attempts to identify even individuals' local subpopulations are less precise than most (geneticists included) expect, because that is usually based on a small portion of a person's ancestry, relative to the much larger pool of comparably related ancestors. It is easier to show that two people have some relationship than to show who or where the actual ancestor was. There is an important distinction between individuals' demographic ancestry and the ancestry of their genes. Despite superficial appearances, these interpretations of genetic data are often based on typological rather than Darwinian thinking, raising important issues about the questions that are actually being asked. PMID:19411595

  9. The galaxy ancestor problem

    NASA Astrophysics Data System (ADS)

    Disney, M. J.; Lang, R. H.

    2012-11-01

    The Hubble Space Telescope (HST) findsgalaxies whose Tolman dimming exceeds 10 mag. Could evolution alone explain these as our ancestor galaxies or could they be representatives of quite a different dynasty whose descendants are no longer prominent today? We explore the latter hypothesis and argue that surface brightness selection effects naturally bring into focus quite different dynasties from different redshifts. Thus, the HST z = 7 galaxies could be examples of galaxies whose descendants are both too small and too choked with dust to be recognizable in our neighbourhood easily today. Conversely, the ancestors of the Milky Way and its obvious neighbours would have completely sunk below the sky at z > 1.2, unless they were more luminous in the past, although their diffused light could account for the missing re-ionization flux. This Succeeding Prominent Dynasties Hypothesis (SPDH) fits the existing observations both naturally and well even without evolution, including the bizarre distributions of galaxy surface brightness found in deep fields, the angular size ˜(1 + z)-1 law, 'downsizing' which turns out to be an 'illusion' in the sense that it does not imply evolution, 'infant mortality', that is, the discrepancy between stars born and stars seen, the existence of 'red nuggets', and finally the recently discovered and unexpected excess of quasar absorption line damped Lyα systems at high redshift. If galaxies were not significantly brighter in the past and the SPDH were true, then a large proportion of galaxies could remain sunk from sight, possibly at all redshifts, and these sunken galaxies could supply the missing re-ionization flux. We show that fishing these sunken galaxies out of the sky by their optical emissions alone is practically impossible, even when they are nearby. More ingenious methods are needed to detect them. It follows that disentangling galaxy evolution through studying ever higher redshift galaxies may be a forlorn hope because one could

  10. Ontogeny of the maxilla in Neanderthals and their ancestors.

    PubMed

    Lacruz, Rodrigo S; Bromage, Timothy G; O'Higgins, Paul; Arsuaga, Juan-Luis; Stringer, Chris; Godinho, Ricardo Miguel; Warshaw, Johanna; Martínez, Ignacio; Gracia-Tellez, Ana; de Castro, José María Bermúdez; Carbonell, Eudald

    2015-01-01

    Neanderthals had large and projecting (prognathic) faces similar to those of their putative ancestors from Sima de los Huesos (SH) and different from the retracted modern human face. When such differences arose during development and the morphogenetic modifications involved are unknown. We show that maxillary growth remodelling (bone formation and resorption) of the Devil's Tower (Gibraltar 2) and La Quina 18 Neanderthals and four SH hominins, all sub-adults, show extensive bone deposition, whereas in modern humans extensive osteoclastic bone resorption is found in the same regions. This morphogenetic difference is evident by ∼5 years of age. Modern human faces are distinct from those of the Neanderthal and SH fossils in part because their postnatal growth processes differ markedly. The growth remodelling identified in these fossil hominins is shared with Australopithecus and early Homo but not with modern humans suggesting that the modern human face is developmentally derived. PMID:26639346

  11. Ontogeny of the maxilla in Neanderthals and their ancestors

    PubMed Central

    Lacruz, Rodrigo S.; Bromage, Timothy G.; O'Higgins, Paul; Arsuaga, Juan-Luis; Stringer, Chris; Godinho, Ricardo Miguel; Warshaw, Johanna; Martínez, Ignacio; Gracia-Tellez, Ana; de Castro, José María Bermúdez; Carbonell, Eudald

    2015-01-01

    Neanderthals had large and projecting (prognathic) faces similar to those of their putative ancestors from Sima de los Huesos (SH) and different from the retracted modern human face. When such differences arose during development and the morphogenetic modifications involved are unknown. We show that maxillary growth remodelling (bone formation and resorption) of the Devil's Tower (Gibraltar 2) and La Quina 18 Neanderthals and four SH hominins, all sub-adults, show extensive bone deposition, whereas in modern humans extensive osteoclastic bone resorption is found in the same regions. This morphogenetic difference is evident by ∼5 years of age. Modern human faces are distinct from those of the Neanderthal and SH fossils in part because their postnatal growth processes differ markedly. The growth remodelling identified in these fossil hominins is shared with Australopithecus and early Homo but not with modern humans suggesting that the modern human face is developmentally derived. PMID:26639346

  12. Origin of Clothing Lice Indicates Early Clothing Use by Anatomically Modern Humans in Africa

    PubMed Central

    Toups, Melissa A.; Kitchen, Andrew; Light, Jessica E.; Reed, David L.

    2011-01-01

    Clothing use is an important modern behavior that contributed to the successful expansion of humans into higher latitudes and cold climates. Previous research suggests that clothing use originated anywhere between 40,000 and 3 Ma, though there is little direct archaeological, fossil, or genetic evidence to support more specific estimates. Since clothing lice evolved from head louse ancestors once humans adopted clothing, dating the emergence of clothing lice may provide more specific estimates of the origin of clothing use. Here, we use a Bayesian coalescent modeling approach to estimate that clothing lice diverged from head louse ancestors at least by 83,000 and possibly as early as 170,000 years ago. Our analysis suggests that the use of clothing likely originated with anatomically modern humans in Africa and reinforces a broad trend of modern human developments in Africa during the Middle to Late Pleistocene. PMID:20823373

  13. What did our ancestors eat?

    PubMed

    Garn, S M; Leonard, W R

    1989-11-01

    Over the millennia various hominoids and hominids have subsisted on very different dietaries, depending on climate, hunting proficiency, food-processing technology, and available foods. The Australopithecines were not browsers and fruit-eaters with very high intakes of vitamin C; rather they were scavengers of kills made by other animals. The hominids who followed did include some cold-climate hunters of large game, but the amount of animal protein decreased with the advent of grain-gathering and decreased further with the introduction of cereal agriculture, with a concomitant decrease in body size. From what we know about food adequacy, preparation, and storage, the notion that the postulated "primitive" diet was generally adequate, safe, and prudent can be rejected. Over evolutionary time, many of our ancestors ate poorly, especially during climate extremes, and they were often at risk for vitamin deficiencies, food-borne diseases, and neurotoxins. Until the advent of modern processing technologies, dirt, grit, and fiber constituted a large part of most early diets. PMID:2689923

  14. Aping our ancestors

    NASA Astrophysics Data System (ADS)

    Ennos, Roland

    2014-08-01

    Roland Ennos argues that the abilities of the great apes to cope in the dangerous mechanical environment of the forest canopy are part of the human species' intellectual inheritance and are intimately connected with our abilities as physicists.

  15. The evolutionary history of the hominin hand since the last common ancestor of Pan and Homo

    PubMed Central

    Tocheri, Matthew W; Orr, Caley M; Jacofsky, Marc C; Marzke, Mary W

    2008-01-01

    Molecular evidence indicates that the last common ancestor of the genus Pan and the hominin clade existed between 8 and 4 million years ago (Ma). The current fossil record indicates the Pan-Homo last common ancestor existed at least 5 Ma and most likely between 6 and 7 Ma. Together, the molecular and fossil evidence has important consequences for interpreting the evolutionary history of the hand within the tribe Hominini (hominins). Firstly, parsimony supports the hypothesis that the hand of the last common ancestor most likely resembled that of an extant great ape overall (Pan, Gorilla, and Pongo), and that of an African ape in particular. Second, it provides a context for interpreting the derived changes to the hand that have evolved in various hominins. For example, the Australopithecus afarensis hand is likely derived in comparison with that of the Pan–Homo last common ancestor in having shorter fingers relative to thumb length and more proximo-distally oriented joints between its capitate, second metacarpal, and trapezium. This evidence suggests that these derived features evolved prior to the intensification of stone tool-related hominin behaviors beginning around 2.5 Ma. However, a majority of primitive features most likely present in the Pan-Homo last common ancestor are retained in the hands of Australopithecus, Paranthropus/early Homo, and Homo floresiensis. This evidence suggests that further derived changes to the hands of other hominins such as modern humans and Neandertals did not evolve until after 2.5 Ma and possibly even later than 1.5 Ma, which is currently the earliest evidence of Acheulian technology. The derived hands of modern humans and Neandertals may indicate a morphological commitment to tool-related manipulative behaviors beyond that observed in other hominins, including those (e.g. H. floresiensis) which may be descended from earlier tool-making species. PMID:18380869

  16. The evolutionary history of the hominin hand since the last common ancestor of Pan and Homo.

    PubMed

    Tocheri, Matthew W; Orr, Caley M; Jacofsky, Marc C; Marzke, Mary W

    2008-04-01

    Molecular evidence indicates that the last common ancestor of the genus Pan and the hominin clade existed between 8 and 4 million years ago (Ma). The current fossil record indicates the Pan-Homo last common ancestor existed at least 5 Ma and most likely between 6 and 7 Ma. Together, the molecular and fossil evidence has important consequences for interpreting the evolutionary history of the hand within the tribe Hominini (hominins). Firstly, parsimony supports the hypothesis that the hand of the last common ancestor most likely resembled that of an extant great ape overall (Pan, Gorilla, and Pongo), and that of an African ape in particular. Second, it provides a context for interpreting the derived changes to the hand that have evolved in various hominins. For example, the Australopithecus afarensis hand is likely derived in comparison with that of the Pan-Homo last common ancestor in having shorter fingers relative to thumb length and more proximo-distally oriented joints between its capitate, second metacarpal, and trapezium. This evidence suggests that these derived features evolved prior to the intensification of stone tool-related hominin behaviors beginning around 2.5 Ma. However, a majority of primitive features most likely present in the Pan-Homo last common ancestor are retained in the hands of Australopithecus, Paranthropus/early Homo, and Homo floresiensis. This evidence suggests that further derived changes to the hands of other hominins such as modern humans and Neandertals did not evolve until after 2.5 Ma and possibly even later than 1.5 Ma, which is currently the earliest evidence of Acheulian technology. The derived hands of modern humans and Neandertals may indicate a morphological commitment to tool-related manipulative behaviors beyond that observed in other hominins, including those (e.g. H. floresiensis) which may be descended from earlier tool-making species. PMID:18380869

  17. Ancestors of modern plant crops.

    PubMed

    Salse, Jérôme

    2016-04-01

    Recent accumulation of plant genomic resources offers the opportunity to compare modern genomes and model their evolutionary history from their reconstructed Most Recent Common Ancestors (MRCAs) that can be used as a guide to unveil the forces driving the evolutionary success of angiosperms and ultimately to perform applied translational research from models to crops. This article reviews the current state of art of recent structural comparative genomics studies through ancestral genome reconstruction, that is, the field of in silico paleogenomics. PMID:26985732

  18. The last common bilaterian ancestor

    NASA Technical Reports Server (NTRS)

    Erwin, Douglas H.; Davidson, Eric H.

    2002-01-01

    Many regulatory genes appear to be utilized in at least superficially similar ways in the development of particular body parts in Drosophila and in chordates. These similarities have been widely interpreted as functional homologies, producing the conventional view of the last common protostome-deuterostome ancestor (PDA) as a complex organism that possessed some of the same body parts as modern bilaterians. Here we discuss an alternative view, in which the last common PDA had a less complex body plan than is frequently conceived. This reconstruction alters expectations for Neoproterozoic fossil remains that could illustrate the pathways of bilaterian evolution.

  19. Transcriptome Encyclopedia of Early Human Development.

    PubMed

    Sahakyan, Anna; Plath, Kathrin

    2016-05-01

    Our understanding of human pre-implantation development is limited by the availability of human embryos and cannot completely rely on mouse studies. Petropoulos et al. now provide an extensive transcriptome analysis of a large number of human pre-implantation embryos at single-cell resolution, revealing previously unrecognized features unique to early human development. PMID:27153491

  20. The Evolution of Brains from Early Mammals to Humans

    PubMed Central

    Kaas, Jon H.

    2012-01-01

    The large size and complex organization of the human brain makes it unique among primate brains. In particular, the neocortex constitutes about 80% of the brain, and this cortex is subdivided into a large number of functionally specialized regions, the cortical areas. Such a brain mediates accomplishments and abilities unmatched by any other species. How did such a brain evolve? Answers come from comparative studies of the brains of present-day mammals and other vertebrates in conjunction with information about brain sizes and shapes from the fossil record, studies of brain development, and principles derived from studies of scaling and optimal design. Early mammals were small, with small brains, an emphasis on olfaction, and little neocortex. Neocortex was transformed from the single layer of output pyramidal neurons of the dorsal cortex of earlier ancestors to the six layers of all present-day mammals. This small cap of neocortex was divided into 20–25 cortical areas, including primary and some of the secondary sensory areas that characterize neocortex in nearly all mammals today. Early placental mammals had a corpus callosum connecting the neocortex of the two hemispheres, a primary motor area, M1, and perhaps one or more premotor areas. One line of evolution, Euarchontoglires, led to present-day primates, tree shrews, flying lemurs, rodents and rabbits. Early primates evolved from small-brained, nocturnal, insect-eating mammals with an expanded region of temporal visual cortex. These early nocturnal primates were adapted to the fine branch niche of the tropical rainforest by having an even more expanded visual system that mediated visually guided reaching and grasping of insects, small vertebrates, and fruits. Neocortex was greatly expanded, and included an array of cortical areas that characterize neocortex of all living primates. Specializations of the visual system included new visual areas that contributed to a dorsal stream of visuomotor processing in a

  1. The Hunt for Dwarf Galaxies' Ancestors

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2016-01-01

    Dwarf galaxies are typically very faint, and are therefore hard to find. Given that, what are our chances of finding their distant ancestors, located billions of light-years away? A recent study aims to find out.Ancient CounterpartsDwarf galaxies are a hot topic right now, especially as we discover more and more of them nearby. Besides being great places to investigate a variety of astrophysical processes, local group dwarf galaxies are also representative of the most common type of galaxy in the universe. For many of these dwarf galaxies, their low masses and typically old stellar populations suggest that most of their stars were formed early in the universes history, and further star formation was suppressed when the universe was reionized at redshifts of z ~ 610. If this is true, most dwarf galaxies are essentially fossils: theyve evolved little since that point.To test this theory, wed like to find counterparts to our local group dwarf galaxies at these higher redshifts of z = 6 or 7. But dwarf galaxies, since they dont exhibit lots of active star formation, have very low surface brightnesses making them very difficult to detect. What are the chances that current or future telescope sensitivities will allow us to detect these? Thats the question Anna Patej and Abraham Loeb, two theorists at Harvard University, have addressed in a recent study.Entering a New RegimeThe surface brightness vs. size for 73 local dwarf galaxies scaled back to redshifts of z=6 (top) and z=7 (bottom). So far weve been able to observe high-redshift galaxies within the boxed region of the parameter space. JWST will open the shaded region of the parameter space, which includes some of the dwarf galaxies. [Patej Loeb 2015]Starting from observational data for 87 Local-Group dwarf galaxies, Patej and Loeb used a stellar population synthesis code to evolve the galaxies backward in time to redshifts of z = 6 and 7. Next, they narrowed this sample to only those dwarfs for which most star

  2. Apparatus Named After Our Academic Ancestors, III

    NASA Astrophysics Data System (ADS)

    Greenslade, Thomas B.

    2014-09-01

    My academic ancestors in physics have called on me once more to tell you about the apparatus that they devised, and that many of you have used in your demonstrations and labs. This article is about apparatus named after François Arago, Heinrich Helmholtz, Leon Foucault, and James Watt.

  3. Apparatus Named after Our Academic Ancestors, III

    ERIC Educational Resources Information Center

    Greenslade, Thomas B., Jr.

    2014-01-01

    My academic ancestors in physics have called on me once more to tell you about the apparatus that they devised, and that many of you have used in your demonstrations and labs. This article is about apparatus named after François Arago, Heinrich Helmholtz, Leon Foucault, and James Watt.

  4. The Five Ancestors--Book 1: Tiger

    ERIC Educational Resources Information Center

    Stone, Jeff

    2004-01-01

    Losing a job is an awfully low point--until it turns into the opportunity to pursue writing full time, and a book like "The Five Ancestors: Tiger" results. Jeff Stone looks back to his own experience as a young reader and taps that experience to help frame his own writing. An intriguing snapshot of his new book follows.

  5. Magnetochronology of early humans in China

    NASA Astrophysics Data System (ADS)

    Deng, C.; Zhu, R.; Pan, Y.

    2009-12-01

    China is a key area for probing into human occupation in the Old World after the initial expansion of early humans out of Africa. Chronology of Chinese Paleolithic/hominin sites in different paleoclimatic and paleoenvironmental settings is paramount for understanding early human migration and adaptation. In recent years, we conducted detailed magnetostratigraphic investigations on the Nihewan Basin in temperate northern China and the Yuanmou Basin in subtropical southern China, both of which contained abundant sites of early humans and mammalian faunas. The age of the sedimentary sequence of the eastern Nihewan Basin can be magnetostratigraphically constrained to an interval from late Pliocene to late Pleistocene. The basal age of the Nihewan Formation in the eastern basin is constrained just prior to the Gauss-Matuyama geomagnetic reversal, that is, between ~2.6 Ma and ~3.0 Ma. The fluvio-lacustrine sequences in this basin were deposited from the late Gauss chron into the late Brunhes chron, and are capped by the last interglacial soil and the last glacial loess , or by the late Pleistocene or Holocene loess sediments. As a result, the Nihewan faunas (sensu lato) can be placed between the Matuyama-Brunhes geomagnetic reversal and the onset of the Olduvai subchron (0.78-1.95 Ma), and a robust chronological sequence of early human colonization in this basin has been established: Maliang (0.8 Ma), Huojiadi (1.0 Ma), Donggutuo and Cenjiawan (1.1 Ma), Feiliang (1.2 Ma), Banshan (1.32 Ma), Xiaochangliang and Xiantai (1.36 Ma), MJG-I (1.55 Ma), MJG-II (1.64 Ma), and MJG-III (1.66 Ma). The age of the sedimentary sequence of the Yuanmou Basin can be magnetostratigraphically constrained to an interval from early Pliocene to Pleistocene. The basal age of this basin sedimentary sequence is constrained just prior to the onset of the Sidufjall subchron, that is, ~4.9 Ma. Accumulation of the Yuanmou sequence was terminated during the Matuyama chron bracketed by the Olduvai and

  6. Magnetostratigraphic dating of early humans in China

    NASA Astrophysics Data System (ADS)

    Zhu, Rixiang; An, Zhisheng; Potts, Richard; Hoffman, Kenneth A.

    2003-06-01

    China is a key area for research into human occupation in the Old World after the initial expansion of early humans out of Africa. Reliable age determinations are pivotal for assessing the patterns of human evolution and dispersal in this region. This paper reviews magnetostratigraphic studies of some early Pleistocene strata bearing hominin remains and/or artifact stone tools from northern to southern China. The quality and reliability of the paleomagnetic dates are also evaluated. New magnetostratigraphic results for the Xihoudu Paleolithic site in north-central China are also presented. Among the few hominin or Paleolithic sites in China from the early Pleistocene, five have been well investigated. Three of these are in northern China at Xiaochangliang, Donggutuo and Gongwangling; the remaining two in southern China at Longgupo and Yuanmou. Considerable progress has been made during the past three decades towards paleomagnetically dating these sites. Indeed, the age estimates at Xiaochangliang and Gongwangling have been widely accepted. Magnetostratigraphic consensus about the age of the Donggutuo site has also been reached. However, the age determination for the two sites in southern China is still contested. The integration of rock-magnetic stratigraphy with magnetic polarity stratigraphy has resulted in a determined age of 1.36 Ma for a stone tool-containing layer of lacustrine sediments at the Xiaochangliang site in the Nihewan Basin. Lithostratigraphic constraints have significantly contributed to determining the age of Lantian Homo erectus at Gongwangling, which occurred in a loess-paleosol sequence of the southern Loess Plateau. Its age, paleomagnetically derived, is about 1.15 Ma. These two paleomagnetic ages suggest an expansion and flourishing of human groups from northern to north-central China during the early Pleistocene. This suggestion has been reinforced by our new magnetostratigraphic age estimate of about 1.27 Ma for the Xihoudu site as will be

  7. Early Defensive Mechanisms against Human Papillomavirus Infection.

    PubMed

    Moerman-Herzog, Andrea; Nakagawa, Mayumi

    2015-08-01

    Cervical cancer is the fourth most common cancer in women and is almost exclusively caused by human papillomavirus (HPV) infection. HPV is also frequently associated with other cancers arising from mucosal epithelium, including anal and oropharyngeal cancers, which are becoming more common in both men and women. Viral persistence and progression through precancerous lesion stages are prerequisites for HPV-associated cancer and reflect the inability of cell-mediated immune mechanisms to clear infections and eliminate abnormal cells in some individuals. Cell-mediated immune responses are initiated by innate pathogen sensing and subsequent secretion of soluble immune mediators and amplified by the recruitment and activation of effector T lymphocytes. This review discusses early defensive mechanisms of innate responders to natural HPV infection, their influence on response polarization, and the underappreciated role of keratinocytes in this process. PMID:26063238

  8. Early Defensive Mechanisms against Human Papillomavirus Infection

    PubMed Central

    Moerman-Herzog, Andrea

    2015-01-01

    Cervical cancer is the fourth most common cancer in women and is almost exclusively caused by human papillomavirus (HPV) infection. HPV is also frequently associated with other cancers arising from mucosal epithelium, including anal and oropharyngeal cancers, which are becoming more common in both men and women. Viral persistence and progression through precancerous lesion stages are prerequisites for HPV-associated cancer and reflect the inability of cell-mediated immune mechanisms to clear infections and eliminate abnormal cells in some individuals. Cell-mediated immune responses are initiated by innate pathogen sensing and subsequent secretion of soluble immune mediators and amplified by the recruitment and activation of effector T lymphocytes. This review discusses early defensive mechanisms of innate responders to natural HPV infection, their influence on response polarization, and the underappreciated role of keratinocytes in this process. PMID:26063238

  9. Punctuated Emergences of Genetic and Phenotypic Innovations in Eumetazoan, Bilaterian, Euteleostome, and Hominidae Ancestors

    PubMed Central

    Wenger, Yvan; Galliot, Brigitte

    2013-01-01

    Phenotypic traits derive from the selective recruitment of genetic materials over macroevolutionary times, and protein-coding genes constitute an essential component of these materials. We took advantage of the recent production of genomic scale data from sponges and cnidarians, sister groups from eumetazoans and bilaterians, respectively, to date the emergence of human proteins and to infer the timing of acquisition of novel traits through metazoan evolution. Comparing the proteomes of 23 eukaryotes, we find that 33% human proteins have an ortholog in nonmetazoan species. This premetazoan proteome associates with 43% of all annotated human biological processes. Subsequently, four major waves of innovations can be inferred in the last common ancestors of eumetazoans, bilaterians, euteleostomi (bony vertebrates), and hominidae, largely specific to each epoch, whereas early branching deuterostome and chordate phyla show very few innovations. Interestingly, groups of proteins that act together in their modern human functions often originated concomitantly, although the corresponding human phenotypes frequently emerged later. For example, the three cnidarians Acropora, Nematostella, and Hydra express a highly similar protein inventory, and their protein innovations can be affiliated either to traits shared by all eumetazoans (gut differentiation, neurogenesis); or to bilaterian traits present in only some cnidarians (eyes, striated muscle); or to traits not identified yet in this phylum (mesodermal layer, endocrine glands). The variable correspondence between phenotypes predicted from protein enrichments and observed phenotypes suggests that a parallel mechanism repeatedly produce similar phenotypes, thanks to novel regulatory events that independently tie preexisting conserved genetic modules. PMID:24065732

  10. Mitochondrial lineage M1 traces an early human backflow to Africa

    PubMed Central

    González, Ana M; Larruga, José M; Abu-Amero, Khaled K; Shi, Yufei; Pestano, José; Cabrera, Vicente M

    2007-01-01

    Background The out of Africa hypothesis has gained generalized consensus. However, many specific questions remain unsettled. To know whether the two M and N macrohaplogroups that colonized Eurasia were already present in Africa before the exit is puzzling. It has been proposed that the east African clade M1 supports a single origin of haplogroup M in Africa. To test the validity of that hypothesis, the phylogeographic analysis of 13 complete mitochondrial DNA (mtDNA) sequences and 261 partial sequences belonging to haplogroup M1 was carried out. Results The coalescence age of the African haplogroup M1 is younger than those for other M Asiatic clades. In contradiction to the hypothesis of an eastern Africa origin for modern human expansions out of Africa, the most ancestral M1 lineages have been found in Northwest Africa and in the Near East, instead of in East Africa. The M1 geographic distribution and the relative ages of its different subclades clearly correlate with those of haplogroup U6, for which an Eurasian ancestor has been demonstrated. Conclusion This study provides evidence that M1, or its ancestor, had an Asiatic origin. The earliest M1 expansion into Africa occurred in northwestern instead of eastern areas; this early spread reached the Iberian Peninsula even affecting the Basques. The majority of the M1a lineages found outside and inside Africa had a more recent eastern Africa origin. Both western and eastern M1 lineages participated in the Neolithic colonization of the Sahara. The striking parallelism between subclade ages and geographic distribution of M1 and its North African U6 counterpart strongly reinforces this scenario. Finally, a relevant fraction of M1a lineages present today in the European Continent and nearby islands possibly had a Jewish instead of the commonly proposed Arab/Berber maternal ascendance. PMID:17620140

  11. Technical comment on "The placental mammal ancestor and the post-K-Pg radiation of placentals".

    PubMed

    Springer, Mark S; Meredith, Robert W; Teeling, Emma C; Murphy, William J

    2013-08-01

    O'Leary et al. (Research Article, 8 February 2013, p. 662) examined mammalian relationships and divergence times and concluded that a single placental ancestor crossed the Cretaceous-Paleogene (K-Pg) boundary. This conclusion relies on phylogenetic analyses that fail to discriminate between homology and homoplasy and further implies virus-like rates of nucleotide substitution in early Paleocene placentals. PMID:23929967

  12. Continuity or discontinuity in the European Early Pleistocene human settlement: the Atapuerca evidence

    NASA Astrophysics Data System (ADS)

    Bermúdez de Castro, José María; Martinón-Torres, María; Blasco, Ruth; Rosell, Jordi; Carbonell, Eudald

    2013-09-01

    The nature, timing, pattern, favourable circumstances and impediments of the human occupation of the European continent during the Early Pleistocene are hot topics in Quaternary studies. In particular, the problem of the (dis) continuity of the settlement of Europe in this period is an important matter of discussion, which has been approached in the last decade from different points of view. The Gran Dolina (TD) and Sima del Elefante (TE) cave sites in the Sierra de Atapuerca, (Spain) include large and quasi-continuous stratigraphic sequences that stretch back from at least 1.2 million years ago (Ma) to the Matuyama/Brunhes boundary. The archaeological and paleontological record from these sites can help to test different hypotheses about the character of the human settlement in this region and period. Furthermore, the TD6 level has yielded a large collection of human fossil remains attributed to Homo antecessor. According to different geochronological methods, as well as to paleomagnetic and biostratigraphical analyses, these hominins belong to an age range of 0.96-0.80 Ma. Unfortunately, the finding in 2007 of some human fossil remains in the TE9 level, dated to about 1.22 Ma, was not enough to conclude whether H. antecessor had deep roots in the European Early Pleistocene. A set of derived features of H. antecessor shared with both the Neanderthal lineage and modern humans suggests that this species is related, and not far, from the most recent common ancestor (MRCA) of Homo neanderthalensis and Homo sapiens. If we assume that there was a lineal biological relationship between the TE9 and TD6 hominins, we should reconsider many of the conclusions achieved in previous paleontological and genetic studies. In addition, we would be obliged to build a highly complicated paleogeographical scenario for the origin of the MRCA. Although continuity in the settlement of Europe during the entire late Early Pleistocene is not discarded (e.g. in refuge areas), it seems that

  13. The existence and abundance of ghost ancestors in biparental populations.

    PubMed

    Gravel, Simon; Steel, Mike

    2015-05-01

    In a randomly-mating biparental population of size N there are, with high probability, individuals who are genealogical ancestors of every extant individual within approximately log2(N) generations into the past. We use this result of J. Chang to prove a curious corollary under standard models of recombination: there exist, with high probability, individuals within a constant multiple of log2(N) generations into the past who are simultaneously (i) genealogical ancestors of each of the individuals at the present, and (ii) genetic ancestors to none of the individuals at the present. Such ancestral individuals-ancestors of everyone today that left no genetic trace-represent 'ghost' ancestors in a strong sense. In this short note, we use simple analytical argument and simulations to estimate how many such individuals exist in finite Wright-Fisher populations. PMID:25703300

  14. Teleoperation support for early human planetary missions.

    PubMed

    Genta, Giancarlo; Perino, Maria Antonietta

    2005-12-01

    A renewed interest in human exploration is flourishing among all the major spacefaring nations. In fact, in the complex scene of planned future space activities, the development of a Moon base and the human exploration of Mars might have the potential to renew the enthusiasm in expanding the human presence beyond the boundaries of Earth. Various initiatives have been undertaken to define scenarios and identify the required infrastructures and related technology innovations. The typical proposed approach follows a multistep strategy, starting with a series of precursor robotic missions to acquire further knowledge of the planet and to select the best potential landing sites, and evolving toward more demanding missions for the development of a surface infrastructure necessary to sustain human presence. The technologies involved in such a demanding enterprise range from typical space technologies, like transportation and propulsion, automation and robotics, rendezvous and docking, entry/reentry, aero-braking, navigation, and deep space communications, to human-specific issues like physiology, psychology, behavioral aspects, and nutritional science for long-duration exposure, that go beyond the traditional boundaries of space activities. Among the required elements to support planetary exploration, both for the precursor robotic missions and to sustain human exploration, rovers and trucks play a key role. A robust level of autonomy will need to be secured to perform preplanned operations, particularly for the surface infrastructure development, and a teleoperated support, either from Earth or from a local base, will enhance the in situ field exploration capability. PMID:16510414

  15. Human Granulocytic Ehrlichiosis Complicating Early Pregnancy

    PubMed Central

    Muffly, Tyler; McCormick, T. Chad; Cook, Christopher; Wall, Jeffrey

    2008-01-01

    Background. The goal of this case is to review the zoonotic infection, human granulocytic ehrlichiosis, presenting with pyrexia. Case. A 22-year-old multigravid female presented to the emergency department with a painful skin rash, high fever, and severe myalgias. The patient underwent a diagnostic evaluation for zoonotic infections due to her geographical and seasonal risk factors. Treatment of human granulocytic ehrlichiosis was successful though the patient spontaneously aborted presumably due to the severity of the acute illness. Conclusion. Treatment of human granulocytic ehrlichiosis in pregnancy presents unique challenges. Management of pyrexia during pregnancy is limited to external cooling in the setting of thrombocytopenia and elevated aminotransferases. Extensive counseling regarding teratogenic potential of medications allows the patient to weigh the pros and cons of treatment. PMID:18509484

  16. The Neurobiological Toll of Early Human Deprivation

    PubMed Central

    Nelson, Charles A.; Bos, Karen; Gunnar, Megan R.; Sonuga-Barke, Edmund J. S.

    2013-01-01

    Children raised in institutions frequently suffer from a variety of behavioral, emotional, and neuropsychological sequelae, including deficits in attention, executive functions, disorders of attachment and in some cases a syndrome that mimics autism. The extent and severity of these disorders appears to be mediated, in part, by the age at which the child entered and, in some cases, left the institution. Here we review the neurobiological literature on early institutionalization that may account for the psychological and neurological sequelae discussed in other chapters in this volume. PMID:25018565

  17. Young Children's Enactments of Human Rights in Early Childhood Education

    ERIC Educational Resources Information Center

    Quennerstedt, Ann

    2016-01-01

    This paper explores ways in which human rights become part of and affect young children's everyday practices in early childhood education and, more particularly, how very young children enact human rights in the preschool setting. The study is conducted in a Swedish preschool through observations of the everyday practices of a group of children…

  18. Algal ancestor of land plants was preadapted for symbiosis.

    PubMed

    Delaux, Pierre-Marc; Radhakrishnan, Guru V; Jayaraman, Dhileepkumar; Cheema, Jitender; Malbreil, Mathilde; Volkening, Jeremy D; Sekimoto, Hiroyuki; Nishiyama, Tomoaki; Melkonian, Michael; Pokorny, Lisa; Rothfels, Carl J; Sederoff, Heike Winter; Stevenson, Dennis W; Surek, Barbara; Zhang, Yong; Sussman, Michael R; Dunand, Christophe; Morris, Richard J; Roux, Christophe; Wong, Gane Ka-Shu; Oldroyd, Giles E D; Ané, Jean-Michel

    2015-10-27

    Colonization of land by plants was a major transition on Earth, but the developmental and genetic innovations required for this transition remain unknown. Physiological studies and the fossil record strongly suggest that the ability of the first land plants to form symbiotic associations with beneficial fungi was one of these critical innovations. In angiosperms, genes required for the perception and transduction of diffusible fungal signals for root colonization and for nutrient exchange have been characterized. However, the origin of these genes and their potential correlation with land colonization remain elusive. A comprehensive phylogenetic analysis of 259 transcriptomes and 10 green algal and basal land plant genomes, coupled with the characterization of the evolutionary path leading to the appearance of a key regulator, a calcium- and calmodulin-dependent protein kinase, showed that the symbiotic signaling pathway predated the first land plants. In contrast, downstream genes required for root colonization and their specific expression pattern probably appeared subsequent to the colonization of land. We conclude that the most recent common ancestor of extant land plants and green algae was preadapted for symbiotic associations. Subsequent improvement of this precursor stage in early land plants through rounds of gene duplication led to the acquisition of additional pathways and the ability to form a fully functional arbuscular mycorrhizal symbiosis. PMID:26438870

  19. Algal ancestor of land plants was preadapted for symbiosis

    PubMed Central

    Delaux, Pierre-Marc; Radhakrishnan, Guru V.; Jayaraman, Dhileepkumar; Cheema, Jitender; Malbreil, Mathilde; Volkening, Jeremy D.; Sekimoto, Hiroyuki; Nishiyama, Tomoaki; Melkonian, Michael; Pokorny, Lisa; Rothfels, Carl J.; Sederoff, Heike Winter; Stevenson, Dennis W.; Surek, Barbara; Zhang, Yong; Sussman, Michael R.; Dunand, Christophe; Morris, Richard J.; Roux, Christophe; Wong, Gane Ka-Shu; Oldroyd, Giles E. D.; Ané, Jean-Michel

    2015-01-01

    Colonization of land by plants was a major transition on Earth, but the developmental and genetic innovations required for this transition remain unknown. Physiological studies and the fossil record strongly suggest that the ability of the first land plants to form symbiotic associations with beneficial fungi was one of these critical innovations. In angiosperms, genes required for the perception and transduction of diffusible fungal signals for root colonization and for nutrient exchange have been characterized. However, the origin of these genes and their potential correlation with land colonization remain elusive. A comprehensive phylogenetic analysis of 259 transcriptomes and 10 green algal and basal land plant genomes, coupled with the characterization of the evolutionary path leading to the appearance of a key regulator, a calcium- and calmodulin-dependent protein kinase, showed that the symbiotic signaling pathway predated the first land plants. In contrast, downstream genes required for root colonization and their specific expression pattern probably appeared subsequent to the colonization of land. We conclude that the most recent common ancestor of extant land plants and green algae was preadapted for symbiotic associations. Subsequent improvement of this precursor stage in early land plants through rounds of gene duplication led to the acquisition of additional pathways and the ability to form a fully functional arbuscular mycorrhizal symbiosis. PMID:26438870

  20. The physiology and habitat of the last universal common ancestor.

    PubMed

    Weiss, Madeline C; Sousa, Filipa L; Mrnjavac, Natalia; Neukirchen, Sinje; Roettger, Mayo; Nelson-Sathi, Shijulal; Martin, William F

    2016-01-01

    The concept of a last universal common ancestor of all cells (LUCA, or the progenote) is central to the study of early evolution and life's origin, yet information about how and where LUCA lived is lacking. We investigated all clusters and phylogenetic trees for 6.1 million protein coding genes from sequenced prokaryotic genomes in order to reconstruct the microbial ecology of LUCA. Among 286,514 protein clusters, we identified 355 protein families (∼0.1%) that trace to LUCA by phylogenetic criteria. Because these proteins are not universally distributed, they can shed light on LUCA's physiology. Their functions, properties and prosthetic groups depict LUCA as anaerobic, CO2-fixing, H2-dependent with a Wood-Ljungdahl pathway, N2-fixing and thermophilic. LUCA's biochemistry was replete with FeS clusters and radical reaction mechanisms. Its cofactors reveal dependence upon transition metals, flavins, S-adenosyl methionine, coenzyme A, ferredoxin, molybdopterin, corrins and selenium. Its genetic code required nucleoside modifications and S-adenosyl methionine-dependent methylations. The 355 phylogenies identify clostridia and methanogens, whose modern lifestyles resemble that of LUCA, as basal among their respective domains. LUCA inhabited a geochemically active environment rich in H2, CO2 and iron. The data support the theory of an autotrophic origin of life involving the Wood-Ljungdahl pathway in a hydrothermal setting. PMID:27562259

  1. Human sexual size dimorphism in early pregnancy.

    PubMed

    Bukowski, Radek; Smith, Gordon C S; Malone, Fergal D; Ball, Robert H; Nyberg, David A; Comstock, Christine H; Hankins, Gary D V; Berkowitz, Richard L; Gross, Susan J; Dugoff, Lorraine; Craigo, Sabrina D; Timor-Tritsch, Ilan E; Carr, Stephen R; Wolfe, Honor M; D'Alton, Mary E

    2007-05-15

    Sexual size dimorphism is thought to contribute to the greater mortality and morbidity of men compared with women. However, the timing of onset of sexual size dimorphism remains uncertain. The authors determined whether human fetuses exhibit sexual size dimorphism in the first trimester of pregnancy. Using a prospective cohort study, conducted in 1999-2002 in the United States, they identified 27,655 women who conceived spontaneously and 1,008 whose conception was assisted by in vitro fertilization or intrauterine insemination and for whom a first-trimester measurement of fetal crown-rump length was available. First-trimester size was expressed as the difference between the observed and expected size of the fetus, expressed as equivalence to days of gestational age. The authors evaluated the association between fetal sex, first-trimester size, and birth weight. Eight to 12 weeks after conception, males were larger than females (mean difference: assisted conception = 0.4 days, 95% confidence interval (CI): 0.1, 0.7, p = 0.008; spontaneous conception = 0.3 days, 95% CI: 0.2, 0.4, p < 0.00001). The size discrepancy remained significant at birth (mean birth weight difference: assisted conception = 90 g, 95% CI: 22, 159, p = 0.009; spontaneous conception = 120 g, 95% CI: 107, 132, p < 0.00001). These data demonstrate that human fetuses exhibit sexual size dimorphism in the first trimester of pregnancy. PMID:17344203

  2. Palmitic Acid in Early Human Development.

    PubMed

    Innis, Sheila M

    2016-09-01

    Palmitic acid (16:0) is a saturated fatty acid present in the diet and synthesized endogenously. Although often considered to have adverse effects on chronic disease in adults, 16:0 is an essential component of membrane, secretory, and transport lipids, with crucial roles in protein palmitoylation and signal molecules. At birth, the term infant is 13-15% body fat, with 45-50% 16:0, much of which is derived from endogenous synthesis in the fetus. After birth, the infant accumulates adipose tissue at high rates, reaching 25% body weight as fat by 4-5 months age. Over this time, human milk provides 10% dietary energy as 16:0, but in unusual triglycerides with 16:0 on the glycerol center carbon. This paper reviews the synthesis and oxidation of 16:0 and possible reasons why the infant is endowed with large amounts of fat and 16:0. The marked deviations in tissues with displacement of 16:0 that can occur in infants fed vegetable oil formulas is introduced. Assuming fetal fatty acid synthesis and the unusual delivery of 16:0 in human milk evolved to afford survival advantage to the neonate, it is timely to question if 16:0 is an essential component of tissue lipids whereby both deficiency and excess are detrimental. PMID:25764297

  3. U.S. Human Immunodeficiency Virus Type 1 Epidemic: Date of Origin, Population History, and Characterization of Early Strains

    PubMed Central

    Robbins, Kenneth E.; Lemey, Philippe; Pybus, Oliver G.; Jaffe, Harold W.; Youngpairoj, Ae S.; Brown, Teresa M.; Salemi, Marco; Vandamme, Anne-Mieke; Kalish, Marcia L.

    2003-01-01

    Human immunodeficiency virus (HIV) type 1 subtype B sequences (whole envelope and the p17 region of gag) were obtained from peripheral blood mononuclear cell samples collected in 1981 from seven HIV-infected U.S. individuals and in 1982 from one infected Canadian resident. Phylogenetic and nucleotide distance analyses were performed by using database sequences representing North American strains collected from 1978 to 1995. The estimated phylogeny was starlike, with early strains represented on different lineages. When sequences were grouped by years of collection, nucleotide distance comparisons demonstrated an increase in diversity over time and indicated that contemporary strains are more closely related to early epidemic strains than to each other. Using a recently developed likelihood ratio reduction procedure, the date of origin of the U.S. epidemic was estimated to be 1968 ± 1.4 years. A coalescent approach was also used to estimate the population history of the U.S. subtype B epidemic. Our analyses provide new information that implies an exponential growth rate from the beginning of the U.S. HIV epidemic. The dating results suggest a U.S. introduction date (or date of divergence from the most recent common ancestor) that precedes the date of the earliest known AIDS cases in the late 1970s. Furthermore, the estimated epidemic growth curve shows a period of exponential growth that preceded most of the early documented cases and also indicates a leveling of prevalence rates in the recent past. PMID:12743293

  4. Early NACA human computers at work

    NASA Technical Reports Server (NTRS)

    1949-01-01

    The women of the Computer Department at NACA High-Speed Flight Research Station are shown busy with test flight calculations. The computers under the direction of Roxanah Yancey were responsible for accurate calculations on the research test flights made at the Station. There were no mechanical computers at the station in 1949, but data was reduced by human computers. Shown in this photograph starting at the left are: Geraldine Mayer and Mary (Tut) Hedgepeth with Friden calculators on the their desks; Emily Stephens conferring with engineer John Mayer; Gertrude (Trudy) Valentine is working on an oscillograph recording reducing the data from a flight. Across the desk is Dorothy Clift Hughes using a slide rule to complete data calculations. Roxanah Yancey completes the picture as she fills out engineering requests for further data.

  5. RNase MRP and the RNA processing cascade in the eukaryotic ancestor

    PubMed Central

    Woodhams, Michael D; Stadler, Peter F; Penny, David; Collins, Lesley J

    2007-01-01

    Background Within eukaryotes there is a complex cascade of RNA-based macromolecules that process other RNA molecules, especially mRNA, tRNA and rRNA. An example is RNase MRP processing ribosomal RNA (rRNA) in ribosome biogenesis. One hypothesis is that this complexity was present early in eukaryotic evolution; an alternative is that an initial simpler network later gained complexity by gene duplication in lineages that led to animals, fungi and plants. Recently there has been a rapid increase in support for the complexity-early theory because the vast majority of these RNA-processing reactions are found throughout eukaryotes, and thus were likely to be present in the last common ancestor of living eukaryotes, herein called the Eukaryotic Ancestor. Results We present an overview of the RNA processing cascade in the Eukaryotic Ancestor and investigate in particular, RNase MRP which was previously thought to have evolved later in eukaryotes due to its apparent limited distribution in fungi and animals and plants. Recent publications, as well as our own genomic searches, find previously unknown RNase MRP RNAs, indicating that RNase MRP has a wide distribution in eukaryotes. Combining secondary structure and promoter region analysis of RNAs for RNase MRP, along with analysis of the target substrate (rRNA), allows us to discuss this distribution in the light of eukaryotic evolution. Conclusion We conclude that RNase MRP can now be placed in the RNA-processing cascade of the Eukaryotic Ancestor, highlighting the complexity of RNA-processing in early eukaryotes. Promoter analyses of MRP-RNA suggest that regulation of the critical processes of rRNA cleavage can vary, showing that even these key cellular processes (for which we expect high conservation) show some species-specific variability. We present our consensus MRP-RNA secondary structure as a useful model for further searches. PMID:17288571

  6. Locomotion and posture from the common hominoid ancestor to fully modern hominins, with special reference to the last common panin/hominin ancestor

    PubMed Central

    Crompton, R H; Vereecke, E E; Thorpe, S K S

    2008-01-01

    Based on our knowledge of locomotor biomechanics and ecology we predict the locomotion and posture of the last common ancestors of (a) great and lesser apes and their close fossil relatives (hominoids); (b) chimpanzees, bonobos and modern humans (hominines); and (c) modern humans and their fossil relatives (hominins). We evaluate our propositions against the fossil record in the context of a broader review of evolution of the locomotor system from the earliest hominoids of modern aspect (crown hominoids) to early modern Homo sapiens. While some early East African stem hominoids were pronograde, it appears that the adaptations which best characterize the crown hominoids are orthogrady and an ability to abduct the arm above the shoulder – rather than, as is often thought, manual suspension sensu stricto. At 7–9 Ma (not much earlier than the likely 4–8 Ma divergence date for panins and hominins, see Bradley, 2008) there were crown hominoids in southern Europe which were adapted to moving in an orthograde posture, supported primarily on the hindlimb, in an arboreal, and possibly for Oreopithecus, a terrestrial context. By 7 Ma, Sahelanthropus provides evidence of a Central African hominin, panin or possibly gorilline adapted to orthogrady, and both orthogrady and habitually highly extended postures of the hip are evident in the arboreal East African protohominin Orrorin at 6 Ma. If the traditional idea that hominins passed through a terrestrial ‘knuckle-walking’ phase is correct, not only does it have to be explained how a quadrupedal gait typified by flexed postures of the hindlimb could have preadapted the body for the hominin acquisition of straight-legged erect bipedality, but we would have to accept a transition from stem-hominoid pronogrady to crown hominoid orthogrady, back again to pronogrady in the African apes and then back to orthogrady in hominins. Hand-assisted arboreal bipedality, which is part of a continuum of orthograde behaviours, is used by

  7. Direct dating of Early Upper Palaeolithic human remains from Mladec.

    PubMed

    Wild, Eva M; Teschler-Nicola, Maria; Kutschera, Walter; Steier, Peter; Trinkaus, Erik; Wanek, Wolfgang

    2005-05-19

    The human fossil assemblage from the Mladec Caves in Moravia (Czech Republic) has been considered to derive from a middle or later phase of the Central European Aurignacian period on the basis of archaeological remains (a few stone artefacts and organic items such as bone points, awls, perforated teeth), despite questions of association between the human fossils and the archaeological materials and concerning the chronological implications of the limited archaeological remains. The morphological variability in the human assemblage, the presence of apparently archaic features in some specimens, and the assumed early date of the remains have made this fossil assemblage pivotal in assessments of modern human emergence within Europe. We present here the first successful direct accelerator mass spectrometry radiocarbon dating of five representative human fossils from the site. We selected sample materials from teeth and from one bone for 14C dating. The four tooth samples yielded uncalibrated ages of approximately 31,000 14C years before present, and the bone sample (an ulna) provided an uncertain more-recent age. These data are sufficient to confirm that the Mladec human assemblage is the oldest cranial, dental and postcranial assemblage of early modern humans in Europe and is therefore central to discussions of modern human emergence in the northwestern Old World and the fate of the Neanderthals. PMID:15902255

  8. Indigenous Ways--Fruits of Our Ancestors

    ERIC Educational Resources Information Center

    Cohn, Itamar

    2011-01-01

    In this paper the human-nature relationship is recognized as a major field of interest and a platform of ideas linked with it is explored. A "new" source to inform an alternative paradigm for outdoor education is proposed; it is millennia old, has roots all over the globe and is a living, breathing, and evolving tradition--indigenous ways. While…

  9. Population Dynamics of Early Human Migration in Britain

    PubMed Central

    Vahia, Mayank N.; Ladiwala, Uma; Mahathe, Pavan; Mathur, Deepak

    2016-01-01

    Background Early human migration is largely determined by geography and human needs. These are both deterministic parameters when small populations move into unoccupied areas where conflicts and large group dynamics are not important. The early period of human migration into the British Isles provides such a laboratory which, because of its relative geographical isolation, may allow some insights into the complex dynamics of early human migration and interaction. Method and Results We developed a simulation code based on human affinity to habitable land, as defined by availability of water sources, altitude, and flatness of land, in choosing the path of migration. Movement of people on the British island over the prehistoric period from their initial entry points was simulated on the basis of data from the megalithic period. Topographical and hydro-shed data from satellite databases was used to define habitability, based on distance from water bodies, flatness of the terrain, and altitude above sea level. We simulated population movement based on assumptions of affinity for more habitable places, with the rate of movement tempered by existing populations. We compared results of our computer simulations with genetic data and show that our simulation can predict fairly accurately the points of contacts between different migratory paths. Such comparison also provides more detailed information about the path of peoples’ movement over ~2000 years before the present era. Conclusions We demonstrate an accurate method to simulate prehistoric movements of people based upon current topographical satellite data. Our findings are validated by recently-available genetic data. Our method may prove useful in determining early human population dynamics even when no genetic information is available. PMID:27148959

  10. Early development of synchrony in cortical activations in the human

    PubMed Central

    Koolen, N.; Dereymaeker, A.; Räsänen, O.; Jansen, K.; Vervisch, J.; Matic, V.; Naulaers, G.; De Vos, M.; Van Huffel, S.; Vanhatalo, S.

    2016-01-01

    Early intermittent cortical activity is thought to play a crucial role in the growth of neuronal network development, and large scale brain networks are known to provide the basis for higher brain functions. Yet, the early development of the large scale synchrony in cortical activations is unknown. Here, we tested the hypothesis that the early intermittent cortical activations seen in the human scalp EEG show a clear developmental course during the last trimester of pregnancy, the period of intensive growth of cortico-cortical connections. We recorded scalp EEG from altogether 22 premature infants at post-menstrual age between 30 and 44 weeks, and the early cortical synchrony was quantified using recently introduced activation synchrony index (ASI). The developmental correlations of ASI were computed for individual EEG signals as well as anatomically and mathematically defined spatial subgroups. We report two main findings. First, we observed a robust and statistically significant increase in ASI in all cortical areas. Second, there were significant spatial gradients in the synchrony in fronto-occipital and left-to-right directions. These findings provide evidence that early cortical activity is increasingly synchronized across the neocortex. The ASI-based metrics introduced in our work allow direct translational comparison to in vivo animal models, as well as hold promise for implementation as a functional developmental biomarker in future research on human neonates. PMID:26876605

  11. Early development of synchrony in cortical activations in the human.

    PubMed

    Koolen, N; Dereymaeker, A; Räsänen, O; Jansen, K; Vervisch, J; Matic, V; Naulaers, G; De Vos, M; Van Huffel, S; Vanhatalo, S

    2016-05-13

    Early intermittent cortical activity is thought to play a crucial role in the growth of neuronal network development, and large scale brain networks are known to provide the basis for higher brain functions. Yet, the early development of the large scale synchrony in cortical activations is unknown. Here, we tested the hypothesis that the early intermittent cortical activations seen in the human scalp EEG show a clear developmental course during the last trimester of pregnancy, the period of intensive growth of cortico-cortical connections. We recorded scalp EEG from altogether 22 premature infants at post-menstrual age between 30 and 44weeks, and the early cortical synchrony was quantified using recently introduced activation synchrony index (ASI). The developmental correlations of ASI were computed for individual EEG signals as well as anatomically and mathematically defined spatial subgroups. We report two main findings. First, we observed a robust and statistically significant increase in ASI in all cortical areas. Second, there were significant spatial gradients in the synchrony in fronto-occipital and left-to-right directions. These findings provide evidence that early cortical activity is increasingly synchronized across the neocortex. The ASI-based metrics introduced in our work allow direct translational comparison to in vivo animal models, as well as hold promise for implementation as a functional developmental biomarker in future research on human neonates. PMID:26876605

  12. Early diagnosis and testing for human immunodeficiency virus.

    PubMed

    Hesman, Amanda

    2016-06-01

    Human immunodeficiency virus (HIV) is now considered a long-term condition. However, HIV can only become a long-term condition if it is diagnosed early and antiretroviral therapy is commenced immediately. Individuals with HIV who are diagnosed late have an increased risk of death in the year after diagnosis compared to those diagnosed promptly. This article outlines HIV testing policy in the UK, the importance of the early diagnosis of HIV, the barriers to HIV testing, and how to offer testing in a range of settings. PMID:27286626

  13. Telomerase Activity is Downregulated Early During Human Brain Development.

    PubMed

    Ishaq, Abbas; Hanson, Peter S; Morris, Christopher M; Saretzki, Gabriele

    2016-01-01

    Changes in hTERT splice variant expression have been proposed to facilitate the decrease of telomerase activity during fetal development in various human tissues. Here, we analyzed the expression of telomerase RNA (hTR), wild type and α-spliced hTERT in developing human fetal brain (post conception weeks, pcw, 6-19) and in young and old cortices using qPCR and correlated it to telomerase activity measured by TRAP assay. Decrease of telomerase activity occurred early during brain development and correlated strongest to decreased hTR expression. The expression of α-spliced hTERT increased between pcw 10 and 19, while that of wild type hTERT remained unchanged. Lack of expression differences between young and old cortices suggests that most changes seem to occur early during human brain development. Using in vitro differentiation of neural precursor stem cells (NPSCs) derived at pcw 6 we found a decrease in telomerase activity but no major expression changes in telomerase associated genes. Thus, they do not seem to model the mechanisms for the decrease in telomerase activity in fetal brains. Our results suggest that decreased hTR levels, as well as transient increase in α-spliced hTERT, might both contribute to downregulation of telomerase activity during early human brain development between 6 and 17 pcw. PMID:27322326

  14. Telomerase Activity is Downregulated Early During Human Brain Development

    PubMed Central

    Ishaq, Abbas; Hanson, Peter S.; Morris, Christopher M.; Saretzki, Gabriele

    2016-01-01

    Changes in hTERT splice variant expression have been proposed to facilitate the decrease of telomerase activity during fetal development in various human tissues. Here, we analyzed the expression of telomerase RNA (hTR), wild type and α-spliced hTERT in developing human fetal brain (post conception weeks, pcw, 6–19) and in young and old cortices using qPCR and correlated it to telomerase activity measured by TRAP assay. Decrease of telomerase activity occurred early during brain development and correlated strongest to decreased hTR expression. The expression of α-spliced hTERT increased between pcw 10 and 19, while that of wild type hTERT remained unchanged. Lack of expression differences between young and old cortices suggests that most changes seem to occur early during human brain development. Using in vitro differentiation of neural precursor stem cells (NPSCs) derived at pcw 6 we found a decrease in telomerase activity but no major expression changes in telomerase associated genes. Thus, they do not seem to model the mechanisms for the decrease in telomerase activity in fetal brains. Our results suggest that decreased hTR levels, as well as transient increase in α-spliced hTERT, might both contribute to downregulation of telomerase activity during early human brain development between 6 and 17 pcw. PMID:27322326

  15. Origins and early development of human body knowledge.

    PubMed

    Slaughter, Virginia; Heron, Michelle

    2004-01-01

    As a knowable object, the human body is highly complex. Evidence from several converging lines of research, including psychological studies, neuroimaging and clinical neuropsychology, indicates that human body knowledge is widely distributed in the adult brain, and is instantiated in at least three partially independent levels of representation. Sensorimotor body knowledge is responsible for on-line control and movement of one's own body and may also contribute to the perception of others' moving bodies; visuo-spatial body knowledge specifies detailed structural descriptions of the spatial attributes of the human body; and lexical-semantic body knowledge contains language-based knowledge about the human body. In the first chapter of this Monograph, we outline the evidence for these three hypothesized levels of human body knowledge, then review relevant literature on infants' and young children's human body knowledge in terms of the three-level framework. In Chapters II and III, we report two complimentary series of studies that specifically investigate the emergence of visuo-spatial body knowledge in infancy. Our technique is to compare infants'responses to typical and scrambled human bodies, in order to evaluate when and how infants acquire knowledge about the canonical spatial layout of the human body. Data from a series of visual habituation studies indicate that infants first discriminate scrambled from typical human body picture sat 15 to 18 months of age. Data from object examination studies similarly indicate that infants are sensitive to violations of three-dimensional human body stimuli starting at 15-18 months of age. The overall pattern of data supports several conclusions about the early development of human body knowledge: (a) detailed visuo-spatial knowledge about the human body is first evident in the second year of life, (b) visuo-spatial knowledge of human faces and human bodies are at least partially independent in infancy and (c) infants' initial

  16. Developmental atlas of the early first trimester human embryo.

    PubMed

    Yamada, Shigehito; Samtani, Rajeev R; Lee, Elaine S; Lockett, Elizabeth; Uwabe, Chigako; Shiota, Kohei; Anderson, Stasia A; Lo, Cecilia W

    2010-06-01

    Rapid advances in medical imaging are facilitating the clinical assessment of first-trimester human embryos at increasingly earlier stages. To obtain data on early human development, we used magnetic resonance (MR) imaging and episcopic fluorescence capture (EFIC) to acquire digital images of human embryos spanning the time of dynamic tissue remodeling and organogenesis (Carnegie stages 13 to 23). These imaging data sets are readily resectioned digitally in arbitrary planes, suitable for rapid high-resolution three-dimensional (3D) observation. Using these imaging datasets, a web-accessible digital Human Embryo Atlas (http://apps.devbio.pitt.edu/humanatlas/) was created containing serial 2D images of human embryos in three standard histological planes: sagittal, frontal, and transverse. In addition, annotations and 3D reconstructions were generated for visualizing different anatomical structures. Overall, this Human Embryo Atlas is a unique resource that provides morphologic data of human developmental anatomy that can accelerate basic research investigations into developmental mechanisms that underlie human congenital anomalies. PMID:20503356

  17. Autophagy in Normal and Abnormal Early Human Pregnancies.

    PubMed

    Avagliano, Laura; Terraneo, Laura; Virgili, Eleonora; Martinelli, Carla; Doi, Patrizia; Samaja, Michele; Bulfamante, Gaetano Pietro; Marconi, Anna Maria

    2015-07-01

    Autophagy is an inducible catabolic process by which cells degrade and recycle materials to survive stress, starvation, and hypoxia. The aim of this study was to evaluate autophagy at the fetal-maternal interface, to assess autophagy involvement during the early phase of human gestation, and to explore autophagic modification in case of early abnormal pregnancy outcome. Specimens were collected from first-trimester normal gestations undergoing legal termination of pregnancy and first-trimester sporadic spontaneous miscarriages. Autophagy was studied in villous and decidual samples by transmission electron microscopy, immunohistochemistry, immunofluorescence, and Western blotting. Autophagy markers were found in cytotrophoblast, syncytiotrophoblast, extravillous trophoblast, and decidual stromal cells. Autophagy is physiologically involved in early normal gestation. Compared with normal pregnancy, spontaneous miscarriage presents an increase in autophagy expression in villous specimens due to an increment in concentration of autophagic vacuole in syncytiotrophoblast, suggesting a cytoprotective mechanism of the cells to respond to microenvironmental challenge. PMID:25544676

  18. European early modern humans and the fate of the Neandertals

    PubMed Central

    Trinkaus, Erik

    2007-01-01

    A consideration of the morphological aspects of the earliest modern humans in Europe (more than ≈33,000 B.P.) and the subsequent Gravettian human remains indicates that they possess an anatomical pattern congruent with the autapomorphic (derived) morphology of the earliest (Middle Paleolithic) African modern humans. However, they exhibit a variable suite of features that are either distinctive Neandertal traits and/or plesiomorphic (ancestral) aspects that had been lost among the African Middle Paleolithic modern humans. These features include aspects of neurocranial shape, basicranial external morphology, mandibular ramal and symphyseal form, dental morphology and size, and anteroposterior dental proportions, as well as aspects of the clavicles, scapulae, metacarpals, and appendicular proportions. The ubiquitous and variable presence of these morphological features in the European earlier modern human samples can only be parsimoniously explained as a product of modest levels of assimilation of Neandertals into early modern human populations as the latter dispersed across Europe. This interpretation is in agreement with current analyses of recent and past human molecular data. PMID:17452632

  19. The Ancestor Project: Aboriginal Computer Education through Storytelling

    ERIC Educational Resources Information Center

    Weston, Marla; Biin, Dianne

    2013-01-01

    The goal of the ANCESTOR program is to use digital storytelling as a means of promoting an interest in technology careers for Aboriginal learners, as well as increasing cultural literacy. A curriculum was developed and first tested with Aboriginal students at the LÁU,WELNEW Tribal School near Victoria, British Columbia, Canada. Based on feedback…

  20. On the tool use behavior of the bonobo-chimpanzee last common ancestor, and the origins of hominine stone tool use.

    PubMed

    Haslam, Michael

    2014-10-01

    The last common ancestor (LCA) shared by chimpanzees (Pan troglodytes) and bonobos (P. paniscus) was an Early Pleistocene African ape, which, based on the behavior of modern chimpanzees, may be assumed to be a tool-using animal. However, the character of tool use in the Pan lineage prior to the 20th century is largely unknown. Here, I use available data on wild bonobo tool use and emerging molecular estimates of demography during Pan evolution to hypothesise the plausible tool use behavior of the bonobo-chimpanzee LCA (or "Pancestor") at the start of the Pleistocene, over 2 million years ago. This method indicates that the common ancestor of living Pan apes likely used plant tools for probing, sponging, and display, but it did not use stone tools. Instead, stone tool use appears to have been independently invented by Western African chimpanzees (P. t. verus) during the Middle Pleistocene in the region of modern Liberia-Ivory Coast-Guinea, possibly as recently as 200,000-150,000 years ago. If this is the case, then the LCA of humans and chimpanzees likely also did not use stone tools, and this trait probably first emerged among hominins in Pliocene East Africa. This review also suggests that the consistently higher population sizes of Central African chimpanzees (P. t. troglodytes) over the past million years may have contributed to the increased complexity of wild tool use seen in this sub-species today. PMID:24710771

  1. Diversity of the Human Skin Microbiome Early in Life

    PubMed Central

    Capone, Kimberly A; Dowd, Scot E; Stamatas, Georgios N; Nikolovski, Janeta

    2011-01-01

    Within days after birth, rapid surface colonization of infant skin coincides with significant functional changes. Gradual maturation of skin function, structure, and composition continues throughout the first years of life. Recent reports have revealed topographical and temporal variations in the adult skin microbiome. Here we address the question of how the human skin microbiome develops early in life. We show that the composition of cutaneous microbial communities evolves over the first year of life, showing increasing diversity with age. Although early colonization is dominated by Staphylococci, their significant decline contributes to increased population evenness by the end of the first year. Similar to what has been shown in adults, the composition of infant skin microflora appears to be site specific. In contrast to adults, we find that Firmicutes predominate on infant skin. Timely and proper establishment of healthy skin microbiome during this early period might have a pivotal role in denying access to potentially infectious microbes and could affect microbiome composition and stability extending into adulthood. Bacterial communities contribute to the establishment of cutaneous homeostasis and modulate inflammatory responses. Early microbial colonization is therefore expected to critically affect the development of the skin immune function. PMID:21697884

  2. The Human Microbiome. Early Life Determinant of Health Outcomes

    PubMed Central

    2014-01-01

    The development of new technologies to isolate and identify microbial genomes has markedly increased our understanding of the role of microbiomes in health and disease. The idea, first proposed as part of the hygiene hypothesis, that environmental microbes influence the developmental trajectories of the immune system in early life, has now been considerably extended and refined. The abundant microbiota present in mucosal surfaces, especially the gut, is actively selected by the host through complex receptor systems that respond differentially depending on the molecular patterns presented to mucosal cells. Germ-free mice are more likely to develop allergic airway inflammation and show alterations in normal motor control and anxiety. These effects can be reversed by neonatal microbial recolonization but remain unchanged if recolonization occurs in adults. What emerges from these recent studies is the discovery of a complex, major early environmental determinant of lifetime human phenotypes. To change the natural course of asthma, obesity, and other chronic inflammatory conditions, active manipulation of the extensive bacterial, phage, and fungal metagenomes present in mucosal surfaces may be required, specifically during the developing years. Domesticating the human microbiome and adapting it to our health needs may be a challenge akin to, but far more complex than, the one faced by humanity when a few dozen species of plants and animals were domesticated during the transition between hunter-gatherer and sedentary societies after the end of the Pleistocene era. PMID:24437411

  3. The human microbiome. Early life determinant of health outcomes.

    PubMed

    Martinez, Fernando D

    2014-01-01

    The development of new technologies to isolate and identify microbial genomes has markedly increased our understanding of the role of microbiomes in health and disease. The idea, first proposed as part of the hygiene hypothesis, that environmental microbes influence the developmental trajectories of the immune system in early life, has now been considerably extended and refined. The abundant microbiota present in mucosal surfaces, especially the gut, is actively selected by the host through complex receptor systems that respond differentially depending on the molecular patterns presented to mucosal cells. Germ-free mice are more likely to develop allergic airway inflammation and show alterations in normal motor control and anxiety. These effects can be reversed by neonatal microbial recolonization but remain unchanged if recolonization occurs in adults. What emerges from these recent studies is the discovery of a complex, major early environmental determinant of lifetime human phenotypes. To change the natural course of asthma, obesity, and other chronic inflammatory conditions, active manipulation of the extensive bacterial, phage, and fungal metagenomes present in mucosal surfaces may be required, specifically during the developing years. Domesticating the human microbiome and adapting it to our health needs may be a challenge akin to, but far more complex than, the one faced by humanity when a few dozen species of plants and animals were domesticated during the transition between hunter-gatherer and sedentary societies after the end of the Pleistocene era. PMID:24437411

  4. Ecosystem variability and early human habitats in eastern Africa.

    PubMed

    Magill, Clayton R; Ashley, Gail M; Freeman, Katherine H

    2013-01-22

    The role of savannas during the course of early human evolution has been debated for nearly a century, in part because of difficulties in characterizing local ecosystems from fossil and sediment records. Here, we present high-resolution lipid biomarker and isotopic signatures for organic matter preserved in lake sediments at Olduvai Gorge during a key juncture in human evolution about 2.0 Ma--the emergence and dispersal of Homo erectus (sensu lato). Using published data for modern plants and soils, we construct a framework for ecological interpretations of stable carbon-isotope compositions (expressed as δ(13)C values) of lipid biomarkers from ancient plants. Within this framework, δ(13)C values for sedimentary leaf lipids and total organic carbon from Olduvai Gorge indicate recurrent ecosystem variations, where open C(4) grasslands abruptly transitioned to closed C(3) forests within several hundreds to thousands of years. Carbon-isotopic signatures correlate most strongly with Earth's orbital geometry (precession), and tropical sea-surface temperatures are significant secondary predictors in partial regression analyses. The scale and pace of repeated ecosystem variations at Olduvai Gorge contrast with long-held views of directional or stepwise aridification and grassland expansion in eastern Africa during the early Pleistocene and provide a local perspective on environmental hypotheses of human evolution. PMID:23267092

  5. Ecosystem variability and early human habitats in eastern Africa

    PubMed Central

    Magill, Clayton R.; Ashley, Gail M.; Freeman, Katherine H.

    2013-01-01

    The role of savannas during the course of early human evolution has been debated for nearly a century, in part because of difficulties in characterizing local ecosystems from fossil and sediment records. Here, we present high-resolution lipid biomarker and isotopic signatures for organic matter preserved in lake sediments at Olduvai Gorge during a key juncture in human evolution about 2.0 Ma—the emergence and dispersal of Homo erectus (sensu lato). Using published data for modern plants and soils, we construct a framework for ecological interpretations of stable carbon-isotope compositions (expressed as δ13C values) of lipid biomarkers from ancient plants. Within this framework, δ13C values for sedimentary leaf lipids and total organic carbon from Olduvai Gorge indicate recurrent ecosystem variations, where open C4 grasslands abruptly transitioned to closed C3 forests within several hundreds to thousands of years. Carbon-isotopic signatures correlate most strongly with Earth’s orbital geometry (precession), and tropical sea-surface temperatures are significant secondary predictors in partial regression analyses. The scale and pace of repeated ecosystem variations at Olduvai Gorge contrast with long-held views of directional or stepwise aridification and grassland expansion in eastern Africa during the early Pleistocene and provide a local perspective on environmental hypotheses of human evolution. PMID:23267092

  6. Early gait development in human infants: Plasticity and clinical applications.

    PubMed

    Teulier, Caroline; Lee, Do Kyeong; Ulrich, Beverly D

    2015-05-01

    In this paper we focus on how a developmental perspective on plasticity in the control of human movement can promote early therapy and improve gait acquisition in infants with developmental disabilities. Current knowledge about stepping development in healthy infants across the first year of life highlights strong plasticity, both in behavioral outcome and in underlying neuro-muscular activation. These data show that stepping, like other motor skills, emerges from the interaction between infant's maturation and the environment. This view is reinforced by showing that infants with different internal resources (like genetic disorder or neural tube defect) show unique developmental trajectories when supported on a treadmill, yet do respond. Moreover, we will show that their behavior can be improved by context manipulations (mostly sensory stimulation) or practice. Overall, plasticity in the neural, skeletal, and muscle tissues create new opportunities for optimizing early intervention by creatively tapping into the same developmental processes experienced by healthy infants. PMID:25782975

  7. An early history of human breast cancer: West meets East

    PubMed Central

    Yan, Shou-He

    2013-01-01

    Cancer has been increasingly recognized as a global issue. This is especially true in countries like China, where cancer incidence has increased likely because of changes in environment and lifestyle. However, cancer is not a modern disease; early cases have been recorded in ancient medical books in the West and in China. Here, we provide a brief history of cancer, focusing on cancer of the breast, and review the etymology of ai, the Chinese character for cancer. Notable findings from both Western and Chinese traditional medicine are presented to give an overview of the most important, early contributors to our evolving understanding of human breast cancer. We also discuss the earliest historical documents to record patients with breast cancer. PMID:23958056

  8. An early modern human from Tianyuan Cave, Zhoukoudian, China

    PubMed Central

    Shang, Hong; Tong, Haowen; Zhang, Shuangquan; Chen, Fuyou; Trinkaus, Erik

    2007-01-01

    Thirty-four elements of an early modern human (EMH) were found in Tianyuan Cave, Zhoukoudian, China in 2003. Dated to 42,000–39,000 calendrical years before present by using direct accelerator mass spectrometry radiocarbon, the Tianyuan 1 skeleton is among the oldest directly dated EMHs in eastern Eurasia. Morphological comparison shows Tianyuan 1 to have a series of derived modern human characteristics, including a projecting tuber symphyseos, a high anterior symphyseal angle, a broad scapular glenoid fossa, a reduced hamulus, a gluteal buttress, and a pilaster on the femora. Other features of Tianyuan 1 that are more common among EMHs are its modest humeral pectoralis major tuberosities, anteriorly rotated radial tuberosity, reduced radial curvature, and modest talar trochlea. It also lacks several mandibular features common among western Eurasian late archaic humans, including mandibular foramen bridging, mandibular notch asymmetry, and a large superior medial pterygoid tubercle. However, Tianyuan 1 exhibits several late archaic human features, such as its anterior to posterior dental proportions, a large hamulus length, and a broad and rounded distal phalangeal tuberosity. This morphological pattern implies that a simple spread of modern humans from Africa is unlikely. PMID:17416672

  9. Water, plants, and early human habitats in eastern Africa.

    PubMed

    Magill, Clayton R; Ashley, Gail M; Freeman, Katherine H

    2013-01-22

    Water and its influence on plants likely exerted strong adaptive pressures in human evolution. Understanding relationships among water, plants, and early humans is limited both by incomplete terrestrial records of environmental change and by indirect proxy data for water availability. Here we present a continuous record of stable hydrogen-isotope compositions (expressed as δD values) for lipid biomarkers preserved in lake sediments from an early Pleistocene archaeological site in eastern Africa--Olduvai Gorge. We convert sedimentary leaf- and algal-lipid δD values into estimates for ancient source-water δD values by accounting for biochemical, physiological, and environmental influences on isotopic fractionation via published water-lipid enrichment factors for living plants, algae, and recent sediments. Reconstructed precipitation and lake-water δD values, respectively, are consistent with modern isotopic hydrology and reveal that dramatic fluctuations in water availability accompanied ecosystem changes. Drier conditions, indicated by less negative δD values, occur in association with stable carbon-isotopic evidence for open, C(4)-dominated grassland ecosystems. Wetter conditions, indicated by lower δD values, are associated with expanded woody cover across the ancient landscape. Estimates for ancient precipitation amounts, based on reconstructed precipitation δD values, range between approximately 250 and 700 mm · y(-1) and are consistent with modern precipitation data for eastern Africa. We conclude that freshwater availability exerted a substantial influence on eastern African ecosystems and, by extension, was central to early human proliferation during periods of rapid climate change. PMID:23267102

  10. Water, plants, and early human habitats in eastern Africa

    PubMed Central

    Magill, Clayton R.; Ashley, Gail M.; Freeman, Katherine H.

    2013-01-01

    Water and its influence on plants likely exerted strong adaptive pressures in human evolution. Understanding relationships among water, plants, and early humans is limited both by incomplete terrestrial records of environmental change and by indirect proxy data for water availability. Here we present a continuous record of stable hydrogen-isotope compositions (expressed as δD values) for lipid biomarkers preserved in lake sediments from an early Pleistocene archaeological site in eastern Africa—Olduvai Gorge. We convert sedimentary leaf- and algal-lipid δD values into estimates for ancient source-water δD values by accounting for biochemical, physiological, and environmental influences on isotopic fractionation via published water–lipid enrichment factors for living plants, algae, and recent sediments. Reconstructed precipitation and lake-water δD values, respectively, are consistent with modern isotopic hydrology and reveal that dramatic fluctuations in water availability accompanied ecosystem changes. Drier conditions, indicated by less negative δD values, occur in association with stable carbon-isotopic evidence for open, C4-dominated grassland ecosystems. Wetter conditions, indicated by lower δD values, are associated with expanded woody cover across the ancient landscape. Estimates for ancient precipitation amounts, based on reconstructed precipitation δD values, range between approximately 250 and 700 mm·y−1 and are consistent with modern precipitation data for eastern Africa. We conclude that freshwater availability exerted a substantial influence on eastern African ecosystems and, by extension, was central to early human proliferation during periods of rapid climate change. PMID:23267102

  11. Debatable questions of Siberia settlement by early humans

    NASA Astrophysics Data System (ADS)

    Kuzmin, Ya. V.; Kazanskii, A. Yu.

    2015-01-01

    Data on the age and natural environment of earliest archaeological sites in Siberia are critically analyzed. Particular attention is paid to the Karama site in the Altai Mountains, whose age was earlier estimated at about 1.77-1.95 Ma. The combination of geological, geomorphological, sedimentological, palynological, and paleomagnetic data makes it possible to determine the lower limit of the age of this object at only about 800 ka. Judging by the results of a preliminary study of the Zasukhino site in Trans-Baikal, early humans could have appeared in Siberia about 1 million years ago, but additional research is required in order to obtain reliable information.

  12. Facilitated early cortical processing of nude human bodies.

    PubMed

    Alho, Jussi; Salminen, Nelli; Sams, Mikko; Hietanen, Jari K; Nummenmaa, Lauri

    2015-07-01

    Functional brain imaging has identified specialized neural systems supporting human body perception. Responses to nude vs. clothed bodies within this system are amplified. However, it remains unresolved whether nude and clothed bodies are processed by same cerebral networks or whether processing of nude bodies recruits additional affective and arousal processing areas. We recorded simultaneous MEG and EEG while participants viewed photographs of clothed and nude bodies. Global field power revealed a peak ∼145ms after stimulus onset to both clothed and nude bodies, and ∼205ms exclusively to nude bodies. Nude-body-sensitive responses were centered first (100-200ms) in the extrastriate and fusiform body areas, and subsequently (200-300ms) in affective-motivational areas including insula and anterior cingulate cortex. We conclude that visibility of sexual features facilitates early cortical processing of human bodies, the purpose of which is presumably to trigger sexual behavior and ultimately ensure reproduction. PMID:25960070

  13. Deciding Termination for Ancestor Match- Bounded String Rewriting Systems

    NASA Technical Reports Server (NTRS)

    Geser, Alfons; Hofbauer, Dieter; Waldmann, Johannes

    2005-01-01

    Termination of a string rewriting system can be characterized by termination on suitable recursively defined languages. This kind of termination criteria has been criticized for its lack of automation. In an earlier paper we have shown how to construct an automated termination criterion if the recursion is aligned with the rewrite relation. We have demonstrated the technique with Dershowitz's forward closure criterion. In this paper we show that a different approach is suitable when the recursion is aligned with the inverse of the rewrite relation. We apply this idea to Kurth's ancestor graphs and obtain ancestor match-bounded string rewriting systems. Termination is shown to be decidable for this class. The resulting method improves upon those based on match-boundedness or inverse match-boundedness.

  14. Photochemical etiology of promising ancestors of the RNA nucleobases.

    PubMed

    Brister, M M; Pollum, M; Crespo-Hernández, C E

    2016-07-27

    RNA is a product of chemical and biological evolution and the identification of its heterocyclic ancestors is essential for understanding the molecular origins of life. Among a diverse array of selection pressures thought to have shaped the composition of the nucleobases on prebiotic Earth, protection against intense ultraviolet radiation must have been essential. In this contribution, a detailed spectroscopic and photophysical investigation of barbituric acid and 2,4,6-triaminopyrimidine, two promising candidates for the prebiotic ancestors of RNA nucleobases, is presented in aqueous solution. It is shown that although these pyrimidine derivatives absorb ultraviolet radiation strongly, both compounds possess efficient electronic relaxation mechanisms for dissipating most of the absorbed ultraviolet energy to their aqueous environment as heat within hundreds of femtoseconds, thus safeguarding their chemical integrity. In fact, these two heterocyclic compounds rival the photostability observed in the canonical nucleobases in aqueous solution, thus supporting the recent proposal that both barbituric acid and 2,4,6-triaminopyrimidine are promising ancestors of the RNA nucleobases. PMID:26898746

  15. Early enteral feeding with human milk for VLBW infants.

    PubMed

    De Nisi, G; Berti, M; De Nisi, M; Bertino, E

    2012-01-01

    In a NICU early enteral feeding is usually possible only when the newborn clinical conditions permit it. Because of the frequent need of umbilical/central catheters, they usually start with parenteral feeding and/or with minimal enteral feeding (trophic feeding). This kind of management is even more frequent in VLBWIs, in which the risk of NEC is very high. In this work we describe a model of early enteral exclusive feeding (EEEF) based on the use of banking human milk followed by mother milk. In the Centre of Neonatology of Trento, as in other Centers, the newborns weighing less than 750g or with a GE< 27 weeks, are treated with parenteral nutrition and minimal enteral feeding. The newborn weighing 750-1249g and with GE > 26 weeks define a group in which we find critical neonates, who can not be treated with enteral feeding, and neonates whose clinical conditions permit EEEF. In particular, in a period of 16 years (1994-2009) in Trento, 308 newborns weighing 750-1249 g and GE > than 26 weeks were admitted. The 90,9 % has been treated with prenatal steroids, the 91,9 % was inborn, the 96,1% survived. In the 59,1 % of the cases (175) we gave EEEF. We could continue with a complete EEEF in the 40,2 % of the total (119 cases). The characteristics of these neonates and our centre management, based mainly on early use of banking human milk and mother milk, are detailed described. PMID:23158518

  16. Early Human Evolution in the Western Palaearctic: Ecological Scenarios

    NASA Astrophysics Data System (ADS)

    Carrión, José S.; Rose, James; Stringer, Chris

    2011-06-01

    This review presents the themes of a special issue dealing with environmental scenarios of human evolution during the Early Pleistocene (2.6-0.78 Ma; MIS 103-MIS 19) and early Middle Pleistocene (0.78-0.47 Ma; MIS 19-base of MIS 12) within the western Palaearctic. This period is one of dramatic changes in the climates and the distribution of Palaearctic biota. These changes have played their role in generating adaptive and phyletic patterns within the human ancestry, involving several species such as Homo habilis, "Homo georgicus", Homo erectus, Homo antecessor and Homo heidelbergensis. In the archaeological record, these species include the Oldowan (Mode 1) and Acheulian (Mode 2) lithic technologies. Taphonomic considerations of palaeoecological research in hominin-bearing sites are provided and evaluated. Syntheses are provided for north Africa, western Asia, the Mediterranean Basin, Britain, and continental Europe. Palaeoenvironmental reconstructions based on multidisciplinary data are given for Ain Boucherit, Ain Hanech and El-Kherba in Algeria, Dmanisi in Georgia, Atapuerca, Cueva Negra, and the Orce Basin in Spain, Monte Poggiolo and Pirro Nord in Italy, Pont-de-Lavaud in France, and Mauer in Germany. The state of the art with the Out of Africa 1 dispersal model is reviewed. A source-sink dynamics model for Palaeolithic Europe is described to explain the morphological disparity of H. heidelbergensis (we will sometimes use the informal name "Heidelbergs") and early Neanderthals. Other aspects debated here are the selective value of habitat mosaics including reconstructions based on mammal and avian databases, and the role of geological instability combined with topographic complexity. This review is completed by addressing the question of whether the appearance of evolutionary trends within hominins is concentrated in regions of highest worldwide biological diversity (biodiversity hotspots). It is concluded that the keys for the activation of evolutionary

  17. UVA Phototransduction Drives Early Melanin Synthesis in Human Melanocytes

    PubMed Central

    Wicks, Nadine L.; Chan, Jason W.; Najera, Julia A.; Ciriello, Jonathan M.; Oancea, Elena

    2013-01-01

    Summary Exposure of human skin to solar ultraviolet radiation (UVR), a powerful carcinogen [1] comprising ~95% UVA and ~5% UVB at the Earth’s surface, promotes melanin synthesis in epidermal melanocytes [2, 3], which protects skin from DNA damage [4, 5]. UVB causes DNA lesions [6] that lead to transcriptional activation of melanin-producing enzymes, resulting in delayed skin pigmentation within days [7]. In contrast, UVA causes primarily oxidative damage [8] and leads to immediate pigment darkening (IPD) within minutes, via an unknown mechanism [9, 10]. No receptor protein directly mediating phototransduction in skin has been identified. Here we demonstrate that exposure of primary human epidermal melanocytes (HEMs) to UVA causes calcium mobilization and early melanin synthesis. Calcium responses were abolished by treatment with G protein or PLC inhibitors, or by depletion of intracellular calcium stores. We show that the visual photopigment rhodopsin [11] is expressed in HEMs and contributes to UVR phototransduction. Upon UVR exposure, significant melanin production was measured within one hour; cellular melanin continued to increase in a retinal- and calcium-dependent manner up to five-fold after 24 hours. Our findings identify a novel UVA-sensitive signaling pathway in melanocytes that leads to calcium mobilization and melanin synthesis, and may underlie the mechanism of IPD in human skin. PMID:22055294

  18. Early Human Prostate Adenocarcinomas Harbor Androgen-Independent Cancer Cells

    PubMed Central

    Fiñones, Rita R.; Yeargin, Jo; Lee, Melissa; Kaur, Aman Preet; Cheng, Clari; Sun, Paulina; Wu, Christopher; Nguyen, Catherine; Wang-Rodriguez, Jessica; Meyer, April N.; Baird, Stephen M.; Donoghue, Daniel J.; Haas, Martin

    2013-01-01

    Although blockade of androgen receptor (AR) signaling represents the main treatment for advanced prostate cancer (PrCa), many patients progress to a lethal phenotype of “Castration-Resistant” prostate cancer (CR-PrCa). With the hypothesis that early PrCa may harbor a population of androgen-unresponsive cancer cells as precursors to CR-recurrent disease, we undertook the propagation of androgen-independent cells from PrCa-prostatectomy samples of early, localized (Stage-I) cases. A collection of 120 surgical specimens from prostatectomy cases was established, among which 54 were adenocarcinomas. Hormone-free cell culture conditions were developed allowing routine propagation of cells expressing prostate basal cell markers and stem/progenitor cell markers, and which proliferated as spheres/spheroids in suspension cultures. Colonies of androgen-independent epithelial cells grew out from 30/43 (70%) of the adenocarcinoma cases studied in detail. Fluorescence microscopy and flow cytometry showed that CR-PrCa cells were positive for CD44, CD133, CK5/14, c-kit, integrin α2β1, SSEA4, E-Cadherin and Aldehyde Dehydrogenase (ALDH). All 30 CR-PrCa cell cultures were also TERT-positive, but negative for TMPRSS2-ERG. Additionally, a subset of 22 of these CR-PrCa cell cultures was examined by orthotopic xenografting in intact and castrated SCID mice, generating histologically typical locally-invasive human PrCa or undifferentiated cancers, respectively, in 6–8 weeks. Cultured PrCa cells and orthotopically-induced in vivo cancers lacked PSA expression. We report here the propagation of Cancer Initiating Cells (CIC) directly from Stage I human PrCa tissue without selection or genetic manipulation. The propagation of stem/progenitor-like CR-PrCa cells derived from early human prostate carcinomas suggests the existence of a subpopulation of cells resistant to androgen-deprivation therapy and which may drive the subsequent emergence of disseminated CR-PrCa. PMID:24086346

  19. Buds from the tree of life: linking compartmentalized prokaryotes and eukaryotes by a non-hyperthermophile common ancestor and implications for understanding Archaean microbial communities

    NASA Astrophysics Data System (ADS)

    Fuerst, John A.; Nisbet, Euan G.

    2004-07-01

    The origin of the first nucleated eukaryote and the nature of the last common ancestor of the three domains of life are major questions in the evolutionary biology of cellular life on Earth, the solutions to which may be linked. Planctomycetes are unusual compartmentalized bacteria that include a membrane-bounded nucleoid. The possibility that they constitute a very deep branch of the domain Bacteria suggests a model for the evolution of the three domains of life from a last common ancestor that was a mesophile or moderate thermophile with a compartmentalized eukaryote-like cell plan. Planctomycetes and some members of the domain Archaea may have retained cell compartmentalization present in an original eukaryote-like last common ancestor of the three domains of life. The implications of this model for possible habitats of the early evolution of domains of cellular life and for interpretation of geological evidence relating to those habitats and the early emergence of life are examined here.

  20. Life cycle evolution: was the eumetazoan ancestor a holopelagic, planktotrophic gastraea?

    PubMed Central

    2013-01-01

    Background Two theories for the origin of animal life cycles with planktotrophic larvae are now discussed seriously: The terminal addition theory proposes a holopelagic, planktotrophic gastraea as the ancestor of the eumetazoans with addition of benthic adult stages and retention of the planktotrophic stages as larvae, i.e. the ancestral life cycles were indirect. The intercalation theory now proposes a benthic, deposit-feeding gastraea as the bilaterian ancestor with a direct development, and with planktotrophic larvae evolving independently in numerous lineages through specializations of juveniles. Results Information from the fossil record, from mapping of developmental types onto known phylogenies, from occurrence of apical organs, and from genetics gives no direct information about the ancestral eumetazoan life cycle; however, there are plenty of examples of evolution from an indirect development to direct development, and no unequivocal example of evolution in the opposite direction. Analyses of scenarios for the two types of evolution are highly informative. The evolution of the indirect spiralian life cycle with a trochophora larva from a planktotrophic gastraea is explained by the trochophora theory as a continuous series of ancestors, where each evolutionary step had an adaptational advantage. The loss of ciliated larvae in the ecdysozoans is associated with the loss of outer ciliated epithelia. A scenario for the intercalation theory shows the origin of the planktotrophic larvae of the spiralians through a series of specializations of the general ciliation of the juvenile. The early steps associated with the enhancement of swimming seem probable, but the following steps which should lead to the complicated downstream-collecting ciliary system are without any advantage, or even seem disadvantageous, until the whole structure is functional. None of the theories account for the origin of the ancestral deuterostome (ambulacrarian) life cycle. Conclusions All

  1. Early Trypanosoma cruzi Infection Reprograms Human Epithelial Cells

    PubMed Central

    Chiribao, María Laura; Libisch, Gabriela; Parodi-Talice, Adriana; Robello, Carlos

    2014-01-01

    Trypanosoma cruzi, the causative agent of Chagas disease, has the peculiarity, when compared with other intracellular parasites, that it is able to invade almost any type of cell. This property makes Chagas a complex parasitic disease in terms of prophylaxis and therapeutics. The identification of key host cellular factors that play a role in the T. cruzi invasion is important for the understanding of disease pathogenesis. In Chagas disease, most of the focus is on the response of macrophages and cardiomyocytes, since they are responsible for host defenses and cardiac lesions, respectively. In the present work, we studied the early response to infection of T. cruzi in human epithelial cells, which constitute the first barrier for establishment of infection. These studies identified up to 1700 significantly altered genes regulated by the immediate infection. The global analysis indicates that cells are literally reprogrammed by T. cruzi, which affects cellular stress responses (neutrophil chemotaxis, DNA damage response), a great number of transcription factors (including the majority of NFκB family members), and host metabolism (cholesterol, fatty acids, and phospholipids). These results raise the possibility that early host cell reprogramming is exploited by the parasite to establish the initial infection and posterior systemic dissemination. PMID:24812617

  2. mRNAs from human adenovirus 2 early region 4.

    PubMed Central

    Virtanen, A; Gilardi, P; Näslund, A; LeMoullec, J M; Pettersson, U; Perricaudet, M

    1984-01-01

    The molecular structure of the mRNAs from early region 4 of human adenovirus 2 has been studied by Northern blot analysis, S1 nuclease analysis, and sequence analysis of cDNA clones. The results make it possible to identify four different splice donor sites and six different splice acceptor sites. The structure of 12 different mRNAs can be deduced from the analysis. The mRNAs have identical 5' and 3' ends and are thus likely to be processed from a common mRNA precursor by differential splicing. The different mRNA species are formed by the removal of one to three introns, and they all carry a short 5' leader segment. The introns appear to serve two functions; they either place a 5' leader segment in juxtaposition with an open reading frame or fuse two open translational reading frames. The early region 4 mRNAs can encode at least seven unique polypeptides. Images PMID:6088804

  3. The early fetal development of human neocortical GABAergic interneurons.

    PubMed

    Al-Jaberi, Nahidh; Lindsay, Susan; Sarma, Subrot; Bayatti, Nadhim; Clowry, Gavin J

    2015-03-01

    GABAergic interneurons are crucial to controlling the excitability and responsiveness of cortical circuitry. Their developmental origin may differ between rodents and human. We have demonstrated the expression of 12 GABAergic interneuron-associated genes in samples from human neocortex by quantitative rtPCR from 8 to 12 postconceptional weeks (PCW) and shown a significant anterior to posterior expression gradient, confirmed by in situ hybridization or immunohistochemistry for GAD1 and 2, DLX1, 2, and 5, ASCL1, OLIG2, and CALB2. Following cortical plate (CP) formation from 8 to 9 PCW, a proportion of cells were strongly stained for all these markers in the CP and presubplate. ASCL1 and DLX2 maintained high expression in the proliferative zones and showed extensive immunofluorescent double-labeling with the cell division marker Ki-67. CALB2-positive cells increased steadily in the SVZ/VZ from 10 PCW but were not double-labeled with Ki-67. Expression of GABAergic genes was generally higher in the dorsal pallium than in the ganglionic eminences, with lower expression in the intervening ventral pallium. It is widely accepted that the cortical proliferative zones may generate CALB2-positive interneurons from mid-gestation; we now show that the anterior neocortical proliferative layers especially may be a rich source of interneurons in the early neocortex. PMID:24047602

  4. Mobile elements reveal small population size in the ancient ancestors of Homo sapiens

    PubMed Central

    Huff, Chad D.; Xing, Jinchuan; Rogers, Alan R.; Witherspoon, David; Jorde, Lynn B.

    2010-01-01

    The genealogies of different genetic loci vary in depth. The deeper the genealogy, the greater the chance that it will include a rare event, such as the insertion of a mobile element. Therefore, the genealogy of a region that contains a mobile element is on average older than that of the rest of the genome. In a simple demographic model, the expected time to most recent common ancestor (TMRCA) is doubled if a rare insertion is present. We test this expectation by examining single nucleotide polymorphisms around polymorphic Alu insertions from two completely sequenced human genomes. The estimated TMRCA for regions containing a polymorphic insertion is two times larger than the genomic average (P < <10−30), as predicted. Because genealogies that contain polymorphic mobile elements are old, they are shaped largely by the forces of ancient population history and are insensitive to recent demographic events, such as bottlenecks and expansions. Remarkably, the information in just two human DNA sequences provides substantial information about ancient human population size. By comparing the likelihood of various demographic models, we estimate that the effective population size of human ancestors living before 1.2 million years ago was 18,500, and we can reject all models where the ancient effective population size was larger than 26,000. This result implies an unusually small population for a species spread across the entire Old World, particularly in light of the effective population sizes of chimpanzees (21,000) and gorillas (25,000), which each inhabit only one part of a single continent. PMID:20133859

  5. Resting state functional connectivity in early blind humans

    PubMed Central

    Burton, Harold; Snyder, Abraham Z.; Raichle, Marcus E.

    2014-01-01

    Task-based neuroimaging studies in early blind humans (EB) have demonstrated heightened visual cortex responses to non-visual paradigms. Several prior functional connectivity studies in EB have shown altered connections consistent with these task-based results. But these studies generally did not consider behavioral adaptations to lifelong blindness typically observed in EB. Enhanced cognitive abilities shown in EB include greater serial recall and attention to memory. Here, we address the question of the extent to which brain intrinsic activity in EB reflects such adaptations. We performed a resting-state functional magnetic resonance imaging study contrasting 14 EB with 14 age/gender matched normally sighted controls (NS). A principal finding was markedly greater functional connectivity in EB between visual cortex and regions typically associated with memory and cognitive control of attention. In contrast, correlations between visual cortex and non-deprived sensory cortices were significantly lower in EB. Thus, the available data, including that obtained in prior task-based and resting state fMRI studies, as well as the present results, indicate that visual cortex in EB becomes more heavily incorporated into functional systems instantiating episodic recall and attention to non-visual events. Moreover, EB appear to show a reduction in interactions between visual and non-deprived sensory cortices, possibly reflecting suppression of inter-sensory distracting activity. PMID:24778608

  6. Origin and Evolution of Water Oxidation before the Last Common Ancestor of the Cyanobacteria

    PubMed Central

    Cardona, Tanai; Murray, James W.; Rutherford, A. William

    2015-01-01

    Photosystem II, the water oxidizing enzyme, altered the course of evolution by filling the atmosphere with oxygen. Here, we reconstruct the origin and evolution of water oxidation at an unprecedented level of detail by studying the phylogeny of all D1 subunits, the main protein coordinating the water oxidizing cluster (Mn4CaO5) of Photosystem II. We show that D1 exists in several forms making well-defined clades, some of which could have evolved before the origin of water oxidation and presenting many atypical characteristics. The most ancient form is found in the genome of Gloeobacter kilaueensis JS-1 and this has a C-terminus with a higher sequence identity to D2 than to any other D1. Two other groups of early evolving D1 correspond to those expressed under prolonged far-red illumination and in darkness. These atypical D1 forms are characterized by a dramatically different Mn4CaO5 binding site and a Photosystem II containing such a site may assemble an unconventional metal cluster. The first D1 forms with a full set of ligands to the Mn4CaO5 cluster are grouped with D1 proteins expressed only under low oxygen concentrations and the latest evolving form is the dominant type of D1 found in all cyanobacteria and plastids. In addition, we show that the plastid ancestor had a D1 more similar to those in early branching Synechococcus. We suggest each one of these forms of D1 originated from transitional forms at different stages toward the innovation and optimization of water oxidation before the last common ancestor of all known cyanobacteria. PMID:25657330

  7. Looking for the Last Universal Common Ancestor (LUCA)

    PubMed Central

    Koskela, Minna; Annila, Arto

    2012-01-01

    Genomic sequences across diverse species seem to align towards a common ancestry, eventually implying that eons ago some universal antecedent organism would have lived on the face of Earth. However, when evolution is understood not only as a biological process but as a general thermodynamic process, it becomes apparent that the quest for the last universal common ancestor is unattainable. Ambiguities in alignments are unavoidable because the driving forces and paths of evolution cannot be separated from each other. Thus tracking down life’s origin is by its nature a non-computable task. The thermodynamic tenet clarifies that evolution is a path-dependent process of least-time consumption of free energy. The natural process is without a demarcation line between animate and inanimate. PMID:24704844

  8. Early Human Occupation on the Northeast Tibetan Plateau

    NASA Astrophysics Data System (ADS)

    Rhode, D.; Madsen, D.; Brantingham, P.; Perrault, C.

    2010-12-01

    The Tibetan Plateau presents great challenges for human occupation: low oxygen, high ultraviolet radiation, harsh seasonal climate, low overall biological productivity. How and when early humans were able to cope physiologically, genetically, and behaviorally with these extremes is important for understanding the history of human adaptive flexibility. Our investigations of prehistoric human settlement on the northeast Tibetan Plateau focus on (a) establishing well-dated evidence for occupation of altitudes >3000 m, (b) the environmental context of high altitude adaptation, and (c) relations of hunting and pastoralism to lower-altitude agrarian systems. We observe two major prehistoric settlement patterns in the Qinghai Lake area. The earliest, ~15,000-7500 yr old, consists of small isolated firehearths with sparse associated stone tools and wild mammal remains (1). Numerous hearths often occur in the same localities, indicating repeated short-duration occupations by small hunting parties. A second pattern, ~9000-4000 yr old, was established during the Holocene climatic optimum. These sites represent prolonged seasonal residential occupation, containing dark anthropogenic midden, hearth and pit constructions, abundant stone tools, occasional ceramics, and abundant diverse faunal remains (including medium-large mammals but lacking domestic sheep/yak)(2). These Plateau-margin base camps allowed greater intensity of use of the high Plateau. Residential occupation was strongly influenced by nearby lower-altitude farming communities; development of the socioeconomic landscape along the Yellow River likely played at least as great a role in Plateau occupation patterns as did Holocene environmental changes. Holocene vegetation changes in the NE Tibetan Plateau have been attributed to climate (3) or anthropogenic modification (4). Our results document changes in shrub/tree presence from ~12,000-4000 BP, similar to pollen records, that likely reflect climate rather than

  9. Autophagy in human keratinocytes: an early step of the differentiation?

    PubMed

    Aymard, Elodie; Barruche, Vincent; Naves, Thomas; Bordes, Sylvie; Closs, Brigitte; Verdier, Mireille; Ratinaud, Marie-Hélène

    2011-03-01

    Studies have established that autophagy constitutes an efficient process to recycle cellular components and certain proteins. The phenomenon was demonstrated primarily in response to nutrient starvation, and there are increasing evidences that it is implied in differentiation. Keratinocyte differentiation was going along an activation of lysosomal enzymes and organelle clearance, and terminal steps are sometimes described as a specialized form of cell death leading to corneocytes. We examined whether initiation of the process in human keratinocyte HaCaT involves autophagy. The KSFM™ culture medium was substituted by M199, which contains a low glucose concentration but a high calcium level (known to induce differentiation). Metabolic stress reduced enhanced cell number in G(1) phase, without apoptotic features (ΔΨmt and membrane integrity are unchanged). Morphological changes were associated with a lower integrin ß1 expression and modifications of protein levels involved in keratinocyte differentiation (involucrin, keratin K10 and ΔNp63α). Whereas autophagic signalling was supported by SIRT1 and pAMPK (T172) increase according to time kinetic, which led to the disappearance of mTOR phosphorylated on S2448 residue. The significant Bcl-X(L) level reduction with stress promoted autophagy, by the release of Beclin-1, whereas ATG5-ATG12 and LC3-II that are involved in autophagosome formation were enhanced significantly. Then, the level of lysosomal protein cathepsin B rose to execute autophagy. Kinetic studies established that autophagy would constitute an early signalling process required for keratinocyte commitment in differentiation pathway. PMID:21166723

  10. Opossum carboxylesterases: sequences, phylogeny and evidence for CES gene duplication events predating the marsupial-eutherian common ancestor

    PubMed Central

    2008-01-01

    residues previously reported for human CES1 involved in catalysis, ligand binding, tertiary structure and organelle localization. Phylogenetic studies indicated the gene duplication events which generated ancestral mammalian CES genes predated the common ancestor for marsupial and eutherian mammals, and appear to coincide with the early diversification of tetrapods. PMID:18289373

  11. Upd3--an ancestor of the four-helix bundle cytokines.

    PubMed

    Oldefest, Mirja; Nowinski, Jana; Hung, Chien-Wen; Neelsen, Denis; Trad, Ahmad; Tholey, Andreas; Grötzinger, Joachim; Lorenzen, Inken

    2013-06-21

    The unpaired-like protein 3 (Upd3) is one of the three cytokines of Drosophila melanogaster supposed to activate the JAK/STAT signaling pathway (Janus tyrosine kinases/signal transducer and activator of transcription). This activation occurs via the type-I cytokine receptor domeless, an orthologue of gp130, the common signal transducer of all four-helix bundle interleukin-6 (IL-6) type cytokines. Both receptors are known to exist as preformed dimers in the plasma membrane and initiate the acute-phase response. These facts indicate an evolutionary relation between vertebrate IL-6 and the Drosophila protein Upd3. Here we presented data which strengthen this notion. Upd3 was recombinantly expressed, a renaturation and purification protocol was established which allows to obtain high amounts of biological active protein. This protein is, like human IL-6, a monomeric-α helical cytokine, implicating that Upd3 is an "ancestor" of the four-helix bundle cytokines. PMID:23707937

  12. Will man wish to prevail? Some fundamental choices facing humanity early in the Third Millennium

    SciTech Connect

    Wood, L.L.

    1994-10-01

    With the subtle but occasionally vital exception of vaccination-induced immunity to many of the major infectious diseases, no human today is other than virtually identical biologically to those who greeted the dawn of the Second Millennium, nearly 1000 years ago. Culturally, however, we of the West are quite highly evolved from our ancestors of a millennium ago, primarily due to the advent of means for communicating with ever smaller latencies and ever higher bandwidths over ever greater distances in space and time: printed documents have been supplemented in succession by telephony, radio, video and, just now, the first personal communications sets. Also, within a fraction of a human lifetime from the present moment, the first prosthesis for the human brain has appeared and just very recently has become quite ubiquitous: digital computing systems. We are hardly members of the same species, culturally speaking; people of 1000 years ago would be truly and utterly lost in our communications-intensive civilization, and even a highly educated person from those times would swear that a personal computer equipped with a wireless communications module was as at least a familiar, if not a golem. Conversely, a computer-using person from our own times somehow translated back to 1000 A.D. would likely find the profound isolation and the ``informational slowness`` of life then to be acutely intolerable, certainly to a far greater extent than would a citizen of the High Middle Ages translated back to Augustus Caesar`s Rome.

  13. Early Holocene human remains from the Argentinean Pampas: additional evidence for distinctive cranial morphology of early South Americans.

    PubMed

    Pucciarelli, Héctor M; Perez, S Ivan; Politis, Gustavo G

    2010-10-01

    The cranial morphology of Early Holocene American human samples is characterized by a long and narrow cranial vault, whereas more recent samples exhibit a shorter and wider cranial vault. Two hypotheses have been proposed to account for the morphological differences between early and late-American samples: (a) the migratory hypothesis that suggests that the morphological variation between early and late American samples was the result of a variable number of migratory waves; and (b) the local diversification hypothesis, that is, the morphological differences between early and late American samples were mainly generated by local, random (genetic drift), and nonrandom factors (selection and phenotypic plasticity). We present the first craniometric study of three early skulls from the Argentinean Pampas, dated ∼8,000 cal. years BP (Arroyo Seco 2, Chocorí, and La Tigra), and one associated with mega-faunal remains (Fontezuelas skull). In addition, we studied several Late Holocene samples. We show that the skulls from the Argentinean Pampas are morphologically similar to other Early Holocene American skulls (i.e., Lagoa Santa from Brazil, Tequendama, Checua, and Aguazuque from Colombia, Lauricocha from Peru, and early Mexicans) that exhibit long and narrow cranial vaults. These samples differ from the Late Holocene American samples that exhibit a shorter and wider cranial vault. Our results underscore the important differences in cranial morphology between early and late-American samples. However, we emphasize the need for further studies to discuss alternative hypotheses regarding such differences. PMID:20623674

  14. East African climate pulses and early human evolution

    NASA Astrophysics Data System (ADS)

    Maslin, Mark A.; Brierley, Chris M.; Milner, Alice M.; Shultz, Susanne; Trauth, Martin H.; Wilson, Katy E.

    2014-10-01

    Current evidence suggests that all of the major events in hominin evolution have occurred in East Africa. Over the last two decades, there has been intensive work undertaken to understand African palaeoclimate and tectonics in order to put together a coherent picture of how the environment of East Africa has varied in the past. The landscape of East Africa has altered dramatically over the last 10 million years. It has changed from a relatively flat, homogenous region covered with mixed tropical forest, to a varied and heterogeneous environment, with mountains over 4 km high and vegetation ranging from desert to cloud forest. The progressive rifting of East Africa has also generated numerous lake basins, which are highly sensitive to changes in the local precipitation-evaporation regime. There is now evidence that the presence of precession-driven, ephemeral deep-water lakes in East Africa were concurrent with major events in hominin evolution. It seems the unusual geology and climate of East Africa created periods of highly variable local climate, which, it has been suggested could have driven hominin speciation, encephalisation and dispersal out of Africa. One example is the significant hominin speciation and brain expansion event at ˜1.8 Ma that seems to have been coeval with the occurrence of highly variable, extensive, deep-water lakes. This complex, climatically very variable setting inspired first the variability selection hypothesis, which was then the basis for the pulsed climate variability hypothesis. The newer of the two suggests that the long-term drying trend in East Africa was punctuated by episodes of short, alternating periods of extreme humidity and aridity. Both hypotheses, together with other key theories of climate-evolution linkages, are discussed in this paper. Though useful the actual evolution mechanisms, which led to early hominins are still unclear and continue to be debated. However, it is clear that an understanding of East African

  15. Investing in early human development: timing and economic efficiency.

    PubMed

    Doyle, Orla; Harmon, Colm P; Heckman, James J; Tremblay, Richard E

    2009-03-01

    Policy discussions to ameliorate socioeconomic (SES) inequalities are increasingly focused on investments in early childhood. Yet such interventions are costly to implement, and clear evidence on the optimal time to intervene to yield a high economic and social return in the future is meagre. The majority of successful early childhood interventions start in the preschool years. However socioeconomic gradients in cognitive skills, socio-emotional functioning and health can be observed by age three, suggesting that preventative programmes starting earlier in childhood may be even more effective. We discuss the optimal timing of early childhood intervention with reference to recent research in developmental neuroscience. We motivate the need for early intervention by providing an overview of the impact of adverse risk factors during the antenatal and early childhood periods on outcomes later in life. We provide a brief review of the economic rationale for investing early in life and propose the "antenatal investment hypothesis". We conclude by discussing a suite of new European interventions that will inform this optimal timing debate. PMID:19213617

  16. Investing in Early Human Development: Timing and Economic Efficiency

    PubMed Central

    Doyle, Orla; Harmon, Colm P.; Heckman, James J.; Tremblay, Richard E.

    2010-01-01

    Policy discussions to ameliorate socioeconomic (SES) inequalities are increasingly focused on investments in early childhood. Yet such interventions are costly to implement, and clear evidence on the optimal time to intervene to yield a high economic and social return in the future is meagre. The majority of successful early childhood interventions start in the preschool years. However socioeconomic gradients in cognitive skills, socio-emotional functioning and health can be observed by age three, suggesting that preventative programmes starting earlier in childhood may be even more effective. We discuss the optimal timing of early childhood intervention with reference to recent research in developmental neuroscience. We motivate the need for early intervention by providing an overview of the impact of adverse risk factors during the antenatal and early childhood periods on outcomes later in life. We provide a brief review of the economic rationale for investing early in life and propose the “antenatal investment hypothesis”. We conclude by discussing a suite of new European interventions that will inform this optimal timing debate. PMID:19213617

  17. Cassava genome from a wild ancestor to cultivated varieties

    PubMed Central

    Wang, Wenquan; Feng, Binxiao; Xiao, Jingfa; Xia, Zhiqiang; Zhou, Xincheng; Li, Pinghua; Zhang, Weixiong; Wang, Ying; Møller, Birger Lindberg; Zhang, Peng; Luo, Ming-Cheng; Xiao, Gong; Liu, Jingxing; Yang, Jun; Chen, Songbi; Rabinowicz, Pablo D.; Chen, Xin; Zhang, Hong-Bin; Ceballos, Henan; Lou, Qunfeng; Zou, Meiling; Carvalho, Luiz J.C.B.; Zeng, Changying; Xia, Jing; Sun, Shixiang; Fu, Yuhua; Wang, Haiyan; Lu, Cheng; Ruan, Mengbin; Zhou, Shuigeng; Wu, Zhicheng; Liu, Hui; Kannangara, Rubini Maya; Jørgensen, Kirsten; Neale, Rebecca Louise; Bonde, Maya; Heinz, Nanna; Zhu, Wenli; Wang, Shujuan; Zhang, Yang; Pan, Kun; Wen, Mingfu; Ma, Ping-An; Li, Zhengxu; Hu, Meizhen; Liao, Wenbin; Hu, Wenbin; Zhang, Shengkui; Pei, Jinli; Guo, Anping; Guo, Jianchun; Zhang, Jiaming; Zhang, Zhengwen; Ye, Jianqiu; Ou, Wenjun; Ma, Yaqin; Liu, Xinyue; Tallon, Luke J.; Galens, Kevin; Ott, Sandra; Huang, Jie; Xue, Jingjing; An, Feifei; Yao, Qingqun; Lu, Xiaojing; Fregene, Martin; López-Lavalle, L. Augusto Becerra; Wu, Jiajie; You, Frank M.; Chen, Meili; Hu, Songnian; Wu, Guojiang; Zhong, Silin; Ling, Peng; Chen, Yeyuan; Wang, Qinghuang; Liu, Guodao; Liu, Bin; Li, Kaimian; Peng, Ming

    2014-01-01

    Cassava is a major tropical food crop in the Euphorbiaceae family that has high carbohydrate production potential and adaptability to diverse environments. Here we present the draft genome sequences of a wild ancestor and a domesticated variety of cassava and comparative analyses with a partial inbred line. We identify 1,584 and 1,678 gene models specific to the wild and domesticated varieties, respectively, and discover high heterozygosity and millions of single-nucleotide variations. Our analyses reveal that genes involved in photosynthesis, starch accumulation and abiotic stresses have been positively selected, whereas those involved in cell wall biosynthesis and secondary metabolism, including cyanogenic glucoside formation, have been negatively selected in the cultivated varieties, reflecting the result of natural selection and domestication. Differences in microRNA genes and retrotransposon regulation could partly explain an increased carbon flux towards starch accumulation and reduced cyanogenic glucoside accumulation in domesticated cassava. These results may contribute to genetic improvement of cassava through better understanding of its biology. PMID:25300236

  18. The early Upper Paleolithic human skeleton from the Abrigo do Lagar Velho (Portugal) and modern human emergence in Iberia

    PubMed Central

    Duarte, Cidália; Maurício, João; Pettitt, Paul B.; Souto, Pedro; Trinkaus, Erik; van der Plicht, Hans; Zilhão, João

    1999-01-01

    The discovery of an early Upper Paleolithic human burial at the Abrigo do Lagar Velho, Portugal, has provided evidence of early modern humans from southern Iberia. The remains, the largely complete skeleton of a ≈4-year-old child buried with pierced shell and red ochre, is dated to ca. 24,500 years B.P. The cranium, mandible, dentition, and postcrania present a mosaic of European early modern human and Neandertal features. The temporal bone has an intermediate-sized juxtamastoid eminence. The mandibular mentum osseum and the dental size and proportions, supported by mandibular ramal features, radial tuberosity orientation, and diaphyseal curvature, as well as the pubic proportions align the skeleton with early modern humans. Body proportions, reflected in femorotibial lengths and diaphyseal robusticity plus tibial condylar displacement, as well as mandibular symphyseal retreat and thoracohumeral muscle insertions, align the skeleton with the Neandertals. This morphological mosaic indicates admixture between regional Neandertals and early modern humans dispersing into southern Iberia. It establishes the complexities of the Late Pleistocene emergence of modern humans and refutes strict replacement models of modern human origins. PMID:10377462

  19. Structure–Function Relationships of Glycoprotein Hormones and Their Subunits’ Ancestors

    PubMed Central

    Cahoreau, Claire; Klett, Danièle; Combarnous, Yves

    2015-01-01

    Glycoprotein hormones (GPHs) are the most complex molecules with hormonal activity. They exist only in vertebrates but the genes encoding their subunits’ ancestors are found in most vertebrate and invertebrate species although their roles are still unknown. In the present report, we review the available structural and functional data concerning GPHs and their subunits’ ancestors. PMID:25767463

  20. Genomic evidence for large, long-lived ancestors to placental mammals.

    PubMed

    Romiguier, J; Ranwez, V; Douzery, E J P; Galtier, N

    2013-01-01

    It is widely assumed that our mammalian ancestors, which lived in the Cretaceous era, were tiny animals that survived massive asteroid impacts in shelters and evolved into modern forms after dinosaurs went extinct, 65 Ma. The small size of most Mesozoic mammalian fossils essentially supports this view. Paleontology, however, is not conclusive regarding the ancestry of extant mammals, because Cretaceous and Paleocene fossils are not easily linked to modern lineages. Here, we use full-genome data to estimate the longevity and body mass of early placental mammals. Analyzing 36 fully sequenced mammalian genomes, we reconstruct two aspects of the ancestral genome dynamics, namely GC-content evolution and nonsynonymous over synonymous rate ratio. Linking these molecular evolutionary processes to life-history traits in modern species, we estimate that early placental mammals had a life span above 25 years and a body mass above 1 kg. This is similar to current primates, cetartiodactyls, or carnivores, but markedly different from mice or shrews, challenging the dominant view about mammalian origin and evolution. Our results imply that long-lived mammals existed in the Cretaceous era and were the most successful in evolution, opening new perspectives about the conditions for survival to the Cretaceous-Tertiary crisis. PMID:22949523

  1. The Malthusian parameter of ascents: What prevents the exponential increase of one’s ancestors?

    PubMed Central

    Ohno, Susumu

    1996-01-01

    The reason that the indefinite exponential increase in the number of one’s ancestors does not take place is found in the law of sibling interference, which can be expressed by the following simple equation:\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} \\begin{equation*}\\begin{matrix}{\\mathit{N}}_{{\\mathit{n}}} \\enskip & \\\\ {\\mathit{{\\blacksquare}}} \\enskip & \\\\ {\\mathit{ASZ}} \\enskip & \\end{matrix} {\\mathrm{\\hspace{.167em}{\\times}\\hspace{.167em}2\\hspace{.167em}=\\hspace{.167em}}}{\\mathit{N_{n+1},}}\\end{equation*}\\end{document} where Nn is the number of ancestors in the nth generation, ASZ is the average sibling size of these ancestors, and Nn+1 is the number of ancestors in the next older generation (n + 1). Accordingly, the exponential increase in the number of one’s ancestors is an initial anomaly that occurs while ASZ remains at 1. Once ASZ begins to exceed 1, the rate of increase in the number of ancestors is progressively curtailed, falling further and further behind the exponential increase rate. Eventually, ASZ reaches 2, and at that point, the number of ancestors stops increasing for two generations. These two generations, named AN SA and AN SA + 1, are the most critical in the ancestry, for one’s ancestors at that point come to represent all the progeny-produced adults of the entire ancestral population. Thereafter, the fate of one’s ancestors becomes the fate of the entire population. If the population to which one belongs is a successful, slowly expanding one, the number of ancestors would slowly decline as you move toward the remote past. This is because ABZ would exceed 2. Only when ABZ is less than 2 would the number of ancestors increase beyond the AN SA and AN SA + 1 generations. Since the above is an indication of a failing population on the way to

  2. Stable isotope dietary analysis of the Tianyuan 1 early modern human

    PubMed Central

    Hu, Yaowu; Shang, Hong; Tong, Haowen; Nehlich, Olaf; Liu, Wu; Zhao, Chaohong; Yu, Jincheng; Wang, Changsui; Trinkaus, Erik; Richards, Michael P.

    2009-01-01

    We report here on the isotopic analysis of the diet of one of the oldest modern humans found in Eurasia, the Tianyuan 1 early modern human dating to ≈40,000 calendar years ago from Tianyuan Cave (Tianyuandong) in the Zhoukoudian region of China. Carbon and nitrogen isotope analysis of the human and associated faunal remains indicate a diet high in animal protein, and the high nitrogen isotope values suggest the consumption of freshwater fish. To confirm this inference, we measured the sulfur isotope values of terrestrial and freshwater animals around the Zhoukoudian area and of the Tianyuan 1 human, which also support the interpretation of a substantial portion of the diet from freshwater fish. This analysis provides the direct evidence for the consumption of aquatic resources by early modern humans in China and has implications for early modern human subsistence and demography. PMID:19581579

  3. Early Differentiation within the Animate Domain: Are Humans Something Special?

    ERIC Educational Resources Information Center

    Pauen, Sabina

    2000-01-01

    Two experiments investigated whether preverbal infants distinguish between humans and mammals. Study 1 found that 7-, 9-, and 11-month-olds distinguished humans from mammals in an object-examination task. Study 2 found that 7-month-olds but not 5-month-olds showed evidence for category discrimination with the 2-dimensional color photos of toy…

  4. Early environmental effects on epigenetic regulation in humans

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We all know our environment affects our risk of disease. But importantly, the health consequences of environmental exposures depend not only on their severity, but also on their timing relative to developmental milestones. The developmental origins hypothesis is based on the fact that certain early ...

  5. Experimental evolution of a facultative thermophile from a mesophilic ancestor.

    PubMed

    Blaby, Ian K; Lyons, Benjamin J; Wroclawska-Hughes, Ewa; Phillips, Grier C F; Pyle, Tyler P; Chamberlin, Stephen G; Benner, Steven A; Lyons, Thomas J; Crécy-Lagard, Valérie de; Crécy, Eudes de

    2012-01-01

    Experimental evolution via continuous culture is a powerful approach to the alteration of complex phenotypes, such as optimal/maximal growth temperatures. The benefit of this approach is that phenotypic selection is tied to growth rate, allowing the production of optimized strains. Herein, we demonstrate the use of a recently described long-term culture apparatus called the Evolugator for the generation of a thermophilic descendant from a mesophilic ancestor (Escherichia coli MG1655). In addition, we used whole-genome sequencing of sequentially isolated strains throughout the thermal adaptation process to characterize the evolutionary history of the resultant genotype, identifying 31 genetic alterations that may contribute to thermotolerance, although some of these mutations may be adaptive for off-target environmental parameters, such as rich medium. We undertook preliminary phenotypic analysis of mutations identified in the glpF and fabA genes. Deletion of glpF in a mesophilic wild-type background conferred significantly improved growth rates in the 43-to-48°C temperature range and altered optimal growth temperature from 37°C to 43°C. In addition, transforming our evolved thermotolerant strain (EVG1064) with a wild-type allele of glpF reduced fitness at high temperatures. On the other hand, the mutation in fabA predictably increased the degree of saturation in membrane lipids, which is a known adaptation to elevated temperature. However, transforming EVG1064 with a wild-type fabA allele had only modest effects on fitness at intermediate temperatures. The Evolugator is fully automated and demonstrates the potential to accelerate the selection for complex traits by experimental evolution and significantly decrease development time for new industrial strains. PMID:22020511

  6. Friend or Foe? Early Social Evaluation of Human Interactions

    PubMed Central

    Buon, Marine; Jacob, Pierre; Margules, Sylvie; Brunet, Isabelle; Dutat, Michel; Cabrol, Dominique; Dupoux, Emmanuel

    2014-01-01

    We report evidence that 29-month-old toddlers and 10-month-old preverbal infants discriminate between two agents: a pro-social agent, who performs a positive (comforting) action on a human patient and a negative (harmful) action on an inanimate object, and an anti-social agent, who does the converse. The evidence shows that they prefer the former to the latter even though the agents perform the same bodily movements. Given that humans can cause physical harm to their conspecifics, we discuss this finding in light of the likely adaptive value of the ability to detect harmful human agents. PMID:24586355

  7. Fine specificity of cellular immune responses in humans to human cytomegalovirus immediate-early 1 protein.

    PubMed Central

    Alp, N J; Allport, T D; Van Zanten, J; Rodgers, B; Sissons, J G; Borysiewicz, L K

    1991-01-01

    Cell-mediated immunity is important in maintaining the virus-host equilibrium in persistent human cytomegalovirus (HCMV) infection. The HCMV 72-kDa major immediate early 1 protein (IE1) is a target for CD8+ cytotoxic T cells in humans, as is the equivalent 89-kDa protein in mouse. Less is known about responses against this protein by CD4+ T cells, which may be important as direct effector cells or helper cells for antibody and CD8+ responses. Proliferative-T-cell responses to HCMV IE1 were studied in normal seropositive subjects. Peripheral blood mononuclear cells from 85% of seropositive subjects proliferated in response to HCMV from infected fibroblasts, and of these, 73% responded to recombinant baculovirus IE1. Responding cells were predominantly CD3+ CD4+. IE1 antigen preparations, including baculovirus recombinant protein, transfected rat cell nuclei, and synthetic peptides, induced IE1-specific T-cell lines which cross-reacted between the preparations. The fine specificity of these IE1-specific T-cell lines was studied by using overlapping synthetic peptides encompassing the entire sequence of the IE1 protein. The regions of the IE1 molecule recognized were identified and these varied between individuals, possibly reflecting differences in major histocompatibility complex (MHC) class II haplotype. In one subject, the peptide specificities of proliferative and MHC class I-restricted cytotoxic determinants on IE1 were spatially distinct. Thus, no single immunodominant T-cell determinant within HCMV IE1 was identified, suggesting that multiple peptides or a region of the 72-kDa IE1 protein would be required to induce specific T-cell responses in humans. PMID:1714519

  8. Early-season avian deaths from West Nile virus as warnings of human infection

    USGS Publications Warehouse

    Guptill, S.C.; Julian, K.G.; Campbell, G.L.; Price, S.D.; Marfin, A.A.

    2003-01-01

    An analysis of 2001 and 2002 West Nile virus (WNV) surveillance data shows that counties that report WNV-infected dead birds early in the transmission season are more likely to report subsequent WNV disease cases in humans than are counties that do not report early WNV-infected dead birds.

  9. Technology, conflict early warning systems, public health, and human rights.

    PubMed

    Pham, Phuong N; Vinck, Patrick

    2012-01-01

    Public health and conflict early warning are evolving rapidly in response to technology changes for the gathering, management, analysis and communication of data. It is expected that these changes will provide an unprecedented ability to monitor, detect, and respond to crises. One of the potentially most profound and lasting expected change affects the roles of the various actors in providing and sharing information and in responding to early warning. Communities and civil society actors have the opportunity to be empowered as a source of information, analysis, and response, while the role of traditional actors shifts toward supporting those communities and building resilience. However, by creating new roles, relationships, and responsibilities, technology changes raise major concerns and ethical challenges for practitioners, pressing the need for practical guidelines and actionable recommendations in line with existing ethical principles. PMID:23568944

  10. Human evolution. Evolution of early Homo: an integrated biological perspective.

    PubMed

    Antón, Susan C; Potts, Richard; Aiello, Leslie C

    2014-07-01

    Integration of evidence over the past decade has revised understandings about the major adaptations underlying the origin and early evolution of the genus Homo. Many features associated with Homo sapiens, including our large linear bodies, elongated hind limbs, large energy-expensive brains, reduced sexual dimorphism, increased carnivory, and unique life history traits, were once thought to have evolved near the origin of the genus in response to heightened aridity and open habitats in Africa. However, recent analyses of fossil, archaeological, and environmental data indicate that such traits did not arise as a single package. Instead, some arose substantially earlier and some later than previously thought. From ~2.5 to 1.5 million years ago, three lineages of early Homo evolved in a context of habitat instability and fragmentation on seasonal, intergenerational, and evolutionary time scales. These contexts gave a selective advantage to traits, such as dietary flexibility and larger body size, that facilitated survival in shifting environments. PMID:24994657

  11. Early modern human diversity suggests subdivided population structure and a complex out-of-Africa scenario

    PubMed Central

    Gunz, Philipp; Bookstein, Fred L.; Mitteroecker, Philipp; Stadlmayr, Andrea; Seidler, Horst; Weber, Gerhard W.

    2009-01-01

    The interpretation of genetic evidence regarding modern human origins depends, among other things, on assessments of the structure and the variation of ancient populations. Because we lack genetic data from the time when the first anatomically modern humans appeared, between 200,000 and 60,000 years ago, instead we exploit the phenotype of neurocranial geometry to compare the variation in early modern human fossils with that in other groups of fossil Homo and recent modern humans. Variation is assessed as the mean-squared Procrustes distance from the group average shape in a representation based on several hundred neurocranial landmarks and semilandmarks. We find that the early modern group has more shape variation than any other group in our sample, which covers 1.8 million years, and that they are morphologically similar to recent modern humans of diverse geographically dispersed populations but not to archaic groups. Of the currently competing models of modern human origins, some are inconsistent with these findings. Rather than a single out-of-Africa dispersal scenario, we suggest that early modern humans were already divided into different populations in Pleistocene Africa, after which there followed a complex migration pattern. Our conclusions bear implications for the inference of ancient human demography from genetic models and emphasize the importance of focusing research on those early modern humans, in particular, in Africa. PMID:19307568

  12. Human Ecology and Television in Early Childhood Education.

    ERIC Educational Resources Information Center

    Schleicher, Klaus

    A human ecological approach to the study of children's television viewing raises questions that researchers have largely neglected. Does television influence the interaction patterns of socializing agents with children and with one another? Are there long-term, psychological consequences of unintegrated and competing influences from television and…

  13. No Evidence of Neandertal mtDNA Contribution to Early Modern Humans

    PubMed Central

    2004-01-01

    The retrieval of mitochondrial DNA (mtDNA) sequences from four Neandertal fossils from Germany, Russia, and Croatia has demonstrated that these individuals carried closely related mtDNAs that are not found among current humans. However, these results do not definitively resolve the question of a possible Neandertal contribution to the gene pool of modern humans since such a contribution might have been erased by genetic drift or by the continuous influx of modern human DNA into the Neandertal gene pool. A further concern is that if some Neandertals carried mtDNA sequences similar to contemporaneous humans, such sequences may be erroneously regarded as modern contaminations when retrieved from fossils. Here we address these issues by the analysis of 24 Neandertal and 40 early modern human remains. The biomolecular preservation of four Neandertals and of five early modern humans was good enough to suggest the preservation of DNA. All four Neandertals yielded mtDNA sequences similar to those previously determined from Neandertal individuals, whereas none of the five early modern humans contained such mtDNA sequences. In combination with current mtDNA data, this excludes any large genetic contribution by Neandertals to early modern humans, but does not rule out the possibility of a smaller contribution. PMID:15024415

  14. A Life-Span Human Development Model of Learning for Early Education.

    ERIC Educational Resources Information Center

    Languis, Marlin; Wilcox, Jean

    1981-01-01

    A life-span human development model of learning in early childhood is presented. Learning is viewed as a human enterprise which spans the entire lifetime and involves interaction among people. The bounds of interaction are derived from philosophy and from the biological and social behavioral sciences. (JN)

  15. Estimating time to the most recent common ancestor (TMRCA): comparison and application of eight methods.

    PubMed

    Zhou, Jin; Teo, Yik-Ying

    2016-08-01

    Investigating how an ancestral population diverges to give rise to distinct subpopulations remains a fundamental pursuit in population genetics. There is broad consensus for the 'Out-of-Africa' hypothesis that states that modern humans arose ∼200 000 years ago in Africa and spread throughout the continent ∼100 000 years ago. This was followed by several waves of major population dispersals across the globe, although the exact nature of the population divergence remains debatable. Existing methods to estimate population divergence time differ in their methodological frameworks and demographic assumptions, and require different types of genetic data as input. These fundamental differences often result in the methods producing inconsistent estimates of the population divergence time, further confounding attempts to robustly uncover the history of human migration, especially when most population genetic studies do not employ multiple methods to estimate the time to the most recent common ancestor (TMRCA). Here, we chose eight popular methods for estimating TMRCA and evaluated their robustness and accuracy in correctly identifying the true TMRCA through a series of simulations that mimicked different evolutionary scenarios. We subsequently applied all eight methods to estimate the population divergence time between Southeast Asian Malays and South Asian Indians using deep whole-genome sequencing data. PMID:26669663

  16. In search of the last common ancestor: new findings on wild chimpanzees

    PubMed Central

    McGrew, W. C.

    2010-01-01

    Modelling the behaviour of extinct hominins is essential in order to devise useful hypotheses of our species' evolutionary origins for testing in the palaeontological and archaeological records. One approach is to model the last common ancestor (LCA) of living apes and humans, based on current ethological and ecological knowledge of our closest living relations. Such referential modelling is based on rigorous, ongoing field studies of the chimpanzee (Pan troglodytes) and the bonobo (Pan paniscus). This paper reviews recent findings from nature, focusing on those with direct implications for hominin evolution, e.g. apes, using elementary technology to access basic resources such as food and water, or sheltering in caves or bathing as thermoregulatory adaptations. I give preference to studies that directly address key issues, such as whether stone artefacts are detectible before the Oldowan, based on the percussive technology of hammer and anvil use by living apes. Detailed comparative studies of chimpanzees living in varied habitats, from rainforest to savannah, reveal that some behavioural patterns are universal (e.g. shelter construction), while others show marked (e.g. extractive foraging) or nuanced (e.g. courtship) cross-populational variation. These findings allow us to distinguish between retained, primitive traits of the LCA versus derived ones in the human lineage. PMID:20855301

  17. Discontinuity of human presence at Atapuerca during the early Middle Pleistocene: a matter of ecological competition?

    PubMed

    Rodríguez-Gómez, Guillermo; Mateos, Ana; Martín-González, Jesús Angel; Blasco, Ruth; Rosell, Jordi; Rodríguez, Jesús

    2014-01-01

    Increasing evidence suggests that the European human settlement is older than 1.2 Ma. However, there is a fierce debate about the continuity or discontinuity of the early human settlement of Europe. In particular, evidence of human presence in the interval 0.7-0.5 Ma is scarce in comparison with evidence for the previous and later periods. Here, we present a case study in which the environmental conditions at Sierra de Atapuerca in the early Middle Pleistocene, a period without evidence of human presence, are compared with the conditions in the previous period, for which a relatively intense human occupation is documented. With this objective in mind, the available resources for a human population and the intensity of competition between secondary consumers during the two periods are compared using a mathematical model. The Gran Dolina site TD8 level, dated to 0.7-0.6 Ma, is taken as representative of the period during which Atapuerca was apparently not occupied by humans. Conditions at TD8 are compared with those of the previous period, represented by the TD6-2 level, which has yielded abundant evidence of intense human occupation. The results show that survival opportunities for a hypothetical human population were lower at TD8 than they were at TD6-2. Increased resource competition between secondary consumers arises as a possible explanation for the absence of human occupation at Atapuerca in the early Middle Pleistocene. PMID:25054305

  18. Discontinuity of Human Presence at Atapuerca during the Early Middle Pleistocene: A Matter of Ecological Competition?

    PubMed Central

    Rodríguez-Gómez, Guillermo; Mateos, Ana; Martín-González, Jesús Angel; Blasco, Ruth; Rosell, Jordi; Rodríguez, Jesús

    2014-01-01

    Increasing evidence suggests that the European human settlement is older than 1.2 Ma. However, there is a fierce debate about the continuity or discontinuity of the early human settlement of Europe. In particular, evidence of human presence in the interval 0.7−0.5 Ma is scarce in comparison with evidence for the previous and later periods. Here, we present a case study in which the environmental conditions at Sierra de Atapuerca in the early Middle Pleistocene, a period without evidence of human presence, are compared with the conditions in the previous period, for which a relatively intense human occupation is documented. With this objective in mind, the available resources for a human population and the intensity of competition between secondary consumers during the two periods are compared using a mathematical model. The Gran Dolina site TD8 level, dated to 0.7−0.6 Ma, is taken as representative of the period during which Atapuerca was apparently not occupied by humans. Conditions at TD8 are compared with those of the previous period, represented by the TD6-2 level, which has yielded abundant evidence of intense human occupation. The results show that survival opportunities for a hypothetical human population were lower at TD8 than they were at TD6-2. Increased resource competition between secondary consumers arises as a possible explanation for the absence of human occupation at Atapuerca in the early Middle Pleistocene. PMID:25054305

  19. Early detection of intentional harm in the human amygdala.

    PubMed

    Hesse, Eugenia; Mikulan, Ezequiel; Decety, Jean; Sigman, Mariano; Garcia, María del Carmen; Silva, Walter; Ciraolo, Carlos; Vaucheret, Esteban; Baglivo, Fabricio; Huepe, David; Lopez, Vladimir; Manes, Facundo; Bekinschtein, Tristan A; Ibanez, Agustin

    2016-01-01

    A decisive element of moral cognition is the detection of harm and its assessment as intentional or unintentional. Moral cognition engages brain networks supporting mentalizing, intentionality, empathic concern and evaluation. These networks rely on the amygdala as a critical hub, likely through frontotemporal connections indexing stimulus salience. We assessed inferences about perceived harm using a paradigm validated through functional magnetic resonance imaging, eye-tracking and electroencephalogram recordings. During the task, we measured local field potentials in three patients with depth electrodes (n = 115) placed in the amygdala and in several frontal, temporal, and parietal locations. Direct electrophysiological recordings demonstrate that intentional harm induces early activity in the amygdala (<200 ms), which--in turn--predicts intention attribution. The amygdala was the only site that systematically discriminated between critical conditions and predicted their classification of events as intentional. Moreover, connectivity analysis showed that intentional harm induced stronger frontotemporal information sharing at early stages. Results support the 'many roads' view of the amygdala and highlight its role in the rapid encoding of intention and salience--critical components of mentalizing and moral evaluation. PMID:26608745

  20. Early electrophysiological markers of visual awareness in the human brain.

    PubMed

    Ohla, Kathrin; Busch, Niko A; Herrmann, Christoph S

    2007-10-01

    The present study investigated neuronal correlates of stimulus processing leading to conscious perception of a task irrelevant global structure in a visual display. To study the underlying neuronal processes, participants were presented different types of dot patterns (Glass patterns) either forming a global structure or forming no global structure while EEG was recorded. Participants were naive about the pattern types and performed a demanding colour discrimination task. Following the experiment, the degree to which participants acquired awareness of the global visual structure was assessed. Early gamma-frequency band responses (gamma, 25-100 Hz) over occipital, parietal, and central areas were enhanced to circular Glass patterns as compared to random dot patterns at 90 ms post-stimulus. This effect was observed exclusively in participants who were subjectively aware of the global pattern structure. In this group of observers, the pattern effect built up gradually during the course of the experiment. The significance of enhanced early gamma responses to global patterns for the production of awareness of the pattern might lie in the increased impact of information conveyed by well synchronised neuronal assemblies to upstream cortical areas. PMID:17656113

  1. Human memory development and its dysfunction after early hippocampal injury.

    PubMed

    de Haan, Michelle; Mishkin, Mortimer; Baldeweg, Torsten; Vargha-Khadem, Faraneh

    2006-07-01

    Cognitive memory involves long-term memories for facts (semantic memory) and personal experiences (episodic memory) that can be brought to mind. There is consensus that the hippocampus and related medial temporal lobe (MTL) structures are crucial for adult cognitive memory, but much less is known about their contribution to memory during infancy and childhood. We argue that the MTL is involved in memory from early in life, supporting recognition memory within the first postnatal months and recall memory within the first year. We propose that normal development involves a sequence in which a form of semantic-like memory emerges first, whereas the characteristics of episodic memory develop only later with progressive development of the hippocampus. Early bilateral injury to the hippocampus disrupts this normal pattern such that memory skills cannot develop beyond the stage of semantic memories. This review is part of the INMED/TINS special issue "Nature and nurture in brain development and neurological disorders", based on presentations at the annual INMED/TINS symposium (http://inmednet.com/). PMID:16750273

  2. Evolution of human brain functions: the functional structure of human consciousness.

    PubMed

    Cloninger, C Robert

    2009-11-01

    The functional structure of self-aware consciousness in human beings is described based on the evolution of human brain functions. Prior work on heritable temperament and character traits is extended to account for the quantum-like and holographic properties (i.e. parts elicit wholes) of self-aware consciousness. Cladistic analysis is used to identify the succession of ancestors leading to human beings. The functional capacities that emerge along this lineage of ancestors are described. The ecological context in which each cladogenesis occurred is described to illustrate the shifting balance of evolution as a complex adaptive system. Comparative neuroanatomy is reviewed to identify the brain structures and networks that emerged coincident with the emergent brain functions. Individual differences in human temperament traits were well developed in the common ancestor shared by reptiles and humans. Neocortical development in mammals proceeded in five major transitions: from early reptiles to early mammals, early primates, simians, early Homo, and modern Homo sapiens. These transitions provide the foundation for human self-awareness related to sexuality, materiality, emotionality, intellectuality, and spirituality, respectively. The functional structure of human self-aware consciousness is concerned with the regulation of five planes of being: sexuality, materiality, emotionality, intellectuality, and spirituality. Each plane elaborates neocortical functions organized around one of the five special senses. The interactions among these five planes gives rise to a 5 x 5 matrix of subplanes, which are functions that coarsely describe the focus of neocortical regulation. Each of these 25 neocortical functions regulates each of five basic motives or drives that can be measured as temperaments or basic emotions related to fear, anger, disgust, surprise, and happiness/sadness. The resulting 5 x 5 x 5 matrix of human characteristics provides a general and testable model of the

  3. 76 FR 20802 - Culturally Significant Objects Imported for Exhibition Determinations: “Ancestors of the Lake...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-13

    ... Sentani and Humboldt Bay'' SUMMARY: Notice is hereby given of the following determinations: Pursuant to... the exhibition ``Ancestors of the Lake: Art from Lake Sentani and Humboldt Bay,'' imported from...

  4. Brightness–Color Interactions in Human Early Visual Cortex

    PubMed Central

    Ouni, Ahmed; Chen, Stephanie; Sahmoud, Hinde; Gordon, James; Shapley, Robert

    2015-01-01

    The interaction between brightness and color causes there to be different color appearance when one and the same object is viewed against surroundings of different brightness. Brightness contrast causes color to be desaturated, as has been found in perceptual experiments on color induction and color-gamut expansion in human vision. However, it is not clear yet where in the cerebral cortex the brightness–color interaction that causes these major perceptual effects is located. One hypothesis is that brightness and color signals are processed separately and in parallel within the primary visual cortex V1 and only interact in extrastriate cortex. Another hypothesis is that color and brightness contrast interact strongly already within V1. We localized the brightness–color interaction in human V1 by means of recording the chromatic visual-evoked potential. The chromatic visual-evoked potential measurements decisively support the idea that brightness–color interaction arises in a recurrent inhibitory network in V1. Furthermore, our results show that the inhibitory signal for brightness–color interaction is generated by local brightness contrast at the boundary between target and surround, instead of by the luminance difference between the interior of the color target and its large background. PMID:25653377

  5. Edwin Grant Dexter: an early researcher in human behavioral biometeorology

    NASA Astrophysics Data System (ADS)

    Stewart, Alan E.

    2015-06-01

    Edwin Grant Dexter (1868-1938) was one of the first researchers to study empirically the effects of specific weather conditions on human behavior. Dexter (1904) published his findings in a book, Weather influences. The author's purposes in this article were to (1) describe briefly Dexter's professional life and examine the historical contexts and motivations that led Dexter to conduct some of the first empirical behavioral biometeorological studies of the time, (2) describe the methods Dexter used to examine weather-behavior relationships and briefly characterize the results that he reported in Weather influences, and (3) provide a historical analysis of Dexter's work and assess its significance for human behavioral biometeorology. Dexter's Weather influences, while demonstrating an exemplary approach to weather, health, and behavior relationships, came at the end of a long era of such studies, as health, social, and meteorological sciences were turning to different paradigms to advance their fields. For these reasons, Dexter's approach and contributions may not have been fully recognized at the time and are, consequently, worthy of consideration by contemporary biometeorologists.

  6. Edwin Grant Dexter: an early researcher in human behavioral biometeorology

    NASA Astrophysics Data System (ADS)

    Stewart, Alan E.

    2014-09-01

    Edwin Grant Dexter (1868-1938) was one of the first researchers to study empirically the effects of specific weather conditions on human behavior. Dexter (1904) published his findings in a book, Weather influences. The author's purposes in this article were to (1) describe briefly Dexter's professional life and examine the historical contexts and motivations that led Dexter to conduct some of the first empirical behavioral biometeorological studies of the time, (2) describe the methods Dexter used to examine weather-behavior relationships and briefly characterize the results that he reported in Weather influences, and (3) provide a historical analysis of Dexter's work and assess its significance for human behavioral biometeorology. Dexter's Weather influences, while demonstrating an exemplary approach to weather, health, and behavior relationships, came at the end of a long era of such studies, as health, social, and meteorological sciences were turning to different paradigms to advance their fields. For these reasons, Dexter's approach and contributions may not have been fully recognized at the time and are, consequently, worthy of consideration by contemporary biometeorologists.

  7. mga genosensor for early detection of human rheumatic heart disease.

    PubMed

    Singh, Swati; Kaushal, Ankur; Khare, Shashi; Kumar, Ashok

    2014-05-01

    The 5' amino-labeled DNA probe complementary to mga gene of Streptococcus pyogenes was immobilized on carboxylated multiwall carbon nanotubes electrode and hybridized with 0.1-100 ng/6 μl single-stranded genomic DNA (ssG-DNA) of S. pyogenes from throat swab of suspected rheumatic heart disease (RHD) patients. Electrochemical response was measured by cyclic voltammetry (CV), differential pulse voltammetry (DPV), and electrochemical impedance (EI). The sensitivity of the sensor was 106.03 (μA/cm(2))/ng and limit of detection (LOD) was found 0.014 ng/6 μl with regression coefficient (R(2)) of 0.921 using DPV. The genosensor was characterized by FTIR and SEM, and electrode was found stable for 6 months on storage at 4 °C with 5-6 % loss in initial DPV current. mga genosensor is the first report on RHD sensor which can save life of several suspected patients by early diagnosis in 30 min. PMID:24639090

  8. Spatial and temporal arrival patterns of Madagascar's vertebrate fauna explained by distance, ocean currents, and ancestor type

    PubMed Central

    Samonds, Karen E.; Godfrey, Laurie R.; Ali, Jason R.; Goodman, Steven M.; Vences, Miguel; Sutherland, Michael R.; Irwin, Mitchell T.; Krause, David W.

    2012-01-01

    How, when, and from where Madagascar's vertebrates arrived on the island is poorly known, and a comprehensive explanation for the distribution of its organisms has yet to emerge. We begin to break that impasse by analyzing vertebrate arrival patterns implied by currently existing taxa. For each of 81 clades, we compiled arrival date, source, and ancestor type (obligate freshwater, terrestrial, facultative swimmer, or volant). We analyzed changes in arrival rates, with and without adjusting for clade extinction. Probability of successful transoceanic dispersal is negatively correlated with distance traveled and influenced by ocean currents and ancestor type. Obligate rafters show a decrease in probability of successful transoceanic dispersal from the Paleocene onward, reaching the lowest levels after the mid-Miocene. This finding is consistent with a paleoceanographic model [Ali JR, Huber M (2010) Nature 463:653–656] that predicts Early Cenozoic surface currents periodically conducive to rafting or swimming from Africa, followed by a reconfiguration to present-day flow 15–20 million years ago that significantly diminished the ability for transoceanic dispersal to Madagascar from the adjacent mainland. PMID:22431643

  9. Early Modern Humans and Morphological Variation in Southeast Asia: Fossil Evidence from Tam Pa Ling, Laos

    PubMed Central

    Demeter, Fabrice; Shackelford, Laura; Westaway, Kira; Duringer, Philippe; Bacon, Anne-Marie; Ponche, Jean-Luc; Wu, Xiujie; Sayavongkhamdy, Thongsa; Zhao, Jian-Xin; Barnes, Lani; Boyon, Marc; Sichanthongtip, Phonephanh; Sénégas, Frank; Karpoff, Anne-Marie; Patole-Edoumba, Elise; Coppens, Yves; Braga, José

    2015-01-01

    Little is known about the timing of modern human emergence and occupation in Eastern Eurasia. However a rapid migration out of Africa into Southeast Asia by at least 60 ka is supported by archaeological, paleogenetic and paleoanthropological data. Recent discoveries in Laos, a modern human cranium (TPL1) from Tam Pa Ling‘s cave, provided the first evidence for the presence of early modern humans in mainland Southeast Asia by 63-46 ka. In the current study, a complete human mandible representing a second individual, TPL 2, is described using discrete traits and geometric morphometrics with an emphasis on determining its population affinity. The TPL2 mandible has a chin and other discrete traits consistent with early modern humans, but it retains a robust lateral corpus and internal corporal morphology typical of archaic humans across the Old World. The mosaic morphology of TPL2 and the fully modern human morphology of TPL1 suggest that a large range of morphological variation was present in early modern human populations residing in the eastern Eurasia by MIS 3. PMID:25849125

  10. Early modern humans and morphological variation in Southeast Asia: fossil evidence from Tam Pa Ling, Laos.

    PubMed

    Demeter, Fabrice; Shackelford, Laura; Westaway, Kira; Duringer, Philippe; Bacon, Anne-Marie; Ponche, Jean-Luc; Wu, Xiujie; Sayavongkhamdy, Thongsa; Zhao, Jian-Xin; Barnes, Lani; Boyon, Marc; Sichanthongtip, Phonephanh; Sénégas, Frank; Karpoff, Anne-Marie; Patole-Edoumba, Elise; Coppens, Yves; Braga, José

    2015-01-01

    Little is known about the timing of modern human emergence and occupation in Eastern Eurasia. However a rapid migration out of Africa into Southeast Asia by at least 60 ka is supported by archaeological, paleogenetic and paleoanthropological data. Recent discoveries in Laos, a modern human cranium (TPL1) from Tam Pa Ling's cave, provided the first evidence for the presence of early modern humans in mainland Southeast Asia by 63-46 ka. In the current study, a complete human mandible representing a second individual, TPL 2, is described using discrete traits and geometric morphometrics with an emphasis on determining its population affinity. The TPL2 mandible has a chin and other discrete traits consistent with early modern humans, but it retains a robust lateral corpus and internal corporal morphology typical of archaic humans across the Old World. The mosaic morphology of TPL2 and the fully modern human morphology of TPL1 suggest that a large range of morphological variation was present in early modern human populations residing in the eastern Eurasia by MIS 3. PMID:25849125

  11. Apparatus Named After Our Academic Ancestors — II

    NASA Astrophysics Data System (ADS)

    Greenslade, Thomas B.

    2011-01-01

    In my previous article on apparatus named after physicists and physics teachers, I discussed five relatively common pieces of apparatus from the 1875-1910 era. Now I will go back to the 18th and early-19th centuries to discuss eponymous2 apparatus that we are still using in lecture demonstrations.

  12. The Dispersed Archaeal Eukaryome and the Complex Archaeal Ancestor of Eukaryotes

    PubMed Central

    Koonin, Eugene V.; Yutin, Natalya

    2014-01-01

    The ancestral set of eukaryotic genes is a chimera composed of genes of archaeal and bacterial origins thanks to the endosymbiosis event that gave rise to the mitochondria and apparently antedated the last common ancestor of the extant eukaryotes. The proto-mitochondrial endosymbiont is confidently identified as an α-proteobacterium. In contrast, the archaeal ancestor of eukaryotes remains elusive, although evidence is accumulating that it could have belonged to a deep lineage within the TACK (Thaumarchaeota, Aigarchaeota, Crenarchaeota, Korarchaeota) superphylum of the Archaea. Recent surveys of archaeal genomes show that the apparent ancestors of several key functional systems of eukaryotes, the components of the archaeal “eukaryome,” such as ubiquitin signaling, RNA interference, and actin-based and tubulin-based cytoskeleton structures, are identifiable in different archaeal groups. We suggest that the archaeal ancestor of eukaryotes was a complex form, rooted deeply within the TACK superphylum, that already possessed some quintessential eukaryotic features, in particular, a cytoskeleton, and perhaps was capable of a primitive form of phagocytosis that would facilitate the engulfment of potential symbionts. This putative group of Archaea could have existed for a relatively short time before going extinct or undergoing genome streamlining, resulting in the dispersion of the eukaryome. This scenario might explain the difficulty with the identification of the archaeal ancestor of eukaryotes despite the straightforward detection of apparent ancestors to many signature eukaryotic functional systems. PMID:24691961

  13. Reconstructing the ancestor of Mycobacterium leprae: The dynamics of gene loss and genome reduction

    PubMed Central

    Gómez-Valero, Laura; Rocha, Eduardo P.C.; Latorre, Amparo; Silva, Francisco J.

    2007-01-01

    We have reconstructed the gene content and order of the last common ancestor of the human pathogens Mycobacterium leprae and Mycobacterium tuberculosis. During the reductive evolution of M. leprae, 1537 of 2977 ancestral genes were lost, among which we found 177 previously unnoticed pseudogenes. We find evidence that a massive gene inactivation took place very recently in the M. leprae lineage, leading to the loss of hundreds of ancestral genes. A large proportion of their nucleotide content (∼89%) still remains in the genome, which allowed us to characterize and date them. The age of the pseudogenes was computed using a new methodology based on the rates and patterns of substitution in the pseudogenes and functional orthologous genes of closely related genomes. The position of the genes that were lost in the ancestor’s genome revealed that the process of function loss and degradation mainly took place through a gene-to-gene inactivation process, followed by the gradual loss of their DNA. This suggests a scenario of massive genome reduction through many nearly simultaneous pseudogenization events, leading to a highly specialized pathogen. PMID:17623808

  14. Early Preferential Responses to Fear Stimuli in Human Right Dorsal Visual Stream - A Meg Study

    PubMed Central

    Meeren, Hanneke K. M.; Hadjikhani, Nouchine; Ahlfors, Seppo P.; Hämäläinen, Matti S.; de Gelder, Beatrice

    2016-01-01

    Emotional expressions of others are salient biological stimuli that automatically capture attention and prepare us for action. We investigated the early cortical dynamics of automatic visual discrimination of fearful body expressions by monitoring cortical activity using magnetoencephalography. We show that right parietal cortex distinguishes between fearful and neutral bodies as early as 80-ms after stimulus onset, providing the first evidence for a fast emotion-attention-action link through human dorsal visual stream. PMID:27095660

  15. Early Preferential Responses to Fear Stimuli in Human Right Dorsal Visual Stream - A Meg Study.

    PubMed

    Meeren, Hanneke K M; Hadjikhani, Nouchine; Ahlfors, Seppo P; Hämäläinen, Matti S; de Gelder, Beatrice

    2016-01-01

    Emotional expressions of others are salient biological stimuli that automatically capture attention and prepare us for action. We investigated the early cortical dynamics of automatic visual discrimination of fearful body expressions by monitoring cortical activity using magnetoencephalography. We show that right parietal cortex distinguishes between fearful and neutral bodies as early as 80-ms after stimulus onset, providing the first evidence for a fast emotion-attention-action link through human dorsal visual stream. PMID:27095660

  16. [Early life stressful experiences and neuropsychiatric vulnerability: evidences from human and animal models].

    PubMed

    Rincel, Marion; Lépinay, Amandine; Gabory, Anne; Théodorou, Vassilia; Koehl, Muriel; Daugé, Valérie; Maccari, Stefania; Darnaudéry, Muriel

    2016-01-01

    The human newborn is highly dependent on parental care for its survival but also for the healthy development of its brain. A large body of literature demonstrates the impact of early life adversity, even during the prenatal period, on the adult's health. The susceptibility to neuropsychiatric diseases is often potentiated by early stress. If there is an agreement that a critical developmental period exists, the mechanisms underlying the long term effects of early life adversity are still poorly understood. Recent studies in animals highlight the involvement of epigenetic processes in the transmission of such vulnerabilities, notably via modifications in germ cells, which can be transmitted in the next generations. PMID:26850613

  17. High early life mortality in free-ranging dogs is largely influenced by humans

    PubMed Central

    Paul, Manabi; Sen Majumder, Sreejani; Sau, Shubhra; Nandi, Anjan K.; Bhadra, Anindita

    2016-01-01

    Free-ranging dogs are a ubiquitous part of human habitations in many developing countries, leading a life of scavengers dependent on human wastes for survival. The effective management of free-ranging dogs calls for understanding of their population dynamics. Life expectancy at birth and early life mortality are important factors that shape life-histories of mammals. We carried out a five year-long census based study in seven locations of West Bengal, India, to understand the pattern of population growth and factors affecting early life mortality in free-ranging dogs. We observed high rates of mortality, with only ~19% of the 364 pups from 95 observed litters surviving till the reproductive age; 63% of total mortality being human influenced. While living near people increases resource availability for dogs, it also has deep adverse impacts on their population growth, making the dog-human relationship on streets highly complex. PMID:26804633

  18. A molecular palaeobiological hypothesis for the origin of aplacophoran molluscs and their derivation from chiton-like ancestors

    PubMed Central

    Vinther, Jakob; Sperling, Erik A.; Briggs, Derek E. G.; Peterson, Kevin J.

    2012-01-01

    Aplacophorans have long been argued to be basal molluscs. We present a molecular phylogeny, including the aplacophorans Neomeniomorpha (Solenogastres) and Chaetodermomorpha (Caudofoveata), which recovered instead the clade Aculifera (Aplacophora + Polyplacophora). Our relaxed Bayesian molecular clock estimates an Early Ordovician appearance of the aculiferan crown group consistent with the presence of chiton-like molluscs with seven or eight dorsal shell plates by the Late Cambrian (approx. 501–490 Ma). Molecular, embryological and palaeontological data indicate that aplacophorans, as well as chitons, evolved from a paraphyletic assemblage of chiton-like ancestors. The recovery of cephalopods as a sister group to aculiferans suggests that the plesiomorphic condition in molluscs might be a morphology similar to that found in monoplacophorans. PMID:21976685

  19. Early Motherhood and Harsh Parenting: The Role of Human, Social, and Cultural Capital

    ERIC Educational Resources Information Center

    Lee, Yookyong

    2009-01-01

    Objective: This study examined the role of maternal human, social, and cultural capital in the relationship between early motherhood and harsh parenting behavior. Methods: This study used data from the Fragile Families and Child Wellbeing (FFCW) Study. Harsh parenting behaviors by mothers who were 19 years or younger at birth of the focal child (n…

  20. Primary Cortical Folding in the Human Newborn: An Early Marker of Later Functional Development

    ERIC Educational Resources Information Center

    Dubois, J.; Benders, M.; Borradori-Tolsa, C.; Cachia, A.; Lazeyras, F.; Leuchter, R. Ha-Vinh; Sizonenko, S. V.; Warfield, S. K.; Mangin, J. F.; Huppi, P. S.

    2008-01-01

    In the human brain, the morphology of cortical gyri and sulci is complex and variable among individuals, and it may reflect pathological functioning with specific abnormalities observed in certain developmental and neuropsychiatric disorders. Since cortical folding occurs early during brain development, these structural abnormalities might be…

  1. Early loss of oligodendrocytes in human and experimental neuromyelitis optica lesions

    PubMed Central

    Wrzos, Claudia; Winkler, Anne; Metz, Imke; Kayser, Dieter M.; Thal, Dietmar R.; Wegner, Christiane; Brück, Wolfgang; Nessler, Stefan; Bennett, Jeffrey L.

    2014-01-01

    Neuromyelitis optica (NMO) is a chronic, mostly relapsing inflammatory demyelinating disease of the CNS characterized by serum anti-aquaporin 4 (AQP4) antibodies in the majority of patients. Anti-AQP4 antibodies derived from NMO patients target and deplete astrocytes in experimental models when co-injected with complement. However, the time course and mechanisms of oligodendrocyte loss and demyelination and the fate of oligodendrocyte precursor cells (OPC) have not been examined in detail. Also, no studies regarding astrocyte repopulation of experimental NMO lesions have been reported. We utilized two rat models using either systemic transfer or focal intracerebral injection of recombinant human anti-AQP4 antibodies to generate NMO-like lesions. Time-course experiments were performed to examine oligodendroglial and astroglial damage and repair. In addition, oligodendrocyte pathology was studied in early human NMO lesions. Apart from early complement-mediated astrocyte destruction, we observed a prominent, very early loss of oligodendrocytes and oligodendrocyte precursor cells (OPCs) as well as a delayed loss of myelin. Astrocyte repopulation of focal NMO lesions was already substantial after 1 week. Olig2-positive OPCs reappeared before NogoA-positive, mature oligodendrocytes. Thus, using two experimental models that closely mimic the human disease, our study demonstrates that oligodendrocyte and OPC loss is an extremely early feature in the formation of human and experimental NMO lesions and leads to subsequent, delayed demyelination, highlighting an important difference in the pathogenesis of MS and NMO. PMID:24292009

  2. The Influence of Theoretical Conceptions of Human Development on the Practice of Early Childhood Education.

    ERIC Educational Resources Information Center

    Gardner, D. Bruce

    Communication is urged between theorists of human development and practitioners in early childhood education. Major psychological theories on maturation, child development, child behavior, personality formation, and affective and intellectual development are summarized and their effects on nursery school practices from the 1920's to the present…

  3. STATIONARY PATTERN ADAPTATION AND THE EARLY COMPONENTS IN HUMAN VISUAL EVOKED POTENTIALS

    EPA Science Inventory

    Pattern-onset visual evoked potentials were elicited from humans by sinusoidal gratings of 0.5., 1, 2 and 4 cpd (cycles/degree) following adaptation to a blank field or one of the gratings. The wave forms recorded after blank field adaptation showed an early positive component, P...

  4. The eukaryotic ancestor had a complex ubiquitin signaling system of archaeal origin.

    PubMed

    Grau-Bové, Xavier; Sebé-Pedrós, Arnau; Ruiz-Trillo, Iñaki

    2015-03-01

    The origin of the eukaryotic cell is one of the most important transitions in the history of life. However, the emergence and early evolution of eukaryotes remains poorly understood. Recent data have shown that the last eukaryotic common ancestor (LECA) was much more complex than previously thought. The LECA already had the genetic machinery encoding the endomembrane apparatus, spliceosome, nuclear pore, and myosin and kinesin cytoskeletal motors. It is unclear, however, when the functional regulation of these cellular components evolved. Here, we address this question by analyzing the origin and evolution of the ubiquitin (Ub) signaling system, one of the most important regulatory layers in eukaryotes. We delineated the evolution of the whole Ub, Small-Ub-related MOdifier (SUMO), and Ub-fold modifier 1 (Ufm1) signaling networks by analyzing representatives from all major eukaryotic, bacterial, and archaeal lineages. We found that the Ub toolkit had a pre-eukaryotic origin and is present in three extant archaeal groups. The pre-eukaryotic Ub toolkit greatly expanded during eukaryogenesis, through massive gene innovation and diversification of protein domain architectures. This resulted in a LECA with essentially all of the Ub-related genes, including the SUMO and Ufm1 Ub-like systems. Ub and SUMO signaling further expanded during eukaryotic evolution, especially labeling and delabeling enzymes responsible for substrate selection. Additionally, we analyzed protein domain architecture evolution and found that multicellular lineages have the most complex Ub systems in terms of domain architectures. Together, we demonstrate that the Ub system predates the origin of eukaryotes and that a burst of innovation during eukaryogenesis led to a LECA with complex posttranslational regulation. PMID:25525215

  5. Human Y chromosome haplogroup R-V88: a paternal genetic record of early mid Holocene trans-Saharan connections and the spread of Chadic languages

    PubMed Central

    Cruciani, Fulvio; Trombetta, Beniamino; Sellitto, Daniele; Massaia, Andrea; Destro-Bisol, Giovanni; Watson, Elizabeth; Beraud Colomb, Eliane; Dugoujon, Jean-Michel; Moral, Pedro; Scozzari, Rosaria

    2010-01-01

    Although human Y chromosomes belonging to haplogroup R1b are quite rare in Africa, being found mainly in Asia and Europe, a group of chromosomes within the paragroup R-P25* are found concentrated in the central-western part of the African continent, where they can be detected at frequencies as high as 95%. Phylogenetic evidence and coalescence time estimates suggest that R-P25* chromosomes (or their phylogenetic ancestor) may have been carried to Africa by an Asia-to-Africa back migration in prehistoric times. Here, we describe six new mutations that define the relationships among the African R-P25* Y chromosomes and between these African chromosomes and earlier reported R-P25 Eurasian sub-lineages. The incorporation of these new mutations into a phylogeny of the R1b haplogroup led to the identification of a new clade (R1b1a or R-V88) encompassing all the African R-P25* and about half of the few European/west Asian R-P25* chromosomes. A worldwide phylogeographic analysis of the R1b haplogroup provided strong support to the Asia-to-Africa back-migration hypothesis. The analysis of the distribution of the R-V88 haplogroup in >1800 males from 69 African populations revealed a striking genetic contiguity between the Chadic-speaking peoples from the central Sahel and several other Afroasiatic-speaking groups from North Africa. The R-V88 coalescence time was estimated at 9200–5600 kya, in the early mid Holocene. We suggest that R-V88 is a paternal genetic record of the proposed mid-Holocene migration of proto-Chadic Afroasiatic speakers through the Central Sahara into the Lake Chad Basin, and geomorphological evidence is consistent with this view. PMID:20051990

  6. HIV epidemiology. The early spread and epidemic ignition of HIV-1 in human populations.

    PubMed

    Faria, Nuno R; Rambaut, Andrew; Suchard, Marc A; Baele, Guy; Bedford, Trevor; Ward, Melissa J; Tatem, Andrew J; Sousa, João D; Arinaminpathy, Nimalan; Pépin, Jacques; Posada, David; Peeters, Martine; Pybus, Oliver G; Lemey, Philippe

    2014-10-01

    Thirty years after the discovery of HIV-1, the early transmission, dissemination, and establishment of the virus in human populations remain unclear. Using statistical approaches applied to HIV-1 sequence data from central Africa, we show that from the 1920s Kinshasa (in what is now the Democratic Republic of Congo) was the focus of early transmission and the source of pre-1960 pandemic viruses elsewhere. Location and dating estimates were validated using the earliest HIV-1 archival sample, also from Kinshasa. The epidemic histories of HIV-1 group M and nonpandemic group O were similar until ~1960, after which group M underwent an epidemiological transition and outpaced regional population growth. Our results reconstruct the early dynamics of HIV-1 and emphasize the role of social changes and transport networks in the establishment of this virus in human populations. PMID:25278604

  7. The early spread and epidemic ignition of HIV-1 in human populations

    PubMed Central

    Faria, Nuno R.; Rambaut, Andrew; Suchard, Marc A.; Baele, Guy; Bedford, Trevor; Ward, Melissa J.; Tatem, Andrew J.; Sousa, João D.; Arinaminpathy, Nimalan; Pépin, Jacques; Posada, David; Peeters, Martine; Pybus, Oliver G.; Lemey, Philippe

    2014-01-01

    Thirty years after the discovery of HIV-1, the early transmission, dissemination, and establishment of the virus in human populations remain unclear. Using statistical approaches applied to HIV-1 sequence data from central Africa, we show that from the 1920s Kinshasa (in what is now the Democratic Republic of Congo) was the focus of early transmission and the source of pre-1960 pandemic viruses elsewhere. Location and dating estimates were validated using the earliest HIV-1 archival sample, also from Kinshasa. The epidemic histories of HIV-1 group M and nonpandemic group O were similar until ~1960, after which group M underwent an epidemiological transition and outpaced regional population growth. Our results reconstruct the early dynamics of HIV-1 and emphasize the role of social changes and transport networks in the establishment of this virus in human populations. PMID:25278604

  8. Apparatus Named After Our Academic Ancestors — I

    NASA Astrophysics Data System (ADS)

    Greenslade, Thomas B.

    2010-12-01

    Let us now praise famous physicists, and the apparatus named after them, with apologies to the writer of Ecclesiastes. I once compiled a list of about 300 pieces of apparatus known to us as X's Apparatus. Some of the values of X are familiar, like Wheatstone and Kelvin and Faraday, but have you heard of Pickering or Rhumkorff or Barlow? In an earlier article about Packard's apparatus,1 I paid homage to an early-20th-century high school teacher, and other articles have mentioned apparatus by a number of other physicists and physics teachers.2 In many cases the apparatus came directly out of research being done by the physicist, or from the need to show the phenomena of physics in the classroom and lecture hall. Here are more stories about apparatus and their makers, starting with three pieces of apparatus that are related to the development of electron physics in the latter half of the 19th century.

  9. Controlled fire use in early humans might have triggered the evolutionary emergence of tuberculosis.

    PubMed

    Chisholm, Rebecca H; Trauer, James M; Curnoe, Darren; Tanaka, Mark M

    2016-08-01

    Tuberculosis (TB) is caused by the Mycobacterium tuberculosis complex (MTBC), a wildly successful group of organisms and the leading cause of death resulting from a single bacterial pathogen worldwide. It is generally accepted that MTBC established itself in human populations in Africa and that animal-infecting strains diverged from human strains. However, the precise causal factors of TB emergence remain unknown. Here, we propose that the advent of controlled fire use in early humans created the ideal conditions for the emergence of TB as a transmissible disease. This hypothesis is supported by mathematical modeling together with a synthesis of evidence from epidemiology, evolutionary genetics, and paleoanthropology. PMID:27457933

  10. Early pregnancy factor is an immunosuppressive contaminant of commercial preparations of human chorionic gonadotrophin.

    PubMed Central

    Rolfe, B E; Morton, H; Clarke, F M

    1983-01-01

    Early pregnancy factor (EPF) is a pregnancy associated substance detected in human serum and urine throughout the first and second trimesters of pregnancy. It has also been detected in several commercial preparations of human chorionic gonadotrophin (hCG). The various molecular weight forms of EPF which occur in human pregnancy serum, urine and commercial hCG preparations have been partially characterized and found to be similar to each other but distinct from hCG. Further evidence is presented which suggests that it is EPF rather than hCG which is responsible for the immunosuppressive activity of some crude hCG preparations. PMID:6831771

  11. Synthesis of human adenovirus early RNA species is similar in productive and abortive infections of monkey and human cells.

    PubMed Central

    Anderson, K P; Klessig, D F

    1982-01-01

    Northern (RNA) blot analysis has been used to show that synthesis of early mRNA species is similar in monkey cells productively or abortively infected with human adenovirus. mRNA species from all five major early regions (1A, 1B, 2, 3, 4) are identical in size and comparable in abundance whether isolated from monkey cells infected with adenovirus type 2 or with the host range mutant Ad2hr400 or coinfected with adenovirus type 2 plus simian virus 40. The mRNA species isolated from monkey cells are identical in size to those isolated from human cells. Production of virus-associated RNA is also identical in productive and abortive infections of monkey cells. Synthesis of virus-associated RNA is, however, significantly greater in HeLa cells than in CV1 cells at late times after infection regardless of which virus is used in the infection. Images PMID:6283181

  12. Uptake of Plasmin-PN-1 Complexes in Early Human Atheroma.

    PubMed

    Boukais, Kamel; Bayles, Richard; Borges, Luciano de Figueiredo; Louedec, Liliane; Boulaftali, Yacine; Ho-Tin-Noé, Benoit; Arocas, Véronique; Bouton, Marie-Christine; Michel, Jean-Baptiste

    2016-01-01

    Zymogens are delivered to the arterial wall by radial transmural convection. Plasminogen can be activated within the arterial wall to produce plasmin, which is involved in evolution of the atherosclerotic plaque. Vascular smooth muscle cells (vSMCs) protect the vessels from proteolytic injury due to atherosclerosis development by highly expressing endocytic LDL receptor-related protein-1 (LRP-1), and by producing anti-proteases, such as Protease Nexin-1 (PN-1). PN-1 is able to form covalent complexes with plasmin. We hypothesized that plasmin-PN-1 complexes could be internalized via LRP-1 by vSMCs during the early stages of human atheroma. LRP-1 is also responsible for the capture of aggregated LDL in human atheroma. Plasmin activity and immunohistochemical analyses of early human atheroma showed that the plasminergic system is activated within the arterial wall, where intimal foam cells, including vSMCs and platelets, are the major sites of PN-1 accumulation. Both PN-1 and LRP-1 are overexpressed in early atheroma at both messenger and protein levels. Cell biology studies demonstrated an increased expression of PN-1 and tissue plasminogen activator by vSMCs in response to LDL. Plasmin-PN-1 complexes are internalized via LRP-1 in vSMCs, whereas plasmin alone is not. Tissue PN-1 interacts with plasmin in early human atheroma via two complementary mechanisms: plasmin inhibition and tissue uptake of plasmin-PN-1 complexes via LRP-1 in vSMCs. Despite this potential protective effect, plasminogen activation by vSMCs remains abnormally elevated in the intima in early stages of human atheroma. PMID:27445860

  13. Uptake of Plasmin-PN-1 Complexes in Early Human Atheroma

    PubMed Central

    Boukais, Kamel; Bayles, Richard; Borges, Luciano de Figueiredo; Louedec, Liliane; Boulaftali, Yacine; Ho-Tin-Noé, Benoit; Arocas, Véronique; Bouton, Marie-Christine; Michel, Jean-Baptiste

    2016-01-01

    Zymogens are delivered to the arterial wall by radial transmural convection. Plasminogen can be activated within the arterial wall to produce plasmin, which is involved in evolution of the atherosclerotic plaque. Vascular smooth muscle cells (vSMCs) protect the vessels from proteolytic injury due to atherosclerosis development by highly expressing endocytic LDL receptor-related protein-1 (LRP-1), and by producing anti-proteases, such as Protease Nexin-1 (PN-1). PN-1 is able to form covalent complexes with plasmin. We hypothesized that plasmin-PN-1 complexes could be internalized via LRP-1 by vSMCs during the early stages of human atheroma. LRP-1 is also responsible for the capture of aggregated LDL in human atheroma. Plasmin activity and immunohistochemical analyses of early human atheroma showed that the plasminergic system is activated within the arterial wall, where intimal foam cells, including vSMCs and platelets, are the major sites of PN-1 accumulation. Both PN-1 and LRP-1 are overexpressed in early atheroma at both messenger and protein levels. Cell biology studies demonstrated an increased expression of PN-1 and tissue plasminogen activator by vSMCs in response to LDL. Plasmin-PN-1 complexes are internalized via LRP-1 in vSMCs, whereas plasmin alone is not. Tissue PN-1 interacts with plasmin in early human atheroma via two complementary mechanisms: plasmin inhibition and tissue uptake of plasmin-PN-1 complexes via LRP-1 in vSMCs. Despite this potential protective effect, plasminogen activation by vSMCs remains abnormally elevated in the intima in early stages of human atheroma. PMID:27445860

  14. Immediate-early gene region of human cytomegalovirus trans-activates the promoter of human immunodeficiency virus

    SciTech Connect

    Davis, M.G.; Kenney, S.C.; Kamine, J.; Pagano, J.S.; Huang, E.S.

    1987-12-01

    Almost all homosexual patients with acquired immunodeficiency syndrome are also actively infected with human cytomegalovirus (HCMV). The authors have hypothesized that an interaction between HCMV and human immunodeficiency virus (HIV), the agent that causes acquired immunodeficiency syndrome, may exist at a molecular level and contribute to the manifestations of HIV infection. In this report, they demonstrate that the immediate-early gene region of HCMV, in particular immediate-early region 2, trans-activates the expression of the bacterial gene chloramphenicol acetyltransferase that is fused to the HIV long terminal repeat and carried by plasmid pHIV-CAT. The HCMV immediate-early trans-activator increases the level of mRNA from the plamid pHIV-CAT. The sequences of HIV that are responsive to trans-activation by the HDMV immediate-early region are distinct from HIV sequences that are required for response to the HIV tat. The stimulation of HIV gene expression by HDMV gene functions could enhance the consequences of HIV infection in persons with previous or concurrent HCMV infection.

  15. Early Pleistocene third metacarpal from Kenya and the evolution of modern human-like hand morphology

    PubMed Central

    Ward, Carol V.; Tocheri, Matthew W.; Plavcan, J. Michael; Brown, Francis H.; Manthi, Fredrick Kyalo

    2014-01-01

    Despite discoveries of relatively complete hands from two early hominin species (Ardipithecus ramidus and Australopithecus sediba) and partial hands from another (Australopithecus afarensis), fundamental questions remain about the evolution of human-like hand anatomy and function. These questions are driven by the paucity of hand fossils in the hominin fossil record between 800,000 and 1.8 My old, a time interval well documented for the emergence and subsequent proliferation of Acheulian technology (shaped bifacial stone tools). Modern and Middle to Late Pleistocene humans share a suite of derived features in the thumb, wrist, and radial carpometacarpal joints that is noticeably absent in early hominins. Here we show that one of the most distinctive features of this suite in the Middle Pleistocene to recent human hand, the third metacarpal styloid process, was present ∼1.42 Mya in an East African hominin from Kaitio, West Turkana, Kenya. This fossil thus provides the earliest unambiguous evidence for the evolution of a key shared derived characteristic of modern human and Neandertal hand morphology and suggests that the distinctive complex of radial carpometacarpal joint features in the human hand arose early in the evolution of the genus Homo and probably in Homo erectus sensu lato. PMID:24344276

  16. Early Pleistocene third metacarpal from Kenya and the evolution of modern human-like hand morphology.

    PubMed

    Ward, Carol V; Tocheri, Matthew W; Plavcan, J Michael; Brown, Francis H; Manthi, Fredrick Kyalo

    2014-01-01

    Despite discoveries of relatively complete hands from two early hominin species (Ardipithecus ramidus and Australopithecus sediba) and partial hands from another (Australopithecus afarensis), fundamental questions remain about the evolution of human-like hand anatomy and function. These questions are driven by the paucity of hand fossils in the hominin fossil record between 800,000 and 1.8 My old, a time interval well documented for the emergence and subsequent proliferation of Acheulian technology (shaped bifacial stone tools). Modern and Middle to Late Pleistocene humans share a suite of derived features in the thumb, wrist, and radial carpometacarpal joints that is noticeably absent in early hominins. Here we show that one of the most distinctive features of this suite in the Middle Pleistocene to recent human hand, the third metacarpal styloid process, was present ∼1.42 Mya in an East African hominin from Kaitio, West Turkana, Kenya. This fossil thus provides the earliest unambiguous evidence for the evolution of a key shared derived characteristic of modern human and Neandertal hand morphology and suggests that the distinctive complex of radial carpometacarpal joint features in the human hand arose early in the evolution of the genus Homo and probably in Homo erectus sensu lato. PMID:24344276

  17. Molecular paleontology and complexity in the last eukaryotic common ancestor

    PubMed Central

    Koumandou, V. Lila; Wickstead, Bill; Ginger, Michael L.; van der Giezen, Mark; Dacks, Joel B.

    2013-01-01

    Eukaryogenesis, the origin of the eukaryotic cell, represents one of the fundamental evolutionary transitions in the history of life on earth. This event, which is estimated to have occurred over one billion years ago, remains rather poorly understood. While some well-validated examples of fossil microbial eukaryotes for this time frame have been described, these can provide only basic morphology and the molecular machinery present in these organisms has remained unknown. Complete and partial genomic information has begun to fill this gap, and is being used to trace proteins and cellular traits to their roots and to provide unprecedented levels of resolution of structures, metabolic pathways and capabilities of organisms at these earliest points within the eukaryotic lineage. This is essentially allowing a molecular paleontology. What has emerged from these studies is spectacular cellular complexity prior to expansion of the eukaryotic lineages. Multiple reconstructed cellular systems indicate a very sophisticated biology, which by implication arose following the initial eukaryogenesis event but prior to eukaryotic radiation and provides a challenge in terms of explaining how these early eukaryotes arose and in understanding how they lived. Here, we provide brief overviews of several cellular systems and the major emerging conclusions, together with predictions for subsequent directions in evolution leading to extant taxa. We also consider what these reconstructions suggest about the life styles and capabilities of these earliest eukaryotes and the period of evolution between the radiation of eukaryotes and the eukaryogenesis event itself. PMID:23895660

  18. Digital Literacy Practices and Pedagogical Moments: Human and Non-Human Intertwining in Early Childhood Education

    ERIC Educational Resources Information Center

    Lafton, Tove

    2015-01-01

    Various forms of digital devices have established themselves as resources within constructions of professional practices in early childhood education. This article is centred on the question of how we might rethink an example of digital practice based on a Foucauldian understanding of discourse and a rhizomatic understanding of digital practice…

  19. Starch grains on human teeth reveal early broad crop diet in northern Peru

    PubMed Central

    Piperno, Dolores R.; Dillehay, Tom D.

    2008-01-01

    Previous research indicates that the Ñanchoc Valley in northern Peru was an important locus of early and middle Holocene human settlement, and that between 9200 and 5500 14C yr B.P. the valley inhabitants adopted major crop plants such as squash (Cucurbita moschata), peanuts (Arachis sp.), and cotton (Gossypium barbadense). We report here an examination of starch grains preserved in the calculus of human teeth from these sites that provides direct evidence for the early consumption of cultivated squash and peanuts along with two other major food plants not previously detected. Starch from the seeds of Phaseolus and Inga feuillei, the flesh of Cucurbita moschata fruits, and the nuts of Arachis was routinely present on numerous teeth that date to between 8210 and 6970 14C yr B.P. Early plant diets appear to have been diverse and stable through time and were rich in cultivated foods typical of later Andean agriculture. Our data provide early archaeological evidence for Phaseolus beans and I. feuillei, an important tree crop, and indicate that effective food production systems that contributed significant dietary inputs were present in the Ñanchoc region by 8000 14C yr B.P. Starch grain studies of dental remains document plants and edible parts of them not normally preserved in archaeological records and can assume primary roles as direct indicators of ancient human diets and agriculture. PMID:19066222

  20. IL-17A mediates inflammatory and tissue remodelling events in early human tendinopathy.

    PubMed

    Millar, Neal L; Akbar, Moeed; Campbell, Abigail L; Reilly, James H; Kerr, Shauna C; McLean, Michael; Frleta-Gilchrist, Marina; Fazzi, Umberto G; Leach, William J; Rooney, Brian P; Crowe, Lindsay A N; Murrell, George A C; McInnes, Iain B

    2016-01-01

    Increasingly, inflammatory mediators are considered crucial to the onset and perpetuation of tendinopathy. We sought evidence of interleukin 17A (IL-17A) expression in early human tendinopathy and thereafter, explored mechanisms whereby IL-17A mediated inflammation and tissue remodeling in human tenocytes. Torn supraspinatus tendon (established pathology) and matched intact subscapularis tendon (representing 'early pathology') along with control biopsies were collected from patients undergoing shoulder surgery. Markers of inflammation and IL-17A were quantified by RT-PCR and immunohistochemistry. Human tendon cells were derived from hamstring tendon obtained during ACL reconstruction. In vitro effects of IL-17A upon tenocytes were measured using RT-PCR, multiplex cytokine assays, apoptotic proteomic profiling, immunohistochemistry and annexin V FACS staining. Increased expression of IL-17A was detected in 'early tendinopathy' compared to both matched samples and non-matched control samples (p < 0.01) by RT-PCR and immunostaining. Double immunofluoresence staining revealed IL-17A expression in leukocyte subsets including mast cells, macrophages and T cells. IL-17A treated tenocytes exhibited increased production of proinflammatory cytokines (p < 0.001), altered matrix regulation (p < 0.01) with increased Collagen type III and increased expression of several apoptosis related factors. We propose IL-17A as an inflammatory mediator within the early tendinopathy processes thus providing novel therapeutic approaches in the management of tendon disorders. PMID:27263531

  1. IL-17A mediates inflammatory and tissue remodelling events in early human tendinopathy

    PubMed Central

    Millar, Neal L.; Akbar, Moeed; Campbell, Abigail L.; Reilly, James H.; Kerr, Shauna C.; McLean, Michael; Frleta-Gilchrist, Marina; Fazzi, Umberto G.; Leach, William J.; Rooney, Brian P.; Crowe, Lindsay A. N.; Murrell, George A. C.; McInnes, Iain B.

    2016-01-01

    Increasingly, inflammatory mediators are considered crucial to the onset and perpetuation of tendinopathy. We sought evidence of interleukin 17A (IL-17A) expression in early human tendinopathy and thereafter, explored mechanisms whereby IL-17A mediated inflammation and tissue remodeling in human tenocytes. Torn supraspinatus tendon (established pathology) and matched intact subscapularis tendon (representing ‘early pathology’) along with control biopsies were collected from patients undergoing shoulder surgery. Markers of inflammation and IL-17A were quantified by RT-PCR and immunohistochemistry. Human tendon cells were derived from hamstring tendon obtained during ACL reconstruction. In vitro effects of IL-17A upon tenocytes were measured using RT-PCR, multiplex cytokine assays, apoptotic proteomic profiling, immunohistochemistry and annexin V FACS staining. Increased expression of IL-17A was detected in ‘early tendinopathy’ compared to both matched samples and non-matched control samples (p < 0.01) by RT-PCR and immunostaining. Double immunofluoresence staining revealed IL-17A expression in leukocyte subsets including mast cells, macrophages and T cells. IL-17A treated tenocytes exhibited increased production of proinflammatory cytokines (p < 0.001), altered matrix regulation (p < 0.01) with increased Collagen type III and increased expression of several apoptosis related factors. We propose IL-17A as an inflammatory mediator within the early tendinopathy processes thus providing novel therapeutic approaches in the management of tendon disorders. PMID:27263531

  2. Starch grains on human teeth reveal early broad crop diet in northern Peru.

    PubMed

    Piperno, Dolores R; Dillehay, Tom D

    2008-12-16

    Previous research indicates that the Nanchoc Valley in northern Peru was an important locus of early and middle Holocene human settlement, and that between 9200 and 5500 (14)C yr B.P. the valley inhabitants adopted major crop plants such as squash (Cucurbita moschata), peanuts (Arachis sp.), and cotton (Gossypium barbadense). We report here an examination of starch grains preserved in the calculus of human teeth from these sites that provides direct evidence for the early consumption of cultivated squash and peanuts along with two other major food plants not previously detected. Starch from the seeds of Phaseolus and Inga feuillei, the flesh of Cucurbita moschata fruits, and the nuts of Arachis was routinely present on numerous teeth that date to between 8210 and 6970 (14)C yr B.P. Early plant diets appear to have been diverse and stable through time and were rich in cultivated foods typical of later Andean agriculture. Our data provide early archaeological evidence for Phaseolus beans and I. feuillei, an important tree crop, and indicate that effective food production systems that contributed significant dietary inputs were present in the Nanchoc region by 8000 (14)C yr B.P. Starch grain studies of dental remains document plants and edible parts of them not normally preserved in archaeological records and can assume primary roles as direct indicators of ancient human diets and agriculture. PMID:19066222

  3. Globin-coupled sensors, protoglobins, and the last universal common ancestor.

    PubMed

    Freitas, Tracey Allen K; Saito, Jennifer A; Hou, Shaobin; Alam, Maqsudul

    2005-01-01

    The strategy for detecting oxygen, carbon monoxide, nitric oxide, and sulfides is predominantly through heme-based sensors utilizing either a globin domain or a PAS domain. Whereas PAS domains bind various cofactors, globins bind only heme. Globin-coupled sensors (GCSs) were first described as regulators of the aerotactic responses in Bacillus subtilis and Halobacterium salinarum. GCSs were also identified in diverse microorganisms that appear to have roles in regulating gene expression. Functional and evolutionary analyses of the GCSs, their protoglobin ancestor, and their relationship to the last universal common ancestor (LUCA) are discussed in the context of globin-based signal transduction. PMID:15598488

  4. DNA analysis of an early modern human from Tianyuan Cave, China.

    PubMed

    Fu, Qiaomei; Meyer, Matthias; Gao, Xing; Stenzel, Udo; Burbano, Hernán A; Kelso, Janet; Pääbo, Svante

    2013-02-01

    Hominins with morphology similar to present-day humans appear in the fossil record across Eurasia between 40,000 and 50,000 y ago. The genetic relationships between these early modern humans and present-day human populations have not been established. We have extracted DNA from a 40,000-y-old anatomically modern human from Tianyuan Cave outside Beijing, China. Using a highly scalable hybridization enrichment strategy, we determined the DNA sequences of the mitochondrial genome, the entire nonrepetitive portion of chromosome 21 (∼30 Mbp), and over 3,000 polymorphic sites across the nuclear genome of this individual. The nuclear DNA sequences determined from this early modern human reveal that the Tianyuan individual derived from a population that was ancestral to many present-day Asians and Native Americans but postdated the divergence of Asians from Europeans. They also show that this individual carried proportions of DNA variants derived from archaic humans similar to present-day people in mainland Asia. PMID:23341637

  5. DNA analysis of an early modern human from Tianyuan Cave, China

    PubMed Central

    Fu, Qiaomei; Meyer, Matthias; Gao, Xing; Stenzel, Udo; Burbano, Hernán A.; Kelso, Janet; Pääbo, Svante

    2013-01-01

    Hominins with morphology similar to present-day humans appear in the fossil record across Eurasia between 40,000 and 50,000 y ago. The genetic relationships between these early modern humans and present-day human populations have not been established. We have extracted DNA from a 40,000-y-old anatomically modern human from Tianyuan Cave outside Beijing, China. Using a highly scalable hybridization enrichment strategy, we determined the DNA sequences of the mitochondrial genome, the entire nonrepetitive portion of chromosome 21 (∼30 Mbp), and over 3,000 polymorphic sites across the nuclear genome of this individual. The nuclear DNA sequences determined from this early modern human reveal that the Tianyuan individual derived from a population that was ancestral to many present-day Asians and Native Americans but postdated the divergence of Asians from Europeans. They also show that this individual carried proportions of DNA variants derived from archaic humans similar to present-day people in mainland Asia. PMID:23341637

  6. Early and Late Damages in Chromosome 3 of Human Lymphocytes After Radiation Exposure

    NASA Technical Reports Server (NTRS)

    Sunagawa, Mayumi; Mangala, Lingegowda; Zhang, Ye; Kahdim, Munira; Wilson, Bobby; Cucinotta, Francis A.; Wu, Honglu

    2011-01-01

    Tumor formation in humans or animals is a multi-step process. An early stage of cancer development is believed to be genomic instability (GI) which accelerates the mutation rate in the descendants of the cells surviving radiation exposure. GI is defined as elevated or persistent genetic damages occurring many generations after the cells are exposed. While early studies have demonstrated radiation-induced GI in several cell types as detected in endpoints such as mutation, apoptosis and damages in chromosomes, the dependence of GI on the quality of radiation remains uncertain. To investigate GI in human lymphocytes induced by both low- and high-LET radiation, we initially exposed white blood cells collected from healthy subjects to gamma rays in vitro, and cultured the cells for multiple generations. Chromosome aberrations were analyzed in cells collected at first mitosis post irradiation and at several intervals during the culture period. Among a number of biological endpoints planned for the project, the multi-color banding fluorescent in situ hybridization (mBAND) allows identification of inversions that were expected to be stable. We present here early and late chromosome aberrations detected with mBAND in chromosome 3 after gamma exposure. Comparison of chromosome damages in between human lymphocytes and human epithelial cells is also discussed

  7. A Re-Appraisal of the Early Andean Human Remains from Lauricocha in Peru.

    PubMed

    Fehren-Schmitz, Lars; Llamas, Bastien; Lindauer, Susanne; Tomasto-Cagigao, Elsa; Kuzminsky, Susan; Rohland, Nadin; Santos, Fabrício R; Kaulicke, Peter; Valverde, Guido; Richards, Stephen M; Nordenfelt, Susanne; Seidenberg, Verena; Mallick, Swapan; Cooper, Alan; Reich, David; Haak, Wolfgang

    2015-01-01

    The discovery of human remains from the Lauricocha cave in the Central Andean highlands in the 1960's provided the first direct evidence for human presence in the high altitude Andes. The skeletons found at this site were ascribed to the Early to Middle Holocene and represented the oldest known population of Western South America, and thus were used in several studies addressing the early population history of the continent. However, later excavations at Lauricocha led to doubts regarding the antiquity of the site. Here, we provide new dating, craniometric, and genetic evidence for this iconic site. We obtained new radiocarbon dates, generated complete mitochondrial genomes and nuclear SNP data from five individuals, and re-analyzed the human remains of Lauricocha to revise the initial morphological and craniometric analysis conducted in the 1960's. We show that Lauricocha was indeed occupied in the Early to Middle Holocene but the temporal spread of dates we obtained from the human remains show that they do not qualify as a single contemporaneous population. However, the genetic results from five of the individuals fall within the spectrum of genetic diversity observed in pre-Columbian and modern Native Central American populations. PMID:26061688

  8. Welcome to the Twilight Zone: a forgotten early phase of human evolutionary studies.

    PubMed

    Delisle, Richard G

    2012-06-01

    The field of paleoanthropology arose out of a strange and unacknowledged early phase of development prior to about the 1930s. It is often assumed that a key pillar of the discipline, the unity of humankind--the notion that humans are clearly separated phylogenetically (genealogically) from other non-human primates--was widely accepted from the inception of paleoanthropology around 1860. However, a final consensus on this fundamental question only appeared later on in the 20th century. This paper will focus on two key areas of disagreement, which reveal the unsettled state of this question during this early period: the question of uncertainty with respect to the number, identity and boundary of primate species (including humans) which prevailed in the 18th, 19th and early 20th centuries; and the matter of uncertainty with respect to the nature of the phylogenetic relationships among the various human populations and the other primate species which prevailed between 1864 and 1931. Consideration of these matters reveals that the modern research structure that paleoanthropologists take for granted today is much more recent than believed. PMID:22305470

  9. A Re-Appraisal of the Early Andean Human Remains from Lauricocha in Peru

    PubMed Central

    Kuzminsky, Susan; Rohland, Nadin; Santos, Fabrício R.; Kaulicke, Peter; Valverde, Guido; Richards, Stephen M.; Nordenfelt, Susanne; Seidenberg, Verena; Mallick, Swapan; Cooper, Alan; Reich, David; Haak, Wolfgang

    2015-01-01

    The discovery of human remains from the Lauricocha cave in the Central Andean highlands in the 1960’s provided the first direct evidence for human presence in the high altitude Andes. The skeletons found at this site were ascribed to the Early to Middle Holocene and represented the oldest known population of Western South America, and thus were used in several studies addressing the early population history of the continent. However, later excavations at Lauricocha led to doubts regarding the antiquity of the site. Here, we provide new dating, craniometric, and genetic evidence for this iconic site. We obtained new radiocarbon dates, generated complete mitochondrial genomes and nuclear SNP data from five individuals, and re-analyzed the human remains of Lauricocha to revise the initial morphological and craniometric analysis conducted in the 1960’s. We show that Lauricocha was indeed occupied in the Early to Middle Holocene but the temporal spread of dates we obtained from the human remains show that they do not qualify as a single contemporaneous population. However, the genetic results from five of the individuals fall within the spectrum of genetic diversity observed in pre-Columbian and modern Native Central American populations. PMID:26061688

  10. Digit ratios predict polygyny in early apes, Ardipithecus, Neanderthals and early modern humans but not in Australopithecus

    PubMed Central

    Nelson, Emma; Rolian, Campbell; Cashmore, Lisa; Shultz, Susanne

    2011-01-01

    Social behaviour of fossil hominoid species is notoriously difficult to predict owing to difficulties in estimating body size dimorphism from fragmentary remains and, in hominins, low canine size dimorphism. Recent studies have shown that the second-to-fourth digit ratio (2D : 4D), a putative biomarker for prenatal androgen effects (PAEs), covaries with intra-sexual competition and social systems across haplorrhines; non-pair-bonded polygynous taxa have significantly lower 2D : 4D ratios (high PAE) than pair-bonded monogamous species. Here, we use proximal phalanx ratios of extant and fossil specimens to reconstruct the social systems of extinct hominoids. Pierolapithecus catalaunicus, Hispanopithecus laietanus and Ardipithecus ramidus have ratios consistent with polygynous extant species, whereas the ratio of Australopithecus afarensis is consistent with monogamous extant species. The early anatomically modern human Qafzeh 9 and Neanderthals have lower digit ratios than most contemporary human populations, indicating increased androgenization and possibly higher incidence of polygyny. Although speculative owing to small sample sizes, these results suggest that digit ratios represent a supplementary approach for elucidating the social systems of fossil hominins. PMID:21047863

  11. Digit ratios predict polygyny in early apes, Ardipithecus, Neanderthals and early modern humans but not in Australopithecus.

    PubMed

    Nelson, Emma; Rolian, Campbell; Cashmore, Lisa; Shultz, Susanne

    2011-05-22

    Social behaviour of fossil hominoid species is notoriously difficult to predict owing to difficulties in estimating body size dimorphism from fragmentary remains and, in hominins, low canine size dimorphism. Recent studies have shown that the second-to-fourth digit ratio (2D : 4D), a putative biomarker for prenatal androgen effects (PAEs), covaries with intra-sexual competition and social systems across haplorrhines; non-pair-bonded polygynous taxa have significantly lower 2D : 4D ratios (high PAE) than pair-bonded monogamous species. Here, we use proximal phalanx ratios of extant and fossil specimens to reconstruct the social systems of extinct hominoids. Pierolapithecus catalaunicus, Hispanopithecus laietanus and Ardipithecus ramidus have ratios consistent with polygynous extant species, whereas the ratio of Australopithecus afarensis is consistent with monogamous extant species. The early anatomically modern human Qafzeh 9 and Neanderthals have lower digit ratios than most contemporary human populations, indicating increased androgenization and possibly higher incidence of polygyny. Although speculative owing to small sample sizes, these results suggest that digit ratios represent a supplementary approach for elucidating the social systems of fossil hominins. PMID:21047863

  12. The backbone of the post-synaptic density originated in a unicellular ancestor of choanoflagellates and metazoans

    PubMed Central

    2010-01-01

    Background Comparative genomics of the early diverging metazoan lineages and of their unicellular sister-groups opens new window to reconstructing the genetic changes which preceded or accompanied the evolution of multicellular body plans. A recent analysis found that the genome of the nerve-less sponges encodes the homologues of most vertebrate post-synaptic proteins. In vertebrate excitatory synapses, these proteins assemble to form the post-synaptic density, a complex molecular platform linking membrane receptors, components of their signalling pathways, and the cytoskeleton. Newly available genomes from Monosiga brevicollis (a member of Choanoflagellata, the closest unicellular relatives of animals) and Trichoplax adhaerens (a member of Placozoa: besides sponges, the only nerve-less metazoans) offer an opportunity to refine our understanding of post-synaptic protein evolution. Results Searches for orthologous proteins and reconstruction of gene gains/losses based on the taxon phylogeny indicate that post-synaptic proteins originated in two main steps. The backbone scaffold proteins (Shank, Homer, DLG) and some of their partners were acquired in a unicellular ancestor of choanoflagellates and metazoans. A substantial additional set appeared in an exclusive ancestor of the Metazoa. The placozoan genome contains most post-synaptic genes but lacks some of them. Notably, the master-scaffold protein Shank might have been lost secondarily in the placozoan lineage. Conclusions The time of origination of most post-synaptic proteins was not concomitant with the acquisition of synapses or neural-like cells. The backbone of the scaffold emerged in a unicellular context and was probably not involved in cell-cell communication. Based on the reconstructed protein composition and potential interactions, its ancestral function could have been to link calcium signalling and cytoskeleton regulation. The complex later became integrated into the evolving synapse through the

  13. Volcanic ash layers illuminate the resilience of Neanderthals and early modern humans to natural hazards.

    PubMed

    Lowe, John; Barton, Nick; Blockley, Simon; Ramsey, Christopher Bronk; Cullen, Victoria L; Davies, William; Gamble, Clive; Grant, Katharine; Hardiman, Mark; Housley, Rupert; Lane, Christine S; Lee, Sharen; Lewis, Mark; MacLeod, Alison; Menzies, Martin; Müller, Wolfgang; Pollard, Mark; Price, Catherine; Roberts, Andrew P; Rohling, Eelco J; Satow, Chris; Smith, Victoria C; Stringer, Chris B; Tomlinson, Emma L; White, Dustin; Albert, Paul; Arienzo, Ilenia; Barker, Graeme; Boric, Dusan; Carandente, Antonio; Civetta, Lucia; Ferrier, Catherine; Guadelli, Jean-Luc; Karkanas, Panagiotis; Koumouzelis, Margarita; Müller, Ulrich C; Orsi, Giovanni; Pross, Jörg; Rosi, Mauro; Shalamanov-Korobar, Ljiljiana; Sirakov, Nikolay; Tzedakis, Polychronis C

    2012-08-21

    Marked changes in human dispersal and development during the Middle to Upper Paleolithic transition have been attributed to massive volcanic eruption and/or severe climatic deterioration. We test this concept using records of volcanic ash layers of the Campanian Ignimbrite eruption dated to ca. 40,000 y ago (40 ka B.P.). The distribution of the Campanian Ignimbrite has been enhanced by the discovery of cryptotephra deposits (volcanic ash layers that are not visible to the naked eye) in archaeological cave sequences. They enable us to synchronize archaeological and paleoclimatic records through the period of transition from Neanderthal to the earliest anatomically modern human populations in Europe. Our results confirm that the combined effects of a major volcanic eruption and severe climatic cooling failed to have lasting impacts on Neanderthals or early modern humans in Europe. We infer that modern humans proved a greater competitive threat to indigenous populations than natural disasters. PMID:22826222

  14. Volcanic ash layers illuminate the resilience of Neanderthals and early modern humans to natural hazards

    PubMed Central

    Lowe, John; Barton, Nick; Blockley, Simon; Ramsey, Christopher Bronk; Cullen, Victoria L.; Davies, William; Gamble, Clive; Grant, Katharine; Hardiman, Mark; Housley, Rupert; Lane, Christine S.; Lee, Sharen; Lewis, Mark; MacLeod, Alison; Menzies, Martin; Müller, Wolfgang; Pollard, Mark; Price, Catherine; Roberts, Andrew P.; Rohling, Eelco J.; Satow, Chris; Smith, Victoria C.; Stringer, Chris B.; Tomlinson, Emma L.; White, Dustin; Albert, Paul; Arienzo, Ilenia; Barker, Graeme; Borić, Dušan; Carandente, Antonio; Civetta, Lucia; Ferrier, Catherine; Guadelli, Jean-Luc; Karkanas, Panagiotis; Koumouzelis, Margarita; Müller, Ulrich C.; Orsi, Giovanni; Pross, Jörg; Rosi, Mauro; Shalamanov-Korobar, Ljiljiana; Sirakov, Nikolay; Tzedakis, Polychronis C.

    2012-01-01

    Marked changes in human dispersal and development during the Middle to Upper Paleolithic transition have been attributed to massive volcanic eruption and/or severe climatic deterioration. We test this concept using records of volcanic ash layers of the Campanian Ignimbrite eruption dated to ca. 40,000 y ago (40 ka B.P.). The distribution of the Campanian Ignimbrite has been enhanced by the discovery of cryptotephra deposits (volcanic ash layers that are not visible to the naked eye) in archaeological cave sequences. They enable us to synchronize archaeological and paleoclimatic records through the period of transition from Neanderthal to the earliest anatomically modern human populations in Europe. Our results confirm that the combined effects of a major volcanic eruption and severe climatic cooling failed to have lasting impacts on Neanderthals or early modern humans in Europe. We infer that modern humans proved a greater competitive threat to indigenous populations than natural disasters. PMID:22826222

  15. Human chronic gonadotropin concentrations in very early pregnancy and subsequent preeclampsia.

    PubMed

    Rabie, Nader Z; Magann, Everett F

    2014-09-01

    Evaluation of: Asvold BO, Vatten LJ, Tanbo TG, Eskild A. Concentrations of human chorionic gonadotrophin in very early pregnancy and subsequent pre-eclampsia: a cohort study. Hum. Reprod. 29(6), 1153-1160 (2014). A total of 2405 consecutive singleton pregnancies were followed to determine if early HCG levels were associated with the development of preeclampsia. All pregnancies were conceived by in vitro fertilization, which allowed very accurate gestational age dating. HCG levels were obtained on day 12, and grouped into 4 categories (<50, 50-99, 100-149, ≥ 150). HCG levels less than 50 were associated with an odds ratio of 2.3 (95% CI: 1.2-4.7) for preeclampsia and and odds ratio of 4.2 (95% CI: 1.4-12.2) for severe preeclampsia. Early HCG levels may serve as a marker for the detection of preeclampsia. PMID:25335537

  16. [On the road to a new humanity: the reception of psychoanalysis in the early Kinderladen movement].

    PubMed

    Kauders, Anthony D

    2014-01-01

    In the late 1960s a group of students in West Germany founded the so-called Kinderläden (day care centers) in order to experiment with new forms of early childhood education. Members of the early Kinderladen movement in particular pursued a radically utopian approach that, they hoped, would engender new human beings. With the aid of psychoanalytic writings, especially those of Wilhelm Reich, they sought to create subjects that would overcome repressive bourgeois norms and live out their sexuality freely. This reliance on Reich entailed a new interpretation of the "base", as psychoanalytic drive theory supplanted Marxist theory. As such, the early Kinderladen ac- tivists regarded the "basis" of society in biological, psychological, and pedagogic rather than economic terms. PMID:25872313

  17. Transcriptional Factor PU.1 Regulates Decidual C1q Expression in Early Pregnancy in Human.

    PubMed

    Madhukaran, Shanmuga Priyaa; Kishore, Uday; Jamil, Kaiser; Teo, Boon Heng Dennis; Choolani, Mahesh; Lu, Jinhua

    2015-01-01

    C1q is the first recognition subcomponent of the complement classical pathway, which in addition to being synthesized in the liver, is also expressed by macrophages and dendritic cells (DCs). Trophoblast invasion during early placentation results in accumulation of debris that triggers the complement system. Hence, both early and late components of the classical pathway are widely distributed in the placenta and decidua. In addition, C1q has recently been shown to significantly contribute to feto-maternal tolerance, trophoblast migration, and spiral artery remodeling, although the exact mechanism remains unknown. Pregnancy in mice, genetically deficient in C1q, mirrors symptoms similar to that of human preeclampsia. Thus, regulated complement activation has been proposed as an essential requirement for normal successful pregnancy. Little is known about the molecular pathways that regulate C1q expression in pregnancy. PU.1, an Ets-family transcription factor, is required for the development of hematopoietic myeloid lineage immune cells, and its expression is tissue-specific. Recently, PU.1 has been shown to regulate C1q gene expression in DCs and macrophages. Here, we have examined if PU.1 transcription factor regulates decidual C1q expression. We used immune-histochemical analysis, PCR, and immunostaining to localize and study the gene expression of PU.1 transcription factor in early human decidua. PU.1 was highly expressed at gene and protein level in early human decidual cells including trophoblast and stromal cells. Surprisingly, nuclear as well as cytoplasmic PU.1 expression was observed. Decidual cells with predominantly nuclear PU.1 expression had higher C1q expression. It is likely that nuclear and cytoplasmic PU.1 localization has a role to play in early pregnancy via regulating C1q expression in the decidua during implantation. PMID:25762996

  18. Expression of immediate early genes after treatment of human astrocytoma cells with radiation and taxol

    SciTech Connect

    Gubits, R.M.; Geard, C.R.; Schiff, P.B.

    1993-10-20

    The promising chemotherapeutic agent, taxol, has been shown to sensitize the G18 line of human astrocytoma cells to ionizing radiation. The present studies were performed to identify specific changes in gene expression associated with this altered sensitivity. The products of immediate early genes, which are induced transiently in cells in response to a variety of treatments, including growth factors, neurotransmitters, and irradiation with UV light or X rays, are thought to initiate a cascade of genetic responses to alterations in cellular environment. The present results demonstrate a dramatic attenuation in one immediate early gene response in association with a treatment that enhances radiosensitivity in a refractory human brain tumor line. 22 refs., 5 figs., 1 tab.

  19. Early Upper Paleolithic in Eastern Europe and implications for the dispersal of modern humans.

    PubMed

    Anikovich, M V; Sinitsyn, A A; Hoffecker, John F; Holliday, Vance T; Popov, V V; Lisitsyn, S N; Forman, Steven L; Levkovskaya, G M; Pospelova, G A; Kuz'mina, I E; Burova, N D; Goldberg, Paul; Macphail, Richard I; Giaccio, Biagio; Praslov, N D

    2007-01-12

    Radiocarbon and optically stimulated luminescence dating and magnetic stratigraphy indicate Upper Paleolithic occupation-probably representing modern humans-at archaeological sites on the Don River in Russia 45,000 to 42,000 years ago. The oldest levels at Kostenki underlie a volcanic ash horizon identified as the Campanian Ignimbrite Y5 tephra that is dated elsewhere to about 40,000 years ago. The occupation layers contain bone and ivory artifacts, including possible figurative art, and fossil shells imported more than 500 kilometers. Thus, modern humans appeared on the central plain of Eastern Europe as early as anywhere else in northern Eurasia. PMID:17218523

  20. Some early uses of evoked brain responses in investigations of human visual function.

    PubMed

    Regan, D

    2009-05-01

    In the context of the technical possibilities of the time, this paper describes early attempts to employ visual-evoked potentials (VEPs) as a tool for investigating human visual function, focussing on the contributions of Henk Spekreijse and his colleagues. The topics covered are as follows: attempts to distinguish between true pattern-specific VEPs and the effects of responses to changes in local luminance; retinal rivalry and interocular sustained suppression; the implications of VEPs elicited by equiluminant chromatic patterns; VEPs specific to real and apparent motion; stereo VEPs; identification of a visual-auditory convergence area in the human brain. PMID:18304602

  1. Early humans' egalitarian politics: runaway synergistic competition under an adapted veil of ignorance.

    PubMed

    Harvey, Marc

    2014-09-01

    This paper proposes a model of human uniqueness based on an unusual distinction between two contrasted kinds of political competition and political status: (1) antagonistic competition, in quest of dominance (antagonistic status), a zero-sum, self-limiting game whose stake--who takes what, when, how--summarizes a classical definition of politics (Lasswell 1936), and (2) synergistic competition, in quest of merit (synergistic status), a positive-sum, self-reinforcing game whose stake becomes "who brings what to a team's common good." In this view, Rawls's (1971) famous virtual "veil of ignorance" mainly conceals politics' antagonistic stakes so as to devise the principles of a just, egalitarian society, yet without providing any means to enforce these ideals (Sen 2009). Instead, this paper proposes that human uniqueness flourished under a real "adapted veil of ignorance" concealing the steady inflation of synergistic politics which resulted from early humans' sturdy egalitarianism. This proposition divides into four parts: (1) early humans first stumbled on a purely cultural means to enforce a unique kind of within-team antagonistic equality--dyadic balanced deterrence thanks to handheld weapons (Chapais 2008); (2) this cultural innovation is thus closely tied to humans' darkest side, but it also launched the cumulative evolution of humans' brightest qualities--egalitarian team synergy and solidarity, together with the associated synergistic intelligence, culture, and communications; (3) runaway synergistic competition for differential merit among antagonistically equal obligate teammates is the single politically selective mechanism behind the cumulative evolution of all these brighter qualities, but numerous factors to be clarified here conceal this mighty evolutionary driver; (4) this veil of ignorance persists today, which explains why humans' unique prosocial capacities are still not clearly understood by science. The purpose of this paper is to start lifting

  2. Behavioral inferences from the Skhul/Qafzeh early modern human hand remains

    PubMed Central

    Niewoehner, Wesley A.

    2001-01-01

    Two groups of humans are found in the Near East ≈100,000 years ago, the late archaic Neanderthals and the early modern Skhul/Qafzeh humans. Observations that Neanderthals were more heavily muscled, had stronger upper-limb bones, and possessed unusual shapes and orientations of some upper-limb joint complexes relative to the Skhul/Qafzeh hominids, have led some researchers to conclude that significant between-group upper-limb-related behavioral differences must have been present, despite the association of the two groups with similar Middle Paleolithic archeological complexes. A three-dimensional morphometric analysis of the hand remains of the Skhul/Qafzeh hominids, Neanderthals, early and late Upper Paleolithic humans, and Holocene humans supports the dichotomy. The Skhul/Qafzeh carpometacarpal remains do not have any unique morphologies relative to the other fossil samples remains examined. However, in the functionally significant metacarpal 1 and 3 bases they resemble Upper Paleolithic humans, not Neanderthals. Furthermore, the Skhul/Qafzeh sample differs significantly from the Neanderthals in many other aspects of hand functional anatomy. Given the correlations between changes in tool technologies and functional adaptations seen in the hands of Upper Paleolithic humans, it is concluded that the Skhul/Qafzeh hand remains were adapted to Upper Paleolithic-like manipulative repertoires. These results support the inference of significant behavioral differences between Neanderthals and the Skhul/Qafzeh hominids and indicate that a significant shift in human manipulative behaviors was associated with the earliest stages of the emergence of modern humans. PMID:11248017

  3. The Effects of Context and Attention on Spiking Activity in Human Early Visual Cortex.

    PubMed

    Self, Matthew W; Peters, Judith C; Possel, Jessy K; Reithler, Joel; Goebel, Rainer; Ris, Peterjan; Jeurissen, Danique; Reddy, Leila; Claus, Steven; Baayen, Johannes C; Roelfsema, Pieter R

    2016-03-01

    Here we report the first quantitative analysis of spiking activity in human early visual cortex. We recorded multi-unit activity from two electrodes in area V2/V3 of a human patient implanted with depth electrodes as part of her treatment for epilepsy. We observed well-localized multi-unit receptive fields with tunings for contrast, orientation, spatial frequency, and size, similar to those reported in the macaque. We also observed pronounced gamma oscillations in the local-field potential that could be used to estimate the underlying spiking response properties. Spiking responses were modulated by visual context and attention. We observed orientation-tuned surround suppression: responses were suppressed by image regions with a uniform orientation and enhanced by orientation contrast. Additionally, responses were enhanced on regions that perceptually segregated from the background, indicating that neurons in the human visual cortex are sensitive to figure-ground structure. Spiking responses were also modulated by object-based attention. When the patient mentally traced a curve through the neurons' receptive fields, the accompanying shift of attention enhanced neuronal activity. These results demonstrate that the tuning properties of cells in the human early visual cortex are similar to those in the macaque and that responses can be modulated by both contextual factors and behavioral relevance. Our results, therefore, imply that the macaque visual system is an excellent model for the human visual cortex. PMID:27015604

  4. Isotopic evidence for the diets of European Neanderthals and early modern humans

    PubMed Central

    Richards, Michael P.; Trinkaus, Erik

    2009-01-01

    We report here on the direct isotopic evidence for Neanderthal and early modern human diets in Europe. Isotopic methods indicate the sources of dietary protein over many years of life, and show that Neanderthals had a similar diet through time (≈120,000 to ≈37,000 cal BP) and in different regions of Europe. The isotopic evidence indicates that in all cases Neanderthals were top-level carnivores and obtained all, or most, of their dietary protein from large herbivores. In contrast, early modern humans (≈40,000 to ≈27,000 cal BP) exhibited a wider range of isotopic values, and a number of individuals had evidence for the consumption of aquatic (marine and freshwater) resources. This pattern includes Oase 1, the oldest directly dated modern human in Europe (≈40,000 cal BP) with the highest nitrogen isotope value of all of the humans studied, likely because of freshwater fish consumption. As Oase 1 was close in time to the last Neanderthals, these data may indicate a significant dietary shift associated with the changing population dynamics of modern human emergence in Europe. PMID:19706482

  5. Sustained live poultry market surveillance contributes to early warnings for human infection with avian influenza viruses.

    PubMed

    Fang, Shisong; Bai, Tian; Yang, Lei; Wang, Xin; Peng, Bo; Liu, Hui; Geng, Yijie; Zhang, Renli; Ma, Hanwu; Zhu, Wenfei; Wang, Dayan; Cheng, Jinquan; Shu, Yuelong

    2016-01-01

    Sporadic human infections with the highly pathogenic avian influenza (HPAI) A (H5N6) virus have been reported in different provinces in China since April 2014. From June 2015 to January 2016, routine live poultry market (LPM) surveillance was conducted in Shenzhen, Guangdong Province. H5N6 viruses were not detected until November 2015. The H5N6 virus-positive rate increased markedly beginning in December 2015, and viruses were detected in LPMs in all districts of the city. Coincidently, two human cases with histories of poultry exposure developed symptoms and were diagnosed as H5N6-positive in Shenzhen during late December 2015 and early January 2016. Similar viruses were identified in environmental samples collected in the LPMs and the patients. In contrast to previously reported H5N6 viruses, viruses with six internal genes derived from the H9N2 or H7N9 viruses were detected in the present study. The increased H5N6 virus-positive rate in the LPMs and the subsequent human infections demonstrated that sustained LPM surveillance for avian influenza viruses provides an early warning for human infections. Interventions, such as LPM closures, should be immediately implemented to reduce the risk of human infection with the H5N6 virus when the virus is widely detected during LPM surveillance. PMID:27485495

  6. The Effects of Context and Attention on Spiking Activity in Human Early Visual Cortex

    PubMed Central

    Reithler, Joel; Goebel, Rainer; Ris, Peterjan; Jeurissen, Danique; Reddy, Leila; Claus, Steven; Baayen, Johannes C.; Roelfsema, Pieter R.

    2016-01-01

    Here we report the first quantitative analysis of spiking activity in human early visual cortex. We recorded multi-unit activity from two electrodes in area V2/V3 of a human patient implanted with depth electrodes as part of her treatment for epilepsy. We observed well-localized multi-unit receptive fields with tunings for contrast, orientation, spatial frequency, and size, similar to those reported in the macaque. We also observed pronounced gamma oscillations in the local-field potential that could be used to estimate the underlying spiking response properties. Spiking responses were modulated by visual context and attention. We observed orientation-tuned surround suppression: responses were suppressed by image regions with a uniform orientation and enhanced by orientation contrast. Additionally, responses were enhanced on regions that perceptually segregated from the background, indicating that neurons in the human visual cortex are sensitive to figure-ground structure. Spiking responses were also modulated by object-based attention. When the patient mentally traced a curve through the neurons’ receptive fields, the accompanying shift of attention enhanced neuronal activity. These results demonstrate that the tuning properties of cells in the human early visual cortex are similar to those in the macaque and that responses can be modulated by both contextual factors and behavioral relevance. Our results, therefore, imply that the macaque visual system is an excellent model for the human visual cortex. PMID:27015604

  7. Conserved epigenetic sensitivity to early life experience in the rat and human hippocampus.

    PubMed

    Suderman, Matthew; McGowan, Patrick O; Sasaki, Aya; Huang, Tony C T; Hallett, Michael T; Meaney, Michael J; Turecki, Gustavo; Szyf, Moshe

    2012-10-16

    Early life experience is associated with long-term effects on behavior and epigenetic programming of the NR3C1 (GLUCOCORTICOID RECEPTOR) gene in the hippocampus of both rats and humans. However, it is unlikely that such effects completely capture the evolutionarily conserved epigenetic mechanisms of early adaptation to environment. Here we present DNA methylation profiles spanning 6.5 million base pairs centered at the NR3C1 gene in the hippocampus of humans who experienced abuse as children and nonabused controls. We compare these profiles to corresponding DNA methylation profiles in rats that received differential levels of maternal care. The profiles of both species reveal hundreds of DNA methylation differences associated with early life experience distributed across the entire region in nonrandom patterns. For instance, methylation differences tend to cluster by genomic location, forming clusters covering as many as 1 million bases. Even more surprisingly, these differences seem to specifically target regulatory regions such as gene promoters, particularly those of the protocadherin α, β, and γ gene families. Beyond these high-level similarities, more detailed analyses reveal methylation differences likely stemming from the significant biological and environmental differences between species. These results provide support for an analogous cross-species epigenetic regulatory response at the level of the genomic region to early life experience. PMID:23045659

  8. Human Herpesvirus 6 Latently Infects Early Bone Marrow Progenitors In Vivo

    PubMed Central

    Luppi, Mario; Barozzi, Patrizia; Morris, Christine; Maiorana, Antonio; Garber, Richard; Bonacorsi, Goretta; Donelli, Amedea; Marasca, Roberto; Tabilio, Antonio; Torelli, Giuseppe

    1999-01-01

    We have studied the in vivo tropism of human herpesvirus 6 (HHV-6) for hemopoietic cells in patients with latent HHV-6 infection. Having used a variety of cell purification, molecular, cytogenetic, and immunocytochemical procedures, we report the first evidence that HHV-6 latently infects early bone marrow progenitor cells and that HHV-6 may be transmitted longitudinally to cells which differentiate along the committed pathways. PMID:9847383

  9. James L. German, a pioneer in early human genetic research turned 90.

    PubMed

    Passarge, Eberhard

    2016-06-01

    In the early 1960s, J. German established the non-synchronous human DNA replication pattern in metaphases of cultured lymphocytes and fibroblasts. This could be used to distinguish several chromosomes of similar morphology. From 1965 on over the next 30 years, he and his coworkers systematically studied Bloom's syndrome in depth, cumulating in the identification in 1995 of the BLM gene as encoding a DNA helicase. © 2016 Wiley Periodicals, Inc. PMID:27016306

  10. Early human cultural and skeletal remains from guitarrero cave, northern peru.

    PubMed

    Lynch, T F; Kennedy, K A

    1970-09-25

    An early man site in highland Peru yielded a rich cultural assemblage in stratigraphic association with faunal remains, botanical remains, and campfire remnants that furnished secure radiocarbon dates. A human mandible and teeth, showing interesting patterns of occlusal wear, were found in a stratum dated by a charcoal sample to 10,610 B.C., the oldest such date in South America. PMID:17772515

  11. Analyzing the Rate at Which Languages Lose the Influence of a Common Ancestor

    ERIC Educational Resources Information Center

    Rafferty, Anna N.; Griffiths, Thomas L.; Klein, Dan

    2014-01-01

    Analyzing the rate at which languages change can clarify whether similarities across languages are solely the result of cognitive biases or might be partially due to descent from a common ancestor. To demonstrate this approach, we use a simple model of language evolution to mathematically determine how long it should take for the distribution over…

  12. Markov-chain approach to the distribution of ancestors in species of biparental reproduction

    NASA Astrophysics Data System (ADS)

    Caruso, M.; Jarne, C.

    2014-08-01

    We studied how to obtain a distribution for the number of ancestors in species of sexual reproduction. Present models concentrate on the estimation of distributions repetitions of ancestors in genealogical trees. It has been shown that it is not possible to reconstruct the genealogical history of each species along all its generations by means of a geometric progression. This analysis demonstrates that it is possible to rebuild the tree of progenitors by modeling the problem with a Markov chain. For each generation, the maximum number of possible ancestors is different. This presents huge problems for the resolution. We found a solution through a dilation of the sample space, although the distribution defined there takes smaller values with respect to the initial problem. In order to correct the distribution for each generation, we introduced the invariance under a gauge (local) group of dilations. These ideas can be used to study the interaction of several processes and provide a new approach on the problem of the common ancestor. In the same direction, this model also provides some elements that can be used to improve models of animal reproduction.

  13. Integration of Morphological Data into Molecular Phylogenetic Analysis: Toward the Identikit of the Stylasterid Ancestor.

    PubMed

    Puce, Stefania; Pica, Daniela; Schiaparelli, Stefano; Negrisolo, Enrico

    2016-01-01

    Stylasteridae is a hydroid family including 29 worldwide-distributed genera, all provided with a calcareous skeleton. They are abundant in shallow and deep waters and represent an important component of marine communities. In the present paper, we studied the evolution of ten morphological characters, currently used in stylasterid taxonomy, using a phylogenetic approach. Our results indicate that stylasterid morphology is highly plastic and that many events of independent evolution and reversion have occurred. Our analysis also allows sketching a possible identikit of the stylasterid ancestor. It had calcareous skeleton, reticulate-granular coenosteal texture, polyps randomly arranged, gastrostyle, and dactylopore spines, while lacking a gastropore lip and dactylostyles. If the ancestor had single or double/multiple chambered gastropore tube is uncertain. These data suggest that the ancestor was similar to the extant genera Cyclohelia and Stellapora. Our investigation is the first attempt to integrate molecular and morphological information to clarify the stylasterid evolutionary scenario and represents the first step to infer the stylasterid ancestor morphology. PMID:27537333

  14. Integration of Morphological Data into Molecular Phylogenetic Analysis: Toward the Identikit of the Stylasterid Ancestor

    PubMed Central

    Puce, Stefania; Pica, Daniela; Schiaparelli, Stefano; Negrisolo, Enrico

    2016-01-01

    Stylasteridae is a hydroid family including 29 worldwide-distributed genera, all provided with a calcareous skeleton. They are abundant in shallow and deep waters and represent an important component of marine communities. In the present paper, we studied the evolution of ten morphological characters, currently used in stylasterid taxonomy, using a phylogenetic approach. Our results indicate that stylasterid morphology is highly plastic and that many events of independent evolution and reversion have occurred. Our analysis also allows sketching a possible identikit of the stylasterid ancestor. It had calcareous skeleton, reticulate-granular coenosteal texture, polyps randomly arranged, gastrostyle, and dactylopore spines, while lacking a gastropore lip and dactylostyles. If the ancestor had single or double/multiple chambered gastropore tube is uncertain. These data suggest that the ancestor was similar to the extant genera Cyclohelia and Stellapora. Our investigation is the first attempt to integrate molecular and morphological information to clarify the stylasterid evolutionary scenario and represents the first step to infer the stylasterid ancestor morphology. PMID:27537333

  15. Genome sequence and annotation of Trichoderma parareesei, the ancestor of the cellulase producer Trichoderma reesei

    DOE PAGESBeta

    Yang, Dongqing; Pomraning, Kyle; Kopchinskiy, Alexey; Karimi, Aghcheh Razieh; Atanasova, Lea; Chenthamara, Komal; Baker, Scott E.; Zhang, Ruifu; Shen, Qirong; Freitag, Michael; et al

    2015-08-13

    The filamentous fungus Trichoderma parareesei is the asexually reproducing ancestor of Trichoderma reesei, the holomorphic industrial producer of cellulase and hemicellulase. Here, we present the genome sequence of the T. parareesei type strain CBS 125925, which contains genes for 9,318 proteins.

  16. Early Parental Care Is Important for Hippocampal Maturation: Evidence from Brain Morphology in Humans

    PubMed Central

    Rao, Hengyi; Betancourt, Laura; Giannetta, Joan M.; Brodsky, Nancy L.; Korczykowski, Marc; Avants, Brian B.; Gee, James C.; Wang, Jiongjiong; Hurt, Hallam; Detre, John A.; Farah, Martha J.

    2009-01-01

    The effects of early life experience on later brain structure and function have been studied extensively in animals, yet the relationship between childhood experience and normal brain development in humans remains largely unknown. Using a unique longitudinal data set including ecologically valid in-home measures of early experience during childhood (at age 4 and 8 years) and high-resolution structural brain imaging during adolescence (mean age 14 years), we examined the effects on later brain morphology of two dimensions of early experience: parental nurturance and environmental stimulation. Parental nurturance at age 4 predicts the volume of the left hippocampus in adolescence, with better nurturance associated with smaller hippocampal volume. In contrast, environmental stimulation did not correlate with hippocampal volume. Moreover, the association between hippocampal volume and parental nurturance disappears at age 8, supporting the existence of a sensitive developmental period for brain maturation. These findings indicate that variation in normal childhood experience is associated with differences in brain morphology, and hippocampal volume is specifically associated with early parental nurturance. Our results provide neuroimaging evidence supporting the important role of warm parental care during early childhood for brain maturation. PMID:19595774

  17. Early Regulation of Profibrotic Genes in Primary Human Cardiac Myocytes by Trypanosoma cruzi

    PubMed Central

    Dykan, Andrey; Rachakonda, Girish; Villalta, Fernando; Mandape, Sammed N.; Lima, Maria F.; Pratap, Siddharth; Nde, Pius N.

    2016-01-01

    The molecular mechanisms of Trypanosoma cruzi induced cardiac fibrosis remains to be elucidated. Primary human cardiomyoctes (PHCM) exposed to invasive T. cruzi trypomastigotes were used for transcriptome profiling and downstream bioinformatic analysis to determine fibrotic-associated genes regulated early during infection process (0 to 120 minutes). The identification of early molecular host responses to T. cruzi infection can be exploited to delineate important molecular signatures that can be used for the classification of Chagasic patients at risk of developing heart disease. Our results show distinct gene network architecture with multiple gene networks modulated by the parasite with an incline towards progression to a fibrogenic phenotype. Early during infection, T. cruzi significantly upregulated transcription factors including activator protein 1 (AP1) transcription factor network components (including FOSB, FOS and JUNB), early growth response proteins 1 and 3 (EGR1, EGR3), and cytokines/chemokines (IL5, IL6, IL13, CCL11), which have all been implicated in the onset of fibrosis. The changes in our selected genes of interest did not all start at the same time point. The transcriptome microarray data, validated by quantitative Real-Time PCR, was also confirmed by immunoblotting and customized Enzyme Linked Immunosorbent Assays (ELISA) array showing significant increases in the protein expression levels of fibrogenic EGR1, SNAI1 and IL 6. Furthermore, phosphorylated SMAD2/3 which induces a fibrogenic phenotype is also upregulated accompanied by an increased nuclear translocation of JunB. Pathway analysis of the validated genes and phospho-proteins regulated by the parasite provides the very early fibrotic interactome operating when T. cruzi comes in contact with PHCM. The interactome architecture shows that the parasite induces both TGF-β dependent and independent fibrotic pathways, providing an early molecular foundation for Chagasic cardiomyopathy

  18. Early Regulation of Profibrotic Genes in Primary Human Cardiac Myocytes by Trypanosoma cruzi.

    PubMed

    Udoko, Aniekanabassi N; Johnson, Candice A; Dykan, Andrey; Rachakonda, Girish; Villalta, Fernando; Mandape, Sammed N; Lima, Maria F; Pratap, Siddharth; Nde, Pius N

    2016-01-01

    The molecular mechanisms of Trypanosoma cruzi induced cardiac fibrosis remains to be elucidated. Primary human cardiomyoctes (PHCM) exposed to invasive T. cruzi trypomastigotes were used for transcriptome profiling and downstream bioinformatic analysis to determine fibrotic-associated genes regulated early during infection process (0 to 120 minutes). The identification of early molecular host responses to T. cruzi infection can be exploited to delineate important molecular signatures that can be used for the classification of Chagasic patients at risk of developing heart disease. Our results show distinct gene network architecture with multiple gene networks modulated by the parasite with an incline towards progression to a fibrogenic phenotype. Early during infection, T. cruzi significantly upregulated transcription factors including activator protein 1 (AP1) transcription factor network components (including FOSB, FOS and JUNB), early growth response proteins 1 and 3 (EGR1, EGR3), and cytokines/chemokines (IL5, IL6, IL13, CCL11), which have all been implicated in the onset of fibrosis. The changes in our selected genes of interest did not all start at the same time point. The transcriptome microarray data, validated by quantitative Real-Time PCR, was also confirmed by immunoblotting and customized Enzyme Linked Immunosorbent Assays (ELISA) array showing significant increases in the protein expression levels of fibrogenic EGR1, SNAI1 and IL 6. Furthermore, phosphorylated SMAD2/3 which induces a fibrogenic phenotype is also upregulated accompanied by an increased nuclear translocation of JunB. Pathway analysis of the validated genes and phospho-proteins regulated by the parasite provides the very early fibrotic interactome operating when T. cruzi comes in contact with PHCM. The interactome architecture shows that the parasite induces both TGF-β dependent and independent fibrotic pathways, providing an early molecular foundation for Chagasic cardiomyopathy

  19. Immunohistochemical Markers of Neural Progenitor Cells in the Early Embryonic Human Cerebral Cortex

    PubMed Central

    Vinci, L.; Ravarino, A.; Fanos, V.; Naccarato, A.G.; Senes, G.; Gerosa, C.; Bevilacqua, G.; Faa, G.; Ambu, R.

    2016-01-01

    The development of the human central nervous system represents a delicate moment of embryogenesis. The purpose of this study was to analyze the expression of multiple immunohistochemical markers in the stem/progenitor cells in the human cerebral cortex during the early phases of development. To this end, samples from cerebral cortex were obtained from 4 human embryos of 11 weeks of gestation. Each sample was formalin-fixed, paraffin embedded and immunostained with several markers including GFAP, WT1, Nestin, Vimentin, CD117, S100B, Sox2, PAX2, PAX5, Tβ4, Neurofilament, CD44, CD133, Synaptophysin and Cyclin D1. Our study shows the ability of the different immunohistochemical markers to evidence different zones of the developing human cerebral cortex, allowing the identification of the multiple stages of differentiation of neuronal and glial precursors. Three important markers of radial glial cells are evidenced in this early gestational age: Vimentin, Nestin and WT1. Sox2 was expressed by the stem/progenitor cells of the ventricular zone, whereas the postmitotic neurons of the cortical plate were immunostained by PAX2 and NSE. Future studies are needed to test other important stem/progenitor cells markers and to better analyze differences in the immunohistochemical expression of these markers during gestation. PMID:26972711

  20. A Novel Fully Humanized 3D Skin Equivalent to Model Early Melanoma Invasion.

    PubMed

    Hill, David S; Robinson, Neil D P; Caley, Matthew P; Chen, Mei; O'Toole, Edel A; Armstrong, Jane L; Przyborski, Stefan; Lovat, Penny E

    2015-11-01

    Metastatic melanoma remains incurable, emphasizing the acute need for improved research models to investigate the underlying biologic mechanisms mediating tumor invasion and metastasis, and to develop more effective targeted therapies to improve clinical outcome. Available animal models of melanoma do not accurately reflect human disease and current in vitro human skin equivalent models incorporating melanoma cells are not fully representative of the human skin microenvironment. We have developed a robust and reproducible, fully humanized three-dimensional (3D) skin equivalent comprising a stratified, terminally differentiated epidermis and a dermal compartment consisting of fibroblast-generated extracellular matrix. Melanoma cells incorporated into the epidermis were able to invade through the basement membrane and into the dermis, mirroring early tumor invasion in vivo. Comparison of our novel 3D melanoma skin equivalent with melanoma in situ and metastatic melanoma indicates that this model accurately recreates features of disease pathology, making it a physiologically representative model of early radial and vertical growth-phase melanoma invasion. PMID:26330548

  1. The first modern human dispersals across Africa.

    PubMed

    Rito, Teresa; Richards, Martin B; Fernandes, Verónica; Alshamali, Farida; Cerny, Viktor; Pereira, Luísa; Soares, Pedro

    2013-01-01

    The emergence of more refined chronologies for climate change and archaeology in prehistoric Africa, and for the evolution of human mitochondrial DNA (mtDNA), now make it feasible to test more sophisticated models of early modern human dispersals suggested by mtDNA distributions. Here we have generated 42 novel whole-mtDNA genomes belonging to haplogroup L0, the most divergent clade in the maternal line of descent, and analysed them alongside the growing database of African lineages belonging to L0's sister clade, L1'6. We propose that the last common ancestor of modern human mtDNAs (carried by "mitochondrial Eve") possibly arose in central Africa ~180 ka, at a time of low population size. By ~130 ka two distinct groups of anatomically modern humans co-existed in Africa: broadly, the ancestors of many modern-day Khoe and San populations in the south and a second central/eastern African group that includes the ancestors of most extant worldwide populations. Early modern human dispersals correlate with climate changes, particularly the tropical African "megadroughts" of MIS 5 (marine isotope stage 5, 135-75 ka) which paradoxically may have facilitated expansions in central and eastern Africa, ultimately triggering the dispersal out of Africa of people carrying haplogroup L3 ~60 ka. Two south to east migrations are discernible within haplogroup LO. One, between 120 and 75 ka, represents the first unambiguous long-range modern human dispersal detected by mtDNA and might have allowed the dispersal of several markers of modernity. A second one, within the last 20 ka signalled by L0d, may have been responsible for the spread of southern click-consonant languages to eastern Africa, contrary to the view that these eastern examples constitute relicts of an ancient, much wider distribution. PMID:24236171

  2. Monitoring of human populations for early markers of cadmium toxicity: A review

    SciTech Connect

    Fowler, Bruce A.

    2009-08-01

    Exposure of human populations to cadmium (Cd) from air, food and water may produce effects in organs such as the kidneys, liver, lungs, cardiovascular, immune and reproductive systems. Since Cd has been identified as a human carcinogen, biomarkers for early detection of susceptibility to cancer are of an importance to public health. The ability to document Cd exposure and uptake of this element through biological monitoring is a first step towards understanding its health effects. Interpretation and application of biological monitoring data for predicting human health outcomes require correlation with biological measures of organ system responses to the documented exposure. Essential to this understanding is the detection and linkage of early biological responses toxic effects in target cell populations. Fortunately, advances in cell biology have resulted in the development of pre-clinical biological markers (biomarkers) that demonstrate measurable and characteristic molecular changes in organ systems following chemical exposures that occur prior to the onset of overt clinical disease or development of cancer. Technical advances have rendered a number of these biomarkers practical for monitoring Cd-exposed human populations. Biomarkers will be increasingly important in relation to monitoring effects from the exposure to new Cd-based high technology materials. For example, cadmium-selenium (CdSe), nano-materials made from combinations of these elements have greatly altered cellular uptake characteristics due to particle size. These differences may greatly alter effects at the target cell level and hence risks for organ toxicities from such exposures. The value of validated biomarkers for early detection of systemic Cd-induced effects in humans cannot be underestimated due to the rapid expansion of nano-material technologies. This review will attempt to briefly summarize the applications, to date, of biomarker endpoints for assessing target organ system effects in

  3. Tools to Support Human Factors and Systems Engineering Interactions During Early Analysis

    NASA Technical Reports Server (NTRS)

    Thronesbery, Carroll; Malin, Jane T.; Holden, Kritina; Smith, Danielle Paige

    2006-01-01

    We describe an approach and existing software tool support for effective interactions between human factors engineers and systems engineers in early analysis activities during system acquisition. We examine the tasks performed during this stage, emphasizing those tasks where system engineers and human engineers interact. The Concept of Operations (ConOps) document is an important product during this phase, and particular attention is paid to its influences on subsequent acquisition activities. Understanding this influence helps ConOps authors describe a complete system concept that guides subsequent acquisition activities. We identify commonly used system engineering and human engineering tools and examine how they can support the specific tasks associated with system definition. We identify possible gaps in the support of these tasks, the largest of which appears to be creating the ConOps document itself. Finally, we outline the goals of our future empirical investigations of tools to support system concept definition.

  4. Tools to Support Human Factors and Systems Engineering Interactions During Early Analysis

    NASA Technical Reports Server (NTRS)

    Thronesbery, Carroll; Malin, Jane T.; Holden, Kritina; Smith, Danielle Paige

    2005-01-01

    We describe an approach and existing software tool support for effective interactions between human factors engineers and systems engineers in early analysis activities during system acquisition. We examine the tasks performed during this stage, emphasizing those tasks where system engineers and human engineers interact. The Concept of Operations (ConOps) document is an important product during this phase, and particular attention is paid to its influences on subsequent acquisition activities. Understanding this influence helps ConOps authors describe a complete system concept that guides subsequent acquisition activities. We identify commonly used system engineering and human engineering tools and examine how they can support the specific tasks associated with system definition. We identify possible gaps in the support of these tasks, the largest of which appears to be creating the ConOps document itself. Finally, we outline the goals of our future empirical investigations of tools to support system concept definition.

  5. Metacarpal torsion in apes, humans, and early Australopithecus: implications for manipulatory abilities

    PubMed Central

    2015-01-01

    Human hands, when compared to that of apes, have a series of adaptations to facilitate manipulation. Numerous studies have shown that Australopithecus afarensis and Au. africanus display some of these adaptations, such as a longer thumb relative to the other fingers, asymmetric heads on the second and fifth metacarpals, and orientation of the second metacarpal joints with the trapezium and capitate away from the sagittal plane, while lacking others such as a very mobile fifth metacarpal, a styloid process on the third, and a flatter metacarpo-trapezium articulation, suggesting some adaptation to manipulation but more limited than in humans. This paper explores variation in metacarpal torsion, a trait said to enhance manipulation, in humans, apes, early australopithecines and specimens from Swartkrans. This study shows that humans are different from large apes in torsion of the third and fourth metacarpals. Humans are also characterized by wedge-shaped bases of the third and fourth metacarpals, making the metacarpal-base row very arched mediolaterally and placing the ulnar-most metacarpals in a position that facilitate opposition to the thumb in power or cradle grips. The third and fourth metacarpals of Au. afarensis are very human-like, suggesting that the medial palm was already well adapted for these kinds of grips in that taxon. Au. africanus present a less clear human-like morphology, suggesting, perhaps, that the medial palm was less suited to human-like manipulation in that taxa than in Au. afarensis. Overall, this study supports previous studies on Au. afarensis and Au. africanus that these taxa had derived hand morphology with some adaptation to human-like power and precision grips and support the hypothesis that dexterous hands largely predated Homo. PMID:26500820

  6. Metacarpal torsion in apes, humans, and early Australopithecus: implications for manipulatory abilities.

    PubMed

    Drapeau, Michelle S M

    2015-01-01

    Human hands, when compared to that of apes, have a series of adaptations to facilitate manipulation. Numerous studies have shown that Australopithecus afarensis and Au. africanus display some of these adaptations, such as a longer thumb relative to the other fingers, asymmetric heads on the second and fifth metacarpals, and orientation of the second metacarpal joints with the trapezium and capitate away from the sagittal plane, while lacking others such as a very mobile fifth metacarpal, a styloid process on the third, and a flatter metacarpo-trapezium articulation, suggesting some adaptation to manipulation but more limited than in humans. This paper explores variation in metacarpal torsion, a trait said to enhance manipulation, in humans, apes, early australopithecines and specimens from Swartkrans. This study shows that humans are different from large apes in torsion of the third and fourth metacarpals. Humans are also characterized by wedge-shaped bases of the third and fourth metacarpals, making the metacarpal-base row very arched mediolaterally and placing the ulnar-most metacarpals in a position that facilitate opposition to the thumb in power or cradle grips. The third and fourth metacarpals of Au. afarensis are very human-like, suggesting that the medial palm was already well adapted for these kinds of grips in that taxon. Au. africanus present a less clear human-like morphology, suggesting, perhaps, that the medial palm was less suited to human-like manipulation in that taxa than in Au. afarensis. Overall, this study supports previous studies on Au. afarensis and Au. africanus that these taxa had derived hand morphology with some adaptation to human-like power and precision grips and support the hypothesis that dexterous hands largely predated Homo. PMID:26500820

  7. The Human Early-Life Exposome (HELIX): Project Rationale and Design

    PubMed Central

    Slama, Rémy; Robinson, Oliver; Chatzi, Leda; Coen, Muireann; van den Hazel, Peter; Thomsen, Cathrine; Wright, John; Athersuch, Toby J.; Avellana, Narcis; Basagaña, Xavier; Brochot, Celine; Bucchini, Luca; Bustamante, Mariona; Carracedo, Angel; Casas, Maribel; Estivill, Xavier; Fairley, Lesley; van Gent, Diana; Gonzalez, Juan R.; Granum, Berit; Gražulevicˇiene˙, Regina; Gutzkow, Kristine B.; Julvez, Jordi; Keun, Hector C.; Kogevinas, Manolis; McEachan, Rosemary R.C.; Meltzer, Helle Margrete; Sabidó, Eduard; Schwarze, Per E.; Siroux, Valérie; Sunyer, Jordi; Want, Elizabeth J.; Zeman, Florence; Nieuwenhuijsen, Mark J.

    2014-01-01

    Background: Developmental periods in early life may be particularly vulnerable to impacts of environmental exposures. Human research on this topic has generally focused on single exposure–health effect relationships. The “exposome” concept encompasses the totality of exposures from conception onward, complementing the genome. Objectives: The Human Early-Life Exposome (HELIX) project is a new collaborative research project that aims to implement novel exposure assessment and biomarker methods to characterize early-life exposure to multiple environmental factors and associate these with omics biomarkers and child health outcomes, thus characterizing the “early-life exposome.” Here we describe the general design of the project. Methods: In six existing birth cohort studies in Europe, HELIX will estimate prenatal and postnatal exposure to a broad range of chemical and physical exposures. Exposure models will be developed for the full cohorts totaling 32,000 mother–child pairs, and biomarkers will be measured in a subset of 1,200 mother–child pairs. Nested repeat-sampling panel studies (n = 150) will collect data on biomarker variability, use smartphones to assess mobility and physical activity, and perform personal exposure monitoring. Omics techniques will determine molecular profiles (metabolome, proteome, transcriptome, epigenome) associated with exposures. Statistical methods for multiple exposures will provide exposure–response estimates for fetal and child growth, obesity, neurodevelopment, and respiratory outcomes. A health impact assessment exercise will evaluate risks and benefits of combined exposures. Conclusions: HELIX is one of the first attempts to describe the early-life exposome of European populations and unravel its relation to omics markers and health in childhood. As proof of concept, it will form an important first step toward the life-course exposome. Citation: Vrijheid M, Slama R, Robinson O, Chatzi L, Coen M, van den Hazel P

  8. From the Cover: Feature Article: Ecosystem variability and early human habitats in eastern Africa

    NASA Astrophysics Data System (ADS)

    Magill, Clayton R.; Ashley, Gail M.; Freeman, Katherine H.

    2013-01-01

    The role of savannas during the course of early human evolution has been debated for nearly a century, in part because of difficulties in characterizing local ecosystems from fossil and sediment records. Here, we present high-resolution lipid biomarker and isotopic signatures for organic matter preserved in lake sediments at Olduvai Gorge during a key juncture in human evolution about 2.0 Ma-the emergence and dispersal of Homo erectus (sensu lato). Using published data for modern plants and soils, we construct a framework for ecological interpretations of stable carbon-isotope compositions (expressed as δ13C values) of lipid biomarkers from ancient plants. Within this framework, δ13C values for sedimentary leaf lipids and total organic carbon from Olduvai Gorge indicate recurrent ecosystem variations, where open C4 grasslands abruptly transitioned to closed C3 forests within several hundreds to thousands of years. Carbon-isotopic signatures correlate most strongly with Earth's orbital geometry (precession), and tropical sea-surface temperatures are significant secondary predictors in partial regression analyses. The scale and pace of repeated ecosystem variations at Olduvai Gorge contrast with long-held views of directional or stepwise aridification and grassland expansion in eastern Africa during the early Pleistocene and provide a local perspective on environmental hypotheses of human evolution.

  9. Matriptase regulates proliferation and early, but not terminal, differentiation of human keratinocytes

    PubMed Central

    Chen, Ya-Wen; Wang, Jehng-Kang; Chou, Fen-Pai; Wu, Bai-Yao; Hsiao, Hui-Chung; Chiu, Han; Xu, Zhonghong; Baksh, Adrienne NH; Shi, Galen; Kaul, Malvika; Barndt, Robert; Shanmugam, Victoria K.; Johnson, Michael D.; Lin, Chen-Yong

    2013-01-01

    Genetic defects in matriptase are linked to two congenital ichthyosis, autosomal recessive ichthyosis with hypotrichosis (ARIH, OMIM 610765) and, ichthyosis, follicular atrophoderma, hypotrichosis, and hypohidrosis (IFAH, OMIM602400). Mouse models with matriptase deficiency indicate an involvement of matriptase in suprabasal keratinocytes in the maintenance of the epidermal barrier. In contrast to what has been reported for mouse skin, we show that in human skin, matriptase is primarily expressed in the basal and spinous keratinocytes, but not in the more differentiated keratinocytes of the granular layer. In addition, matriptase zymogen activation was predominantly detected in the basal cells. Furthermore, using skin organotypic cultures as a model system to monitor the course of human epidermal differentiation, we found elevated matriptase zymogen activation during early stages of epidermal differentiation, coupled with a loss of matriptase expression in the late stages of this process. We also show here that matriptase deficiency in HaCaT cells modestly reduces cell proliferation and temporally affects calcium-induced expression of differentiation markers. These collective data suggests that, unlike mouse matriptase, human matriptase may be involved in regulation of keratinocyte growth and early differentiation, rather than terminal differentiation, providing mechanistic insights for the pathology of the two congenital ichthyoses, ARIH and IFAH. PMID:23900022

  10. Variability of Gene Expression Identifies Transcriptional Regulators of Early Human Embryonic Development

    PubMed Central

    Hasegawa, Yu; Taylor, Deanne; Ovchinnikov, Dmitry A.; Wolvetang, Ernst J.; de Torrenté, Laurence; Mar, Jessica C.

    2015-01-01

    An analysis of gene expression variability can provide an insightful window into how regulatory control is distributed across the transcriptome. In a single cell analysis, the inter-cellular variability of gene expression measures the consistency of transcript copy numbers observed between cells in the same population. Application of these ideas to the study of early human embryonic development may reveal important insights into the transcriptional programs controlling this process, based on which components are most tightly regulated. Using a published single cell RNA-seq data set of human embryos collected at four-cell, eight-cell, morula and blastocyst stages, we identified genes with the most stable, invariant expression across all four developmental stages. Stably-expressed genes were found to be enriched for those sharing indispensable features, including essentiality, haploinsufficiency, and ubiquitous expression. The stable genes were less likely to be associated with loss-of-function variant genes or human recessive disease genes affected by a DNA copy number variant deletion, suggesting that stable genes have a functional impact on the regulation of some of the basic cellular processes. Genes with low expression variability at early stages of development are involved in regulation of DNA methylation, responses to hypoxia and telomerase activity, whereas by the blastocyst stage, low-variability genes are enriched for metabolic processes as well as telomerase signaling. Based on changes in expression variability, we identified a putative set of gene expression markers of morulae and blastocyst stages. Experimental validation of a blastocyst-expressed variability marker demonstrated that HDDC2 plays a role in the maintenance of pluripotency in human ES and iPS cells. Collectively our analyses identified new regulators involved in human embryonic development that would have otherwise been missed using methods that focus on assessment of the average expression

  11. Genetic programs in human and mouse early embryos revealed by single-cell RNA sequencing

    PubMed Central

    Xue, Zhigang; Huang, Kevin; Cai, Chaochao; Cai, Lingbo; Jiang, Chun-yan; Feng, Yun; Liu, Zhenshan; Zeng, Qiao; Cheng, Liming; Sun, Yi E.; Liu, Jia-yin; Horvath, Steve; Fan, Guoping

    2016-01-01

    Mammalian pre-implantation development is a complex process involving dramatic changes in the transcriptional architecture1–4. We report here a comprehensive analysis of transcriptome dynamics from oocyte to morula in both human and mouse embryos, using single-cell RNA sequencing. Based on single-nucleotide variants in human blastomere messenger RNAs and paternal-specific single-nucleotide polymorphisms, we identify novel stage-specific monoallelic expression patterns for a significant portion of polymorphic gene transcripts (25 to 53%). By weighted gene co-expression network analysis5,6, we find that each developmental stage can be delineated concisely by a small number of functional modules of co-expressed genes. This result indicates a sequential order of transcriptional changes in pathways of cell cycle, gene regulation, translation and metabolism, acting in a step-wise fashion from cleavage to morula. Cross-species comparisons with mouse pre-implantation embryos reveal that the majority of human stage-specific modules (7out of 9) are notably preserved, but developmental specificity and timing differ between human and mouse. Furthermore, we identify conserved key members (or hub genes) of the human and mouse networks. These genes represent novel candidates that are likely to be key in driving mammalian pre-implantation development. Together, the results provide a valuable resource to dissect gene regulatory mechanisms underlying progressive development of early mammalian embryos. PMID:23892778

  12. New Archaeological Evidence for an Early Human Presence at Monte Verde, Chile

    PubMed Central

    Dillehay, Tom D.; Ocampo, Carlos; Saavedra, José; Sawakuchi, Andre Oliveira; Vega, Rodrigo M.; Pino, Mario; Collins, Michael B.; Scott Cummings, Linda; Arregui, Iván; Villagran, Ximena S.; Hartmann, Gelvam A.; Mella, Mauricio; González, Andrea; Dix, George

    2015-01-01

    Questions surrounding the chronology, place, and character of the initial human colonization of the Americas are a long-standing focus of debate. Interdisciplinary debate continues over the timing of entry, the rapidity and direction of dispersion, the variety of human responses to diverse habitats, the criteria for evaluating the validity of early sites, and the differences and similarities between colonization in North and South America. Despite recent advances in our understanding of these issues, archaeology still faces challenges in defining interdisciplinary research problems, assessing the reliability of the data, and applying new interpretative models. As the debates and challenges continue, new studies take place and previous research reexamined. Here we discuss recent exploratory excavation at and interdisciplinary data from the Monte Verde area in Chile to further our understanding of the first peopling of the Americas. New evidence of stone artifacts, faunal remains, and burned areas suggests discrete horizons of ephemeral human activity in a sandur plain setting radiocarbon and luminescence dated between at least ~18,500 and 14,500 cal BP. Based on multiple lines of evidence, including sedimentary proxies and artifact analysis, we present the probable anthropogenic origins and wider implications of this evidence. In a non-glacial cold climate environment of the south-central Andes, which is challenging for human occupation and for the preservation of hunter-gatherer sites, these horizons provide insight into an earlier context of late Pleistocene human behavior in northern Patagonia. PMID:26580202

  13. New Archaeological Evidence for an Early Human Presence at Monte Verde, Chile.

    PubMed

    Dillehay, Tom D; Ocampo, Carlos; Saavedra, José; Sawakuchi, Andre Oliveira; Vega, Rodrigo M; Pino, Mario; Collins, Michael B; Scott Cummings, Linda; Arregui, Iván; Villagran, Ximena S; Hartmann, Gelvam A; Mella, Mauricio; González, Andrea; Dix, George

    2015-01-01

    Questions surrounding the chronology, place, and character of the initial human colonization of the Americas are a long-standing focus of debate. Interdisciplinary debate continues over the timing of entry, the rapidity and direction of dispersion, the variety of human responses to diverse habitats, the criteria for evaluating the validity of early sites, and the differences and similarities between colonization in North and South America. Despite recent advances in our understanding of these issues, archaeology still faces challenges in defining interdisciplinary research problems, assessing the reliability of the data, and applying new interpretative models. As the debates and challenges continue, new studies take place and previous research reexamined. Here we discuss recent exploratory excavation at and interdisciplinary data from the Monte Verde area in Chile to further our understanding of the first peopling of the Americas. New evidence of stone artifacts, faunal remains, and burned areas suggests discrete horizons of ephemeral human activity in a sandur plain setting radiocarbon and luminescence dated between at least ~18,500 and 14,500 cal BP. Based on multiple lines of evidence, including sedimentary proxies and artifact analysis, we present the probable anthropogenic origins and wider implications of this evidence. In a non-glacial cold climate environment of the south-central Andes, which is challenging for human occupation and for the preservation of hunter-gatherer sites, these horizons provide insight into an earlier context of late Pleistocene human behavior in northern Patagonia. PMID:26580202

  14. Defining the genomic signature of totipotency and pluripotency during early human development.

    PubMed

    Galan, Amparo; Diaz-Gimeno, Patricia; Poo, Maria Eugenia; Valbuena, Diana; Sanchez, Eva; Ruiz, Veronica; Dopazo, Joaquin; Montaner, David; Conesa, Ana; Simon, Carlos

    2013-01-01

    The genetic mechanisms governing human pre-implantation embryo development and the in vitro counterparts, human embryonic stem cells (hESCs), still remain incomplete. Previous global genome studies demonstrated that totipotent blastomeres from day-3 human embryos and pluripotent inner cell masses (ICMs) from blastocysts, display unique and differing transcriptomes. Nevertheless, comparative gene expression analysis has revealed that no significant differences exist between hESCs derived from blastomeres versus those obtained from ICMs, suggesting that pluripotent hESCs involve a new developmental progression. To understand early human stages evolution, we developed an undifferentiation network signature (UNS) and applied it to a differential gene expression profile between single blastomeres from day-3 embryos, ICMs and hESCs. This allowed us to establish a unique signature composed of highly interconnected genes characteristic of totipotency (61 genes), in vivo pluripotency (20 genes), and in vitro pluripotency (107 genes), and which are also proprietary according to functional analysis. This systems biology approach has led to an improved understanding of the molecular and signaling processes governing human pre-implantation embryo development, as well as enabling us to comprehend how hESCs might adapt to in vitro culture conditions. PMID:23614026

  15. From the Cover: Feature Article: Water, plants, and early human habitats in eastern Africa

    NASA Astrophysics Data System (ADS)

    Magill, Clayton R.; Ashley, Gail M.; Freeman, Katherine H.

    2013-01-01

    Water and its influence on plants likely exerted strong adaptive pressures in human evolution. Understanding relationships among water, plants, and early humans is limited both by incomplete terrestrial records of environmental change and by indirect proxy data for water availability. Here we present a continuous record of stable hydrogen-isotope compositions (expressed as δD values) for lipid biomarkers preserved in lake sediments from an early Pleistocene archaeological site in eastern Africa-Olduvai Gorge. We convert sedimentary leaf- and algal-lipid δD values into estimates for ancient source-water δD values by accounting for biochemical, physiological, and environmental influences on isotopic fractionation via published water-lipid enrichment factors for living plants, algae, and recent sediments. Reconstructed precipitation and lake-water δD values, respectively, are consistent with modern isotopic hydrology and reveal that dramatic fluctuations in water availability accompanied ecosystem changes. Drier conditions, indicated by less negative δD values, occur in association with stable carbon-isotopic evidence for open, C4-dominated grassland ecosystems. Wetter conditions, indicated by lower δD values, are associated with expanded woody cover across the ancient landscape. Estimates for ancient precipitation amounts, based on reconstructed precipitation δD values, range between approximately 250 and 700 mm.y-1 and are consistent with modern precipitation data for eastern Africa. We conclude that freshwater availability exerted a substantial influence on eastern African ecosystems and, by extension, was central to early human proliferation during periods of rapid climate change.

  16. Early Detection of Human Epileptic Seizures Based on Intracortical Local Field Potentials.

    PubMed

    Park, Yun S; Hochberg, Leigh R; Eskandar, Emad N; Cash, Sydney S; Truccolo, Wilson

    2013-01-01

    The unpredictability of re-occurring seizures dramatically impacts the quality of life and autonomy of people with epilepsy. Reliable early seizure detection could open new therapeutic possibilities and thus substantially improve quality of life and autonomy. Though many seizure detection studies have shown the potential of scalp electroencephalogram (EEG) and intracranial EEG (iEEG) signals, reliable early detection of human seizures remains elusive in practice. Here, we examined the use of intracortical local field potentials (LFPs) recorded from 4×4-mm(2) 96-microelectrode arrays (MEA) for early detection of human epileptic seizures. We adopted a framework consisting of (1) sampling of intracortical LFPs; (2) denoising of LFPs with the Kalman filter; (3) spectral power estimation in specific frequency bands using 1-sec moving time windows; (4) extraction of statistical features, such as the mean, variance, and Fano factor (calculated across channels) of the power in each frequency band; and (5) cost-sensitive support vector machine (SVM) classification of ictal and interictal samples. We tested the framework in one-participant dataset, including 4 seizures and corresponding interictal recordings preceding each seizure. The participant was a 52-year-old woman suffering from complex partial seizures. LFPs were recorded from an MEA implanted in the participant's left middle temporal gyrus. In this participant, spectral power in 0.3-10 Hz, 20-55 Hz, and 125-250 Hz changed significantly between ictal and interictal epochs. The examined seizure detection framework provided an event-wise sensitivity of 100% (4/4) and only one 20-sec-long false positive event in interictal recordings (likely an undetected subclinical event under further visual inspection), and a detection latency of 4.35 ± 2.21 sec (mean ± std) with respect to iEEG-identified seizure onsets. These preliminary results indicate that intracortical MEA recordings may provide key signals to quickly and

  17. Plant foods and the dietary ecology of Neanderthals and early modern humans.

    PubMed

    Henry, Amanda G; Brooks, Alison S; Piperno, Dolores R

    2014-04-01

    One of the most important challenges in anthropology is understanding the disappearance of Neanderthals. Previous research suggests that Neanderthals had a narrower diet than early modern humans, in part because they lacked various social and technological advances that lead to greater dietary variety, such as a sexual division of labor and the use of complex projectile weapons. The wider diet of early modern humans would have provided more calories and nutrients, increasing fertility, decreasing mortality and supporting large population sizes, allowing them to out-compete Neanderthals. However, this model for Neanderthal dietary behavior is based on analysis of animal remains, stable isotopes, and other methods that provide evidence only of animal food in the diet. This model does not take into account the potential role of plant food. Here we present results from the first broad comparison of plant foods in the diets of Neanderthals and early modern humans from several populations in Europe, the Near East, and Africa. Our data comes from the analysis of plant microremains (starch grains and phytoliths) in dental calculus and on stone tools. Our results suggest that both species consumed a similarly wide array of plant foods, including foods that are often considered low-ranked, like underground storage organs and grass seeds. Plants were consumed across the entire range of individuals and sites we examined, and none of the expected predictors of variation (species, geographic region, or associated stone tool technology) had a strong influence on the number of plant species consumed. Our data suggest that Neanderthal dietary ecology was more complex than previously thought. This implies that the relationship between Neanderthal technology, social behavior, and food acquisition strategies must be better explored. PMID:24612646

  18. [Early human transplants: 60th anniversary of the first successful kidney transplants].

    PubMed

    Gentili, Marc E

    2015-11-01

    First kidney transplant attempts begin with the 20th century: improving vascular sutures, understanding the phenomena of rejection or tolerance, then progress in HLA groups enable early success in the second half of the century. Definition of brain death, use of corticosteroids, radiotherapy and prime immunosuppressors promote the development of transplants. Discover of cyclosporine in the 1980s, and legislative developments augur a new era. Many advances are arising: use of stem cells from the donor, enhancement of Maastricht 3 donor or living donation. Finally organ transplantation remains an immense human adventure, but also scientific and ethic. PMID:26206772

  19. Differential diagnosis of early human pregnancies: impact of different diagnostic measures.

    PubMed

    Thorburn, J; Bryman, I; Hahlin, M; Lindblom, B

    1992-01-01

    A total of 261 women in early pregnancy, either with mild symptoms of ectopic pregnancy (EP) or being at an increased risk for this condition, were included in a longitudinal study. The effectiveness of different diagnostic measures in obtaining correct final diagnoses was analyzed. In addition to clinical findings and symptoms, the use of serum human chorionic gonadotropin, serum progesterone, endovaginal sonography and a risk score for EP were all proven to be valuable in distinguishing normal intrauterine pregnancies from pathological pregnancies. PMID:1505809

  20. Early influence of auditory stimuli on upper-limb movements in young human infants: an overview

    PubMed Central

    Ferronato, Priscilla A. M.; Domellöf, Erik; Rönnqvist, Louise

    2014-01-01

    Given that the auditory system is rather well developed at the end of the third trimester of pregnancy, it is likely that couplings between acoustics and motor activity can be integrated as early as at the beginning of postnatal life. The aim of the present mini-review was to summarize and discuss studies on early auditory-motor integration, focusing particularly on upper-limb movements (one of the most crucial means to interact with the environment) in association with auditory stimuli, to develop further understanding of their significance with regard to early infant development. Many studies have investigated the relationship between various infant behaviors (e.g., sucking, visual fixation, head turning) and auditory stimuli, and established that human infants can be observed displaying couplings between action and environmental sensory stimulation already from just after birth, clearly indicating a propensity for intentional behavior. Surprisingly few studies, however, have investigated the associations between upper-limb movements and different auditory stimuli in newborns and young infants, infants born at risk for developmental disorders/delays in particular. Findings from studies of early auditory-motor interaction support that the developing integration of sensory and motor systems is a fundamental part of the process guiding the development of goal-directed action in infancy, of great importance for continued motor, perceptual, and cognitive development. At-risk infants (e.g., those born preterm) may display increasing central auditory processing disorders, negatively affecting early sensory-motor integration, and resulting in long-term consequences on gesturing, language development, and social communication. Consequently, there is a need for more studies on such implications. PMID:25278927

  1. Early developmental exposures shape trade-offs between acquired and innate immunity in humans

    PubMed Central

    Georgiev, Alexander V.; Kuzawa, Christopher W.; McDade, Thomas W.

    2016-01-01

    Background and objectives Life history theory predicts resource allocation trade-offs between competing functions and processes. We test the hypothesis that relative investment towards innate versus acquired immunity in humans is subject to such trade-offs and that three types of early developmental exposures are particularly salient in shaping adult immunophenotype: (i) pathogen exposure, (ii) nutritional resources; and (iii) extrinsic mortality cues. Methodology We quantified one aspect each of innate and acquired immune function, via C-reactive protein and Epstein–Barr virus antibodies, respectively, in a sample of 1248 men and women from the Philippines (ca. 21.5 years old). Early developmental exposures were assessed via long-term data collected prospectively since participants’ birth (1983–4). We calculated a standardized ratio to assess relative bias towards acquired versus innate immune function and examined its relationship to a suite of predictors via multiple regression. Results In partial support of our predictions, some of the measures of higher pathogen exposure, greater availability of nutritional resources, and lower extrinsic mortality cues in early life were associated with a bias toward acquired immunity in both men and women. The immune profile of women, in particular, appeared to be more sensitive to early life pathogen exposures than those of men. Finally, contrary to prediction, women exhibited a greater relative investment toward innate, not acquired, immunity. Conclusions and implications Early environments can exert considerable influence on the development of immunity. They affect trade-offs between innate and acquired immunity, which show adaptive plasticity and may differ in their influence in men and women. PMID:27530543

  2. Early influence of auditory stimuli on upper-limb movements in young human infants: an overview.

    PubMed

    Ferronato, Priscilla A M; Domellöf, Erik; Rönnqvist, Louise

    2014-01-01

    Given that the auditory system is rather well developed at the end of the third trimester of pregnancy, it is likely that couplings between acoustics and motor activity can be integrated as early as at the beginning of postnatal life. The aim of the present mini-review was to summarize and discuss studies on early auditory-motor integration, focusing particularly on upper-limb movements (one of the most crucial means to interact with the environment) in association with auditory stimuli, to develop further understanding of their significance with regard to early infant development. Many studies have investigated the relationship between various infant behaviors (e.g., sucking, visual fixation, head turning) and auditory stimuli, and established that human infants can be observed displaying couplings between action and environmental sensory stimulation already from just after birth, clearly indicating a propensity for intentional behavior. Surprisingly few studies, however, have investigated the associations between upper-limb movements and different auditory stimuli in newborns and young infants, infants born at risk for developmental disorders/delays in particular. Findings from studies of early auditory-motor interaction support that the developing integration of sensory and motor systems is a fundamental part of the process guiding the development of goal-directed action in infancy, of great importance for continued motor, perceptual, and cognitive development. At-risk infants (e.g., those born preterm) may display increasing central auditory processing disorders, negatively affecting early sensory-motor integration, and resulting in long-term consequences on gesturing, language development, and social communication. Consequently, there is a need for more studies on such implications. PMID:25278927

  3. Human in vitro reporter model of neuronal development and early differentiation processes

    PubMed Central

    Couillard-Despres, Sebastien; Quehl, Eike; Altendorfer, Katrin; Karl, Claudia; Ploetz, Sonja; Bogdahn, Ulrich; Winkler, Juergen; Aigner, Ludwig

    2008-01-01

    Background During developmental and adult neurogenesis, doublecortin is an early neuronal marker expressed when neural stem cells assume a neuronal cell fate. To understand mechanisms involved in early processes of neuronal fate decision, we investigated cell lines for their capacity to induce expression of doublecortin upon neuronal differentiation and develop in vitro reporter models using doublecortin promoter sequences. Results Among various cell lines investigated, the human teratocarcinoma cell line NTERA-2 was found to fulfill our criteria. Following induction of differentiation using retinoic acid treatment, we observed a 16-fold increase in doublecortin mRNA expression, as well as strong induction of doublecortin polypeptide expression. The acquisition of a neuronal precursor phenotype was also substantiated by the establishment of a multipolar neuronal morphology and expression of additional neuronal markers, such as Map2, βIII-tubulin and neuron-specific enolase. Moreover, stable transfection in NTERA-2 cells of reporter constructs encoding fluorescent or luminescent genes under the control of the doublecortin promoter allowed us to directly detect induction of neuronal differentiation in cell culture, such as following retinoic acid treatment or mouse Ngn2 transient overexpression. Conclusion Induction of doublecortin expression in differentiating NTERA-2 cells suggests that these cells accurately recapitulate some of the very early events of neuronal determination. Hence, the use of reporter genes under the control of the doublecortin promoter in NTERA-2 cells will help us to investigate factors involved early in the course of neuronal differentiation processes. Moreover the ease to detect the induction of a neuronal program in this model will permit to perform high throughput screening for compounds acting on the early neuronal differentiation mechanisms. PMID:18312642

  4. Heterokont Predator Develorapax marinus gen. et sp. nov. – A Model of the Ochrophyte Ancestor

    PubMed Central

    Aleoshin, Vladimir V.; Mylnikov, Alexander P.; Mirzaeva, Gulnara S.; Mikhailov, Kirill V.; Karpov, Sergey A.

    2016-01-01

    Heterotrophic lineages of Heterokonta (or stramenopiles), in contrast to a single monophyletic group of autotrophs, Ochrophyta, form several clades that independently branch off the heterokont stem lineage. The nearest neighbors of Ochrophyta in the phylogenetic tree appear to be almost exclusively bacterivorous, whereas the hypothesis of plastid acquisition by the ancestors of the ochrophyte lineage suggests an ability to engulf eukaryotic alga. In line with this hypothesis, the heterotrophic predator at the base of the ochrophyte lineage may be regarded as a model for the ochrophyte ancestor. Here, we present a new genus and species of marine free-living heterotrophic heterokont Develorapax marinus, which falls into an isolated heterokont cluster, along with the marine flagellate Developayella elegans, and is able to engulf eukaryotic cells. Together with environmental sequences D. marinus and D. elegans form a class-level clade Developea nom. nov. represented by species adapted to different environmental conditions and with a wide geographical distribution. The position of Developea among Heterokonta in large-scale phylogenetic tree is discussed. We propose that members of the Developea clade represent a model for transition from bacterivory to a predatory feeding mode by selection for larger prey. Presumably, such transition in the grazing strategy is possible in the presence of bacterial biofilms or aggregates expected in eutrophic environment, and has likely occurred in the ochrophyte ancestor. PMID:27536283

  5. Heterokont Predator Develorapax marinus gen. et sp. nov. - A Model of the Ochrophyte Ancestor.

    PubMed

    Aleoshin, Vladimir V; Mylnikov, Alexander P; Mirzaeva, Gulnara S; Mikhailov, Kirill V; Karpov, Sergey A

    2016-01-01

    Heterotrophic lineages of Heterokonta (or stramenopiles), in contrast to a single monophyletic group of autotrophs, Ochrophyta, form several clades that independently branch off the heterokont stem lineage. The nearest neighbors of Ochrophyta in the phylogenetic tree appear to be almost exclusively bacterivorous, whereas the hypothesis of plastid acquisition by the ancestors of the ochrophyte lineage suggests an ability to engulf eukaryotic alga. In line with this hypothesis, the heterotrophic predator at the base of the ochrophyte lineage may be regarded as a model for the ochrophyte ancestor. Here, we present a new genus and species of marine free-living heterotrophic heterokont Develorapax marinus, which falls into an isolated heterokont cluster, along with the marine flagellate Developayella elegans, and is able to engulf eukaryotic cells. Together with environmental sequences D. marinus and D. elegans form a class-level clade Developea nom. nov. represented by species adapted to different environmental conditions and with a wide geographical distribution. The position of Developea among Heterokonta in large-scale phylogenetic tree is discussed. We propose that members of the Developea clade represent a model for transition from bacterivory to a predatory feeding mode by selection for larger prey. Presumably, such transition in the grazing strategy is possible in the presence of bacterial biofilms or aggregates expected in eutrophic environment, and has likely occurred in the ochrophyte ancestor. PMID:27536283

  6. Human radiation studies: Remembering the early years. Oral history of Julie Langham Grilly, February 3, 1995

    SciTech Connect

    1995-09-01

    Julie Langham Grilly was interviewed by representatives of the US DOE Office of Human Radiation Experiments (OHRE) being the widow of Dr. Wright Langham, an investigator of principal interest of the committee. Her extensive experience with research at LANL was also of interest to the committee. Following a brief biographical sketch, Ms. Grilly relates her early postwar experience and her knowledge of Wright Langham`s involvement in animal research at Los Alamos, radiolanthanum tests on monkeys, Eniwetok tissue examinations, research on tritium uptake in humans, plutonium injections, tritium injections, EDTA, and etc. In addition to illuminating her former husband as a researcher and as an individual, she also relates her remembrances of Louis Hempelman, Enrico Fermi, Oppenheimer, Edward Teller, and many others.

  7. Early human use of anadromous salmon in North America at 11,500 y ago

    PubMed Central

    Halffman, Carrin M.; Potter, Ben A.; McKinney, Holly J.; Finney, Bruce P.; Rodrigues, Antonia T.; Yang, Dongya Y.; Kemp, Brian M.

    2015-01-01

    Salmon represented a critical resource for prehistoric foragers along the North Pacific Rim, and continue to be economically and culturally important; however, the origins of salmon exploitation remain unresolved. Here we report 11,500-y-old salmon associated with a cooking hearth and human burials from the Upward Sun River Site, near the modern extreme edge of salmon habitat in central Alaska. This represents the earliest known human use of salmon in North America. Ancient DNA analyses establish the species as Oncorhynchus keta (chum salmon), and stable isotope analyses indicate anadromy, suggesting that salmon runs were established by at least the terminal Pleistocene. The early use of this resource has important implications for Paleoindian land use, economy, and expansions into northwest North America. PMID:26392548

  8. Early human use of anadromous salmon in North America at 11,500 y ago.

    PubMed

    Halffman, Carrin M; Potter, Ben A; McKinney, Holly J; Finney, Bruce P; Rodrigues, Antonia T; Yang, Dongya Y; Kemp, Brian M

    2015-10-01

    Salmon represented a critical resource for prehistoric foragers along the North Pacific Rim, and continue to be economically and culturally important; however, the origins of salmon exploitation remain unresolved. Here we report 11,500-y-old salmon associated with a cooking hearth and human burials from the Upward Sun River Site, near the modern extreme edge of salmon habitat in central Alaska. This represents the earliest known human use of salmon in North America. Ancient DNA analyses establish the species as Oncorhynchus keta (chum salmon), and stable isotope analyses indicate anadromy, suggesting that salmon runs were established by at least the terminal Pleistocene. The early use of this resource has important implications for Paleoindian land use, economy, and expansions into northwest North America. PMID:26392548

  9. Early-onset binocularity in preterm infants reveals experience-dependent visual development in humans

    PubMed Central

    Jandó, Gábor; Mikó-Baráth, Eszter; Markó, Katalin; Hollódy, Katalin; Török, Béla; Kovacs, Ilona

    2012-01-01

    Although there is a great deal of knowledge regarding the phylo- and ontogenetic plasticity of the neocortex, the precise nature of environmental impact on the newborn human brain is still one of the most controversial issues of neuroscience. The leading model–system of experience-dependent brain development is binocular vision, also called stereopsis. Here, we show that extra postnatal visual experience in preterm human neonates leads to a change in the developmental timing of binocular vision. The onset age of binocular function, as measured by the visual evoked response to dynamic random dot correlograms (DRDC-VEP), appears to be at around the same time after birth in preterm (4.07 mo) and full-term (3.78 mo) infants. To assess the integrity of the visual pathway in the studied infants, we also measured the latency of the visual-evoked response to pattern reversal stimuli (PR-VEP). PR-VEP latency is not affected by premature birth, demonstrating that the maturation of the visual pathway follows a preprogrammed developmental course. Despite the immaturity of the visual pathway, clearly demonstrated by the PR-VEP latencies, our DRCD-VEP data show that the visual cortex is remarkably ready to accept environmental stimulation right after birth. This early plasticity makes full use of the available extra stimulation time in preterm human infants and results in an early onset of cortical binocularity. According to our data, the developmental processes preceding the onset of binocular function are not preprogrammed, and the mechanisms turning on stereopsis are extremely experience-dependent in humans. PMID:22711824

  10. Origin of the genetic components of the vomeronasal system in the common ancestor of all extant vertebrates.

    PubMed

    Grus, Wendy E; Zhang, Jianzhi

    2009-02-01

    Comparative genomics provides a valuable tool for inferring the evolutionary history of physiological systems, particularly when this information is difficult to ascertain by morphological traits. One such example is the vomeronasal system (VNS), a vertebrate nasal chemosensory system that is responsible for detecting intraspecific pheromonal cues as well as environmental odorants. The morphological components of the VNS are found only in tetrapods, but the genetic components of the system have been found in teleost fish, in addition to tetrapods. To determine when the genetic components of the VNS originated, we searched for the VNS-specific genes in the genomes of two early diverging vertebrate lineages: the sea lamprey from jawless fishes and the elephant shark from cartilaginous fishes. Genes encoding vomeronasal type 1 receptors (V1Rs) and Trpc2, two components of the vomeronasal signaling pathway, are present in the sea lamprey genome, and both are expressed in the olfactory organ, revealing that the genetic components of the present-day VNS existed in the common ancestor of all extant vertebrates. Additionally, all three VNS genes, Trpc2, V1Rs, and vomeronasal type 2 receptors (V2Rs), are found in the elephant shark genome. Because V1Rs and V2Rs are related to two families of taste receptors, we also searched the early diverging vertebrate genomes for taste system genes and found them in the shark genome but not in the lamprey. Coupled with known distributions of the genetic components of the vertebrate main olfactory system, our results suggest staggered origins of vertebrate sensory systems. These findings are important for understanding the evolution of vertebrate sensory systems and illustrate the utility of the genome sequences of early diverging vertebrates for uncovering the evolution of vertebrate-specific traits. PMID:19008528

  11. Differences between human and mouse alpha-fetoprotein expression during early development

    PubMed Central

    JONES, ELIZABETH A.; CLEMENT-JONES, MARK; JAMES, OLIVER F. W.; WILSON, DAVID I.

    2001-01-01

    Alpha-fetoprotein (AFP) is the major serum protein during development. AFP is one of the earliest proteins to be synthesised by the embryonic liver. The synthesis of AFP decreases dramatically after birth and only trace amounts are expressed in the adult liver. The tissue distribution of AFP in early human embryogenesis has not been defined. We have studied the expression pattern of AFP mRNA in human and mouse embryos by in situ hybridisation. In humans, AFP is expressed in the hepatic diverticulum at 26 d postovulation as it differentiates from the foregut endoderm (i.e. in the most primitive hepatocytes). It is also expressed in the endoderm of the gastrointestinal tract and in the yolk sac at this age. AFP is subsequently expressed in the mesonephros and transiently in the developing pancreas. In the mouse, no expression of AFP was observed in the mesonephros but other sites of expression were similar. Thus AFP has a distinct temporospatial expression pattern during the embryonic period and this differs between human and mouse species. It is interesting that AFP is expressed by tumours such as primitive gastrointestinal, renal cell and pancreatic tumours as well as those of hepatocyte origin. This distribution reflects the sites of AFP expression during development. PMID:11430694

  12. Distinct vestibular effects on early and late somatosensory cortical processing in humans.

    PubMed

    Pfeiffer, Christian; van Elk, Michiel; Bernasconi, Fosco; Blanke, Olaf

    2016-01-15

    In non-human primates several brain areas contain neurons that respond to both vestibular and somatosensory stimulation. In humans, vestibular stimulation activates several somatosensory brain regions and improves tactile perception. However, less is known about the spatio-temporal dynamics of such vestibular-somatosensory interactions in the human brain. To address this issue, we recorded high-density electroencephalography during left median nerve electrical stimulation to obtain Somatosensory Evoked Potentials (SEPs). We analyzed SEPs during vestibular activation following sudden decelerations from constant-velocity (90°/s and 60°/s) earth-vertical axis yaw rotations and SEPs during a non-vestibular control period. SEP analysis revealed two distinct temporal effects of vestibular activation: An early effect (28-32ms post-stimulus) characterized by vestibular suppression of SEP response strength that depended on rotation velocity and a later effect (97-112ms post-stimulus) characterized by vestibular modulation of SEP topographical pattern that was rotation velocity-independent. Source estimation localized these vestibular effects, during both time periods, to activation differences in a distributed cortical network including the right postcentral gyrus, right insula, left precuneus, and bilateral secondary somatosensory cortex. These results suggest that vestibular-somatosensory interactions in humans depend on processing in specific time periods in somatosensory and vestibular cortical regions. PMID:26466979

  13. Mitochondria, the Cell Cycle, and the Origin of Sex via a Syncytial Eukaryote Common Ancestor.

    PubMed

    Garg, Sriram G; Martin, William F

    2016-01-01

    Theories for the origin of sex traditionally start with an asexual mitosing cell and add recombination, thereby deriving meiosis from mitosis. Though sex was clearly present in the eukaryote common ancestor, the order of events linking the origin of sex and the origin of mitosis is unknown. Here, we present an evolutionary inference for the origin of sex starting with a bacterial ancestor of mitochondria in the cytosol of its archaeal host. We posit that symbiotic association led to the origin of mitochondria and gene transfer to host's genome, generating a nucleus and a dedicated translational compartment, the eukaryotic cytosol, in which-by virtue of mitochondria-metabolic energy was not limiting. Spontaneous protein aggregation (monomer polymerization) and Adenosine Tri-phosphate (ATP)-dependent macromolecular movement in the cytosol thereby became selectable, giving rise to continuous microtubule-dependent chromosome separation (reduction division). We propose that eukaryotic chromosome division arose in a filamentous, syncytial, multinucleated ancestor, in which nuclei with insufficient chromosome numbers could complement each other through mRNA in the cytosol and generate new chromosome combinations through karyogamy. A syncytial (or coenocytic, a synonym) eukaryote ancestor, or Coeca, would account for the observation that the process of eukaryotic chromosome separation is more conserved than the process of eukaryotic cell division. The first progeny of such a syncytial ancestor were likely equivalent to meiospores, released into the environment by the host's vesicle secretion machinery. The natural ability of archaea (the host) to fuse and recombine brought forth reciprocal recombination among fusing (syngamy and karyogamy) progeny-sex-in an ancestrally meiotic cell cycle, from which the simpler haploid and diploid mitotic cell cycles arose. The origin of eukaryotes was the origin of vertical lineage inheritance, and sex was required to keep vertically

  14. Early developmental emergence of human amygdala–prefrontal connectivity after maternal deprivation

    PubMed Central

    Gee, Dylan G.; Gabard-Durnam, Laurel J.; Flannery, Jessica; Goff, Bonnie; Humphreys, Kathryn L.; Telzer, Eva H.; Hare, Todd A.; Bookheimer, Susan Y.; Tottenham, Nim

    2013-01-01

    Under typical conditions, medial prefrontal cortex (mPFC) connections with the amygdala are immature during childhood and become adult-like during adolescence. Rodent models show that maternal deprivation accelerates this development, prompting examination of human amygdala–mPFC phenotypes following maternal deprivation. Previously institutionalized youths, who experienced early maternal deprivation, exhibited atypical amygdala–mPFC connectivity. Specifically, unlike the immature connectivity (positive amygdala–mPFC coupling) of comparison children, children with a history of early adversity evidenced mature connectivity (negative amygdala–mPFC coupling) and thus, resembled the adolescent phenotype. This connectivity pattern was mediated by the hormone cortisol, suggesting that stress-induced modifications of the hypothalamic–pituitary–adrenal axis shape amygdala–mPFC circuitry. Despite being age-atypical, negative amygdala–mPFC coupling conferred some degree of reduced anxiety, although anxiety was still significantly higher in the previously institutionalized group. These findings suggest that accelerated amygdala–mPFC development is an ontogenetic adaptation in response to early adversity. PMID:24019460

  15. Neural Correlates of Natural Human Echolocation in Early and Late Blind Echolocation Experts

    PubMed Central

    Thaler, Lore; Arnott, Stephen R.; Goodale, Melvyn A.

    2011-01-01

    Background A small number of blind people are adept at echolocating silent objects simply by producing mouth clicks and listening to the returning echoes. Yet the neural architecture underlying this type of aid-free human echolocation has not been investigated. To tackle this question, we recruited echolocation experts, one early- and one late-blind, and measured functional brain activity in each of them while they listened to their own echolocation sounds. Results When we compared brain activity for sounds that contained both clicks and the returning echoes with brain activity for control sounds that did not contain the echoes, but were otherwise acoustically matched, we found activity in calcarine cortex in both individuals. Importantly, for the same comparison, we did not observe a difference in activity in auditory cortex. In the early-blind, but not the late-blind participant, we also found that the calcarine activity was greater for echoes reflected from surfaces located in contralateral space. Finally, in both individuals, we found activation in middle temporal and nearby cortical regions when they listened to echoes reflected from moving targets. Conclusions These findings suggest that processing of click-echoes recruits brain regions typically devoted to vision rather than audition in both early and late blind echolocation experts. PMID:21633496

  16. Early Pleistocene human humeri from the Gran Dolina-TD6 site (Sierra de Atapuerca, Spain).

    PubMed

    Bermúdez de Castro, José María; Carretero, José Miguel; García-González, Rebeca; Rodríguez-García, Laura; Martinón-Torres, María; Rosell, Jordi; Blasco, Ruth; Martín-Francés, Laura; Modesto, Mario; Carbonell, Eudald

    2012-04-01

    In this report, we present a morphometric comparative study of two Early Pleistocene humeri recovered from the TD6 level of the Gran Dolina cave site in Sierra de Atapuerca, northern Spain. ATD6-121 belongs to a child between 4 and 6 years old, whereas ATD6-148 corresponds to an adult. ATD6-148 exhibits the typical pattern of the genus Homo, but it also shows a large olecranon fossa and very thin medial and lateral pillars (also present in ATD6-121), sharing these features with European Middle Pleistocene hominins, Neandertals, and the Bodo Middle Pleistocene humerus. The morphology of the distal epiphysis, together with a few dental traits, suggests a phylogenetic relationship between the TD6 hominins and the Neandertal lineage. Given the older geochronological age of these hominins (ca. 900 ka), which is far from the age estimated by palaeogenetic studies for the population divergence of modern humans and Neandertals (ca. 400 ka), we suggest that this suite of derived "Neandertal" features appeared early in the evolution of the genus Homo. Thus, these features are not "Neandertal" apomorphies but traits which appeared in an ancestral and polymorphic population during the Early Pleistocene. PMID:22328492

  17. Reactivation of Epstein-Barr virus during early infection with human immunodeficiency virus.

    PubMed Central

    Rahman, M A; Kingsley, L A; Atchison, R W; Belle, S; Breinig, M C; Ho, M; Rinaldo, C R

    1991-01-01

    Reactivation of Epstein-Barr virus (EBV) in early human immunodeficiency virus (HIV) infection was investigated in 49 homosexual men who seroconverted to HIV (cases) as compared with 49 matched controls who remained seronegative to HIV during a longitudinal study. EBV infection was reactivated in cases 6 months, but not 12 months, prior to HIV seroconversion as compared with controls and remained reactivated during 18 months of follow-up after HIV seroconversion, as shown by increases in immunoglobulin (Ig) G antibody titers to EBV early antigen. Antibody titers to EBV viral capsid antigen did not differ between cases and controls prior to the time of seroconversion to HIV but were significantly increased among cases by the first seropositive study visit and remained elevated during the 18 months after HIV seroconversion. Total serum IgG levels were increased in cases at the visit of seroconversion, and during 18 months of follow-up, but did not correlate with enhanced IgG production specific for EBV antigens. Significant decreases in numbers of CD4+ cells and increases in numbers of CD8+ cells during this early phase of HIV infection were not associated with changes in patterns of EBV antibody responses. Reactivation of EBV beginning 6 months before HIV seroconversion may have implications regarding the role of this herpesvirus in the pathogenesis of HIV. PMID:1650790

  18. Changes in Laminin Expression Pattern during Early Differentiation of Human Embryonic Stem Cells

    PubMed Central

    Pook, Martin; Teino, Indrek; Kallas, Ade; Maimets, Toivo; Ingerpuu, Sulev; Jaks, Viljar

    2015-01-01

    Laminin isoforms laminin-511 and -521 are expressed by human embryonic stem cells (hESC) and can be used as a growth matrix to culture these cells under pluripotent conditions. However, the expression of these laminins during the induction of hESC differentiation has not been studied in detail. Furthermore, the data regarding the expression pattern of laminin chains in differentiating hESC is scarce. In the current study we aimed to fill this gap and investigated the potential changes in laminin expression during early hESC differentiation induced by retinoic acid (RA). We found that laminin-511 but not -521 accumulates in the committed cells during early steps of hESC differentiation. We also performed a comprehensive analysis of the laminin chain repertoire and found that pluripotent hESC express a more diverse range of laminin chains than shown previously. In particular, we provide the evidence that in addition to α1, α5, β1, β2 and γ1 chains, hESC express α2, α3, β3, γ2 and γ3 chain proteins and mRNA. Additionally, we found that a variant of laminin α3 chain—145 kDa—accumulated in RA-treated hESC showing that these cells produce prevalently specifically modified version of α3 chain in early phase of differentiation. PMID:26378917

  19. Early Human Activity (pre-332 BC) in Alexandria, Egypt: New findings in Eastern Harbor Cores

    NASA Astrophysics Data System (ADS)

    Stanley, J.; Landau, E. A.

    2005-12-01

    Historians have long postulated that a settlement called Rhakotis was present on Egypt's Mediterranean coast in the area subsequently occupied by the city of Alexandria. To date, however, the precise position of that site has not been located in the immediate area of the city founded by Alexander the Great. Also undefined are the earliest phases of occupation that pre-date Alexandria on Pharos Island and in the harbour area. A geoarchaeological project emphasizing sediment cores in Alexandria's Eastern Harbour now provides evidence of human occupation adjacent to these settings prior to establishment of Greece's great port in 332 BC. A radiocarbon-dated stratigraphic unit, defined as Middle Sand (III) and older than the 4th century BC, includes locally produced ceramics, along with rock fragments of non-local origin, and increased content of sand-sized heavy mineral and organic matter. Together, these date at least to Egypt's Late Dynastic Period (712-332 BC). Moreover, the geographic positions of core sites containing these markers indicate that early habitation occurred both at Pharos Island and on the mainland where the future Alexandria would be built. New findings in cores recovered in this marine environment are adding to knowledge of both natural processes and effects of human activity in early Alexandria.

  20. Early embryonic failure: Expression and imprinted status of candidate genes on human chromosome 21

    SciTech Connect

    Sherman, L.S.; Bennett, P.R.; Moore, G.E.

    1994-09-01

    Two cases of maternal uniparental (hetero)disomy for human chromosome 21 (mUPD21) have been identified in a systematic search for UPD in 23 cases of early embryonic failure (EEF). Bi-parental origin of the other chromosome pairs was confirmed using specific VNTR probes or dinucleotide repeat analysis. Both maternally and paternally derived isochromosomes 21q have previously been identified in two individuals with normal phenotypes. Full UPD21 has a different mechanism of origin than uniparental isochromosome 21q and its effect on imprinted genes and phenotypic outcome will therefore not necessarily be the same. EEF associated with mUPD21 suggests that developmentally important genes on HSA 21 may be imprinted such that they are only expressed from either the maternally or paternally derived alleles. We have searched for monoallelic expression of candidate genes on HSA 21 in human pregnancy (CBS, IFNAR, COL6A1) using intragenic DNA polymorphisms. These genes were chosen either because their murine homologues lie in imprinted regions or because they are potentially important in embryogenesis. Once imprinted candidate genes have been identified, their methylation status and expression in normal, early embryonic failure and uniparental disomy 21 pregnancies will be studied. At the same time, a larger number of cases of EEF are being examined to further investigate the incidence of UPD21 in this group.

  1. Early short-term treatment with neutralizing human monoclonal antibodies halts SHIV infection in infant macaques.

    PubMed

    Hessell, Ann J; Jaworski, J Pablo; Epson, Erin; Matsuda, Kenta; Pandey, Shilpi; Kahl, Christoph; Reed, Jason; Sutton, William F; Hammond, Katherine B; Cheever, Tracy A; Barnette, Philip T; Legasse, Alfred W; Planer, Shannon; Stanton, Jeffrey J; Pegu, Amarendra; Chen, Xuejun; Wang, Keyun; Siess, Don; Burke, David; Park, Byung S; Axthelm, Michael K; Lewis, Anne; Hirsch, Vanessa M; Graham, Barney S; Mascola, John R; Sacha, Jonah B; Haigwood, Nancy L

    2016-04-01

    Prevention of mother-to-child transmission (MTCT) of HIV remains a major objective where antenatal care is not readily accessible. We tested HIV-1-specific human neutralizing monoclonal antibodies (NmAbs) as a post-exposure therapy in an infant macaque model for intrapartum MTCT. One-month-old rhesus macaques were inoculated orally with the simian-human immunodeficiency virus SHIVSF162P3. On days 1, 4, 7 and 10 after virus exposure, we injected animals subcutaneously with NmAbs and quantified systemic distribution of NmAbs in multiple tissues within 24 h after antibody administration. Replicating virus was found in multiple tissues by day 1 in animals that were not treated. All NmAb-treated macaques were free of virus in blood and tissues at 6 months after exposure. We detected no anti-SHIV T cell responses in blood or tissues at necropsy, and no virus emerged after CD8(+) T cell depletion. These results suggest that early passive immunotherapy can eliminate early viral foci and thereby prevent the establishment of viral reservoirs. PMID:26998834

  2. Synchrotron FTIR microspectroscopy reveals early adipogenic differentiation of human mesenchymal stem cells at single-cell level.

    PubMed

    Liu, Zhixiao; Tang, Yuzhao; Chen, Feng; Liu, Xia; Liu, Zhaojian; Zhong, Jiajia; Hu, Jun; Lü, Junhong

    2016-09-23

    Human mesenchymal stem cells (hMSCs) have been used as an ideal in vitro model to study human adipogenesis. However, little knowledge of the early stage differentiation greatly hinders our understanding on the mechanism of the adipogenesis processes. In this study, synchrotron radiation-based Fourier transform infrared (SR-FTIR) microspectroscopy was applied to track the global structural and compositional changes of lipids, proteins and nucleic acids inside individual hMSCs along the time course. The multivariate analysis of the SR-FTIR spectra distinguished the dynamic and significant changes of the lipids and nucleic acid at early differentiation stage. Importantly, changes of lipid structure during early days (Day 1-3) of differentiation might serve as a potential biomarker in identifying the state in early differentiation at single cell level. These results proved that SR-FTIR is a powerful tool to study the stem cell fate determination and early lipogenesis events. PMID:27553281

  3. A More-than-Social Movement: The Post-Human Condition of Quality in the Early Years

    ERIC Educational Resources Information Center

    Arndt, Sonja; Tesar, Marek

    2016-01-01

    This article explores quality in early childhood education by de-elevating the importance of the human subject and experience, and heightening instead a focus on and tensions with the post-human. The argument traces the intricate web of "qualities" woven throughout entanglements of subjects, objects and things that constitute what is…

  4. The Early Development of Human Mirror Mechanisms: Evidence from Electromyographic Recordings at 3 and 6 Months

    ERIC Educational Resources Information Center

    Turati, Chiara; Natale, Elena; Bolognini, Nadia; Senna, Irene; Picozzi, Marta; Longhi, Elena; Cassia, Viola Macchi

    2013-01-01

    In primates and adult humans direct understanding of others' action is provided by mirror mechanisms matching action observation and action execution (e.g. Casile, Caggiano & Ferrari, 2011). Despite the growing body of evidence detailing the existence of these mechanisms in the adult human brain, their origins and early development are…

  5. The cult of amphioxus in German Darwinism; or, our gelatinous ancestors in Naples' blue and balmy bay.

    PubMed

    Hopwood, Nick

    2015-01-01

    Biologists having rediscovered amphioxus, also known as the lancelet or Branchiostoma, it is time to reassess its place in early Darwinist debates over vertebrate origins. While the advent of the ascidian-amphioxus theory and challenges from various competitors have been, documented, this article offers a richer account of the public appeal of amphioxus as a primitive ancestor. The focus is on how the 'German Darwin' Ernst Haeckel persuaded general magazine and newspaper readers to revere this "flesh of our flesh and blood of our blood", and especially on Das neue Laienbrevier des Haeckelismus (The new lay breviary of Haeckelism) by Moritz Reymond with cartoons by Fritz Steub. From the late 1870s these successful little books of verse introduced the Neapolitan discoveries that made the animal's name and satirized Haeckel's rise as high priest of its cult. One song is reproduced and translated here, with a contemporary "imitation" by the Canadian palaeontologist Edward John Chapman, and extracts from others. Predating the American "It's a long way from amphioxus" by decades, these rhymes dramatize neglected 'species politics' of Darwinism and highlight the roles of humour in negotiating evolution. PMID:26013195

  6. Isolation, promoter analysis and expression profile of Dreb2 in response to drought stress in wheat ancestors.

    PubMed

    Tavakol, Elahe; Sardaro, Maria Luisa Savo; Shariati, J Vahid; Rossini, Laura; Porceddu, Enrico

    2014-10-01

    Drought is one of the most important abiotic stresses, constraining crop production seriously. The dehydration responsive element binding proteins (DREBs) are important plant-specific transcription factors that respond to various abiotic stresses and consequently induce abiotic stress-related genes that impart stress endurance in plants. Wild species are naturally exposed to various abiotic stresses and potentially harbor suitable alleles through natural selection. In this study we isolated and characterized Dreb2 from Triticum urartu (GenBank: KF731664), Aegilops speltoides (GenBank: KF731665) and Aegilops tauschii (GenBank: KF731663), the A, B and D genome ancestors of bread wheat, respectively. Analysis of over 1.3 kb upstream region of the gene revealed the presence of several conserved cis-acting regulatory elements including ABA-responsive elements, low temperature responsive elements, and several light and environmental signaling related motifs potentially vindicate Dreb2 responses to environmental signals. Moreover, the gene exhibited an alternative splicing, conserved among orthologous genes in grasses, and produced a non-functional isoform due to splicing in an exon resulted frame-shift creating an early stop codon before the functional domain. The expression analysis of Dreb2 under normal and different levels of dehydration stress conditions indicated that the two active spliced isoforms are upregulated when the plant exposed to drought stress whereas the non-functional isoform is downregulated in severe drought. PMID:25017054

  7. Early detection of human focal seizures based on cortical multiunit activity.

    PubMed

    Park, Yun S; Hochberg, Leigh R; Eskandar, Emad N; Cash, Sydney S; Truccolo, Wilson

    2014-01-01

    Approximately 50 million people in the world suffer from epileptic seizures. Reliable early seizure detection could bring significantly beneficial therapeutic alternatives. In recent decades, most approaches have relied on scalp EEG and intracranial EEG signals, but practical early detection for closed-loop seizure control remains challenging. In this study, we present preliminary analyses of an early detection approach based on intracortical neuronal multiunit activity (MUA) recorded from a 96-microelectrode array (MEA). The approach consists of (1) MUA detection from broadband field potentials recorded at 30 kHz by the MEA; (2) MUA feature extraction; (3) cost-sensitive support vector machine classification of ictal and interictal samples; and (4) Kalman-filtering postprocessing. MUA was here defined as the number of threshold crossing (spike counts) applied to the 300 Hz-6 kHz bandpass filtered local field potentials in 0.1 sec time windows. MUA features explored in this study included the mean, variance, and Fano-factor, computed across the MEA channels. In addition, we used the leading eigenvalues of MUA spatial and temporal correlation matrices computed in 1-sec moving time windows. We assessed the seizure detection approach on out-of-sample data from one-participant recordings with six seizure events and 4.73-hour interictal data. The proposed MUA-based detection approach yielded a 100% sensitivity (6/6) and no false positives, and a latency of 4.17 ± 2.27 sec (mean ± SD) with respect to ECoG-identified seizure onsets. These preliminary results indicate intracortical MUA may be a useful signal for early detection of human epileptic seizures. PMID:25571313

  8. How We Got Here: Evolutionary Changes in Skull Shape in Humans & Their Ancestors

    ERIC Educational Resources Information Center

    Price, Rebecca M.

    2012-01-01

    This activity uses inquiry to investigate how large changes in shape can evolve from small changes in the timing of development. Students measure skull shape in fetal, infant, juvenile, and adult chimpanzees and compare them to adult skulls of "Homo sapiens," "Homo erectus," and "Australopithecus afarensis." They conclude by re-interpreting their…

  9. Sleep-wake states and their regulatory mechanisms throughout early human development.

    PubMed

    Peirano, Patricio; Algarín, Cecilia; Uauy, Ricardo

    2003-10-01

    The emergence of sleep states is one of the most significant aspects of development. Descriptions of both neonatal and late fetal behavior and studies on the organization of sleep have shown that fetus and newborns exhibit spontaneously discrete and cyclic patterns of active sleep (AS) and quiet sleep (QS). Human fetuses and neonates sleep most of their life, and AS is the prevailing state even during the first postnatal months. Several hypotheses to explain central nervous system development consider that AS is the expression of a basic activation program for the central nervous system that increases the functional competence of neurons, circuits, and complex patterns before the organism is called on to use them. Current results indicate the maturation of QS not only coincides with the formation of thalamocortical and intracortical patterns of innervation and periods of heightened synaptogenesis, since this sleep state is also associated with important processes in synaptic remodeling. In fact, several studies suggest that the information acquired during wakefulness is further processed during AS and QS. This article reviews the processes involved in the timing of both AS/QS and sleep/wake alternating patterns throughout early human development. A growing body of evidence indicates that the duration of unmodulated parental care and noncircadian environmental conditions may be detrimental for the establishment of these basic rhythmicities. As a consequence, alterations in parental/environmental entraining factors may well contribute to disturb sleep and feeding commonly experienced by preterm infants. Further knowledge on the early establishment of sleep-wake states regulatory mechanisms is needed to improve modalities for appropriate stimulation in the developing human being. PMID:14597916

  10. Early afterdepolarizations promote transmural reentry in ischemic human ventricles with reduced repolarization reserve

    PubMed Central

    Dutta, Sara; Mincholé, Ana; Zacur, Ernesto; Quinn, T. Alexander; Taggart, Peter; Rodriguez, Blanca

    2016-01-01

    Aims Acute ischemia is a major cause of sudden arrhythmic death, further promoted by potassium current blockers. Macro-reentry around the ischemic region and early afterdepolarizations (EADs) caused by electrotonic current have been suggested as potential mechanisms in animal and isolated cell studies. However, ventricular and human-specific arrhythmia mechanisms and their modulation by repolarization reserve remain unclear. The goal of this paper is to unravel multiscale mechanisms underlying the modulation of arrhythmic risk by potassium current (IKr) block in human ventricles with acute regional ischemia. Methods and results A human ventricular biophysically-detailed model, with acute regional ischemia is constructed by integrating experimental knowledge on the electrophysiological ionic alterations caused by coronary occlusion. Arrhythmic risk is evaluated by determining the vulnerable window (VW) for reentry following ectopy at the ischemic border zone. Macro-reentry around the ischemic region is the main reentrant mechanism in the ischemic human ventricle with increased repolarization reserve due to the ATP-sensitive potassium current (IK(ATP)) activation. Prolongation of refractoriness by 4% caused by 30% IKr reduction counteracts the establishment of macro-reentry and reduces the VW for reentry (by 23.5%). However, a further decrease in repolarization reserve (50% IKr reduction) is less anti-arrhythmic despite further prolongation of refractoriness. This is due to the establishment of transmural reentry enabled by electrotonically-triggered EADs in the ischemic border zone. EADs are produced by L-type calcium current (ICaL) reactivation due to prolonged low amplitude electrotonic current injected during the repolarization phase. Conclusions Electrotonically-triggered EADs are identified as a potential mechanism facilitating intramural reentry in a regionally-ischemic human ventricles model with reduced repolarization reserve. PMID:26850675

  11. Differentiation of early germ cells from human skin-derived stem cells without exogenous gene integration.

    PubMed

    Ge, Wei; Ma, Hua-Gang; Cheng, Shun-Feng; Sun, Yuan-Chao; Sun, Li-Lan; Sun, Xiao-Feng; Li, Lan; Dyce, Paul; Li, Julang; Shi, Qing-Hua; Shen, Wei

    2015-01-01

    Infertility has long been a difficult issue for many couples. The successful differentiation of germ cells and live progeny from pluripotent stem cells brings new hope to the couples suffering with infertility. Here we successfully isolated human fetus skin-derived stem cells (hfSDSCs) from fetus skin tissue and demonstrated that hfSDSCs can be differentiated into early human germ cell-like cells (hGCLCs). These cells express human germ cell markers DAZL and VASA. Moreover, these pluripotent stem cell-derived hGCLCs are free of exogenous gene integration. When hfSDSCs were differentiated in porcine follicle fluid (PFF) conditioned media, which has been shown to promote the differentiation of mouse and porcine SDSCs into oocyte-like cells (OLCs), we observed some vesicular structures formed from hfSDSCs. Moreover, when hfSDSCs were cultured with specific conditioned media, we observed punctate and elongated SCP3 staining foci, indicating the initiation of meiosis. Ploidy analysis and fluorescent in situ hybridization (FISH) analysis indicated that a small percentage of putative 1N populations formed from hfSDSCs when compared with positive controls. In conclusion, our data here, for the first time, demonstrated that hfSDSCs possess the differentiation potential into germ lines, and they may differentiate both male and female hGCLCs in vitro under appropriate conditions. PMID:26347377

  12. Angiogenin expression during early human placental development; association with blood vessel formation.

    PubMed

    Pavlov, Nadine; Frendo, Jean-Louis; Guibourdenche, Jean; Degrelle, Séverine A; Evain-Brion, Danièle; Badet, Josette

    2014-01-01

    The placenta is a transient organ essential for fetal development. During human placental development, chorionic villi grow in coordination with a large capillary network resulting from both vasculogenesis and angiogenesis. Angiogenin is one of the most potent inducers of neovascularisation in experimental models in vivo. We and others have previously mapped angiogenin expression in the human term placenta. Here, we explored angiogenin involvement in early human placental development. We studied, angiogenin expression by in situ hybridisation and/or by RT-PCR in tissues and primary cultured trophoblastic cells and angiogenin cellular distribution by coimmunolabelling with cell markers: CD31 (PECAM-1), vascular endothelial cadherin (VE-cadherin), vascular endothelial growth factor receptor-2 (VEGF-R2), Tie-2, von Willebrand factor, CD34, erythropoeitin receptor (Epo-R), alpha-smooth muscle actin, CD45, cytokeratin 7, and Ki-67. Extravillous and villous cytotrophoblasts, isolated and differentiated in vitro, expressed and secreted angiogenin. Angiogenin was detected in villous trophoblastic layers, and structured and nascent fetal vessels. In decidua, it was expressed by glandular epithelial cells, vascular cells and macrophages. The observed pattern of angiogenin expression is compatible with a role in blood vessel formation and in cross-talk between trophoblasts and endothelial cells. In view of angiogenin properties, we suggest that angiogenin may participate in placental vasculogenesis and organogenesis. PMID:25093183

  13. Proactive Integration of Planetary Protection Needs Into Early Design Phases of Human Exploration Missions

    NASA Astrophysics Data System (ADS)

    Race, Margaret; Conley, Catharine

    yet been developed. Looking ahead, it is recognized that these planetary protection policies will apply to both governmental and non-governmental entities for the more than 100 countries that are signatories to the Outer SpaceTreaty. Fortunately, planetary protection controls for human missions are supportive of many other important mission needs, such as maximizing closed-loop and recycling capabilities to minimize mass required, minimizing exposure of humans to planetary materials for multiple health reasons, and minimizing contamination of planetary samples and environments during exploration and science activities. Currently, there is progress on a number of fronts in translating the basic COSPAR PP Principles and Implementation Guidelines into information that links with early engineering and process considerations. For example, an IAA Study Group on Planetary Protection and Human Missions is engaging robotic and human mission developers and scientists in exploring detailed technical, engineering and operational approaches by which planetary protection objectives can be accomplished for human missions in synergism with robotic exploration and in view of other constraints. This on-going study aims to highlight important information for the early stages of planning, and identify key research and technology development (R&TD) areas for further consideration and work. Such R&TD challenges provide opportunities for individuals, institutions and agencies of emerging countries to be involved in international exploration efforts. In January 2014, the study group presented an Interim Report to the IAA Heads of Agencies Summit in Washington DC. Subsequently, the group has continued to work on expanding the initial technical recommendations and findings, focusing especially on information useful to mission architects and designers as they integrate PP considerations in their varied plans-- scientific, commercial and otherwise. Already the findings and recommendations

  14. Dynamic expression of calretinin in embryonic and early fetal human cortex

    PubMed Central

    González-Gómez, Miriam; Meyer, Gundela

    2014-01-01

    Calretinin (CR) is one of the earliest neurochemical markers in human corticogenesis. In embryos from Carnegie stages (CS) 17 to 23, calbindin (CB) and CR stain opposite poles of the incipient cortex suggesting early regionalization: CB marks the neuroepithelium of the medial boundary of the cortex with the choroid plexus (cortical hem). By contrast, CR is confined to the subventricular zone (SVZ) of the lateral and caudal ganglionic eminences at the pallial-subpallial boundary (PSB, or antihem), from where CR+/Tbr1- neurons migrate toward piriform cortex and amygdala as a component of the lateral cortical stream. At CS 19, columns of CR+ cells arise in the rostral cortex, and contribute at CS 20 to the “monolayer” of horizontal Tbr1+/CR+ and GAD+ cells in the preplate. At CS 21, the “pioneer cortical plate” appears as a radial aggregation of CR+/Tbr1+ neurons, which cover the entire future neocortex and extend the first corticofugal axons. CR expression in early human corticogenesis is thus not restricted to interneurons, but is also present in the first excitatory projection neurons of the cortex. At CS 21/22, the cortical plate is established following a lateral to medial gradient, when Tbr1+/CR- neurons settle within the pioneer cortical plate, and thus separate superficial and deep pioneer neurons. CR+ pioneer neurons disappear shortly after the formation of the cortical plate. Reelin+ Cajal-Retzius cells begin to express CR around CS21 (7/8 PCW). At CS 21–23, the CR+ SVZ at the PSB is the source of CR+ interneurons migrating into the cortical SVZ. In turn, CB+ interneurons migrate from the subpallium into the intermediate zone following the fibers of the internal capsule. Early CR+ and CB+ interneurons thus have different origins and migratory routes. CR+ cell populations in the embryonic telencephalon take part in a complex sequence of events not analyzed so far in other mammalian species, which may represent a distinctive trait of the initial

  15. Proactive Integration of Planetary Protection Needs Into Early Design Phases of Human Exploration Missions

    NASA Astrophysics Data System (ADS)

    Race, Margaret; Conley, Catharine

    yet been developed. Looking ahead, it is recognized that these planetary protection policies will apply to both governmental and non-governmental entities for the more than 100 countries that are signatories to the Outer SpaceTreaty. Fortunately, planetary protection controls for human missions are supportive of many other important mission needs, such as maximizing closed-loop and recycling capabilities to minimize mass required, minimizing exposure of humans to planetary materials for multiple health reasons, and minimizing contamination of planetary samples and environments during exploration and science activities. Currently, there is progress on a number of fronts in translating the basic COSPAR PP Principles and Implementation Guidelines into information that links with early engineering and process considerations. For example, an IAA Study Group on Planetary Protection and Human Missions is engaging robotic and human mission developers and scientists in exploring detailed technical, engineering and operational approaches by which planetary protection objectives can be accomplished for human missions in synergism with robotic exploration and in view of other constraints. This on-going study aims to highlight important information for the early stages of planning, and identify key research and technology development (R&TD) areas for further consideration and work. Such R&TD challenges provide opportunities for individuals, institutions and agencies of emerging countries to be involved in international exploration efforts. In January 2014, the study group presented an Interim Report to the IAA Heads of Agencies Summit in Washington DC. Subsequently, the group has continued to work on expanding the initial technical recommendations and findings, focusing especially on information useful to mission architects and designers as they integrate PP considerations in their varied plans-- scientific, commercial and otherwise. Already the findings and recommendations

  16. Evolution of influenza A virus nucleoprotein genes: implications for the origins of H1N1 human and classical swine viruses.

    PubMed Central

    Gorman, O T; Bean, W J; Kawaoka, Y; Donatelli, I; Guo, Y J; Webster, R G

    1991-01-01

    A phylogenetic analysis of 52 published and 37 new nucleoprotein (NP) gene sequences addressed the evolution and origin of human and swine influenza A viruses. H1N1 human and classical swine viruses (i.e., those related to Swine/Iowa/15/30) share a single common ancestor, which was estimated to have occurred in 1912 to 1913. From this common ancestor, human and classical swine virus NP genes have evolved at similar rates that are higher than in avian virus NP genes (3.31 to 3.41 versus 1.90 nucleotide changes per year). At the protein level, human virus NPs have evolved twice as fast as classical swine virus NPs (0.66 versus 0.34 amino acid change per year). Despite evidence of frequent interspecies transmission of human and classical swine viruses, our analysis indicates that these viruses have evolved independently since well before the first isolates in the early 1930s. Although our analysis cannot reveal the original host, the ancestor virus was avianlike, showing only five amino acid differences from the root of the avian virus NP lineage. The common pattern of relationship and origin for the NP and other genes of H1N1 human and classical swine viruses suggests that the common ancestor was an avian virus and not a reassortant derived from previous human or swine influenza A viruses. The new avianlike H1N1 swine viruses in Europe may provide a model for the evolution of newly introduced avian viruses into the swine host reservoir. The NPs of these viruses are evolving more rapidly than those of human or classical swine viruses (4.50 nucleotide changes and 0.74 amino acid change per year), and when these rates are applied to pre-1930s human and classical swine virus NPs, the predicted date of a common ancestor is 1918 rather than 1912 to 1913. Thus, our NP phylogeny is consistent with historical records and the proposal that a short time before 1918, a new H1N1 avianlike virus entered human or swine hosts (O. T. Gorman, R. O. Donis, Y. Kawaoka, and R. G. Webster

  17. Comparing salt tolerance of beet cultivars and their halophytic ancestor: consequences of domestication and breeding programmes

    PubMed Central

    Rozema, Jelte; Cornelisse, Danny; Zhang, Yuancheng; Li, Hongxiu; Bruning, Bas; Katschnig, Diana; Broekman, Rob; Ji, Bin; van Bodegom, Peter

    2015-01-01

    Salt tolerance of higher plants is determined by a complex set of traits, the timing and rate of evolution of which are largely unknown. We compared the salt tolerance of cultivars of sugar beet and their ancestor, sea beet, in hydroponic studies and evaluated whether traditional domestication and more recent breeding have changed salt tolerance of the cultivars relative to their ancestor. Our comparison of salt tolerance of crop cultivars is based on values of the relative growth rate (RGR) of the entire plant at various salinity levels. We found considerable salt tolerance of the sea beet and slightly, but significantly, reduced salt tolerance of the sugar beet cultivars. This indicates that traditional domestication by selection for morphological traits such as leaf size, beet shape and size, enhanced productivity, sugar content and palatability slightly affected salt tolerance of sugar beet cultivars. Salt tolerance among four sugar beet cultivars, three of which have been claimed to be salt tolerant, did not differ. We analysed the components of RGR to understand the mechanism of salt tolerance at the whole-plant level. The growth rate reduction at higher salinity was linked with reduced leaf area at the whole-plant level (leaf area ratio) and at the individual leaf level (specific leaf area). The leaf weight fraction was not affected by increased salinity. On the other hand, succulence and leaf thickness and the net assimilation per unit of leaf area (unit leaf rate) increased in response to salt treatment, thus partially counteracting reduced capture of light by lower leaf area. This compensatory mechanism may form part of the salt tolerance mechanism of sea beet and the four studied sugar beet cultivars. Together, our results indicate that domestication of the halophytic ancestor sea beet slightly reduced salt tolerance and that breeding for improved salt tolerance of sugar beet cultivars has not been effective. PMID:25492122

  18. Early innate responses to pathogens: pattern recognition by unconventional human T-cells

    PubMed Central

    Liuzzi, Anna Rita; McLaren, James E; Price, David A; Eberl, Matthias

    2015-01-01

    Although typically viewed as a feature of innate immune responses, microbial pattern recognition is increasingly acknowledged as a function of particular cells nominally categorized within the adaptive immune system. Groundbreaking research over the past three years has shown how unconventional human T-cells carrying invariant or semi-invariant TCRs that are not restricted by classical MHC molecules sense microbial compounds via entirely novel antigen presenting pathways. This review will focus on the innate-like recognition of non-self metabolites by Vγ9/Vδ2 T-cells, mucosal-associated invariant T (MAIT) cells and germline-encoded mycolyl-reactive (GEM) T-cells, with an emphasis on early immune responses in acute infection. PMID:26182978

  19. The transcriptional architecture of early human hematopoiesis identifies multilevel control of lymphoid commitment

    PubMed Central

    Laurenti, Elisa; Doulatov, Sergei; Zandi, Sasan; Plumb, Ian; Chen, Jing; April, Craig; Fan, Jian-Bing; Dick, John E.

    2016-01-01

    Understanding how differentiation programs originate from within the gene expression landscape of hematopoietic stem cells (HSC) is crucial to develop new clinical therapies. We mapped the transcriptional dynamics underlying the first steps of commitment by tracking transcriptome changes in human HSC and eight early progenitor populations. Transcriptional programs are extensively shared, extend across lineage-potential boundaries, and are not strictly lineage-affiliated. Elements of stem, lymphoid and myeloid programs are retained in multi-lymphoid progenitors (MLP), reflecting a hybrid transcriptional state. Based on functional single cell analysis, BCL11A, SOX4 and TEAD1 governed transcriptional networks within MLPs, leading to B cell specification. Overall, we show that integrated transcriptome approaches can identify novel regulators of multipotency and uncover additional complexity in lymphoid commitment. PMID:23708252

  20. Isolated and bilateral simultaneous facial palsy disclosing early human immunodeficiency virus infection

    PubMed Central

    Sathirapanya, Pornchai

    2015-01-01

    Bilateral lower motor neuron type facial palsy is an unusual neurological disorder. There are few reports that associate it with the human immunodeficiency virus (HIV) infection on initial presentation. A 51-year-old married woman, who was previously healthy and had no risk of HIV infection, presented solely with bilateral simultaneous facial palsy. A positive HIV serology test was confirmed by an enzyme-linked immunosorbent assay test. Following a short course of oral prednisolone, the patient recovered completely from facial palsy in three months, even though an antiretroviral treatment was suspended. Exclusion of HIV infection in patients with bilateral facial palsy is essential for early diagnosis and management of HIV. PMID:26106247

  1. The impact of early human data on clinical development: there is time to win.

    PubMed

    Swart, Piet; Lozac'h, Frederic; Simon, Marjorie; van Duijn, Esther; Vaes, Wouter H J

    2016-06-01

    Modern accelerator mass spectrometry (AMS) methods enable the routine application of this technology in drug development. By the administration of a (14)C-labelled microdose or microtrace, pharmacokinetic (PK) data, such as mass balance, metabolite profiling, and absolute bioavailability (AB) data, can be generated easier, faster, and at lower costs. Here, we emphasize the advances and impact of this technology for pharmaceutical companies. The availability of accurate intravenous (iv) PK and human absorption, distribution, metabolism, and excretion (ADME) information, even before or during Phase I trials, can improve the clinical development plan. Moreover, applying the microtrace approach during early clinical development might impact the number of clinical pharmacology and preclinical safety pharmacology studies required, and shorten the overall drug discovery program. PMID:27046542

  2. Improving human activity recognition and its application in early stroke diagnosis.

    PubMed

    Villar, José R; González, Silvia; Sedano, Javier; Chira, Camelia; Trejo-Gabriel-Galan, Jose M

    2015-06-01

    The development of efficient stroke-detection methods is of significant importance in today's society due to the effects and impact of stroke on health and economy worldwide. This study focuses on Human Activity Recognition (HAR), which is a key component in developing an early stroke-diagnosis tool. An overview of the proposed global approach able to discriminate normal resting from stroke-related paralysis is detailed. The main contributions include an extension of the Genetic Fuzzy Finite State Machine (GFFSM) method and a new hybrid feature selection (FS) algorithm involving Principal Component Analysis (PCA) and a voting scheme putting the cross-validation results together. Experimental results show that the proposed approach is a well-performing HAR tool that can be successfully embedded in devices. PMID:25684369

  3. "On the Augmented Cognition Approach to Early Warning Systems- Human System Integration NASA Experiance

    NASA Astrophysics Data System (ADS)

    Achimowicz, Jerzy; Bakowski, Rafal; Mazur, Andrzej

    2014-05-01

    The authors present results related to the implementation of augmented cognition approach to severe weather early warning systems in aviation and aerospace operational environment. The limitations of automation and adaptive approach in severe weather warning systems are discussed. Also the positive impact of HSI (Human System Integration) NASA approach will be shown, in the process of pilot training in minimal weather conditions. The flight safety procedures related to weather conditions will be analyzed and the meteorological general aviation weather support product developed at IMGW will be presented. Special emphasis will be put on the integration of the military and civilian weather radar/lighting detection systems and the impact of space weather on aerospace operations including the use of unmanned RPAS (Remotely Controlled Aircraf Systems). J.Z. Achimowicz is also affiliated with Flight Safety Division of Military Institute of Aviation Medicine, Warsaw, Poland.

  4. Human evolution.

    PubMed

    Wood, B

    1996-12-01

    The common ancestor of modern humans and the great apes is estimated to have lived between 5 and 8 Myrs ago, but the earliest evidence in the human, or hominid, fossil record is Ardipithecus ramidus, from a 4.5 Myr Ethiopian site. This genus was succeeded by Australopithecus, within which four species are presently recognised. All combine a relatively primitive postcranial skeleton, a dentition with expanded chewing teeth and a small brain. The most primitive species in our own genus, Homo habilis and Homo rudolfensis, are little advanced over the australopithecines and with hindsight their inclusion in Homo may not be appropriate. The first species to share a substantial number of features with later Homo is Homo ergaster, or 'early African Homo erectus', which appears in the fossil record around 2.0 Myr. Outside Africa, fossil hominids appear as Homo erectus-like hominids, in mainland Asia and in Indonesia close to 2 Myr ago; the earliest good evidence of 'archaic Homo' in Europe is dated at between 600-700 Kyr before the present. Anatomically modern human, or Homo sapiens, fossils are seen first in the fossil record in Africa around 150 Kyr ago. Taken together with molecular evidence on the extent of DNA variation, this suggests that the transition from 'archaic' to 'modern' Homo may have taken place in Africa. PMID:8976151

  5. Single-cell analysis delineates a trajectory toward the human early otic lineage.

    PubMed

    Ealy, Megan; Ellwanger, Daniel C; Kosaric, Nina; Stapper, Andres P; Heller, Stefan

    2016-07-26

    Efficient pluripotent stem cell guidance protocols for the production of human posterior cranial placodes such as the otic placode that gives rise to the inner ear do not exist. Here we use a systematic approach including defined monolayer culture, signaling modulation, and single-cell gene expression analysis to delineate a developmental trajectory for human otic lineage specification in vitro. We found that modulation of bone morphogenetic protein (BMP) and WNT signaling combined with FGF and retinoic acid treatments over the course of 18 days generates cell populations that develop chronological expression of marker genes of non-neural ectoderm, preplacodal ectoderm, and early otic lineage. Gene expression along this differentiation path is distinct from other lineages such as endoderm, mesendoderm, and neural ectoderm. Single-cell analysis exposed the heterogeneity of differentiating cells and allowed discrimination of non-neural ectoderm and otic lineage cells from off-target populations. Pseudotemporal ordering of human embryonic stem cell and induced pluripotent stem cell-derived single-cell gene expression profiles revealed an initially synchronous guidance toward non-neural ectoderm, followed by comparatively asynchronous occurrences of preplacodal and otic marker genes. Positive correlation of marker gene expression between both cell lines and resemblance to mouse embryonic day 10.5 otocyst cells implied reasonable robustness of the guidance protocol. Single-cell trajectory analysis further revealed that otic progenitor cell types are induced in monolayer cultures, but further development appears impeded, likely because of lack of a lineage-stabilizing microenvironment. Our results provide a framework for future exploration of stabilizing microenvironments for efficient differentiation of stem cell-generated human otic cell types. PMID:27402757

  6. Ancestor-descendant relationships in evolution: origin of the extant pygmy right whale, Caperea marginata.

    PubMed

    Tsai, Cheng-Hsiu; Fordyce, R Ewan

    2015-01-01

    Ancestor-descendant relationships (ADRs), involving descent with modification, are the fundamental concept in evolution, but are usually difficult to recognize. We examined the cladistic relationship between the only reported fossil pygmy right whale, †Miocaperea pulchra, and its sole living relative, the enigmatic pygmy right whale Caperea marginata, the latter represented by both adult and juvenile specimens. †Miocaperea is phylogenetically bracketed between juvenile and adult Caperea marginata in morphologically based analyses, thus suggesting a possible ADR-the first so far identified within baleen whales (Cetacea: Mysticeti). The †Miocaperea-Caperea lineage may show long-term morphological stasis and, in turn, punctuated equilibrium. PMID:25589485

  7. The Current State of Early Childhood Education Programs: How Early Childhood Center Directors Manage Their Human Resources

    ERIC Educational Resources Information Center

    Arend, Lauren E.

    2010-01-01

    Purpose: Research in the field of early childhood education (ECE) demonstrated the association between skilled directors and high quality programs. Still, most state licensing requirements do not delineate the requisite knowledge or experience necessary to be an effective director. Many ECE directors advance to their position directly from the…

  8. Malocclusion in Early Anatomically Modern Human: A Reflection on the Etiology of Modern Dental Misalignment

    PubMed Central

    Sarig, Rachel; Slon, Viviane; Abbas, Janan; May, Hila; Shpack, Nir; Vardimon, Alexander Dan; Hershkovitz, Israel

    2013-01-01

    Malocclusions are common in modern populations. Yet, as the study of occlusion requires an almost intact dentition in both the maxilla and mandible, searching for the ultimate cause of malocclusion is a challenge: relatively little ancient material is available for research on occlusal states. The Qafzeh 9 skull is unique, as its preserved dentition allowed us to investigate the presence and manifestations of malocclusion. The aim of this study was thus to examine the occlusal condition in the Qafzeh 9 specimen in light of modern knowledge regarding the etiology of malocclusion. We revealed a pathologic occlusion in the Qafzeh 9 skull that probably originated in the early developmental stage of the dentition, and was aggravated by forces applied by mastication. When arch continuity is interrupted due to misalignment of teeth as in this case, force transmission is not equal on both sides, causing intra-arch outcomes such as mesialization of the teeth, midline deviation, rotations and the aggravation of crowding. All are evident in the Qafzeh 9 skull: the midline deviates to the left; the incisors rotate mesio-buccally; the left segment is constricted; the left first molar is buccally positioned and the left premolars palatally tilted. The inter-arch evaluation revealed anterior cross bite with functional shift that might affect force transmission and bite force. In conclusion, the findings of the current study suggest that malocclusion of developmental origin was already present in early anatomically modern humans (AMH) (the present case being the oldest known case, dated to ca. 100,000 years); that there is no basis to the notion that early AMH had a better adjustment between teeth and jaw size; and that jaw-teeth size discrepancy could be found in prehistoric populations and is not a recent phenomenon. PMID:24278319

  9. Specific requirement for ATP at an early step of in vitro transcription of human mitochondrial DNA

    SciTech Connect

    Narasimhan, N.; Attardi, G.

    1987-06-01

    The ATP concentrations allowing transcription of heavy- and light-strand of human mtDNA in a HeLa cell mitochrondrial lysate were found to cover a broad range, with a maximum around 2.5 mM, and with reproducible differences in the ATP response curves for the two transcription events. Direct measurements showed that nonspecific ATP degradation during the assay did not account for the high ATP requirement. 5'-Adenylyl imidodiphosphate (p(NH)ppA), an ATP analog with a nonhydrolyzable ..beta..-..gamma.. bond, was unable to substitute for ATP in supporting mtDNA transcription but greatly stimulated this transcription in the presence of a low concentration of exogenous APT, measured with (/sup 32/P)-labeled nucleotides. Evidence was obtained indicating that p(NH)ppA did not support an early event in mtDNA transcription (formation of preinitiation complex or initiation), whereas this analog could substitute effectively for ATP in the subsequent elongation steps. These results pointed to a specific requirement for ATP at an early step of the transcription process.

  10. Behavior of homologous chromosomes in early meiotic stages of human spermatocytes as revealed by FISH

    SciTech Connect

    Bar-Am, I.; Avivi, L.; Mukame, E.

    1994-09-01

    The process by which homologous chromosomes recognize each other at the beginning of meiosis, prior to synapsis, is poorly understood. To gain a better understanding as to when, where and how a given chromosome approaches its pairing partner, chromosome behavior at early stages of meiosis in human spermatocytes was studied. Using multi-color FISH with centromeric- and telomeric-specific probes, as well as with whole chromosome DNA libraries, it was clearly aligned. Rather, similarly to non-homologous chromosomes, they were well separated from each other. At the commencement of synapsis, during the process of homology search, homologues underwent a drastic conformational change, elongating into strands that approached each other by their telomeres. Just preceding the co-alignment of the homologous centromeres, telomeres changed their interphase random distribution and occupied a confined region of the nuclear periphery. Following synapsis, telomeres spread over the whole nuclear periphery. These dynamics in the telomeres distribution, which are unique to early stages of meiosis, are presumably related to the role that telomeres play in the process of homology search and the commencement of synapsis.

  11. Early Human Speciation, Brain Expansion and Dispersal Influenced by African Climate Pulses

    PubMed Central

    Shultz, Susanne; Maslin, Mark

    2013-01-01

    Early human evolution is characterised by pulsed speciation and dispersal events that cannot be explained fully by global or continental paleoclimate records. We propose that the collated record of ephemeral East African Rift System (EARS) lakes could be a proxy for the regional paleoclimate conditions experienced by early hominins. Here we show that the presence of these lakes is associated with low levels of dust deposition in both West African and Mediterranean records, but is not associated with long-term global cooling and aridification of East Africa. Hominin expansion and diversification seem to be associated with climate pulses characterized by the precession-forced appearance and disappearance of deep EARS lakes. The most profound period for hominin evolution occurs at about 1.9 Ma; with the highest recorded diversity of hominin species, the appearance of Homo (sensu stricto) and major dispersal events out of East Africa into Eurasia. During this period, ephemeral deep-freshwater lakes appeared along the whole length of the EARS, fundamentally changing the local environment. The relationship between the local environment and hominin brain expansion is less clear. The major step-wise expansion in brain size around 1.9 Ma when Homo appeared was coeval with the occurrence of ephemeral deep lakes. Subsequent incremental increases in brain size are associated with dry periods with few if any lakes. Plio-Pleistocene East African climate pulses as evinced by the paleo-lake records seem, therefore, fundamental to hominin speciation, encephalisation and migration. PMID:24146922

  12. Heatwave Early Warning Systems and Adaptation Advice to Reduce Human Health Consequences of Heatwaves

    PubMed Central

    Lowe, Dianne; Ebi, Kristie L.; Forsberg, Bertil

    2011-01-01

    Introduction: With climate change, there has been an increase in the frequency, intensity and duration of heatwave events. In response to the devastating mortality and morbidity of recent heatwave events, many countries have introduced heatwave early warning systems (HEWS). HEWS are designed to reduce the avoidable human health consequences of heatwaves through timely notification of prevention measures to vulnerable populations. Objective: To identify the key characteristics of HEWS in European countries to help inform modification of current, and development of, new systems and plans. Methods: We searched the internet to identify HEWS policy or government documents for 33 European countries and requested information from relevant organizations. We translated the HEWS documents and extracted details on the trigger indicators, thresholds for action, notification strategies, message intermediaries, communication and dissemination strategies, prevention strategies recommended and specified target audiences. Findings and Conclusions: Twelve European countries have HEWS. Although there are many similarities among the HEWS, there also are differences in key characteristics that could inform improvements in heatwave early warning plans. PMID:22408593

  13. Early responses of human cancer cells upon photodynamic treatment monitored by laser phase microscopy

    NASA Astrophysics Data System (ADS)

    Roelofs, Theo A.; Graschew, Georgi; Perevedentseva, Elena V.; Rakowsky, Stefan; Dressler, Cathrin; Beuthan, Juergen; Schlag, Peter M.

    2001-04-01

    Photodynamic treatment of cancer cells is known to eventually cause cell death in most cases. The precise pathways and the time course seem to vary among different cell types and modes of photodynamic treatment. In this contribution, the focus was put on the responses of human colon carcinoma cells HCT-116 within the first 15 minutes after laser irradiation in the presence of Photofrin« II (PII). To monitor the cell response in this early time period laser phase microscopic imaging was used, a method sensitive to changes in overall cell shape and intracellular structures, mediated by changes in the local refractive index. Laser irradiation of cells loaded with PII induced a significant reduction of the phase shifts, which probably reflects the induced damage to the different cellular membrane structures. The data suggest that even within the first 30 s after the onset of laser illumination, a significant reduction of the phase shifts can be detected. These results underline that laser phase microscopy is a suitable diagnostic tool for cellular research, also in the early time domain.

  14. Mitochondrial respiratory control and early defects of oxidative phosphorylation in the failing human heart.

    PubMed

    Lemieux, Hélène; Semsroth, Severin; Antretter, Herwig; Höfer, Daniel; Gnaiger, Erich

    2011-12-01

    Heart failure is a consequence of progressive deterioration of cardiac performance. Little is known about the role of impaired oxidative phosphorylation in the progression of the disease, since previous studies of mitochondrial injuries are restricted to end-stage chronic heart failure. The present study aimed at evaluating the involvement of mitochondrial dysfunction in the development of human heart failure. We measured the control of oxidative phosphorylation with high-resolution respirometry in permeabilized myocardial fibres from donor hearts (controls), and patients with no or mild heart failure but presenting with heart disease, or chronic heart failure due to dilated or ischemic cardiomyopathy. The capacity of the phosphorylation system exerted a strong limitation on oxidative phosphorylation in the human heart, estimated at 121 pmol O(2)s(-1)mg(-1) in the healthy left ventricle. In heart disease, a specific defect of the phosphorylation system, Complex I-linked respiration, and mass-specific fatty acid oxidation were identified. These early defects were also significant in chronic heart failure, where the capacities of the oxidative phosphorylation and electron transfer systems per cardiac tissue mass were decreased with all tested substrate combinations, suggesting a decline of mitochondrial density. Oxidative phosphorylation and electron transfer system capacities were higher in ventricles compared to atria, but the impaired mitochondrial quality was identical in the four cardiac chambers of chronic heart failure patients. Coupling was preserved in heart disease and chronic heart failure, in contrast to the mitochondrial dysfunction observed after prolonged cold storage of cardiac tissue. Mitochondrial defects in the phosphorylation system, Complex I respiration and mass-specific fatty acid oxidation occurred early in the development of heart failure. Targeting these mitochondrial injuries with metabolic therapy may offer a promising approach to delay

  15. The spatiotemporal hormonal orchestration of human folliculogenesis, early embryogenesis and blastocyst implantation.

    PubMed

    Atwood, Craig S; Vadakkadath Meethal, Sivan

    2016-07-15

    The early reproductive events starting with folliculogenesis and ending with blastocyst implantation into the uterine endometrium are regulated by a complex interplay among endocrine, paracrine and autocrine factors. This review examines the spatiotemporal integration of these maternal and embryonic signals that are required for successful reproduction. In coordination with hypothalamic-pituitary-gonadal (HPG) hormones, an intraovarian HPG-like axis regulates folliculogenesis, follicular quiescence, ovulation, follicular atresia, and corpus luteal functions. Upon conception and passage of the zygote through the fallopian tube, the contribution of maternal hormones in the form of paracrine secretions from the endosalpinx to embryonic development declines, with autocrine and paracrine signaling becoming increasingly important as instructional signals for the differentiation of the early zygote/morula into a blastocyst. These maternal and embryonic signals include activin and gonadotropin-releasing hormone 1 (GnRH1) that are crucial for the synthesis and secretion of the 'pregnancy' hormone human chorionic gonadotropin (hCG). hCG in turn signals pre-implantation embryonic cell division and sex steroid production required for stem cell differentiation, and subsequent blastulation, gastrulation, cavitation and blastocyst formation. Upon reaching the uterus, blastocyst hatching occurs under the influence of decreased activin signaling, while the attachment and invasion of the trophoblast into the endometrium appears to be driven by a decrease in activin signaling, and by increased GnRH1 and hCG signaling that allows for tissue remodeling and the controlled invasion of the blastocyst into the uterine endometrium. This review demonstrates the importance of integrative endocrine, paracrine, and autocrine signaling for successful human reproduction. PMID:27045358

  16. Ranging in Human Sonar: Effects of Additional Early Reflections and Exploratory Head Movements

    PubMed Central

    Wallmeier, Ludwig; Wiegrebe, Lutz

    2014-01-01

    Many blind people rely on echoes from self-produced sounds to assess their environment. It has been shown that human subjects can use echolocation for directional localization and orientation in a room, but echo-acoustic distance perception - e.g. to determine one's position in a room - has received little scientific attention, and systematic studies on the influence of additional early reflections and exploratory head movements are lacking. This study investigates echo-acoustic distance discrimination in virtual echo-acoustic space, using the impulse responses of a real corridor. Six blindfolded sighted subjects and a blind echolocation expert had to discriminate between two positions in the virtual corridor, which differed by their distance to the front wall, but not to the lateral walls. To solve this task, participants evaluated echoes that were generated in real time from self-produced vocalizations. Across experimental conditions, we systematically varied the restrictions for head rotations, the subjects' orientation in virtual space and the reference position. Three key results were observed. First, all participants successfully solved the task with discrimination thresholds below 1 m for all reference distances (0.75–4 m). Performance was best for the smallest reference distance of 0.75 m, with thresholds around 20 cm. Second, distance discrimination performance was relatively robust against additional early reflections, compared to other echolocation tasks like directional localization. Third, free head rotations during echolocation can improve distance discrimination performance in complex environmental settings. However, head movements do not necessarily provide a benefit over static echolocation from an optimal single orientation. These results show that accurate distance discrimination through echolocation is possible over a wide range of reference distances and environmental conditions. This is an important functional benefit of human echolocation

  17. Ranging in human sonar: effects of additional early reflections and exploratory head movements.

    PubMed

    Wallmeier, Ludwig; Wiegrebe, Lutz

    2014-01-01

    Many blind people rely on echoes from self-produced sounds to assess their environment. It has been shown that human subjects can use echolocation for directional localization and orientation in a room, but echo-acoustic distance perception--e.g. to determine one's position in a room--has received little scientific attention, and systematic studies on the influence of additional early reflections and exploratory head movements are lacking. This study investigates echo-acoustic distance discrimination in virtual echo-acoustic space, using the impulse responses of a real corridor. Six blindfolded sighted subjects and a blind echolocation expert had to discriminate between two positions in the virtual corridor, which differed by their distance to the front wall, but not to the lateral walls. To solve this task, participants evaluated echoes that were generated in real time from self-produced vocalizations. Across experimental conditions, we systematically varied the restrictions for head rotations, the subjects' orientation in virtual space and the reference position. Three key results were observed. First, all participants successfully solved the task with discrimination thresholds below 1 m for all reference distances (0.75-4 m). Performance was best for the smallest reference distance of 0.75 m, with thresholds around 20 cm. Second, distance discrimination performance was relatively robust against additional early reflections, compared to other echolocation tasks like directional localization. Third, free head rotations during echolocation can improve distance discrimination performance in complex environmental settings. However, head movements do not necessarily provide a benefit over static echolocation from an optimal single orientation. These results show that accurate distance discrimination through echolocation is possible over a wide range of reference distances and environmental conditions. This is an important functional benefit of human echolocation

  18. Motor stereotypies and cognitive perseveration in non-human primates exposed to early gestational irradiation.

    PubMed

    Selemon, L D; Friedman, H R

    2013-09-17

    A number of psychiatric illnesses have been associated with prenatal disturbance of brain development, including autism, attention deficit hyperactivity disorder, and schizophrenia. Individuals afflicted with these disorders exhibit both repetitive motor and cognitive behavior. The potential role that environmental insult to the developing brain may play in generating these aberrant behaviors is unclear. Here we examine the behavioral consequences of an early gestational insult in the non-human primate. Rhesus macaques were exposed to x-irradiation during the first trimester of development to disrupt neurogenesis. The behavior of five fetally irradiated monkeys (FIMs) and five control monkeys (CONs) was observed as they matured from juvenile (1.5 years) to adult ages (4-5 years). Home-cage behavior was indistinguishable in the two groups. In the testing cage, circling was prevalent in both groups at juvenile ages, persisting to adulthood in three of the five FIMs. One FIM executed a ritualized motor sequence marked by semi-circling and undulating head movements. Seven macaques (4 FIMs, 3 CONs) were tested on a spatial Delayed Alternation (DA) task as adults. Perseverative errors and non-perseverative errors were recorded in early stages of the testing, at the 0 delay interval. While performing DA, FIMs made more errors of perseveration than CONs yet the number of total errors committed did not differ between groups. The presence of motor stereotypies and cognitive perseveration in fetally irradiated non-human primates suggests that environmental insult to the embryonic brain may contribute to repetitive motor and cognitive behaviors in neuropsychiatric diseases. PMID:23769911

  19. Early Components of the Complement Classical Activation Pathway in Human Systemic Autoimmune Diseases

    PubMed Central

    Lintner, Katherine E.; Wu, Yee Ling; Yang, Yan; Spencer, Charles H.; Hauptmann, Georges; Hebert, Lee A.; Atkinson, John P.; Yu, C. Yung

    2016-01-01

    The complement system consists of effector proteins, regulators, and receptors that participate in host defense against pathogens. Activation of the complement system, via the classical pathway (CP), has long been recognized in immune complex-mediated tissue injury, most notably systemic lupus erythematosus (SLE). Paradoxically, a complete deficiency of an early component of the CP, as evidenced by homozygous genetic deficiencies reported in human, are strongly associated with the risk of developing SLE or a lupus-like disease. Similarly, isotype deficiency attributable to a gene copy-number (GCN) variation and/or the presence of autoantibodies directed against a CP component or a regulatory protein that result in an acquired deficiency are relatively common in SLE patients. Applying accurate assay methodologies with rigorous data validations, low GCNs of total C4, and heterozygous and homozygous deficiencies of C4A have been shown as medium to large effect size risk factors, while high copy numbers of total C4 or C4A as prevalent protective factors, of European and East-Asian SLE. Here, we summarize the current knowledge related to genetic deficiency and insufficiency, and acquired protein deficiencies for C1q, C1r, C1s, C4A/C4B, and C2 in disease pathogenesis and prognosis of SLE, and, briefly, for other systemic autoimmune diseases. As the complement system is increasingly found to be associated with autoimmune diseases and immune-mediated diseases, it has become an attractive therapeutic target. We highlight the recent developments and offer a balanced perspective concerning future investigations and therapeutic applications with a focus on early components of the CP in human systemic autoimmune diseases. PMID:26913032

  20. Lead Exposure during Early Human Development and DNA Methylation of Imprinted Gene Regulatory Elements in Adulthood

    PubMed Central

    Li, Yue; Xie, Changchun; Murphy, Susan K.; Skaar, David; Nye, Monica; Vidal, Adriana C.; Cecil, Kim M.; Dietrich, Kim N.; Puga, Alvaro; Jirtle, Randy L.; Hoyo, Cathrine

    2015-01-01

    Background: Lead exposure during early development causes neurodevelopmental disorders by unknown mechanisms. Epidemiologic studies have focused recently on determining associations between lead exposure and global DNA methylation; however, such approaches preclude the identification of loci that may alter human disease risk. Objectives: The objective of this study was to determine whether maternal, postnatal, and early childhood lead exposure can alter the differentially methylated regions (DMRs) that control the monoallelic expression of imprinted genes involved in metabolism, growth, and development. Methods: Questionnaire data and serial blood lead levels were obtained from 105 participants (64 females, 41 males) of the Cincinnati Lead Study from birth to 78 months. When participants were adults, we used Sequenom EpiTYPER assays to test peripheral blood DNA to quantify CpG methylation in peripheral blood leukocytes at DMRs of 22 human imprinted genes. Statistical analyses were conducted using linear regression. Results: Mean blood lead concentration from birth to 78 months was associated with a significant decrease in PEG3 DMR methylation (β = –0.0014; 95% CI: –0.0023, –0.0005, p = 0.002), stronger in males (β = –0.0024; 95% CI: –0.0038, –0.0009, p = 0.003) than in females (β = –0.0009; 95% CI: –0.0020, 0.0003, p = 0.1). Elevated mean childhood blood lead concentration was also associated with a significant decrease in IGF2/H19 (β = –0.0013; 95% CI: –0.0023, –0.0003, p = 0.01) DMR methylation, but primarily in females, (β = –0.0017; 95% CI: –0.0029, –0.0006, p = 0.005) rather than in males, (β = –0.0004; 95% CI: –0.0023, 0.0015, p = 0.7). Elevated blood lead concentration during the neonatal period was associated with higher PLAGL1/HYMAI DMR methylation regardless of sex (β = 0.0075; 95% CI: 0.0018, 0.0132, p = 0.01). The magnitude of associations between cumulative lead exposure and CpG methylation remained unaltered from

  1. Structural basis for early-onset neurological disorders caused by mutations in human selenocysteine synthase

    PubMed Central

    Puppala, Anupama K.; French, Rachel L.; Matthies, Doreen; Baxa, Ulrich; Subramaniam, Sriram; Simonović, Miljan

    2016-01-01

    Selenocysteine synthase (SepSecS) catalyzes the terminal reaction of selenocysteine, and is vital for human selenoproteome integrity. Autosomal recessive inheritance of mutations in SepSecS–Ala239Thr, Thr325Ser, Tyr334Cys and Tyr429*–induced severe, early-onset, neurological disorders in distinct human populations. Although harboring different mutant alleles, patients presented remarkably similar phenotypes typified by cerebellar and cerebral atrophy, seizures, irritability, ataxia, and extreme spasticity. However, it has remained unclear how these genetic alterations affected the structure of SepSecS and subsequently elicited the development of a neurological pathology. Herein, our biophysical and structural characterization demonstrates that, with the exception of Tyr429*, pathogenic mutations decrease protein stability and trigger protein misfolding. We propose that the reduced stability and increased propensity towards misfolding are the main causes for the loss of SepSecS activity in afflicted patients, and that these factors contribute to disease progression. We also suggest that misfolding of enzymes regulating protein synthesis should be considered in the diagnosis and study of childhood neurological disorders. PMID:27576344

  2. Vestibular Activation Differentially Modulates Human Early Visual Cortex and V5/MT Excitability and Response Entropy

    PubMed Central

    Guzman-Lopez, Jessica; Arshad, Qadeer; Schultz, Simon R; Walsh, Vincent; Yousif, Nada

    2013-01-01

    Head movement imposes the additional burdens on the visual system of maintaining visual acuity and determining the origin of retinal image motion (i.e., self-motion vs. object-motion). Although maintaining visual acuity during self-motion is effected by minimizing retinal slip via the brainstem vestibular-ocular reflex, higher order visuovestibular mechanisms also contribute. Disambiguating self-motion versus object-motion also invokes higher order mechanisms, and a cortical visuovestibular reciprocal antagonism is propounded. Hence, one prediction is of a vestibular modulation of visual cortical excitability and indirect measures have variously suggested none, focal or global effects of activation or suppression in human visual cortex. Using transcranial magnetic stimulation-induced phosphenes to probe cortical excitability, we observed decreased V5/MT excitability versus increased early visual cortex (EVC) excitability, during vestibular activation. In order to exclude nonspecific effects (e.g., arousal) on cortical excitability, response specificity was assessed using information theory, specifically response entropy. Vestibular activation significantly modulated phosphene response entropy for V5/MT but not EVC, implying a specific vestibular effect on V5/MT responses. This is the first demonstration that vestibular activation modulates human visual cortex excitability. Furthermore, using information theory, not previously used in phosphene response analysis, we could distinguish between a specific vestibular modulation of V5/MT excitability from a nonspecific effect at EVC. PMID:22291031

  3. Last glacial megafaunal death assemblage and early human occupation at Lake Menindee, southeastern Australia

    NASA Astrophysics Data System (ADS)

    Cupper, Matthew L.; Duncan, Jacqui

    2006-09-01

    The Tedford subfossil locality at Lake Menindee preserves a diverse assemblage of marsupials, monotremes and placental rodents. Of the 38 mammal taxa recorded at the site, almost a third are of extinct megafauna. Some of the bones are articulated or semi-articulated and include almost complete skeletons, indicating that aeolian sediments rapidly buried the animals following death. New optical ages show the site dates to the early part of the last glacial (55,700 ± 1300 yr weighted mean age). This is close to the 51,200-39,800 yr Australia-wide extinction age for megafauna suggested by Roberts et al. [2001, Science 292:1888-1892], but like all previous researchers, we cannot conclusively determine whether humans were implicated in the deaths of the animals. Although an intrusive hearth at the site dating to 45,100 ± 1400 yr ago is the oldest evidence of human occupation of the Darling River, no artifacts were identified in situ within the sub-fossil-bearing unit. Non-anthropogenic causes, such as natural senescence or ecosystem stress due to climatic aridity, probably explain the mortality of the faunal assemblage at Lake Menindee.

  4. Structural basis for early-onset neurological disorders caused by mutations in human selenocysteine synthase.

    PubMed

    Puppala, Anupama K; French, Rachel L; Matthies, Doreen; Baxa, Ulrich; Subramaniam, Sriram; Simonović, Miljan

    2016-01-01

    Selenocysteine synthase (SepSecS) catalyzes the terminal reaction of selenocysteine, and is vital for human selenoproteome integrity. Autosomal recessive inheritance of mutations in SepSecS-Ala239Thr, Thr325Ser, Tyr334Cys and Tyr429*-induced severe, early-onset, neurological disorders in distinct human populations. Although harboring different mutant alleles, patients presented remarkably similar phenotypes typified by cerebellar and cerebral atrophy, seizures, irritability, ataxia, and extreme spasticity. However, it has remained unclear how these genetic alterations affected the structure of SepSecS and subsequently elicited the development of a neurological pathology. Herein, our biophysical and structural characterization demonstrates that, with the exception of Tyr429*, pathogenic mutations decrease protein stability and trigger protein misfolding. We propose that the reduced stability and increased propensity towards misfolding are the main causes for the loss of SepSecS activity in afflicted patients, and that these factors contribute to disease progression. We also suggest that misfolding of enzymes regulating protein synthesis should be considered in the diagnosis and study of childhood neurological disorders. PMID:27576344

  5. Occurring of In Vitro Functional Vasculogenic Pericytes from Human Circulating Early Endothelial Precursor Cell Culture

    PubMed Central

    Bianchi, Francesca; Galletti, Margherita; Galiè, Nazzareno; Ventura, Carlo

    2015-01-01

    Pericytes are periendothelial cells of the microcirculation which contribute to tissue homeostasis and hemostasis by regulating microvascular morphogenesis and stability. Because of their multipotential ex vivo differentiation capabilities, pericytes are becoming very interesting in regenerative medicine field. Several studies address this issue by attempting to isolate pericyte/mesenchymal-like cells from peripheral blood; however the origin of these cells and their culture conditions are still debated. Here we showed that early Endothelial Progenitor Cells (EPCs) expressing CD45+/CD146+/CD31+ can be a source of cells with pericyte/mesenchymal phenotype and function, identified as human Progenitor Perivascular Cells (hPPCs). We provided evidence that hPPCs have an immunophenotype consistent with Mesenchymal Stem Cells (MSCs) from human adipose tissue (hASCs) and fetal membranes of term placenta (FM-hMSCs). In addition, hPPCs can be subcultured and exhibit expression of pluripotent genes (OCT-4, KLF-4, and NANOG) as well as a remarkable vasculogenic potential. Our findings could be helpful to develop innovative cell-based therapies for future clinical applications with distinct therapeutic purposes. PMID:26064139

  6. Epigenetic modulations in early endothelial cells and DNA hypermethylation in human skin after sulfur mustard exposure.

    PubMed

    Steinritz, Dirk; Schmidt, Annette; Balszuweit, Frank; Thiermann, Horst; Simons, Thilo; Striepling, Enno; Bölck, Birgit; Bloch, Wilhelm

    2016-02-26

    Victims that were exposed to the chemical warfare agent sulfur mustard (SM) suffer from chronic dermal and ocular lesions, severe pulmonary problems and cancer development. It has been proposed that epigenetic perturbations might be involved in that process but this has not been investigated so far. In this study, we investigated epigenetic modulations in vitro using early endothelial cells (EEC) that were exposed to different SM concentrations (0.5, 1.0, 23.5 and 50μM). A comprehensive analysis of 78 genes related to epigenetic pathways (i.e., DNA-methylation and post-translational histone modifications) was performed. Moreover, we analyzed global DNA methylation in vitro in EEC after SM exposure as a maker for epigenetic modulations and in vivo using human skin samples that were obtained from a patient 1 year after an accidently exposure to pure SM. SM exposure resulted in a complex regulation pattern of epigenetic modulators which was accompanied by a global increase of DNA methylation in vitro. Examination of the SM exposed human skin samples also revealed a significant increase of global DNA methylation in vivo, underlining the biological relevance of our findings. Thus, we demonstrated for the first time that SM affects epigenetic pathways and causes epigenetic modulations both in vivo and in vitro. PMID:26392148

  7. Prediction model for aneuploidy in early human embryo development revealed by single-cell analysis

    PubMed Central

    Vera-Rodriguez, Maria; Chavez, Shawn L.; Rubio, Carmen; Pera, Renee A. Reijo; Simon, Carlos

    2015-01-01

    Aneuploidies are prevalent in the human embryo and impair proper development, leading to cell cycle arrest. Recent advances in imaging and molecular and genetic analyses are postulated as promising strategies to unveil the mechanisms involved in aneuploidy generation. Here we combine time-lapse, complete chromosomal assessment and single-cell RT–qPCR to simultaneously obtain information from all cells that compose a human embryo until the approximately eight-cell stage (n=85). Our data indicate that the chromosomal status of aneuploid embryos (n=26), including those that are mosaic (n=3), correlates with significant differences in the duration of the first mitotic phase when compared with euploid embryos (n=28). Moreover, gene expression profiling suggests that a subset of genes is differentially expressed in aneuploid embryos during the first 30 h of development. Thus, we propose that the chromosomal fate of an embryo is likely determined as early as the pronuclear stage and may be predicted by a 12-gene transcriptomic signature. PMID:26151134

  8. Increases in Human Papillomavirus Detection During Early HIV Infection Among Women in Zimbabwe

    PubMed Central

    Nowak, Rebecca G.; Morrison, Charles S.; Gange, Stephen J.; Kwok, Cynthia; Oliver, Amy E.; Howard, Roslyn; Van Der Pol, Barbara; Salata, Robert A.; Padian, Nancy S.; Chipato, Tsungai; Munjoma, Marshall; Celentano, David D.

    2011-01-01

    Background. Individuals who acquire human immunodeficiency virus (HIV) may experience an immediate disruption of genital tract immunity, altering the ability to mount a local and effective immune response. This study examined the impact of early HIV infection on new detection of human papillomavirus (HPV). Methods. One hundred fifty-five Zimbabwean women with observation periods before and after HIV acquisition and 486 HIV-uninfected women were selected from a cohort study evaluating hormonal contraceptive use and risk of HIV acquisition. Study visits occurred at 3-month intervals. Cervical swab samples available from up to 6 months before, at, and up to 6 months after the visit when HIV was first detected were typed for 37 HPV genotypes or subtypes. Results. We observed ∼5-fold higher odds of multiple (≥2) new HPV detections only after HIV acquisition, relative to HIV-negative women after adjusting for sexual behavior and concurrent genital tract infections. We also observed ∼2.5-fold higher odds of single new HPV detections at visits before and after HIV acquisition, relative to HIV-uninfected women in multivariable models. Conclusions. These findings suggest that HIV infection has an immediate impact on genital tract immunity, as evidenced by the high risk of multiple new HPV detections immediately after HIV acquisition. PMID:21451006

  9. Magnetostratigraphic age of the Xiantai Paleolithic site in the Nihewan Basin and implications for early human colonization of Northeast Asia

    NASA Astrophysics Data System (ADS)

    Deng, Chenglong; Wei, Qi; Zhu, Rixiang; Wang, Hongqiang; Zhang, Rui; Ao, Hong; Chang, Liao; Pan, Yongxin

    2006-04-01

    Timing of the early habitation and stone technologies in the Nihewan Basin, North China has provided insights into our understanding of early human adaptability to high northern latitudes in East Asia. Here we contribute to this topic with detailed magnetostratigraphic investigation, coupled with mineral magnetic measurements and palynological analyses on a lacustrine sequence in this basin, which contains the Xiantai Paleolithic site. Magnetite and hematite were identified as the main carriers for the characteristic remanent magnetizations. Magnetostratigraphic results show that the Xiantai lacustrine sequence recorded the Brunhes chron, the Jaramillo and the Olduvai subchrons, and successive reverse polarity portions of the intervening Matuyama chron. Stratigraphic correlation in terms of lithology, magnetic susceptibility and magnetic polarity sequences between the Xiantai and Xiaochangliang sections indicates that the Xiantai artefact layer is readily contemporary with the Xiaochangliang artefact layer, which has been previously estimated to be about 1.36 Ma [R.X. Zhu, K.A. Hoffman, R. Potts, C.L. Deng, Y.X. Pan, B. Guo, C.D. Shi, Z.T. Guo, B.Y. Yuan, Y.M. Hou, W.W. Huang, Earliest presence of humans in northeast Asia, Nature 413 (2001) 413-417.]. Early humans of the Xiantai Paleolithic site lived in a steppe paleoenvironment indicated from fossil pollens. Furthermore, the combined evidence of our magnetostratigraphy and previously published magnetochronology and paleoclimate data documents that early humans of North China were able to adjust to an increasing variability of paleoclimates and paleoenvironments over the Early Pleistocene.

  10. Did Viruses Evolve As a Distinct Supergroup from Common Ancestors of Cells?

    PubMed Central

    Harish, Ajith; Abroi, Aare; Gough, Julian; Kurland, Charles

    2016-01-01

    The evolutionary origins of viruses according to marker gene phylogenies, as well as their relationships to the ancestors of host cells remains unclear. In a recent article Nasir and Caetano-Anollés reported that their genome-scale phylogenetic analyses based on genomic composition of protein structural-domains identify an ancient origin of the “viral supergroup” (Nasir et al. 2015. A phylogenomic data-driven exploration of viral origins and evolution. Sci Adv. 1(8):e1500527.). It suggests that viruses and host cells evolved independently from a universal common ancestor. Examination of their data and phylogenetic methods indicates that systematic errors likely affected the results. Reanalysis of the data with additional tests shows that small-genome attraction artifacts distort their phylogenomic analyses, particularly the location of the root of the phylogenetic tree of life that is central to their conclusions. These new results indicate that their suggestion of a distinct ancestry of the viral supergroup is not well supported by the evidence. PMID:27497315

  11. Did Viruses Evolve As a Distinct Supergroup from Common Ancestors of Cells?

    PubMed

    Harish, Ajith; Abroi, Aare; Gough, Julian; Kurland, Charles

    2016-01-01

    The evolutionary origins of viruses according to marker gene phylogenies, as well as their relationships to the ancestors of host cells remains unclear. In a recent article Nasir and Caetano-Anollés reported that their genome-scale phylogenetic analyses based on genomic composition of protein structural-domains identify an ancient origin of the "viral supergroup" (Nasir et al. 2015. A phylogenomic data-driven exploration of viral origins and evolution. Sci Adv. 1(8):e1500527.). It suggests that viruses and host cells evolved independently from a universal common ancestor. Examination of their data and phylogenetic methods indicates that systematic errors likely affected the results. Reanalysis of the data with additional tests shows that small-genome attraction artifacts distort their phylogenomic analyses, particularly the location of the root of the phylogenetic tree of life that is central to their conclusions. These new results indicate that their suggestion of a distinct ancestry of the viral supergroup is not well supported by the evidence. PMID:27497315

  12. Testing modern human out-of-Africa dispersal models and implications for modern human origins.

    PubMed

    Reyes-Centeno, Hugo; Hubbe, Mark; Hanihara, Tsunehiko; Stringer, Chris; Harvati, Katerina

    2015-10-01

    The modern human expansion process out of Africa has important implications for understanding the genetic and phenotypic structure of extant populations. While intensely debated, the primary hypotheses focus on either a single dispersal or multiple dispersals out of the continent. Here, we use the human fossil record from Africa and the Levant, as well as an exceptionally large dataset of Holocene human crania sampled from Asia, to model ancestor-descendant relationships along hypothetical dispersal routes. We test the spatial and temporal predictions of competing out-of-Africa models by assessing the correlation of geographical distances between populations and measures of population differentiation derived from quantitative cranial phenotype data. Our results support a model in which extant Australo-Melanesians are descendants of an initial dispersal out of Africa by early anatomically modern humans, while all other populations are descendants of a later migration wave. Our results have implications for understanding the complexity of modern human origins and diversity. PMID:26164107

  13. Early reversal cells in adult human bone remodeling: osteoblastic nature, catabolic functions and interactions with osteoclasts.

    PubMed

    Abdelgawad, Mohamed Essameldin; Delaisse, Jean-Marie; Hinge, Maja; Jensen, Pia Rosgaard; Alnaimi, Ragad Walid; Rolighed, Lars; Engelholm, Lars H; Marcussen, Niels; Andersen, Thomas Levin

    2016-06-01

    The mechanism coupling bone resorption and formation is a burning question that remains incompletely answered through the current investigations on osteoclasts and osteoblasts. An attractive hypothesis is that the reversal cells are likely mediators of this coupling. Their nature is a big matter of debate. The present study performed on human cancellous bone is the first one combining in situ hybridization and immunohistochemistry to demonstrate their osteoblastic nature. It shows that the Runx2 and CD56 immunoreactive reversal cells appear to take up TRAcP released by neighboring osteoclasts. Earlier preclinical studies indicate that reversal cells degrade the organic matrix left behind by the osteoclasts and that this degradation is crucial for the initiation of the subsequent bone formation. To our knowledge, this study is the first addressing these catabolic activities in adult human bone through electron microscopy and analysis of molecular markers. Periosteoclastic reversal cells show direct contacts with the osteoclasts and with the demineralized resorption debris. These early reversal cells show (1) ¾-collagen fragments typically generated by extracellular collagenases of the MMP family, (2) MMP-13 (collagenase-3) and (3) the endocytic collagen receptor uPARAP/Endo180. The prevalence of these markers was lower in the later reversal cells, which are located near the osteoid surfaces and morphologically resemble mature bone-forming osteoblasts. In conclusion, this study demonstrates that reversal cells colonizing bone surfaces right after resorption are osteoblast-lineage cells, and extends to adult human bone remodeling their role in rendering eroded surfaces osteogenic. PMID:26860863

  14. Tracking the fate of iron in early development of human blood flukes.

    PubMed

    Jones, Malcolm K; McManus, Donald P; Sivadorai, Padma; Glanfield, Amber; Moertel, Luke; Belli, Sabina I; Gobert, Geoffrey N

    2007-01-01

    Iron (Fe) is an important trace element found in nearly all organisms, and is used as a cofactor in many biological reactions. One role for Fe in some invertebrates is in stabilization of extracellular matrices. The human blood fluke, Schistosoma japonicum, is responsible for significant human disease in developing and tropical nations. Disease in humans arises from host immunological reaction to parasite eggs that lodge in tissues. Schistosomes require Fe for development in their hosts, and store abundant Fe in vitelline (eggshell-forming) cells of the female system. The understanding of Fe metabolism and functionality are aspects of its biology that may be exploited in future therapeutics. The biology of Fe stores in vitelline cells of S. japonicum was investigated to illuminate possible functions of this element in early development of these parasites. Vitelline Fe is stored in yolk ferritin that is upregulated in females and is also expressed at low levels in egg-stages and adult males. Laser microdissection microscopy, coupled with reverse transcriptase- and real time-PCR amplification of schistosome ferritin sequences, confirmed that the vitelline cells are the likely progenitor cells of yolk ferritin. Assessment of Fe concentrations in whole male and whole female adult worms, eggs and purified eggshells by colorimetric assays and mass spectroscopy demonstrated higher levels of Fe in the female parasite, but also high levels of the element in whole parasite eggs and purified eggshell. Qualitative energy dispersive spectroscopy of purified eggshells, revealed that Fe is abundant in the eggshell, the matrix of which is composed of heavily cross-linked eggshell precursor proteins. Thus, vitelline stores of Fe are implicated in eggshell cross-linking in platyhelminths. These observations emphasise the importance of Fe in schistosome metabolism and egg formation and suggest new avenues for disruption of egg formation in these pathogenic parasites. PMID:17556009

  15. Cell Cycle Arrest in G2/M Promotes Early Steps of Infection by Human Immunodeficiency Virus

    PubMed Central

    Groschel, Bettina; Bushman, Frederic

    2005-01-01

    We have identified four small molecules that boost transduction of cells by human immunodeficiency virus (HIV) and investigated their mechanism of action. These molecules include etoposide and camptothecin, which induce DNA damage by inhibiting religation of cleaved topoisomerase-DNA complexes, taxol, which interferes with the function of microtubules, and aphidicolin, which inhibits DNA polymerases. All four compounds arrest the cell cycle at G2/M, though in addition high concentrations of aphidicolin arrest in G1. We find that early events of HIV replication, including synthesis of late reverse transcription products, two-long terminal repeat circles, and integrated proviruses, were increased after treatment of cells with concentrations of each compound that arrested in G2/M. Stimulation was seen for both transformed cell lines (293T and HeLa cells) and primary cells (IMR90 lung fibroblasts). Arrest in G1 with high concentrations of aphidicolin boosted transduction, though not much as with lower concentrations that arrested in G2/M. Arrest of IMR90 cells in G1 by serum starvation and contact inhibition reduced transduction. Previously, the proteasome inhibitor MG132 was reported to increase HIV infection—here we investigated the effects of combinations of the cell cycle inhibitors with MG132 and obtained data suggesting that MG132 may also boost transduction by causing G2/M cell cycle arrest. These data document that cell cycle arrest in G2/M boosts the early steps of HIV infection and suggests methods for increasing transduction with HIV-based vectors. PMID:15827184

  16. Characterization of human mesenchymal stem cell secretome at early steps of adipocyte and osteoblast differentiation

    PubMed Central

    Chiellini, Chiara; Cochet, Olivia; Negroni, Luc; Samson, Michel; Poggi, Marjorie; Ailhaud, Gérard; Alessi, Marie-Christine; Dani, Christian; Amri, Ez-Zoubir

    2008-01-01

    Background It is well established that adipose tissue plays a key role in energy storage and release but is also a secretory organ and a source of stem cells. Among different lineages, stem cells are able to differentiate into adipocytes and osteoblasts. As secreted proteins could regulate the balance between both lineages, we aimed at characterizing the secretome of human multipotent adipose-derived stem cell (hMADS) at an early step of commitment to adipocytes and osteoblasts. Results A proteomic approach, using mono-dimensional electrophoresis and tandem mass spectrometry, allowed us to identify a total of 73 proteins at day 0 and day 3 of adipocyte and osteoblast differentiation. Analysis of identified proteins showed that 52 % corresponded to classical secreted proteins characterized by a signal peptide, that 37 % previously described in the extracellular compartment were devoid of signal peptide and that 11 % neither exhibited a signal peptide nor had been previously described extracellularly. These proteins were classified into 8 clusters according to their function. Quantitative analysis has been performed for 8 candidates: PAI-1, PEDF, BIGH3, PTX3, SPARC, ENO1, GRP78 and MMP2. Among them, PAI-1 was detected at day 0 and day 3 of osteoblast differentiation but never in adipocyte secretome. Furthermore we showed that PAI-1 mRNA was down-regulated in the bone of ovariectomized mice. Conclusion Given its regulation during the early events of hMADS cell differentiation and its status in ovariectomized mice, PAI-1 could play a role in the adipocyte/osteoblast balance and thus in bone diseases such as osteoporosis. PMID:18302751

  17. Osteoarchaeological Studies of Human Systemic Stress of Early Urbanization in Late Shang at Anyang, China.

    PubMed

    Zhang, Hua; Merrett, Deborah C; Jing, Zhichun; Tang, Jigen; He, Yuling; Yue, Hongbin; Yue, Zhanwei; Yang, Dongya Y

    2016-01-01

    Through the analysis of human skeletal remains and mortuary practice in Yinxu, this study investigates the impact of early urbanization on the commoners during the Late Shang dynasty (ca. 1250-1046 B.C.). A total of 347 individuals examined in this study represent non-elites who were recovered from two different burial contexts (formally buried in lineage cemeteries and randomly scattered in refuse pits). Frequencies of enamel hypoplasia (childhood stress), cribra orbitalia (childhood stress and frailty) and osteoperiostitis (adult stress) were examined to assess systemic stress exposure. Our results reveal that there was no significant difference in the frequency of enamel hypoplasia between two burial groups and between sexes, suggesting these urban commoners experienced similar stresses during childhood, but significantly elevated levels of cribra orbitalia and osteoperiostitis were observed in the refuse pit female cohort. Theoretically, urbanization would have resulted in increased population density in the urban centre, declining sanitary conditions, and increased risk of resource shortage. Biologically, children would be more vulnerable to such physiological disturbance; as a result, high percentages of enamel hypoplasia (80.9% overall) and cribra orbitalia (30.3% overall) are observed in Yin commoners. Adults continued to suffer from stress, resulting in high frequencies of osteoperiostitis (40.0% total adults); in particular, in the refuse pit females who may also reflect a compound impact of gender inequality. Our data show that the non-elite urban population in the capital city of Late Shang Dynasty had experienced extensive stress exposure due to early urbanization with further social stratification only worsening the situation, and eventually contributing to collapse of the Shang Dynasty. PMID:27050400

  18. Osteoarchaeological Studies of Human Systemic Stress of Early Urbanization in Late Shang at Anyang, China

    PubMed Central

    Zhang, Hua; Merrett, Deborah C.; Jing, Zhichun; Tang, Jigen; He, Yuling; Yue, Hongbin; Yue, Zhanwei; Yang, Dongya Y.

    2016-01-01

    Through the analysis of human skeletal remains and mortuary practice in Yinxu, this study investigates the impact of early urbanization on the commoners during the Late Shang dynasty (ca. 1250–1046 B.C.). A total of 347 individuals examined in this study represent non-elites who were recovered from two different burial contexts (formally buried in lineage cemeteries and randomly scattered in refuse pits). Frequencies of enamel hypoplasia (childhood stress), cribra orbitalia (childhood stress and frailty) and osteoperiostitis (adult stress) were examined to assess systemic stress exposure. Our results reveal that there was no significant difference in the frequency of enamel hypoplasia between two burial groups and between sexes, suggesting these urban commoners experienced similar stresses during childhood, but significantly elevated levels of cribra orbitalia and osteoperiostitis were observed in the refuse pit female cohort. Theoretically, urbanization would have resulted in increased population density in the urban centre, declining sanitary conditions, and increased risk of resource shortage. Biologically, children would be more vulnerable to such physiological disturbance; as a result, high percentages of enamel hypoplasia (80.9% overall) and cribra orbitalia (30.3% overall) are observed in Yin commoners. Adults continued to suffer from stress, resulting in high frequencies of osteoperiostitis (40.0% total adults); in particular, in the refuse pit females who may also reflect a compound impact of gender inequality. Our data show that the non-elite urban population in the capital city of Late Shang Dynasty had experienced extensive stress exposure due to early urbanization with further social stratification only worsening the situation, and eventually contributing to collapse of the Shang Dynasty. PMID:27050400

  19. Early and delayed reproductive death in human cells exposed to high energy iron-ion beams

    NASA Astrophysics Data System (ADS)

    Bettega, D.; Calzolari, P.; Doneda, L.; Durante, M.; Tallone, L.

    For radiation protection of the astronauts it is important to know both the acute and the late effects of charged particles. Iron is the most abundant high charge and energy (HZE) specie in galactic cosmic radiation. (HZE) ions are considered to be the major contributors to equivalent dose in space, but the Relative Biological Effectiveness of HZE particles has large uncertainties, expecially for late effects. We have determined early and delayed reproductive death in human fibroblast cells (AG1522) exposed to iron ion beams of energies between 0.2 and 1 GeV/n. The cells were irradiated at the HIMAC accelerator in Chiba (0.2 and 0.5 GeV/n) and at the AGS accelerator at the NASA Space Radiation Laboratory in Brookhaven (1 GeV/n). For each beam the dose--effect curves were measured at least twice in the dose range between 0.5 and 2 Gy. 60 Co gamma rays were used as reference radiation. The following results were obtained: 1) the 1 GeV/n beam effectiveness for inactivation of the AG1522 cells is higher than that of any other beam. 2) the progeny of the irradiated cells show the presence of delayed damage in the form of reproductive death for all the beams with the 1 GeV/n being the most effective. 3) the relative biological effectiveness of the iron beams is higher for delayed compared to early reproductive death. A comparison with preliminary results obtained with 970 MeV/n Ti and 490 MeV/n Si ions will be also reported .

  20. Early suppression effect in human primary visual cortex during Kanizsa illusion processing: A magnetoencephalographic evidence.

    PubMed

    Chernyshev, Boris V; Pronko, Platon K; Stroganova, Tatiana A

    2016-01-01

    Detection of illusory contours (ICs) such as Kanizsa figures is known to depend primarily upon the lateral occipital complex. Yet there is no universal agreement on the role of the primary visual cortex in this process; some existing evidence hints that an early stage of the visual response in V1 may involve relative suppression to Kanizsa figures compared with controls. Iso-oriented luminance borders, which are responsible for Kanizsa illusion, may evoke surround suppression in V1 and adjacent areas leading to the reduction in the initial response to Kanizsa figures. We attempted to test the existence, as well as to find localization and timing of the early suppression effect produced by Kanizsa figures in adult nonclinical human participants. We used two sizes of visual stimuli (4.5 and 9.0°) in order to probe the effect at two different levels of eccentricity; the stimuli were presented centrally in passive viewing conditions. We recorded magnetoencephalogram, which is more sensitive than electroencephalogram to activity originating from V1 and V2 areas. We restricted our analysis to the medial occipital area and the occipital pole, and to a 40-120 ms time window after the stimulus onset. By applying threshold-free cluster enhancement technique in combination with permutation statistics, we were able to detect the inverted IC effect-a relative suppression of the response to the Kanizsa figures compared with the control stimuli. The current finding is highly compatible with the explanation involving surround suppression evoked by iso-oriented collinear borders. The effect may be related to the principle of sparse coding, according to which V1 suppresses representations of inner parts of collinear assemblies as being informationally redundant. Such a mechanism is likely to be an important preliminary step preceding object contour detection. PMID:27485162

  1. Expression of early activation antigen (CD69) during human thymic development.

    PubMed Central

    Jung, L K; Haynes, B F; Nakamura, S; Pahwa, S; Fu, S M

    1990-01-01

    The novel early activation antigen, EA1, has been shown to be induced by mitogens, antigens and the tumour promoter, phorbol myristate acetate (PMA), on human lymphocytes. This antigen has been designated to be CD69. EA1 has also been shown to be expressed on thymocytes without exogenous activation stimuli. In order to characterize further the expression of EA1 on thymocytes, the ontogeny of its expression was studied. EA1 appeared between 7 and 9.5 weeks of gestation, after colonization of the thymic rudiment with CD7+ T cell precursors, but before the onset of compartmentalization of the thymus into cortical and medullary zones. After cortico-medullary differentiation, the majority of medullary thymocytes expressed EA1 while only a fraction of the cortical thymocytes expressed this antigen. In the fetal and post-natal cortex, EA1 expression appeared to cluster in the subcapsular cortex. EA1+ cells were also scattered throughout the inner cortex. By two-colour fluorocytometric analysis of post-natal thymocytes, it was shown that EA1 was expressed on 30 to 65% of thymocytes. EA1 was expressed on CD4+ CD8+ as well as on the more immature CD4- CD8- thymocytes. In contrast to circulating T cells, thymocytes were much less responsive to PMA stimulation for the expression of EA1. Molecular characterization showed that EA1 on thymocytes had the same structure as that of activated peripheral T cells. In addition, thymic EA1 was constitutively phosphorylated. Thus, EA1 expression is acquired early during thymic development after colonization of the thymic rudiment by CD7+ T cell precursors. However, the specific role that EA1 may play in the activation and function of developing thymocytes remains to be determined. Images Fig. 7 Fig. 8 PMID:2204504

  2. Metabolomic markers reveal novel pathways of ageing and early development in human populations

    PubMed Central

    Menni, Cristina; Kastenmüller, Gabriella; Petersen, Ann Kristin; Bell, Jordana T; Psatha, Maria; Tsai, Pei-Chien; Gieger, Christian; Schulz, Holger; Erte, Idil; John, Sally; Brosnan, M Julia; Wilson, Scott G; Tsaprouni, Loukia; Lim, Ee Mun; Stuckey, Bronwyn; Deloukas, Panos; Mohney, Robert; Suhre, Karsten; Spector, Tim D; Valdes, Ana M

    2013-01-01

    Background Human ageing is a complex, multifactorial process and early developmental factors affect health outcomes in old age. Methods Metabolomic profiling on fasting blood was carried out in 6055 individuals from the UK. Stepwise regression was performed to identify a panel of independent metabolites which could be used as a surrogate for age. We also investigated the association with birthweight overall and within identical discordant twins and with genome-wide methylation levels. Results We identified a panel of 22 metabolites which combined are strongly correlated with age (R2 = 59%) and with age-related clinical traits independently of age. One particular metabolite, C-glycosyl tryptophan (C-glyTrp), correlated strongly with age (beta = 0.03, SE = 0.001, P = 7.0 × 10−157) and lung function (FEV1 beta = −0.04, SE = 0.008, P = 1.8 × 10−8 adjusted for age and confounders) and was replicated in an independent population (n = 887). C-glyTrp was also associated with bone mineral density (beta = −0.01, SE = 0.002, P = 1.9 × 10−6) and birthweight (beta = −0.06, SE = 0.01, P = 2.5 × 10−9). The difference in C-glyTrp levels explained 9.4% of the variance in the difference in birthweight between monozygotic twins. An epigenome-wide association study in 172 individuals identified three CpG-sites, associated with levels of C-glyTrp (P < 2 × 10−6). We replicated one CpG site in the promoter of the WDR85 gene in an independent sample of 350 individuals (beta = −0.20, SE = 0.04, P = 2.9 × 10−8). WDR85 is a regulator of translation elongation factor 2, essential for protein synthesis in eukaryotes. Conclusions Our data illustrate how metabolomic profiling linked with epigenetic studies can identify some key molecular mechanisms potentially determined in early development that produce long-term physiological changes influencing human health and ageing. PMID:23838602

  3. Implications of Nubian-Like Core Reduction Systems in Southern Africa for the Identification of Early Modern Human Dispersals

    PubMed Central

    Phillips, Natasha

    2015-01-01

    Lithic technologies have been used to trace dispersals of early human populations within and beyond Africa. Convergence in lithic systems has the potential to confound such interpretations, implying connections between unrelated groups. Due to their reductive nature, stone artefacts are unusually prone to this chance appearance of similar forms in unrelated populations. Here we present data from the South African Middle Stone Age sites Uitpanskraal 7 and Mertenhof suggesting that Nubian core reduction systems associated with Late Pleistocene populations in North Africa and potentially with early human migrations out of Africa in MIS 5 also occur in southern Africa during early MIS 3 and with no clear connection to the North African occurrence. The timing and spatial distribution of their appearance in southern and northern Africa implies technological convergence, rather than diffusion or dispersal. While lithic technologies can be a critical guide to human population flux, their utility in tracing early human dispersals at large spatial and temporal scales with stone artefact types remains questionable. PMID:26125972

  4. EFFECT OF ARSENICALS ON THE EXPRESSION OF CELL CYCLE PROTEINS AND EARLY SIGNALING EVENTS IN PRIMARY HUMAN KERATINOCYTES.

    EPA Science Inventory

    Effect of Arsenicals on the Expression of Cell Cycle Proteins and Early Signaling Events in Primary Human Keratinocytes.

    Mudipalli, A, Owen R. D. and R. J. Preston, Environmental Carcinogenesis Division, USEPA, RTP, NC 27711.

    Environmental exposure to arsenic is a m...

  5. Misbinding of color and motion in human early visual cortex: Evidence from event-related potentials.

    PubMed

    Zhang, Yanyu; Zhang, Xilin; Wang, Yizhou; Fang, Fang

    2016-05-01

    One of the central tasks for the visual system is to integrate visual features into objects, which is referred to as the binding problem. To study the binding mechanisms, it has been suggested to use phenomena of feature misbinding to separate active feature binding from feature co-occurence. Taking advantage of a steady-state misbinding of color and motion, we performed psychophysical and event-related potential (ERP) adaptation experiments to investigate the neural mechanisms of the misbinding (i.e., the active color-motion binding). Human subjects adapted to the misbinding of color and motion, as well as their correct binding that was used for identifying neural processes associated with the co-occurrence of color and motion. We found that adaptation to the misbinding and the correct binding could generate color-contingent motion aftereffects (CCMAEs), but in opposite directions. ERP adaptation effects manifested in the earliest ERP component C1. The C1 latency in the misbinding condition was 11ms longer than that in the correct binding condition. In the correct binding condition, the C1 adaptation effect (i.e., the C1 amplitude reduction after adaptation) took place in the peak phase of the C1. The dipole source of the adaptation effect was located in V1. In the misbinding condition, the C1 adaptation effect occurred in the descending phase of the C1 and its dipole source was in V2. In both conditions, the C1 adaptation effects correlated with the CCMAEs across individual subjects. These findings provide human electrophysiological evidence that active feature binding takes place in early visual cortex, but at later processing stages than feature co-occurrence. PMID:27038562

  6. Chimerism in humans after intragenic recombination at the haptoglobin locus during early embryogenesis.

    PubMed

    Asakawa, J; Kodaira, M; Nakamura, N; Satoh, C; Fujita, M

    1999-08-31

    The human haptoglobin (HP) HP*2 allele contains a 1.7-kilobase (kb) intragenic duplication that arose after a unique nonhomologous recombination between the prototype HP*1 alleles. During a genetic screening of 13,000 children of survivors exposed to atomic-bomb radiation and 10,000 children of unexposed persons, two children suspected of carrying de novo mutations at the haptoglobin locus were identified (one in each group). DNA analyses of single-cell-derived colonies of Epstein-Barr virus-transformed B cells revealed that the two children were mosaics comprising HP*2/HP*2 and HP*2/HP*1 cells at a ratio of approximately 3:1. We infer that the latter cells are caused by reversion of one HP*2 allele to HP*1 through an intramolecular homologous recombination between the duplicated segments of the Hp*2 allele that excised one of the segments. Because the mosaicism is substantial (approximately 25%), this recombination must have occurred in early embryogenesis. The frequency of finding these children and the extent of their mosaicisms corresponds to an HP*2 to HP*1 reversion rate of 8 x 10(-6) per cell during development. This leads to the prediction that the HP*1 allele also will be represented, although usually at a very low frequency, in any HP2-2 person. We tested this prediction by using PCR for a single individual and found the HP*1 allele at frequencies of 4 x 10(-6) and 3 x 10(-6) in somatic and sperm cells. The HP*1 allele was detected by PCR in all four other HP2-2 individuals, which supports the regular but rare occurrence somatically of homologous recombination within duplicated regions in humans, in agreement with previous observations in mouse and Drosophila. PMID:10468605

  7. Role of human cytomegalovirus in the proliferation and invasion of extravillous cytotrophoblasts isolated from early placentae

    PubMed Central

    Liu, Tao; Zheng, Xiaofei; Li, Qin; Chen, Juanjuan; Yin, Zongzhi; Xiao, Juan; Zhang, Dandan; Li, Wei; Qiao, Yuan; Chen, Suhua

    2015-01-01

    Aim: We investigated the role of human cytomegalovirus (HCMV) and its mechanism in extravillous cytotrophoblast (EVT) proliferation and invasion in vitro. Methods: Differential enzymatic digestion combined with gradient centrifugation, was used to isolate primary EVT from human chorionic villi collected from early placentae of healthy pregnant women. HCMV infection was determined by immunofluorescence staining of HCMVpp65 antigen expression. An MTT assay was used to examine the role of HCMV in the proliferation of EVT. Quantitative real-time polymerase chain reaction (qRT-PCR), immunocytochemical staining and Western blots were carried out in a control group (EVT) and a virus group (EVT+HCMV) to examine the expression of major genes and protein in TGF-β/Smad signaling pathways in EVT 48 h after inoculation with HCMV. An in vitro cell invasion assay was performed to analyze the influence of HCMV on EVT invasion. Results: HCMV significantly inhibited the proliferation of EVT 48 h after viral infection (P < 0.05). The expression of TGF-β1, Smad1, Smad2, Smad3, Smad4, and Smad5 genes was significantly increased (P < 0.05), but that of TGF-β2, TGF-β3, TGFβRI, TGFβRII, Smad7, MMP2, and MMP9 was significantly decreased in the virus group 48 h after HCMV infection (P < 0.05). Smad7, MMP-2 and MMP-9 protein levels were significantly decreased and the TGF-β1 protein level was significantly increased in infected EVT (all P < 0.05). Conclusions: HCMV may act on multiple steps of the TGF-β/Smad signaling pathway to impede EVT proliferation and invasion. PMID:26770317

  8. Combined chemical and optical methods for monitoring the early decay stages of surrogate human models.

    PubMed

    Statheropoulos, M; Agapiou, A; Zorba, E; Mikedi, K; Karma, S; Pallis, G C; Eliopoulos, C; Spiliopoulou, C

    2011-07-15

    As the body decays shortly after death, a variety of gases and volatile organic compounds (VOCs) constantly emanate. Ethical and practical reasons limit the use of human corpses in controlled, time-dependent, intervening experiments for monitoring the chemistry of body decay. Therefore the utilization of pig carcasses serves as a potential surrogate to human models. The aim of this work was to study buried body decay in conditions of entrapment in collapsed buildings. Six domestic pigs were used to study carcass decay. They were enclosed in plastic body bags after being partially buried with rubbles, resembling entrapment in collapsed buildings. Three experimental cycles were performed, employing two pig carcasses in each cycle; VOCs and inorganic gases were measured daily, along with daily visible and thermal images. VOCs were collected in standard sorbent tubes and subsequently analyzed using a Thermal Desorption/Gas Chromatograph/high sensitivity bench-top Time-of-Flight Mass Spectrometer (TD/GC/TOF-MS). A comprehensive, stage by stage, detailed information on the decay process is being presented based on the experimental macroscopic observations, justifying thus the use of pig carcasses as surrogate material. A variety of VOCs were identified including almost all chemical classes: sulfur, nitrogen, oxygen compounds (aldehydes, alcohols, ketones, acids and esters), hydrocarbons, fluorides and chlorides. Carcasses obtained from a pig farm resulted in more sulfur and nitrogen cadaveric volatiles. Carbon dioxide was by far the most abundant inorganic gas identified along with carbon monoxide, hydrogen sulfide and sulfur dioxide. Visual monitoring was based on video captured images allowing for macroscopic observations, while thermal camera monitoring which is mostly temperature dependent, resulted in highlighting the local micro-changes on the carcasses, as a result of the intense microbial activity. The combination of chemical and optical methods proved very

  9. A study of early afterdepolarizations in a model for human ventricular tissue.

    PubMed

    Vandersickel, Nele; Kazbanov, Ivan V; Nuitermans, Anita; Weise, Louis D; Pandit, Rahul; Panfilov, Alexander V

    2014-01-01

    Sudden cardiac death is often caused by cardiac arrhythmias. Recently, special attention has been given to a certain arrhythmogenic condition, the long-QT syndrome, which occurs as a result of genetic mutations or drug toxicity. The underlying mechanisms of arrhythmias, caused by the long-QT syndrome, are not fully understood. However, arrhythmias are often connected to special excitations of cardiac cells, called early afterdepolarizations (EADs), which are depolarizations during the repolarizing phase of the action potential. So far, EADs have been studied mainly in isolated cardiac cells. However, the question on how EADs at the single-cell level can result in fibrillation at the tissue level, especially in human cell models, has not been widely studied yet. In this paper, we study wave patterns that result from single-cell EAD dynamics in a mathematical model for human ventricular cardiac tissue. We induce EADs by modeling experimental conditions which have been shown to evoke EADs at a single-cell level: by an increase of L-type Ca currents and a decrease of the delayed rectifier potassium currents. We show that, at the tissue level and depending on these parameters, three types of abnormal wave patterns emerge. We classify them into two types of spiral fibrillation and one type of oscillatory dynamics. Moreover, we find that the emergent wave patterns can be driven by calcium or sodium currents and we find phase waves in the oscillatory excitation regime. From our simulations we predict that arrhythmias caused by EADs can occur during normal wave propagation and do not require tissue heterogeneities. Experimental verification of our results is possible for experiments at the cell-culture level, where EADs can be induced by an increase of the L-type calcium conductance and by the application of I[Formula: see text] blockers, and the properties of the emergent patterns can be studied by optical mapping of the voltage and calcium. PMID:24427289

  10. Metabolic effects of growth factors and polycyclic aromatic hydrocarbons on cultured human placental cells of early and late gestation

    SciTech Connect

    Guyda, H.J. )

    1991-03-01

    The metabolic effects of epidermal growth factor (EGF), insulin, insulin-like growth factor-I (IGF-I), and IGF-II were determined on human placental cells in monolayer culture obtained from early gestation (less than 20 weeks) and late gestation (38-42 weeks). Parameters studied were uptake of aminoisobutyric acid (AIB), uptake of 3-O-methylglucose and (3H)thymidine incorporation into cell protein. Since benzo(alpha)pyrene (BP) inhibits EGF binding and autophosphorylation in cultured human placental cells, particularly in early gestation, we also studied the effect of benzo(alpha)pyrene and other polycyclic aromatic hydrocarbons (PAHs) on EGF-mediated AIB uptake. The metabolic effects of EGF, insulin, and the IGFs in cultured human placental cells varied with gestational age and the growth factor studied. All three classes of growth factors stimulated AIB uptake in both early and late gestation at concentrations from 10-100 micrograms/L, well within a physiological range. However, insulin stimulation of AIB uptake was maximal at a high concentration in both early and late gestation cells, suggesting an action via type 1 IGF receptors rather than via insulin receptors. EGF stimulated 3-O-methylglucose uptake only in term placental cells. No significant stimulation of (3H)thymidine incorporation by any of the growth factors tested was seen with either early or late gestation cells. The effect of PAHs on AIB uptake by cultured placental cells was variable. BP alone stimulated AIB uptake by both very early and late gestation cells and enhanced EGF-stimulated AIB uptake. alpha-naphthoflavone alone inhibited AIB uptake at all gestational ages and inhibited EGF-stimulated AIB uptake. beta-Naphthoflavone and 3-methylcholanthrene minimally inhibited AIB uptake by early gestation cells and did not modify EGF-stimulated uptake at any gestational period.

  11. Ordinary Variations in Human Maternal Caregiving in Infancy and Biobehavioral Development in Early Childhood: A Follow-up Study

    PubMed Central

    Hane, Amie Ashley; Henderson, Heather A.; Fox, Nathan A.; Reeb-Sutherland, Bethany C.

    2016-01-01

    Rodent models of early caregiving find that pups reared by dams providing low levels of early stimulation subsequently display heightened stress reactivity and social aggression. We examined these effects in humans by investigating the effects of early caregiving on markers of biobehavioral development at ages 2 and 3 years. This study extended the findings reported by Hane and Fox (2006) in which 185 mothers and infants were observed and scored for variations in maternal caregiving behavior (MCB) at age 9 months. Relative to young children who received high quality MCB in infancy, those who received low-quality MCB showed significantly higher socially inhibited behavior with adults, right frontal electroencephalographam (EEG) asymmetry, aggressive play, and maternal reported internalizing behavior problems and anger proneness. These effects were independent of early temperamental reactivity. Results parallel rodent models and demonstrate that ordinary variations in MCB influence stress reactivity and social behavior in young children. (149 words) PMID:20806328

  12. Palaeophylogenomics of the vertebrate ancestor--impact of hidden paralogy on hagfish and lamprey gene phylogeny.

    PubMed

    Kuraku, Shigehiro

    2010-07-01

    In dissecting the transition from invertebrates to vertebrates at the molecular level, whole-genome duplications are recognized as a key event. This gave rise to more copies of genes in jawed vertebrates (gnathostomes), such as the four Hox clusters in the human, compared to the single ancestral cluster in invertebrates. To date, as the most early-branching lineages in vertebrates, cyclostomes (hagfishes and lampreys) have been used for comparative analyses of gene regulations and functions. However, assignment of orthology/paralogy for cyclostomes' genes is not unambiguously demonstrated. Thus, there is a high degree of incongruence in tree topologies between gene families, although whole genome duplications postulate uniform patterns in gene phylogeny. In this review, we demonstrate how expansion of an ancient genome before the cyclostome-gnathostome split, followed by reciprocal gene loss, can cause this incongruence. This is sometimes referred to as 'hidden paralogy'. PMID:21558193

  13. Ultrastructural and immunohistochemical analysis of intestinal myofibroblasts during the early organogenesis of the human small intestine.

    PubMed

    Artells, Rosa; Navarro, Alfons; Diaz, Tània; Monzó, Mariano

    2011-03-01

    Intestinal myofibroblasts (IMFs), also known as pericryptal fibroblasts, are found at the basement membrane of the intestinal epithelium. They are characterized by well-developed endoplasmic reticulum, cytoplasmic fibers, and fibrous extensions called fibronexi. IMFs have structural features in common both with fibroblasts and smooth cells. Vimentin, desmin, and α-smooth-muscle actin (α-SM) are markers commonly used to discriminate between IMFs and smooth muscle cells. Immunohistochemical studies have shown that, when α-SM and vimentin are positive in both IMFs and smooth muscle cells, desmin is negative in IMFs but positive in smooth muscle cells. In the adult intestine, IMFs play an important role in various functions, especially in tissue repair and scar formation during wound healing. In the embryonic intestine, however, wound healing does not occur, and to date, no studies have investigated the first appearance and subsequent evolution of IMFs. In this study, we have examined the human small intestine in embryos at 7, 9, and 11 weeks of development by ultrastructural and immunohistochemical analysis to shed light on the formation of IMFs during these early phases of organogenesis. At 7 weeks, the embryonic mesenchymal cells are similar to proto-myofibroblasts and may be the precursors of the IMFs detected at 9 weeks and more abundantly at 11 weeks by immunohistochemistry. These IMFs seem to mediate information flow between the epithelium and the mesenchyme and thus contribute to the development of the small intestine. PMID:21284092

  14. Early pathogenesis of Duchenne muscular dystrophy modelled in patient-derived human induced pluripotent stem cells

    PubMed Central

    Shoji, Emi; Sakurai, Hidetoshi; Nishino, Tokiko; Nakahata, Tatsutoshi; Heike, Toshio; Awaya, Tomonari; Fujii, Nobuharu; Manabe, Yasuko; Matsuo, Masafumi; Sehara-Fujisawa, Atsuko

    2015-01-01

    Duchenne muscular dystrophy (DMD) is a progressive and fatal muscle degenerating disease caused by a dystrophin deficiency. Effective suppression of the primary pathology observed in DMD is critical for treatment. Patient-derived human induced pluripotent stem cells (hiPSCs) are a promising tool for drug discovery. Here, we report an in vitro evaluation system for a DMD therapy using hiPSCs that recapitulate the primary pathology and can be used for DMD drug screening. Skeletal myotubes generated from hiPSCs are intact, which allows them to be used to model the initial pathology of DMD in vitro. Induced control and DMD myotubes were morphologically and physiologically comparable. However, electric stimulation of these myotubes for in vitro contraction caused pronounced calcium ion (Ca2+) influx only in DMD myocytes. Restoration of dystrophin by the exon-skipping technique suppressed this Ca2+ overflow and reduced the secretion of creatine kinase (CK) in DMD myotubes. These results suggest that the early pathogenesis of DMD can be effectively modelled in skeletal myotubes induced from patient-derived iPSCs, thereby enabling the development and evaluation of novel drugs. PMID:26290039

  15. The effect of early experience on odor perception in humans: psychological and physiological correlates.

    PubMed

    Poncelet, Johan; Rinck, Fanny; Bourgeat, Fanny; Schaal, Benoist; Rouby, Catherine; Bensafi, Moustafa; Hummel, Thomas

    2010-04-01

    The olfactory function in humans is characterized by wide variability between individuals. One of the prominent factors that contribute to this plasticity is early exposure. The present study examined how brain activity is modulated by such olfactory experience. To this end, two groups of people living in France but originating from different cultures ("European-French" (EF, 18 subjects) vs. "Algerian-French" (AF, 19 subjects)) were tested, and their perceptual and physiological responses to the smells of mint (presumed to be experienced earlier in life by "Algerian-French" subjects) and of rose (control odorant) were compared. Neurophysiological responses were obtained in the form of chemosensory event-related potentials (CSERP). The results confirmed that the AF group was exposed to Mint tea earlier than the EF group. On the perceptual level, when asked to associate the smell of mint with objects or events retrieved from memory, the discourse of AF subjects included more "experience-oriented" associations than that of EF subjects. This was associated with longer P2 latency in CSERPs in response to the smell of mint in the AF group. These findings highlight the plasticity of behavioral and neural olfactory processes as a result of differential lifetime exposure. PMID:20035792

  16. Monitoring chicken flock behaviour provides early warning of infection by human pathogen Campylobacter

    PubMed Central

    Colles, Frances M.; Cain, Russell J.; Nickson, Thomas; Smith, Adrian L.; Roberts, Stephen J.; Maiden, Martin C. J.; Lunn, Daniel; Dawkins, Marian Stamp

    2016-01-01

    Campylobacter is the commonest bacterial cause of gastrointestinal infection in humans, and chicken meat is the major source of infection throughout the world. Strict and expensive on-farm biosecurity measures have been largely unsuccessful in controlling infection and are hampered by the time needed to analyse faecal samples, with the result that Campylobacter status is often known only after a flock has been processed. Our data demonstrate an alternative approach that monitors the behaviour of live chickens with cameras and analyses the ‘optical flow’ patterns made by flock movements. Campylobacter-free chicken flocks have higher mean and lower kurtosis of optical flow than those testing positive for Campylobacter by microbiological methods. We show that by monitoring behaviour in this way, flocks likely to become positive can be identified within the first 7–10 days of life, much earlier than conventional on-farm microbiological methods. This early warning has the potential to lead to a more targeted approach to Campylobacter control and also provides new insights into possible sources of infection that could transform the control of this globally important food-borne pathogen. PMID:26740618

  17. Monitoring chicken flock behaviour provides early warning of infection by human pathogen Campylobacter.

    PubMed

    Colles, Frances M; Cain, Russell J; Nickson, Thomas; Smith, Adrian L; Roberts, Stephen J; Maiden, Martin C J; Lunn, Daniel; Dawkins, Marian Stamp

    2016-01-13

    Campylobacter is the commonest bacterial cause of gastrointestinal infection in humans, and chicken meat is the major source of infection throughout the world. Strict and expensive on-farm biosecurity measures have been largely unsuccessful in controlling infection and are hampered by the time needed to analyse faecal samples, with the result that Campylobacter status is often known only after a flock has been processed. Our data demonstrate an alternative approach that monitors the behaviour of live chickens with cameras and analyses the 'optical flow' patterns made by flock movements. Campylobacter-free chicken flocks have higher mean and lower kurtosis of optical flow than those testing positive for Campylobacter by microbiological methods. We show that by monitoring behaviour in this way, flocks likely to become positive can be identified within the first 7-10 days of life, much earlier than conventional on-farm microbiological methods. This early warning has the potential to lead to a more targeted approach to Campylobacter control and also provides new insights into possible sources of infection that could transform the control of this globally important food-borne pathogen. PMID:26740618

  18. The Human Factors of an Early Space Accident: Flight 3-65 of the X-15

    NASA Technical Reports Server (NTRS)

    Barshi, Immanuel; Statler, Irving C.; Orr, Jeb S.

    2015-01-01

    The X-15 was a critical research vehicle in the early days of space flight. On November 15, 1967, the X-15-3 suffered an in-flight breakup. This 191st flight of the X-15 and the 65th flight of this third configuration was the only fatal accident of the X-15 program. This paper presents an analysis, from a human factors perspective, of the events that led up to the accident. The analysis is based on the information contained in the report of the Air Force-NASA Accident Investigation Board (AIB) dated January, 1968. The AIBs analysis addressed, primarily, the events that occurred subsequent to the pilots taking direct control of the reaction control system. The analysis described here suggests that all of the events that caused the accident occurred well before the moment when the pilot switched to direct control. Consequently, the analyses and conclusions regarding the causal factors of, and the contributing factors to, the loss of Flight 3-65 presented here differ from those of the AIB based on the same evidence. Although the accident occurred in 1967, the results of the presented analysis are still relevant today. We present our analysis and discuss its implications for the safety of space operations.

  19. In-vivo measurement of intrauterine gases and acid-base values early in human pregnancy.

    PubMed

    Jauniaux, E; Watson, A; Ozturk, O; Quick, D; Burton, G

    1999-11-01

    A new multiparameter sensor that combines electrochemical and fibre-optic technology was used for continuous in-vivo investigation of pH, carbon dioxide partial pressure (PCO(2)), oxygen partial pressure (PO(2)), bicarbonate concentration (HCO(3)(-)), base excess, and oxygen saturation (O(2)Sat) early in human pregnancy. The sensor was inserted into the amniotic cavity and the placental bed of 16 pregnancies at 10-15 weeks gestation, before termination under general anaesthesia. Amniotic fluid and retroplacental blood from the same site were also aspirated and analysed by means of cartridges and a portable blood gas analyser. Eleven series of measurements were obtained. The variation in measurements over the 5 min of monitoring was

  20. Early processing in human LOC is highly responsive to illusory contours but not to salient regions

    PubMed Central

    Shpaner, Marina; Murray, Micah M.; Foxe, John J.

    2011-01-01

    Human electrophysiological studies support a model whereby sensitivity to so-called illusory contour stimuli is first seen within the lateral occipital complex. A challenge to this model posits that the lateral occipital complex is a general site for crude region-based segmentation, based on findings of equivalent hemodynamic activations in the lateral occipital complex to illusory contour and so-called salient region stimuli, a stimulus class that lacks the classic bounding contours of illusory contours. Using high-density electrical mapping of visual evoked potentials, we show that early lateral occipital cortex activity is substantially stronger to illusory contour than to salient region stimuli, while later lateral occipital complex activity is stronger to salient region than to illusory contour stimuli. Our results suggest that equivalent hemodynamic activity to illusory contour and salient region stimuli likely reflects temporally integrated responses, a result of the poor temporal resolution of hemodynamic imaging. The temporal precision of visual evoked potentials is critical for establishing viable models of completion processes and visual scene analysis. We propose that crude spatial segmentation analyses, which are insensitive to illusory contours, occur first within dorsal visual regions, not lateral occipital complex, and that initial illusory contour sensitivity is a function of the lateral occipital complex. PMID:19895562

  1. A proposal of the proteome before the last universal common ancestor (LUCA)

    NASA Astrophysics Data System (ADS)

    de Farias, Sávio Torres; Rêgo, Thais Gaudêncio; José, Marco V.

    2016-01-01

    The search for understanding the biological nature of the last universal common ancestor (LUCA) has been a theoretical challenge and has sparked intense debate in the scientific community. We reconstructed the ancestral sequences of tRNAs in order to test the hypothesis that these molecules originated the first genes. The results showed that the proteome before LUCA may have been composed of basal energy metabolism, namely, compounds with three carbons in the glycolytic pathway, which operated as a distribution centre of substrates for the development of metabolic pathways of nucleotides, lipids and amino acids. Thus, we present a proposal for metabolism in organisms before LUCA that was the initial core for the assembly of further metabolic pathways.

  2. The genome sequences of Arachis duranensis and Arachis ipaensis, the diploid ancestors of cultivated peanut.

    PubMed

    Bertioli, David John; Cannon, Steven B; Froenicke, Lutz; Huang, Guodong; Farmer, Andrew D; Cannon, Ethalinda K S; Liu, Xin; Gao, Dongying; Clevenger, Josh; Dash, Sudhansu; Ren, Longhui; Moretzsohn, Márcio C; Shirasawa, Kenta; Huang, Wei; Vidigal, Bruna; Abernathy, Brian; Chu, Ye; Niederhuth, Chad E; Umale, Pooja; Araújo, Ana Cláudia G; Kozik, Alexander; Kim, Kyung Do; Burow, Mark D; Varshney, Rajeev K; Wang, Xingjun; Zhang, Xinyou; Barkley, Noelle; Guimarães, Patrícia M; Isobe, Sachiko; Guo, Baozhu; Liao, Boshou; Stalker, H Thomas; Schmitz, Robert J; Scheffler, Brian E; Leal-Bertioli, Soraya C M; Xun, Xu; Jackson, Scott A; Michelmore, Richard; Ozias-Akins, Peggy

    2016-04-01

    Cultivated peanut (Arachis hypogaea) is an allotetraploid with closely related subgenomes of a total size of ∼2.7 Gb. This makes the assembly of chromosomal pseudomolecules very challenging. As a foundation to understanding the genome of cultivated peanut, we report the genome sequences of its diploid ancestors (Arachis duranensis and Arachis ipaensis). We show that these genomes are similar to cultivated peanut's A and B subgenomes and use them to identify candidate disease resistance genes, to guide tetraploid transcript assemblies and to detect genetic exchange between cultivated peanut's subgenomes. On the basis of remarkably high DNA identity of the A. ipaensis genome and the B subgenome of cultivated peanut and biogeographic evidence, we conclude that A. ipaensis may be a direct descendant of the same population that contributed the B subgenome to cultivated peanut. PMID:26901068

  3. The effect of inbreeding constraints and offspring distribution on time to the most recent common ancestor.

    PubMed

    Campbell, R B

    2015-10-01

    The expected time to the most recent common ancestor (MRCA) of two alleles in a diploid individual is 4N+2 under random mating with a Poisson progeny distribution, but 8N-2 under maximum avoidance of inbreeding, which entails two progeny per mating pair. (N is the number of mating pairs, hence 2N is the number of individuals, hence 4N is the number of alleles.) The interrelationship of inbreeding constraints and offspring distribution is investigated by varying the level of sib mating: prohibiting sib mating increases the time to MRCA by four generations and decreases the variance of the offspring distribution by 2/N. With two progeny per mating pair, the expected time to the MRCA is 8N-2 under both random mating and sib mating prohibited, as well as under maximum avoidance of inbreeding, but this result does not hold for all mating structures with two progeny per mating pair. PMID:26144024

  4. Age of the last common ancestor of extant Plasmodium parasite lineages.

    PubMed

    Hayakawa, Toshiyuki; Tachibana, Shin-Ichiro; Hikosaka, Kenji; Arisue, Nobuko; Matsui, Atsushi; Horii, Toshihiro; Tanabe, Kazuyuki

    2012-07-01

    Parasites of the genus Plasmodium infect all classes of amniotes (mammals, birds and reptiles) and display host specificity in their infections. It is therefore generally believed that Plasmodium parasites co-evolved intimately with their hosts. Here, we report that based on an evolutionary analysis using 22 genes in the nuclear genome, extant lineages of Plasmodium parasites originated roughly in the Oligocene epoch after the emergence of their hosts. This timing on the age of the common ancestor of extant Plasmodium parasites suggest the importance of host switches and lends support to the evolutionary scenario of a "malaria big bang" that was proposed based on the evolutionary analysis using the mitochondrial genome. PMID:22555021

  5. Mitochondrial DNA sequences in ancient Australians: Implications for modern human origins

    PubMed Central

    Adcock, Gregory J.; Dennis, Elizabeth S.; Easteal, Simon; Huttley, Gavin A.; Jermiin, Lars S.; Peacock, W. James; Thorne, Alan

    2001-01-01

    DNA from ancient human remains provides perspectives on the origin of our species and the relationship between molecular and morphological variation. We report analysis of mtDNA from the remains of 10 ancient Australians. These include the morphologically gracile Lake Mungo 3 [≈60 thousand years (ka) before present] and three other gracile individuals from Holocene deposits at Willandra Lakes (<10 ka), all within the skeletal range of living Australians, and six Pleistocene/early Holocene individuals (15 to <8 ka) from Kow Swamp with robust morphologies outside the skeletal range of contemporary indigenous Australians. Lake Mungo 3 is the oldest (Pleistocene) “anatomically modern” human from whom DNA has been recovered. His mtDNA belonged to a lineage that only survives as a segment inserted into chromosome 11 of the nuclear genome, which is now widespread among human populations. This lineage probably diverged before the most recent common ancestor of contemporary human mitochondrial genomes. This timing of divergence implies that the deepest known mtDNA lineage from an anatomically modern human occurred in Australia; analysis restricted to living humans places the deepest branches in East Africa. The other ancient Australian individuals we examined have mtDNA sequences descended from the most recent common ancestor of living humans. Our results indicate that anatomically modern humans were present in Australia before the complete fixation of the mtDNA lineage now found in all living people. Sequences from additional ancient humans may further challenge current concepts of modern human origins. PMID:11209053

  6. Mitochondrial DNA sequences in ancient Australians: Implications for modern human origins.

    PubMed

    Adcock, G J; Dennis, E S; Easteal, S; Huttley, G A; Jermiin, L S; Peacock, W J; Thorne, A

    2001-01-16

    DNA from ancient human remains provides perspectives on the origin of our species and the relationship between molecular and morphological variation. We report analysis of mtDNA from the remains of 10 ancient Australians. These include the morphologically gracile Lake Mungo 3 [ approximately 60 thousand years (ka) before present] and three other gracile individuals from Holocene deposits at Willandra Lakes (<10 ka), all within the skeletal range of living Australians, and six Pleistocene/early Holocene individuals (15 to <8 ka) from Kow Swamp with robust morphologies outside the skeletal range of contemporary indigenous Australians. Lake Mungo 3 is the oldest (Pleistocene) "anatomically modern" human from whom DNA has been recovered. His mtDNA belonged to a lineage that only survives as a segment inserted into chromosome 11 of the nuclear genome, which is now widespread among human populations. This lineage probably diverged before the most recent common ancestor of contemporary human mitochondrial genomes. This timing of divergence implies that the deepest known mtDNA lineage from an anatomically modern human occurred in Australia; analysis restricted to living humans places the deepest branches in East Africa. The other ancient Australian individuals we examined have mtDNA sequences descended from the most recent common ancestor of living humans. Our results indicate that anatomically modern humans were present in Australia before the complete fixation of the mtDNA lineage now found in all living people. Sequences from additional ancient humans may further challenge current concepts of modern human origins. PMID:11209053

  7. Reptiles and Mammals Have Differentially Retained Long Conserved Noncoding Sequences from the Amniote Ancestor

    PubMed Central

    Janes, D.E.; Chapus, C.; Gondo, Y.; Clayton, D.F.; Sinha, S.; Blatti, C.A.; Organ, C.L.; Fujita, M.K.; Balakrishnan, C.N.; Edwards, S.V.

    2011-01-01

    Many noncoding regions of genomes appear to be essential to genome function. Conservation of large numbers of noncoding sequences has been reported repeatedly among mammals but not thus far among birds and reptiles. By searching genomes of chicken (Gallus gallus), zebra finch (Taeniopygia guttata), and green anole (Anolis carolinensis), we quantified the conservation among birds and reptiles and across amniotes of long, conserved noncoding sequences (LCNS), which we define as sequences ≥500 bp in length and exhibiting ≥95% similarity between species. We found 4,294 LCNS shared between chicken and zebra finch and 574 LCNS shared by the two birds and Anolis. The percent of genomes comprised by LCNS in the two birds (0.0024%) is notably higher than the percent in mammals (<0.0003% to <0.001%), differences that we show may be explained in part by differences in genome-wide substitution rates. We reconstruct a large number of LCNS for the amniote ancestor (ca. 8,630) and hypothesize differential loss and substantial turnover of these sites in descendent lineages. By contrast, we estimated a small role for recruitment of LCNS via acquisition of novel functions over time. Across amniotes, LCNS are significantly enriched with transcription factor binding sites for many developmental genes, and 2.9% of LCNS shared between the two birds show evidence of expression in brain expressed sequence tag databases. These results show that the rate of retention of LCNS from the amniote ancestor differs between mammals and Reptilia (including birds) and that this may reflect differing roles and constraints in gene regulation. PMID:21183607

  8. Genetic organization, size, and complete sequence of early region 3 genes of human adenovirus type 41.

    PubMed Central

    Yeh, H Y; Pieniazek, N; Pieniazek, D; Luftig, R B

    1996-01-01

    The complete nucleotide and predicted amino acid sequences for open reading frames (ORFs) of the human adenovirus type 41 (Ad41) early region 3 (E3) gene have been determined. The sequence of the Ad41 E3 gene (map units 74 to 83.9) consists of 3,373 nucleotides and has one TATA box and two polyadenylation signals (AATAAA). Analysis of the nucleotide sequence reveals that the E3 gene can encode six ORFs, designated RL1 to RL6. These are all expressed at the mRNA level, as determined by reverse transcription-PCR analysis of AD41-infected cell RNA. When compared with known E3 sequences of most other human adenoviruses deposited in GenBank, the sequences of RL1 to RL3 were found to be unique to subgroup F adenoviruses (Ad40 and Ad41). They encode putative proteins of 173 amino acids (19.4 kDa) and 276 amino acids (31.6 kDa) in one reading frame as well as a 59- amino-acid (6.7 kDa) protein in an overlapping reading frame. RL4 encodes a 90-amino-acid protein (10.1 kDa) with 40% homology to the Ad2 E3 10.4-kDa protein, which induces degradation of the epidermal growth factor receptor and functions together with the Ad2 E3 14.5-kDa protein to protect mouse cell lines against lysis. RL5 encodes a protein of 107 amino acid residues (12.3 kDa) and is analogous to the Ad E3 14.5-kDa protein. RL6 codes for a protein of 122 amino acids (14.7 kDa) that is analogous to the Ad2 14.7-kDa protein, which functions to protect Ad-infected cells from tumor necrosis factor-induced cytolysis. This finding of three unique (RL1 to RL3) E3 gene ORFs may explain why subgroup F adenoviruses differ substantially from other human adenoviruses in their host range; i.e., they replicate predominantly in the host's gastrointestinal rather than respiratory tract. A recent phylogenetic study that compared subgroup F Ad40 DNA sequences with representatives of subgroups B (Ad3), C (Ad2), and E (Ad4) reached a similar conclusion about the uniqueness of RL1 and RL2. PMID:8642703

  9. An iPS Cell Line From Human Pancreatic Ductal Adenocarcinoma Undergoes Early to Invasive Stages of Pancreatic Cancer Progression

    PubMed Central

    Kim, Jungsun; Hoffman, John P.; Alpaugh, R. Katherine; Rhim, Andrew D.; Reichert, Maximilian; Stanger, Ben Z.; Furth, Emma E.; Sepulveda, Antonia R.; Yuan, Chao-Xing; Won, Kyoung-Jae; Donahue, Greg; Sands, Jessica; Gumbs, Andrew A.; Zaret, Kenneth S.

    2013-01-01

    Pancreatic ductal adenocarcinoma (PDAC) carries a dismal prognosis and lacks a human cell model of early disease progression. When human PDAC cells are injected into immunodeficient mice, they generate advanced stage cancer. We hypothesized that if human PDAC cells were converted to pluripotency and then allowed to differentiate back into pancreatic tissue, they might undergo early stages of cancer. Although most induced pluripotent stem (iPS) cell lines were not of the expected cancer genotype, one PDAC line, 10-22 cells, when injected into immunodeficient mice, generates pancreatic intraepithelial neoplasia (PanIN) precursors to PDAC that progress to the invasive stage. The PanIN-like cells secrete or release proteins corresponding to genes and networks expressed in human pancreatic cancer progression and which predicted an HNF4α network also seen a mouse model. Thus, rare events allow iPS technology to provide a live human cell model of early pancreatic cancer and new insights into disease progression. PMID:23791528

  10. Human radiation studies: Remembering the early years: Oral history of pathologist Clarence Lushbaugh, M.D., conducted October 5, 1994

    SciTech Connect

    1995-04-01

    This report provides a transcript of an interview with Dr. Clarance Lushbaugh by representatives of the DOE Office of Human Radiation Experiments. Dr. Lushbaugh was chosen for this interview because of his research involving experimental use of irradiation with human beings at Los Alamos and at the Oak Ridge Institute of Nuclear Science (ORINS). After a brief biographical sketch Dr. Lushbaugh and his assistant Mrs. Ann Swipe defend their use of total body irradiation using the LETBI (Low Exposure Total Body Irradiation) and the LETBI (Medium Energy Total Body Irradiator). Dr. Lushbaugh also discusses his earlier experiments involving use of nitrogen mustards in chemotherapy application, his early interest in the LD50 for man, his early impressions of low-level spray radiation as introduced by Heubline, anedotal information for his duties a pathologist for Los Alamos, and his developing interest in establishing safer radiation limits for human exposure.

  11. From Toumai to Lucy: climate and orographic forcing on Environment and Early Human

    NASA Astrophysics Data System (ADS)

    Ramstein, Gilles; Contoux, Camille; Sepulchre, Pierre; Schuster, Mathieu; Jost, Anne

    2014-05-01

    This abstract will present a summary of several studies we conducted at LSCE to understand through modeling simulations how the climate and topography variations may drive the evolution/migration of Early Humans. Tectonics and orbital forcing are major forcing factors on environment which act at different time scales. African Uplift spans over Millions of years whereas at low latitudes precession cycles will produce drastic hydrologic variations at the pluri millennial time scale. Therefore, in a first step it is necessary to investigate the impact of long term topographic changes on climate and vegetation. The long term forcing of the African uplift has been first tested and investigated through a set of numerical experiments using different heights for the Rift. We pointed out that this issue was the key factor to explain the dryness of the East part of the Rift associated with the disappearance of the forests when the rift was uplifted during the late Pliocene. Prior to this, much more water penetrates from the Indian Ocean over East Africa and forests can sustain. Therefore, this pattern of Dry East of the Rift and Wet west of the Rift is driven by the uplift and consistent with the evolution of vegetation. On the other side, the Mega Lake Chad (MLC) region was not really sensitive to this topographic change but much more to orbital forcing. Two species of early hominids (Australopithecus bahrelghazali, 3,6 Ma, and Sahelanthropus tchadensis, Toumai, 7 Ma) were found in this region, associated with other vertebrate fossil remains, which seem to be associated to the presence of the Mega Lake Chad. It is thus crucial to understand how it is possible to produce and sustain such a large lake (350 000 km2) at these latitudes. Through a second series of simulations, we demonstrated that during the Pliocene, occurrences of such megalake episodes were possible (similarly as during most recent Holocene) and may be sustained during half a precession cycle (10 kyr

  12. Determinants of motion response anisotropies in human early visual cortex: the role of configuration and eccentricity.

    PubMed

    Maloney, Ryan T; Watson, Tamara L; Clifford, Colin W G

    2014-10-15

    Anisotropies in the cortical representation of various stimulus parameters can reveal the fundamental mechanisms by which sensory properties are analysed and coded by the brain. One example is the preference for motion radial to the point of fixation (i.e. centripetal or centrifugal) exhibited in mammalian visual cortex. In two experiments, this study used functional magnetic resonance imaging (fMRI) to explore the determinants of these radial biases for motion in functionally-defined areas of human early visual cortex, and in particular their dependence upon eccentricity which has been indicated in recent reports. In one experiment, the cortical response to wide-field random dot kinematograms forming 16 different complex motion patterns (including centrifugal, centripetal, rotational and spiral motion) was measured. The response was analysed according to preferred eccentricity within four different eccentricity ranges. Response anisotropies were characterised by enhanced activity for centripetal or centrifugal patterns that changed systematically with eccentricity in visual areas V1-V3 and hV4 (but not V3A/B or V5/MT+). Responses evolved from a preference for centrifugal over centripetal patterns close to the fovea, to a preference for centripetal over centrifugal at the most peripheral region stimulated, in agreement with previous work. These effects were strongest in V2 and V3. In a second experiment, the stimuli were restricted to within narrow annuli either close to the fovea (0.75-1.88°) or further in the periphery (4.82-6.28°), in a way that preserved the local motion information available in the first experiment. In this configuration a preference for radial motion (centripetal or centrifugal) persisted but the dependence upon eccentricity disappeared. Again this was clearest in V2 and V3. A novel interpretation of the dependence upon eccentricity of motion anisotropies in early visual cortex is offered that takes into account the spatiotemporal

  13. The artiodactyl APOBEC3 innate immune repertoire shows evidence for a multi-functional domain organization that existed in the ancestor of placental mammals

    PubMed Central

    LaRue, Rebecca S; Jónsson, Stefán R; Silverstein, Kevin AT; Lajoie, Mathieu; Bertrand, Denis; El-Mabrouk, Nadia; Hötzel, Isidro; Andrésdóttir, Valgerdur; Smith, Timothy PL; Harris, Reuben S

    2008-01-01

    Background APOBEC3 (A3) proteins deaminate DNA cytosines and block the replication of retroviruses and retrotransposons. Each A3 gene encodes a protein with one or two conserved zinc-coordinating motifs (Z1, Z2 or Z3). The presence of one A3 gene in mice (Z2–Z3) and seven in humans, A3A-H (Z1a, Z2a-Z1b, Z2b, Z2c-Z2d, Z2e-Z2f, Z2g-Z1c, Z3), suggests extraordinary evolutionary flexibility. To gain insights into the mechanism and timing of A3 gene expansion and into the functional modularity of these genes, we analyzed the genomic sequences, expressed cDNAs and activities of the full A3 repertoire of three artiodactyl lineages: sheep, cattle and pigs. Results Sheep and cattle have three A3 genes, A3Z1, A3Z2 and A3Z3, whereas pigs only have two, A3Z2 and A3Z3. A comparison between domestic and wild pigs indicated that A3Z1 was deleted in the pig lineage. In all three species, read-through transcription and alternative splicing also produced a catalytically active double domain A3Z2-Z3 protein that had a distinct cytoplasmic localization. Thus, the three A3 genes of sheep and cattle encode four conserved and active proteins. These data, together with phylogenetic analyses, indicated that a similar, functionally modular A3 repertoire existed in the common ancestor of artiodactyls and primates (i.e., the ancestor of placental mammals). This mammalian ancestor therefore possessed the minimal A3 gene set, Z1-Z2-Z3, required to evolve through a remarkable series of eight recombination events into the present day eleven Z domain human repertoire. Conclusion The dynamic recombination-filled history of the mammalian A3 genes is consistent with the modular nature of the locus and a model in which most of these events (especially the expansions) were selected by ancient pathogenic retrovirus infections. PMID:19017397

  14. Heritability and genetic correlations of fear-related behaviour in Red Junglefowl--possible implications for early domestication.

    PubMed

    Agnvall, Beatrix; Jöngren, Markus; Strandberg, Erling; Jensen, Per

    2012-01-01

    Domesticated species differ from their wild ancestors in a number of traits, generally referred to as the domesticated phenotype. Reduced fear of humans is assumed to have been an early prerequisite for the successful domestication of virtually all species. We hypothesized that fear of humans is linked to other domestication related traits. For three generations, we selected Red Junglefowl (ancestors of domestic chickens) solely on the reaction in a standardized Fear of Human-test. In this, the birds were exposed for a gradually approaching human, and their behaviour was continuously scored. This generated three groups of animals, high (H), low (L) and intermediate (I) fearful birds. The birds in each generation were additionally tested in a battery of behaviour tests, measuring aspects of fearfulness, exploration, and sociality. The results demonstrate that the variation in fear response of Red Junglefowl towards humans has a significant genetic component and is genetically correlated to behavioural responses in other contexts, of which some are associated with fearfulness and others with exploration. Hence, selection of Red Junglefowl on low fear for humans can be expected to lead to a correlated change of other behavioural traits over generations. It is therefore likely that domestication may have caused an initial suite of behavioural modifications, even without selection on anything besides tameness. PMID:22536354

  15. Specific interactions between transcription factors and the promoter-regulatory region of the human cytomegalovirus major immediate-early gene

    SciTech Connect

    Ghazal, P.; Lubon, H.; Hennighausen, L. )

    1988-03-01

    Repeat sequence motifs as well as unique sequences between nucleotides {minus}150 and {minus}22 of the human cytomegalovirus immediate-early 1 gene interact in vitro with nuclear proteins. The authors show that a transcriptional element between nucleotides {minus}91 and {minus}65 stimulated promoter activity in vivo and in vitro by binding specific cellular transcription factors. Finally, a common sequence motif, (T)TGG/AC, present in 15 of the determined binding sites suggests a particular class of nuclear factors associated with the immediate-early 1 gene.

  16. Early-life disease exposure and associations with adult survival, cause of death, and reproductive success in preindustrial humans.

    PubMed

    Hayward, Adam D; Rigby, Francesca L; Lummaa, Virpi

    2016-08-01

    A leading hypothesis proposes that increased human life span since 1850 has resulted from decreased exposure to childhood infections, which has reduced chronic inflammation and later-life mortality rates, particularly from cardiovascular disease, stroke, and cancer. Early-life cohort mortality rate often predicts later-life survival in humans, but such associations could arise from factors other than disease exposure. Additionally, the impact of early-life disease exposure on reproduction remains unknown, and thus previous work ignores a major component of fitness through which selection acts upon life-history strategy. We collected data from seven 18th- and 19th-century Finnish populations experiencing naturally varying mortality and fertility levels. We quantified early-life disease exposure as the detrended child mortality rate from infectious diseases during an individual's first 5 y, controlling for important social factors. We found no support for an association between early-life disease exposure and all-cause mortality risk after age 15 or 50. We also found no link between early-life disease exposure and probability of death specifically from cardiovascular disease, stroke, or cancer. Independent of survival, there was no evidence to support associations between early-life disease exposure and any of several aspects of reproductive performance, including lifetime reproductive success and age at first birth, in either males or females. Our results do not support the prevailing assertion that exposure to infectious diseases in early life has long-lasting associations with later-life all-cause mortality risk or mortality putatively linked to chronic inflammation. Variation in adulthood conditions could therefore be the most likely source of recent increases in adult life span. PMID:27457937

  17. Biomolecule-Mineral Interactions in the Geochemical Environment on Early Earth and in the Human Body

    NASA Astrophysics Data System (ADS)

    Sahai, N.

    2011-12-01

    We worked on four projects consistent with the broad goals of the grant to investigate (i) the potential impacts of mineral surface chemistry and particle size on the stability and viability of cell membranes, bacteria and human cells and (ii) the influence of biomolecules on mineral nucleation and growth. The projects are of relevance to the origin and early evolution of life, biomineralization, medical mineralogy, and environmental biogeochemistry. The freedom enabled by the five-year grant to explore high-risk scientific areas, and the resulting high impact outcomes, cannot be overstated. We developed an almost entirely new field of Medical Mineralogyy and extended our concepts and knowledge-base to the potential roles of mineral surfaces in the evolution of protocells and the earliest cells. These exciting connections to medical mineralogy, and to the origin and evolution of life on early Earth are fascinating topics to the general public and even to other scientists, especially when the links to mineralogy and geochemistry are highlighted. In brief, we examined the stability of lipid bilayers representing model protocell membranes comprised of phospholipid bilayers with mineral surfaces. We found that the stability of lipid bilayers depends on mineral surface charge and increases as silica glass ~ quartz < rutile ~ mica < corundum. In a second project, we investigated whether the evolution of bacterial extra-cellular polymeric substances (EPS) may have been driven by nanomineral toxicity. Results showed that EPS does protect against mineral toxicity, and toxicity increases as amorphous SiO2 < β-TiO2 (anatase) < γ-Al2O3. A commonly accepted mechanism for Biomineralization is protein-templated nucleation. We used Molecular Dynamics and Bioinformatics computational chemistry approaches and showed that the random coil structure of a specific peptide promotes formation of an amorphous Ca-PO4 cluster, but not direct templation of hydroxyapatite. The consistency

  18. Reduced expression of aquaporins in human intestinal mucosa in early stage inflammatory bowel disease

    PubMed Central

    Ricanek, Petr; Lunde, Lisa K; Frye, Stephan A; Støen, Mari; Nygård, Ståle; Morth, Jens P; Rydning, Andreas; Vatn, Morten H; Amiry-Moghaddam, Mahmood; Tønjum, Tone

    2015-01-01

    Objectives The aim of this study was to investigate the relationship between aquaporin (AQP) water channel expression and the pathological features of early untreated inflammatory bowel disease (IBD) in humans. Methods Patients suspected to have IBD on the basis of predefined symptoms, including abdominal pain, diarrhea, and/or blood in stool for more than 10 days, were examined at the local hospital. Colonoscopy with biopsies was performed and blood samples were taken. Patients who did not meet the diagnostic criteria for IBD and who displayed no evidence of infection or other pathology in the gut were included as symptomatic non-IBD controls. AQP1, 3, 4, 5, 7, 8, and 9 messenger RNA (mRNA) levels were quantified in biopsies from the distal ileum and colon by quantitative real-time polymerase chain reaction. Protein expression of selected AQPs was assessed by confocal microscopy. Through multiple alignments of the deduced amino acid sequences, the putative three-dimensional structures of AQP1, 3, 7, and 8 were modeled. Results AQP1, 3, 7, and 8 mRNAs were detected in all parts of the intestinal mucosa. Notably, AQP1 and AQP3 mRNA levels were reduced in the ileum of patients with Crohn’s disease, and AQP7 and AQP8 mRNA levels were reduced in the ileum and the colon of patients with ulcerative colitis. Immunofluorescence confocal microscopy showed localization of AQP3, 7, and 8 at the mucosal epithelium, whereas the expression of AQP1 was mainly confined to the endothelial cells and erythrocytes. The reduction in the level of AQP3, 7, and 8 mRNA was confirmed by immunofluorescence, which also indicated a reduction of apical immunolabeling for AQP8 in the colonic surface epithelium and crypts of the IBD samples. This could indicate loss of epithelial polarity in IBD, leading to disrupted barrier function. Conclusion AQPs 1 and 8 and the aquaglyceroporins AQPs 3 and 7 are the AQPs predominantly expressed in the lower intestinal tract of humans. Their expression is

  19. Landscape patterns from plant biomarkers across early human habitats (ca. 1.845 Ma)

    NASA Astrophysics Data System (ADS)

    Magill, C. R.; Ashley, G. M.; Freeman, K. H.

    2012-12-01

    Fine-scale spatial resolution reconstructions of early human (hominin) landscapes are key to understanding environmental and evolutionary processes that have shaped the genus Homo. Spatial distributions of artifacts and fossils are often interpreted in relation to specific landscape features (e.g., woody cover), but archaeological and faunal assemblages are indirect paleoecological indicators and lack stringent spatial constraints. Here, we present carbon-isotopic data for organic matter and plant biomarkers preserved in paleosols from the FLK Zinjanthropus archaeological level 22 (FLK Zinj) at Olduvai Gorge and 15 surrounding sites of stratigraphic equivalency. Plant biomarkers (leaf waxes and lignin oxidation products) reveal distinct differences in plant community composition, which were juxtaposed within just 100s of meters of each other. Central sites (including FLK Zinj) cover about 250 m2 and contain leaf waxes with low δ13C values, which we interpret as evidence for woodland habitat. About 200 m to the north, aquatic leaf waxes and sedge lipids (5-n-alkylresorcinols) occur in conjunction with mound-like tufa deposits, suggesting freshwater wetland habitat. At southern sites, strongly 13C-enriched leaf waxes and lignin components diagnostic for non-woody plant tissues suggest open grassland habitat. Taken together, these data delimit the heterogeneous landscape at FLK Zinj, which has been hinted at by its archaeological assemblage, and reinforce that the site was a 'central place' for hominin activities because it afforded arboreal refuge and freshwater in an otherwise open and arid landscape. Taken together, this study highlights that fine-scale spatial habitat heterogeneities can be preserved by biomarkers in paleosols over geologic timescales.

  20. Variability in Thyroid-Stimulating Hormone Suppression by Human Chronic Gonadotropin during Early Pregnancy

    PubMed Central

    Haddow, James E.; McClain, Monica R.; Lambert-Messerlian, Geralyn; Palomaki, Glenn E.; Canick, Jacob A.; Cleary-Goldman, Jane; Malone, Fergal D.; Porter, T. Flint; Nyberg, David A.; Bernstein, Peter; D'Alton, Mary E.

    2008-01-01

    Objective: The objective of the study was to further explore relationships between human chorionic gonadotropin (hCG), TSH, and free T4 in pregnant women at 11 through 18 wk gestation. Study Design: The design of the study was to analyze hCG in comparison with TSH and free T4, in paired first- and second-trimester sera from 9562 women in the First and Second Trimester Evaluation of Risk for Fetal Aneuploidy trial study. Results: hCG is strongly correlated with body mass index, smoking, and gravidity. Correlations with selected maternal covariates also exist for TSH and free T4. As hCG deciles increase, body mass index and percent of women who smoke both decrease, whereas the percent of primigravid women increases (P < 0.0001). hCG/TSH correlations are weak in both trimesters (r2 = 0.03 and r2 = 0.02). TSH concentrations at the 25th and fifth centiles become sharply lower at higher hCG levels, whereas 50th centile and above TSH concentrations are only slightly lower. hCG/free T4 correlations are weak in both trimesters (r2 = 0.06 and r2 = 0.003). At 11–13 wk gestation, free T4 concentrations rise uniformly at all centiles, as hCG increases (test for trend, P < 0.0001), but not at 15–18 wk gestation. Multivariate analyses with TSH and free T4 as dependent variables and selected maternal covariates and hCG as independent variables do not alter these observations. Conclusions: In early pregnancy, a woman’s centile TSH level appears to determine susceptibility to the TSH being suppressed at any given hCG level, suggesting that hCG itself may be the primary analyte responsible for stimulating the thyroid gland. hCG affects lower centile TSH values disproportionately. PMID:18544616

  1. Early suppressive mechanisms and the negative BOLD response in human visual cortex

    PubMed Central

    Wade, Alex R.; Rowland, Jess

    2010-01-01

    Functional magnetic resonance imaging (fMRI) studies of early sensory cortex often measure stimulus-driven increases in the blood oxygenation level-dependent (BOLD) signal. However, these positive responses are frequently accompanied by reductions in the BOLD signal in adjacent regions of cortex. Although this negative BOLD response (NBR) is thought to result from neuronal suppression, the precise relationship between local activity, suppression and perception remains unknown. By measuring BOLD signals in human primary visual cortex while varying the baseline contrast levels in the region affected by the NBR, we tested three physiologically-plausible computational models of neuronal modulation which could explain this phenomenon: a subtractive model, a response gain model and a contrast gain model. We also measured the ability of isoluminant contrast to generate an NBR. We show that the NBR can be modeled as a pathway-specific contrast gain modulation that is strongest outside the fovea. We found a similar spatial bias in a psychophysical study using identical stimuli, although these data indicated a response- rather than a contrast-gain mechanism. We reconcile these findings by proposing 1) that the NBR is associated with a long-range suppressive mechanism that hyperpolarizes a subset of magnocellularly-driven neurons at the input to V1; 2) that this suppression is broadly-tuned to match the spatial features of the mask region; 3) that increasing the baseline contrast in the suppressed region drives all neurons in the input layer, reducing the relative contribution of the suppressing subpopulation in the fMRI signal. PMID:20371821

  2. Estimation of left ventricular operating stiffness from Doppler early filling deceleration time in humans

    NASA Technical Reports Server (NTRS)

    Garcia, M. J.; Firstenberg, M. S.; Greenberg, N. L.; Smedira, N.; Rodriguez, L.; Prior, D.; Thomas, J. D.

    2001-01-01

    Shortened early transmitral deceleration times (E(DT)) have been qualitatively associated with increased filling pressure and reduced survival in patients with cardiac disease and increased left ventricular operating stiffness (K(LV)). An equation relating K(LV) quantitatively to E(DT) has previously been described in a canine model but not in humans. During several varying hemodynamic conditions, we studied 18 patients undergoing open-heart surgery. Transesophageal echocardiographic two-dimensional volumes and Doppler flows were combined with high-fidelity left atrial (LA) and left ventricular (LV) pressures to determine K(LV). From digitized Doppler recordings, E(DT) was measured and compared against changes in LV and LA diastolic volumes and pressures. E(DT) (180 +/- 39 ms) was inversely associated with LV end-diastolic pressures (r = -0.56, P = 0.004) and net atrioventricular stiffness (r = -0.55, P = 0.006) but had its strongest association with K(LV) (r = -0.81, P < 0.001). K(LV) was predicted assuming a nonrestrictive orifice (K(nonrest)) from E(DT) as K(nonrest) = (0.07/E(DT))(2) with K(LV) = 1.01 K(nonrest) - 0.02; r = 0.86, P < 0.001, DeltaK (K(nonrest) - K(LV)) = 0.02 +/- 0.06 mm Hg/ml. In adults with cardiac disease, E(DT) provides an accurate estimate of LV operating stiffness and supports its application as a practical noninvasive index in the evaluation of diastolic function.

  3. Early developmental gene enhancers affect subcortical volumes in the adult human brain.

    PubMed

    Becker, Martin; Guadalupe, Tulio; Franke, Barbara; Hibar, Derrek P; Renteria, Miguel E; Stein, Jason L; Thompson, Paul M; Francks, Clyde; Vernes, Sonja C; Fisher, Simon E

    2016-05-01

    Genome-wide association screens aim to identify common genetic variants contributing to the phenotypic variability of complex traits, such as human height or brain morphology. The identified genetic variants are mostly within noncoding genomic regions and the biology of the genotype-phenotype association typically remains unclear. In this article, we propose a complementary targeted strategy to reveal the genetic underpinnings of variability in subcortical brain volumes, by specifically selecting genomic loci that are experimentally validated forebrain enhancers, active in early embryonic development. We hypothesized that genetic variation within these enhancers may affect the development and ultimately the structure of subcortical brain regions in adults. We tested whether variants in forebrain enhancer regions showed an overall enrichment of association with volumetric variation in subcortical structures of >13,000 healthy adults. We observed significant enrichment of genomic loci that affect the volume of the hippocampus within forebrain enhancers (empirical P = 0.0015), a finding which robustly passed the adjusted threshold for testing of multiple brain phenotypes (cutoff of P < 0.0083 at an alpha of 0.05). In analyses of individual single nucleotide polymorphisms (SNPs), we identified an association upstream of the ID2 gene with rs7588305 and variation in hippocampal volume. This SNP-based association survived multiple-testing correction for the number of SNPs analyzed but not for the number of subcortical structures. Targeting known regulatory regions offers a way to understand the underlying biology that connects genotypes to phenotypes, particularly in the context of neuroimaging genetics. This biology-driven approach generates testable hypotheses regarding the functional biology of identified associations. Hum Brain Mapp 37:1788-1800, 2016. © 2016 Wiley Periodicals, Inc. PMID:26890892

  4. Differential oxidative status and immune characterization of the early and advanced stages of human breast cancer.

    PubMed

    Panis, C; Victorino, V J; Herrera, A C S A; Freitas, L F; De Rossi, T; Campos, F C; Simão, A N Colado; Barbosa, D S; Pinge-Filho, P; Cecchini, R; Cecchini, A L

    2012-06-01

    Breast cancer is the malignant neoplasia with the highest incidence in women worldwide. Chronic oxidative stress and inflammation have been indicated as major mediators during carcinogenesis and cancer progression. Human studies have not considered the complexity of tumor biology during the stages of cancer advance, limiting their clinical application. The purpose of this study was to characterize systemic oxidative stress and immune response parameters in early (ED; TNM I and II) and advanced disease (AD; TNM III and IV) of patients diagnosed with infiltrative ductal carcinoma breast cancer. Oxidative stress parameters were evaluated by plasmatic lipoperoxidation, carbonyl content, thiobarbituric reactive substances (TBARS), nitric oxide levels (NO), total radical antioxidant parameter (TRAP), superoxide dismutase, and catalase activities and GSH levels. Immune evaluation was determined by TNF-α, IL-1β, IL-12, and IL-10 levels and leukocytes oxidative burst evaluation by chemiluminescence. Tissue damage analysis included heart (total CK and CKMB), liver (AST, ALT, GGT), and renal (creatinine, urea, and uric acid) plasmatic markers. C-reactive protein (CRP) and iron metabolism were also evaluated. Analysis of the results verified different oxidative stress statuses occur at distinct cancer stages. ED was characterized by reduction in catalase, 8-isoprostanes, and GSH levels, with enhanced lipid peroxidation and TBARS levels. AD exhibited more pronounced oxidative status, with reduction in catalase activity and TRAP, intense lipid peroxidation and high levels of NO, TBARs, and carbonyl content. ED patients presented a Th2 immune pattern, while AD exhibited Th1 status. CRP levels and ferritin were increased in both stages of disease. Leukocytes burst impairment was observed in both the groups. Plasma iron levels were significantly elevated in AD. The data obtained indicated that oxidative stress enhancement and immune response impairment may be necessary to ensure

  5. DHCR7 mutations linked to higher vitamin D status allowed early human migration to Northern latitudes

    PubMed Central

    2013-01-01

    Background Vitamin D is essential for a wide range of physiological processes including immune function and calcium homeostasis. Recent investigations have identified candidate genes which are strongly linked to concentrations of 25-hydroxyvitamin D. Since there is insufficient UVB radiation to induce year-round cutaneous synthesis of vitamin D at latitudes distant from the equator it is likely that these genes were subject to forces of natural selection. We used the fixation index (FST) to measure differences in allele frequencies in 993 individuals from ten populations to identify the presence of evolutionary selection in genes in the vitamin D pathway. We then explored the length of haplotypes in chromosomes to confirm recent positive selection. Results We find evidence of positive selection for DHCR7, which governs availability of 7-dehydrocholesterol for conversion to vitamin D3 by the action of sunlight on the skin. We show that extended haplotypes related to vitamin D status are highly prevalent at Northern latitudes (Europe 0.72, Northeast Asia 0.41). The common DHCR7 haplotype underwent a recent selective sweep in Northeast Asia, with relative extended haplotype homozygosity of 5.03 (99th percentile). In contrast, CYP2R1, which 25-hydroxylates vitamin D, is under balancing selection and we found no evidence of recent selection pressure on GC, which is responsible for vitamin D transport. Conclusions Our results suggest that genetic variation in DHCR7 is the major adaptation affecting vitamin D metabolism in recent evolutionary history which helped early humans to avoid severe vitamin D deficiency and enabled them to inhabit areas further from the equator. PMID:23837623

  6. NDUFAF5 Hydroxylates NDUFS7 at an Early Stage in the Assembly of Human Complex I*

    PubMed Central

    Rhein, Virginie F.; Carroll, Joe; Ding, Shujing; Fearnley, Ian M.; Walker, John E.

    2016-01-01

    Complex I (NADH ubiquinone oxidoreductase) in mammalian mitochondria is an L-shaped assembly of 45 proteins. One arm lies in the inner membrane, and the other extends about 100 Å into the matrix of the organelle. The extrinsic arm contains binding sites for NADH, the primary electron acceptor FMN, and seven iron-sulfur clusters that form a pathway for electrons linking FMN to the terminal electron acceptor, ubiquinone, which is bound in a tunnel in the region of the junction between the arms. The membrane arm contains four antiporter-like domains, energetically coupled to the quinone site and involved in pumping protons from the matrix into the intermembrane space contributing to the proton motive force. Seven of the subunits, forming the core of the membrane arm, are translated from mitochondrial genes, and the remaining subunits, the products of nuclear genes, are imported from the cytosol. Their assembly is coordinated by at least thirteen extrinsic assembly factor proteins that are not part of the fully assembled complex. They assist in insertion of co-factors and in building up the complex from smaller sub-assemblies. One such factor, NDUFAF5, belongs to the family of seven-β-strand S-adenosylmethionine-dependent methyltransferases. However, similar to another family member, RdmB, it catalyzes the introduction of a hydroxyl group, in the case of NDUFAF5, into Arg-73 in the NDUFS7 subunit of human complex I. This modification occurs early in the pathway of assembly of complex I, before the formation of the juncture between peripheral and membrane arms. PMID:27226634

  7. NDUFAF5 Hydroxylates NDUFS7 at an Early Stage in the Assembly of Human Complex I.

    PubMed

    Rhein, Virginie F; Carroll, Joe; Ding, Shujing; Fearnley, Ian M; Walker, John E

    2016-07-01

    Complex I (NADH ubiquinone oxidoreductase) in mammalian mitochondria is an L-shaped assembly of 45 proteins. One arm lies in the inner membrane, and the other extends about 100 Å into the matrix of the organelle. The extrinsic arm contains binding sites for NADH, the primary electron acceptor FMN, and seven iron-sulfur clusters that form a pathway for electrons linking FMN to the terminal electron acceptor, ubiquinone, which is bound in a tunnel in the region of the junction between the arms. The membrane arm contains four antiporter-like domains, energetically coupled to the quinone site and involved in pumping protons from the matrix into the intermembrane space contributing to the proton motive force. Seven of the subunits, forming the core of the membrane arm, are translated from mitochondrial genes, and the remaining subunits, the products of nuclear genes, are imported from the cytosol. Their assembly is coordinated by at least thirteen extrinsic assembly factor proteins that are not part of the fully assembled complex. They assist in insertion of co-factors and in building up the complex from smaller sub-assemblies. One such factor, NDUFAF5, belongs to the family of seven-β-strand S-adenosylmethionine-dependent methyltransferases. However, similar to another family member, RdmB, it catalyzes the introduction of a hydroxyl group, in the case of NDUFAF5, into Arg-73 in the NDUFS7 subunit of human complex I. This modification occurs early in the pathway of assembly of complex I, before the formation of the juncture between peripheral and membrane arms. PMID:27226634

  8. Combined Genetic and Genealogic Studies Uncover a Large BAP1 Cancer Syndrome Kindred Tracing Back Nine Generations to a Common Ancestor from the 1700s

    PubMed Central

    Johnson, Todd A.; Tsunoda, Tatsuhiko; Behner, Dusty; Hoffman, Harriet; Hesdorffer, Mary; Nasu, Masaki; Napolitano, Andrea; Powers, Amy; Minaai, Michael; Baumann, Francine; Bryant-Greenwood, Peter; Lauk, Olivia; Kirschner, Michaela B.; Weder, Walter; Opitz, Isabelle; Pass, Harvey I.; Gaudino, Giovanni; Pastorino, Sandra; Yang, Haining

    2015-01-01

    We recently discovered an inherited cancer syndrome caused by BRCA1-Associated Protein 1 (BAP1) germline mutations, with high incidence of mesothelioma, uveal melanoma and other cancers and very high penetrance by age 55. To identify families with the BAP1 cancer syndrome, we screened patients with family histories of multiple mesotheliomas and melanomas and/or multiple cancers. We identified four families that shared an identical BAP1 mutation: they lived across the US and did not appear to be related. By combining family histories, molecular genetics, and genealogical approaches, we uncovered a BAP1 cancer syndrome kindred of ~80,000 descendants with a core of 106 individuals, whose members descend from a couple born in Germany in the early 1700s who immigrated to North America. Their descendants spread throughout the country with mutation carriers affected by multiple malignancies. Our data show that, once a proband is identified, extended analyses of these kindreds, using genomic and genealogical studies to identify the most recent common ancestor, allow investigators to uncover additional branches of the family that may carry BAP1 mutations. Using this knowledge, we have identified new branches of this family carrying BAP1 mutations. We have also implemented early-detection strategies that help identify cancers at early-stage, when they can be cured (melanomas) or are more susceptible to therapy (MM and other malignancies). PMID:26683624

  9. Combined Genetic and Genealogic Studies Uncover a Large BAP1 Cancer Syndrome Kindred Tracing Back Nine Generations to a Common Ancestor from the 1700s.

    PubMed

    Carbone, Michele; Flores, Erin G; Emi, Mitsuru; Johnson, Todd A; Tsunoda, Tatsuhiko; Behner, Dusty; Hoffman, Harriet; Hesdorffer, Mary; Nasu, Masaki; Napolitano, Andrea; Powers, Amy; Minaai, Michael; Baumann, Francine; Bryant-Greenwood, Peter; Lauk, Olivia; Kirschner, Michaela B; Weder, Walter; Opitz, Isabelle; Pass, Harvey I; Gaudino, Giovanni; Pastorino, Sandra; Yang, Haining

    2015-12-01

    We recently discovered an inherited cancer syndrome caused by BRCA1-Associated Protein 1 (BAP1) germline mutations, with high incidence of mesothelioma, uveal melanoma and other cancers and very high penetrance by age 55. To identify families with the BAP1 cancer syndrome, we screened patients with family histories of multiple mesotheliomas and melanomas and/or multiple cancers. We identified four families that shared an identical BAP1 mutation: they lived across the US and did not appear to be related. By combining family histories, molecular genetics, and genealogical approaches, we uncovered a BAP1 cancer syndrome kindred of ~80,000 descendants with a core of 106 individuals, whose members descend from a couple born in Germany in the early 1700s who immigrated to North America. Their descendants spread throughout the country with mutation carriers affected by multiple malignancies. Our data show that, once a proband is identified, extended analyses of these kindreds, using genomic and genealogical studies to identify the most recent common ancestor, allow investigators to uncover additional branches of the family that may carry BAP1 mutations. Using this knowledge, we have identified new branches of this family carrying BAP1 mutations. We have also implemented early-detection strategies that help identify cancers at early-stage, when they can be cured (melanomas) or are more susceptible to therapy (MM and other malignancies). PMID:26683624

  10. The 6-Aminoquinolone WC5 Inhibits Human Cytomegalovirus Replication at an Early Stage by Interfering with the Transactivating Activity of Viral Immediate-Early 2 Protein ▿ †

    PubMed Central

    Loregian, Arianna; Mercorelli, Beatrice; Muratore, Giulia; Sinigalia, Elisa; Pagni, Silvana; Massari, Serena; Gribaudo, Giorgio; Gatto, Barbara; Palumbo, Manlio; Tabarrini, Oriana; Cecchetti, Violetta; Palù, Giorgio

    2010-01-01

    WC5 is a 6-aminoquinolone that potently inhibits the replication of human cytomegalovirus (HCMV) but has no activity, or significantly less activity, against other herpesviruses. Here we investigated the nature of its specific anti-HCMV activity. Structure-activity relationship studies on a small series of analogues showed that WC5 possesses the most suitable pattern of substitutions around the quinolone scaffold to give potent and selective anti-HCMV activity. Studies performed to identify the possible target of WC5 indicated that it prevents viral DNA synthesis but does not significantly affect DNA polymerase activity. In yield reduction experiments with different multiplicities of infection, the anti-HCMV activity of WC5 appeared to be highly dependent on the viral inoculum, suggesting that WC5 may act at an initial stage of virus replication. Consistently, time-of-addition and time-of-removal studies demonstrated that WC5 affects a phase of the HCMV replicative cycle that precedes viral DNA synthesis. Experiments to monitor the effects of the compound on virus attachment and entry showed that it does not inhibit either process. Evaluation of viral mRNA and protein expression revealed that WC5 targets an event of the HCMV replicative cycle that follows the transcription and translation of immediate-early genes and precedes those of early and late genes. In cell-based assays to test the effects of WC5 on the transactivating activity of the HCMV immediate-early 2 (IE2) protein, WC5 markedly interfered with IE2-mediated transactivation of viral early promoters. Finally, WC5 combined with ganciclovir in checkerboard experiments exhibited highly synergistic activity. These findings suggest that WC5 deserves further investigation as a candidate anti-HCMV drug with a novel mechanism of action. PMID:20194695

  11. Educating Human Nature: "Nature" and "Nurture" in Early Confucian Moral Education

    ERIC Educational Resources Information Center

    Murray, Judson B.

    2012-01-01

    This study examines early Chinese moral education--its curriculum, objectives and the philosophical assumptions underlying them--in its classical Confucian expression. It analyzes early Confucian debates on moral psychology, the Confucian moral curriculum consisting of model emulation, cultural practices and canonical instruction, and the methods…

  12. Design Choices: Universal Financing for Early Care and Education. Human Services Policy Center Policy Brief.

    ERIC Educational Resources Information Center

    Brandon, Richard N.; Kagan, Sharon Lynn; Joesch, Jutta M.

    This policy brief describes the components of a computer model to compare different financing approaches for universal early care and education programs as developed by the Financing Universal Early Care and Education (ECE) for America's Children Project. The brief also discusses lessons learned from analyzing key features of existing…

  13. Studies in Historical Replication in Psychology VII: The Relative Utility of "Ancestor Analysis" from Scientific and Educational Vantages

    ERIC Educational Resources Information Center

    Ranney, Michael Andrew

    2008-01-01

    This article discusses, from various vantages, Ryan Tweney's (this issue) pedagogical technique of employing historical replications of psychological experiments with graduate students in psychology. A "prima facie" perspective suggests great promise for this sort of academic "ancestor analysis," particularly given the enthusiasm and skill…

  14. The Last Universal Common Ancestor: emergence, constitution and genetic legacy of an elusive forerunner

    PubMed Central

    Glansdorff, Nicolas; Xu, Ying; Labedan, Bernard

    2008-01-01

    Background Since the reclassification of all life forms in three Domains (Archaea, Bacteria, Eukarya), the identity of their alleged forerunner (Last Universal Common Ancestor or LUCA) has been the subject of extensive controversies: progenote or already complex organism, prokaryote or protoeukaryote, thermophile or mesophile, product of a protracted progression from simple replicators to complex cells or born in the cradle of "catalytically closed" entities? We present a critical survey of the topic and suggest a scenario. Results LUCA does not appear to have been a simple, primitive, hyperthermophilic prokaryote but rather a complex community of protoeukaryotes with a RNA genome, adapted to a broad range of moderate temperatures, genetically redundant, morphologically and metabolically diverse. LUCA's genetic redundancy predicts loss of paralogous gene copies in divergent lineages to be a significant source of phylogenetic anomalies, i.e. instances where a protein tree departs from the SSU-rRNA genealogy; consequently, horizontal gene transfer may not have the rampant character assumed by many. Examining membrane lipids suggest LUCA had sn1,2 ester fatty acid lipids from which Archaea emerged from the outset as thermophilic by "thermoreduction," with a new type of membrane, composed of sn2,3 ether isoprenoid lipids; this occurred without major enzymatic reconversion. Bacteria emerged by reductive evolution from LUCA and some lineages further acquired extreme thermophily by convergent evolution. This scenario is compatible with the hypothesis that the RNA to DNA transition resulted from different viral invasions as proposed by Forterre. Beyond the controversy opposing "replication first" to metabolism first", the predictive arguments of theories on "catalytic closure" or "compositional heredity" heavily weigh in favour of LUCA's ancestors having emerged as complex, self-replicating entities from which a genetic code arose under natural selection. Conclusion Life

  15. Practical halving; the Nelumbo nucifera evidence on early eudicot evolution.

    PubMed

    Zheng, Chunfang; Sankoff, David

    2014-06-01

    We present a stepwise optimal genome halving algorithm designed for large eukaryote genomes with largely single-copy genes, taking advantage of a signature pattern of paralog distribution in ancient polyploids. This is applied to the genome of Nelumbo nucifera, the sacred lotus, which is the descendant of a duplicated basal eudicot genome. In concert with the reconstructed ancestor of the grape, we investigate early events in eudicot evolution and show that the chromosome number of the common ancestor of lotus and grape was likely between 5 and 7. We show that the duplication of the ancestor of lotus and the triplication of the ancestor of grape were not closely preceded by any additional such event before the divergence of their two lineages. PMID:24525373

  16. Edaphics, active tectonics and animal movements in the Kenyan Rift - implications for early human evolution and dispersal

    NASA Astrophysics Data System (ADS)

    Kübler, Simon; Owenga, Peter; Rucina, Stephen; King, Geoffrey C. P.

    2014-05-01

    The quality of soils (edaphics) and the associated vegetation strongly controls the health of grazing animals. Until now, this has hardly been appreciated by paleo-anthropologists who only take into account the availability of water and vegetation in landscape reconstruction attempts. A lack of understanding the importance of the edaphics of a region greatly limits interpretations of the relation between our ancestors and animals over the last few million years. If a region lacks vital trace elements then wild grazing and browsing animals will avoid it and go to considerable length and take major risks to seek out better pasture. As a consequence animals must move around the landscape at different times of the year. In complex landscapes, such as tectonically active rifts, hominins can use advanced group behaviour to gain strategic advantage for hunting. Our study in the southern Kenya rift in the Lake Magadi region shows that the edaphics and active rift structures play a key role in present day animal movements as well as the for the location of an early hominin site at Mt. Olorgesailie. We carried out field analysis based on studying the relationship between the geology and soil development as well as the tectonic geomorphology to identify 'good' and 'bad' regions both in terms of edaphics and accessibility for grazing animals. We further sampled different soils that developed on the volcanic bedrock and sediment sources of the region and interviewed the local Maasai shepherds to learn about present-day good and bad grazing sites. At the Olorgesailie site the rift valley floor is covered with flood trachytes; basalts only occur at Mt. Olorgesailie and farther east up the rift flank. The hominin site is located in lacustrine sediments at the southern edge of a playa that extends north and northwest of Mt. Olorgesailie. The lakebeds are now tilted and eroded by motion on two north-south striking faults. The lake was trapped by basalt flows from Mt. Olorgesailie

  17. Plio-Pleistocene vegetation response on orbitally forced climatic cycles in Southern Europe - implications for early human environments

    NASA Astrophysics Data System (ADS)

    Bruch, Angela; Bertini, Adele

    2013-04-01

    The pace and causes of the early human colonization, in one or several migratory waves from Africa in new environments of the Eurasian continent during the Early Pleistocene, are still a matter of debate. However, climate change is considered a major driving factor of hominin evolution and dispersal patterns. In fact directly or indirectly by its severe influence on vegetation, physiography of landscape, and animal distribution, climate modulates the availability of resources. Plant fossils usually are rare or even absent at hominin sites. Thus, direct evidence on local vegetation and environment is generally missing. Independent from such localities, pollen profiles from the Mediterranean realm show the response of regional vegetation on global climate changes and cyclicity, with distinct spatial and temporal differences. Furthermore, plant fossils provide proxies for climate quantification that can be compared to the global signal, and add data to understanding the regional differentiation of Mediterranean environments. In this presentation we will discuss various palaeobotanical data from Southern Europe to assess Early Pleistocene climate and vegetation in time and space as part of the environment during the first expansions of early humans out of Africa.

  18. Fossils, feet and the evolution of human bipedal locomotion.

    PubMed

    Harcourt-Smith, W E H; Aiello, L C

    2004-05-01

    We review the evolution of human bipedal locomotion with a particular emphasis on the evolution of the foot. We begin in the early twentieth century and focus particularly on hypotheses of an ape-like ancestor for humans and human bipedal locomotion put forward by a succession of Gregory, Keith, Morton and Schultz. We give consideration to Morton's (1935) synthesis of foot evolution, in which he argues that the foot of the common ancestor of modern humans and the African apes would be intermediate between the foot of Pan and Hylobates whereas the foot of a hypothetical early hominin would be intermediate between that of a gorilla and a modern human. From this base rooted in comparative anatomy of living primates we trace changing ideas about the evolution of human bipedalism as increasing amounts of postcranial fossil material were discovered. Attention is given to the work of John Napier and John Robinson who were pioneers in the interpretation of Plio-Pleistocene hominin skeletons in the 1960s. This is the period when the wealth of evidence from the southern African australopithecine sites was beginning to be appreciated and Olduvai Gorge was revealing its first evidence for Homo habilis. In more recent years, the discovery of the Laetoli footprint trail, the AL 288-1 (A. afarensis) skeleton, the wealth of postcranial material from Koobi Fora, the Nariokotome Homo ergaster skeleton, Little Foot (Stw 573) from Sterkfontein in South Africa, and more recently tantalizing material assigned to the new and very early taxa Orrorin tugenensis, Ardipithecus ramidus and Sahelanthropus tchadensis has fuelled debate and speculation. The varying interpretations based on this material, together with changing theoretical insights and analytical approaches, is discussed and assessed in the context of new three-dimensional morphometric analyses of australopithecine and Homo foot bones, suggesting that there may have been greater diversity in human bipedalism in the earlier phases

  19. Fossils, feet and the evolution of human bipedal locomotion

    PubMed Central

    Harcourt-Smith, W E H; Aiello, L C

    2004-01-01

    We review the evolution of human bipedal locomotion with a particular emphasis on the evolution of the foot. We begin in the early twentieth century and focus particularly on hypotheses of an ape-like ancestor for humans and human bipedal locomotion put forward by a succession of Gregory, Keith, Morton and Schultz. We give consideration to Morton's (1935) synthesis of foot evolution, in which he argues that the foot of the common ancestor of modern humans and the African apes would be intermediate between the foot of Pan and Hylobates whereas the foot of a hypothetical early hominin would be intermediate between that of a gorilla and a modern human. From this base rooted in comparative anatomy of living primates we trace changing ideas about the evolution of human bipedalism as increasing amounts of postcranial fossil material were discovered. Attention is given to the work of John Napier and John Robinson who were pioneers in the interpretation of Plio-Pleistocene hominin skeletons in the 1960s. This is the period when the wealth of evidence from the southern African australopithecine sites was beginning to be appreciated and Olduvai Gorge was revealing its first evidence for Homo habilis. In more recent years, the discovery of the Laetoli footprint trail, the AL 288-1 (A. afarensis) skeleton, the wealth of postcranial material from Koobi Fora, the Nariokotome Homo ergaster skeleton, Little Foot (Stw 573) from Sterkfontein in South Africa, and more recently tantalizing material assigned to the new and very early taxa Orrorin tugenensis, Ardipithecus ramidus and Sahelanthropus tchadensis has fuelled debate and speculation. The varying interpretations based on this material, together with changing theoretical insights and analytical approaches, is discussed and assessed in the context of new three-dimensional morphometric analyses of australopithecine and Homo foot bones, suggesting that there may have been greater diversity in human bipedalism in the earlier phases

  20. Early Impacts of a Human-in-the-Loop Evaluation in a Space Vehicle Mock-up Facility

    NASA Technical Reports Server (NTRS)

    Byrne, Vicky; Vos, Gordon; Whitmore, Mihriban

    2008-01-01

    The development of a new space vehicle, the Orion Crew Exploration Vehicle (CEV), provides Human Factors engineers an excellent opportunity to have an impact early in the design process. This case study highlights a Human-in-the-Loop (HITL) evaluation conducted in a Space Vehicle Mock-Up Facility and will describe the human-centered approach and how the findings are impacting design and operational concepts early in space vehicle design. The focus of this HITL evaluation centered on the activities that astronaut crewmembers would be expected to perform within the functional internal volume of the Crew Module (CM) of the space vehicle. The primary objective was to determine if there are aspects of a baseline vehicle configuration that would limit or prevent the performance of dynamically volume-driving activities (e.g. six crewmembers donning their suits in an evacuation scenario). A second objective was to step through concepts of operations for known systems and evaluate them in integrated scenarios. The functional volume for crewmember activities is closely tied to every aspect of system design (e.g. avionics, safety, stowage, seats, suits, and structural support placement). As this evaluation took place before the Preliminary Design Review of the space vehicle with some designs very early in the development, it was not meant to determine definitely that the crewmembers could complete every activity, but rather to provide inputs that could improve developing designs and concepts of operations definition refinement.

  1. Regulation of early human growth: impact on long-term health.

    PubMed

    Koletzko, Berthold; Chourdakis, Michael; Grote, Veit; Hellmuth, Christian; Prell, Christine; Rzehak, Peter; Uhl, Olaf; Weber, Martina

    2014-01-01

    Growth and development are central characteristics of childhood. Deviations from normal growth can indicate serious health challenges. The adverse impact of early growth faltering and malnutrition on later health has long been known. In contrast, the impact of rapid early weight and body fat gain on programming of later disease risk have only recently received increased attention. Numerous observational studies related diet in early childhood and rapid early growth to the risk of later obesity and associated disorders. Causality was confirmed in a large, double-blind randomised trial testing the 'Early Protein Hypothesis'. In this trial we found that attenuation of protein supply in infancy normalized early growth and markedly reduced obesity prevalence in early school age. These results indicate the need to describe and analyse growth patterns and their regulation through diet in more detail and to characterize the underlying metabolic and epigenetic mechanisms, given the potential major relevance for public health and policy. Better understanding of growth patterns and their regulation could have major benefits for the promotion of public health, consumer-orientated nutrition recommendations, and the development of improved food products for specific target populations. PMID:25413647

  2. Polyploids with different origins and ancestors form a single sexual polyploid species.

    PubMed

    Holloway, Alisha K; Cannatella, David C; Gerhardt, H Carl; Hillis, David M

    2006-04-01

    Polyploidization is one of the few mechanisms that can produce instantaneous speciation. Multiple origins of tetraploid lineages from the same two diploid progenitors are common, but here we report the first known instance of a single tetraploid species that originated repeatedly from at least three diploid ancestors. Parallel evolution of advertisement calls in tetraploid lineages of gray tree frogs has allowed these lineages to interbreed, resulting in a single sexually interacting polyploid species despite the separate origins of polyploids from different diploids. Speciation by polyploidization in these frogs has been the source of considerable debate, but the various published hypotheses have assumed that polyploids arose through either autopolyploidy or allopolyploidy of extant diploid species. We utilized molecular markers and advertisement calls to infer the origins of tetraploid gray tree frogs. Previous hypotheses did not sufficiently account for the observed data. Instead, we found that tetraploids originated multiple times from extant diploid gray tree frogs and two other, apparently extinct, lineages of tree frogs. Tetraploid lineages then merged through interbreeding to result in a single species. Thus, polyploid species may have complex origins, especially in systems in which isolating mechanisms (such as advertisement calls) are affected directly through hybridization and polyploidy. PMID:16670990

  3. A Universal Trend among Proteomes Indicates an Oily Last Common Ancestor

    PubMed Central

    Mannige, Ranjan V.; Brooks, Charles L.; Shakhnovich, Eugene I.

    2012-01-01

    Despite progresses in ancestral protein sequence reconstruction, much needs to be unraveled about the nature of the putative last common ancestral proteome that served as the prototype of all extant lifeforms. Here, we present data that indicate a steady decline (oil escape) in proteome hydrophobicity over species evolvedness (node number) evident in 272 diverse proteomes, which indicates a highly hydrophobic (oily) last common ancestor (LCA). This trend, obtained from simple considerations (free from sequence reconstruction methods), was corroborated by regression studies within homologous and orthologous protein clusters as well as phylogenetic estimates of the ancestral oil content. While indicating an inherent irreversibility in molecular evolution, oil escape also serves as a rare and universal reaction-coordinate for evolution (reinforcing Darwin's principle of Common Descent), and may prove important in matters such as (i) explaining the emergence of intrinsically disordered proteins, (ii) developing composition- and speciation-based “global” molecular clocks, and (iii) improving the statistical methods for ancestral sequence reconstruction. PMID:23300421

  4. How Old Is the Most Recent Ancestor of Two Copies of an Allele?

    PubMed Central

    Patterson, Nick J.

    2005-01-01

    An important clue to the evolutionary history of an allele is the structure of the neighboring region of the genome, which we term the genomic background of the allele. Consider two copies of the allele. How similar we expect their genomic background to be is strongly influenced by the age of their most recent common ancestor (MRCA). We apply diffusion theory, first used by Motoo Kimura as a tool for predicting the changes in allele frequencies over time and developed by him in many articles in this journal, to prove a variety of new results on the age of the MRCA under the simplest demographic assumptions. In particular, we show that the expected age of the MRCA of two copies of an allele with population frequency f is just 2Nf generations, where N is the effective population size. Our results are a first step in running exact coalescent simulations, where we also simulate the history of the population frequency of an allele. PMID:15520271

  5. Buoyancy differences among two deepwater ciscoes from the Great Lakes and their putative ancestor

    USGS Publications Warehouse

    Krause, A.E.; Eshenroder, R.L.; Begnoche, L.J.

    2002-01-01

    We analyzed buoyancy in two deepwater ciscoes, Coregonus hoyi and C. kiyi, and in C. artedi, their putative ancestor, and also analyzed how variations in fish weight, water content, and lipid content affected buoyancy. Buoyancy was significantly different among the three species (p < 0.0001). Estimates of percent buoyancy (neutral buoyancy = 0.0%) were: kiyi, 3.8%; hoyi, 4.7%; and artedi, 5.7%. Buoyancy did not change with fish weight alone (p = 0.38). Fish weight was negatively related to water content for all three species (p = 0.037). Lipid content was not significantly different between hoyi and kiyi, but artedi had significantly fewer lipids than hoyi and kiyi (p < 0.10). When artedi was removed from the analysis, fish weight and lipids accounted for 48% of the variation in buoyancy (p = 0.003), fatter hoyi were less dense than leaner hoyi, but fatter and leaner kiyi were no different in density. Our findings provide additional evidence that buoyancy regulation was a speciating mechanism in deepwater ciscoes and that kiyi is more specialized than hoyi for diel-vertical migration in deep water.

  6. Ectomycorrhizal fungi decompose soil organic matter using oxidative mechanisms adapted from saprotrophic ancestors.

    PubMed

    Shah, Firoz; Nicolás, César; Bentzer, Johan; Ellström, Magnus; Smits, Mark; Rineau, Francois; Canbäck, Björn; Floudas, Dimitrios; Carleer, Robert; Lackner, Gerald; Braesel, Jana; Hoffmeister, Dirk; Henrissat, Bernard; Ahrén, Dag; Johansson, Tomas; Hibbett, David S; Martin, Francis; Persson, Per; Tunlid, Anders

    2016-03-01

    Ectomycorrhizal fungi are thought to have a key role in mobilizing organic nitrogen that is trapped in soil organic matter (SOM). However, the extent to which ectomycorrhizal fungi decompose SOM and the mechanism by which they do so remain unclear, considering that they have lost many genes encoding lignocellulose-degrading enzymes that are present in their saprotrophic ancestors. Spectroscopic analyses and transcriptome profiling were used to examine the mechanisms by which five species of ectomycorrhizal fungi, representing at least four origins of symbiosis, decompose SOM extracted from forest soils. In the presence of glucose and when acquiring nitrogen, all species converted the organic matter in the SOM extract using oxidative mechanisms. The transcriptome expressed during oxidative decomposition has diverged over evolutionary time. Each species expressed a different set of transcripts encoding proteins associated with oxidation of lignocellulose by saprotrophic fungi. The decomposition 'toolbox' has diverged through differences in the regulation of orthologous genes, the formation of new genes by gene duplications, and the recruitment of genes from diverse but functionally similar enzyme families. The capacity to oxidize SOM appears to be common among ectomycorrhizal fungi. We propose that the ancestral decay mechanisms used primarily to obtain carbon have been adapted in symbiosis to scavenge nutrients instead. PMID:26527297

  7. Structural Similarities between Thiamin-Binding Protein and Thiaminase-I Suggest a Common Ancestor

    SciTech Connect

    Soriano, Erika V.; Rajashankar, Kanagalaghatta R.; Hanes, Jeremiah W.; Bale, Shridhar; Begley, Tadhg P.; Ealick, Steven E.

    2008-06-30

    ATP-binding cassette (ABC) transporters are responsible for the transport of a wide variety of water-soluble molecules and ions into prokaryotic cells. In Gram-negative bacteria, periplasmic-binding proteins deliver ions or molecules such as thiamin to the membrane-bound ABC transporter. The gene for the thiamin-binding protein tbpA has been identified in both Escherichia coli and Salmonella typhimurium. Here we report the crystal structure of TbpA from E. coli with bound thiamin monophosphate. The structure was determined at 2.25 {angstrom} resolution using single-wavelength anomalous diffraction experiments, despite the presence of nonmerohedral twinning. The crystal structure shows that TbpA belongs to the group II periplasmic-binding protein family. Equilibrium binding measurements showed similar dissociation constants for thiamin, thiamin monophosphate, and thiamin pyrophosphate. Analysis of the binding site by molecular modeling demonstrated how TbpA binds all three forms of thiamin. A comparison of TbpA and thiaminase-I, a thiamin-degrading enzyme, revealed structural similarity between the two proteins, especially in domain 1, suggesting that the two proteins evolved from a common ancestor.

  8. Wild mallards have more "goose-like" bills than their ancestors: a case of anthropogenic influence?

    PubMed

    Söderquist, Pär; Norrström, Joanna; Elmberg, Johan; Guillemain, Matthieu; Gunnarsson, Gunnar

    2014-01-01

    Wild populations of the world's most common dabbling duck, the mallard (Anas platyrhynchos), run the risk of genetic introgression by farmed conspecifics released for hunting purposes. We tested whether bill morphology of free-living birds has changed since large-scale releases of farmed mallards started. Three groups of mallards from Sweden, Norway and Finland were compared: historical wild (before large-scale releases started), present-day wild, and present-day farmed. Higher density of bill lamellae was observed in historical wild mallards (only males). Farmed mallards had wider bills than present-day and historical wild ones. Present-day wild and farmed mallards also had higher and shorter bills than historical wild mallards. Present-day mallards thus tend to have more "goose-like" bills (wider, higher, and shorter) than their ancestors. Our study suggests that surviving released mallards affect morphological traits in wild population by introgression. We discuss how such anthropogenic impact may lead to a maladapted and genetically compromised wild mallard population. Our study system has bearing on other taxa where large-scale releases of conspecifics with 'alien genes' may cause a cryptic invasive process that nevertheless has fitness consequences for individual birds. PMID:25514789

  9. Hybrid apomicts trapped in the ecological niches of their sexual ancestors.

    PubMed

    Mau, Martin; Lovell, John T; Corral, José M; Kiefer, Christiane; Koch, Marcus A; Aliyu, Olawale M; Sharbel, Timothy F

    2015-05-01

    Asexual reproduction is expected to reduce the adaptive potential to novel or changing environmental conditions, restricting or altering the ecological niche of asexual lineages. Asexual lineages of plants and animals are typically polyploid, an attribute that may influence their genetic variation, plasticity, adaptive potential, and niche breadth. The genus Boechera (Brassicaceae) represents an ideal model to test the relative ecological and biogeographic impacts of reproductive mode and ploidy because it is composed of diploid sexual and both diploid and polyploid asexual (i.e., apomictic) lineages. Here, we demonstrate a strong association between a transcriptionally conserved allele and apomictic seed formation. We then use this allele as a proxy apomixis marker in 1,649 accessions to demonstrate that apomixis is likely to be a common feature across the Boechera phylogeny. Phylogeographic analyses of these data demonstrate (i) species-specific niche differentiation in sexuals, (ii) extensive niche conservation between differing reproductive modes of the same species, (iii) ploidy-specific niche differentiation within and among species, and (iv) occasional niche drift between apomicts and their sexual ancestors. We conclude that ploidy is a substantially stronger and more common driver of niche divergence within and across Boechera species although variation in both traits may not necessarily lead to niche evolution on the species scale. PMID:25902513

  10. Hybrid apomicts trapped in the ecological niches of their sexual ancestors

    PubMed Central

    Mau, Martin; Lovell, John T.; Corral, José M.; Kiefer, Christiane; Koch, Marcus A.; Aliyu, Olawale M.; Sharbel, Timothy F.

    2015-01-01

    Asexual reproduction is expected to reduce the adaptive potential to novel or changing environmental conditions, restricting or altering the ecological niche of asexual lineages. Asexual lineages of plants and animals are typically polyploid, an attribute that may influence their genetic variation, plasticity, adaptive potential, and niche breadth. The genus Boechera (Brassicaceae) represents an ideal model to test the relative ecological and biogeographic impacts of reproductive mode and ploidy because it is composed of diploid sexual and both diploid and polyploid asexual (i.e., apomictic) lineages. Here, we demonstrate a strong association between a transcriptionally conserved allele and apomictic seed formation. We then use this allele as a proxy apomixis marker in 1,649 accessions to demonstrate that apomixis is likely to be a common feature across the Boechera phylogeny. Phylogeographic analyses of these data demonstrate (i) species-specific niche differentiation in sexuals, (ii) extensive niche conservation between differing reproductive modes of the same species, (iii) ploidy-specific niche differentiation within and among species, and (iv) occasional niche drift between apomicts and their sexual ancestors. We conclude that ploidy is a substantially stronger and more common driver of niche divergence within and across Boechera species although variation in both traits may not necessarily lead to niche evolution on the species scale. PMID:25902513

  11. Convergent evolution of Hawaiian and Australo-Pacific honeyeaters from distant songbird ancestors.

    PubMed

    Fleischer, Robert C; James, Helen F; Olson, Storrs L

    2008-12-23

    The Hawaiian "honeyeaters," five endemic species of recently extinct, nectar-feeding songbirds in the genera Moho and Chaetoptila, looked and acted like Australasian honeyeaters (Meliphagidae), and no taxonomist since their discovery on James Cook's third voyage has classified them as anything else. We obtained DNA sequences from museum specimens of Moho and Chaetoptila collected in Hawaii 115-158 years ago. Phylogenetic analysis of these sequences supports monophyly of the two Hawaiian genera but, surprisingly, reveals that neither taxon is a meliphagid honeyeater, nor even in the same part of the songbird radiation as meliphagids. Instead, the Hawaiian species are divergent members of a passeridan group that includes deceptively dissimilar families of songbirds (Holarctic waxwings, neotropical silky flycatchers, and palm chats). Here we designate them as a new family, the Mohoidae. A nuclear-DNA rate calibration suggests that mohoids diverged from their closest living ancestor 14-17 mya, coincident with the estimated earliest arrival in Hawaii of a bird-pollinated plant lineage. Convergent evolution, the evolution of similar traits in distantly related taxa because of common selective pressures, is illustrated well by nectar-feeding birds, but the morphological, behavioral, and ecological similarity of the mohoids to the Australasian honeyeaters makes them a particularly striking example of the phenomenon. PMID:19084408

  12. Divergent genetic mechanisms underlie reversals to radial floral symmetry from diverse zygomorphic flowered ancestors

    PubMed Central

    Zhang, Wenheng; Steinmann, Victor W.; Nikolov, Lachezar; Kramer, Elena M.; Davis, Charles C.

    2013-01-01

    Malpighiaceae possess flowers with a unique bilateral symmetry (zygomorphy), which is a hypothesized adaptation associated with specialization on neotropical oil bee pollinators. Gene expression of two representatives of the CYC2 lineage of floral symmetry TCP genes, CYC2A and CYC2B, demarcate the adaxial (dorsal) region of the flower in the characteristic zygomorphic flowers of most Malpighiaceae. Several clades within the family, however, have independently lost their specialized oil bee pollinators and reverted to radial flowers (actinomorphy) like their ancestors. Here, we investigate CYC2 expression associated with four independent reversals to actinomorphy. We demonstrate that these reversals are always associated with alteration of the highly conserved CYC2 expression pattern observed in most New World (NW) Malpighiaceae. In NW Lasiocarpus and Old World (OW) Microsteria, the expression of CYC2-like genes has expanded to include the ventral region of the corolla. Thus, the pattern of gene expression in these species has become radialized, which is comparable to what has been reported in the radial flowered legume clade Cadia. In striking contrast, in NW Psychopterys and OW Sphedamnocarpus, CYC2-like expression is entirely absent or at barely detectable levels. This is more similar to the pattern of CYC2 expression observed in radial flowered Arabidopsis. These results collectively indicate that, regardless of geographic distribution, reversals to similar floral phenotypes in this large tropical angiosperm clade have evolved via different genetic changes from an otherwise highly conserved developmental program. PMID:23970887

  13. Crops gone wild: evolution of weeds and invasives from domesticated ancestors

    PubMed Central

    Ellstrand, Norman C; Heredia, Sylvia M; Leak-Garcia, Janet A; Heraty, Joanne M; Burger, Jutta C; Yao, Li; Nohzadeh-Malakshah, Sahar; Ridley, Caroline E

    2010-01-01

    The evolution of problematic plants, both weeds and invasives, is a topic of increasing interest. Plants that have evolved from domesticated ancestors have certain advantages for study. Because of their economic importance, domesticated plants are generally well-characterized and readily available for ecogenetic comparison with their wild descendants. Thus, the evolutionary history of crop descendants has the potential to be reconstructed in some detail. Furthermore, growing crop progenitors with their problematic descendants in a common environment allows for the identification of significant evolutionary differences that correlate with weediness or invasiveness. We sought well-established examples of invasives and weeds for which genetic and/or ethnobotanical evidence has confirmed their evolution from domesticates. We found surprisingly few cases, only 13. We examine our list for generalizations and then some selected cases to reveal how plant pests have evolved from domesticates. Despite their potential utility, crop descendants remain underexploited for evolutionary study. Promising evolutionary research opportunities for these systems are abundant and worthy of pursuit. PMID:25567942

  14. The evolution of air resonance power efficiency in the violin and its ancestors

    PubMed Central

    Nia, Hadi T.; Jain, Ankita D.; Liu, Yuming; Alam, Mohammad-Reza; Barnas, Roman; Makris, Nicholas C.

    2015-01-01

    The fact that acoustic radiation from a violin at air-cavity resonance is monopolar and can be determined by pure volume change is used to help explain related aspects of violin design evolution. By determining the acoustic conductance of arbitrarily shaped sound holes, it is found that air flow at the perimeter rather than the broader sound-hole area dominates acoustic conductance, and coupling between compressible air within the violin and its elastic structure lowers the Helmholtz resonance frequency from that found for a corresponding rigid instrument by roughly a semitone. As a result of the former, it is found that as sound-hole geometry of the violin's ancestors slowly evolved over centuries from simple circles to complex f-holes, the ratio of inefficient, acoustically inactive to total sound-hole area was decimated, roughly doubling air-resonance power efficiency. F-hole length then slowly increased by roughly 30% across two centuries in the renowned workshops of Amati, Stradivari and Guarneri, favouring instruments with higher air-resonance power, through a corresponding power increase of roughly 60%. By evolution-rate analysis, these changes are found to be consistent with mutations arising within the range of accidental replication fluctuations from craftsmanship limitations with subsequent selection favouring instruments with higher air-resonance power. PMID:25792964

  15. Ascomatal morphogenesis in Myxotrichum arcticum supports the derivation of the Myxotrichaceae from a discomycetous ancestor.

    PubMed

    Tsuneda, A; Currah, R S

    2004-01-01

    Electron microscopy shows that ascomata of Myxotricum arcticum bear a striking resemblance to discocarps in morphogenesis and in previously overlooked aspects of gross morphology. Although mature ascomata of M. arcticum superficially resemble reticuloperidial cleistothecia common in the Onygenales, the bramble-like aggregation of thick-walled hyphae, previously considered to represent a closed peridium, forms a basket-like apothecium that overarches a distinct hymenium of stipitate, protunicate asci interspersed with paraphyses. There is no evidence of asci developing in chains and at different levels as is characteristic of the centrum of many Eurotiomycetes. Instead, more or less globose, stipitate and evanescent asci arise individually from penultimate cells of croziers and develop almost synchronously across a distinct hymenial layer derived from a richly branched network of crozier-bearing hyphae. After dissolution of the ascus wall, ascospores adhere to a membranous sheath that underlies the hymenium. These observations provide strong support for prior suggestions based on molecular phylogenetic comparisons that the Myxotrichaceae recently are derived from a helotialean ancestor. Observations of conidiogenesis show that the typical Oidiodendron anamorph is accompanied by a second conidiogenous form with ampullae and botryose clusters of blastic conidia. PMID:21148882

  16. Tempo and mode in human evolution.

    PubMed Central

    McHenry, H M

    1994-01-01

    The quickening pace of paleontological discovery is matched by rapid developments in geochronology. These new data show that the pattern of morphological change in the hominid lineage was mosaic. Adaptations essential to bipedalism appeared early, but some locomotor features changed much later. Relative to the highly derived postcrania of the earliest hominids, the craniodental complex was quite primitive (i.e., like the reconstructed last common ancestor with the African great apes). The pattern of craniodental change among successively younger species of Hominidae implies extensive parallel evolution between at least two lineages in features related to mastication. Relative brain size increased slightly among successively younger species of Australopithecus, expanded significantly with the appearance of Homo, but within early Homo remained at about half the size of Homo sapiens for almost a million years. Many apparent trends in human evolution may actually be due to the accumulation of relatively rapid shifts in successive species. PMID:8041697

  17. Early-life compartmentalization of human T cell differentiation and regulatory function in mucosal and lymphoid tissues.

    PubMed

    Thome, Joseph J C; Bickham, Kara L; Ohmura, Yoshiaki; Kubota, Masaru; Matsuoka, Nobuhide; Gordon, Claire; Granot, Tomer; Griesemer, Adam; Lerner, Harvey; Kato, Tomoaki; Farber, Donna L

    2016-01-01

    It is unclear how the immune response in early life becomes appropriately stimulated to provide protection while also avoiding excessive activation as a result of diverse new antigens. T cells are integral to adaptive immunity; mouse studies indicate that tissue localization of T cell subsets is important for both protective immunity and immunoregulation. In humans, however, the early development and function of T cells in tissues remain unexplored. We present here an analysis of lymphoid and mucosal tissue T cells derived from pediatric organ donors in the first two years of life, as compared to adult organ donors, revealing early compartmentalization of T cell differentiation and regulation. Whereas adult tissues contain a predominance of memory T cells, in pediatric blood and tissues the main subset consists of naive recent thymic emigrants, with effector memory T cells (T(EM)) found only in the lungs and small intestine. Additionally, regulatory T (T(reg)) cells comprise a high proportion (30-40%) of CD4(+) T cells in pediatric tissues but are present at much lower frequencies (1-10%) in adult tissues. Pediatric tissue T(reg) cells suppress endogenous T cell activation, and early T cell functionality is confined to the mucosal sites that have the lowest T(reg):T(EM) cell ratios, which suggests control in situ of immune responses in early life. PMID:26657141

  18. When Humans Become Animals: Development of the Animal Category in Early Childhood

    ERIC Educational Resources Information Center

    Herrmann, Patricia A.; Medin, Douglas L.; Waxman, Sandra R.

    2012-01-01

    The current study examines 3- and 5-year-olds' representation of the concept we label "animal" and its two nested concepts--"animal"[subscript contrastive] (including only non-human animals) and "animal"[subscript inclusive] (including both humans and non-human animals). Building upon evidence that naming promotes object categorization, we…

  19. Changes of MR and DTI appearance in early human brain development

    NASA Astrophysics Data System (ADS)

    Marc, Cassian; Vachet, Clement; Gerig, Guido; Blocher, Joseph; Gilmore, John; Styner, Martin

    2010-03-01

    Understanding myelination in early brain development is of clinical importance, as many neurological disorders have their origin in early cerebral organization and maturation. The goal of this work is to study a large neonate database acquired with standard MR imagery to illuminate effects of early development in MRI. 90 neonates were selected from a study of healthy brain development. Subjects were imaged via MRI postnatally. MR acquisition included high-resolution structural and diffusion tensor images. Unbiased atlases for structural and DTI data were generated and co-registered into a single coordinate frame for voxel-wise comparison of MR and DTI appearance across time. All original datasets were mapped into this frame and structural image data was additionally intensity normalized. In addition, myelinated white matter probabilistic segmentations from our neonate tissue segmentation were mapped into the same space to study how our segmentation results were affected by the changing intensity characteristics in early development Linear regression maps and p-value maps were computed and visualized. The resulting visualization of voxelswise corresponding maps of all MR and DTI properties captures early development information in MR imagery. Surprisingly, we encountered regions of seemingly decreased myelinated WM probability over time even though we expected a confident increase for all of the brain. The intensity changes in the MR images in those regions help explain this counterintuitive result. The regressional results indicate that this is an effect of intensity changes due not solely to myelination processes but also likely brain dehydration processes in early postnatal development.

  20. The late Early Pleistocene human dental remains from Uadi Aalad and Mulhuli-Amo (Buia), Eritrean Danakil: macromorphology and microstructure.

    PubMed

    Zanolli, Clément; Bondioli, Luca; Coppa, Alfredo; Dean, Christopher M; Bayle, Priscilla; Candilio, Francesca; Capuani, Silvia; Dreossi, Diego; Fiore, Ivana; Frayer, David W; Libsekal, Yosief; Mancini, Lucia; Rook, Lorenzo; Medin Tekle, Tsegai; Tuniz, Claudio; Macchiarelli, Roberto

    2014-09-01

    Fieldwork performed during the last 15 years in various Early Pleistocene East African sites has significantly enlarged the fossil record of Homo erectus sensu lato (s.l.). Additional evidence comes from the Danakil Depression of Eritrea, where over 200 late Early to early Middle Pleistocene sites have been identified within a ∼1000 m-thick sedimentary succession outcropping in the Dandiero Rift Basin, near Buia. Along with an adult cranium (UA 31), which displays a blend of H. erectus-like and derived morpho-architectural features and three pelvic remains, two isolated permanent incisors (UA 222 and UA 369) have also been recovered from the 1 Ma (millions of years ago) Homo-bearing outcrop of Uadi Aalad. Since 2010, our surveys have expanded to the nearby (4.7 km) site of Mulhuli-Amo (MA). This is a fossiliferous area that has been preliminarily surveyed because of its exceptional concentration of Acheulean stone tools. So far, the site has yielded 10 human remains, including the unworn crown of a lower permanent molar (MA 93). Using diverse analytical tools (including high resolution μCT and μMRI), we analysed the external and internal macromorphology and microstructure of the three specimens, and whenever possible compared the results with similar evidence from early Homo, H. erectus s.l., H. antecessor, H. heidelbergensis (from North Africa), Neanderthals and modern humans. We also assessed the UA 369 lower incisor from Uadi Aalad for root completion timing and showed that it compares well with data for root apex closure in modern human populations. PMID:24852385

  1. Autoantibodies to Ezrin are an early sign of pancreatic cancer in humans and in genetically engineered mouse models

    PubMed Central

    2013-01-01

    Background Pancreatic Ductal Adenocarcinoma (PDAC) is a highly aggressive malignancy with only a 5% 5-year survival rate. Reliable biomarkers for early detection are still lacking. The goals of this study were (a) to identify early humoral responses in genetically engineered mice (GEM) spontaneously developing PDAC; and (b) to test their diagnostic/predictive value in newly diagnosed PDAC patients and in prediagnostic sera. Methods and results The serum reactivity of GEM from inception to invasive cancer, and in resectable or advanced human PDAC was tested by two-dimensional electrophoresis Western blot against proteins from murine and human PDAC cell lines, respectively. A common mouse-to-human autoantibody signature, directed against six antigens identified by MALDI-TOF mass spectrometry, was determined. Of the six antigens, Ezrin displayed the highest frequency of autoantibodies in GEM with early disease and in PDAC patients with resectable disease. The diagnostic value of Ezrin-autoantibodies to discriminate PDAC from controls was further shown by ELISA and ROC analyses (P < 0.0001). This observation was confirmed in prediagnostic sera from the EPIC prospective study in patients who eventually developed PDAC (with a mean time lag of 61.2 months between blood drawing and PDAC diagnosis). A combination of Ezrin-autoantibodies with CA19.9 serum levels and phosphorylated α-Enolase autoantibodies showed an overall diagnostic accuracy of 0.96 ± 0.02. Conclusions Autoantibodies against Ezrin are induced early in PDAC and their combination with other serological markers may provide a predictive and diagnostic signature. PMID:24010981

  2. Neurobiological consequences of early stress and childhood maltreatment: are results from human and animal studies comparable?

    PubMed

    Teicher, Martin H; Tomoda, Akemi; Andersen, Susan L

    2006-07-01

    Recent studies have reported an association between exposure to childhood abuse or neglect and alterations in brain structure or function. One limitation of these studies is that they are correlational and do not provide evidence of a cause-effect relationship. Preclinical studies on the effects of exposure to early life stress can demonstrate causality, and can enrich our understanding of the clinical research if we hypothesize that the consequences of early abuse are predominantly mediated through the induction of stress responses. Exposure to early abuse and early stress has each been associated with the emergence of epileptiform electroencephalogram (EEG) abnormalities, alterations in corpus callosum area, and reduced volume or synaptic density of the hippocampus. Further, there is evidence that different brain regions have unique periods when they are maximally sensitive to the effects of early stress. To date, preclinical studies have guided clinical investigations and will continue to provide important insight into studies on molecular mechanisms and gene-environment interactions. PMID:16891580

  3. Topographic representation of an occluded object and the effects of spatiotemporal context in human early visual areas.

    PubMed

    Ban, Hiroshi; Yamamoto, Hiroki; Hanakawa, Takashi; Urayama, Shin-Ichi; Aso, Toshihiko; Fukuyama, Hidenao; Ejima, Yoshimichi

    2013-10-23

    Occlusion is a primary challenge facing the visual system in perceiving object shapes in intricate natural scenes. Although behavior, neurophysiological, and modeling studies have shown that occluded portions of objects may be completed at the early stage of visual processing, we have little knowledge on how and where in the human brain the completion is realized. Here, we provide functional magnetic resonance imaging (fMRI) evidence that the occluded portion of an object is indeed represented topographically in human V1 and V2. Specifically, we find the topographic cortical responses corresponding to the invisible object rotation in V1 and V2. Furthermore, by investigating neural responses for the occluded target rotation within precisely defined cortical subregions, we could dissociate the topographic neural representation of the occluded portion from other types of neural processing such as object edge processing. We further demonstrate that the early topographic representation in V1 can be modulated by prior knowledge of a whole appearance of an object obtained before partial occlusion. These findings suggest that primary "visual" area V1 has the ability to process not only visible or virtually (illusorily) perceived objects but also "invisible" portions of objects without concurrent visual sensation such as luminance enhancement to these portions. The results also suggest that low-level image features and higher preceding cognitive context are integrated into a unified topographic representation of occluded portion in early areas. PMID:24155304

  4. Indian Hedgehog in Synovial Fluid Is a Novel Marker for Early Cartilage Lesions in Human Knee Joint

    PubMed Central

    Zhang, Congming; Wei, Xiaochun; Chen, Chongwei; Cao, Kun; Li, Yongping; Jiao, Qiang; Ding, Juan; Zhou, Jingming; Fleming, Braden C.; Chen, Qian; Shang, Xianwen; Wei, Lei

    2014-01-01

    To determine whether there is a correlation between the concentration of Indian hedgehog (Ihh) in synovial fluid (SF) and the severity of cartilage damage in the human knee joints, the knee cartilages from patients were classified using the Outer-bridge scoring system and graded using the Modified Mankin score. Expression of Ihh in cartilage and SF samples were analyzed with immunohistochemistry (IHC), western blot, and enzyme-linked immunosorbent assay (ELISA). Furthermore, we detected and compared Ihh protein levels in rat and mice cartilages between normal control and surgery-induced osteoarthritis (OA) group by IHC and fluorescence molecular tomography in vivo respectively. Ihh expression was increased 5.2-fold in OA cartilage, 3.1-fold in relative normal OA cartilage, and 1.71-fold in OA SF compared to normal control samples. The concentrations of Ihh in cartilage and SF samples was significantly increased in early-stage OA samples when compared to normal samples (r = 0.556; p < 0.001); however, there were no significant differences between normal samples and late-stage OA samples. Up-regulation of Ihh protein was also an early event in the surgery-induced OA models. Increased Ihh is associated with the severity of OA cartilage damage. Elevated Ihh content in human knee joint synovial fluid correlates with early cartilage lesions. PMID:24786088

  5. SARS-Coronavirus ancestor's foot-prints in South-East Asian bat colonies and the refuge theory.

    PubMed

    Gouilh, Meriadeg Ar; Puechmaille, Sébastien J; Gonzalez, Jean-Paul; Teeling, Emma; Kittayapong, Pattamaporn; Manuguerra, Jean-Claude

    2011-10-01

    One of the great challenges in the ecology of infectious diseases is to understand what drives the emergence of new pathogens including the relationship between viruses and their hosts. In the case of the emergence of SevereAcute Respiratory Syndrome Coronavirus (SARS-CoV), several studies have shown coronavirus diversity in bats as well as the existence of SARS-CoV infection in apparently healthy bats, suggesting that bats may be a crucial host in the genesis of this disease. To elucidate the biogeographic origin of SARS-CoV and investigate the role that bats played in its emergence, we amplified coronavirus sequences from bat species captured throughout Thailand and assessed the phylogenetic relationships to each other and to other published coronavirus sequences. To this end, RdRp sequence of Coronavirinae was targeted by RT-PCR in non-invasive samples from bats collected in Thailand. Two new coronaviruses were detected in two bat species: one Betacoronavirus in Hipposideros larvatus and one Alphacoronavirus in Hipposiderosarmiger. Interestingly, these viruses from South-East Asia are related to those previously detected in Africa (Betacoronavirus-b) or in Europe (Alphacoronavirus & Betacoronavirus-b). These findings illuminate the origin and the evolutionary history of the SARS-CoV group found in bats by pushing forward the hypothesis of a Betacoronavirus spill-over from Hipposideridae to Rhinolophidae and then from Rhinolophidae to civets and Human. All reported Betacoronaviruses-b (SARS-CoV group) of Hipposideridae and Rhinolophidae respectively cluster in two groups despite their broad geographic distribution and the sympatry of their hosts, which is in favor of an ancient and genetically independent evolution of Betacoronavirus-b clusters in these families. Moreover, despite its probable pathogenicity, we found that a Betacoronavirus-b can persistently infect a medium-sized hipposiderid bat colony. These findings illustrate the importance of the host

  6. The compact Brachypodium genome conserves centromeric regions of a common ancestor with wheat and rice.

    PubMed

    Qi, Lili; Friebe, Bernd; Wu, Jiajie; Gu, Yongqiang; Qian, Chen; Gill, Bikram S

    2010-11-01

    The evolution of five chromosomes of Brachypodium distachyon from a 12-chromosome ancestor of all grasses by dysploidy raises an interesting question about the fate of redundant centromeres. Three independent but complementary approaches were pursued to study centromeric region homologies among the chromosomes of Brachypodium, wheat, and rice. The genes present in pericentromeres of the basic set of seven chromosomes of wheat and the Triticeae, and the 80 rice centromeric genes spanning the CENH3 binding domain of centromeres 3, 4, 5, 7, and 8 were used as "anchor" markers to identify centromere locations in the B. distachyon chromosomes. A total of 53 B. distachyon bacterial artificial chromosome (BAC) clones anchored by wheat pericentromeric expressed sequence tags (ESTs) were used as probes for BAC-fluorescence in situ hybridization (FISH) analysis of B. distachyon mitotic chromosomes. Integrated sequence alignment and BAC-FISH data were used to determine the approximate positions of active and inactive centromeres in the five B. distachyon chromosomes. The following syntenic relationships of the centromeres for Brachypodium (Bd), rice (R), and wheat (W) were evident: Bd1-R6, Bd2-R5-W1, Bd3-R10, Bd4-R11-W4, and Bd5-R4. Six rice centromeres syntenic to five wheat centromeres were inactive in Brachypodium chromosomes. The conservation of centromere gene synteny among several sets of homologous centromeres of three species indicates that active genes can persist in ancient centromeres with more than 40 million years of shared evolutionary history. Annotation of a BAC contig spanning an inactive centromere in chromosome Bd3 which is syntenic to rice Cen8 and W7 pericentromeres, along with BAC FISH data from inactive centromeres revealed that the centromere inactivation was accompanied by the loss of centromeric retrotransposons and turnover of centromere-specific satellites during Bd chromosome evolution. PMID:20842403

  7. Molecular Epidemiology of Helicobacter pylori Infection in Nepal: Specific Ancestor Root

    PubMed Central

    Miftahussurur, Muhammad; Sharma, Rabi Prakash; Shrestha, Pradeep Krishna; Suzuki, Rumiko; Uchida, Tomohisa; Yamaoka, Yoshio

    2015-01-01

    Prevalence of Helicobacter pylori infection in Nepal, a low-risk country for gastric cancer, is debatable. To our knowledge, no studies have examined H. pylori virulence factors in Nepal. We determined the prevalence of H. pylori infection by using three different tests, and the genotypes of virulence factors were determined by PCR followed by sequencing. Multilocus sequence typing was used to analyze the population structure of the Nepalese strains. The prevalence of H. pylori infection in dyspeptic patients was 38.4% (56/146), and was significantly related with source of drinking water. In total, 51 strains were isolated and all were cagA-positive. Western-type-cagA (94.1%), cagA pre-EPIYA type with no deletion (92.2%), vacA s1a (74.5%), and m1c (54.9%) were the predominant genotypes. Antral mucosal atrophy levels were significantly higher in patients infected with vacA s1 than in those infected with s2 genotypes (P = 0.03). Several Nepalese strains were H. pylori recombinants with genetic features of South Asian and East Asian genotypes. These included all East-Asian-type-cagA strains, with significantly lesser activity and inflammation in the corpus than the strains of the specific South Asian genotype (P = 0.03 and P = 0.005, respectively). Although the population structure confirmed that most Nepalese strains belonged to the hpAsia2 population, some strains shared hpEurope- and Nepalese-specific components. Nepalese patients infected with strains belonging to hpEurope showed higher inflammation in the antrum than strains from the Nepalese specific population (P = 0.05). These results support that ancestor roots of Kathmandu`s people not only connected with India alone. PMID:26226153

  8. Evidence of a chimeric genome in the cyanobacterial ancestor of plastids

    PubMed Central

    2008-01-01

    Background Horizontal gene transfer (HGT) is a vexing fact of life for microbial phylogeneticists. Given the substantial rates of HGT observed in modern-day bacterial chromosomes, it is envisaged that ancient prokaryotic genomes must have been similarly chimeric. But where can one find an ancient prokaryotic genome that has maintained its ancestral condition to address this issue? An excellent candidate is the cyanobacterial endosymbiont that was harnessed over a billion years ago by a heterotrophic protist, giving rise to the plastid. Genetic remnants of the endosymbiont are still preserved in plastids as a highly reduced chromosome encoding 54 – 264 genes. These data provide an ideal target to assess genome chimericism in an ancient cyanobacterial lineage. Results Here we demonstrate that the origin of the plastid-encoded gene cluster for menaquinone/phylloquinone biosynthesis in the extremophilic red algae Cyanidiales contradicts a cyanobacterial genealogy. These genes are relics of an ancestral cluster related to homologs in Chlorobi/Gammaproteobacteria that we hypothesize was established by HGT in the progenitor of plastids, thus providing a 'footprint' of genome chimericism in ancient cyanobacteria. In addition to menB, four components of the original gene cluster (menF, menD, menC, and menH) are now encoded in the nuclear genome of the majority of non-Cyanidiales algae and plants as the unique tetra-gene fusion named PHYLLO. These genes are monophyletic in Plantae and chromalveolates, indicating that loci introduced by HGT into the ancestral cyanobacterium were moved over time into the host nucleus. Conclusion Our study provides unambiguous evidence for the existence of genome chimericism in ancient cyanobacteria. In addition we show genes that originated via HGT in the cyanobacterial ancestor of the plastid made their way to the host nucleus via endosymbiotic gene transfer (EGT). PMID:18433492

  9. Molecular Epidemiology of Helicobacter pylori Infection in Nepal: Specific Ancestor Root.

    PubMed

    Miftahussurur, Muhammad; Sharma, Rabi Prakash; Shrestha, Pradeep Krishna; Suzuki, Rumiko; Uchida, Tomohisa; Yamaoka, Yoshio

    2015-01-01

    Prevalence of Helicobacter pylori infection in Nepal, a low-risk country for gastric cancer, is debatable. To our knowledge, no studies have examined H. pylori virulence factors in Nepal. We determined the prevalence of H. pylori infection by using three different tests, and the genotypes of virulence factors were determined by PCR followed by sequencing. Multilocus sequence typing was used to analyze the population structure of the Nepalese strains. The prevalence of H. pylori infection in dyspeptic patients was 38.4% (56/146), and was significantly related with source of drinking water. In total, 51 strains were isolated and all were cagA-positive. Western-type-cagA (94.1%), cagA pre-EPIYA type with no deletion (92.2%), vacA s1a (74.5%), and m1c (54.9%) were the predominant genotypes. Antral mucosal atrophy levels were significantly higher in patients infected with vacA s1 than in those infected with s2 genotypes (P = 0.03). Several Nepalese strains were H. pylori recombinants with genetic features of South Asian and East Asian genotypes. These included all East-Asian-type-cagA strains, with significantly lesser activity and inflammation in the corpus than the strains of the specific South Asian genotype (P = 0.03 and P = 0.005, respectively). Although the population structure confirmed that most Nepalese strains belonged to the hpAsia2 population, some strains shared hpEurope- and Nepalese-specific components. Nepalese patients infected with strains belonging to hpEurope showed higher inflammation in the antrum than strains from the Nepalese specific population (P = 0.05). These results support that ancestor roots of Kathmandu`s people not only connected with India alone. PMID:26226153

  10. Comparative Genomic Evidence for a Complete Nuclear Pore Complex in the Last Eukaryotic Common Ancestor

    PubMed Central

    Neumann, Nadja; Lundin, Daniel; Poole, Anthony M.

    2010-01-01

    Background The Nuclear Pore Complex (NPC) facilitates molecular trafficking between nucleus and cytoplasm and is an integral feature of the eukaryote cell. It exhibits eight-fold rotational symmetry and is comprised of approximately 30 nucleoporins (Nups) in different stoichiometries. Nups are broadly conserved between yeast, vertebrates and plants, but few have been identified among other major eukaryotic groups. Methodology/Principal Findings We screened for Nups across 60 eukaryote genomes and report that 19 Nups (spanning all major protein subcomplexes) are found in all eukaryote supergroups represented in our study (Opisthokonts, Amoebozoa, Viridiplantae, Chromalveolates and Excavates). Based on parsimony, between 23 and 26 of 31 Nups can be placed in LECA. Notably, they include central components of the anchoring system (Ndc1 and Gp210) indicating that the anchoring system did not evolve by convergence, as has previously been suggested. These results significantly extend earlier results and, importantly, unambiguously place a fully-fledged NPC in LECA. We also test the proposal that transmembrane Pom proteins in vertebrates and yeasts may account for their variant forms of mitosis (open mitoses in vertebrates, closed among yeasts). The distribution of homologues of vertebrate Pom121 and yeast Pom152 is not consistent with this suggestion, but the distribution of fungal Pom34 fits a scenario wherein it was integral to the evolution of closed mitosis in ascomycetes. We also report an updated screen for vesicle coating complexes, which share a common evolutionary origin with Nups, and can be traced back to LECA. Surprisingly, we find only three supergroup-level differences (one gain and two losses) between the constituents of COPI, COPII and Clathrin complexes. Conclusions/Significance Our results indicate that all major protein subcomplexes in the Nuclear Pore Complex are traceable to the Last Eukaryotic Common Ancestor (LECA). In contrast to previous screens

  11. The Early Middle Palaeolithic in Britain: archaeology, settlement history and human behaviour

    NASA Astrophysics Data System (ADS)

    White, Mark; Scott, Beccy; Ashton, Nick

    2006-07-01

    A number of archaeological sites dated to MIS 8 and MIS 7 and containing Early Middle Palaeolithic Levalloisian assemblages can now be identified within the British Palaeolithic record. These provide a mixture of high- and low-resolution signatures, which together permit the reconstruction of aspects of early Neanderthal behaviour, settlement history and technological organisation within the British Isles. Much is certainly missing, but it is now possible to begin the task of disentangling the previously conflated Middle Palaeolithic, separating those sites belonging to the Middle Pleistocene from those dating to the last climatic cycle. This paper presents the first attempt to synthesise the data from the Early Middle Palaeolithic and presents some of our preliminary and tentatively held interpretations of what it might mean. Copyright

  12. Early Trabecular Development in Human Vertebrae: Overproduction, Constructive Regression, and Refinement

    PubMed Central

    Acquaah, Frank; Robson Brown, Katharine A.; Ahmed, Farah; Jeffery, Nathan; Abel, Richard L.

    2015-01-01

    Early bone development may have a significant impact upon bone health in adulthood. Bone mineral density (BMD) and bone mass are important determinants of adult bone strength. However, several studies have shown that BMD and bone mass decrease after birth. If early development is important for strength, why does this reduction occur? To investigate this, more data characterizing gestational, infant, and childhood bone development are needed in order to compare with adults. The aim of this study is to document early vertebral trabecular bone development, a key fragility fracture site, and infer whether this period is important for adult bone mass and structure. A series of 120 vertebrae aged between 6 months gestation and 2.5 years were visualized using microcomputed tomography. Spherical volumes of interest were defined, thresholded, and measured using 3D bone analysis software (BoneJ, Quant3D). The findings showed that gestation was characterized by increasing bone volume fraction whilst infancy was defined by significant bone loss (≈2/3rds) and the appearance of a highly anisotropic trabecular structure with a predominantly inferior–superior direction. Childhood development progressed via selective thickening of some trabeculae and the loss of others; maintaining bone volume whilst creating a more anisotropic structure. Overall, the pattern of vertebral development is one of gestational overproduction followed by infant “sculpting” of bone tissue during the first year of life (perhaps in order to regulate mineral homeostasis or to adapt to loading environment) and then subsequent refinement during early childhood. Comparison of early bone developmental data in this study with adult bone volume values taken from the literature shows that the loss in bone mass that occurs during the first year of life is never fully recovered. Early development could therefore be important for developing bone strength, but through structural changes in trabecular

  13. Comparison of vitrified outcomes between human early blastocysts and expanded blastocysts.

    PubMed

    Song, Wen-Yan; Wang, Xue-Gai; Jin, Hai-Xia; Yao, Gui-Dong; Zhang, Xiang-Yang; Shi, Sen-Lin; Yang, Hong-Yi; Peng, Zhao-Feng; Sun, Ying-Pu

    2016-05-01

    We compared the vitrified outcomes between early and expanded blastocysts with or without laser drilling. The grade III embryos from the patients undergoing in vitro fertilization-embryo transfer (IVF-ET) in our reproductive center from September 2009 to February 2015 were incubated into early blastocysts and expanded blastocysts. The early blastocysts and expanded blastocysts were, respectively, divided into laser group (vitrification after laser drilling), non-laser group (direct vitrification), and control group (fresh non-vitrified blastocysts). After thawing, the blastular anabiosis rate, expansion rate, hatching rate, and apoptosis were observed in each group and then were compared amongst groups. This study indicated that the blastular expansion rate (all P < 0.01) and hatching rate (all P < 0.01) were significantly lower, but the blastular apoptosis (all P < 0.05) was significantly higher in both laser and non-laser groups than in the control group in the early blastocysts. In the expanded blastocysts, the blastular anabiosis rate was significantly higher in the laser group than in the non-laser group (P < 0.01), and the blastular expansion rate was significantly higher, but the blastular apoptosis was significantly lower in both laser group and control group than in the non-laser group (all P < 0.05). The blastular expansion rate (all P < 0.01) and hatching rate (all P < 0.01) were significantly higher, but the blastular apoptosis (all P < 0.05) was significantly lower in the expanded laser group than in both early laser and early non-laser groups. We conclude that vitrification for laser-drilling expanded blastocysts can achieve the best outcomes. PMID:26956359

  14. Early Trabecular Development in Human Vertebrae: Overproduction, Constructive Regression, and Refinement.

    PubMed

    Acquaah, Frank; Robson Brown, Katharine A; Ahmed, Farah; Jeffery, Nathan; Abel, Richard L

    2015-01-01

    Early bone development may have a significant impact upon bone health in adulthood. Bone mineral density (BMD) and bone mass are important determinants of adult bone strength. However, several studies have shown that BMD and bone mass decrease after birth. If early development is important for strength, why does this reduction occur? To investigate this, more data characterizing gestational, infant, and childhood bone development are needed in order to compare with adults. The aim of this study is to document early vertebral trabecular bone development, a key fragility fracture site, and infer whether this period is important for adult bone mass and structure. A series of 120 vertebrae aged between 6 months gestation and 2.5 years were visualized using microcomputed tomography. Spherical volumes of interest were defined, thresholded, and measured using 3D bone analysis software (BoneJ, Quant3D). The findings showed that gestation was characterized by increasing bone volume fraction whilst infancy was defined by significant bone loss (≈2/3rds) and the appearance of a highly anisotropic trabecular structure with a predominantly inferior-superior direction. Childhood development progressed via selective thickening of some trabeculae and the loss of others; maintaining bone volume whilst creating a more anisotropic structure. Overall, the pattern of vertebral development is one of gestational overproduction followed by infant "sculpting" of bone tissue during the first year of life (perhaps in order to regulate mineral homeostasis or to adapt to loading environment) and then subsequent refinement during early childhood. Comparison of early bone developmental data in this study with adult bone volume values taken from the literature shows that the loss in bone mass that occurs during the first year of life is never fully recovered. Early development could therefore be important for developing bone strength, but through structural changes in trabecular

  15. The early Middle Pleistocene archeopaleontological site of Wadi Sarrat (Tunisia) and the earliest record of Bos primigenius

    NASA Astrophysics Data System (ADS)

    Martínez-Navarro, Bienvenido; Karoui-Yaakoub, Narjess; Oms, Oriol; Amri, Lamjed; López-García, Juan Manuel; Zerai, Kamel; Blain, Hugues-Alexandre; Mtimet, Moncef-Saïd; Espigares, María-Patrocinio; Ben Haj Ali, Nebiha; Ros-Montoya, Sergio; Boughdiri, Mabrouk; Agustí, Jordi; Khayati-Ammar, Hayet; Maalaoui, Kamel; El Khir, Maahmoudi Om; Sala, Robert; Othmani, Abdelhak; Hawas, Ramla; Gómez-Merino, Gala; Solè, Àlex; Carbonell, Eudald; Palmqvist, Paul

    2014-04-01

    Here we describe the new, rich lacustrine paleontological and archeological site of Wadi Sarrat (Le Kef, northeastern Tunisia), dated to the beginning of the Middle Pleistocene, ˜0.7 Ma, by a combination of paleomagnetism and biochronology. This locality preserves the earliest record of auroch, Bos primigenius, the ancestor of the worldwide extant domestic cattle species Bos taurus, which is represented by a nearly complete, giant-sized cranium (specimen OS1). Both the cranial anatomy and the size of this specimen reflect the phylogenetic legacy inherited from its ancestor, the late Early Pleistocene African Bos buiaensis, recorded in the eastern African paleoanthropological site of Buia, Eritrea (1.0 Ma). Given that the latter species is an evolved form of the classical Early Pleistocene African buffalo Pelorovis oldowayensis, the finding of B. primigenius at Wadi Sarrat shows that the genus Bos evolved in Africa and dispersed into Eurasia at the beginning of the Middle Pleistocene, which coincides with the spread of the Acheulian technocomplex in northern Africa and Europe. Therefore, the lineage of Pelorovis-Bos has been part of the human ecological landscape since the appearance of the genus Homo in the African Early Pleistocene.

  16. Identifying genomic and metabolic features that can underlie early successional and opportunistic lifestyles of human gut symbionts

    PubMed Central

    Lozupone, Catherine; Faust, Karoline; Raes, Jeroen; Faith, Jeremiah J.; Frank, Daniel N.; Zaneveld, Jesse; Gordon, Jeffrey I.; Knight, Rob

    2012-01-01

    We lack a deep understanding of genetic and metabolic attributes specializing in microbial consortia for initial and subsequent waves of colonization of our body habitats. Here we show that phylogenetically interspersed bacteria in Clostridium cluster XIVa, an abundant group of bacteria in the adult human gut also known as the Clostridium coccoides or Eubacterium rectale group, contains species that have evolved distribution patterns consistent with either early successional or stable gut communities. The species that specialize to the infant gut are more likely to associate with systemic infections and can reach high abundances in individuals with Inflammatory Bowel Disease (IBD), indicating that a subset of the microbiota that have adapted to pioneer/opportunistic lifestyles may do well in both early development and with disease. We identified genes likely selected during adaptation to pioneer/opportunistic lifestyles as those for which early succession association and not phylogenetic relationships explain genomic abundance. These genes reveal potential mechanisms by which opportunistic gut bacteria tolerate osmotic and oxidative stress and potentially important aspects of their metabolism. These genes may not only be biomarkers of properties associated with adaptation to early succession and disturbance, but also leads for developing therapies aimed at promoting reestablishment of stable gut communities following physiologic or pathologic disturbances. PMID:22665442

  17. Human radiation studies: Remembering the early years. Oral history of Merril Eisenbud, January 26, 1995

    SciTech Connect

    1995-05-01

    Merril Eisenbud was interviewed on January 26, 1995 by representatives of the US DOE Office of Human Radiation Experiments. Following a brief biographical sketch, Mr. Eisenbud relates his remembrances as the AEC`s first industrial hygienist, the setting up of AEC`s Health and Safety Laboratory, monitoring radioactive fallout, and use or exposure of humans to radiation.

  18. Linking Human and Robotic Missions: Early Leveraging of the Code S Missions

    NASA Technical Reports Server (NTRS)

    Cooke, Doug

    2001-01-01

    A major long term NASA objective is to enable human exploration beyond low Earth orbit. This will take a strange approach, with a concentration on new, enabling technologies and capabilities. Mars robotic missions are logical and necessary steps in the progression toward eventual human missions.

  19. Tuberin and PRAS40 are anti-apoptotic gatekeepers during early human amniotic fluid stem-cell differentiation.

    PubMed

    Fuchs, Christiane; Rosner, Margit; Dolznig, Helmut; Mikula, Mario; Kramer, Nina; Hengstschläger, Markus

    2012-03-01

    Embryoid bodies (EBs) are three-dimensional multicellular aggregates allowing the in vitro investigation of stem-cell differentiation processes mimicking early embryogenesis. Human amniotic fluid stem (AFS) cells harbor high proliferation potential, do not raise the ethical issues of embryonic stem cells, have a lower risk for tumor development, do not need exogenic induction of pluripotency and are chromosomal stable. Starting from a single human AFS cell, EBs can be formed accompanied by the differentiation into cells of all three embryonic germ layers. Here, we report that siRNA-mediated knockdown of the endogenous tuberous sclerosis complex-2 (TSC2) gene product tuberin or of proline-rich Akt substrate of 40 kDa (PRAS40), the two major negative regulators of mammalian target of rapamycin (mTOR), leads to massive apoptotic cell death during EB development of human AFS cells without affecting the endodermal, mesodermal and ectodermal cell differentiation spectrum. Co-knockdown of endogenous mTOR demonstrated these effects to be mTOR-dependent. Our findings prove this enzyme cascade to be an essential anti-apoptotic gatekeeper of stem-cell differentiation during EB formation. These data allow new insights into the regulation of early stem-cell maintenance and differentiation and identify a new role of the tumor suppressor tuberin and the oncogenic protein PRAS40 with the relevance for a more detailed understanding of the pathogenesis of diseases associated with altered activities of these gene products. PMID:22090422

  20. Modeling the Early Steps of Ovarian Cancer Dissemination in an Organotypic Culture of the Human Peritoneal Cavity.

    PubMed

    Peters, Pamela N; Schryver, Elizabeth M; Lengyel, Ernst; Kenny, Hilary

    2015-01-01

    The pattern of ovarian cancer metastasis is markedly different from that of most other epithelial tumors, because it rarely spreads hematogenously. Instead, ovarian cancer cells exfoliated from the primary tumor are carried by peritoneal fluid to metastatic sites within the peritoneal cavity. These sites, most notably the abdominal peritoneum and omentum, are organs covered by a mesothelium-lined surface. To investigate the processes of ovarian cancer dissemination, we assembled a complex three-dimensional culture system that reconstructs the lining of the peritoneal cavity in vitro. Primary human fibroblasts and mesothelial cells were isolated from human omentum. The fibroblasts were then mixed with extracellular matrix and covered with a layer of the primary human mesothelial cells to mimic the peritoneal and omental surfaces encountered by metastasizing ovarian cancer cells. The resulting organotypic model is, as shown, used to examine the early steps of ovarian cancer dissemination, including cancer cell adhesion, invasion, and proliferation. This model has been used in a number of studies to investigate the role of the microenvironment (cellular and acellular) in early ovarian cancer dissemination. It has also been successfully adapted to high throughput screening and used to identify and test inhibitors of ovarian cancer metastasis. PMID:26780294

  1. The superantigen-homologous viral immediate-early gene ie14/vsag in herpesvirus saimiri-transformed human T cells.

    PubMed Central

    Knappe, A; Hiller, C; Thurau, M; Wittmann, S; Hofmann, H; Fleckenstein, B; Fickenscher, H

    1997-01-01

    Herpesvirus saimiri C488 transforms human T lymphocytes to stable growth in culture. The growth-transformed human T cells harbor the viral genome in a nonintegrated episomal form without production of virus particles. In these cells, virus gene expression was previously found to be confined to the transforming genes stpC and tip. In order to analyze virus gene expression in more detail, we applied a subtractive hybridization technique and compared stimulated virus-transformed cells with uninfected parental T cells of the same donor. A number of known T-cell activation genes were isolated. Viral stpC/tip cDNAs were enriched after subtraction. In addition, the viral immediate-early, superantigen-homologous gene ie14/vsag was represented by numerous cDNA clones that comprised the entire spliced transcript. Whereas a weak basal expression of ie14/vsag was detected by reverse transcription-PCR only, the phorbol ester-induced transcripts were readily shown by Northern blotting. ie14/vsag, which before had been classified as a major immediate-early gene of herpesvirus saimiri, is localized within a highly conserved region with extensive homologies to the cellular genome. Mutant viruses without the ie14/vsag gene are replication competent and fully capable of transforming human and marmoset T cells. Since ie14/vsag is transiently expressed after stimulation, it may increase T-cell proliferation in an activation-dependent and superantigen-like but apparently Vbeta-independent way. PMID:9371569

  2. Early activation of MyD88-mediated autophagy sustains HSV-1 replication in human monocytic THP-1 cells.

    PubMed

    Siracusano, Gabriel; Venuti, Assunta; Lombardo, Daniele; Mastino, Antonio; Esclatine, Audrey; Sciortino, Maria Teresa

    2016-01-01

    Autophagy is a cellular degradation pathway that exerts numerous functions in vital biological processes. Among these, it contributes to both innate and adaptive immunity. On the other hand, pathogens have evolved strategies to manipulate autophagy for their own advantage. By monitoring autophagic markers, we showed that HSV-1 transiently induced autophagosome formation during early times of the infection of monocytic THP-1 cells and human monocytes. Autophagy is induced in THP-1 cells by a mechanism independent of viral gene expression or viral DNA accumulation. We found that the MyD88 signaling pathway is required for HSV-1-mediated autophagy, and it is linked to the toll-like receptor 2 (TLR2). Interestingly, autophagy inhibition by pharmacological modulators or siRNA knockdown impaired viral replication in both THP-1 cells and human monocytes, suggest that the virus exploits the autophagic machinery to its own benefit in these cells. Taken together, these findings indicate that the early autophagic response induced by HSV-1 exerts a proviral role, improving viral production in a semi-permissive model such as THP-1 cells and human monocytes. PMID:27509841

  3. Early activation of MyD88-mediated autophagy sustains HSV-1 replication in human monocytic THP-1 cells

    PubMed Central

    Siracusano, Gabriel; Venuti, Assunta; Lombardo, Daniele; Mastino, Antonio; Esclatine, Audrey; Sciortino, Maria Teresa

    2016-01-01

    Autophagy is a cellular degradation pathway that exerts numerous functions in vital biological processes. Among these, it contributes to both innate and adaptive immunity. On the other hand, pathogens have evolved strategies to manipulate autophagy for their own advantage. By monitoring autophagic markers, we showed that HSV-1 transiently induced autophagosome formation during early times of the infection of monocytic THP-1 cells and human monocytes. Autophagy is induced in THP-1 cells by a mechanism independent of viral gene expression or viral DNA accumulation. We found that the MyD88 signaling pathway is required for HSV-1-mediated autophagy, and it is linked to the toll-like receptor 2 (TLR2). Interestingly, autophagy inhibition by pharmacological modulators or siRNA knockdown impaired viral replication in both THP-1 cells and human monocytes, suggest that the virus exploits the autophagic machinery to its own benefit in these cells. Taken together, these findings indicate that the early autophagic response induced by HSV-1 exerts a proviral role, improving viral production in a semi-permissive model such as THP-1 cells and human monocytes. PMID:27509841

  4. International Human Rights to Early Intervention for Infants and Young Children with Disabilities: Tools for Global Advocacy

    PubMed Central

    Brown, Sharan E.; Guralnick, Michael J.

    2015-01-01

    With almost universal ratification of the Convention on the Rights of the Child and the growing number of States Parties that have signed or ratified the Convention on the Rights of Persons with Disabilities, the majority of countries in the world have now committed to implementing the human rights articulated in these treaties. In this article we first provide an overview of both Conventions, highlight the articles in the treaties that are relevant to early intervention for infants and young children with disabilities, and describe the specific duties required of States Parties to ensure compliance including international cooperation. Second, a series of early intervention action principles are put forward that can help States Parties translate the underlying values of the Conventions into practice. PMID:26213446

  5. Early BrdU-responsive genes constitute a novel class of senescence-associated genes in human cells

    SciTech Connect

    Minagawa, Sachi; Nakabayashi, Kazuhiko; Fujii, Michihiko; Scherer, Stephen W.; Ayusawa, Dai . E-mail: dayusawa@yokohama-cu.ac.jp

    2005-04-01

    We identified genes that immediately respond to 5-bromodeoxyuridine (BrdU) in SUSM-1, an immortal fibroblastic line, with DNA microarray and Northern blot analysis. At least 29 genes were found to alter gene expression greater than twice more or less than controls within 36 h after addition of BrdU. They took several different expression patterns upon addition of BrdU, and the majority showed a significant alteration within 12 h. When compared among SUSM-1, HeLa, and TIG-7 normal human fibroblasts, 19 genes behaved similarly upon addition of BrdU. In addition, 14 genes, 9 of which are novel as regards senescence, behaved similarly in senescent TIG-7 cells. The genes do not seem to have a role in proliferation or cell cycle progression. These results suggest that the early BrdU-responsive genes represent early signs of cellular senescence and can be its new biomarkers.

  6. Antibody Responses After Analytic Treatment Interruption in Human Immunodeficiency Virus-1-Infected Individuals on Early Initiated Antiretroviral Therapy

    PubMed Central

    Stephenson, Kathryn E.; Neubauer, George H.; Bricault, Christine A.; Shields, Jennifer; Bayne, Madeleine; Reimer, Ulf; Pawlowski, Nikolaus; Knaute, Tobias; Zerweck, Johannes; Seaman, Michael S.; Rosenberg, Eric S.; Barouch, Dan H.

    2016-01-01

    The examination of antibody responses in human immunodeficiency virus (HIV)-1-infected individuals in the setting of antiretroviral treatment (ART) interruption can provide insight into the evolution of antibody responses during viral rebound. In this study, we assessed antibody responses in 20 subjects in AIDS Clinical Trials Group A5187, wherein subjects were treated with antiretroviral therapy during acute/early HIV-1 infection, underwent analytic treatment interruption, and subsequently demonstrated viral rebound. Our data suggest that early initiation of ART arrests the maturation of HIV-1-specific antibody responses, preventing epitope diversification of antibody binding and the development of functional neutralizing capacity. Antibody responses do not appear permanently blunted, however, because viral rebound triggered the resumption of antibody maturation in our study. We also found that antibody responses measured by these assays did not predict imminent viral rebound. These data have important implications for the HIV-1 vaccine and eradication fields. PMID:27419172

  7. [The saga of aspirin: centuries-old ancestors of an old lady who doesn't deserve to die].

    PubMed

    Queneau, P

    2001-01-01

    Where do analgics come from? If their ancestors are many centuries old, we observe that the four main drugs of modern analgesia, morphine (1816), codeine (1832), paracetamol (1893) and aspirin (1897) were discovered during the 19th century. And through what 'sagas'! The first known prescriptions, written on earthenware shelves in Mesopotamia 3 centuries BC, already mentioned medications derived from willow to cure headaches. The Greeks dedicated to Asclepios, god of therapeutics, a statue carved in a willow trunk as a symbol! Thus, before becoming a drug, aspirin was born from the willow, which grows with its feet in water 'without suffering', as the ancestors put it. But before it walked on the moon with Neil Armstrong in 1969, the discovery of aspirin as a drug was the consequence of the filial love of a young researcher, Felix Hoffmann, who wanted to decrease the resistant pain of his rheumatic old father. PMID:11878097

  8. Treatment with human immunoglobulin G improves the early disease course in a mouse model of Duchenne muscular dystrophy.

    PubMed

    Zschüntzsch, Jana; Zhang, Yaxin; Klinker, Florian; Makosch, Gregor; Klinge, Lars; Malzahn, Dörthe; Brinkmeier, Heinrich; Liebetanz, David; Schmidt, Jens

    2016-01-01

    Duchenne muscular dystrophy (DMD) is a severe hereditary myopathy. Standard treatment by glucocorticosteroids is limited because of numerous side effects. The aim of this study was to test immunomodulation by human immunoglobulin G (IgG) as treatment in the experimental mouse model (mdx) of DMD. 2 g/kg human IgG compared to human albumin was injected intraperitoneally in mdx mice at the age of 3 and 7 weeks. Advanced voluntary wheel running parameters were recorded continuously. At the age of 11 weeks, animals were killed so that blood, diaphragm, and lower limb muscles could be removed for quantitative PCR, histological analysis and ex vivo muscle contraction tests. IgG compared to albumin significantly improved the voluntary running performance and reduced muscle fatigability in an ex vivo muscle contraction test. Upon IgG treatment, serum creatine kinase values were diminished and mRNA expression levels of relevant inflammatory markers were reduced in the diaphragm and limb muscles. Macrophage infiltration and myopathic damage were significantly ameliorated in the quadriceps muscle. Collectively, this study demonstrates that, in the early disease course of mdx mice, human IgG improves the running performance and diminishes myopathic damage and inflammation in the muscle. Therefore, IgG may be a promising approach for treatment of DMD. Two monthly intraperitoneal injections of human immunoglobulin G (IgG) improved the early 11-week disease phase of mdx mice. Voluntary running was improved and serum levels of creatine kinase were diminished. In the skeletal muscle, myopathic damage was ameliorated and key inflammatory markers such as mRNA expression of SPP1 and infiltration by macrophages were reduced. The study suggests that IgG could be explored as a potential treatment option for Duchenne muscular dystrophy and that pre-clinical long-term studies should be helpful. PMID:26230042

  9. Establishing the volatile profile of pig carcasses as analogues for human decomposition during the early postmortem period.

    PubMed

    Armstrong, P; Nizio, K D; Perrault, K A; Forbes, S L

    2016-02-01

    Following a mass disaster, it is important that victims are rapidly located as the chances of survival decrease greatly after approximately 48 h. Urban search and rescue (USAR) teams may use a range of tools to assist their efforts but detector dogs still remain one of the most effective search tools to locate victims of mass disasters. USAR teams can choose to deploy human scent dogs (trained to locate living victims) or human remains detection (HRD) dogs (trained to locate deceased victims). However, little is known about the variation between live human scent and postmortem human remains scent and the timeframe during which one type of scent transitions to the other. The aim of the current study was to measure the change in the scent profile of human decomposition analogues during the first 72 h postmortem by measuring the volatile organic compounds (VOCs) that comprise the odour. Three pig carcasses (Sus scrofa domesticus L.) were placed on a soil surface and allowed to decompose under natural conditions. Decomposition odour was sampled frequently up to 75 h postmortem and analysed using comprehensive two-dimensional gas chromatography - time-of-flight mass spectrometry (GC×GC-TOFMS). A total of 105 postmortem VOCs were identified during the early postmortem period. The VOC profile during the early postmortem period was highly dynamic, changing both hourly and daily. A transition period was observed after 43 h postmortem, where the VOC profile appeared to shift from a distinct antemortem odour to a more generalised postmortem odour. These findings are important in informing USAR teams and their use of detector dogs for disaster victim recovery. PMID:27441249

  10. Arab Republic of Egypt: Review of Early Childhood Education and Human Capital Formation.

    ERIC Educational Resources Information Center

    Ushiogi, Morikazu; Tanaka, Shinichira; O'Gara, Chloe; Sprague, David

    This report submitted to the World Bank analyzes the early childhood development (ECD) policies, strategies, and programs in Egypt in 2001. Information was gathered from documents, observations in kindergartens and nurseries, interviews with more than 50 teachers and parents, and a survey of policymakers and program managers in Cairo, Egypt. The…

  11. Thermophotonic lock-in imaging of early demineralized and carious lesions in human teeth.

    PubMed

    Tabatabaei, Nima; Mandelis, Andreas; Amaechi, Bennett Tochukwu

    2011-07-01

    As an extension of frequency-domain photothermal radiometry, a novel dental-imaging modality, thermophotonic lock-in imaging (TPLI), is introduced. This methodology uses photothermal wave principles and is capable of detecting early carious lesions and cracks on occlusal and approximal surfaces as well as early caries induced by artificial demineralizing solutions. The increased light scattering and absorption within early carious lesions increases the thermal-wave amplitude and shifts the thermal-wave centroid, producing contrast between the carious lesion and the intact enamel in both amplitude and phase images. Samples with artificial and natural occlusal and approximal caries were examined in this study. Thermophotonic effective detection depth is controlled by the modulation frequency according to the well-known concept of thermal diffusion length. TPLI phase images are emissivity normalized and therefore insensitive to the presence of stains. Amplitude images, on the other hand, provide integrated information from deeper enamel regions. It is concluded that the results of our noninvasive, noncontacting imaging methodology exhibit higher sensitivity to very early demineralization than dental radiographs and are in agreement with the destructive transverse microradiography mineral density profiles. PMID:21806248

  12. Thermophotonic lock-in imaging of early demineralized and carious lesions in human teeth

    NASA Astrophysics Data System (ADS)

    Tabatabaei, Nima; Mandelis, Andreas; Amaechi, Bennett Tochukwu

    2011-07-01

    As an extension of frequency-domain photothermal radiometry, a novel dental-imaging modality, thermophotonic lock-in imaging (TPLI), is introduced. This methodology uses photothermal wave principles and is capable of detecting early carious lesions and cracks on occlusal and approximal surfaces as well as early caries induced by artificial demineralizing solutions. The increased light scattering and absorption within early carious lesions increases the thermal-wave amplitude and shifts the thermal-wave centroid, producing contrast between the carious lesion and the intact enamel in both amplitude and phase images. Samples with artificial and natural occlusal and approximal caries were examined in this study. Thermophotonic effective detection depth is controlled by the modulation frequency according to the well-known concept of thermal diffusion length. TPLI phase images are emissivity normalized and therefore insensitive to the presence of stains. Amplitude images, on the other hand, provide integrated information from deeper enamel regions. It is concluded that the results of our noninvasive, noncontacting imaging methodology exhibit higher sensitivity to very early demineralization than dental radiographs and are in agreement with the destructive transverse microradiography mineral density profiles.

  13. Depictions of Human Bodies in the Illustrations of Early Childhood Textbooks

    ERIC Educational Resources Information Center

    Martínez-Bello, Vladimir E.; Martínez-Bello, Daniel A.

    2016-01-01

    In many Ibero-American countries children in the early childhood education (ECE) system have the opportunity to interact with textbooks on a regular basis. The powerful social function of textbooks in socializing children in primary and secondary school, and in legitimizing what counts as cultural norms and officially sanctioned values and…

  14. MAP2 Immunostaining in Thick Sections for Early Ischemic Stroke Infarct Volume in Non-Human Primate Brain

    PubMed Central

    Kharlamov, Alexander; LaVerde, George C.; Nemoto, Edwin M.; Jungreis, Charles A.; Yushmanov, Victor E.; Jones, Stephen C.; Boada, Fernando E.

    2009-01-01

    The delineation of early infarction in large gyrencephalic brain cannot be accomplished with triphenyl-tetrazolium chloride (TTC) due to its limitations in the early phase, nor can it be identified with microtubule-associated protein 2 (MAP2) immunohistochemistry, due to the fragility of large thin sections. We hypothesize that MAP2 immunostaining of thick whole-brain sections can accurately identify early ischemia in the entire monkey brain. Using ischemic brains of one rat and three monkeys, a thick-section MAP2 immunostaining protocol was developed to outline the infarct region over the entire non-human primate brain. Comparison of adjacent thick and thin sections in a rat brain indicated complete correspondence between ischemic regions (100.4 mm3 ± 1.2%, n = 7, p = 0.44). Thick sections in monkey brain possessed the increased structural stability necessary for the extensive MAP2 immunostaining procedure permitting quantification of the ischemic region as a percent of total monkey brain, giving infarct volumes of 11.4, 16.3, and 19.0% of total brain. Stacked 2D images of the intact thick brain tissue sections provided a 3D representation for comparison to MRI images. The infarct volume of 16.1 cm3 from the MAP2 sections registered with MRI images agreed well with the volume calculated directly from the stained sections of 16.6 cm3. Thick brain tissue section MAP2 immunostaining provides a new method for determining infarct volume over the entire brain at early time points in a non-human primate model of ischemic stroke. PMID:19540877

  15. Human cannibalism in the Early Pleistocene of Europe (Gran Dolina, Sierra de Atapuerca, Burgos, Spain).

    PubMed

    Fernández-Jalvo, Y; Carlos Díez, J; Cáceres, I; Rosell, J

    1999-01-01

    Human remains belonging to at least six individuals were found in an exploratory excavation made at the site of Gran Dolina (Sierra de Atapuerca, Burgos, Spain). These remains were recovered from the Aurora Stratum of Unit TD6. This stratum has a thickness of approximately 30 cm. The area of the exploratory excavation is about 7 m(2). According to palaeomagnetic analyses, Unit TD6 shows reversed polarity, which is considered to belong to the Matuyama chron. This unit is immediately below TD7, where the Matuyama-Brunhes boundary has been detected, indicating an age of around 780,000 years BP. There is no specific distribution, treatment, or arrangement of the human remains, which were found randomly mixed with abundant faunal remains and stone tools. Most of the faunal and human fossil bones from the Aurora Stratum have human induced damage. Stone tool cutmarks are frequent, and peeling (a type of fracture similar to bending a fresh twig between the hands) provides a specific breakage pattern together with percussion marks and chopmarks. Both nonhuman and human remains show similar intensive exploitation. Slight differences, however, have been observed between fauna and humans (e.g., peeling frequent in humans, rare in fauna), that appear related to different musculature, weight, and bone structure. The characteristics of this fossil assemblage suggest that it is solely the result of consumptive activities as there is no evidence of ritual or other intention. The possibility of distinguishing between dietary vs. survival cannibalism is discussed here. PMID:10497001

  16. The origin of life and the last universal common ancestor: do we need a change of perspective?

    PubMed

    Glansdorff, Nicolas; Xu, Ying; Labedan, Bernard

    2009-09-01

    A complete tree with roots, trunk and crown remains an appropriate model to represent all steps of life's development, from the emergence of a unique genetic code up to the last universal common ancestor and its further radiation. Catalytic closure of a mixture of prebiotic polymers is a heuristic alternative to the RNA world. Conjectures about emergence of life in an infinite multiverse should not confuse probability with possibility. PMID:19524037

  17. Human cytomegalovirus (HCMV) immediate-early enhancer/promoter specificity during embryogenesis defines target tissues of congenital HCMV infection.

    PubMed Central

    Koedood, M; Fichtel, A; Meier, P; Mitchell, P J

    1995-01-01

    Congenital human cytomegalovirus (HCMV) infection is a common cause of deafness and neurological disabilities. Many aspects of this prenatal infection, including which cell types are infected and how infection proceeds, are poorly understood. Transcription of HCMV immediate-early (IE) genes is required for expression of all other HCMV genes and is dependent on host cell transcription factors. Cell type-specific differences in levels of IE transcription are believed to underlie differences in infection permissivity. However, DNA transfection experiments have paradoxically suggested that the HCMV major IE enhancer/promoter is a broadly active transcriptional element with little cell type specificity. In contrast, we show here that expression of a lacZ gene driven by the HCMV major IE enhancer/promoter -524 to +13 segment is restricted in transgenic mouse embryos to sites that correlate with known sites of congenital HCMV infection in human fetuses. This finding suggests that the IE enhancer/promoter is a major determinant of HCMV infection sites in humans and that transcription factors responsible for its regulation are cell type-specifically conserved between humans and mice. The lacZ expression patterns of these transgenic embryos yield insight into congenital HCMV pathogenesis by providing a spatiotemporal map of the sets of vascular, neural, and epithelial cells that are likely targets of infection. These transgenic mice may constitute a useful model system for investigating IE enhancer/promoter regulation in vivo and for identifying factors that modulate active and latent HCMV infections in humans. PMID:7884867

  18. Utility of a human FcRn transgenic mouse model in drug discovery for early assessment and prediction of human pharmacokinetics of monoclonal antibodies.

    PubMed

    Avery, Lindsay B; Wang, Mengmeng; Kavosi, Mania S; Joyce, Alison; Kurz, Jeffrey C; Fan, Yao-Yun; Dowty, Martin E; Zhang, Minlei; Zhang, Yiqun; Cheng, Aili; Hua, Fei; Jones, Hannah M; Neubert, Hendrik; Polzer, Robert J; O'Hara, Denise M

    2016-01-01

    Therapeutic antibodies continue to develop as an emerging drug class, with a need for preclinical tools to better predict in vivo characteristics. Transgenic mice expressing human neonatal Fc receptor (hFcRn) have potential as a preclinical pharmacokinetic (PK) model to project human PK of monoclonal antibodies (mAbs). Using a panel of 27 mAbs with a broad PK range, we sought to characterize and establish utility of this preclinical animal model and provide guidance for its application in drug development of mAbs. This set of mAbs was administered to both hemizygous and homozygous hFcRn transgenic mice (Tg32) at a single intravenous dose, and PK parameters were derived. Higher hFcRn protein tissue expression was confirmed by liquid chromatography-high resolution tandem mass spectrometry in Tg32 homozygous versus hemizygous mice. Clearance (CL) was calculated using non-compartmental analysis and correlations were assessed to historical data in wild-type mouse, non-human primate (NHP), and human. Results show that mAb CL in hFcRn Tg32 homozygous mouse correlate with human (r(2) = 0.83, r = 0.91, p < 0.01) better than NHP (r(2) = 0.67, r = 0.82, p < 0.01) for this dataset. Applying simple allometric scaling using an empirically derived best-fit exponent of 0.93 enabled the prediction of human CL from the Tg32 homozygous mouse within 2-fold error for 100% of mAbs tested. Implementing the Tg32 homozygous mouse model in discovery and preclinical drug development to predict human CL may result in an overall decreased usage of monkeys for PK studies, enhancement of the early selection of lead molecules, and ultimately a decrease in the time for a drug candidate to reach the clinic. PMID:27232760

  19. Proliferative re-modeling of the spatial organization of human superficial chondrocytes distant to focal early osteoarthritis (OA)

    PubMed Central

    Rolauffs, Bernd; Williams, James M.; Aurich, Matthias; Grodzinsky, Alan J.; Kuettner, Klaus E.; Cole, Ada A.

    2010-01-01

    Objective Human superficial chondrocytes show distinct spatial organizations whereas they commonly aggregate near osteoarthritic (OA) fissures. It is not known whether remodeling or destruction of the spatial chondrocyte organization may occur distant to focal (early) OA lesions. Methods The intact cartilages (condyles, patellofemoral groove, proximal tibia) distant to focal OA lesions of human grade 2 joints were compared to location-matched non-degenerative (grade 0–1) cartilages. Chondrocyte nuclei were stained with propidium iodide and recorded by fluorescence-microscopy in a top-down view. Chondrocyte arrangements were tested for randomness or significant grouping via point pattern analyses (Clark and Evans Aggregation Index), and were correlated with OA grade and surface cell densities. Results In grade 2 cartilages, superficial chondrocytes were situated in horizontal patterns such as strings, cluster, pairs and singles comparable to non-degenerative cartilage. In the intact cartilages of grade 2 joints, the spatial organization included a novel pattern, consisting of chondrocytes that were aligned in two parallel lines building double strings. These double strings correlated with an increased number of chondrocytes per group (p<0.05), increased corresponding superficial zone cell density (p<0.001), and were observed in all grade 2 condyles (p<0.001), some grade 2 tibiae (p<0.05) but never in grade 0–1 cartilage (p<0.001). Conclusion The present study is the first to identify a distinct spatial re-organization of human superficial chondrocytes in response to distant early OA lesions and suggests that proliferation had occurred distant to focal early OA. This spatial re-organization may serve to recruit metabolically active units as attempt to repair focal damage. PMID:20112377

  20. Human T-lymphotropic virus tax activates human cytomegalovirus major-immediate early promoter and improves production of recombinant proteins in HEK293 cells.

    PubMed

    Lwa, Teng Rhui; Lee, Jialing; Ng, Chew Har; Lew, Qiao Jing; Hia, Hui Ching; Chao, Sheng-Hao

    2011-01-01

    The human cytomegalovirus (CMV) major immediate-early (MIE) promoter is widely used in mammalian cells for production of recombinant proteins. It is of great interest to further enhance protein production driven by the CMV promoter. Here, we report that the Tax protein of human T-lymphotropic virus stimulates the transgene expression under the control of CMV MIE promoter in HEK293 cells. At least threefold increases in transient production of recombinant proteins, including luciferase and two biopharmaceutical proteins (erythropoietin and interferon-γ), were detected. Furthermore, cyclic adenosine monophosphate (AMP)-response element binding protein 2 (CREB2) was identified as a cellular cofactor, which might be responsible for Tax transactivation of the CMV MIE promoter. Our results not only demonstrate the potential use of this novel expression strategy for improvement of recombinant protein production in HEK293 cells but also provide the molecular mechanism for Tax-mediated activation of CMV MIE promoter. PMID:21425252

  1. Late Mesolithic and early Neolithic forest disturbance: a high resolution palaeoecological test of human impact hypotheses

    NASA Astrophysics Data System (ADS)

    Innes, James B.; Blackford, Jeffrey J.; Rowley-Conwy, Peter A.

    2013-10-01

    The transition in north-west Europe from the hunter-gatherer societies of the Late Mesolithic to the pioneer farming societies of the early Neolithic is not well understood, either culturally or palaeoecologically. In Britain the final transition was rapid but it is unclear whether novel Neolithic attributes were introduced by immigrants who supplanted the native hunter-gatherers, or whether the latest Mesolithic foragers gradually adopted elements of the Neolithic economic package. In this study, relatively coarse- (10 mm interval) and fine-resolution (2 mm), multi-proxy palaeoecological data including pollen, charcoal and NPPs including fungi, have been used to investigate two phases of vegetation disturbance of (a) distinctly Late Mesolithic and (b) early Neolithic age, at an upland site in northern England in a region with both a Neolithic and a Late Mesolithic archaeological presence. We identify and define the palaeoecological characteristics of these two disturbance phases, about a millennium apart, in order to investigate whether differing land-use techniques can be identified and categorised as of either foraging or early farming cultures. The Late Mesolithic phase is defined by the repetitive application of fire to the woodland to encourage a mosaic of productive vegetation regeneration patches, consistent with the promotion of Corylus and to aid hunting. In this phase, weed species including Plantago lanceolata, Rumex and Chenopodiaceae are frequent, taxa which are normally associated with the first farmers. The early Neolithic phase, including an Ulmus decline, has characteristics consistent with 'forest farming', possibly mainly for domestic livestock, with an inferred succession of tree girdling, fire-prepared cultivation, and coppice-woodland management. Such fine-resolution, potentially diagnostic land-use signatures may in future be used to recognise the cultural complexion of otherwise enigmatic woodland disturbance phases during the centuries of

  2. The proteomic complexity and rise of the primordial ancestor of diversified life

    PubMed Central

    2011-01-01

    Background The last universal common ancestor represents the primordial cellular organism from which diversified life was derived. This urancestor accumulated genetic information before the rise of organismal lineages and is considered to be either a simple 'progenote' organism with a rudimentary translational apparatus or a more complex 'cenancestor' with almost all essential biological processes. Recent comparative genomic studies support the latter model and propose that the urancestor was similar to modern organisms in terms of gene content. However, most of these studies were based on molecular sequences, which are fast evolving and of limited value for deep evolutionary explorations. Results Here we engage in a phylogenomic study of protein domain structure in the proteomes of 420 free-living fully sequenced organisms. Domains were defined at the highly conserved fold superfamily (FSF) level of structural classification and an iterative phylogenomic approach was used to reconstruct max_set and min_set FSF repertoires as upper and lower bounds of the urancestral proteome. While the functional make up of the urancestral sets was complex, they represent only 5-11% of the 1,420 FSFs of extant proteomes and their make up and reuse was at least 5 and 3 times smaller than proteomes of free-living organisms, repectively. Trees of proteomes reconstructed directly from FSFs or from molecular functions, which included the max_set and min_set as articial taxa, showed that urancestors were always placed at their base and rooted the tree of life in Archaea. Finally, a molecular clock of FSFs suggests the min_set reflects urancestral genetic make up more reliably and confirms diversified life emerged about 2.9 billion years ago during the start of planet oxygenation. Conclusions The minimum urancestral FSF set reveals the urancestor had advanced metabolic capabilities, was especially rich in nucleotide metabolism enzymes, had pathways for the biosynthesis of membrane sn1

  3. HYPERGLYCOSYLATED HUMAN CHORIONIC GONADOTROPIN AS AN EARLY PREDICTOR OF PREGNANCY OUTCOMES AFTER IN VITRO FERTILIZATION

    PubMed Central

    Chuan, Sandy; Homer, Michael; Pandian, Raj; Conway, Deirdre; Garzo, Gabriel; Yeo, Lisa; Su, H. Irene

    2014-01-01

    Objective To determine if hyperglycosylated hCG (hhCG), produced by invasive trophoblasts, measured as early as 9 days after egg retrieval can predict ongoing pregnancies (OP) after in vitro fertilization and fresh embryo transfer (IVF-ET). Design Cohort Setting Academic ART center Patients Consecutive patients undergoing IVF-ET Interventions Serum hhCG and hCG levels measured 9 (D9) and 16 (D16) days after egg retrieval Outcome Ongoing pregnancy (OP) beyond 9 weeks of gestation Results OP (62 of 112 participants) was associated with higher D9 levels of hhCG and hCG However, hhCG was detectable in all D9 OP samples, while hCG was detectable in only 22%. D9 hhCG levels >110 pg/mL was 96% specific for OP, yielding a positive predictive value of 95%. Compared to D9 hCG levels, hhCG was more sensitive and had a larger area under the curve (0.87 vs. 0.67). Diagnostic test characteristics were similar between D16 hhCG and hCG levels. Conclusions In patients undergoing assisted reproduction, a test to detect pregnancy early and predict outcomes is highly desirable. HhCG is detectable in serum 9 days after egg retrieval IVF-ET cycles. At this early assessment, hhCG is superior to traditional hCG and highly predictive of ongoing pregnancies. PMID:24355054

  4. FTIR microspectroscopy defines early drug resistant human hepatocellular carcinoma (HepG2) cells.

    PubMed

    Junhom, Cholpajsorn; Weerapreeyakul, Natthida; Tanthanuch, Waraporn; Thumanu, Kanjana

    2016-01-01

    Characterization and identification of cancer cell, chemotherapy, resistance is important for both routine cancer therapy and trouble-shooting the medication treatment regimen. Present techniques for characterizing cancer cell resistance require multiple methods and steps, which are time-consuming and expensive. We present a protocol for simple sample handling, rapid detection, and spectral characterization of early resistant hepatocellular carcinoma (HepG2) cells, using Fourier transform infrared microspectroscopy (FTIR). Studies on alteration of the biochemical properties in a resistant HepG2 cell were evaluated-viz., increase efflux proteins (MRP-1 and P-gp) activity, total GSH content, anti-apoptotic (Bcl2) expression, and reduction of pro-apoptotic (Bax) proteins. Principle component analysis (PCA) was used to discriminate resistant HepG2 cells from parental HepG2 cells. Three important FTIR spectral regions were evaluated for reproducibility and discrimination ability-viz., lipid (3,000-2,800 cm(-1)), protein (1,700-1,500 cm(-1)) and carbohydrate and nucleic acid (1,300-900 cm(-1)). These 3 spectral regions can be used as spectroscopic biomarkers for differentiation of early or low resistance. This work presents a novel concept for high-throughput, FTIR spectroscopic discrimination of early resistance; thus enabling identification and characterization of cancer cell resistance. PMID:26708618

  5. Early induction of a prechondrogenic population allows efficient generation of stable chondrocytes from human induced pluripotent stem cells

    PubMed Central

    Lee, Jieun; Taylor, Sarah E. B.; Smeriglio, Piera; Lai, Janice; Maloney, William J.; Yang, Fan; Bhutani, Nidhi

    2015-01-01

    Regeneration of human cartilage is inherently inefficient; an abundant autologous source, such as human induced pluripotent stem cells (hiPSCs), is therefore attractive for engineering cartilage. We report a growth factor-based protocol for differentiating hiPSCs into articular-like chondrocytes (hiChondrocytes) within 2 weeks, with an overall efficiency >90%. The hiChondrocytes are stable and comparable to adult articular chondrocytes in global gene expression, extracellular matrix production, and ability to generate cartilage tissue in vitro and in immune-deficient mice. Molecular characterization identified an early SRY (sex-determining region Y) box (Sox)9low cluster of differentiation (CD)44lowCD140low prechondrogenic population during hiPSC differentiation. In addition, 2 distinct Sox9-regulated gene networks were identified in the Sox9low and Sox9high populations providing novel molecular insights into chondrogenic fate commitment and differentiation. Our findings present a favorable method for generating hiPSC-derived articular-like chondrocytes. The hiChondrocytes are an attractive cell source for cartilage engineering because of their abundance, autologous nature, and potential to generate articular-like cartilage rather than fibrocartilage. In addition, hiChondrocytes can be excellent tools for modeling human musculoskeletal diseases in a dish and for rapid drug screening.—Lee, J., Taylor, S. E. B., Smeriglio, P., Lai, J., Maloney, W. J., Yang, F., Bhutani, N. Early induction of a prechondrogenic population allows efficient generation of stable chondrocytes from human induced pluripotent stem cells. PMID:25911615

  6. Genomic and Proteomic Analyses Indicate that Banchine and Campoplegine Polydnaviruses Have Similar, if Not Identical, Viral Ancestors

    PubMed Central

    Béliveau, Catherine; Cohen, Alejandro; Stewart, Don; Periquet, Georges; Djoumad, Abdelmadjid; Kuhn, Lisa; Stoltz, Don; Boyle, Brian; Volkoff, Anne-Nathalie; Herniou, Elisabeth A.; Drezen, Jean-Michel

    2015-01-01

    ABSTRACT Polydnaviruses form a group of unconventional double-stranded DNA (dsDNA) viruses transmitted by endoparasitic wasps during egg laying into caterpillar hosts, where viral gene expression is essential to immature wasp survival. A copy of the viral genome is present in wasp chromosomes, thus ensuring vertical transmission. Polydnaviruses comprise two taxa, Bracovirus and Ichnovirus, shown to have distinct viral ancestors whose genomes were “captured” by ancestral wasps. While evidence indicates that bracoviruses derive from a nudivirus ancestor, the identity of the ichnovirus progenitor remains unknown. In addition, ichnoviruses are found in two ichneumonid wasp subfamilies, Campopleginae and Banchinae, where they constitute morphologically and genomically different virus types. To address the question of whether these two ichnovirus subgroups have distinct ancestors, we used genomic, proteomic, and transcriptomic analyses to characterize particle proteins of the banchine Glypta fumiferanae ichnovirus and the genes encoding them. Several proteins were found to be homologous to those identified earlier for campoplegine ichnoviruses while the corresponding genes were located in clusters of the wasp genome similar to those observed previously in a campoplegine wasp. However, for the first time in a polydnavirus system, these clusters also revealed sequences encoding enzymes presumed to form the replicative machinery of the progenitor virus and observed to be overexpressed in the virogenic tissue. Homology searches pointed to nucleocytoplasmic large DNA viruses as the likely source of these genes. These data, along with an analysis of the chromosomal form of five viral genome segments, provide clear evidence for the relatedness of the banchine and campoplegine ichnovirus ancestors. IMPORTANCE Recent work indicates that the two recognized polydnavirus taxa, Bracovirus and Ichnovirus, are derived from distinct viruses whose genomes integrated into the genomes

  7. The Brazilian megamastofauna of the Pleistocene/Holocene transition and its relationship with the early human settlement of the continent

    NASA Astrophysics Data System (ADS)

    Hubbe, Alex; Hubbe, Mark; Neves, Walter A.

    2013-03-01

    One of the most intriguing questions regarding the Brazilian Late Quaternary extinct megafauna and Homo sapiens is to what extent they coexisted and how humans could have contributed to the former's extinction. The aim of this article is to review the chronological and archaeological evidences of their coexistence in Brazil and to evaluate the degree of direct interaction between them. Critical assessment of the Brazilian megafauna chronological data shows that several of the late Pleistoscene/early Holocene dates available so far cannot be considered reliable, but the few that do suggest that at least two species (Catonyx cuvieri, ground sloth; Smilodon populator, saber-toothed cat) survived until the beginning of the Holocene in Southeast Brazil. Archaeological data indicates that the first human groups arrived in Brazil and were inhabiting this region during the last millennia of the Pleistocene and, consequently, they coexisted with the extinct fauna in some parts of Brazil for at least one thousand years. There is no robust evidence favoring any kind of direct interaction between humans and megafauna prior to their extinction. To date, it is not possible to properly judge the indirect influence of humans (landscape transformation, introduction of predators, among others) in this extinction event. Intense and to some extent unique climate changes between the Last Glacial Maximum and the Holocene favors the interpretation that they had a major contribution to the megafauna extinction, although the scarcity of data impedes the proper testing of this hypothesis.

  8. Pairwise Comparisons of Mitochondrial DNA Sequences in Subdivided Populations and Implications for Early Human Evolution

    PubMed Central

    Marjoram, P.; Donnelly, P.

    1994-01-01

    We consider the effect on the distribution of pairwise differences between mitochondrial DNA sequences of the incorporation into the underlying population genetics model of two particular effects that seem realistic for human populations. The first is that the population size was roughly constant before growing to its current level. The second is that the population is geographically subdivided rather than panmictic. In each case these features tend to encourage multimodal distributions of pairwise differences, in contrast to existing, unimodal datasets. We argue that population genetics models currently used to analyze such data may thus fail to reflect important features of human mitochondrial DNA evolution. These may include selection on the mitochondrial genome, more realistic mutation mechanisms, or special population or migration dynamics. Particularly in view of the variability inherent in the single available human mitochondrial genealogy, it is argued that until these effects are better understood, inferences from such data should be rather cautious. PMID:8150290

  9. Effect of intron A from human cytomegalovirus (Towne) immediate-early gene on heterologous expression in mammalian cells.

    PubMed Central

    Chapman, B S; Thayer, R M; Vincent, K A; Haigwood, N L

    1991-01-01

    A 2.4 kb fragment of hCMV (Towne strain), containing the 5' end of the major immediate-early gene, has been cloned, sequenced, and used to construct a series of mammalian cell expression plasmids. The effects of regulatory regions present on this fragment were assessed using human glycoproteins as reporter molecules. We compared secreted levels of Factor VIII, t-PA, and HIV-1 envelope glycoproteins in cells transfected with plasmids in which intron A of the immediate-early gene was present or absent. Secretion of several glycoproteins was significantly higher when cells were transfected with intron A-containing plasmids. Mutation of three basepairs in the strong nuclear factor 1 (NF1) binding site in intron A led to reduced transient expression levels, but not to the level observed in the absence of intron A. Reduced expression from NF1 mutant plasmids was roughly correlated with reduced binding in vitro of NF1 proteins to a synthetic oligonucleotide containing the mutation. The evidence indicates that sequences in intron A positively regulate expression from the hCMV immediate-early enhancer/promoter in transformed monkey kidney cells. Images PMID:1650459

  10. Platelet rich concentrate promotes early cellular proliferation and multiple lineage differentiation of human mesenchymal stromal cells in vitro.

    PubMed

    Shani, Samuel; Ahmad, Raja Elina; Naveen, Sangeetha Vasudevaraj; Murali, Malliga Raman; Puvanan, Karunanithi; Abbas, Azlina Amir; Kamarul, Tunku

    2014-01-01

    Platelet rich concentrate (PRC) is a natural adjuvant that aids in human mesenchymal stromal cell (hMSC) proliferation in vitro; however, its role requires further exploration. This study was conducted to determine the optimal concentration of PRC required for achieving the maximal proliferation, and the need for activating the platelets to achieve this effect, and if PRC could independently induce early differentiation of hMSC. The gene expression of markers for osteocytes (ALP, RUNX2), chondrocytes (SOX9, COL2A1), and adipocytes (PPAR-γ) was determined at each time point in hMSC treated with 15% activated and nonactivated PRC since maximal proliferative effect was achieved at this concentration. The isolated PRC had approximately fourfold higher platelet count than whole blood. There was no significant difference in hMSC proliferation between the activated and nonactivated PRC. Only RUNX2 and SOX9 genes were upregulated throughout the 8 days. However, protein expression study showed formation of oil globules from day 4, significant increase in ALP at days 6 and 8 (P ≤ 0.05), and increased glycosaminoglycan levels at all time points (P < 0.05), suggesting the early differentiation of hMSC into osteogenic and adipogenic lineages. This study demonstrates that the use of PRC increased hMSC proliferation and induced early differentiation of hMSC into multiple mesenchymal lineages, without preactivation or addition of differentiation medium. PMID:25436230

  11. Human Type 1 Diabetes Is Characterized by an Early, Marked, Sustained, and Islet-Selective Loss of Sympathetic Nerves.

    PubMed

    Mundinger, Thomas O; Mei, Qi; Foulis, Alan K; Fligner, Corinne L; Hull, Rebecca L; Taborsky, Gerald J

    2016-08-01

    In humans, the glucagon response to moderate-to-marked insulin-induced hypoglycemia (IIH) is largely mediated by the autonomic nervous system. Because this glucagon response is impaired early in type 1 diabetes, we sought to determine if these patients, like animal models of autoimmune diabetes, have an early and severe loss of islet sympathetic nerves. We also tested whether this nerve loss is a permanent feature of type 1 diabetes, is islet-selective, and is not seen in type 2 diabetes. To do so, we quantified pancreatic islet and exocrine sympathetic nerve fiber area from autopsy samples of patients with type 1 or 2 diabetes and control subjects without diabetes. Our central finding is that patients with either very recent onset (<2 weeks) or long duration (>10 years) of type 1 diabetes have a severe loss of islet sympathetic nerves (Δ = -88% and Δ = -79%, respectively). In contrast, patients with type 2 diabetes lose no islet sympathetic nerves. There is no loss of exocrine sympathetic nerves in either type 1 or type 2 diabetes. We conclude that patients with type 1, but not type 2, diabetes have an early, marked, sustained, and islet-selective loss of sympathetic nerves, one that may impair their glucagon response to IIH. PMID:27207540

  12. East African megadroughts between 135 and 75 thousand years ago and bearing on early-modern human origins

    PubMed Central

    Scholz, Christopher A.; Johnson, Thomas C.; Cohen, Andrew S.; King, John W.; Peck, John A.; Overpeck, Jonathan T.; Talbot, Michael R.; Brown, Erik T.; Kalindekafe, Leonard; Amoako, Philip Y. O.; Lyons, Robert P.; Shanahan, Timothy M.; Castañeda, Isla S.; Heil, Clifford W.; Forman, Steven L.; McHargue, Lanny R.; Beuning, Kristina R.; Gomez, Jeanette; Pierson, James

    2007-01-01

    The environmental backdrop to the evolution and spread of early Homo sapiens in East Africa is known mainly from isolated outcrops and distant marine sediment cores. Here we present results from new scientific drill cores from Lake Malawi, the first long and continuous, high-fidelity records of tropical climate change from the continent itself. Our record shows periods of severe aridity between 135 and 75 thousand years (kyr) ago, when the lake's water volume was reduced by at least 95%. Surprisingly, these intervals of pronounced tropical African aridity in the early late-Pleistocene were much more severe than the Last Glacial Maximum (LGM), the period previously recognized as one of the most arid of the Quaternary. From these cores and from records from Lakes Tanganyika (East Africa) and Bosumtwi (West Africa), we document a major rise in water levels and a shift to more humid conditions over much of tropical Africa after ≈70 kyr ago. This transition to wetter, more stable conditions coincides with diminished orbital eccentricity, and a reduction in precession-dominated climatic extremes. The observed climate mode switch to decreased environmental variability is consistent with terrestrial and marine records from in and around tropical Africa, but our records provide evidence for dramatically wetter conditions after 70 kyr ago. Such climate change may have stimulated the expansion and migrations of early modern human populations. PMID:17785420

  13. Early-life reproduction is associated with increased mortality risk but enhanced lifetime fitness in pre-industrial humans

    PubMed Central

    Hayward, Adam D.; Nenko, Ilona; Lummaa, Virpi

    2015-01-01

    The physiology of reproductive senescence in women is well understood, but the drivers of variation in senescence rates are less so. Evolutionary theory predicts that early-life investment in reproduction should be favoured by selection at the cost of reduced survival and faster reproductive senescence. We tested this hypothesis using data collected from preindustrial Finnish church records. Reproductive success increased up to age 25 and was relatively stable until a decline from age 41. Women with higher early-life fecundity (ELF; producing more children before age 25) subsequently had higher mortality risk, but high ELF was not associated with accelerated senescence in annual breeding success. However, women with higher ELF experienced faster senescence in offspring survival. Despite these apparent costs, ELF was under positive selection: individuals with higher ELF had higher lifetime reproductive success. These results are consistent with previous observations in both humans and wild vertebrates that more births and earlier onset of reproduction are associated with reduced survival, and with evolutionary theory predicting trade-offs between early reproduction and later-life survival. The results are particularly significant given recent increases in maternal ages in many societies and the potential consequences for offspring health and fitness. PMID:25740893

  14. Floral homeotic genes were recruited from homologous MADS-box genes preexisting in the common ancestor of ferns and seed plants

    PubMed Central

    Münster, Thomas; Pahnke, Jens; Di Rosa, Alexandra; Kim, Jan T.; Martin, William; Saedler, Heinz; Theissen, Günter

    1997-01-01

    Flowers sensu lato are short, specialized axes bearing closely aggregated sporophylls. They are typical for seed plants (spermatophytes) and are prominent in flowering plants sensu stricto (angiosperms), where they often comprise an attractive perianth. There is evidence that spermatophytes evolved from gymnosperm-like plants with a fern-like mode of reproduction called progymnosperms. It seems plausible, therefore, that the stamens/carpels and pollen sacs/nucelli of spermatophytes are homologous to fern sporophylls and sporangia, respectively. However, the exact mode and molecular basis of early seed and flower evolution is not yet known. Comparing flower developmental control genes to their homologs from lower plants that do not flower may help to clarify the issue. We have isolated and characterized MADS-box genes expressed in gametophytes and sporophytes of the fern Ceratopteris. The data indicate that at least two different MADS-box genes homologous to floral homeotic genes existed in the last common ancestor of contemporary vascular plants, some descendants of which underwent multiple duplications and diversifications and were recruited into novel developmental networks during the evolution of floral organs. PMID:9122209

  15. Using Simcyp to project human oral pharmacokinetic variability in early drug research to mitigate mechanism-based adverse events.

    PubMed

    Shaffer, Christopher L; Scialis, Renato J; Rong, Haojing; Obach, R Scott

    2012-03-01

    Positive allosteric modulators ('potentiators') of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) have been shown to display a mechanism-based exposure-response continuum in preclinical species with procognitive electrophysiological and behavioral effects ('efficacy') at low exposures and motor coordination disruptions at progressively higher exposures. Due to the dose-capping nature of such motor coordination deficits, an exposure threshold-mediated adverse event (C(AE) ), the adequacy of separation between the maximal total plasma compound concentration (C(max) ) at a predicted clinically efficacious oral dose and this adverse event (AE) was explored in early drug research with three AMPAR potentiators considered potential candidates for clinical trials. In vitro metabolism studies in human liver microsomes and human hepatocytes demonstrated the metabolic clearance for each compound was predominately due to cytochromes P450 (CYP). Thus, for each compound's anticipated clinically efficacious dose, human C(max) variability following oral administration was assessed using Simcyp software, which combines its virtual human populations database using extensive demographic, physiological and genomic information with routinely collected compound-specific in vitro biochemical data to simulate and predict drug disposition. Using a combination of experimentally determined recombinant human CYP intrinsic clearances for CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP3A4, human binding factors, expected fraction absorbed and estimated steady-state volume of distribution, Simcyp simulations demonstrated that two of the three potentiators had acceptable projected C(max) variability (i.e. the 95th percentile C(max) did not breach C(AE) ). This evaluation aided in the selection of compounds for preclinical progression, and represents a novel application of pharmacologically based pharmacokinetic (PBPK) software approaches to predict interpatient

  16. Proteomic analysis of enriched lysosomes at early phase of camptothecin-induced apoptosis in human U-937 cells

    PubMed Central

    Parent, Nicolas; Winstall, Eric; Beauchemin, Myriam; Paquet, Claudie; Poirier, Guy G.; Bertrand, Richard

    2013-01-01

    A lysosomal pathway, characterized by partial rupture or labilization of lysosomal membranes and cathepsin activation, is evoked during camptothecin-induced apoptosis in human cancer cells, including human histiocytic lymphoma U-937 cells. These lysosomal events begin rapidly and simultaneously with mitochondrial permeabilization and caspase activation within 3 h after drug treatment. In this study, comparative and quantitative proteome analyses were performed to identify early changes in lysosomal protein expression/localization from U-937 cells undergoing apoptosis. In 2 independent experiments, among a total of more than 538 proteins putatively identified and quantitated by iTRAQ isobaric labeling and LC-ESI-MS/MS, 18 proteins were found to be upregulated and 9 downregulated in lysosomes purified from early apoptotic compared to control cells. Protein expression was validated by Western blotting on enriched lysosome fractions, and protein localization confirmed by fluorescence confocal microscopy of representative protein candidates, whose functions are associated with lysosomal membrane fluidity and dynamics. These include sterol-4-alpha-carboxylate 3-dehydrogenase (NSDHL), prosaposin (PSAP) and protein kinase C delta (PKC-δ). This comparative proteome analysis provides the basis for novel hypothesis and rationale functional experimentation, where the 3 validated candidate proteins are associated with lysosomal membrane fluidity and dynamics, particularly cholesterol, sphingolipid and glycosphingolipid metabolism. PMID:19393779

  17. Characterization of human vascular smooth muscle cells transformed by the early genetic region of SV40 virus.

    PubMed Central

    Legrand, A.; Greenspan, P.; Nagpal, M. L.; Nachtigal, S. A.; Nachtigal, M.

    1991-01-01

    Human arterial smooth muscle cells transfected with the plasmid pSV3-neo, which contains the SV40 virus early region and the neor gene, developed colonies of morphologically transformed cells. Five cell strains were initiated from these colonies and could be subcultivated for up to 9 months before entering a stage of crisis that ended their life span. Deoxyribonucleic acid (DNA) molecules containing viral sequences were found free and integrated in the transformed cells. The intranuclear SV40 large T antigen and the p53 cellular protein were expressed in the transformed cells. Most of the transformed cells were spindle shaped but some were large and multinucleated. The modal chromosome numbers were in the triploid range, and aberrations, particularly dicentrics, were common. The transcripts for smooth muscle actins were significantly reduced and there were less alpha-actin filaments detected by immunofluorescence. Cytochemical staining disclosed a large accumulation of lipid droplets in the transformed cells incubated with rabbit hypercholesterolemic beta-very-low-density lipoprotein. Chemical analysis showed that cholesteryl esters were significantly elevated in these cells. Phenotypic changes induced in human vascular smooth muscle cells by SV40 early genes are similar to those found in smooth muscle cells from atherosclerotic lesions and may indicate common pathogenetic mechanisms. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:1653520

  18. Early Pleistocene human hand phalanx from the Sima del Elefante (TE) cave site in Sierra de Atapuerca (Spain).

    PubMed

    Lorenzo, Carlos; Pablos, Adrián; Carretero, José Miguel; Huguet, Rosa; Valverdú, Josep; Martinón-Torres, María; Arsuaga, Juan Luis; Carbonell, Eudald; Bermúdez de Castro, José María

    2015-01-01

    In this study, a new Early Pleistocene proximal hand phalanx (ATE9-2) from the Sima del Elefante cave site (TE - Sierra de Atapuerca, Spain), ascribed to Homo sp., is presented and comparatively described in the context of the evolution of the genus Homo. The ATE9-2 specimen is especially important because of the paucity of hand bones in the human fossil record during the Early Pleistocene. The morphological and metrical analyses of the phalanx ATE9-2 indicate that there are no essential differences between it and comparator fossil specimens for the genus Homo after 1.3 Ma (millions of years ago). Similar to Sima de los Huesos and Neandertal specimens, ATE9-2 is a robust proximal hand phalanx, probably reflecting greater overall body robusticity in these populations or a higher gracility in modern humans. The age of level TE9 from Sima del Elefante and morphological and metrical studies of ATE9-2 suggest that the morphology of the proximal hand phalanges and, thus, the morphology of the hand could have remained stable over the last 1.2-1.3 Ma. Taking into account the evidence recently provided by a metacarpal from Kaitio (Kenya) from around 1.42 Ma, we argue that modern hand morphology is present in the genus Homo subsequent to Homo habilis. PMID:25200886

  19. Six1 overexpression at early stages of HPV16-mediated transformation of human keratinocytes promotes differentiation resistance and EMT

    SciTech Connect

    Xu, Hanwen; Pirisi, Lucia; Creek, Kim E.

    2015-01-01

    Previous studies in our laboratory discovered that SIX1 mRNA expression increased during in vitro progression of HPV16-immortalized human keratinocytes (HKc/HPV16) toward a differentiation-resistant (HKc/DR) phenotype. In this study, we explored the role of Six1 at early stages of HPV16-mediated transformation by overexpressing Six1 in HKc/HPV16. We found that Six1 overexpression in HKc/HPV16 increased cell proliferation and promoted cell migration and invasion by inducing epithelial–mesenchymal transition (EMT). Moreover, the overexpression of Six1 in HKc/HPV16 resulted in resistance to serum and calcium-induced differentiation, which is the hallmark of the HKc/DR phenotype. Activation of MAPK in HKc/HPV16 overexpressing Six1 is linked to resistance to calcium-induced differentiation. In conclusion, this study determined that Six1 overexpression resulted in differentiation resistance and promoted EMT at early stages of HPV16-mediated transformation of human keratinocytes. - Highlights: • Six1 expression increases during HPV16-mediated transformation. • Six1 overexpression causes differentiation resistance in HPV16-immortalized cells. • Six1 overexpression in HPV16-immortalized keratinocytes activates MAPK. • Activation of MAPK promotes EMT and differentiation resistance. • Six1 overexpression reduces Smad-dependent TGF-β signaling.

  20. Biodemography of Exceptional Longevity: Early-life and Mid-life predictors of Human Longevity

    PubMed Central

    Gavrilov, Leonid A.; Gavrilova, Natalia S.

    2011-01-01

    Effects of early-life and middle-life conditions on exceptional longevity are explored in this study using two matched case-control studies. The first study compares 198 validated centenarians born in the United States in 1890-1893 to their shorter-lived siblings. Family histories of centenarians were reconstructed and exceptional longevity validated using early U.S. censuses, Social Security Administration Death Master File, state death indexes, online genealogies and other supplementary data resources. Siblings born to young mothers (<25 years) had significantly higher chances to live to 100 compared to siblings born to older mothers (odds ratio = 2.03, 95% CI = 1.33 - 3.11, P = 0.001) while paternal age and birth order were not associated with exceptional longevity. The second study explores whether people living to 100 and beyond are any different in physical characteristics at young age from their shorter-lived peers. A random representative sample of 240 men born in 1887 and survived to age 100 was selected from the US Social Security Administration database and linked to the US WWI civil draft registration cards collected in 1917 when these men were 30 years old. These validated centenarians were then compared to randomly selected controls matched by calendar year of birth, race and place of draft registration in 1917. It was found that ‘stout’ body build (being in the heaviest 15% of population) was negatively associated with survival to age 100 years. Farmer occupation and large number of children (4+) at age 30 increased the chances of exceptional longevity. Detailed description of dataset development, data cleaning procedure and validation of exceptional longevity is provided for both studies. These results demonstrate that matched case-control design is a useful approach in exploring effects of early-life conditions and middle-life characteristics on exceptional longevity. PMID:22582891

  1. Human Adipose Tissue-Derived Stromal/Stem Cells Promote Migration and Early Metastasis of Triple Negative Breast Cancer Xenografts

    PubMed Central

    Rowan, Brian G.; Gimble, Jeffrey M.; Sheng, Mei; Anbalagan, Muralidharan; Jones, Ryan K.; Frazier, Trivia P.; Asher, Majdouline; Lacayo, Eduardo A.; Friedlander, Paul L.; Kutner, Robert; Chiu, Ernest S.

    2014-01-01

    Background Fat grafting is used to restore breast defects after surgical resection of breast tumors. Supplementing fat grafts with adipose tissue-derived stromal/stem cells (ASCs) is proposed to improve the regenerative/restorative ability of the graft and retention. However, long term safety for ASC grafting in proximity of residual breast cancer cells is unknown. The objective of this study was to determine the impact of human ASCs derived from abdominal lipoaspirates of three donors, on a human breast cancer model that exhibits early metastasis. Methodology/Principal Findings Human MDA-MB-231 breast cancer cells represents “triple negative” breast cancer that exhibits early micrometastasis to multiple mouse organs [1]. Human ASCs were derived from abdominal adipose tissue from three healthy female donors. Indirect co-culture of MDA-MB-231 cells with ASCs, as well as direct co-culture demonstrated that ASCs had no effect on MDA-MB-231 growth. Indirect co-culture, and ASC conditioned medium (CM) stimulated migration of MDA-MB-231 cells. ASC/RFP cells from two donors co-injected with MDA-MB-231/GFP cells exhibited a donor effect for stimulation of primary tumor xenografts. Both ASC donors stimulated metastasis. ASC/RFP cells were viable, and integrated with MDA-MB-231/GFP cells in the tumor. Tumors from the co-injection group of one ASC donor exhibited elevated vimentin, matrix metalloproteinase-9 (MMP-9), IL-8, VEGF and microvessel density. The co-injection group exhibited visible metastases to the lung/liver and enlarged spleen not evident in mice injected with MDA-MB-231/GFP alone. Quantitation of the total area of GFP fluorescence and human chromosome 17 DNA in mouse organs, H&E stained paraffin sections and fluorescent microscopy confirmed multi-focal metastases to lung/liver/spleen in the co-injection group without evidence of ASC/RFP cells. Conclusions Human ASCs derived from abdominal lipoaspirates of two donors stimulated metastasis of MDA-MB-231

  2. Form and function of the human and chimpanzee forefoot: implications for early hominin bipedalism.

    PubMed

    Fernández, Peter J; Holowka, Nicholas B; Demes, Brigitte; Jungers, William L

    2016-01-01

    During bipedal walking, modern humans dorsiflex their forefoot at the metatarsophalangeal joints (MTPJs) prior to push off, which tightens the plantar soft tissues to convert the foot into a stiff propulsive lever. Particular features of metatarsal head morphology such as "dorsal doming" are thought to facilitate this stiffening mechanism. In contrast, chimpanzees are believed to possess MTPJ morphology that precludes high dorsiflexion excursions during terrestrial locomotion. The morphological affinity of the metatarsal heads has been used to reconstruct locomotor behavior in fossil hominins, but few studies have provided detailed empirical data to validate the assumed link between morphology and function at the MTPJs. Using three-dimensional kinematic and morphometric analyses, we show that humans push off with greater peak dorsiflexion angles at all MTPJs than do chimpanzees during bipedal and quadrupedal walking, with the greatest disparity occurring at MTPJ 1. Among MTPJs 2-5, both species exhibit decreasing peak angles from medial to lateral. This kinematic pattern is mirrored in the morphometric analyses of metatarsal head shape. Analyses of Australopithecus afarensis metatarsals reveal morphology intermediate between humans and chimpanzees, suggesting that this species used different bipedal push-off kinematics than modern humans, perhaps resulting in a less efficient form of bipedalism. PMID:27464580

  3. Mastering a mediator: blockade of CCN-2 shows early promise in human diabetic kidney disease

    PubMed Central

    2010-01-01

    In diabetes complications, CCN-2 (known originally as CTGF) has been implicated in diabetic nephropathy both as a marker and a mediator of disease. This commentary addresses CCN-2 in diabetic nephropathy, in the context of the recent publication of the first human study to inhibit CCN-2 bioactivity in diabetic kidney disease. PMID:21234125

  4. Form and function of the human and chimpanzee forefoot: implications for early hominin bipedalism

    PubMed Central

    Fernández, Peter J.; Holowka, Nicholas B.; Demes, Brigitte; Jungers, William L.

    2016-01-01

    During bipedal walking, modern humans dorsiflex their forefoot at the metatarsophalangeal joints (MTPJs) prior to push off, which tightens the plantar soft tissues to convert the foot into a stiff propulsive lever. Particular features of metatarsal head morphology such as “dorsal doming” are thought to facilitate this stiffening mechanism. In contrast, chimpanzees are believed to possess MTPJ morphology that precludes high dorsiflexion excursions during terrestrial locomotion. The morphological affinity of the metatarsal heads has been used to reconstruct locomotor behavior in fossil hominins, but few studies have provided detailed empirical data to validate the assumed link between morphology and function at the MTPJs. Using three-dimensional kinematic and morphometric analyses, we show that humans push off with greater peak dorsiflexion angles at all MTPJs than do chimpanzees during bipedal and quadrupedal walking, with the greatest disparity occurring at MTPJ 1. Among MTPJs 2–5, both species exhibit decreasing peak angles from medial to lateral. This kinematic pattern is mirrored in the morphometric analyses of metatarsal head shape. Analyses of Australopithecus afarensis metatarsals reveal morphology intermediate between humans and chimpanzees, suggesting that this species used different bipedal push-off kinematics than modern humans, perhaps resulting in a less efficient form of bipedalism. PMID:27464580

  5. Early gene response of human brain endothelial cells to Listeria monocytogenes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The gene expression of human brain microvascular endothelial cells (HBMEC) to Listeria monocytogenes at 4 hour infection was analyzed. Four hours after infection, the expression of 456 genes of HBMEC had changed (p<0.05). We noted that many active genes were involved in the formyl-methionylleucylph...

  6. A Biosocial View of Population: Fertility Behavior in Animal Groups and Early Human Societies. A Review.

    ERIC Educational Resources Information Center

    Murphy, Elaine M.

    The paper discusses the relationship between social structure and fertility behavior in man. Focusing upon human fertility within the context of varying social groups, the document reviews recent interdisciplinary population studies. Information and interpretations from biology, ethnology, anthropology, history, and sociology are presented in four…

  7. Arab Republic of Egypt: Review of Early Childhood Education and Human Capital Formation.

    ERIC Educational Resources Information Center

    O'Gara, Chloe; Lusk, Diane

    This study analyzes human resources for kindergarten in Egypt, focusing on the provision of kindergarten programs as part of the public education system and as part of the private sector. The report is organized in 10 parts. Following an executive summary and introductory remarks, the report provides an inventory of public and private kindergarten…

  8. Preference for Language in Early Infancy: The Human Language Bias Is Not Speech Specific

    ERIC Educational Resources Information Center

    Krentz, Ursula C.; Corina, David P.

    2008-01-01

    Fundamental to infants' acquisition of their native language is an inherent interest in the language spoken around them over non-linguistic environmental sounds. The following studies explored whether the bias for linguistic signals in hearing infants is specific to speech, or reflects a general bias for all human language, spoken and signed.…

  9. The evolution of human warfare.

    PubMed

    Pitman, George R

    2011-01-01

    Here we propose a new theory for the origins and evolution of human warfare as a complex social phenomenon involving several behavioral traits, including aggression, risk taking, male bonding, ingroup altruism, outgroup xenophobia, dominance and subordination, and territoriality, all of which are encoded in the human genome. Among the family of great apes only chimpanzees and humans engage in war; consequently, warfare emerged in their immediate common ancestor that lived in patrilocal groups who fought one another for females. The reasons for warfare changed when the common ancestor females began to immigrate into the groups of their choice, and again, during the agricultural revolution. PMID:22081837

  10. Intracellular Aβ pathology and early cognitive impairments in a transgenic rat overexpressing human amyloid precursor protein: a multidimensional study.

    PubMed

    Iulita, M Florencia; Allard, Simon; Richter, Luise; Munter, Lisa-Marie; Ducatenzeiler, Adriana; Weise, Christoph; Do Carmo, Sonia; Klein, William L; Multhaup, Gerhard; Cuello, A Claudio

    2014-01-01

    Numerous studies have implicated the abnormal accumulation of intraneuronal amyloid-β (Aβ) as an important contributor to Alzheimer's disease (AD) pathology, capable of triggering neuroinflammation, tau hyperphosphorylation and cognitive deficits. However, the occurrence and pathological relevance of intracellular Aβ remain a matter of controversial debate. In this study, we have used a multidimensional approach including high-magnification and super-resolution microscopy, cerebro-spinal fluid (CSF) mass spectrometry analysis and ELISA to investigate the Aβ pathology and its associated cognitive impairments, in a novel transgenic rat model overexpressing human APP. Our microscopy studies with quantitative co-localization analysis revealed the presence of intraneuronal Aβ in transgenic rats, with an immunological signal that was clearly distinguished from that of the amyloid precursor protein (APP) and its C-terminal fragments (CTFs). The early intraneuronal pathology was accompanied by a significant elevation of soluble Aβ42 peptides that paralleled the presence and progression of early cognitive deficits, several months prior to amyloid plaque deposition. Aβ38, Aβ39, Aβ40 and Aβ42 peptides were detected in the rat CSF by MALDI-MS analysis even at the plaque-free stages; suggesting that a combination of intracellular and soluble extracellular Aβ may be responsible for impairing cognition at early time points. Taken together, our results demonstrate that the intraneuronal development of AD-like amyloid pathology includes a mixture of molecular species (Aβ, APP and CTFs) of which a considerable component is Aβ; and that the early presence of these species within neurons has deleterious effects in the CNS, even before the development of full-blown AD-like pathology. PMID:24903713

  11. Multispectral fluorescence imaging of human ovarian and Fallopian tube tissue for early stage cancer detection

    NASA Astrophysics Data System (ADS)

    Tate, Tyler; Baggett, Brenda; Rice, Photini; Watson, Jennifer; Orsinger, Gabe; Nymeyer, Ariel C.; Welge, Weston A.; Keenan, Molly; Saboda, Kathylynn; Roe, Denise J.; Hatch, Kenneth; Chambers, Setsuko; Black, John; Utzinger, Urs; Barton, Jennifer

    2015-03-01

    With early detection, five year survival rates for ovarian cancer are over 90%, yet no effective early screening method exists. Emerging consensus suggests that perhaps over 50% of the most lethal form of the disease, high grade serous ovarian cancer, originates in the Fallopian tube. Cancer changes molecular concentrations of various endogenous fluorophores. Using specific excitation wavelengths and emissions bands on a Multispectral Fluorescence Imaging (MFI) system, spatial and spectral data over a wide field of view can be collected from endogenous fluorophores. Wavelength specific reflectance images provide additional information to normalize for tissue geometry and blood absorption. Ratiometric combination of the images may create high contrast between neighboring normal and abnormal tissue. Twenty-six women undergoing oophorectomy or debulking surgery consented the use of surgical discard tissue samples for MFI imaging. Forty-nine pieces of ovarian tissue and thirty-two pieces of Fallopian tube tissue were collected and imaged with excitation wavelengths between 280 nm and 550 nm. After imaging, each tissue sample was fixed, sectioned and HE stained for pathological evaluation. Comparison of mean intensity values between normal, benign, and cancerous tissue demonstrate a general trend of increased fluorescence of benign tissue and decreased fluorescence of cancerous tissue when compared to normal tissue. The predictive capabilities of the mean intensity measurements are tested using multinomial logistic regression and quadratic discriminant analysis. Adaption of the system for in vivo Fallopian tube and ovary endoscopic imaging is possible and is briefly described.

  12. Tuberculosis in Late Neolithic-Early Copper Age human skeletal remains from Hungary.

    PubMed

    Pósa, Annamária; Maixner, Frank; Mende, Balázs Gusztáv; Köhler, Kitti; Osztás, Anett; Sola, Christophe; Dutour, Olivier; Masson, Muriel; Molnár, Erika; Pálfi, György; Zink, Albert

    2015-06-01

    Alsónyék-Bátaszék in Southern Hungary is one of the largest late Neolithic settlements and cemeteries excavated in Central Europe. In total, 2359 burials from the Late Neolithic - Early Copper Age Lengyel culture were found between 2006 and 2009 [1]. Anthropological investigations previously carried out on individuals from this site revealed an interesting paleopathological case of tuberculosis in the form of Pott's disease dated to the early 5(th) millennium BC. In this study, selected specimens from this osteoarcheological series were subjected to paleomicrobiological analysis to establish the presence of MTBC bacteria. As all individuals showing clear osteological signs of TB infection belonged to a single grave group, 38 individuals from this grave group were analysed. The sample included the case of Pott's disease as well as individuals both with and without osseous TB manifestations. The detection of TB DNA in the individual with Pott's disease provided further evidence for the occurrence of TB in Neolithic populations of Europe. Moreover, our molecular analysis indicated that several other individuals of the same grave group were also infected with TB, opening the possibility for further analyses of this unique Neolithic skeletal series. PMID:25857937

  13. Early life dynamics of the human gut virome and bacterial microbiome in infants

    PubMed Central

    Lim, Efrem S.; Zhou, Yanjiao; Zhao, Guoyan; Bauer, Irma K.; Droit, Lindsay; Ndao, I. Malick; Warner, Barbara B.; Tarr, Phillip I.; Wang, David; Holtz, Lori R.

    2016-01-01

    The early years of life are important for immune development and influences health in adulthood. While it has been established that the gut bacterial microbiome is rapidly acquired after birth, less is known about the viral microbiome (or, virome), consisting of bacteriophages and eukaryotic RNA and DNA viruses, during the first years of life. Here, we characterized the gut virome and bacterial microbiome in a longitudinal cohort of healthy infant twins. The virome and bacterial microbiome are more similar between co-twins than between non-related infants. From birth to two years of age, the eukaryotic virome and the bacterial microbiome expanded, but this was accompanied by a contraction of and shift in the bacteriophage virome composition. The bacteriophage-bacteria relationship begins from birth with a high predator-low prey dynamic, consistent with the Lotka-Volterra predator-prey model. Thus, in contrast to the stable microbiome observed in adults, the infant microbiome is highly dynamic and associated with early life changes in the composition of bacteria, viruses and bacteriophage with age. PMID:26366711

  14. Early life dynamics of the human gut virome and bacterial microbiome in infants.

    PubMed

    Lim, Efrem S; Zhou, Yanjiao; Zhao, Guoyan; Bauer, Irma K; Droit, Lindsay; Ndao, I Malick; Warner, Barbara B; Tarr, Phillip I; Wang, David; Holtz, Lori R

    2015-10-01

    The early years of life are important for immune development and influence health in adulthood. Although it has been established that the gut bacterial microbiome is rapidly acquired after birth, less is known about the viral microbiome (or 'virome'), consisting of bacteriophages and eukaryotic RNA and DNA viruses, during the first years of life. Here, we characterized the gut virome and bacterial microbiome in a longitudinal cohort of healthy infant twins. The virome and bacterial microbiome were more similar between co-twins than between unrelated infants. From birth to 2 years of age, the eukaryotic virome and the bacterial microbiome expanded, but this was accompanied by a contraction of and shift in the bacteriophage virome composition. The bacteriophage-bacteria relationship begins from birth with a high predator-low prey dynamic, consistent with the Lotka-Volterra prey model. Thus, in contrast to the stable microbiome observed in adults, the infant microbiome is highly dynamic and associated with early life changes in the composition of bacteria, viruses and bacteriophages with age. PMID:26366711

  15. Linkage of early-onset osteoarthritis and chondrocalcinosis to human chromosome 8q

    SciTech Connect

    Baldwin, C.T.; Farrer, L.A.; Adair, R.; Dharmavaram, R.; Jimenez, S.; Anderson, L.

    1995-03-01

    Calcium pyrophosphate-deposition disease (CPDD), also called {open_quotes}chondrocalcinosis{close_quotes} or {open_quotes}pseudogout{close_quotes}, is a disorder characterized by the deposition of calcium-containing crystals in joint tissue, which leads to arthritis-like symptoms. The presence of these crystals in joint tissue is a common finding in the elderly, and, in this population, there is a poor correlation with joint pain. In contrast, early-onset CPDD has been described in several large families in which the disease progresses to severe degenerative osteoarthritis (OA). In these families, an autosomal dominant mode of inheritance is observed, with an age at onset between the 2nd and 5th decades of life. In this report, we describe a large New England family with early-onset CPDD and severe degenerative OA. We found genetic linkage between the disease in this family and chromosome 8q, with a multipoint lod score of 4.06. These results suggest that a defective gene at this location causes the disease in this family. 29 refs., 2 figs., 1 tab.

  16. Multispectral fluorescence imaging of human ovarian and fallopian tube tissue for early-stage cancer detection

    NASA Astrophysics Data System (ADS)

    Tate, Tyler H.; Baggett, Brenda; Rice, Photini F. S.; Koevary, Jennifer Watson; Orsinger, Gabriel V.; Nymeyer, Ariel C.; Welge, Weston A.; Saboda, Kathylynn; Roe, Denise J.; Hatch, Kenneth D.; Chambers, Setsuko K.; Utzinger, Urs; Barton, Jennifer Kehlet

    2016-05-01

    With early detection, 5-year survival rates for ovarian cancer exceed 90%, yet no effective early screening method exists. Emerging consensus suggests over 50% of the most lethal form of the disease originates in the fallopian tube. Twenty-eight women undergoing oophorectomy or debulking surgery provided informed consent for the use of surgical discard tissue samples for multispectral fluorescence imaging. Using multiple ultraviolet and visible excitation wavelengths and emissions bands, 12 fluorescence and 6 reflectance images of 47 ovarian and 31 fallopian tube tissue samples were recorded. After imaging, each sample was fixed, sectioned, and stained for pathological evaluation. Univariate logistic regression showed cancerous tissue samples had significantly lower intensity than noncancerous tissue for 17 image types. The predictive power of multiple image types was evaluated using multivariate logistic regression (MLR) and quadratic discriminant analysis (QDA). Two MLR models each using two image types had receiver operating characteristic curves with area under the curve exceeding 0.9. QDA determined 56 image type combinations with perfect resubstituting using as few as five image types. Adaption of the system for future in vivo fallopian tube and ovary endoscopic imaging is possible, which may enable sensitive detection of ovarian cancer with no exogenous contrast agents.

  17. Changes in vascular extracellular matrix composition during decidual spiral arteriole remodeling in early human pregnancy.

    PubMed

    Smith, Samantha D; Choudhury, Ruhul H; Matos, Patricia; Horn, James A; Lye, Stephen J; Dunk, Caroline E; Aplin, John D; Jones, Rebecca L; Harris, Lynda K

    2016-05-01

    Uterine spiral arteriole (SA) remodeling in early pregnancy involves a coordinated series of events including decidual immune cell recruitment, vascular cell disruption and loss, and colonization by placental-derived extravillous trophoblast (EVT). During this process, decidual SA are converted from narrow, muscular vessels into dilated channels lacking vasomotor control. We hypothesized that this extensive alteration in SA architecture must require significant reorganization and/or breakdown of the vascular extracellular matrix (ECM). First trimester decidua basalis (30 specimens) was immunostained to identify spiral arterioles undergoing trophoblast-independent and -dependent phases of remodeling. Serial sections were then immunostained for a panel of ECM markers, to examine changes in vascular ECM during the remodeling process. The initial stages of SA remodeling were characterized by loss of laminin, elastin, fibrillin, collagen types III, IV and VI from the basement membrane, vascular media and/or adventitia, and surrounding decidual stromal cells. Loss of ECM correlated with disruption and disorganization of vascular smooth muscle cells, and the majority of changes occurred prior to extensive colonization of the vessel wall by EVT. The final stages of SA remodeling, characterized by the arrival of EVT, were associated with the increased mural deposition of fibronectin and fibrinoid. This study provides the first detailed analysis of the spatial and temporal loss of ECM from the walls of remodeling decidual SA in early pregnancy. PMID:26602431

  18. Expression of mitogen-activated protein kinase phosphatase-1 in the early phases of human epithelial carcinogenesis.

    PubMed Central

    Loda, M.; Capodieci, P.; Mishra, R.; Yao, H.; Corless, C.; Grigioni, W.; Wang, Y.; Magi-Galluzzi, C.; Stork, P. J.

    1996-01-01

    Many mitogens and human oncogenes activate extracellular regulated kinases (ERKs), which in turn convey proliferation signals. ERKs or mitogen-activated protein (MAP) kinases are inactivated in vitro by MAP kinase phosphatases (MKPs). The gene encoding one of these MKPs, MKP-1, is a serum-inducible gene and is transcriptionally activated by mitogenic signals in cultured cells. As MKP-1 has been shown to block DNA synthesis by inhibiting ERKs when expressed at elevated levels in cultured cells, it has been suggested that it may act as a tumor suppressor. MKP-1 mRNA and MAP kinase (ERK-1 and -2) protein expression was assessed in 164 human epithelial tumors of diverse tissue origin by in situ hybridization and immunohistochemistry. MKP-1 was overexpressed in the early phases of prostate, colon, and bladder carcinogenesis, with progressive loss of expression with higher histological grade and in metastases. In contrast, breast carcinomas showed significant MKP-1 expression even when poorly differentiated or in late stages of the disease. MKP-1, ERK-1, and ERK-2 were co-expressed in most tumors examined. In a subset of 15 tumors, ERK-1 enzymatic activity as well as structural alterations that might be responsible for loss of function of MKP-1 during tumor progression, were examined. ERK-1 enzymatic activity was found to be elevated despite MKP-1 overexpression. No loss of 5q35-ter (containing the MKP-1 locus) was detected by polymerase chain reaction in metastases compared with primary tumors. Finally, no mutations were found in the catalytic domain of MKP-1. These data indicate that MKP-1 is an early marker for a wide range of human epithelial tumors and suggest that MKP-1 does not behave as a tumor suppressor in epithelial tumors. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:8909245

  19. The long sediment record of lake Challa: a unique equatorial archive, potentially crucial for understanding early human dispersal

    NASA Astrophysics Data System (ADS)

    Van Daele, Maarten; Moernaut, Jasper; De Batist, Marc; Verschuren, Dirk

    2013-04-01

    Lake Challa (Mt. Kilimanjaro, Kenya/Tanzania) is located in a key site for reconstructing the climate and landscape history of equatorial East Africa and hence, climatic influences on the living environment of early modern humans, Homo sapiens. Seismic-reflection data from this crater lake reveal a ~210-m thick sedimentary infill containing distinct seismic-stratigraphic signatures of late-Quaternary lake-level fluctuations. Extrapolation of a well-constrained age model on the cored upper part of the sequence shows that the signatures of these lake-level fluctuations represent a detailed record of climatic moisture-balance variation in equatorial East Africa, continuous over at least the last 140 kyr and encompassing in total ~250 kyr. The most severe aridity occurred during peak Penultimate glacia